RxPG News : Dermatology

Drug could provide first treatment for scleroderma

Sat, 17 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Investigators have identified a drug that is currently approved to treat certain types of cancer, Gleevec, that could provide the first treatment for scleroderma, a chronic connective tissue disease for which a treatment has remained elusive. The news will be presented at the annual meeting of the American College of Rheumatology on October 18 in Philadelphia.

There has never been a drug that has been shown to be effective for this condition. I think there is a very good chance of Gleevec becoming a real treatment for a previously untreatable disease, said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery who led the study.

For the study, investigators at Hospital for Special Surgery enrolled 30 patients with diffuse scleroderma, a widespread severe form of the disease, and gave them 400 mg of Gleevec per day. Patients were evaluated monthly for 12 months during treatment and were seen for follow-up three months after discontinuing the drug.

To measure the effectiveness of the drug, researchers used a tool known as the modified Rodnan skin score, a measure of how much skin is affected by the disease. The skin score seems to be a very good marker of disease status and most scleroderma trials use this as an outcome measure, said Dr. Spiera, who is also an associate professor at Weill Cornell Medical College. The investigators also measured lung function using tests for forced vital capacity (FVC), the maximum volume of air that a person can exhale after maximum inhalation, and diffusion capacity, a measurement of the lung's capacity to transfer gases. Lung disease is the main cause of mortality in scleroderma.

The investigators reported an interim analysis of their results, although the study is ongoing. At one year, the investigators saw a 23 percent improvement in skin scores. The researchers also saw an improvement in forced vital capacity scores by 9.6 percent and diffusion capacity scores by 11 percent in the 18 patients who had completed one year of treatment.

The lung function data was really exciting, Dr. Spiera said. In patients with scleroderma, you usually see lung function tests getting worse over time, and if doctors try a therapy for a year and a patient doesn't get any worse, we get pretty excited. What is amazing to me in this study is that we actually saw improvements in both lung function tests.

The study is the largest single center trial of Gleevec in scleroderma to date with the longest duration of treatment and follow-up. Before this trial, test tube studies of human cells indicated that Gleevec might have some activity in combating the disease, and the drug was shown to be effective in a rodent model of the disease. Only anecdotal evidence, however, had been published on the drug's effectiveness in treating the disease in humans. Dr. Spiera said the findings of his open-label study need to be interpreted cautiously, and ultimately corroborated by evidence from a randomized controlled trial, the gold standard of clinical trials.

Until now, no drug has been shown to be effective in treating scleroderma in a clinical trial. Several years ago, a small study provided some evidence that a chemotherapy drug called cyclophosphamide may help scleroderma patients, but the benefit was minimal and this drug causes side effects including infertility and secondary cancers.

Dr. Spiera's study was funded primarily through the Rudolph Rupert Scleroderma Program at the Hospital for Special Surgery. Novartis, the manufacturer of Gleevec, provided some monetary support and donated drug. The company is not involved in the design or analysis of the trial. Gleevec is approved in the United States for two types of cancer: chronic myeloid leukemia and gastrointestinal stromal tumor.

Systemic scleroderma affects not only the skin, but also underlying blood vessels, and often muscles and joints, as well as the gastrointestinal tract, kidneys, lungs and heart. According to the Scleroderma Foundation, roughly 300,000 individuals have scleroderma in the United States and roughly a third of these have the systemic kind. The disease typically strikes in the prime of patients' lives, when they are 30-50 years old.

Alzheimer's, asthma, cancer, malaria and TB focus of new Singapore grants

Tue, 28 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Over 50 research grants totaling $24 million in U.S. dollars have been awarded to Singapore universities, research institutes and hospitals to fund studies related to asthma and other immune system disorders, infectious diseases, aging and cancer.

The extramural grants were awarded by the Biomedical Research Council (BMRC) of A*STAR (Agency for Science, Technology and Research), the government agency driving Singapore's transformation into an international powerhouse in the biomedical and physical sciences.

In addition to extramural research grants, A*STAR sponsors the research institutes at Singapore's Biopolis and Fusionopolis.

The common dust mite, Blomia tropicalis, which can have an immense impact on quality of life and even be life threatening when it causes allergies in patients with chronic diseases such as cancer, is the focus of three grants awarded to Chua Kaw Yan, Ph.D., of the National University of Singapore's Department of Pediatrics.

One of Dr. Chua's studies will examine the mechanisms of an oral vaccine against the predominant allergen, the Blo t 5 protein, in B. tropicalis, which is responsible for 60-70% of allergy cases in Singapore, including asthma, allergic rhinitis and eczema.

Optimizing the potency of a genetic vaccine against the dust mite will be the focus of her second grant, while the third project will be directed at creating a modified or recombinant protein to foster immunity against Blo t 5.

Immunotherapy remains the only truly disease-modifying treatment for asthma and allergic rhinitis, said Dr. Chua. Traditional forms of immunotherapy use natural sources of allergens and have numerous disadvantages, such as the presence of undefined material, huge variability in sample composition, and contamination of allergens from other sources.

We therefore hope to use the major allergen, Blo t 5, to develop a novel and effective therapeutic vaccine for immunotherapy, she added.

Grants also were awarded to support research using genomics, proteomics and bioimaging to investigate the mechanisms of infection in tuberculosis and malaria, which cause deaths as well as serious illness despite widespread efforts to prevent their transmission.

In their studies of Mycobacterium tuberculosis (MTB), which infects an estimated two billion people worldwide, National Cancer Centre of Singapore (NCCS) scientists will sift through a bank of DNA samples extracted from drug-resistant MTB strains to identify novel mutated genes conferring resistance to Isoniazid, the main drug now used to treat tuberculosis.

In Singapore, the incidence rate of tuberculosis has increased for the first time in 10 years, leading to concerns over increased transmission of the MTB bacteria.

Ann Lee, Ph.D., who heads the NCCS research team that will investigate MTB, said: The identification of additional genes associated with Isoniazid resistance is important for the development of comprehensive molecular strategies that are potentially more efficient than current susceptibility testing methods, and could aid in giving more appropriate treatment to patients and decrease the spread of resistant strains. In addition, the discovery of new genes may reveal novel targets suitable for the development of alternative therapeutic options.

At Nanyang Technological University (NTU), a research team led by Peter Preiser, Ph.D., was awarded a grant to conduct basic research on the pathology of malaria, which infects as many as 600 million people worldwide and kills over 1 million yearly.

Dr. Huda Zoghbi to receive 2009 Vilcek Prize in biomedical research

Mon, 09 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Internationally renowned scientist Dr. Huda Zoghbi, a pioneer in the study of Rett Syndrome and related autism spectrum disorders, will receive the 2009 Vilcek Prize in biomedical science. We have been awarding these prizes annually since 2006, said Dr. Jan Vilcek, President and Cofounder of the Vilcek Foundation, and this year I'm proud to announce the expansion of our awards program with the Vilcek Prize for Creative Promise, to recognize the successes of foreign-born individuals in the early stages of their careers in the arts and biomedical sciences. Biologist Dr. Howard Chang has been named the first Creative Promise Prize recipient in biomedical science.

Of the new prize category, Marica Vilcek, Vice President and Cofounder of the Vilcek Foundation, explained, We have always wanted to honor and publicize the contributions of a younger generation of immigrants working in the arts and sciences, to help them maximize their potential. Jan and I were in the early stages of our careers when we immigrated to the United States, and the professional support we received here was pivotal to our success. The Vilcek Prizes for Creative Promise are presented to foreign-born individuals, 38 years old or younger, in the fields of biomedical science and the arts.

At the awards presentation, to be held at the Mandarin Oriental Hotel in New York City, Thursday, April 2, 2009, Dr. Zoghbi and Mike Nichols, the 2009 recipient of the Vilcek Prize in the arts, will each receive a $50,000 cash award and a commemorative trophy created by designer Stefan Sagmeister. Creative Promise Prize winners Dr. Chang and Ham Tran, the 2009 recipient of the Vilcek Prize for Creative Promise in the arts, will each receive a $25,000 cash award and a plaque, also designed by Mr. Sagmeister.

The Vilcek Foundation, in meeting its primary purpose, to call attention to the accomplishments of immigrants currently working in United States, also serves to remind the public of the immeasurable contributions of the foreign-born to this country throughout its history. Dr. Vilcek points out, Much of the advancement of science in the United States from the first half of the twentieth century onward rests on the achievements of foreign-born individuals. The outstanding work of this year's science honoree, Dr. Huda Zoghbi, underscores the importance of remembering this fact.

This year's Vilcek Prize recipients demonstrate the truly global influence of America's immigrants: Mike Nichols was born in Berlin, Germany; Dr. Huda Zoghbi in Beirut, Lebanon; Ham Tran in Saigon, Vietnam; and Dr. Howard Chang, in Taipei, Taiwan.

UT Medical School receives $6 million NIH grant to study scleroderma

Wed, 10 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Within five years, researchers at The University of Texas Health Science Center at Houston expect to have identified the genetic clues to scleroderma, a chronic, often progressive, autoimmune disease.

The National Institutes of Health awarded a rheumatologist at the health science center's University of Texas Medical School at Houston a $6 million, five-year grant to conduct a genome-wide association study. The study's goal is to identify gene regions that influence a patient's susceptibility to a serious form of scleroderma known as systemic sclerosis.

Scleroderma, a condition that causes the immune system to attack its own body, affects an estimated 300,000 patients nationwide, mostly women ages 25-55. The disease can result in thickening and tightening of the skin and, in systemic cases, causes serious damage to internal organs, oftentimes targeting the lungs.

I've been studying scleroderma for 20 years, and to see the research field mature to the point where we can do this genotyping, and at the end of five years have an answer is very exciting, said principal investigator Maureen D. Mayes, M.D., MPH, professor of internal medicine in the Division of Rheumatology and Clinical Immunogenetics. Right now we don't know what causes scleroderma, and there is no cure. With this genetic information, we can change that. We can develop better treatments and improve or eliminate symptoms.

For the first phase of the research, which is supported in part by the UT Health Science Center at Houston's Center for Clinical and Translational Sciences, Mayes and collaborators will study the genes of 1,500 patients with scleroderma, plus 3,000 in a control group. Most patients from scleroderma centers at the UT Medical School at Houston, Johns Hopkins School of Medicine and Fred Hutchinson Cancer Research Center have already been identified, and Mayes estimates that the genotyping can be completed as soon as the end of this year. Olga Gorlova, Ph.D., a co-investigator at The University of Texas M. D. Anderson Cancer Center, will then conduct an in-depth statistical analysis of the genome-wide association scan.

During the second phase of the study, to validate the results from the first patient group, Mayes will lead efforts to collect and analyze another 1,500 genetic samples from patients at 10 scleroderma centers in the United States and Canada. Genetic data from a control group of 3,000 healthy individuals will be used for comparison.

This is the tip of the iceberg. With this study, we'll be able to identify gene regions, and from those regions, we will be able to identify specific genes, Mayes said. This provides us a map to the pathways that cause scleroderma, and if we know the pathways, we could interrupt them and prevent disease.

In addition, the study could help investigators identify genes that are markers of severe disease, as well as genes that are indicators of mild disease that is not likely to progress. This, Mayes said, would help physicians determine the best course of treatment. For those with genes that indicate mild disease, rheumatologists could treat their symptoms, which often include joint pain and heartburn. Physicians could pursue a more aggressive approach to treatment, including chemotherapy, for patients with genes that are identified to increase likelihood of severe disease.

The goal is to improve their quality of life, and one of the most important ways we can do that is to first identify and learn more about the genes that influence scleroderma, Mayes said.

Study shows quantum dots can penetrate skin through minor abrasions

Wed, 02 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at North Carolina State University have found that quantum dot nanoparticles can penetrate the skin if there is an abrasion, providing insight into potential workplace concerns for healthcare workers or individuals involved in the manufacturing of quantum dots or doing research on potential biomedical applications of the tiny nanoparticles.

While the study shows that quantum dots of different sizes, shapes and surface coatings do not penetrate rat skin unless there is an abrasion, it shows that even minor cuts or scratches could potentially allow these nanoparticles to penetrate deep into the viable dermal layer - or living part of the skin - and potentially reach the bloodstream.

Dr. Nancy Monteiro-Riviere, professor of investigative dermatology and toxicology at NC State's College of Veterinary Medicine, tested the ability of the quantum dots to penetrate rat skin at 8 and 24 hour intervals. The experiment evaluated rat skin in various stages of distress - including healthy skin, skin that had been stripped using adhesive tape and skin that had been abraded by a rough surface. The researchers also assessed whether flexing the skin affected the quantum dots' ability to penetrate into the dermal layer. Monteiro-Riviere co-authored the study with doctoral student Leshuai Zhang.

While the study indicates that acute - or short-term - dermal exposure to quantum dots does not pose a risk of penetration (unless there is an abrasion), Monteiro-Riviere notes there is still uncertainty on long-term exposure. Monteiro-Riviere explains that the nanoparticles may be able to penetrate skin if there is prolonged, repeated exposure, but so far no studies have been conducted to date to examine that possibility. Quantum dots are fluorescent nanoparticles that may be used to improve biomedical imaging, drug delivery and diagnostic testing.

This finding is of importance to risk assessment for nanoscale materials because it indicates that skin barrier alterations - such as wounds, scrapes, or dermatitis conditions - could affect nanoparticle penetration and that skin is a potential route of exposure and should not be overlooked.

The study found that the quantum dots did not penetrate even after flexing the skin, and that the nanoparticles only penetrated deep into the dermal layer when the skin was abraded. Although quantum dots are incredibly small, they are significantly larger than the fullerenes - or buckyballs - that Monteiro-Riviere showed in a 2007 study in Nano Letters can deeply and rapidly penetrate healthy skin when there is repetitive flexing of the skin.

Additionally, Monteiro-Riviere's laboratory previously showed quantum dots of different size, shape and surface coatings could penetrate into pig skin. The anatomical complexity of skin and species differences should be taken into consideration when selecting an animal model to study nanoparticle absorption/penetration. Human skin studies are also being conducted, but it is important to investigate species differences and to determine an appropriate animal model to study nanoparticle penetration, Monteiro-Riviere says. Not everyone can obtain fresh human skin for research.

Nanoparticles are generally defined as being smaller than 100 nanometers (thousands of times thinner than a human hair), and are expected to have widespread uses in medicine, consumer products and industrial processes.

U of M sets course for cure of fatal childhood skin disease

Tue, 03 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Physicians at the University of Minnesota and University of Minnesota Children's Hospital, Fairview have set the path to a cure for a young boy's fatal genetic skin disease, recessive dystrophic epidermolysis bullosa (RDEB), by using a cord blood and bone marrow transplant. Nate Liao, a 25-month-old from Clarksburg, N.J., underwent the experimental therapy in October 2007.

We have established a new standard of care for these EB patients, beginning with Nate, said John Wagner, M.D., the lead University of Minnesota Medical School physician who developed the clinical trial. Nate's quality of life is forever changed.

Because they lack collagen type VII, children with RDEB have skin that is exquisitely delicate. The skin and lining of their gastrointestinal (GI) tract is fragile; tearing and blistering occur with minimal friction. Coughing and vomiting often result in tears in the lining of the esophagus and stomach. Those affected must have their entire body continuously wrapped in bandages. Those who do not succumb from malnutrition and infection in childhood will acquire a uniformly fatal, aggressive cancer of the skin in young adulthood.

In collaboration with Angela M. Christiano, Ph.D., professor of dermatology and genetics and development at Columbia University Medical Center (New York, N.Y.), and investigators at Asahikawa Medical College (Asahikawa, Japan), and Jefferson Medical College (Philadelphia, Penn.), University of Minnesota researchers, Jakub Tolar, M.D., Ph.D., and Bruce Blazar, M.D., discovered that certain stem cells found in bone marrow could correct the biochemical defect in RDEB in a mouse model of the disease. Marrow-derived stem cells greatly lengthened the life expectancy of the mice and healed existing blisters. Further testing by Columbia demonstrated that for the first time, these mice were producing collagen type VII and anchoring fibrils, the structures needed to bind skin to the body.

This is the first time physicians have approached the treatment of RDEB from a systemic perspective, using marrow-derived stem cells as a means to replace the missing protein, collagen type VII, throughout the body. Through the infusion of cells obtained from a healthy donor, the stem cells produce collagen type VII and correct the underlying genetic defect.

In October 2007, Nate Liao received marrow- and umbilical cord blood-derived stem cells and progenitor cells from his healthy, tissue-matched brother. Over the next six months, the skin and lining of his GI tract slowly improved, and skin biopsies on days 60, 130, and 200 documented increasing amounts of collagen type VII. By day 130, Nate's skin and the lining of his GI tract were beginning to show clinical signs that his skin was anchoring to his body.

Wagner and his team sought an external review of the skin biopsies. Photographs of the biopsies have been sent to dermatopathologists in London, England, and Portland, Ore., for independent analysis. Based on the success seen in Nate, Wagner will enroll additional RDEB patients into the clinical trial. Jacob Liao, Nate's brother who also has RDEB, received an unrelated donor cord blood transplant on May 30.

U of Minnesota researcher discovers the starting point of sun-induced skin cancer

Thu, 15 May 2008 03:59:37 PST

( from http://www.rxpgnews.com ) According to a new study from the University of Minnesota, the earliest event in the development of sun-induced skin cancer may have been identified. The researchers found that the point of entry for skin cancer in response to sun exposure is in receptor molecules, molecular hooks on the outer surface of cells that also pull cannabinoid compounds found in marijuana out of the bloodstream. The research appears in the May 15 issue of Cancer Research.

The question at the core of this research was, 'Why does ultraviolet light induce skin cancer?' said lead researcher Zigang Dong, a professor of cellular and molecular biology and director of the university's Hormel Institute, which supported the study. The idea is to find an agent that can prevent skin cancers after exposure to the sun.

The receptor molecules are protein structures that are components of cells's outer membranes. Acting like receiving docks, their function is to catch specific compounds from the blood and enable the cells to engulf or otherwise interact with the compounds. Receptors have been identified for many substances, including hormones and other chemical signals that regulate what cells do.

The researchers found that two receptors for cannabinoids also responded to UV light. They made the discovery during a search for the initial interaction between UV light and human skin cells.

The researchers began their search with plant cells because plants must interact with UV light in order to harness its energy for photosynthesis. They concluded that the UV receptors in plants ought to be similar to any found in humans, and, therefore, the genes for the plant and human receptors must also be similar. When they compared plant genes for UV receptors to human genetic material, they found that the human genes for cannabinoid receptors matched.

If cannabinoid receptors are important in the initiation of skin cancer by UV light, then animals that lack the receptors should be relatively protected from the ravages of the light. Working with mouse embryos, the researchers removed the genes for the cannabinoid receptors. They found that the skin of the resulting adult mice, which lacked the receptors, was resistant to the development of UV-induced inflammation and skin tumors called papillomas.

Also, when they exposed cannabinoid receptors to UV light, the receptors changed from an inactive to an active state, indicating they had absorbed and responded to the light.

Why should evolution have produced receptors that respond to both UV light and cannabinoids

That we don't know, said Dong.

Researchers uncover new genetic links to psoriasis

Thu, 03 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) In the first comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition. They also found that variations in one genetic region link psoriasis and a related joint disorder, psoriatic arthritis, to four autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease and rheumatoid arthritis.

The study's results appear April 4 in the open-access journal PLoS Genetics.

Common diseases like psoriasis are incredibly complex at the genetic level, says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis.

The DNA variations uncovered by the researchers point to different biological pathways that underlie psoriasis and may eventually lead to new targeted drugs and treatments that hit specific pathways, Bowcock says.

An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is characterized by red, scaly patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, a condition that is often excruciatingly painful and debilitating.

The Washington University researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that comprise DNA are thought to be identical from one person to the next, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person's predisposition to disease or good health.

Using an approach known as whole genome association, the investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in 519 healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients -- 577 with psoriasis and 576 with psoriatic arthritis -- and more than 1,200 healthy controls.

Bowcock and her team found seven novel DNA variations linked to psoriasis. Four other variations associated with the disease that had been identified previously by other researchers also were confirmed by the current study.

Whole genome association studies have recently been used to identify common genetic variations that increase the risk of diseases such as breast cancer, heart disease and type 2 diabetes. They typically involve more than 1,000 patients with a particular disease to help ensure that the genetic variations identified in the study do not occur by chance. While the current study included fewer patients, nearly half of them had a sibling and, in some cases, a parent with psoriasis, which increases the odds of finding genetic variations that contribute to the disease.

The researchers found the strongest genetic risk for psoriasis lies in a region of the genome that contains the major histocompatibility complex, a collection of genes involved in distinguishing the body's own cells from foreign invaders. Although this region has been known to play a major role in psoriasis, DNA variations in the MHC alone have been known to not be enough to trigger disease, Bowcock says. Only 10 percent of patients with variations in the major histocompatibility complex developed psoriasis. This tells us that other genetic or environmental factors also contribute to the disease.

One MHC variation linked to psoriasis and psoriatic arthritis occurs in the gene HCP5, the scientists noted. That variation was recently reported to delay the onset of AIDS in people infected with HIV. This is particularly interesting, Bowcock says, because psoriasis can be triggered by infection with HIV or other viruses. It may be that in people with this SNP variant, viral infection triggers a larger immune response that slows the development of AIDS but also leads to excessive inflammation in the skin and bone joints in genetically susceptible individuals, leading to the onset of psoriasis and psoriatic arthritis.

Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland) and celiac disease (caused by the inability to digest gluten). Doctors have noticed that some psoriasis patients have autoimmune diseases such as celiac disease, Grave's disease, and type 1 diabetes, Bowcock says. But we didn't know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases.

The same region of chromosome 4 contains genes that code for the signaling molecules IL2 and IL21. This opens the door to investigating whether existing drugs that block either molecule may be effective in some psoriasis patients, especially those with psoriatic arthritis.

The researchers also uncovered significant DNA variations on chromosome 13 in a genetic region involved in modifying proteins, and on chromosome 15, in a region responsible for producing a protein that activates TNF alpha (tumor necrosis factor-alpha) in a specialized immune cell known as a dendritic cell. While TNF alpha normally helps fight infections, it is thought to be a major player in psoriasis and psoriatic arthritis. Several FDA-approved psoriasis medications work by binding to TNF-alpha, thereby preventing it from communicating with cells.

Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis.

Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.

The goal of this study and other genome-association studies is to get to personalized medicine, where you can diagnose a disease and ask what genetic risk factors this person has that points to altered pathways, she says. Then, we can target those pathways for specific therapeutic interventions.

Short RNA strand helps exposed skin cells protect body from bacteria, dehydration and even cancer

Sun, 02 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Every minute, 30,000 of our outermost skin cells die so that we can live. When they do, new cells migrate from the inner layer of the skin to the surface of it, where they form a tough protective barrier. In a series of elegant experiments in mice, researchers at Rockefeller University have now discovered a tiny RNA molecule that helps create this barrier. The results not only yield new insight into how skin first evolved, but also suggest how healthy cells can turn cancerous.

Hundreds of these tiny RNA molecules, called microRNAs, are expressed in skin, But there was something curious about one in particular, microRNA-203, says Rui Yi, a postdoc who works with Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development. As an embryo develops, the expression of microRNA-203 jumps very quickly over just two days. From being barely detectable at day 13, this microRNA becomes the most abundant expressed in skin, says Yi, whose work will be published as an advance online publication in Nature March 2. MicroRNAs, which were discovered in mammals in 2001, regulate genes outside of the cell's nucleus.

Yi and Fuchs, who is also a Howard Hughes Medical Institute investigator and Rebecca C. Lancefield Professor at Rockefeller, found that during the 13th day of development, mouse skin is primarily composed of undifferentiated stem cells. Two days later, these stem cells exit the inner layer of the skin and begin to differentiate into cells that form the outermost, protective layer. MicroRNA-203's expression skyrockets precisely during this period, suggesting that it plays some key role in the barrier's development.

In order to figure out its role, Yi and Fuchs needed to pinpoint exactly where microRNA-203 is expressed. Other microRNAs have been found to be specific to heart and muscle tissues; some exist almost exclusively in the brain. However, this microRNA was found only in very specific types of skin -- stratified epithelial tissues, to be exact -- and only in this skin type's outer layers. What's more, this expression pattern is identical to that found in humans, zebrafish, chickens and the like -- in other words, vertebrates that evolved more than 400 million years apart.

If it has been expressed in this very specific tissue for a long time and across several species, it means that it probably plays an important role there, says Yi. To find out its function, Yi, in one set of experiments, used a genetic technique to precociously express microRNA in the inner layer of the skin, where stem cells proliferate at a fast clip. In a second set of experiments, he blocked microRNA-203 from functioning in the outer layer using an antagomir, a molecule that binds directly to microRNA-203 and shuts down its ability to carry out its function.

In the first set, he found that the stem cells proliferated significantly less than they did when microRNA-203 wasn't expressed, and, as a result, the mice formed very thin skin -- hardly a protective layer at all. The stem cells, the researchers saw, lost their ability to proliferate not because microRNA-203 killed them off but because it suppressed the activity of a molecule called p63, whose job is to keep cells, primarily stem cells, proliferating. In the second set of experiments, Yi found that the cells in the outer layer proliferated significantly more than they did when microRNA-203 was expressed. The reason: because microRNA-203 wasn't available to shut down p63's busy work.

We found that microRNA-203 acts to stop the translation of the p63 protein, says Fuchs. The result is a swift transition from proliferating stem cells within the innermost layer of the epidermis and terminally differentiating cells as they exit this layer and move outward to the skin surface.

The findings have intriguing implications for cancer, since p63 is found in excess in cancer cells. As a next step, we are going to examine whether low expression of microRNA-203 is associated with squamous cell carcinomas, says Fuchs, and whether by putting back microRNA-203 we can inhibit the growth of these cancer cells.

Natural secretion marks difference between mole and melanoma

Fri, 08 Feb 2008 03:29:37 PST

( from http://www.rxpgnews.com ) A protein naturally produced and secreted by the body can make the difference between your average mole and melanoma, which killed more than 8,000 people in the United States last year, reveals a new study in the February 8 issue of the journal Cell, a publication of Cell Press.

If this natural anti-cancer agent, called IGFBP7, can be produced and delivered to tumors, it might serve as a targeted chemotherapy for metastatic melanoma, a condition which is basically untreatable today, said Michael Green, a Howard Hughes Medical Institute investigator at the University of Massachusetts Medical School. It might also be used to treat other cancers with mutations in the oncogene known as BRAF.

This is a natural mechanism by which cells try to prevent cancer, Green said. The secretion of this protein gets lost in the formation of cancer. But, because it is secreted, it might also be converted to a therapeutic.

Mutations that leave BRAF permanently activated are found at high frequency in human cancers, the researchers explained. Such mutations are particularly prevalent in melanoma, where they occur in as many as 70 percent of cases. Those mutations, which are also found in some colorectal, ovarian and lung cancers, have been linked to cell proliferation and tumor growth.

Yet activating BRAF mutations are also present in up to 82 percent of benign moles (which go by the clinical term nevi). Pigmented moles progress to melanoma only very rarely, and studies have shown that the same BRAF mutations tied to cancer also cause pigment-producing human melanocytes to undergo senescence and cease dividing.

How, then, does an activated BRAF oncogene induce uncontrolled proliferation in melanoma and senescence in benign nevi? Green's team wanted to know. They suspected that melanomas might feature a second defect that inactivates the senescence otherwise induced in response to the mutant BRAF.

To find those factors, the researchers conducted a genome-wide screen of cells made to express the BRAF mutation (known as BRAFV600E) found in both melanoma and moles. They then disabled other genes in search of those that would allow the cells to begin dividing as they would in cancer.

Protein that controls hair growth also keeps stem cells slumbering

Thu, 24 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Like fine china and crystal, which tend to be used sparingly, stem cells divide infrequently. It was thought they did so to protect themselves from unnecessary wear and tear. But now new research from Rockefeller University has unveiled the protein that puts the brakes on stem cell division and shows that stem cells may not need such guarded protection to maintain their potency.

This research, to be published in the January 25 issue of Cell, raises questions about what stem cells need in order to maintain their ability to regenerate tissue. It may also be key in developing new treatments for thinning hair.

The impetus for the work began five years ago when Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development, and several researchers in her lab discovered that the protein NFATc1 was one of only a few that are highly expressed within the stem cell compartment of the hair follicle. Clinical research, meanwhile, showed that a particular immunosuppressant that inhibits NFATc1, a drug called cyclosporine A, has a rather unsightly side effect: excessive hair growth.

Fuchs and Valerie Horsley, a postdoc in her lab, realized that there was a connection between the drug's side effect and the abundance of NFATc1 within the hair follicle's stem cell compartment -- the bulge. The mice they treated with the drug grew fur at a much faster rate than mice they did not treat. The researchers then showed that this excessive hair growth was due to increased stem cell activity within the bulge, a process that cranked up the production of hair. Specifically, the hair cycle shifted gears from its resting phase, when stem cells slumber, to its growth phase, when stem cells proliferate.

To maintain their multipotent properties, though, it appears that these stem cells hardly needed much rest at all. These findings came as a surprise to the researchers, who, like their colleagues, had believed that stem cells proliferating infrequently protected them from depletion or mutations that would lead to hair loss. It seems like the resting phase isn't as necessary as was once thought, says Horsley. Even though these stem cells are highly proliferative, they still maintain their stem cell character.

Using genetically engineered mice bred by colleagues at Harvard Medical School, Horsley and Fuchs then further explored what happens when skin stem cells lack NFATc1. They found that these mice looked exactly like the hairy mice that were treated with cyclosporine A: The loss of NFATc1 didn't stop the hair cycle, but rather shortened the resting phase and prompted precocious entry to the growth state.

In probing the underlying mechanisms mediating this process, Horsley and Fuchs discovered that NFATc1, a transcription factor, blocks the expression of a gene that provides the cell cycle with go ahead signals at certain checkpoints. By blocking these signals, NFATc1 prevents the stem cells from dividing, preventing unnecessary wear and tear. These same cells, if treated with cyclosporine A, show a rapid loss of the transcription factor, an effect that turns the light green at these checkpoints.

For those with thinning hair, this research may hold promise. As people age, the resting phase of the hair cycle gets longer and longer such that the stem cells proliferate less frequently and hair does not grow at the rate it once did. If we could use a local and more specific inhibitor of NFATc1 than cyclosporine A to stimulate these stem cells, which are just sitting there during an extended resting phase, we might be able to promote new hair growth, says Fuchs, who is Rebecca C. Lancefield Professor at Rockefeller and an investigator at the Howard Hughes Medical Institute. In a sense, by blocking NFATc1 activity in our older mice, their hair follicles were brought back to what appeared to be a more youthful state.

So far, these proliferating stem cells lacking NFATc1 have not led to increased tumor formation, which is often a dangerous byproduct of triggering stem cells into action. This is the first case where we have been able to activate the hair cycle without accompanying signs of tumorigenesis, says Fuchs. If we can control the activation process of follicle stem cells without promoting tumorigenesis, then this would be a big move in the right direction.

More sun exposure may be good for some people

Mon, 07 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) UPTON, NY - A new study by scientists at the U.S. Department of Energy's Brookhaven National Laboratory and colleagues in Norway suggests that the benefits of moderately increased exposure to sunlight - namely the production of vitamin D, which protects against the lethal effects of many forms of cancer and other diseases - may outweigh the risk of developing skin cancer in populations deficient in vitamin D. The study will be published online in the Proceedings of the National Academy of Sciences the week of January 7, 2008.

We know that solar radiation is the leading cause of skin cancer, said communicating author Richard Setlow, a Senior Biophysicist Emeritus at Brookhaven and a well-known expert on the link between solar radiation and skin cancer. Setlow's group was the first to establish that ultraviolet A (UVA) radiation and visible light are the primary causes of malignant melanoma, the deadliest form of skin cancer. He and his colleagues emphasize that people need to protect themselves from the harmful effects of sun exposure.

But solar radiation is also a major, if not the main, source of vitamin D in humans. In the presence of sunlight, the body converts certain precursor chemicals to active vitamin D.

Since vitamin D has been shown to play a protective role in a number of internal cancers and possibly a range of other diseases, it is important to study the relative risks to determine whether advice to avoid sun exposure may be causing more harm than good in some populations. The concern, he says, is particularly great in populations from northern latitudes, such as Scandinavia, where sun exposure is extremely limited.

In the current study, Setlow and his colleagues used a model incorporating information on solar radiation intensity and a vertical cylinder shape to represent the human body's skin surface to calculate the relative production of vitamin D via sunlight as a function of latitude, or distance from the equator. The cylindrical model more realistically represents human body sun exposure than flat surface exposure measurements used in previous models. The scientists also examined the incidence of and survival rates for various forms of cancer by latitude.

According to the calculations, people residing in Australia (just below the equator) produce 3.4 times more vitamin D as a result of sun exposure than people in the United Kingdom, and 4.8 times more than people in Scandinavia.

There is a clear north-south gradient in vitamin D production, Setlow says, with people in the northern latitudes producing significantly less than people nearer the equator.

In populations with similar skin types, there is also a clear increase in the incidence of all forms of skin cancer from north to south. This gradient in skin cancer rates indicates that there is a true north-south gradient in real sun exposure, Setlow says.

The scientists also found that the incidence rates of major internal cancers such as colon cancer, lung cancer, and cancers of the breast and prostate also increased from north to south. However, when the scientists examined the survival rates for these cancers, they found that people from the southern latitudes were significantly less likely to die from these internal cancers than people in the north.

In previous work, we have shown that survival rates for these cancers improve when the diagnosis coincides with the season of maximum sun exposure, indicating a positive role for sun-induced vitamin D in prognosis - or at least that a good vitamin-D status is advantageous when combined with standard cancer therapies, Setlow says. The current data provide a further indication of the beneficial role of sun-induced vitamin D for cancer prognosis.

So, how can people get the benefits of vitamin D without running the risk of deadly skin cancer

As far as skin cancer goes, we need to be most worried about melanoma, a serious disease with significant mortality, Setlow says.

Melanoma is triggered by UVA (the long UV wavelengths) and visible light. Vitamin-D production in the body, on the other hand, is triggered by UVB (the short UV wavelengths at the earth's surface). So perhaps we should redesign sunscreens so they don't screen out as much UVB while still protecting us from the melanoma-inducing UVA and visible light, Setlow says.

Increased UVB exposure may result in an increase in non-melanoma skin cancers. But these are relatively easy to cure and have very low mortality rates compared with the internal cancers vitamin D appears to protect against, Setlow adds.

Another option would be to increase vitamin D consumption while continuing to wear sunscreen. Vitamin D is easily accessible in many foods and liquids, such as cod liver oil and milk, and in dietary supplements.

Stanford researchers produce short-term reversal of skin aging in mice

Thu, 29 Nov 2007 04:59:37 PST

( from http://www.rxpgnews.com ) STANFORD, Calif. - Researchers at the Stanford University School of Medicine have reversed the effects of aging on the skin of mice, at least for a short period, by blocking the action of a single critical protein.

The work could one day be useful in helping older people heal from an injury as quickly as they did when they were younger, said senior author Howard Chang, MD, PhD, assistant professor of dermatology. However, Chang and his colleagues warned their finding will likely be useful in short-term therapies in older people but not as a potential fountain of youth.

The work backs up the theory that aging is the result of specific genetic changes rather than accumulated wear and tear, Chang said. What's more, those genetic changes can be reversed even late in life.

The implication is that the aging process is plastic and potentially amenable to intervention, Chang said. The results will be published in the Dec. 15 issue of the journal Genes and Development.

The work came about thanks to existing data from experiments using microarrays, which detect the activity of all genes in a cell. In past experiments, researchers have found a large number of diverse genes that become either more active or less active in older people.

Chang and graduate student Adam Adler, the study's first author, searched through this existing data to see if those age-related genes had anything in common. It turned out that their activity gets dialed up or down with the help of the protein called NF-kappa-B.

Chang said people had long known that NF-kappa-B winds its way into a cell's nucleus to control which genes were active. What they didn't know is that many of those genes regulated by the protein have a role in aging.

Chang and Adler tested whether blocking the activity of NF-kappa-B in the skin of older mice for two weeks had a youthful effect. We found a pretty striking reversal to that of the young skin, Chang said.

First they looked at the genetic changes resulting from blocking NF-kappa-B. After two weeks, the skin of 2-year-old mice had the same genes active as cells in the skin of newborn mice-a striking difference when compared with the skin of a normal 2-year-old mouse. The skin looked more youthful too. It was thicker and more cells appeared to be dividing, much like the skin of a younger mouse.

Chang and Adler caution that their findings aren't likely to be the source of the long-sought fountain of youth. That's because they don't know if the rejuvenating effects of NF-kappa-B are long-lasting. Also, the protein has roles in cancer, the immune system and a range of other functions throughout the body. Suppressing the protein on a long-term basis could very well result in cancers or other diseases that undermine its otherwise youthful effect.

You might get a longer lifespan but at the expense of something else, Chang said.

Instead, the researchers believe their work could point to a way of helping older people heal more quickly after surgery or boost organ function during illness. These short-term applications aren't as likely to risk side effects that could accompany blocking such a critical protein.

Medical College of Wisconsin receives FDA grant

Thu, 25 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The Food and Drug Administration (FDA) has awarded the Medical College of Wisconsin in Milwaukee a three-year, $1 million Orphan Products Development grant to study infantile hemangiomas � a vascular tumor of the skin or internal organs.

The unique, interdisciplinary, and multi-institutional study is led by co-principal investigators Beth Drolet, M.D., professor of dermatology and pediatrics, at the Medical College and medical director of the vascular anomalies and dermatology program at Children�s Hospital of Wisconsin; and Michael E. Kelly, M.D., Ph.D., assistant professor of pediatrics - hematology/oncology.

�This is a major achievement for Drs. Drolet and Kelly to receive an FDA grant to study a neglected but important health issue in infants,� says Dean and Executive Vice President Michael Dunn, M.D. �Dr. Drolet noted the increase in incidence of this disease and found a way to fund research to develop better treatment options.�

The new research builds on earlier Medical College studies supported by Children�s Hospital and Health System Foundation, the Dermatology Foundation, Children�s Research Institute, the Greater Milwaukee Foundation, and the NOVO Foundation.

�Partnering with Children�s Hospital, Children�s Research Institute, our patient families, and private donors in the community was truly inspiring,� says Dr. Drolet. �Their generosity and support has empowered our center to create a vision for our research that will change the way infants with this disorder are cared for around the country.�

In 2004, Children�s Hospital and the Medical College created the Birthmarks and Vascular Anomalies Center to better care for infants with hemangiomas and other vascular anomalies. This interdisciplinary program, composed of surgeons, oncologists, radiologists, and pathologists, treats patients from around the country.

�Our preliminary studies show that the increased incidence of hemangiomas may be related to the increase in the rate of low birth weight infants in the United States,� says Dr. Drolet. �We are treating more of these infants while uniform guidelines for therapy and methods used to measure response to treatment of infants with hemangiomas are lacking.�

Infantile hemangiomas are a common, yet poorly understood vascular tumor. Most hemangiomas are found in the skin, but sometimes, they occur in other organs in the body such as the liver, spleen, intestine, airway, lungs and the central nervous system. Unlike most birthmarks, cutaneous hemangiomas are tumors that undergo cellular proliferation. They are either absent or barely evident at birth proliferating in the first few weeks to months of life, followed by a phase where they tend to decrease in size over several months to years.

Although most hemangiomas eventually resolve, many infants will suffer complications such as permanent disfigurement, ulceration, bleeding, loss of vision, airway obstruction, congestive heart failure and even death. Since hemangiomas can behave in vastly different ways and affect many different areas of the body, even physicians who are knowledgeable about hemangiomas and have access to diagnostic resources often find caring for affected infants challenging.

Drs. Drolet and Kelly will study infants diagnosed with large, complicated hemangiomas to determine and compare the effectiveness and safety of steroids in the current standard of care with a drug currently used for cancer.

Fifty infants with large and complicated hemangiomas will be randomly assigned to receive daily oral corticosteroid, prednisolone, or weekly IV vincristine for up to six months. The diagnostic, therapeutic and response criteria determined in this study may be used as a framework for future multi-institutional clinical trials to treat hemangiomas.

The study will provide answers as to which drug is more effective while at the same time providing opportunities for several additional investigators at the Medical College and at the Children�s Research Institute to examine pathogenesis of hemangiomas and genetic factors that influence disease susceptibility and response treatment. These unique partnerships should help develop even better and safer treatment options for these infants.

New type of drug shows promise in attacking melanoma in an innovative way

Wed, 26 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: An experimental drug that attacks cancer in an entirely new way has shown promise in treating advanced melanoma, delaying progression of the disease and prolonging the lives of patients.

New research presented today (Wednesday) at the European Cancer Conference (ECCO 14) in Barcelona found that giving the new drug in addition to chemotherapy more than doubled the amount of time patients survived without progression of their cancer.

The study, according to Dr Anthony Williams, vice president of clinical research at Synta Pharmaceuticals Corp. in Lexington, Massachusetts, USA, included 81 patients with metastatic melanoma. Of those, 28 received treatment with the chemotherapy drug paclitaxel alone and 53 received paclitaxel plus the new drug, STA-4783.

�The median progression free survival was 1.8 months in the group who got chemotherapy alone, but 3.7 months in the group who got the combination,� Williams said. �This doubling in progression free survival is impressive for this cancer, and the result was achieved without substantial additional toxicity.�

He added: �Progression-free survival was linked to improvements in overall survival. Patients on the experimental combination survived on average for 12 months after being diagnosed, while those getting only paclitaxel survived on average 7.8 months. This is the first time an improvement in survival has been seen in a randomised, double-blind, multi-centre controlled trial for metastatic melanoma.�

The drug is the first in a new class called oxidative stress inducers. It works by increasing the amount of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, in cells. When the level exceeds the antioxidant capacity of cells, the cells are in a state of oxidative stress. All cells have some low level of ROS, but cancer cells naturally operate with a higher level of ROS and oxidative stress relative to normal cells. However, too much oxidative stress for too long results in cell death. STA-4783 kills only tumour cells because the additional stress introduced pushes cancer cells, but not healthy cells, over the critical threshold. Melanoma is one of several cancer types that are known to operate at a higher level of oxidative stress.

The concept of cancer cells operating at a higher level of oxidative stress than normal cells has been around for many years. However, it is only recently becoming a greater focus of attention in the oncology field.

Metastatic melanoma, where the skin cancer has spread to other parts of the body, is difficult to treat. Current therapies either have limited power or are highly toxic. The average survival of patients diagnosed with advanced melanoma is about six months.

The study also indicated that STA-4783 might boost the efficiency of chemotherapy drugs that induce cell death, or apoptosis, because it appears to lower the hurdle for activating that process, Williams said.

�These results are encouraging not only because of the findings in themselves but also because there are so few treatment options for patients. We believe STA-4783 has the potential to improve survival with a manageable side effect profile,� he said.

�We also believe there is nothing unique about metastatic melanoma and that oxidative stress has the potential to be an entirely new class of cancer treatment that could have applications in other types of cancer,� Williams added.

A larger study of STA-4783 in melanoma patients across Europe is now under way to further investigate the drug�s potential. Synta, the drug�s developer, funded the study presented at ECCO.

New study suggests cause of debilitating skin condition

Mon, 24 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WINSTON-SALEM, N.C. � New findings from researchers at Wake Forest University Baptist Medical Center and colleagues suggest why some people with kidney failure can develop a rare tightening and swelling of the skin and other organs, including the lungs and heart.

Reporting in the October issue of the American Journal of Dermatopathology, the authors suggest a possible explanation for why some patients on kidney dialysis who are injected with a �contrast agent� during a magnetic resonance imaging (MRI) develop nephrogenic systemic fibrosis (NSF).

The U.S. Food and Drug Administration now requires a warning about the potential risk on the products� labels. NSF leads to thickened, rough or hard skin usually on the arms, legs or trunk. In some cases, the limbs can become difficult or even impossible to move.

�The cause of this syndrome has been unclear,� said David C. Sane, M.D., senior researcher on the project. �Our research suggests both a potential cause and the possibility of preventing or treating NSF.�

Sane said the finding � that an enzyme known as transglutaminase-2 (TG2) may be involved � is the first to suggest how exposure to contrast agents may lead to NSF.

It has not been known what causes NSF, but a risk factor is exposure to gadolinium, an agent injected into patient�s veins during some MRI procedures to help improve the visibility of internal organs during the test. The condition is relatively rare � it occurs in about 2 percent to 4 percent of kidney patients on dialysis who are exposed to gadolinium.

The researchers tested the hypothesis that TG2 may be involved in the response. The enzyme is found throughout the body and is involved in blood clotting and wound healing. They hypothesized that gadolinium may activate the enzyme and cause NSF.

The group obtained skin biopsies from five people with NSF and three healthy people. All NSF patients had renal failure and had previously had imaging procedures using gadolinium. The researchers tested for the presence of TG2 in the skin samples.

�Compared to the healthy subjects, there was a marked increase in TG2 in the subjects with NSF,� said Sane. �This suggests that activation of TG2 can produce the syndrome. TG2 is expressed in virtually all tissues and may explain why the fibrosis can occur in the heart and lungs, as well as the skin.�

Sane said the results also suggest a strategy for preventing or treating NSF � drugs such as cysteamine that inhibit the activation of TG-2.

�Our research is a pilot study, but we believe the results warrant further research into the use of TG-2 inhibitors in the treatment and prevention of NSF,� said Gil Yosipovitch, M.D., co-senior researcher, and a dermatologist. �Solving this puzzle might allow dialysis patients to take full advantage of the diagnostic capabilities of MRI.�

�This could be a general mechanism for a broad range of disorders that involve fibrosis, or tissue thickening,� said Sane.

New topical therapy safely treats nail fungus without systemic side effects

Fri, 21 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Ann Arbor, Mich. -- A new topical lotion that penetrates the skin deeply enough to target and eliminate serious skin infections, but without being systemically absorbed, has shown a high degree of safety and tolerability in patients with onychomycosis, or toenail fungus, a new study has shown.

�Results of the phase 1 clinical trial are important to the fields of dermatology and infectious diseases because currently approved systemic medications for onychomycosis carry serious risks of cardiac and liver toxicity,� said James Baker, MD, chief science officer and founder of NanoBio Corporation in Ann Arbor, Mich.

The phase 1 data for the new lotion, NB-002, were presented at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting Sept. 17 -20, 2007, in Chicago. �At present, the vast majority of people with onychomycosis are untreated as a result of concerns for the serious toxicities associated with the available oral medications,� said Baker, whose team developed the lotion. �Our safety data, combined with early information from the ongoing phase 2 trial, indicate that NB-002 is potentially the first treatment for onychomycosis that is highly efficacious and very safe.� NanoBio Corporation is a spin-off from the University of Michigan. The company develops novel anti-infective products and mucosal vaccines to treat or prevent a wide range of infections, from cold sores and toenail fungus to influenza and hepatitis B. Its lead products are NB-001 to treat herpes labialis and NB-002 to treat onychomycosis.

NB-002 is a topical oil-in-water nanoemulsion combined with an antimicrobial agent commonly used in oral products to treat gingivitis and other conditions of the mouth and throat. The nanoemulsion undergoes a high-energy process to shrink or �nano-size� the particles so they are small enough to enter the skin through pores and hair follicles but too large to penetrate the tight junctions of the epithelium.

As a result, NB-002 is not systemically absorbed, as the phase 1 study has demonstrated. In the study, 20 subjects with advanced onychomycosis were randomized to receive two strengths of NB-002. Treatments were applied twice daily for 28 days to both affected and unaffected toenails and a small area of surrounding skin. Blood samples were collected periodically to determine if the drug was absorbed systemically.

Results showed the drug was below the quantifiable limit of systemic absorption for all subjects throughout the study period. Additionally, the trial showed that, unlike the current treatments for onychomycosis, NB-002 had no safety or dermal irritation concerns.

Results of a phase 2 clinical trial for onychomycosis are expected in early 2008.

In addition to its topical agents, NanoBio is developing a rich pipeline of needle-free vaccines based on using the same oil-in-water emulsion technology as an adjuvant. Mucosal vaccines against influenza and hepatitis are scheduled for human testing beginning next year, while an anthrax vaccine has demonstrated safety and strong efficacy in animal studies.

Skin cooling associated with increased risk of discoloration after laser treatment

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A cooling technique intended to protect the skin may actually increase the risk of discoloration in dark-skinned patients undergoing laser treatments for mole-like skin lesions, according to a report in the September issue of Archives of Dermatology, one of the JAMA/Archives journals.

Hyperpigmentation, when the skin�s cells increase their production of the brown or black pigment melanin, is the most common adverse effect of laser treatments in dark-skinned individuals, according to background information in the article. �It is not life-threatening, but postinflammatory hyperpigmentation may cause substantial psychological problems,� the authors write. �The treatment of postinflammatory hyperpigmentation is difficult and time-consuming, often lasting many months to achieve the desired results, which causes frustration in patients and physicians.� Some clinicians have hypothesized that skin cooling, which decreases pain and allows the use of higher laser frequencies, could also reduce hyperpigmentation after laser treatment.

Woraphong Manuskiatti, M.D., and colleagues at Mahidol University, Bangkok, Thailand, used laser irradiation (from a 1,064-nanometer Q-switched Nd:YAG laser) to treat 23 Thai women (average age 43) with Hori nevus, blue-brown pigmented spots on the skin that develop later in life. �One randomly selected face side of each patient was cooled using a cold air cooling device during and 30 seconds before and after laser irradiation, and the other side was irradiated without cooling,� the authors write. Two dermatologists not involved in treatment examined digital photographs to measure the occurrence of hyperpigmentation before treatment and one, two, three, four and 12 weeks after treatment.

Of the 21 patients who completed the study, 13 (62 percent) developed hyperpigmentation on the cooled side, five (24 percent) developed it on the uncooled side, one patient (5 percent) developed it on both sides and two (10 percent) did not experience any hyperpigmentation. The cooled sides were three times more likely to become hyperpigmented after laser treatment than the uncooled sides. Most (62 percent) of the cases of hyperpigmentation developed two weeks after treatment, and all but one case completely resolved 12 weeks after treatment.

All patients showed less than 25 percent lightening of their Hori nevi at 12 weeks post-treatment. �No difference in clinical improvement was observed regarding the cooling used on one side during treatment,� the authors write.

It is unclear why cold air cooling would increase the risk of hyperpigmentation following laser treatment, but skin cells may have reacted to the combination of laser treatment and cold air, the authors note. �Future studies should address the question of whether the other methods of epidermal cooling are associated with an increased risk of postinflammatory hyperpigmentation,� they conclude.

M.D. Anderson-led team reports possible key to autoimmune disease

Sun, 16 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) HOUSTON � A human peptide that acts as a natural antibiotic against invading microbes can also bind to the body�s own DNA and trigger an immune response in the absence of an infection, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in an early online publication in Nature.

�This combination of the peptide and self-DNA activates the same immune response pathway as a virus does,� says senior author Michel Gilliet, M.D., assistant professor in M. D. Anderson�s Departments of Immunology and Melanoma Medical Oncology.

Researchers believe this response is both a likely key driver of autoimmune disease and an integral part of an early warning system that flags tissue damage to launch a protective inflammatory response to injury.

�We show that this pathway may drive autoimmunity in psoriasis, a chronic inflammatory skin disease,� Gilliet says. But the key peptide, called both LL37 and CAMP, is also heavily expressed in other autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis.

LL37 provides a new potential target to block in the treatment of chronic inflammatory diseases and a possible component for vaccines against infectious diseases and cancers, the authors note.

The team tracked down this new pathway by studying the activation of important immune defense cells in psoriasis. Plasmacytoid dendritic cells (pDCs) are highly specialized to recognize viral and other microbial infections. They engulf a virus and set off an immune system cascade to fight the infection by producing interferons.

�These dendritic cells normally do not respond to self-DNA,� Gilliet explains. This unresponsiveness prevents the cells from launching an attack on the body�s own tissue. However, researchers had accumulated evidence of a connection between skin damage with release of self-DNA and pDC activation in psoriatic skin leading to disease formation. They lacked a molecular mechanism connecting these factors.

In a series of lab experiments, they identified LL37 as the key ingredient in psoriatic tissue that activates the dendritic cells. The peptide is a member of a family of antimicrobial peptides long known to defend against infection through their ability to directly destroy bacteria and viruses.

The team then demonstrated that LL37 activates the dendritic cells by binding to the self-DNA to form a structure that allows it into the dendritic cells, as if it were an invading microbe.

The complex is taken up inside a walled-off chamber in the pDCs called an endosome, where it connects to a sensitive internal receptor that launches production of interferon-alpha, setting off the immune response.

�We think LL37�s normal job is to alert the immune system to tissue damage and stimulate a temporary inflammatory response that enhances resistance to infection and initiates wound healing,� Gilliet says.

�When tissue is injured, cells are destroyed and they spill DNA into the areas surrounding the cells. LL37, released by epithelial cells, binds this extracellular DNA, which is then taken up by the pDCs to launch the protective inflammatory immune response,� Gilliet says.

But in the case of autoimmune disease, LL-37 remains persistently produced, well beyond the temporary jolt needed to dampen infection and promote healing.

Gilliet says follow-up research to better understand the pathway and to exploit it to treat autoimmune disease and cancer is under way.

Dermatologists identify North Texas leishmaniasis outbreak

Fri, 14 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DALLAS � Sept. 14, 2007 � A team of dermatologists and dermatopathologists at UT Southwestern Medical Center has identified nine North Texas cases of an infectious skin disease common in South America, Mexico and in the Middle East, where it is sometimes referred to as a �Baghdad boil.�

Numerous cases of the disease, called leishmaniasis, have been reported in troops returning from Iraq and Afghanistan. But for the first time, cases of this dangerous infection are appearing in North Texas in patients who have not traveled to endemic areas.

The infection causes nonhealing sores that can be the size of a half-dollar or larger and that look like boils. These sores usually last for 6 to 12 months and because they are often mistaken for a staph infection, patients may have been given multiple courses of standard antibiotics without success.

The disease is caused by a single-celled parasite called Leishmania, and special cultures must be done in order to confirm the diagnosis of leishmaniasis.

The identified cases were from Waxahachie, Hillsboro and Glenn Heights, all areas south of Dallas; Tom Bean, Anna, Savoy and Nevada, all north of Dallas; and North Richland Hills.

North Texas doctors must have a high index of suspicion and understand that this organism must now be considered endemic in this area, said Dr. Kent Aftergut, a clinical instructor of dermatology at UT Southwestern and in private practice at Methodist Charlton Medical Center.

�Luckily, all of the leishmaniasis cases in North Texas that have been cultured have grown Leishmania mexicana, which is less dangerous than other forms of the parasite,� he said. �It makes skin sores, but the infection doesn�t spread and become a full body disease like some of the others species of Leishmania. Usually, if patients have a normal immune system, the sores will resolve in six to 12 months and won�t make the patients ill.�

In North Texas, doctors suspect that the process leading to human infection begins when a sand fly bites a rodent called the burrowing wood rat, which carries the parasite. When the sand fly later bites a person, the sores may develop, said Dr. Aftergut, who began tracking cases in North Texas after identifying the ailment in a patient who had been simply working outside in his yard and had no travel history to areas of infection.

�If a patient has been in Iraq or another known endemic area, we are very used to looking for leishmaniasis. But in the past, you just would not have suspected it in a patient living in North Texas with no travel history. This is why I think it�s important to get the word out to other health-care professionals,� Dr. Aftergut said.

For many years sporadic cases have been seen in South Texas. But no one has ever reported cases this far north, Dr. Aftergut said. He said this may be due to a movement in either the burrowing wood rat or the sand flies that transmit the infection to humans, although the reason for this movement is unclear.

�There are nine cases of leishmaniasis in North Texas residents who had no travel history in the last two years,� said Dr. Aftergut. �This is very strong evidence that the areas we need to consider endemic are moving north.�

Dr. Aftergut said he believes that rural areas are more at risk due to their proximity to wooded areas, where the burrowing wood rat and sand flies are more likely to be found.

Dr. Aftergut said using insecticides, bug repellant and protective clothing while working in areas where sand flies might be present should help reduce exposure. Once bitten, there are two types of medicines to treat the infection; however, one treatment can be toxic to some patients.

Doctors who identify a possible case of leishmaniasis should contact the Centers for Disease Control and Prevention, which can assist with the special tests needed to verify it. The federal agency also is tracking cases, Dr. Aftergut said.

Skin as a living coloring book

Thu, 06 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The pigment melanin, which is responsible for skin and hair color in mammals, is produced in specialized cells called melanocytes and then distributed to other cells. But not every cell in the complex layers of skin becomes pigmented. The question of how melanin is delivered to appropriate locations may have been answered by a study from researchers at the Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC).

�Pigment recipient cells essentially tell melanocytes where to deposit melanin, and the pattern of those recipients determines pigment patterns,� says Janice Brissette, PhD, who led the study. �Recipient cells act like the outlines in a child�s coloring book; as recipient cells develop, they form a �picture� that is initially colorless but is then �colored in� by the melanocytes.� The report appears in the Sept. 7 issue of Cell.

In humans, melanin is deposited in both the skin and the hair; but in some other mammals such as mice, melanin is primarily deposited in the coat, leaving the skin beneath the coat unpigmented. Melanocytes deposit melanin via cellular extensions called dendrites that reach out to other cells in the epidermis (the outer layer of skin) or the hair follicles. But the mechanism determining whether melanin is delivered to a particular cell has been unknown.

The MGH-CBRC researchers theorized that a mouse gene known as Foxn1 might play a role. Lack of Foxn1 is responsible for so-called �nude mice,� which have hair that is so brittle it breaks off, resulting in virtually total hairlessnes, and other defects of the skin. A similar phenomenon exists in humans with inactivation of the corresponding gene.

When the researchers developed a strain of transgenic mice in which Foxn1 is misexpressed in cells that do not usually contain melanin, they found those normally colorless areas became pigmented. Examining the skin of the transgenic mice revealed that melanocytes were contacting and delivering melanin to the cells in which Foxn1 was abnormally activated. No pigment was observed in the corresponding tissues of normal mice. Examination of human skin samples showed that the human version of Foxn1 was also expressed in cells known to be pigment recipients. Further experiments revealed that Foxn1 signals melanocytes through a protein called Fgf2, levels of which rise as Foxn1 espression increases.

�Foxn1 makes epithelial cells into pigment recipients, which attract melanocytes and stimulate pigment transfer, engineering their own pigmentation,� says Brissette, an associate professor of Dermatology at Harvard Medical School. She and her colleagues note that the Foxn1/Fgf2 pathway probably has additional functions in the skin and that it is probably not the only pathway responsible for the targeting of pigment.

�We know that Foxn1 and Fgf2 act in concert with other factors and function within a larger network of genes. Our next step will be to identify other genes that can confer the pigment recipient phenotype or control the targeting of pigment,� Brissette adds. Her research may eventually be relevant to disorders such as vitiligo � in which pigment disappears from patches of skin � age spots, the greying of hair and even the deadly melanocyte-based skin cancer melanoma.

Bench-to-bedside look at MSC research at Case Western Reserve conference in Cleveland

Fri, 24 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CLEVELAND�Researchers from 22 countries will come to Cleveland for a bench to bedside examination of the developing mesenchymal stem cells (MSC) from regenerative medicine and stem cell research to therapeutics in patient care. The National Center for Regenerative Medicine for Stem Cell and Regenerative Medicine (NCRM) and founding partner Case Western Reserve University have organized the 2007 Adult Mesenchymal Stem Cells in Regenerative Medicine Conference, August 27-29, at the Marriott Hotel in downtown Cleveland, to highlight advances in MSC research. The conference is the first organized by the two groups on MSCs.

It leads off with Arnold Caplan, Case Western Reserve professor of biology and director of the Skeletal Research Center in the College of Arts and Sciences. In the late 1980s, science literature hinted of MSCs� existence, but it was research by Caplan - with Case collaborators Stephen Haynesworth (biology, associate dean of the College of Arts and Sciences), Stanton Gerson (director of NCRM and the Ireland Cancer Center) and Hillard Lazarus (director of the Blood and Marrow Transplant Program at the Ireland Cancer Center) - that led to the MSC discovery in Case labs.

When Caplan first discovered the MSCs, little was known about their potential uses, but that has changed. �MSC research is exploding and getting more recognition as the research moves into the clinic,� he said. �The therapeutic field has finally caught up with the research potentials.�

His discovery paved the way for a great deal of research, at Case and other institutions, to develop MSC applications.

Since MSCs were found to have regenerative properties, Caplan, Haynesworth and Gerson established Osiris Therapeutics, Inc., to take the lab research into human therapies. This company, although originally started in Cleveland, Ohio, relocated to Baltimore, Md., and has successfully become a publically traded company. Randall Mills, the CEO of Osiris, will give the concluding talk on Wednesday to provide insight into running clinical trials using MSCs to almost 300 doctors and researchers attending the conference.

�Educating researchers in methods and models in mesenchymal stem cell technology has been a priority of our key investigators Drs. Caplan and Gerson, who are part of the MSC 2007 organizing committee,� said Michael Gilkey, NCMR�s marketing and operations manager. �We also are establishing Cleveland in the biotechnology world as the place to be for stem cell research.�

Cleveland has been a leader in regenerative medicine and stem cell applications. The multi-institutional NCRM, including Case, University Hospitals Case Medical Center and the Cleveland Clinic, provides a comprehensive approach, including basic and clinical research as well as biomedical and tissue engineering, to develop new adult (non-embryonic) stem cell therapies for patients suffering from chronic and debilitating diseases including heart disease, cancer, genetic disorders and neurodegenerative diseases and injuries such as multiple sclerosis. Currently, NCRM has more than 27 ongoing clinical trials using adult stem cells and provides a comprehensive approach to developing therapies for patients suffering from chronic and debilitating diseases.

Caplan stated that Case Western Reserve and Cleveland health care institutions have done more protocols in MSC clinical research than other cities. Currently Osiris Therapeutic has clinical trials for MSC use in regenerating tissue and repairing the body injuries from cancer, Crohn�s disease, heart attacks and cartilage damage.

MSC research by Caplan and colleagues has focused on ways in which these cells can be used to restore and repair bone and cartilage. His most recent discovery was a method in which bone marrow cells were grown on three-dimensional scaffolds made of a substance called hyaluronon, which is found naturally in the body. Hyaluronon acts as a lubricant for joints, absorbing the impact caused by everyday movements. Hyaluronon also makes cartilage more elastic. Signals from hyaluronon trigger MSC to migrate to specific tissue. The results of the most recent research indicates great potential for treating musculoskeletal conditions such as fractures or bone loss.

Research suggests new options in treating skin pigment problems

Wed, 22 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Melanocytes are not the only cells responsible for differences in skin coloration. New research from the University of Cincinnati (UC) has shown that some of the most basic cells on the skin�s surface influence pigment production and help regulate skin coloration.

The finding offers hope for new approaches to the treatment of pigmentation disorders that leave the skin disfigured by light or dark blotches.

In a two-year, preclinical dermatological study, Raymond Boissy, PhD, and his team found that cells known as keratinocytes express certain characteristics that could control skin pigmentation.

Keratinocytes are surface skin cells that make up about 96 percent of the skin�s outer layer (epidermis). The cells give the skin structural integrity and protect the body from infection.

Melanocytes, the body�s melanin-producing cells, make up another 2 percent of the epidermis. Melanin is the chemical responsible for skin pigmentation or color.

Boissy says his team�s findings could help scientists develop new drugs that alter the physiological processes that cause pigmentation disorders such as vitiligo�white blotches that occur near the body�s orifices and joints�and melasma, a disorder characterized by dark pigmented lesions.

�We�ve isolated specific physiological properties that regulate the melanocytes� functional abilities,� explains Boissy, UC professor of dermatology and principal investigator for the study. �This is an important discovery because many pigment diseases are the result of deregulation of the melanocyte.�

�Now we have a new set of molecules to investigate that may help create uniform skin color�both for patients with pigment disorders or serious burn wounds as well as those seeking improved cosmetic skin appearance,� he adds.

The UC-led study, published in the September issue of The FASEB Journal, is the first to identify a specific model for manipulating melanin production in the body by using keratinocytes.

Previous research has shown that keratinocytes receive �packages� of pigment granules (melanosomes) from melanocytes. In dark-skinned people, these packages are dispersed throughout the cell individually, creating a larger surface area that absorbs more light than skin cells of light-skinned people, which disperse pigment in clusters.

�This was the first clue that keratinocytes played a role in skin coloration outside of genetic factors regulating the melanocyte,� says Boissy. �Further study showed there was no informational difference between the melanosomes in keratinocytes for dark and light skin responsible for sorting within the keratinocyte. The cells sorted themselves based on ethnic background, so we wanted to learn more about the factors that influence skin pigmentation.�

For this study, Boissy and his team developed a human skin substitute model using a combination of keratinocytes and melanocytes derived from donated light and dark skin. These mixed cells were transplanted into a mouse model and allowed to grow into the skin substitute for about three months.

�We found that by transplanting keratinocytes from light-skinned individuals to bioengineered skin substitutes produced a lightening effect,� says Boissy. �The same effect resulted when keratinocytes from dark-skinned individuals were transplanted into the skin substitute, creating a darkening effect.

�Surprisingly,� he adds, �intermediate skin color was obtained when melanocytes and keratinocytes were combined from light and dark skin together.�

In addition, the researchers discovered that the keratinocytes also influenced how much pigment is actually produced. Boissy says the effect is subtle, but it shows that it�s not just genetics of the melanocyte that determines skin coloration.

Increased distance to physician associated with thicker skin cancer at diagnosis

Mon, 20 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The farther patients travel to reach the physician who diagnoses their melanoma, the more likely they are to have thicker skin cancer at diagnosis, according to a report in the August issue of Archives of Dermatology, one of the JAMA/Archives journals.

�Survival for patients with melanoma is dependent on stage at diagnosis. As Breslow [depth of tumor cells in the skin] thickness increases, overall survival decreases,� according to background information in the article. �Consequently, early diagnosis may substantially improve patient outcomes. Because melanoma can only be definitively diagnosed based on biopsy findings, diagnosis requires detection of the suspicious lesion and biopsy. Some primary care providers perform diagnostic biopsies, but many prefer to refer patients to dermatologists or surgeons.�

Karyn B. Stitzenberg M.D., M.P.H., of the School of Public Health, University of North Carolina at Chapel Hill, and colleagues examined the effect of travel distance�and other factors such as age, sex, poverty rate, living in rural areas and the number of physicians in the area�on access to diagnosing clinicians for 615 patients with melanoma. Patients� Breslow thickness was also measured.

The median (midpoint) distance to a diagnosing physician was 8 miles. The median Breslow thickness was 0.6 millimeters. For each one-mile increase in distance, average Breslow thickness at diagnosis increased by 0.6 percent. Patients who traveled more than 15 miles had tumors 20 percent thicker than those of patients who traveled 15 miles or less. Patients from rural counties traveled an average 2.4 miles farther to their diagnosing clinician than those from metropolitan counties. Those from counties with at least one dermatologist traveled an average 8.3 miles less than those without a dermatologist in their counties.

Breslow thickness was also associated with age and poverty. �For each 1 percent increase in poverty rate, Breslow thickness increased by 1 percent. Breslow thickness was 19 percent greater for patients aged 51 to 80 years than for those aged 0 to 50 years and was 109 percent greater for patients older than 80 years than for those aged 0 to 50 years,� the authors write. �Sex, rurality and supply of dermatologists were not associated with Breslow thickness.�

�Further work is needed to characterize the determinants of distance to diagnosing provider, as well as the pathways and barriers to melanoma care,� the authors conclude. �Once potential barriers are identified, interventions can be developed to minimize the effect of travel distance and other sociodemographic factors on access to melanoma care.�

Natural chemical found in broccoli helps combat skin blistering disease

Mon, 20 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Johns Hopkins scientists have found yet another reason why you should listen to your mother when she tells you to eat your vegetables. Sulforaphane, a chemical present at high levels in a precursor form in broccoli and related veggies (cauliflower, Brussels sprouts, etc.), helps prevent the severe blistering and skin breakage brought on by the rare and potentially fatal genetic disease epidermolysis bullosa simplex (EBS).

The researchers treated newborn mice with a severe form of EBS�so bad they all died within three days�with a topical solution containing sulforaphane and found marked improvement; after four days more than 85 percent of the treated mice were alive and blister-free. These findings appear online this week in Proceedings of the National Academy of Sciences.

The basis of EBS, notes study author Pierre Coulombe, Ph.D., professor of biological chemistry, lies in two specific genes that make proteins known as keratins. Normally, the keratins join together and form highly resilient fibers in the lower portion of skin, helping make it durable. If either keratin is defective, they don�t mesh and the lower skin tissue becomes unusually fragile and gets damaged from the mildest mechanical stress � leading to blistering pain, a higher risk of infection, and in the most severe cases, death.

�Humans have around 54 distinct keratins, many of which are similar in structure and function,� says Coulombe. �We figured we might be able to exploit this similarity and dial up a replacement by triggering the activation of a suitable signaling pathway in skin.� He predicted that sulforaphane might stimulate the formation of a surrogate skin-strengthening keratin to stand in for the defective one.

The desire to learn more about sulforaphane led Coulombe and his co-workers to Paul Talalay, M.D., professor of pharmacology who had previously identified sulforaphane as a cancer-preventive agent. �It turns out that treatment with low doses of sulforaphane triggers the expression of selected keratin genes in skin,� says Coulombe. �So we began what evolved into a highly rewarding collaboration and found it does indeed work in a mouse model for EBS.�

�This is the first suggestion that we may be able to treat this terrible disease,� adds Talalay, a co-author of this study. �And we didn�t need to invent a new drug; sulforaphane is naturally found in our diet.�

The team will next test whether sulforaphane can stimulate the proper keratin protein in the appropriate subset of human skin cells � a vital matter for any future medical hopes. Beyond that are issues of how effective a topical application would be on human skin, which is considerably thicker than mouse skin, as well as examining the long term effects of sulforaphane treatment.

�If we can clear these important hurdles, then sulforaphane can potentially be a tremendous therapeutic, with the added benefit of having anticancer properties,� Coulombe says. �And when you consider that the only current option for EBS is wrapping gauze around trauma-prone areas to minimize breakage, and otherwise avoiding infection and making sure blisters heal properly, then even a mild success would be a significant benefit for these patients.�

Role seen for cannabis in helping to alleviate allergic skin disease

Thu, 16 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Administering a substance found in the cannabis plant can help the body's natural protective system alleviate an allergic skin disease (allergic contact dermatitis), an international group of researchers from Germany, Israel, Italy, Switzerland and the U.S. has found.

Allergic contact dermatitis is caused by reaction to something that directly contacts the skin. Many different substances (allergens) can cause allergic contact dermatitis. Usually these substances cause no trouble for most people, but if the skin is sensitive or allergic to the substance, any exposure will produce a rash, which may become very severe. Allergic contact dermatitis affects about 5 percent of men and 11percent of women in industrialized countries and is one of the leading causes for occupational diseases.

An article describing the work of the international research group, led by Dr Andreas Zimmer from the University of Bonn, was published recently in the journal Science. The article deals with alleviating allergic skin disease through what is called the endocannabinoid system. Among the members of the group is Prof. Raphael Mechoulam of the Hebrew University of Jerusalem School of Pharmacy.

In earlier work, Prof.Mechoulam's research group at the Hebrew University isolated two naturally occurring cannabinoid (cannabis-like) components - one from the brain, named anandamide (from the word ananda, meaning supreme joy in Sanskrit), and another from the intestines named 2-AG. These two cannabinoids, plus their receptors and various enzymes that are involved in the cannnabinoids' syntheses and degradations, comprise the endocannabinoid system. These materials have similar effects to those of the active components in hashish and marijuana, produced from the cannabis plant.

Research by groups throughout the world has since shown that the endocannabinoid system is involved in many physiological processes, including the protective reaction of the mammalian body to a long list of neurological diseases, such as multiple sclerosis, Alzheimer's and Parkinson's.

In the article in Science, the researchers detail how the endocannabinoid system serves as a major regulator of cutaneous (skin) contact hypersensitivity (CHS) in a mouse model. In this model, they showed, for example, that mice lacking cannabinoid receptors display exacerbated inflammatory skin responses to an allergen.

Because the data indicate that enhanced activation of the endocannabinoid system may function to dampen the CHS response, the researchers administered cannabinoids such as tetrahydrocannabinol (THC), a constituent derived from the cannabis plant, to the experimental animals. They findings showed that the THC significantly decreased the allergic reaction in comparison to untreated mice.

In order to better understand the molecular mechanism that may contribute to the increased CHS in cannabinoid-receptor deficient mice, the researchers performed a series of experiments which showed that mouse skin cells produce a specific chemical (a chemokine) which is involved in the annoying disease reaction. Activation of the endocannabinoid system in the skin upon exposure to a contact allergen lowers the allergic responses through modulating the production of this chemokine.

The results thus clearly show a protective role for the endocannabinoid system in contact allergy in the skin and suggest that development of cannabinoid compounds based on elements produced from the cannabis plant could enhance therapeutic treatment for humans.

Green tea holds promise as new treatment for inflammatory skin diseases

Mon, 06 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Green tea could hold promise as a new treatment for skin disorders such as psoriasis and dandruff, Medical College of Georgia researchers say.

Researchers studied an animal model for inflammatory skin diseases, which are often characterized by patches of dry, red, flaky skin caused by the inflammation and overproduction of skin cells. Those treated with green tea showed slower growth of skin cells and the presence of a gene that regulates the cells life cycles.

Psoriasis, an autoimmune disease, causes the skin to become thicker because the growth of skin cells is out of control, says Dr. Stephen Hsu, an oral biologist in the MCG School of Dentistry and lead investigator on the study published in the Aug. 18 edition of Experimental Dermatology. In psoriasis, immune cells, which usually protect against infection, instead trigger the release of cytokines, which causes inflammation and the overproduction of skin cells.

Other autoimmune diseases with similar side effects include lupus, which can lead to skin lesions, and dandruff.

Green tea, already shown to suppress inflammation, helps by regulating the expression of Caspase-14, a protein in genes that regulates the life cycle of a skin cell.

That marker guides cells by telling them when to differentiate, die off and form a skin barrier, Dr. Hsu says. In people with psoriasis, that process is interrupted and the skin cells dont die before more are created and the resulting lesions form.

Animal models treated with green tea also showed reduced levels of proliferating cell nuclear antigen, a gene expressed when skin cells multiply. In psoriasis, the gene is over-expressed and speeds production of skin cells.

Before treatment, the antigen, PCNA, was present in all layers of the skin, Dr. Hsu says. Typically, PCNA is only found in the basal layer, the innermost layer where skin cells continually divide and new cells push the older ones to the skin surface, where they eventually slough off. After being treated with green tea, the animal models showed near-normal levels of PCNA in only the basal layers.

This research is important because some treatments for psoriasis and dandruff can have dangerous side effects, he says.

The traditional treatment of ultraviolet light and medication, while it can control the lesions and be used long term, may cause squamous cell carcinoma the second most common form of skin cancer, Dr. Hsu says. Some of the most effective anti-dandruff shampoos also have carcinogens in them. While the U.S. Food and Drug Administration allows that in small amounts, the bottom line is that we dont know the long-term effects of using those products continuously.

Green tea, which is plant-derived, may be an alternative, he says. But scientists must work to overcome some barriers with the treatment.

The chemicals in green tea are so active that they are oxidized too quickly when mixed with other ingredients. They also dissolve in water, which cannot penetrate the skins barrier.

Researchers are looking for a balanced formula that can dissolve in fats, which can permeate the skin, Dr. Hsu says.

There are no cures for autoimmune diseases. But it is possible that this is a non-toxic way to regulate them. We need further study on humans to determine the full effects.

Computer graphics spills from milk to medicine

Mon, 06 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new UC San Diego computer graphics model capable of generating realistic milk images based on the fat and protein content will likely push the field of computer graphics into the realms of diagnostic medicine, food safety and atmospheric science, according to a new study.

Computer graphics is no longer just about pretty pictures and realism for the sake of aesthetics. We have harnessed the math and physics necessary to generate realistic images of a wide range of natural materials based on what they are made of. With our approach, computer graphics can contribute to a handful of pressing problems, said Henrik Wann Jensen, a UC San Diego computer science professor and Academy Award winning computer graphics researcher. Jensen created the model with two colleagues from the Technical University of Denmark Niels Jørgen Christensen, an associate professor, and Jeppe Revall Frisvad, a Ph.D. student.

On August 8, 2007, the new graphics research will be presented at the Association for Computing Machinerys SIGGRAPH conference, the premier annual conference for the graphics and interactive techniques community.

If you tell the new computer graphics model how much fat and protein you want in your milk, the model will spit out the information you need to create a life-like milk image by determining how light will interact with your specified ratio of milk fats and proteins. Similarly, if you specify the concentration of algae and different minerals in a sample of ocean water, the same theoretical model will render the color of the water.

The new work extends well beyond milk and ocean water to a wide range of materials called participating media. The word participating refers to the fact that some of the light that hits the material is absorbed and not reflected.

In addition to creating images based on what the material is made of, the authors used the milk example to show that the new model can work backwards and determine how much fat and protein a sample of milk contains, based on just a digital picture of the milk.

Putting the model in reverse, grocery stores could identify spoiled meats, contaminants or other food safety issues if a particular food problem consistently and detectably changed the light scattering properties of the food, said Jensen.

The model has already provided insights into the mystery of bottle-green icebergs. In the SIGGRAPH paper, the authors show that their model agrees with the claim that bottle-green icebergs are, in fact, clean (non-green) icebergs that appear blue during the day but turn green as the sun sets.

The new research eliminates a long-standing roadblock and describes a way to use theoretical math and physics to generate realistic computer graphics of materials that absorb some light and are not made of perfect spheres. In other words, the paper marks a vast extension of the Lorenz-Mie theory, which is a complete solution to Maxwells equation for scattering of electromagnetic waves by a homogenous, spherical particle embedded in a non-absorbing medium. The Lorenz-Mie theory has been around for more than a century and was introduced to graphics in 1995. In computer graphics, it has been used to compute the optical properties of certain paints, plastics, clouds, atmospheric phenomena and other media that can be described as spherical particles embedded in a non-absorbing medium. The theory, however, has not been used to render the vast class of participating media, until now. In the past, determining the optical properties of participating media necessary for rendering realistic images has required extensive measurements and/or trial-and-error manual adjustments.

The new model eliminates the restrictions of the Lorenz-Mie theory for participating media such as milk, in which the embedded particles (primarily proteins, fat and vitamin B2) are not perfect spheres and the host medium (water) absorbs light.

If you are trying to generate realistic computer graphics, it is intuitive to specify what the material is made of, like the amount of fat and protein in the milk. In the past, we had to do a lot of observing and measuring to determine how the milk would scatter and absorb light, said Jensen. With our theoretical approach, a much wider range to people will be able to play a role in creating realistic images of natural materials.

We can visualize what specific particles like milk fats or proteins look like on their own. We can also visualize what a medium would look like if one particle type were missing. Having knowledge about the visual effect caused by each type of particle is incredibly valuable in many different contexts, explained Jeppe Revall Frisvad, a Ph.D. student from the Technical University of Denmark.

The new work may also help Jensen and colleagues extend their theoretical model for human skin, work that earned Jensen an Academy Award in 2004.

In 2006, at SIGRAPH, Jensen and UCSD computer science graduate student Craig Donner published a paper describing a model that generates realistic looking skin based on specified amounts of hemoglobin and melanin.

Jensen is now looking to extend the skin shading model so that it can predict the appearance of skin based on a detailed description of dermal structures other than hemoglobin and melanin. Understanding how structures within the skin scatter and absorb light could be important to the doctors who are using light to treat skin cancer and other skin diseases, Jensen explained.

Some of the inspiration for their model being presented at SIGGRAPH 2007 came from equations that physicists studying coated soot particles derived to deal with shortcomings in the Lorenz-Mie theory. Jensen and the students from Denmark also called upon their mother tongue, Danish, to pick apart a little-known paper published in 1890 in Denmark by the physicist Ludvig Lorenz, one of the two namesakes of the Lorenz-Mie theory. The report clearly outlined the math and many of the assumptions that are central to Lorenz-Mie theory.

Going through his assumptions carefully, we hit a series of ah-hah! moments in which we saw ways to address some of the assumptions that had made it difficult to generalize the Lorenz-Mie theory beyond perfect spheres, said Jensen.

Once their new theoretical model predicted the relevant physics for light hitting participating media, the researchers took the next step and made the results useful for computer graphics by determining how the light would actually scatter and be absorbed. It is this information that is used to render realistic images.

We have the first complete, bottom-up theoretical model that addresses the shortcoming of the Lorenz-Mie theory for participating media. It allows us to render computer graphics for absorbing materials and with non-spherical particles based on the contents of the material. I cant wait to see how others implement our model, said Jensen, who is making the model available to other researchers.

UCSD researchers discover cause of rosacea

Sun, 05 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Doctors can describe the symptoms of rosacea, a common inflammatory skin disease that causes facial redness and affects nearly 14 million Americans. They can tell patients what triggers can worsen their condition: spicy foods, heat, alcohol, even embarrassment. But until now, they could not explain what caused rosacea.

A team of researchers, led by Richard L. Gallo, M.D., Ph.D., professor of medicine and chief of the Division of Dermatology at the University of California, San Diego (UCSD) School of Medicine and the Dermatology section of the Veterans Affairs San Diego Healthcare System, has determined that it is not one, but a combination of two abnormal factors, that result in rosacea.

Its like having lots of gasolineand a match, said Gallo, principal investigator of the study which will be published in the August 5 online edition of Nature Medicine. In essence, the researchers found that over-production of two interactive inflammatory proteins results in excessive levels of a third protein that causes rosacea symptoms, a trifecta of unfortunate factors in people with rosacea, according to Gallo.

Rosacea, which has been called adult acne, usually affects people with fair skin, between the ages of 30 and 60. Unlike acne, rosacea isnt associated with a skin infection by one type of bacteria, although antibiotics are sometimes prescribed to treat its symptoms. A chronic condition, it gets worse over time and is generally cyclic, flaring up for a period of weeks to months, and then subsiding for a time. Current treatments are often not effective.

Gallo and his colleagues first observed in the laboratory that anti-microbial peptides small proteins of the bodys host defense system caused the exact same symptoms in the skin that rosacea does, such as redness, an increase in visible blood vessels, bumps or pimples. The peptides also reacted to the same triggers.

When we then looked at patients with the disease, every one of them had far more peptides than normal. said Gallo.

To learn why these patients have abnormal peptides, the researchers examined the source of these molecules. The precursor form of these peptides, called cathelicidin, is normally known for its function to protect the skin against infection. In other skin diseases, a deficiency of cathelicidin correlates with increased infection. In rosacea patients, researchers found the opposite was true; too much cathelicidin was present in their skin. They also observed that it was a different form than found in people without the skin disorder.

Patients with rosacea also had greatly elevated levels of enzymes called stratum corneum tryptic enzymes (SCTE). These enzymes turned the precursor into the disease-causing peptide. By injecting mice with the cathelicidin peptides found in rosacea, or adding SCTE, they increased inflammation in the mouse skin, thus proving that these abnormalities can cause the disease.

Too much SCTE and too much cathelicidin leads to the abnormal peptides that cause the symptoms of this disease, said Gallo. Antibiotics tend to alleviate the symptoms of rosacea in patients because some of them work to inhibit these enzymes. Our findings may modify the therapeutic approach to treating rosacea, since bacteria arent the right target.

Screening for fragile skin

Tue, 31 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) White Dorper breeders and owners are hoping to eradicate a genetic disorder causing a lethal fragile skin condition among some of their drought-hardy flocks.

The disease dermatosparaxis also exists in other breeds but White Dorper breeders are the first to opt for a mass flock screening program in Australia.

Their early adoption of a newly developed test should ensure this disease is effectively managed, NSW DPI research scientist, Dr Tracey Berg, said.

Dermatosparaxis is an inherited connective tissue disorder attributable to abnormal collagen in the skin which causes extreme skin fragility. Normal collagen provides elasticity and strength.

Dermatosparaxis most often affects lambs. They suffer tearing of the skin, usually in their inner thighs and under armpits. The severity of the condition results in death or euthanasia.

Attempts to stitch the skin usually fall apart, exacerbated when animals are handled to check the repair. Mild forms of the disease have been seen in adult sheep.

If unchecked now, there could be a potential problem for the sheep industry in the future, Angus McTaggart, federal board president of the Dorper Sheep Breeders Society of Australia, said.

The disease has been reported elsewhere in Merino, South African White Dorper and Border Leicester-Southdown sheep.

Similar conditions occur in cattle, cats and humans (Ehlers- Danlos Syndrome type VIIC).

After Brendon ORourke and Dr Berg confirmed and defined the disorder in Australian White Dorper flocks at the Elizabeth Macarthur Agricultural Institute (EMAI) at Camden in 2006, they then developed a DNA test to screen individual sheep for the defective gene.

They developed the test in mid-2006 at the request of breeder Malcolm Green with subsequent support from the Breeders Society.

The mutation exists in sheep from most of the Australian flocks weve tested, Dr Berg said.

Technical assistant Nelson Jimenez selects White Dorper hairs for analysis in the Regional Veterinary Laboratory at Camden. Of the substantial number of sheep tested, 20 per cent were carriers.

We have also received overseas submissions and detected carriers from several countries, so it is a world wide problem.

Dr Berg and her colleagues at EMAI are consequently recommending screening of all breeding stock, or at the very minimum, screening of all sires.

The latter is the first step in managing both damage to reputations and economic loss, former head of the Regional Veterinary Laboratory at EMAI, Dr Keith Walker, said.

The DNA test provides an avenue for genetically smarter breeding programs.

The breed society is taking advantage of reduced rate testing by being responsible for administering samples, invoicing and reporting results.

It will also note all results on its stud book registration records, to enable public scrutiny of both positive and negative pedigree discrimination by all breeders.

A number of cattle breed societies have embraced this approach, to reduce the incidence of genetic disorders. The new genetic test is available commercially from the Genetics laboratory at EMAI.

Scleroderma outlook improves as survival increases

Thu, 12 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Washington, D.C. -- Individuals with scleroderma are living significantly longer today, compared with 30 years ago, and the physicians who treat this rare disease of connective tissue hope the newer drugs now on the market may extend lives even further.

Scleroderma, a rare autoimmune disorder of unknown origin, results when collagen builds up in the bodys connective tissue and causes thickening of the skin. In the chronic and often progressive systemic form, scleroderma causes stiff joints and hardening of the internal organs and blood vessels.

In the July issue of the journal Annals of the Rheumatic Diseases, Georgetown University Medical Center professor Virginia Steen, M.D., studied 2,000 patients with scleroderma (also known as systemic sclerosis) treated between 1972 and 2001 at the University of Pittsburgh and found that 10-year survival steadily improved over those years by 12 percent-- from 54 percent to 66 percent.

This is really good progress, which we hope to improve upon, said Steen, a leading expert on the disorder who has helped make Georgetown University Hospital a national treatment center for scleroderma. In the 1980s, while at the University of Pittsburgh, she developed a natural history database of scleroderma patients and this database has continued to evolve into the largest in the United States.

The reason overall mortality has dropped, Steen says, is partly because a class of medications, angiotensin converting enzyme (ACE) inhibitors became available which dramatically improved the treatment of renal crisis. Renal crisis used to be almost always fatal and now it is a very treatable complication of scleroderma, she said. Now pulmonary arterial hypertension and pulmonary fibrosis, a condition that is traditionally the second-most frequent cause of death, is responsible for most of the mortality, but these conditions may be increasingly treatable, she said. Patients may develop either disorder, or both.

Before, it was kidney and then lung disorders that affected most of our patients, and now that we have successfully treated the kidneys, mortality due to lung disease has become the issue, Steen said. We are working on ways to use the newer medications to help treat these disorders, hoping to further improve overall survival.

While all scleroderma-related disorders are believed to affect as many as 900,000 people in the United States, only between 40,000 and 165,000 are diagnosed with systemic scleroderma, according to the National Institutes of Health (NIH). Like all scleroderma disorders, systemic scleroderma affects more women than men, and varies in severity.

In this study, Steen collaborated with co-author Thomas Medsger, M.D., professor of medicine at the University of Pittsburgh to study patients with systemic scleroderma enrolled in the registry. They studied patients evaluated at the University of Pittsburgh between 1972 and 2001, dividing them into five-year time periods, depending on when they were seen.

They found survival improved in each of the five-year periods, and that the frequency of death due to renal crisis significantly decreased over the 30 years, from 42 percent to 6 percent. But the proportion of patients who died from pulmonary fibrosis increased from 6 percent to 33 percent, Steen said. The frequency of pulmonary hypertension also increased, but there was no change in gastrointestinal and heart-related deaths.

Use of ACE inhibitors made all the difference in saving patients from renal failure, and now it is important that physicians use drugs now available to treat lung disorders and researchers continue to search for new therapies, Steen said.

Skin rash actually signifies better outcomes for pancreatic and lung cancer patients

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The appearance of a rash in cancer patients treated with erlotinib (Tarceva) is strongly associated with longer survival, according to researchers from the drugs developer, OSI Pharmaceuticals, Inc. This is not the first time that rash has been associated with a survival advantage with EGFR inhibitors a class of drugs which includes erlotinib, cetuximab, panitumumab and others designed to block overproduction of the epidermal growth factor receptor but it is the most detailed analysis to date.

The study, published in the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, reports that for patients taking Tarceva who developed a moderate to severe rash, survival without progression of disease was 245 percent longer than in patients who had a mild rash or none at all. In fact, in the majority of cases, the more severe the rash, the longer a patients cancer was held in check, researchers found.

This rash, which often looks like acne, can be unpleasant enough for some people to consider discontinuing treatment, but it is important for physicians and patients to understand that this a positive event because it means there is likely to be a better clinical outcome, said the lead author, Bret Wacker, MS Director of Biostatistics at OSI Pharmaceuticals, Inc. Further studies are needed to both identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy.

Although few patients dropped out of the large Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer due to the rash, Wacker said he fears those who are taking Tarceva outside of a clinical trial may be likely to stop treatment.

Some patients are stopping treatment because of the rash, yet those are the ones who are most likely to benefit, Wacker said. This is a critical problem and rather than permanently discontinue treatment, patients should talk to their doctor about an effective and proactive strategy to manage the rash while continuing Tarceva therapy.

According to the researchers, these rashes can be controlled with mild steroids or antibiotics, and in most cases, they will improve with treatment. They are believed to be due to an inflammatory response as a result of EGFR inhibition in skin tissue, Wacker said.

The analysis looked at two placebo-controlled, double-blind, randomized, Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer - studies which led to approval of the agent for treating both cancers. Wacker and his team excluded patients who died in the first month after starting the study because they may not have had time to develop the rash or the rash may have been under-reported in these ill patients.

Of the 673 patients in the lung cancer study, called BR.21, and in the Tarceva-treated group, 81 percent developed a rash, the majority of which was grade 2 (The study graded rashes from 1, relatively mild, to 4, severe). The researchers found that the presence of any rash correlated with overall and progression-free survival and that these correlations increased with the grade of rash. Specifically, Tarceva-treated patients who did not develop a rash survived a median of 3.3 months, compared to 7.1 months for those with a grade 1 rash, and 11.1 months for patients with more severe, grade 2 rashes.

They also found, however, that 18 percent of patients treated with a placebo also developed a rash, and that overall survival in these patients was also significantly longer (a median of 8.2 months compared to 4.7 months), compared to placebo patients who didnt develop a rash. We dont know why some patients treated with a placebo developed a rash, but it could be due to the strength of their immune system, and that is why they survived longer, Wacker said.

In the second clinical trial (known as PA.3) that tested Tarceva and the chemotherapy drug gemcitabine against a placebo drug and gemcitabine in 521 patients with advanced pancreatic cancer, 71 percent of patients using Tarceva/gemcitabine developed a rash, compared with 30 percent of patients in the placebo group.

This increased rate of rashes in the placebo group makes some sense, Wacker said, because rashes are known to occur with use of gemcitabine chemotherapy. But, unlike the BR.21 study, these pancreatic cancer patients with rashes in the placebo group did not experience an increase in survival compared to placebo group patients without a rash.

In the Tarceva treatment group, only a more severe rash of grade 2 or higher was associated with increased survival. Patients with a grade 2 rash survived a median of 10.8 months, compared to treated patients with no rash (5.4 months) or a grade 1 rash (5.7 months). These different results may be associated with the addition of gemcitabine with Tarceva, or the lower dose of Tarceva in this study, but we just dont know, he said.

Wacker points out that lack of a rash doesnt necessarily mean that patients will not benefit from Tarceva. A small percentage of patients who didnt develop a rash still had relatively long survival, he said. But, still, overall, patients who dont develop a rash dont do as well as those who do.

Natural signal holds promise for psoriasis, age-related skin damage

Thu, 28 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The body may hold a secret to normalizing skin cell growth that is over zealous in psoriasis and non-melanoma skin cancers and too slow in aging and sun-damaged skin, researchers say.

Phosphatidylglycerol, a natural body lipid or fat, appears to signal cells to normalize growth and maturation or differentiation. When we apply it to skin cells, we see the normalization ability, says Dr. Wendy B. Bollag, cell physiologist at the Medical College of Georgia.

Her research, published online in The Journal of Investigative Dermatology, helps piece together the signaling pathway that prompts skin cells to stop multiplying and start differentiating.

Perhaps most importantly it shows that bypassing that pathway one researchers suspect becomes dysfunctional in diseases like psoriasis and giving the signal itself restores normal differentiation of skin cells or keratinocytes.

The findings prompted Dr. Bollag and John Edwards, CEO of Apeliotus Technologies of Atlanta, to seek National Institutes of Health funding for yearlong study in animal models of mild psoriasis to see if it works, with human trials as the goal. Proof of principle is the first phase. If in vivo data looks promising, well put together a study we can take into the clinic, says Dr. Bollag. She and Apeliotus received an NIH Small Business Technology Transfer grant, which supports small businesses collaborating with U.S. research institutions to develop technologies and methodologies with commercial potential.

A Georgia Research Alliance Industry Partnership Grant will allow parallel studies in animal models of chronological aging and photoaging from too much sun exposure, Dr. Bollag says.

MCG and Apeliotus will work with Avanti® Polar Lipids, Inc., of Alabaster, Ala., which has a chicken-egg derived phosphatidylglycerol used primarily for lipid research. Avanti is developing different phosphatidylglycerol ointments or salves for the new studies. Dr. Bollag notes that the lipid, already used as drug-delivery mechanism in humans, has been ingested at higher doses, so she believes lower doses applied externally will be safe.

Glycerol, a precursor of phosphatidylglycerol, also is available commercially and used in many skin care products because its long been known to help skin retain moisture, so it looks and feels better. We think that, yes, its a water attractor, but we think it also has this additional role as a precursor for an important lipid signal in the skin, says Dr. Bollag. Naturally occurring glycerol is an important precursor for many things such as fat, phospholipids, various sugars and metabolic pathways in the body. Glycerol levels go up when you exercise, because you are using fats as fuel.

Shes shown that the channel, aquaporin-3, delivers glycerol to phospholipase D, resulting in the skin cell differentiation signal, phosphatidylglycerol. This is serving as a signal, like an elevator operator who says, This way for normal keratinocyte differentiation, says Dr. Bollag. Thats good because without it, you get abnormal differentiation in skin diseases like psoriasis, non-melanoma skin cancer, some of the dermatitises; in a lot of these conditions, the cells proliferate too much and dont differentiate properly. We think maybe in psoriasis, the phospholipase D and aquaporin-3 become disconnected so now they cant produce phosphatidylglycerol. If you only put glycerol on it, it may not help.

But it looks as though the signal does.

Her newest research, done in mouse skin cells in culture, showed that aquaporin-3 manipulation impacted phosphatidylglycerol generation. The glycerol was coming through aquaporin. If we blocked it, we stopped glycerol from coming through and we also blocked phosphatidylglycerol. Then we started manipulating the various players. We did some over expression of aquaporin and showed it promoted differentiated status of the keratinocytes.

Then we wondered what would happen if we actually gave phosphatidylglycerol itself, so we bypassed the whole aquaporin-phospholipase D system and we saw some interesting results.

Phosphatidylglycerol inhibited growth of rapidly growing skin cells and increased growth in slow-growing cells. MCG has a patent pending on the ability of phosphatidylglycerol to normalize skin cell function.

The key is cells are supposed to proliferate in this one layer, she says of the basal layer, where a skin cell divides, with one staying to divide again and the other expressing different genes, proteins and functions as it moves toward the surface. Without phosphatidylglycerol, cells can proliferate too much and differentiate improperly, Dr. Bollag explains.

Right before cells reach the layer that we actually see, called the cornified layer, they spit out lipids they synthesize to make the water permeability barrier then they basically die. But they leave behind these hard shells that give skin its mechanical strength. When you get older, you dont turn it over as well, Dr. Bollag says, explaining why despite ongoing cell turnover old skin looks, well, old.

As its name implies, aquaporin also transports water, but interestingly, researchers have learned its a lot better at delivering glycerol. Phospholipids are the fats that comprise most of the plasma membranes that encase cells. Skin cells secrete extra lipids to help provide the water permeability barrier that keeps organs and fluids inside where they belong as well as the mechanical barrier that protects the body from invaders. That would just kill a normal cell, but the skin can survive that, she says, plopping her elbow down on a table. Temperature regulation and sensation are two other major skin functions.

Long-term etanercept treatment reduces psoriasis severity without increased adverse events

Mon, 18 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Extended exposure to the psoriasis medication etanercept does not appear to cause more infections or adverse events than placebo, and improvements in several measures of disease severity were observed for up to 96 weeks of therapy, according to a study in the June issue of Archives of Dermatology, one of the JAMA/Archives journals.

Psoriasis, a chronic inflammatory skin disorder, usually requires long-term therapy, according to background information in the article. Serum and affected tissue levels of tumor necrosis factor (TNF) are elevated in patients with psoriasis compared with levels in uninvolved skin of patients with psoriasis and in healthy individuals, suggesting that TNF plays an important role in the pathogenesis of the disease, the authors write. Etanercept, which binds with TNF, has been approved to treat several inflammatory diseases, including psoriasis.

Stephen Tyring, M.D., Ph.D., The University of Texas Health Science Center at Houston, and colleagues conducted a phase 3 randomized, double-blind trial with an open-label extension (during which all patients were aware that they were taking the active drug) from May 23, 2003, through June 22, 2005. After a 12-week period during which 618 patients with moderate to severe psoriasis were randomly assigned to receive either placebo or 50 milligrams of etanercept twice weekly (the current recommended dosage for psoriasis) for 12 weeks, all 591 continuing patients (average age 45.7) received etanercept for up to 84 weeks. During this open-label period, safety and efficacy evaluations were completed every 12 weeks. Psoriasis severity was measured using the Psoriasis Area and Severity Index (PASI) score, where zero means no disease and 72 is the most severe disease.

Exposure-adjusted rates of adverse events, serious adverse events, infections and serious infections were similar for placebo and etanercept treatments, the authors write. Patients responded within two weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group.

Improvements in PASI scores peaked at week 48, and at the end of the study, 51.6 percent of the original placebo group and 51.1 percent of the original etanercept group improved by at least 75 percent. A total of 18.3 percent of patients developed antibodies to etanercept during the study, but these antibodies did not appear to cause adverse events or reduce the drugs effectiveness.

In conclusion, this study represents, to our knowledge, the longest continuous exposure of patients with psoriasis to 50 milligrams of etanercept biweekly and provides further insights into the safety and efficacy of high-dose etanercept therapy for the management of moderate to severe psoriasis, the authors conclude.

Rising skin cancer rates are more likely to affect wealthy people, says 12-year review

Mon, 11 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Skin cancer levels have shown a significant increase in Northern Ireland since the early 1990s and are more likely to affect men, older people and those living in more affluent areas, according to a study just published in the June issue of British Journal of Dermatology.

Researchers who looked at official cancer statistics for nearly 23,000 patients over a 12-year period, reported a 20 per cent increase in patients and a 62 per cent increase in skin cancer samples processed by pathology laboratories.

The figures also showed that the three most common skin cancers - basal cell carcinoma, squamous cell carcinoma and malignant melanoma - accounted for 27 per cent of all male cancers and 26 per cent of all female cancers.

These findings show that many patients will have more than one skin cancer, highlighting the need to analyse both patient numbers and sample numbers to provide an accurate picture of cancer levels says co-author Dr Susannah Hoey from the Dermatology Department at the Royal Victoria Hospital, part of theBelfast Health and Social Care Trust.

The three skin cancers we looked at all increased with age, with the exception of malignant melanomas, which showed a decrease in men aged 75 and over.

And there was a link between more patients living in wealthier areas and increased levels of malignant melanomas and basal cell carcinomas.

The team looked at data collected by the Northern Ireland Cancer Registry, at Queens University Belfast, from 1993 to 2004, analysing the records of patients diagnosed with the three most common skin cancers.

They found that men were 30 per cent more likely to suffer from basal cell carcinoma, the most common form of skin cancer, which affected some 1,444 people a year in Northern Ireland during the study period and accounted for 17 per cent of all reported cancers.

And men were twice as likely to suffer from squamous cell carcinoma than women, accounting for 357 of the 640 cases reported each year.

Women were, however, 30 per cent more likely than men to suffer from malignant melanoma - the least common, but most serious skin cancer - which averages 186 cases a year.

Being well-off was a disadvantage when it came to skin cancer.

Women living in affluent areas were 29 per cent more likely than people living in disadvantaged areas to suffer from basal cell carcinoma and nearly two and a half times more likely to suffer from malignant melanoma.

Men displayed a similar pattern. They were 41 per cent more likely to suffer from basal cell carcinoma if they lived in an affluent area and two and a half times more likely to suffer from malignant melanoma.

Affluence didnt, however, seem to affect squamous cell carcinoma.

Malignant melanomas showed the greatest increase over the 12-year study period, with a 48 per cent rise in patients and a 71 per cent rise in samples. Squamous cell caricoma patients rose by 28 per cent, with a 57 per cent rise in samples, and basal cell carcinoma patients rose by 13 per cent, with a 62 per cent rise in samples.

The majority of the people who live in Northern Ireland have fair skin and the 2001 census revealed that less than one per cent of the population belongs to a black or minority ethnic group adds co-author Dr Olivia Dolan, consultant dermatologist at the Royal Victoria Hospital.

This means that our results are less likely to be affected by different skin tones and ethnic origin than research carried out in countries with a greater ethnic mix.

The authors point out that the general increase in incidences of skin cancer, coupled with ageing populations, will place greater demands on dermatology and other related specialties over the coming years.

The number of people aged 60 and over is set to rise by more than a half by 2030 and 80 per cent of all skin cancers occur in this age group says Dr Dolan.

It is important that we plan ahead so that we are able to care for patients with skin cancer without compromising other chronic dermatological diseases.

The authors from the Dermatology Department at the Royal Victoria Hospital and Queens University Belfast - say that their research reinforces the need for anyone exposed to the sun to take sensible precautions, whether they are at home or on holiday.

Although our research highlights that some section of society face greater risks than others, the safe sun message is one that we all need to heed if we are to halt rising skin cancer rates concludes Dr Hoey.

Topical retinol helps reduce wrinkles associated with natural skin aging

Mon, 21 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Applying vitamin A to the skin appears to improve the wrinkles associated with natural aging and may help to promote the production of skin-building compounds, according to a report in the May issue of Archives of Dermatology, one of the JAMA/Archives journals.

The wrinkles and brown spots associated with aging appear first and most prominently on skin exposed to the sun, according to background information in the article. Human skin not exposed to the sun also ages but less dramatically, the authors write. In intrinsic, natural or chronological aging, skin loses its youthful appearance by becoming thinner, laxer and more finely wrinkled. These changes are readily appreciated by inspecting the upper inner arm. Thinner skin results from a reduced production of the protein collagen and may slow wound healing, presenting a public health issue. Safe and effective therapies to reverse the atrophy of natural skin aging do not exist currently, the authors note.

Reza Kafi, M.D., then of the University of Michigan Medical School, Ann Arbor, and now of Stanford Medical School, Palo Alto, Calif., and colleagues assessed the effectiveness of vitamin A (retinol) lotion in 36 elderly individuals (average age 87 years). Researchers applied a lotion containing 0.4 percent retinol to participants right or left upper inner arms, and lotion with no retinol to the other arm, up to three times a week for 24 weeks. Wrinkles, roughness and overall severity of aging were each graded on a scale from zero (none) to nine (severe) before treatment and two, four, eight, 16 and 24 weeks after beginning treatment. In addition, 4-millimeter biopsy specimens of skin were taken from both arms at the beginning and end of the 24-week treatment period.

A total of 23 individuals completed the full study and 13 withdrew from the study prior to completion. When the researchers included the individuals who had dropped out of the study by assuming their skin did not change after their last measurement, wrinkles, roughness and overall aging severity were all significantly reduced in the retinol-treated arm compared with the control arm. The skin biopsies revealed that the retinol increased the production of glycosaminoglycan and procollagen, structural components of the skin.

Topical retinol improves fine wrinkles associated with natural aging, the authors conclude. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement [reduction]. With greater skin matrix synthesis [production of compounds that form new skin], retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

First Demonstration of New Hair Follicle Generation

Thu, 17 May 2007 08:25:28 PST

( from http://www.rxpgnews.com ) Researchers at the University of Pennsylvania School of Medicine have found that hair follicles in adult mice regenerate by re-awakening genes once active only in developing embryos. These findings provide unequivocal evidence for the first time that, like other animals such as newts and salamanders, mammals have the power to regenerate.

âWe showed that wound healing triggered an embryonic state in the skin which made it receptive to receiving instructions from wnt proteins,â says senior author George Cotsarelis, MD, Associate Professor of Dermatology. âThe wnts are a network of proteins implicated in hair-follicle development.â

Researchers previously believed that adult mammal skin could not regenerate hair follicles. In fact, investigators generally believe that mammals had essentially no true regenerative qualities. The liver can regenerate large portions, but it is not de novo regeneration; some of the original liver has to remain so that it can regenerate.

In this study, researchers found that wound healing in a mouse model created an âembryonic windowâ of opportunity. Dormant embryonic molecular pathways were awakened, sending stem cells to the area of injury. Unexpectedly, the regenerated hair follicles originated from non-hair-follicle stem cells.

âWeâve found that we can influence wound healing with wnts or other proteins that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, such as hair follicles and oil glands, rather than just a scar,â explains Cotsarelis.

By introducing more wnt proteins to the wound, the researchers found that they could take advantage of the embryonic genes to promote hair-follicle growth, thus making skin regenerate instead of just repair. Conversely by blocking wnt proteins, they also found that they could stop the production of hair follicles in healed skin.

Increased wnt signaling doubled the number of new hair follicles. This suggests that the embryonic window created by the wound-healing process can be used to manipulate hair-follicle regeneration, leading to novel ways to treat hair loss and hair overgrowth.

These findings go beyond just a possible treatment for male-pattern baldness. If researchers can effectively control hair growth, then they could potentially find cures for people with hair and scalp disorders, such as scarring alopecia where the skin scars, and hair overgrowth.

Growth of regenerated hair follicles over 45 days. Arrows indicate hair shaft. The bulge is the area from which new hair shafts arise. The regenerated follicles possess normal stem cells and function normally by producing a hair shaft and cycling through growth phases. Image Credit: George Cotsarelis, MD, University of Pennsylvania School of Medicine; Nature

New survey ranks the nation's most and least sun-smart cities

Mon, 07 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) SCHAUMBURG, ILL. (May 7, 2007) -- Most Americans are familiar with the popular city rankings of the fattest cities, the fittest cities, the most livable cities and the most expensive cities. Now, in the first-of-its-kind survey, the American Academy of Dermatology (Academy) has identified the cities that take sun protection seriously and those that fail to make the grade despite repeated health warnings.

The RAYS: Your Grade survey polled adults in 32 U.S. metropolitan regions spanning 29 states on their knowledge, attitudes and behaviors toward tanning and sun protection. Cities were then ranked based on the percentage of people who scored As and Bs.

Based on our initial review of what people are currently doing, know and believe about sun protection, 35 percent of the national public score above average, with grades of A or B, said dermatologist Diane R. Baker, MD, FAAD, president of the Academy. From here, our goal is to move the needle so that we have 45 percent or even 50 percent starting to score in the A or B range.

Of the 32 cities and states ranked on their percentage of A and B grades, Washington, DC, was ranked No. 1, with 47 percent of its residents receiving As and Bs, followed closely by New York City which earned the No. 2 ranking. Dr. Baker also observed that Miami, Tampa and Los Angeles each noted for year-round sunny weather rounded out the top five rankings.

At the other end of the sun-smart spectrum, Chicago was ranked last of the 32 cities polled, earning the designation of the least sun-smart city and demonstrating the need for increased efforts to educate residents on the dangers of sun exposure. In this case, only 21 percent of Chicagoans received As and Bs on their tanning and sun protection knowledge, attitudes and behaviors.

In examining how the respondents in the top- and bottom-ranked cities fared in answering the 17 sun-smart survey questions, notable differences were found within specific cities. For example, in Washington, DC, there were three specific questions where respondents rated significantly higher than average. First, 45 percent of residents disagreed with the statement People look healthier with a tan the highest percent of all respondents who did not agree with this popular belief and 13 percentage points higher than the 32 percent average for all adults.

District of Columbia (DC) residents also werent fooled by the statement It is smarter to tan indoors using a tanning bed where ultraviolet rays can be controlled, stated Dr. Baker. Specifically, 68 percent of adults in the nations capital disagreed with this statement versus 58 percent of adults polled across all cities.

When asked whether Getting a base tan is a healthy way to protect skin from sun damage, DC residents also rated significantly higher than average 66 percent of respondents correctly disagreed with this statement, the highest of any city, versus 52 percent of adults overall. By comparison, Chicago ranked significantly lower than average when residents responses to 10 of the survey questions were examined. For example, Chicagoans laissez-faire attitudes toward sun protection were evident when comparing their answers about how much they worry about sun exposure to adults in other cities.

When asked if they agree or disagree with the statement I prefer to enjoy sunshine and not worry about what I should do to protect myself from it, 41 percent of Chicago respondents agreed, representing the highest number of respondents across all cities and 10 percentage points higher than the average of 31 percent. Similarly, approximately half of Chicagoans (49 percent) agreed with the statement Given my skin type, I dont worry too much about sun exposure far exceeding the 37 percent of all adults who agreed with this statement.

In addition, a high proportion of Chicagoans (40 percent) felt that the climate in which they live was a reason why they were not that worried about skin cancer implying that somehow their short period of sun exposure during the summer months could not cause enough damage to their skin to develop skin cancer. The notion that only people living in year-round sunny climates are prone to developing skin cancer is completely untrue, explained Dr. Baker. As dermatologists, we treat skin cancer patients living in all areas of the country from big cities to small towns, in tropical climates and snowbelt states. Studies also show that intense, intermittent sun exposure which typically involves residents of colder climates vacationing in warm, tropical areas during the winter months is a significant risk factor for developing future skin cancers.

Dr. Baker also noted 80 percent of the suns UV rays can pass through light clouds, mist, and fog and that snow can reflect more than 80 percent of the suns damaging ultraviolet radiation. The bottom line is that everyone needs to be concerned about protecting themselves from skin cancer, no matter where you live.

The rankings of the 32 metropolitan areas are as follows:

Clinical studies evaluate potential treatments for mouth ulcers

Mon, 16 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The drug pentoxifylline appears to have limited benefit in the first-line treatment of mouth ulcers due to recurrent apthous stomatitis, according to a report in the April issue of Archives of Dermatology, one of the JAMA/Archives journals. However, a second report in the same issue finds that a cream commonly used to treat eczema may be effective in patients with another ulcer-causing mouth disease, oral erosive lichen planus.

Mouth ulcers are among the most common oral health problems, according to background information in the articles. Recurrent apthous stomatitis is characterized by recurring episodes of mouth ulcers in an otherwise healthy individual, and affects approximately 20 percent of the population. Oral erosive lichen planus is a severe inflammatory condition that causes painful wounds in the mouth. Approximately 1 percent of the population is affectedabout the same percentage as are affected by psoriasisand those who develop the condition may lose weight because of pain during eating. Few effective treatments are available for either condition.

In the first study, Martin H. Thornhill, M.B.B.S., Ph.D., of the University of Sheffield School of Clinical Dentistry, Sheffield, England, and colleagues conducted a 60-day, randomized, double-blind trial in 26 individuals (average age 33) with recurrent apthous stomatitis. In a 60-day pre-trial phase, participants kept a daily ulcer diary in which they recorded the number and size of ulcers if any were present, and also the pain associated with them on a scale of one to 10. Then, 14 patients were assigned to take one tablet containing 400 milligrams of pentoxifylline three times per day for 60 days, while 12 took three placebo pills per day. Both groups continued to keep diaries and also returned to the clinic for examinations after 30 and 60 days, and again 60 days after completing treatment.

Patients taking pentoxifylline had less pain and reported smaller and fewer ulcers compared with baseline, the authors write. Patients taking placebo reported no improvement in these variables. Patients taking pentoxifylline also reported more ulcer-free days than those taking placebo. However, the differences were small and, with the exception of median ulcer size, did not reach statistical significance.

More patients taking the active treatment experienced adverse effects, including dizziness, headaches, stomach upset, increased heart rate and nausea. Sixty days after stopping treatment, all patients reported ulcers similar to those they had in the pre-trial phase.

Pentoxifylline did not prevent the ulcer episodes from occurring or result in a long-term cure, the authors conclude. Thus, given the potential for significant adverse effects and the small benefits of the drug demonstrated in this clinical trial, we cannot recommend pentoxifylline as the drug of first choice for treatment of recurrent apthous stomatitis, although it may have a second-line role in the management of patients unresponsive to other treatments or as an adjunct to other treatments.

In the second article, Thierry Passeron, M.D., and colleagues at the University of Nice, France, conducted a double-blind randomized trial of 1 percent pimecrolimus cream for the treatment of oral erosive lichen planus. Six patients received pimecrolimus cream and six received a placebo cream without the active ingredient; both applied the cream on mouth sores twice a day for four weeks. The efficacy of the treatment was measured along a 12-point clinical score, and the blood level of pimecrolimus was measured at the beginning of the study and again after 14 and 28 days.

In the pimecrolimus group, all the patients but one reported a moderate to important improvement of their symptoms and were satisfied by the treatment, the authors write. This improvement was observed from the first week of treatment, usually within the first two days, and most notably patients reported less pain when eating.

The average clinical score among those taking pimecrolimus decreased from 6.83 at baseline to 3.33 at day 28 of the study, while scores for the placebo group decreased from 4.67 to 3.33. The treatment was well tolerated in both groups with few adverse effects. However, all patients who improved during the trial had a relapse within a month following treatment.

According to the present data, 1 percent pimecrolimus cream seems to be an effective and well-tolerated treatment for oral erosive lichen planus, the authors write. Further studies on a larger population with long-term follow-up and monitoring of the blood level of pimecrolimus are required to better evaluate its usefulness and safety compared with other therapeutic modalities.

(Arch Dermatol. 2007;143:463-470, 472-476. Available pre-embargo to the media at

Detection of melanoma by dermatologists linked with earlier tumor stage, higher survival rates

Mon, 16 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Individuals whose melanoma is diagnosed by a dermatologist may be more likely to have early-stage cancer and to survive five years than those with melanoma diagnosed by a non-dermatologist, according to a report in the April issue of Archives of Dermatology, one of the JAMA/Archives journals.

Estimates suggest that melanoma will affect 1 in 52 men and 1 in 77 women in the United States during their lifetimes, according to background information in the article. If melanoma is removed at an early stage, when the tumor is still relatively thin (less than 1 millimeter thick), patients have a 90 percent cure rate. However, metastastic melanoma that has spread to other areas usually requires both surgery and chemotherapy and five-year survival rates are less than 20 percent. From a health policy perspective, whether a difference in melanoma outcome is associated with a patients physician type (specifically, dermatologists vs. non-dermatologists) is of particular interest to this discussion, the authors write.

Michelle L. Pennie, M.D., Emory University School of Medicine, Atlanta, and colleagues attempted to determine whether such a difference exists using data from two sources: Medicare enrollment and claims files from the government and a National Cancer Institute (NCI) database that includes information about patients demographics, date of diagnosis, stage of cancer at diagnosis and date of death. The researchers linked records from the two databases for 2,020 patients, comparing codes for different kinds of physician visits in the Medicare database to cancer diagnoses and outcomes in the NCI database.

Of the 2,020 patients, 1,467 (73 percent) were diagnosed with melanoma by a dermatologist and 553 (27 percent) were diagnosed by a non-dermatologist. Tumors diagnosed by dermatologists were thinner on average than those diagnosed by non-dermatologists (.86 millimeters vs. 1 millimeter). We also looked at melanoma stage at diagnosis and observed significant differences between provider types, with a preponderance of thin melanoma (stage zero, or stage I or II) in the dermatologist group and a preponderance of thick melanoma (stage III or stage IV) in the non-dermatologist group, the authors write.

After six months, two years and five years, patients whose cancer was diagnosed by a dermatologist had a higher survival rate than those diagnosed by a non-dermatologist. The two-year and five-year survival rates were 86.5 percent and 73.9 percent for the dermatologist group compared with 78.8 percent and 68.7 percent for the non-dermatologist group, the authors write. When looking at the mortality rates by cause of death, both groups had similar non-cancerrelated mortality rates. However, the dermatologist group had lower cancer-related mortality rates and a lower overall mortality rate.

Patients who visited dermatologists most likely had higher survival rates because their tumors were thinner and detected earlier, the authors note. Although the difference between a melanoma that is .86 millimeters thick and one that is 1 millimeter thick does not correlate with different clinical stages, tumor thickness is a powerful predictor of patient survival and a likely driver of the outcomes we observed, the authors write.

These results suggest that increasing access to dermatologists, particularly for older patients who have higher rates of melanoma, may represent one approach to improving melanoma-related health outcomes from a health policy perspective, the authors conclude.

MacroChem completes patient enrollment for Phase II trial of EcoNail for treatment of onychomycosis

Wed, 11 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Wellesley Hills, MA, April 11 -- MacroChem Corporation (OTCBB: MACM.OB) announced the completion of patient enrollment in a 40 patient U.S. multi-center open label Phase II efficacy study of EcoNail, a topical antifungal lacquer for the treatment of onychomycosis (nail fungus). EcoNail is the company's patented lacquer which contains the antifungal econazole and MacroChem's enhancer SEPA®.

Patients participating in the study, which is being conducted under MacroChem's U.S. Investigational New Drug application filed with the FDA, will receive 48 weeks of treatment and will undergo efficacy assessments using standard criteria of nail appearance and mycology. However, the Company will collect and evaluate 24-week interim data later this year. This trial was specifically designed, with the assistance of well-known onychomycosis experts, to address three important objectives: to assess early signs of efficacy, to maintain robust clinical endpoints in the full study, and, if successful, to facilitate advancement to Phase III as soon as possible.

Full enrollment in this Phase II study is an important milestone in advance of our planned interim assessment later this year. An earlier than originally intended evaluation of clinical data from a subset of patients treated for 24 weeks may be conducted to facilitate planning for potential future clinical development, stated Robert DeLuccia, President and CEO of MacroChem. He continued, I believe that the recent precedent-setting deal activity for topical nail fungus products in clinical development by two major international pharmaceutical companies reflects the high level of interest in the marketplace for new treatments for onychomycosis.

DeLuccia further noted: If we can develop a topical therapy without the treatment-limiting side effects experienced with the current market-leading oral products and with better efficacy than the only currently available topical product, we believe this could be a substantial commercial opportunity. We also believe that an effective, well-tolerated and easy-to-use topical onychomycosis therapy could both attract patients currently receiving other treatments and also expand the existing market to include patients who are not currently being treated.

Onychomycosis affects 20-30 million people in the United States alone, including nearly half of those over age 70. Untreated, the disease causes nails to thicken, resulting in localized pressure-related pain. Topical treatments currently marketed in the U.S. reportedly succeed in fewer than 12 percent of patients, and existing systemic treatments, which are effective in less than half of all cases, have known toxicity. Despite the shortcomings of these existing drugs, sales of treatments for onychomycosis top $1.5 billion annually worldwide.

Scientists implicate gene in vitiligo and other autoimmune diseases

Tue, 10 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In a study appearing in the March 22 New England Journal of Medicine, scientists supported by the National Institutes of Healths National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered a connection between a specific gene and the inflammatory skin condition vitiligo, as well as a possible host of autoimmune diseases.

Vitiligo is a chronic condition in which melanocytes (the cells that make pigment) in the skin are destroyed. As a result, white patches appear on the skin in different parts of the body. Similar patches also appear on both the mucous membranes (tissues that line the inside of the mouth and nose), and perhaps in the retina (inner layer of the eyeball). The hair that grows on areas affected by vitiligo sometimes turns white.

The researchers began a search for genes involved in vitiligo almost a decade ago with the help of the Vitiligo Society in the United Kingdom. In the beginning we were looking for multiple family members with vitiligo, says Richard Spritz, M.D., director of the Human Medical Genetics Program at the University of Colorado at Denver and Health Sciences Center and lead investigator for the study. The researchers sent a questionnaire to members of the society, asking them about their own vitiligo and whether other family members were affected. As part of the questionnaire, they also asked about other autoimmune diseases. What they learned was that vitiligo was very highly associated with a number of other autoimmune diseases, mostly thyroid disease, but also pernicious anemia, rheumatoid arthritis, psoriasis, lupus, Addisons disease, and adult-onset autoimmune diabetes.

That finding prompted the researchers to study families with multiple affected members and to look for similarities in genes among those who were affected. By searching the genome, they discovered a gene, NALP1, that was key to predisposing people to vitiligo and other autoimmune diseases, particularly autoimmune thyroid disease, says Dr. Spritz. We know that about 20 percent of people with vitiligo also get autoimmune thyroid disease, and this gene may be involved in mediating both of those, he says.

Dr. Spritz says the implications of this finding are exciting. The identified gene controls part of what is called the innate immune system, which is our bodys first defense against infection, he says. When we are attacked by viruses or bacteria, the innate immune system stimulates the inflammatory pathways and calls the rest of the immune system to action. NALP1 is probably a receptor for bacterial or viral signals. We dont know what these signals are, but now that we know what the gene is, we can use that knowledge to search for the signals that trigger autoimmune disease.

All autoimmune diseases involve the interaction of multiple genes and environmental triggers, he continues. You are born with your genes, but you are not born with these diseases. Something happens. We dont know what the triggers are that start these diseases, but if we did, maybe we could avoid them or even block the process. In fact, it may even be possible to actually stop the autoimmune disease, he says.

The most immediate application of this research might be for the disease that began the research: vitiligo. Doctors usually treat vitiligo with ultraviolet (UV) light to stimulate skin repigmentation. Scientists also know that there is one medication available (approved for treating rheumatoid arthritis) that blocks an inflammatory pathway thought to be controlled by NALP1. The possibility of combining a drug with UV light to improve vitiligo treatment is intriguing, and Dr. Spritz is now interested in finding out more about how the medication might affect people with vitiligo.

NIAMS Director Stephen I. Katz, M.D., Ph.D., calls the discovery of the NALP1-autoimmunity connection an important advance in the understanding of autoimmune diseases that collectively affect an estimated 15 million to 25 million Americans. The more we understand about these diseases, including the genes that predispose to them and the environmental factors that trigger them, the closer we come to better treatments and even preventive measures, he says.

Apple consumption during pregnancy reduces risk for childhood wheezing and asthma

Thu, 05 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON (April 5, 2007) -- Eating apples while pregnant may give new meaning to an apple a day keeping the doctor away. Compelling new research has concluded that mothers who eat apples during pregnancy may protect their children from developing asthma later in life. The study was published in Thorax online.

This unique longitudinal study tracked dietary intake by nearly 2000 pregnant women, then examined the effects of the maternal diet on airway development in more than 1200 of their children five years later. Among a wide variety of foods consumed and recorded by the pregnant women, the researchers concluded that the children of mothers who ate apples had a significantly reduced risk for the development of asthma and childhood wheezing.

This study focuses on medical evaluations for asthma and related symptoms (i.e., wheezing) when the children were five years old. As a result of the evaluations cited in this research, other than apples, there were no consistent associations found between prenatal consumption of a range of healthful foods and asthma in the 1253 children who were evaluated.

Children of mothers who ate apples during pregnancy were much less likely to exhibit symptoms of asthma (including wheezing), say the researchers who hail from institutions in The Netherlands and Scotland. These same researchers previously reported positive associations between maternal consumption of vitamins A, E, D and zinc with reduced risk of asthma, wheeze and eczema in children.

The only other positive association found between prenatal food intake and risk reduction in the children was with fish, for which the researchers found that children of mothers who ate fish had a lowered incidence of doctor-confirmed eczema.

According to the research, The present study suggests beneficial associations between maternal apple intake during pregnancy and wheeze and asthma at age five years. They add that their findings suggest an apple specific effect, possibly because of its phytochemical content, such as flavonoids. The research paper cites other related studies on apples, including those which found that intake of apples as a significant source of flavonoids and other polyphenols has been beneficially associated with asthma, bronchial hypersensitivity, and lung function in adults.

In 2004, the National Center for Health Statistics reported that nine million U.S. children have been diagnosed with asthma at one point in their lives and four million children suffered from asthma attacks that year. Others suffer from hidden asthma undetected or undiagnosed asthma, according the American Lung Association. The cost of this disease is great statistics show asthma to be the third-ranking cause of hospitalization among children under 15 and is among the leading causes of school absenteeism.

Gender linked to development of skin cancer

Sun, 01 Apr 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio -- Inherent gender differences instead of more sun exposure may be one reason why men are three times more likely than women to develop certain kinds of skin cancer, say researchers at Ohio State University Medical Center.

Squamous cell carcinoma is the second most common form of skin cancer, accounting for nearly 200,000 new cases in the United States each year. While occurring more often than melanoma, squamous cell carcinoma is not nearly as worrisome. Still, it can be lethal in some patients, especially those with suppressed immune systems, including transplant recipients or people who are HIV-positive.

Many studies have shown that the risk of squamous cell carcinoma increases with greater exposure to the sun. For years, investigators assumed that lifestyle had a lot to do with the disparity in the incidence of SCC believing that men spend more time outside and are less likely to use sun protection than women.

While that may be true, scientists at Ohio State have shown that there may be another, even more critical factor involved gender-linked differences in the amount of naturally occurring antioxidants in the skin.

The study appears in the April 1 issue of Cancer Research.

Dr. Tatiana Oberyszyn, an assistant professor of pathology and of molecular virology, immunology and medical genetics at Ohio State University Medical Center, has been studying non-melanoma skin cancers for years. She had a hunch there might be gender-related variables that accounted for the difference between male and female rates of developing these malignancies, and designed an experiment to find out what they might be.

A doctoral student in Oberyszyns laboratory, Jennifer Thomas-Ahner, subjected male and female mice to a single, identical, acute exposure to UVB light. It is UVB rays, as opposed to UVA or UVC rays in sunlight, that cause the most damage to the skin. Even a single, prolonged exposure is enough to cause inflammation (sunburn) and its attendant redness, swelling and increased vascular flow.

Thomas-Ahner compared various measures of the inflammatory response in the male and female groups, noting the degree of swelling, antioxidant levels, DNA damage in the skin and the levels of myeloperoxidase in the tissue. Myeloperoxidase is an enzyme that reflects the extent of neutrophil infiltration, the first step in the inflammatory response. Antioxidants help repair damaged DNA and also help clean up toxic byproducts of injured tissue.

She discovered significant differences between the two groups. The male mice registered a weaker inflammatory response than did the females, as measured by the thickness of their skin and myeloperoxidase levels. They also had more extensive DNA damage in their skin and lower antioxidant levels in their skin than the females.

In a second experiment, Thomas-Ahner exposed male and female mice to longer, chronic sun exposure, irradiating them three times weekly for 16 weeks. When the mice were 25 weeks old, she examined them for differences in tumor growth, size and number.

She found that male mice developed tumors earlier and had more tumors than did female mice. The tumors in the male mice also tended to be larger and more aggressive than were those in the female mice.

Oberyszyn and Thomas-Ahner also noted that the difference in the antioxidant capacity between male and female mice was present in the untreated skin as well as the treated skin. Oberyszyn, a member of the Ohio State University Comprehensive Cancer Center, believes that the greater amount of naturally occurring antioxidant capacity in the females accounted for their ability to thwart a certain degree of tumor growth and spread.

This is the first time anyone has ever looked at the effect of gender on the development of UVB-induced skin cancers in such a controlled environment, says Oberyszyn. Its given us clear evidence of a biological basis for the gender bias in developing squamous cell carcinoma.

Oberyszyn says other studies need to be done to validate the findings, but noted the data are compatible with other studies suggesting a potential biological basis for gender difference in the development of cancer and other diseases.

Smoking associated with aging of nonfacial skin

Mon, 19 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A history of smoking may be associated with a higher degree of aging in skin not regularly exposed to light, such as that of the upper inner arm, according to an article in the March issue of Archives of Dermatology, one of the JAMA/Archives journals.

The features of skin aged by the sun and exposure to light are well documented and include coarseness, wrinkling, discoloration and a pale yellow tint, according to background information in the article. The progression of this type of aging can be measured with photonumeric scales, which use standard photographs to assign numbers that correspond to grades of severity. However, no such scale exists for photo-protected (not exposed to sunlight) skin in areas such as the buttocks and upper arm. The principle sign of aging in this type of skin is fine wrinkling.

Yolanda R. Helfrich, M.D., and colleagues at the University of Michigan, Ann Arbor, used photographs of 82 healthy participants upper inner right arms to create a nine-point scale on which to grade aging of photo-protected skin as well as to analyze factors that affect the degree of aging. Participants ranged from age 22 to 91 and had an average age of 56.1, were 46 percent male and 54 percent female, and were all photographed in the same position by a professional medical photographer. Five photographs were selected from each individual to be analyzed by three separate judges and graded for severity of aging on a scale of zero (no fine wrinkling) to eight (severe fine wrinkling). Interviews were conducted to obtain health and lifestyle information.

The three judges largely agreed on the grading scale for each participant; the maximum range of difference in scores for a single individual was less than one unit on the nine-point scale. These results indicate that this scale is an uncomplicated evaluation system for the clinical investigator involved in the assessment and treatment of photo-protected aging skin, the authors write.

In this study examining non-facial, photo-protected skin, we found that the number of packs of cigarettes smoked per day, total years of smoking and pack-years of smoking [an average of packs per day over the number of years were smoking] were correlated with the degree of skin aging. After controlling for participant age and other variables in a multiple regression model, we found that only packs of cigarettes smoked per day was a major predictor of the degree of photo-protected skin aging, they continue. In participants older than 65 years, smokers had significantly more fine wrinkling than non-smokers. Similar findings were seen in participants aged 45 to 65 years.

The process by which photo-protected skin ages, and how smoking may affect that process, remains unclear. Additional research is needed to shed light on independent risk factors for fine wrinkles in this skin type, the authors note.

Molecular differences between early and advanced melanomas could provide new drug targets

Mon, 12 Mar 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The cell-signaling molecule Akt is a primary trigger that leads malignant melanomas on the skin's surface to begin growing vertically beneath the skin and turn into deadly invasive cancers, scientists have found. Understanding this key molecular difference between radial melanomas that spread on the surface of the skin and melanomas that grow vertically and invasively could provide new targets for the development of drugs to treat individuals with advanced stage melanomas.

Radial melanomas that have not spread below the skin can be treated surgically and have a survival rate of 98 percent beyond five years, according to the American Cancer Society. But when melanomas grow downward, the tumors become highly resistant to chemotherapy and radiation and the five-year survival rate falls rapidly, to 64 percent if the disease has reached the lymph nodes and 16 percent if it has spread to other organs.

The discovery of Akt's significant role in the progression of melanomas was made by scientists in the Department of Dermatology at Emory University School of Medicine and published in the March issue of the Journal of Clinical Investigation. Senior author is Jack L. Arbiser, MD, PhD, and lead author is Baskaran Govindarajan, PhD.

When the scientists introduced the gene for Akt into radial growth melanoma cells, the cells expressed nearly eight times as much of the growth factor protein VEGF. VEGF is known to be a powerful stimulator of angiogenesis Ð the growth of microscopic blood vessels that nourish cancerous tumors and lead to unregulated cell growth. When melanoma cells overexpressing Akt were introduced into immunocompromised (nude) mice, the mice developed aggressive tumors that expressed high levels of VEGF, whereas a control group of mice developed no tumors.

Another result of Akt overexpression was the increased production of reactive oxygen (ROS). Reactive oxygen is created during cellular metabolism and has long been associated with triggering angiogenesis and the resulting growth of tumors. The scientists also found that the Akt-induced melanoma cells produced more of the enzyme NOX4, one of the NOX family of genes known to increase generation of ROS and to trigger angiogenesis.

The scientists also found that in cells with greater Akt expression, there was an increase in impaired mitochondria-- the energy factories of cells. Their research showed, however, that these mutations in mitochondria were likely the result of the prolonged exposure to increased oxidative stress caused by Akt overexpression, but that the mitochondrial mutations were not essential for the aggressive growth of melanomas induced by Akt.

Our research shows that Akt overexpression on its own is sufficient to transform radial growth melanoma cells into highly invasive tumors via reactive oxygen pathways, says Dr. Arbiser. This could provide us with promising targets for anti-cancer drug therapy. We will continue to work on refining the exact mechanisms of how Akt influences the aggressive growth of melanomas.

Injection of 'skin filler' material appears to stimulate collagen production

Mon, 19 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Injections with dermal fillers containing hyaluronic acid appear to stimulate production of collagen, a primary protein in the skin, and may partially restore the structure of sun-damaged skin, according to an article in the February issue of Archives of Dermatology, one of the JAMA/Archives journals.

Injectable skin fillers have become increasingly popular for correcting the lines and wrinkles associated with aging, as well as acne scars and other skin conditions, according to background information in the article. Hyaluronic acid, a compound that occurs naturally in the skin and connective tissue, is among the most widely used fillers in the United States. Its molecules bind to water in the skin, hydrating and firming its structure, and the loss of hyaluronic acid with aging is associated with skin dehydration and wrinkling. Because hyaluronic acid degrades rapidly in the skin, the commercially available version is cross-linked, or bound to itself chemically to increase stabilization.

Frank Wang, M.D., and colleagues at the University of Michigan Medical School, Ann Arbor, injected non-animal stabilized hyaluronic acid (NASHA), one of the most commonly used forms, into the forearms of 11 healthy volunteers (average age of 74 years). All participants were fair-skinned, and eight had moderate sun damagevisible as brown spots, drooping skin, wrinkles or uneven pigmentationwhile three had mild to moderate damage. They received three injections of .7 milliliters of stabilized hyaluronic acid 2 to 5 centimeters apart in one forearm, and three injections of saline solution at the same volume and spacing in the other arm. Skin biopsy samples approximately 4 millimeters in diameter were taken from the site of the injection four and 13 weeks later.

It is commonly assumed that fillers achieve their effects by filling space in the skin; through examining the skin samples under an electron microscope, the researchers found that this appeared to be the case with stabilized hyaluronic acid. To further investigate potential mechanisms for this filler's long-lasting cosmetic benefits, we assessed the biological response of skin to NASHA, the authors write. We found that NASHA injections induce type 1 collagen production in photo-damaged forearm skin. Because there is currently no evidence that skin on different parts of the body behave differently, it is likely that hyaluronic acid has the same effect on facial skin.

Overall, our findings indicate that NASHA injections induce robust collagen production through several potential mechanisms, including the mechanical stretching of fibroblasts [cells that secrete collagen proteins], stimulation of growth factors and inhibition of collagen breakdown, the authors write. Of these, mechanical stretching may be the most important. This physical stretching of the cells encourages them to produce compounds that both support collagen growth and suppress chemicals that break down cells' structures.

These findings suggest that, in addition to its cosmetic benefits, hyaluronic acid may be beneficial in skin-wasting diseases that involve collagen deficiencies, such as those associated with HIV or steroid use.

Multiple low-energy plasma skin treatments may help diminish facial wrinkles

Mon, 19 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) A study involving eight patients suggests that multiple low-energy treatments with a plasma skin regeneration tool may help to reduce wrinkles and improve facial appearance with minimal healing time, according to an article in the February issue of Archives of Dermatology, one of the JAMA/Archives journals. The multiple treatments have about the same effect as one high-energy session but with less healing time.

Plasma is a unique state of matter in which electrons are stripped from atoms to form an ionized gas, the authors write as background information in the article. During plasma skin regeneration, energy from plasma is emitted in millisecond-long pulses to target skin tissues. The energy level is set manually on the device, which is, according to the authors, cleared by the U.S. Food and Drug Administration for multiple, single-pass, low-energy treatments and single-treatment, one-pass, high-energy treatment of facial rhytids (wrinkles) and for the treatment of superficial skin lesions. Previous studies have primarily focused on high-energy single treatments for acne scarring or wrinkle reductions, which may be effective but require a week or more for healing.

Melissa A. Bogle, M.D., then at SkinCare Physicians, Chestnut Hill, Mass., and now at the Laser and Cosmetic Surgery Center of Houston, and colleagues gave three full-face, low-energy treatments to eight volunteers every three weeks. Before the second and third treatment, the quality of the new skin grown over the treated area, amount of healing time and redness was recorded. Four days following each procedure, and again one and three months after the last procedure, patients were photographed and their skin was examined. Physicians rated participants' wrinkles on a nine-point scale, which was based on rated photos of other patients and not previous photos of the same patient; patients also rated the treatments' effectiveness. Skin biopsies were also taken from six patients before and 90 days after all three procedures.

Three months after treatment, the participants had 37 percent fewer wrinkles as judged by the researchers, and the patients reported a 68 percent improvement in overall facial appearance. Tissue had re-grown over the treated area after four days, while patient-reported redness lasted six days. No scarring or loss of pigment occurred. When examining the biopsied skin tissue under a microscope, the researchers found that a new band of collagen, the primary protein in skin, had formed in the inner layers of the skin.

The healing time in our study averaged approximately five days per treatment; however, this was a patient-assessed number that included days it took for any residual redness and peeling to completely resolve, the authors write. While nearly a week of healing time may not seem to be an improvement over other minimally invasive resurfacing procedures and micropeels, the intensity of the healing process is quite minor, which makes it an attractive option for many patients.

Vitamin D3 protects the skin from harmful microbes

Fri, 09 Feb 2007 03:02:45 PST

( from http://www.rxpgnews.com )

Skin wounds breach the physical barrier that protects the body from harmful microbes in the environment. To counter this breach, wounding triggers an immune response that includes the production of antimicrobial peptides and the upregulation of receptors that recognize microbial components. However, the factors that trigger this immune response have not been well defined.

In a study appearing online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, Richard Gallo and colleagues from the University of California at San Diego now show that wounding to the skin of humans triggers the production (by skin cells known as keratinocytes) of the active form of vitamin D3, and that this induces increased expression of the antimicrobial peptide cathelicidin and the microbial recognition receptors TLR2 and CD14. Further analysis showed that wounding induced keratinocyte expression of the enzyme responsible for converting inactive vitamin D3 to active vitamin D3 (CYP27B1) and that this could be recapitulated in vitro by culturing keratinocytes in the presence of the soluble factor TGF-beta-1. The authors therefore suggest that soluble factors present in wounds, such as TGF-beta-1, induce the expression of CYP27B1, which enables keratinocytes to produce active vitamin D3 that, in turn, induces the upregulation of some components of the immune response and protects us from harmful microbes.

Human skin harbors completely unknown bacteria

Mon, 05 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK, Feb. 5, 2007It appears that the skin, the largest organ in our body, is a kind of zoo and some of the inhabitants are quite novel, according to a new study. Researchers found evidence for 182 species of bacteria in skin samples. Eight percent were unknown species that had never before been described.

It is the first study to identify the composition of bacterial populations on the skin using a powerful molecular method. Not only were the bacteria more diverse than previously estimated, but some of them had not been found before, says Martin J. Blaser, M.D., Frederick King Professor and Chair of the Department of Medicine and Professor of Microbiology at NYU School of Medicine, one of the authors of the study.

The skin is home to a virtual zoo of bacteria, he says. This study is publishedFebruary 5, 2007, in the online edition of the Proceedings of the National Academy of Sciences.

The researchers analyzed the bacteria on the forearms of six healthy subjects; three men and three women. This is essentially the first molecular study of the skin, says Dr. Blaser. The skin has been, he says, terra incognita, an unknown world that he and his colleagues have set out to understand much like explorers.

There are probably fewer than ten labs in the U.S. looking at this question, says Dr. Blaser. It is very intensive work, he adds. Zhan Gao, M.D., senior research scientist in Dr. Blaser's lab, led the research, which took more than three years to complete.

Some of the bacteria on the skin appear to be more or less permanent residents; others are transient, according to the study.

This research is part of an emerging effort to study human microbial ecology. Dr. Blaser's laboratory has previously examined the bacterial population in the stomach and the esophagus. Many of the bacteria of the human body are still unknown, he says. We all live with bacteria all our lives and occasionally we smile, so they're not that bad for us.

The most numerous cells in our body are microbialthey outnumber our cells 10 to 1. The body has microbes native to the body, including the skin, and these populations change according to how we live, he says. Ultimately what we want to do is compare disease and health, says Dr. Blaser. Keeping bacterial populations in our body stable may be part of staying healthy, he says.

In the new study, the researchers took swabs from the inner right and left forearms of six individuals picking the region halfway between the wrist and the elbow for its convenience. It's not where they wash their hands, explains Dr. Blaser. And they don't have to undress. The researchers wanted to be able to compare two similar parts of the body. Because they also wanted to study change over time, they took swabs from four of the individuals 8 to10 months after the first test.

Roughly half, or 54.4%, of the bacteria identified in the samples represented the genera Propionibacteria, Corynebacteria, Staphylococcus and Streptococcus, which have long been considered more or less permanent residents in human skin.

The six individuals differed markedly in the overall composition of the bacterial populations on their skin. They only had four species of bacteria in common: Propionibacterium acnes, Corynebacterium tuberculostearicum, Streptococcus mitis, and Finegoldia AB109769. This is a surprise, says Dr. Gao. But many things affecting the skin affect bacteria, such as the weather, exposure to light, and cosmetics use.

Almost three-quarters, or 71.4%, of the total number of bacterial species were unique to individual subjects, suggesting that the skin surface is highly diversified in terms of the bacteria it harbors, according to the study.

Three bacterial species were only found in the male subjects: Propionibacterium granulosum, Corynebacterium singulare, and Corynebacterium appendixes. While the sample is too small to draw conclusions, the scientists believe that women and men may harbor some different bacterial species on their skin.

In each individual, the bacterial populations varied over time while revealing a core set of bacteria for each individual. The predominant bacteria don't change much, says Dr. Gao. But the more transient bacteria did change over time, she says.

What that suggests, adds Dr. Blaser, is that there is a scaffold of bacteria present in everybody's skin. Some stay and others come and go.

Scientists see DNA get 'sunburned' for the first time

Thu, 01 Feb 2007 04:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS , Ohio -- For the first time, scientists have observed DNA being damaged by ultraviolet (UV) light.

Ohio State University chemists and their colleagues in Germany used a special technique to watch strands of DNA in the laboratory sustain damage in real time.

They observed the most common chemical reaction among a family of reactions on the DNA molecule that are linked to sunburn, and discovered that this key reaction happens with astounding speed -- in less than one picosecond, or one millionth of one millionth of a second.

Scientists are studying UV damage to understand the role it plays in sunburn and diseases such as skin cancer. This new finding, reported in the current issue of the journal Science, shows that the damage depends greatly on the position of the DNA at the moment the UV strikes the molecule.

UV light excites the DNA molecule by adding energy, said Bern Kohler, associate professor of chemistry at Ohio State. Some exited energy states last a long time, and others a short time. The energy often decays away harmlessly, but occasionally it triggers a chemical reaction that alters the DNA's molecular structure.

Previously, scientists believed that the longer a DNA molecule was excited by UV energy, the greater the chance that it would sustain damage. So long-lived excited states were thought to be more dangerous than short-lived ones. But this study shows that the most common UV damage is caused by a very short-lived excited state.

The speed of this reaction has important consequences for understanding how DNA is damaged by UV light, said Kohler. In this study, we didn't see any evidence that long-lived energy states are responsible for damage. Now it seems more likely that short-lived states cause the most common chemical damage to DNA.

That damage consists of two tiny molecular bonds that form where they shouldn't -- between two thymine bases stacked together among the billions of bases in the DNA double helix.

DNA employs some chemical reactions of its own to heal itself. But when DNA sustains too much damage, it can't replicate properly. Badly damaged cells simply die -- the effect that gives sunburn its sting. Scientists also believe that chronic damage creates mutations that lead to diseases such as skin cancer.

For this study, the chemists used a technique called transient absorption to observe the DNA damage. Transient absorption is based on the idea that molecules absorb light at specific wavelengths, and it allows researchers to study events that happen in less than a picosecond.

They took specially designed strands of DNA -- ones made solely of thymine bases, in order to boost the chance of observing a reaction between adjacent thymines -- and exposed them to UV light. Then they timed the reactions that caused the new thymine bonds to form.

Kohler stressed that he and his colleagues examined damage to isolated DNA strands, not DNA within a cell. Sunburn results from a series of chemical reactions in a living cell, and so this experiment did not allow them to see a cell sustain sunburn.

This is, however, the first time anyone has observed the initial molecular events behind damage to DNA. Kohler thinks the results might make scientists attack the problem of UV damage in a new way.

DNA in a cell is always moving, he explained. It bends and twists one way or another because it is a relatively flexible molecule. This flexibility enables the normal chemical reactions that are constantly happening in the cell. Each shape-shift can require anywhere from a few to several hundred picoseconds to complete.

That's fast, but this new study shows that UV damage happens many times faster. On the timescale that the unwanted bonds form, even a rapidly moving DNA molecule would essentially appear frozen.

That means that whether or not two thymine bases are damaged depends on the position of the DNA during the extremely brief time required for it to absorb UV light. Either two thymine bases are lined up in just the right way to bond when the UV hits, or they're not.

This insight explains why some pairs of thymine bases get damaged more frequently than others, and it suggests that scientists can understand damage patterns to DNA by studying the factors that influence how the bases are arranged in space, Kohler said.

In our efforts to understand photo-damage, this new result shifts our attention to the DNA structure, and the kinds of arrangements that exist at the moment DNA absorbs light.

Chemicals in brown algae may protect against skin cancer

Thu, 25 Jan 2007 04:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS , Ohio Substances extracted from a marine seaweed may protect against skin cancer caused by too much sun, new research suggests.

The animal study indicates that chemicals called brown algae polyphenols (BAPs), which are found in a type of brown marine seaweed, might protect against skin cancers caused by ultraviolet B (UVB) radiation.

UVB radiation in sunlight is thought responsible for 90 percent of the estimated 1.3 million cases of non-melanoma skin cancer diagnosed in the United States annually.

Researchers applied the BAPs to the skin of hairless mice and fed it to the animals in their diet. In both cases, the substances reduced the number of skin tumors by up to 60 percent and their size by up to 43 percent. They also reduced inflammation.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center, is published in the Dec. 15 issue of the International Journal of Cancer.

These compounds seemed to be dramatically effective at fairly low doses both orally and topically, says principal investigator Gary D. Stoner, professor emeritus of internal medicine and a cancer chemoprevention researcher.

These findings suggest that, even when eaten, these compounds get to skin cells and neutralize the cancer-causing oxygen radicals that are produced by UV exposure.

Laboratory research has shown that BAPs are strong antioxidants and may have anticancer properties.

For this study, Stoner and his collaborators used a strain of hairless mice that are particularly susceptible to UVB-induced skin cancer. Nine experimental groups were used, each with 20 mice.

In two groups, BAPs were applied to the skin in concentrations of 3 milligrams or 6 milligrams in a mild solvent. In two other groups, BAPs made up 0.1 percent or 0.5 percent of the diet.

A group of untreated control mice was also exposed to UVB.

The remaining groups were additional controls: Two were fed the standard diet with and without UV exposure, and two had the BAP solvent applied to the skin with and without UV exposure.

The mice received the BAPs for two weeks before UVB exposure began, followed by 24 weeks of increasing UVB exposure according to a standardized schedule.

The researchers then counted the number of tumors in the treatment and control groups and calculated their size.

Animals exposed only to UVB developed an average of 8.5 skin tumors. The animals fed the lower and the higher dose of BAPs developed an average of 4.7 and 3.7 tumors respectively. Of those given the topical treatment, the lower and higher doses developed 3.4 and 4.6 tumors respectively.

In terms of tumor volume, the animals fed BAPs at the lower and higher doses had tumors that were 34 percent and 40 percent smaller than those in animals exposed to UVB alone. Of those given the topical treatment, the lower and higher dose animals had tumors that were 27 percent to 43 percent smaller than animals exposed to UVB alone.

In addition, the researchers compared the groups for skin levels of the enzyme cyclooxygenase-2 (COX-2) and of the hormone-like substance prostaglandin E2, both of which are strong indicators of inflammation, and for cell proliferation rates.

Animals treated with BAPs showed lower levels of both COX-2 and prostaglandin E2.

The researchers found that the dietary BAPs reduced COX-2 activity by 74-82 percent, and that the topical BAPs reduced it by 66-82 percent. They also measured lower rates of cell proliferation in BAP-treated animals.

Both the oral and topical BAP treatment reduced COX-2 and prostaglandin E2 cell proliferation levels in the skin, Stoner says, which corresponds with fewer tumors and small tumors in the treated animals.

Phototherapy for neonatal jaundice associated with increased risk of skin moles in childhood

Mon, 18 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Children who received light therapy (phototherapy) for jaundice as infants appear to have an increased risk of developing skin moles in childhood, according to a report in the December issue of Archives of Dermatology, one of the JAMA/Archives journals. Some types of moles are risk factors for developing the skin cancer melanoma.

Jaundice or hyperbilirubinemia occurs when bilirubin, a yellow pigment created as a byproduct of the normal breakdown of red blood cells, cannot yet be processed by a newborns liver and builds up in the blood, turning the skin, whites of the eyes and mucous membranes yellow. The condition affects between 45 percent and 60 percent of healthy babies and as many as 80 percent of infants born prematurely, according to background information in the article. During phototherapy, the treatment of choice for jaundice, babies are placed under blue lights (bili lights) that convert the bilirubin into compounds that can be eliminated from the body. Studies have been performed to assess the safety of this therapy, but many have not focused on its effects on the skin, the authors write.

Emmanuelle Matichard, M.D., Bichat-Claude Bernard Hospital, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, and colleagues assessed the presence of melanocytic nevi (moles) in 58 French children who were 8 or 9 years old at the time of the study. Eighteen children had phototherapy as newborns; 40 who were the same age but did not have phototherapy were recruited from a public school and served as controls. All the children and their parents were interviewed about the use of phototherapy, history of sun exposure and sunscreen use. A dermatologist performed physical examinations on the children and recorded their skin color, eye color, hair color, skin type and the number and size of moles.

Thirty-seven children (63 percent) had moles that were 2 millimeters or larger, and there was an average of 2.09 moles per child. Those who were exposed to phototherapy had significantly more moles of this size than those who did notan average of 3.5 vs. 1.45 per child. When the analysis was limited to moles between 2 millimeters and 5 millimeters, the association was stronger. Lentigo simplex [moles smaller than 2 millimeters in diameter] may represent more recent nevi, whereas those nevi due to early events should be larger, the authors write. Nevi larger than 5 millimeters probably are congenital nevi and are most probably associated with genetic predisposition. These associations did not change when other risk factors for the frequency of moles, including skin type and light hair, were considered. Sun exposure, particularly during vacations, was also associated with the number of moles of all sizes, and light hair color was correlated with the number of moles smaller than 2 millimeters.

The study did not examine whether phototherapy increases the risk for melanoma in adults, and it is possible that the small difference in the number of moles between the two groups would not change their risk of developing cancer. However, further study could help illuminate the association. Higher numbers of acquired benign nevi are associated with increased risk of melanoma, they conclude. A detailed evaluation of the factors responsible for the development of nevi in children would be useful to identify high-risk groups to be targeted for prevention. The link between melanoma and phototherapy should be the focus of such a study.

Study identifies characteristics of fast-growing skin cancers

Mon, 18 Dec 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Melanomas (skin cancers) are more likely to grow rapidly if they are thicker, symmetrical, elevated, have regular borders or have symptoms, according to a report in the December issue of Archives of Dermatology, one of the JAMA/Archives journals. In addition, rapidly progressing melanoma is more likely to occur in elderly men and individuals with fewer moles and freckles, and its cells tend to divide more quickly and have fewer pigments than those of slower-growing cancers.

Anecdotal experience suggests that there is a form of rapidly growing melanoma, but little is known about its frequency, rate of growth, or associations, the authors write as background information in the article. One previous study suggested that how quickly a melanoma grew predicted how likely the patient was to relapse at one year or to survive without relapsing. Other research indicates that different types of melanoma grow at different rates; for instance, an aggressive type known as nodular melanoma grows more quickly than any other kind.

Wendy Liu, M.B.Ch.B., Ph.D., Peter MacCallum Cancer Center, East Melbourne, Australia, and colleagues investigated melanoma growth rate in 404 consecutive patients (222 male, 182 female, average age 54.2) with invasive melanoma. Participants skin was examined by a dermatologist and information about such characteristics as the number of typical and atypical moles was recorded. In addition, the patients were interviewed as soon as possible after diagnosis and preferably with a friend or family present. The researchers gathered information about demographics, skin cancer risk factors, the characteristics of the tumor and who first detected the cancerthe patient, a family member or friend, or a physician.

In addition, all patients and their families were asked to recall the date at which they first noticed a spot on their skin from which the melanoma later developed and then the date at which they noticed the marking had changed or become suspicious. The researchers used these two dates, the date that the melanoma was removed as obtained from medical records, and the thickness of the tumor at the time of removal to estimate the approximate rate of growth. This method was doubled-checked by comparing the rate of growth with the tumor mitotic rate, or the rate at which the cancer cells multiply. Those tumors with a faster mitotic rate also had a faster rate of growth as determined by the researchers formula.

Approximately one-third of all the melanomas (141) grew less than .1 millimeters per month, another one-third (136) grew between .1 millimeters and .49 millimeters per month, and one-third grew by .5 millimeters or more per month. A high rate of growth was associated with tumor thickness, ulceration (formation of a break or sore on the skin), amelanosis (lack of pigment in the tumor), regular borders, elevation and symptoms. Faster-growing melanomas were more likely to occur in individuals 70 years or older, in men and in those with fewer moles and freckles. Factors that were not associated with the rate of growth were the number of atypical moles or solar lentigines (age spots or liver spots), history of sun damage or blistering sunburns, skin type, eye color, family or personal history of melanoma, and current or childhood sun exposure.

In summary, this study provides descriptive data on the spectrum of melanoma rates of growth and insights into subgroups of patients with melanoma that are associated with rapid growth, the authors conclude. We propose that this information on melanoma rate of growth be incorporated into education programs for patients and health professionals. Awareness of the clinical features of faster-growing melanomas could help ensure that aggressive cancers are diagnosed and treated quickly.

(Arch Dermatol. 2006;142:1551-1558. Available pre-embargo to the media at

Control mechanism for biological pattern formation decoded

Thu, 23 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) How are simple embryonic structures able to produce the varied and complex manifestations of living nature Scientists in Freiburg have now identified proteins which regulate the pattern of hair formation in mice. They have found that proteins produced by the skin, WNTs, which are essential for the induction of hair follicles, together with so-called DKK inhibitors control the spacing of the follicles. Using a mathematical model based on protein reactions and diffusions, researchers have been able to explain the dynamics and parameters of hair formation and to provide for the first time experimental confirmation of the Turing hypothesis of biological pattern formation (Science Express, 2 November 2006).

As skin matures, a well-ordered sequence of molecular processes leads to the creation of different epidermal structures including the hair follicles of mammals and the feather follicles of birds. A particular feature of these follicles is their characteristic special distribution and density. Signal molecules from the WNT family play a dominant role among the substances which are involved in the induction and maturation of the follicles. Should these proteins not fulfil their function, then there are no morphological or molecular indications of pattern formation at all. The effect of WNTs is regulated by inhibitors from the DKK family of proteins, among others. These are also produced during follicle induction.

A possible explanation for the creation of biological patterns was offered during the 1950s by the English mathematician Alan Turing, who is also known for his participation in decoding the German Enigma code during WWII and his fundamental work on computer theory. Based on purely theoretical considerations, Turing proposed a reaction and diffusion mechanism between two chemical substances. Using mathematics, he proved that such a simple system could produce a multitude of patterns. If one substance, the activator, produces itself and an inhibitor, while the inhibitor breaks down or inhibits the activator, a spontaneous distribution pattern of substances in the form of stripes and patches can be created. An essential requirement for this is that the inhibitor can be distributed faster through diffusion than the activator, thereby stabilizing the irregular distribution. This kind of dynamic could determine the arrangement of periodic body structures and the pattern of fur markings.

Biologists from the Max Planck Institute of Immunobiology in Freiburg, in collaboration with theoretical physicists and mathematicians at the University of Freiburg, have for the first time supplied experimental proof of the Turing hypothesis of pattern formation. They succeeded in identifying substances which determine the distribution of hair follicles in mice. Taking a system biological approach, which linked experimental results with mathematical models and computer simulations, they were able to show that proteins in the WNT and DKK family play a crucial role in controlling the spatial arrangement of hair follicles and satisfy the theoretical requirements of the Turing hypothesis of pattern formation. In accordance with the predictions of the mathematical model, the density and arrangement of the hair follicles change with increased or reduced expression of the WNT and DKK proteins (see fig.).

As well as the fundamental significance for understanding biological pattern formation, these findings form the basis for explaining in detail the process of hair formation, taking into account other factors which presumably work by controlling the WNTs and DKKs. As far as the general role of WNT signals in the creation of epidermal structures is concerned, the current study could be of long-term significance for the in vitro production of skin suitable for transplants.

Scientists harness diptheria toxin and interleukin 2 to help the immune system attack melanoma

Thu, 09 Nov 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Prague, Czech Republic: Researchers investigating ways of prompting the immune system to recognise and kill tumour cells have found that a drug containing parts of the diptheria toxin appears to work well in patients with advanced melanoma (skin cancer).

In the first part of a phase II clinical trial to test the drug denileukin diftitox (also known as DAB(389)IL2 or ONTAK) in melanoma, five out of seven patients with stage IV disease experienced significant regression or stabilisation of both tumours and metastases. The two other patients in whom the disease progressed were on a lower dose of the drug. All the patients are still alive after 12 months.

Dr Jason Chesney, associate director for translational research at the JG Brown Cancer Center, University of Louisville, Kentucky, USA, told a news briefing at the EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Thursday 9 November): We are seeing some exciting results in stage IV melanoma patients whose median life expectancy is normally only about eight months. The phase II trial is continuing to examine the efficacy of denileukin diftitox in patients with melanoma.

The immune system that attacks cancer cells in humans depends on a balance between T cells, which specifically recognise and attack antigens such as tumour cells, and suppressive or regulatory T cells (Tregs), which turn off activated immune cells in order to prevent autoimmunity.

Dr Chesney explained: Recently a subset of regulatory T cells has been found to directly suppress the activation of the anti-tumour T cells, but it was also discovered that, if the Tregs were depleted by targeting them with denileukin diftitox, then particular T cells in the immune system known as CD8+ T lymphocytes were able to attack and kill the melanoma cells in mice.

Denileukin diftitox is a fusion protein made up of amino acid sequences for the diptheria toxin and the T cell growth factor, interleukin 2 (IL2). It targets Tregs that have IL2 receptors on their cell surface, and it binds to part of the receptor called CD25. Once it reaches the inside of the cell it prevents protein synthesis, which leads to cell death within hours.

We thought that if denileukin diftitox could selectively deplete Tregs in patients with melanoma, this would allow the CD8+ T cells to do their job of recognising and attacking the melanoma cells, said Dr Chesney.

Dr Chesney and his colleagues gave seven patients with stage IV melanoma nine or twelve micrograms per kilogram of body weight daily for four days, every three weeks for four cycles. The two patients on the lower dose had newly detectable tumours and tumour growth after two cycles. However, the five patients on the higher dose experienced significant regression of several metastatic tumours after four cycles, including subcutaneous tumours and metastases in the liver and lymph nodes.

One patient had two tumours on the leg that had died and became infected, requiring surgery. When the researchers examined the tumour tissue they found that it was surrounded by CD8+ T lymphocytes. This meant that the lymphocytes had been successfully activated to attack the tumour, which consequently had died. We also found that the concentration of Tregs in this patient decreased by more than a half after the second day's dose of denileukin diftitox, said Dr Chesney.

To our knowledge, this is the only trial to study the effects of Treg depletion in human cancer patients. From the results, we conclude that depleting Treg cells in patients with melanoma may allow the immune system to be activated successfully to kill cancer cells. These patients have survived longer than the median average life expectancy of a patient with stage IV melanoma.

We also believe that, in the future, immunotherapies that depend on depleting Treg cells may prove to be useful in all types of cancer.

Adult beachgoers participating in research study accurately report their sun habits

Tue, 17 Oct 2006 14:25:37 PST

( from http://www.rxpgnews.com ) Adult beachgoers participating in a research study accurately report their sun habits, including sunscreen use and clothing worn on the beach, according to a report in the October issue of Archives of Dermatology, one of the JAMA/Archives journals.

The skin cancer cutaneous melanoma has become much more common and deadly in the United States over the past few decades, according to background information in the article. To reduce the risk of developing skin cancer, physicians recommend limiting the amount of time spent in the sun; seeking shade, especially during the hours at which ultraviolet rays are strongest; applying sunscreen with a sun protection factor (SPF) of 15 or higher; and wearing protective clothing, such as a hat, shirt, pants and sunglasses. Research on skin cancer prevention generally depends on the honesty of study participants reporting their behaviors.

David L. ORiordan, Ph.D., and colleagues at the University of Hawaii, Honolulu, surveyed and assessed the behavior of 88 adults (51 percent men, average age 40) who visited a beach in Honolulu on one of three days in February or March 2004. The participants answered questions about sun habits when they arrived at the beach and again when they left; their arms, legs and face were swabbed to detect the presence of sunscreen; and an observer took notes on their clothing and whether they appeared to have a sunburn. Twenty-five of the study participants were given fluorescent wristbands; these participants were located by an observer who took additional notes about clothing worn during their stay at the beach.

Overall, most participants reports were consistent with what the observers recorded regarding time spent outside, sunscreen use and clothing worn. Thirty-eight (44 percent) of participants reported spending two to three hours at the beach, 18 (21 percent) one to two hours, 17 (18 percent) three to four hours, 10 (11 percent) four to five hours and five (6 percent) zero to one hour, which was consistent with what the researchers recorded. Most of the beachgoers, including those who were observed during the day, accurately reported what they wore on their upper body, lower body and head, but were less likely to wear sunglasses than reported. There was moderate to substantial agreement between participants who reported wearing sunscreen and those whose skin swabs indicated they had applied sunscreen either at the beach or before they arrived.

This study contributes to the paucity of existing research describing the validity of self-report sun habits and has demonstrated that multiple strategies can be effectively adopted to achieve this goal, the authors write. The moderate to substantial agreement obtained for many self-report measures when compared with objective procedures confirms that self-report is a suitable approach to assess sun habits of beachgoers.

The sunscreen-swabbing procedure, previously used only in indoor, controlled environments, proved effective in real-world conditions as well, the authors continue. When used as an adjunct to other assessment instruments, this innovative procedure could be a useful addition to interventions aimed at improving the sun protection practices of individuals, they write.

Most beachgoers accurately report their sun habits

Mon, 16 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Adult beachgoers participating in a research study accurately report their sun habits, including sunscreen use and clothing worn on the beach, according to a report in the October issue of Archives of Dermatology, one of the JAMA/Archives journals.

The skin cancer cutaneous melanoma has become much more common and deadly in the United States over the past few decades, according to background information in the article. To reduce the risk of developing skin cancer, physicians recommend limiting the amount of time spent in the sun; seeking shade, especially during the hours at which ultraviolet rays are strongest; applying sunscreen with a sun protection factor (SPF) of 15 or higher; and wearing protective clothing, such as a hat, shirt, pants and sunglasses. Research on skin cancer prevention generally depends on the honesty of study participants reporting their behaviors.

David L. O'Riordan, Ph.D., and colleagues at the University of Hawaii, Honolulu, surveyed and assessed the behavior of 88 adults (51 percent men, average age 40) who visited a beach in Honolulu on one of three days in February or March 2004. The participants answered questions about sun habits when they arrived at the beach and again when they left; their arms, legs and face were swabbed to detect the presence of sunscreen; and an observer took notes on their clothing and whether they appeared to have a sunburn. Twenty-five of the study participants were given fluorescent wristbands; these participants were located by an observer who took additional notes about clothing worn during their stay at the beach.

Overall, most participants' reports were consistent with what the observers recorded regarding time spent outside, sunscreen use and clothing worn. Thirty-eight (44 percent) of participants reported spending two to three hours at the beach, 18 (21 percent) one to two hours, 17 (18 percent) three to four hours, 10 (11 percent) four to five hours and five (6 percent) zero to one hour, which was consistent with what the researchers recorded. Most of the beachgoers, including those who were observed during the day, accurately reported what they wore on their upper body, lower body and head, but were less likely to wear sunglasses than reported. There was moderate to substantial agreement between participants who reported wearing sunscreen and those whose skin swabs indicated they had applied sunscreen either at the beach or before they arrived.

This study contributes to the paucity of existing research describing the validity of self-report sun habits and has demonstrated that multiple strategies can be effectively adopted to achieve this goal, the authors write. The moderate to substantial agreement obtained for many self-report measures when compared with objective procedures confirms that self-report is a suitable approach to assess sun habits of beachgoers.

The sunscreen-swabbing procedure, previously used only in indoor, controlled environments, proved effective in real-world conditions as well, the authors continue. When used as an adjunct to other assessment instruments, this innovative procedure could be a useful addition to interventions aimed at improving the sun protection practices of individuals, they write.

Psoriasis increases risk for heart attack

Wed, 11 Oct 2006 04:43:37 PST

( from http://www.rxpgnews.com ) Adults with psoriasis, especially younger patients with severe psoriasis, appear to be at increased risk for a heart attack, according to a study in the October 11 issue of JAMA.

Psoriasis is a common, chronic disease that affects about 2 percent to 3 percent of the adult population. It is associated with markers of systemic inflammation, such as increased C-reactive protein levels, which have been linked to the development of atherosclerosis and myocardial infarction (MI; heart attack), according to background information in the article. Several hospital-based studies have indicated that psoriasis is associated with a higher prevalence of cardiovascular diseases, including heart attack, but these studies did not control for major cardiovascular risk factors.

Joel M. Gelfand, M.D., M.S.C.E., and colleagues from the University of Pennsylvania, Philadelphia, conducted a perspective population-based cohort study to determine the risk of heart attack in patients with psoriasis when controlling for major cardiovascular risk factors. The study, which included a total of 556,995 control patients, and patients with mild (n = 127,139) and severe psoriasis (n = 3,837), compared outcomes among patients with and without a diagnosis of psoriasis. The patients, living in the United Kingdom, were 20 to 90 years of age. Adjustments were made for hypertension, diabetes, history of heart attack, hyperlipidemia (an excess of fats or lipids in the blood), age, sex, smoking, and body mass index. Up to five controls without psoriasis were randomly selected from the same practices and start dates as the patients with psoriasis.

The researchers found that the incidence of heart attack was higher in patients with severe psoriasis (5.13 MIs per 1,000 person-years) and mild psoriasis (4.04 MIs per 1,000 person-years) compared with control patients (3.58 MIs per 1,000 person-years), with patients who were younger and had severe psoriasis having the highest rate. For example, a 30-year-old patient with mild psoriasis had a 29 percent greater risk of having a heart attack than a patient without psoriasis; a 30-year-old patient with severe psoriasis had about three times the risk. A 60-year-old patient with severe psoriasis had a 36 percent increased risk for heart attack.

The magnitude of association between severe psoriasis and MI in those patients younger than 50 years is similar to the magnitude of association for other major cardiac risk factors, the authors write.

Our findings are novel and therefore it is important that additional studies be performed to confirm these results and determine their therapeutic implications. In particular, it is important to determine the impact of clinical markers of psoriasis activity, such as body surface area, as well as biomarkers of systemic inflammation (e.g., C-reactive protein) on the risk of MI in patients with psoriasis. In the meantime, as part of good medical care, patients with psoriasis should be encouraged to aggressively address their modifiable cardiovascular risk factors, the researchers conclude.

Psoriasis associated with increased risk for heart attack

Tue, 10 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Adults with psoriasis, especially younger patients with severe psoriasis, appear to be at increased risk for a heart attack, according to a study in the October 11 issue of JAMA.

Psoriasis is a common, chronic, disease that affects about 2 percent to 3 percent of the adult population. It is associated with markers of systemic inflammation, such as increased C-reactive protein levels, which have been linked to the development of atherosclerosis and myocardial infarction (MI; heart attack), according to background information in the article. Several hospital-based studies have indicated that psoriasis is associated with a higher prevalence of cardiovascular diseases, including heart attack, but these studies did not control for major cardiovascular risk factors.

Joel M. Gelfand, M.D., M.S.C.E., and colleagues from the University of Pennsylvania, Philadelphia, conducted a perspective population-based cohort study to determine the risk of heart attack in patients with psoriasis when controlling for major cardiovascular risk factors. The study, which included a total of 556,995 control patients, and patients with mild (n = 127,139) and severe psoriasis (n = 3,837), compared outcomes among patients with and without a diagnosis of psoriasis. The patients, living in the United Kingdom, were 20 to 90 years of age. Adjustments were made for hypertension, diabetes, history of heart attack, hyperlipidemia (an excess of fats or lipids in the blood), age, sex, smoking, and body mass index. Up to five controls without psoriasis were randomly selected from the same practices and start dates as the patients with psoriasis.

The researchers found that the incidence of heart attack was higher in patients with severe psoriasis (5.13 MIs per 1,000 person-years) and mild psoriasis (4.04 MIs per 1,000 person-years) compared with control patients (3.58 MIs per 1,000 person-years), with patients who were younger and had severe psoriasis having the highest relative risk. For example, a 30-year-old patient with mild psoriasis had a 29 percent greater risk of having a heart attack than a patient without psoriasis; a 30-year-old patient with severe psoriasis had about three times the risk. A 60-year-old patient with severe psoriasis had a 36 percent increased risk for heart attack.

The magnitude of association between severe psoriasis and MI in those patients younger than 50 years is similar to the magnitude of association for other major cardiac risk factors, the authors write.

Our findings are novel and therefore it is important that additional studies be performed to confirm these results and determine their therapeutic implications. In particular, it is important to determine the impact of clinical markers of psoriasis activity, such as body surface area, as well as biomarkers of systemic inflammation (e.g., C-reactive protein) on the risk of MI in patients with psoriasis. In the meantime, as part of good medical care, patients with psoriasis should be encouraged to aggressively address their modifiable cardiovascular risk factors, the researchers conclude.

New data reinforce safety profile of ENBREL®

Thu, 05 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Rhodes, Greece, 5 October 2006 -- There was good news for psoriasis patients today as the latest study confirming the established safety profile of ENBREL® (etanercept) for up to 2.5 years , was presented at the 15th European Academy of Dermatology and Venereology (EADV) Congress. ENBREL is a biologic, meaning a biotechnologically produced medicine, which acts on one of the root causes of psoriasis by targeting one of the key mediators of the inflammatory process. It is the number one biologic prescribed worldwide and is now approved in 25 mg and 50 mg prefilled syringes offering flexibility to tailor treatment according to patient needs.

According to Bruce Strober MD PhD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University, These results are important because they confirm the safety profile of ENBREL, which is key information in the context of wider discussion about the long-term use of biologics.

The 48-week open label (OL) extension study (n=921) enrolled patients from two blinded, randomized, placebo-controlled parent studies (PS). The OL study confirmed that the overall safety profile of ENBREL did not change with extended dosing for up to 2.5 years.1,2 No cases of demyelinating diseases, tuberculosis, opportunistic infections or lymphoma were reported in the study.1,2 These findings reinforce the conclusions of an earlier 96-week study of ENBREL 50 mg twice weekly in which the rate of adverse events was similar to that of placebo, and no new safety signals were identified.

In one of the parent studies, at 24 weeks patients were discontinued from treatment and treatment was re-initiated when at least half of the improvement achieved through week 24 was lost. With re-treatment, PASI 75 rates were similar to those attained during the initial treatment course, resulting in repeated success after re-treatment. , There was no treatment interruption in the other parent study.

In Europe, the recommended dose of ENBREL for plaque psoriasis is 25 mg administered twice weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if necessary, by a dose of 25 mg twice weekly. Treatment with ENBREL should continue until remission is achieved, for up to 24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks. If re-treatment with ENBREL is indicated, the dose should be 25 mg twice weekly for up to 24 weeks.

These data reveal an important, practical characteristic of ENBREL in showing that patients on interrupted treatment, after reinitiating therapy, regained similar positive efficacy results as the patients with uninterrupted treatment, said Dr Wolfram Sterry, professor and chairman, department of dermatology, University Hospital Charité, Humboldt University, Germany. In real life, treatment of psoriasis patients is often suspended for a variety of reasons and then restarted.

The new ENBREL prefilled syringes offer patients an easy to use treatment option because it does not require reconstitution as all doses are premixed and prefilled.5 ENBREL is the only biologic with two ready to use dosing options.5, , , The prefilled formulation is bioequivalent to ENBREL powder-for-mixing.

In the European Union, ENBREL is approved for the treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (Psoralen [a light-sensitizing medication] combined with exposure to ultraviolet light A [UVA]).3 ENBREL is also approved for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate.3

Also in the European Union, ENBREL in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrextate (unless contraindicated), has been inadequate. ENBREL can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. ENBREL is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. ENBREL, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function. 3 ENBREL is also approved for the treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate.3 ENBREL has not been studied in children aged less than 4 years. ENBREL is also approved for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.3

European physicians have become familiar with the benefits and long-term tolerability profile of ENBREL since it was approved six years ago. Worldwide, 441,000 patients have been treated with ENBREL. It acts by binding tumor necrosis factor (TNF),3 one of the dominant inflammatory cytokines or regulatory proteins that plays an important role in both normal immune function and the cascade of reactions that causes the inflammatory processes of psoriasis, psoriatic arthritis and RA.3 The binding of ENBREL to TNF inhibits the activity of the bound TNF.3

Since the product was first introduced, serious infections, some involving death, have been reported in patients using ENBREL.3 Patients should tell their doctors if they currently have an infection or are prone to getting infections. Patients should not start ENBREL if they have an infection3 of any type or an allergy to ENBREL or its components. ENBREL should be used with caution in patients prone to infection.3

There have been reports of serious nervous-system disorders such as multiple sclerosis and/or inflammation of the nerves of the eyes.3 Patients should inform their doctor if they have ever had any of these disorders or if they develop them after starting ENBREL. Patients should also tell their doctor if they have ever been treated for heart failure.3 There also have been rare reports of serious blood disorders, some involving death.3

Patients should contact their doctor immediately if they develop symptoms such as persistent fever, bruising, bleeding, or paleness.3 If a patient's doctor confirms serious blood problems, patients may need to stop using ENBREL.3

The most common adverse events observed during the double blind, placebo-controlled portions of three clinical trials in patients with psoriasis were infections and injection-site reactions.3 Among patients with plaque psoriasis treated in placebo-controlled trials, the frequency of serious adverse events was about 1% of 933 patients treated with Enbrel compared with 1% of 414 placebo-treated patients.3

Twenty-three (23) malignancies were reported in patients with plaque psoriasis treated with ENBREL in double blind and open- label studies of up to 15 months involving 1,261 patients treated with ENBREL.3

Psoriasis affects 5.1 million people in Europe. The most common form of psoriasis is plaque psoriasis (psoriasis vulgaris), which occurs in approximately 80% of all patients with psoriasis. In plaque psoriasis, it is likely that a response in the immune system causes the skin cells to grow quickly, resulting in plaques or lesions. , These lesions are reddish and thick with silvery white scales that are loose and easily removed by scratching.16,17

The most common symptom associated with psoriasis is dry, flaky scaling of the skin, which is experienced by nearly 95% of patients. Itching and skin redness are the other two most prominent symptoms.18

Infants targeted in the fight against skin disease

Thu, 05 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Residents and researchers in the Top End are fighting back against skin disease by targeting the prevention and treatment of scabies, tinea and skin sores in infants living in remote indigenous communities.

Often the disease of poverty and poor housing, scabies and skin sores is rife in many remote indigenous communities. Recent research conducted in East Arnhem found a previously unrecognised level of scabies and skin sores in the first year of life, with six out of every ten babies having contracted scabies at least once by their first birthday. A similarly high rate (seven out of ten) had contracted skin sores.

Scabies and skin sores in childhood have been linked with high rates of kidney disease in later life. There is also strong evidence to suggest that skin infections are closely linked to the world-record rates of rheumatic heart disease found in some remote indigenous communities.

To help in their fight to rid their region of this scourge, communities in East Arnhem have joined forces with researchers from the Menzies School of Health Research (MSHR) to develop and implement a new program which includes training for local aboriginal community workers involved in the prevention and treatment of the disease.

Speaking at the 'Healthy Lifestyle Festival' at Galiwinku community this week, MSHR's Healthy Skin Educator, Loyla Leysley said that communities across the region had embraced the new training program which was equipping local community workers with the skills and knowledge needed to help their communities beat this disease.

The training program not only provides crucial on the job training but also allows participants to gain a formal qualification at VET Certificate II level which can be used as a stepping stone towards qualification as an Aboriginal Health Worker.

In addition to the essential clinical training, the program also includes community based education training with a particular focus on prevention through good family hygiene Mrs Leysley said.

If we can prevent infants from contracting skin diseases in the early years, they stand a much better chance of living healthy lives in the future and also reduces the likelihood of them going on to suffer from debilitating kidney and heat disease she concluded.

Bundhala Bhuiikay, Senior Aboriginal Health Worker at Galiwinku community said that since the introduction of the Healthy Skin Program and associated training she and her fellow workers had been better able to help and educate the wider community.

The Healthy Skin Program has helped many people of all ages in this community. It helps to tell everyone about scabies, what it can do to your body and what you can do to stop it she said.

The communities Galiwinku, Milingimbi, Yirrkala, Marngarr, Ramingining and Gapuwiyak are holding Healthy Skin Days during October 2006.

German researchers develop first non-invasive test to measure skin aging

Tue, 03 Oct 2006 03:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, Oct. 3 -- Physicists and medical researchers for the first time have demonstrated a new technique that non-invasively measures in real time the level of damage to the skin from sun exposure and aging, and initial results suggest that women's skin ages faster than men's. Findings appear in the October 1 issue of Optics Letters, a journal of the Optical Society of America.

This new laser-based technique images the fabric of the deeper layers of the skin, combining methods for imaging collagen and elastin, whose degeneration causes the appearance of wrinkles and the progressive loss of skin smoothness. The technique measures relative amounts of collagen and elastin by a single factor, which can be positive or negative, like temperatures. Higher values of the factor correspond to higher collagen content, and to lower elastin content. Previously, each of the imaging techniques had only been tested on tissue extracted from live patients. Last year, Sung-Jan Lin, of National Taiwan University in Taipei, and collaborators, defined the collagen/elastin factor and demonstrated that it gave results consistent with the results of existing lab techniques.

In the new paper, researchers at Friedrich Schiller University, in Jena, Germany, at the Fraunhofer Institute of Biomedical Technology, in St. Ingbert, Germany, and at JenLab GmbH, a Jena-based laser technology company, tested the technique directly on the forearms of 18 patients, measuring the collagen/elastin factor. The team was also able to obtain images of tiny swaths -- one-fifth of a millimeter wide -- of the proteins' fibrous matrices, showing the physical appearance of the dermis, the white lower-layer of skin that gets exposed in deep abrasions.

Large variations appeared from patient to patient, and even from one part of a patient's forearm to another. In a healthy 35-year-old, some areas can appear like the skin of a 25-year-old, and others like that of someone who's 50, said Johannes Koehler, a dermatologist at Friedrich Schiller University and a coauthor of the Optics Letters paper. But on average, both the collagen/elastin factor and the physical appearance of the network showed a clear dependence on the patients' age. The dependence appeared to be sex-dependent, with women's skin losing collagen at faster rates than men's.

The two methods combined in the imaging technique use the ability of ultra-brief pulses of laser infrared light to stimulate tissues to emit light at shorter wavelengths -- blue in the case of collagen, and green in the case of elastin. Since the upper layer of the skin, called the epidermis, is virtually transparent to infrared light, the infrared laser can reach the dermis with intense pulses of light without damaging the upper layers. By two different quantum processes, collagen and elastin will then respond by glowing blue and green.

Currently, dermatologists who want to check out the collagen network of a patient's dermis need to remove a sample of tissue and analyze it in the lab, under a microscope or by other methods. In particular, it is impossible to monitor variations in the very same spot as aging progresses. You would like to measure changes in collagen content over time, Dr. Koehler said. Moreover, current techniques provide a qualitative assessment of the state of the matrix, but no precise measure of the collagen or of the elastin content, which is what the new technique does, he said.

Although the technique is still at the experimental stage, the authors hope that someday it could become useful in studying skin diseases that affect the collagen structure. Those include scleroderma, a poorly understood disease characterized by excessive deposits of collagen in the skin, and some chronic complications of graft-versus-host disease, which occur when the tissues of bone marrow transplant patients are attacked by immune cells coming from the donor. Perhaps the technique could help monitor the progress of the disease, or the success of a treatment, Dr. Koehler said. Testing the effectiveness of anti-aging cosmetic products could also become easier. Some cosmetics are thought to change the content of collagen in the skin, Dr. Koehler said, but until now, to measure that you had to cut out a piece of skin.

New insight into skin-tanning process suggests novel way of preventing skin cancer

Wed, 20 Sep 2006 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON--Findings from a study led by researchers at Dana-Farber Cancer Institute and Children's Hospital Boston have rewritten science's understanding of the process of skin tanning -- an insight that has enabled them to develop a promising way of protecting fair-skinned people from skin cancer caused by exposure to sunlight.

The study, to be published by the journal Nature in its Sept. 21 issue, involved giving tans to specially engineered mice, not by exposing them to ultraviolet rays in sunlight (the usual route to a tan), but by applying a cream that switched on the tanning machinery in their skin cells. Because people who tan easily, or have naturally dark skin, are far less likely to develop skin cancer than fair-skinned individuals -- who tend to get sunburns rather than tans -- the findings suggests that medicinally-induced tans can protect at-risk individuals from the disease.

The study involved using a small molecule to essentially mimic the process that occurs when skin cells are struck by ultraviolet light from the sun, says the study's senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston. While the compound used in the study has not yet been tested in humans, the results demonstrate the principle that actual tanning can be 'rescued' by recognizing the normal pathway and the precise step where it is blocked in people who do not tan well, he remarks.

Melanoma is the fastest-increasing form of cancer in the world, accounting for 62,000 new cases in the United States every year and nearly 8,000 deaths, according to the American Cancer Society. It occurs when pigment-making skin cells called melanocytes begin dividing rampantly as a result of damage to their DNA. If melanoma tumors are detected and surgically removed before their cells spread to other parts of the body, patients have an almost 100 percent chance of surviving. The odds drop sharply, however, if treatment doesn't begin until the disease has spread, or metastasized.

One trigger for melanoma development appears to be ultraviolet (UV) light from the sun, which can damage the skin's DNA. For most of human history, fair-skinned people, who tan poorly, occupied regions with low sun exposure, such as Nordic areas with winter months of darkness. As human populations have scattered throughout the globe, increasing numbers of fair-skinned people have come to live in sunny climes, and melanoma and other skin cancer rates have shot up.

The new Dana-Farber report grew out of efforts by Fisher's laboratory to study melanoma in mice whose fair skin stemmed from the same genetic roots as fair-skinned people. The researchers succeeded in generating red-haired mice whose light skin contained melanocytes, but when the mice were subjected to low levels of UV radiation, they did not tan. Nor did they tan when the UV levels were raised slightly; but when they increased slightly more, the animals got skin sunburns.

These animals couldn't tan, Fisher remarks, who is also a professor of pediatrics at Harvard Medical School. We'd proven in a rigorous genetic system what people have known for hundreds of years: Redheads don't tan well.

This suggested that the mice were a good model for fair-skinned humans. It also led researchers to propose a new theory about how sun exposure triggers pigmentation in people who tan easily. If the researchers' theory was correct, it should be possible to induce dark pigmentation in fair-skinned mice with specific, targeted drugs.

The most common origin of red hair and pale skin in humans is found in a tiny pouch-like receptor, called MC1R, on the surface of melanocytes. When the hormone MSH -- for Melanocyte Stimulating Hormone -- drops into the pouch, it causes a surge in the melanocyte's production of the chemical cAMP. cAMP then stimulates melanocytes to turn on a large number of genes, causing a pigment called melanin to be produced. If cAMP levels are low, the melanocytes make red/blond melanin. If cAMP levels are high, they make brown/black melanin. The melanin is eventually discharged from melanocytes and taken up by keratinocytes. MC1R is shaped differently in red-haired people, so that MSH cannot stimulate it strongly. The result is that cAMP production stays at low levels. Less cAMP means less red/blond pigment production, which results in fair skin.

Many scientists have theorized that tanning occurs when ultraviolet radiation strikes the nuclei of melanocytes, causing DNA damage that prompts the melanocytes to produce pigment. This supposition, however, conflicted with the results of Fisher's experiments. Our work suggested that a peculiarity in the MC1R receptor on melanocytes is responsible for a failure to tan, Fisher relates. But that sort of change on the cell surface shouldn't impede UV radiation from reaching the melanocyte's DNA.

If Fisher's results were correct, the traditional picture of the biology of tanning was wrong. In a series of experiments, Fisher's team found evidence to bolster their theory, leading to a new model of how tanning occurs.

The experiments demonstrated that, rather than acting directly on the nuclei of melanocytes, UV radiation acts on keratinocytes (the most abundant as well as superficial cells in the skin), causing them to produce and secrete MSH, which attaches to adjacent melanocytes and starts the pigment-making process.

While Fisher's model adequately explains why redheads do not tan, it isn't the only possibility. Suppose that during the embryonic or fetal period MC1R never activated cAMP production in developing melanocytes, Fisher proposes. Would mature melanocytes then be permanently 'crippled,' unable to respond to UV, regardless of how its signals were transmitted?

One way to disprove that permanently crippled scenario would be to see if melanocytes with abnormal MC1R receptors can be coaxed into producing pigment in adult mice. To attempt this, Fisher and his associates treated the skin of red-haired, fair-skinned mice with a compound known to increase cAMP levels. The compound, called forskolin, is derived from the root of the forskohlii plant found in India. The mice involved in the experiment turned dark, proving that melanocytes in redheads aren't inherently unable to make pigment if appropriately stimulated.

Further experiments showed that not only can red-haired mice be given tans without exposing them to UV light, but this sunless tanning process is virtually indistinguishable from that in dark-haired mice that tan naturally.

When keratinocytes absorb melanin pigment, the pigment isn't randomly distributed within them, Fisher explains. It forms arcs that look like tiny umbrellas over the keratinocyte's nucleus. When we artificially caused our red-haired mice to tan, the pigment in their keratinocytes made the exact same umbrella-like pattern.

The Dana-Farber researchers also showed that tans acquired through forskolin conferred significant protection against skin cancer caused by exposure to UV light. Fisher notes that while it is unknown whether forskolin will penetrate deeply enough in human skin to activate melanocytes, these results suggest that the search for other substances that do reach deep into the skin may well have the same pigmentation effects in people.

These studies suggest that a drug-induced 'rescue' of the tanning mechanism may correspondingly rescue at least some aspect of skin cancer protection, Fisher observes. Such sunless tanning may also dissuade sun-seeking behaviors, which undoubtedly contribute significantly to high skin cancer incidence.

Short-term topical corticosteroid use may offer relief for patients with acute form of psoriasis

Mon, 18 Sep 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers suggest a short-term application of topical corticosteroids and maintenance with a less potent agent for patients with intertriginous psoriasis (IP), according to a study published in the September issue of Archives of Dermatology, one of the JAMA/Archives journals.

Psoriasis is an inflammatory skin disease. In a subset of patients, psoriasis is located in the intertriginous areas, including the skin folds of the underarms, breasts, groin, buttocks and genitals, according to background information in the article. Patients who exhibit intertriginous psoriasis often complain about intense itching, irritation from sweating and soreness. These symptoms may have devastating psychological and emotional consequences. Management of IP usually includes the application of topical corticosteroids, but those medications have adverse effects with long-term use.

In this study, Alexander Kreuter, M.D, from Ruhr University of Bochum, Germany, and colleagues conducted a randomized controlled trial that compared 1 percent pimecrolimus (a new anti-inflammatory drug), 0.005 percent calcipotriol, 0.1 percent betamethasone and the vehicle (a similarly appearing cream with no active drug) in the treatment of IP with a four-week treatment period and a six-week follow-up without therapy. A total of 80 adult patients with the clinical diagnosis of IP were included, 20 patients in each of the four treatment groups.

After four weeks of treatment, the three active compounds and the vehicle resulted in a significant decrease in mean (average) M-PASI score [Modified Psoriasis Area and Severity Index] (86.4 percent for 0.1 percent betamethasone, 62.4 percent for 0.005 percent calcipotriol, 39.7 percent for 1 percent pimecrolimus and 21.1 percent for vehicle), the researchers found. The 0.1 percent betamethasone was significantly more effective than 1 percent pimecrolimus during the study period. The researchers report 25 percent of patients treated with pimecrolimus reported an increase in itching and burning shortly after application, however, most reactions lasted less than 30 minutes and resolved in a few days.

In conclusion, this study indicated the efficacy of all three active compounds, 1 percent pimecrolimus, 0.1 percent betamethasone, and 0.005 percent calcipotriol (as well as the vehicle) in the treatment of IP. The 0.1 percent betamethasone was clearly more effective than 1 percent pimecrolimus, confirming that treatment with corticosteroids is still the most effective topical approach for psoriasis. However, their use in long-term management, particularly for the treatment of intertriginous areas, which are more prone to steroid adverse effects, is limited. To combine the rapid anti-inflammatory effects of a topical corticosteroid with the favorable long-term effects and safety profile of pimecrolimus or calcipotriol, short-term application of topical corticosteroids for acute disease followed by maintenance treatment with one of these agents seems to be a reasonable approach in the treatment of IP.

How do you use your sunscreen?

Thu, 07 Sep 2006 00:48:37 PST

( from http://www.rxpgnews.com ) WHEN out in the sun, how often do you apply sunscreen? If it's anything less than once every 2 hours, you might be better off not using any in the first place.

So says Kerry Hanson, a chemist at the University of California at Riverside. She and her colleagues exposed human skin samples grown in the lab to UV radiation while they were covered with three common UV filters found in sunscreens: benzophenone-3, octocrylene and octylmethoxycinnamate. After just 1 hour, they found each compound had sunk into the skin, meaning its protective effect was greatly reduced. Worse, Hanson's team found that the samples contained more reactive oxygen species (ROS) than skin exposed to UV with no sunscreen on it. ROS are free radicals that can damage skin cells and increase the risk of skin cancer (Free Radical Biology and Medicine, DOI: 10.1016/j. freeradbiomed.2006.06.011).

The Skin Cancer Foundation in New York recommends that people go no more than 2 hours between reapplications of sunscreen. Our findings tend to support that, says Hanson.

It might actually be necessary to reapply even more often. One way of counteracting free radicals, Hanson says, might be to add antioxidants such as vitamins C and E to sunscreens. "In previous work, we've shown that antioxidants can help neutralise ROS in the skin," she says, though she has yet to perform the same experiment with sunscreen.

The notion that sunscreen can increase damage to skin caused by UV rays is startling, says a spokeswoman for the Skin Cancer Foundation. "It's a very strong statement they're making." The take-home message? Reapply regularly.

Even Superman couldn't win battle with pressure ulcers

Tue, 22 Aug 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Toronto - While pressure ulcers are common among people with impaired mobility, a new study has found surprisingly inadequate scientific evidence on the best strategies to prevent them.

The study, led by researchers at Women's College Hospital and Baycrest Geriatric Health Care System in Toronto, is reported in the August 23, 2006 issue of the Journal of the American Medical Association (JAMA).

The late actor Christopher Reeve, best known as Superman, spoke openly about his struggle with pressure ulcers after being paralyzed in a horseback riding accident. He died at the age of 52 from complications reportedly associated with an infected pressure ulcer.

It is not just spinal cord injury patients who are vulnerable to pressure ulcers. Sixty percent of pressure ulcers develop in patients admitted to hospital. Many of these patients are elderly and/or have diabetes or vascular disease. Immobile patients can develop pressure ulcers within three to six hours of lying on an emergency room stretcher. Elderly persons in long-term care, particularly those who are immobile, incontinent or have dementia, are also at risk.

Pressure ulcers are common in a variety of settings and are associated with adverse health outcomes and high treatment costs, says lead author Dr. Madhuri Reddy, a geriatrician and chronic wound specialist who conducted the study at Women's College Hospital in collaboration with Baycrest.

We found that the majority of published studies which have examined interventions to prevent pressure ulcers have been inadequate in their design and have not generated robust scientific evidence from which to develop comprehensive and unequivocal best practice guidelines.

Pressure ulcers can range from a slight discoloration of the skin to open sores that go all the way to the bone. They frequently develop in the tail bone area, hip and heel, may prolong hospital stay and be complicated by pain and infection which may even result in death.

In the U.S., 2.5 million pressure ulcers are treated each year in acute care facilities alone, estimated at a staggering cost of $11 billion. The cost of treating an individual pressure ulcer ranges from $500 to $40,000 depending on the severity of the wound. The prevalence of pressure ulcers in Canada has been found to be at least as high as in the U.S., with an average of one in four patients across healthcare settings suffering from a pressure ulcer (ref: Prevalence of pressure ulcers in Canadian healthcare settings, Ostomy Wound Management; 2004; 50 (10): 22 38).

There seems to be a huge mismatch between the billions of dollars we're spending on treating this condition, including an incredible amount of nursing time, and the relatively little effort in determining best practices for prevention, says Dr. Paula Rochon, a geriatrician and senior scientist at Baycrest, and senior author on the study.

Using MEDLINE and other databases, the research team identified only 59 randomized control trials of pressure ulcer prevention conducted over the last 30 years, involving a total of 13,845 patients. Fifty-nine studies in 30 years, say researchers, is a surprisingly meager research effort given the magnitude of the problem. Most of the patients in the studies were in acute care hospitals (67%), 17% were in long-term care, and the rest in rehabilitation or mixed care settings. Prevention methods included use of specialized mattresses, repositioning, mixed nutritional supplements and skin lotions.

To assess the scientific rigor of the studies, investigators applied a checklist (CLEAR NPT quality-rating guidelines) for non-pharmacological interventions. The checklist included indicators such as adequate randomized selection of participants for the study, assessor and patient blinding to the intervention, and consistent follow-up schedule.

ResultsOnly three of the 59 studies fulfilled all six criteria on the quality checklist. While repositioning is certainly thought to be a crucial intervention, it is still not known how often patients should be turned, or the best method to use. The use of support surfaces, optimizing nutritional status, and moisturizing skin around vulnerable areas requires more rigorous evaluation, say investigators.

The bottom line is we still don't know what the most cost-effective strategies are for preventing pressure ulcers in different high risk populations, says Dr. Reddy who recently moved to Hebrew Rehabilitation Centre in Boston.

We need to do more head-to-head comparisons of the most promising interventions, ensure the studies are single or even double blinded where possible, and use a high quality randomized selection protocol.

The JAMA study researchers included Dr. Reddy (Women's College Hospital), Dr. Rochon (Baycrest) and Dr. Sudeep Gill (Queen's University). Funding was provided in part by the Canadian Institutes of Health Research.

Acne medication associated with abnormal blood test results

Mon, 21 Aug 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Elevated cholesterol levels and liver enzyme levels appear to be more common than previously thought among patients taking the acne medication isoretinoin, including those who had normal blood test results before beginning therapy, according to a report in the August issue of Archives of Dermatology, one of the JAMA/Archives journals.

Isoretinoin, commonly marketed as Accutane, is the most effective acne treatment currently available, according to background information in the article. As many as 89 percent of patients taking the medication achieve long-term remission from acne. Side effects include elevations in the levels of triglycerides, blood fats that can have an adverse effect on cardiovascular health; liver enzymes, the presence of which indicates liver disease or inflammation; and total blood cholesterol. According to the article, the Accutane package insert notes that 25 percent of patients develop elevated triglycerides and 15 percent elevated liver enzymes. Other studies have found elevated triglycerides in 5 to 18 percent and elevated total cholesterol in 6 to 32 percent of individuals taking the drug.

Lee T. Zane, M.D., M.A.S., University of California, San Francisco, and colleagues assessed the frequency of abnormal laboratory tests in a population of 13,772 patients (aged 13 to 50 years, 51 percent male and 49 percent female) with acne who underwent isoretinoin therapy between 1995 and 2002. The researchers analyzed medical records for each patient before, during and after they took the medication, using information from laboratory tests of triglycerides; total cholesterol; liver transaminase (enzymes) levels; white blood cell (cells that fight infection) count; hemoglobin (which carries oxygen through the body) level; and platelet (involved in blood clotting) count.

Patients taking isoretinoins had an increased incidence of elevated triglyceride, total cholesterol and liver enzyme levels, but not hemoglobin levels, white blood cell counts or platelet counts. Among patients with normal pretreatment laboratory tests, 44 percent developed high triglycerides, 31 percent high cholesterol and 11 percent high liver enzymes while taking the medication. Moderate to severe abnormalities in triglyceride, total cholesterol and transaminase levels were generally transient and reversible, the authors write. Among those subjects with such abnormalities who received posttreatment testing, the proportion returning to normal or grade 1 [slightly elevated] levels by the end of the posttreatment period was 92 percent for transaminase level, 80 percent for triglyceride level and 79 percent for total cholesterol level.

Our study did not examine adverse clinical outcomes and thus cannot estimate the ability of abnormal laboratory results to predict such outcomes, they conclude. In clinical practice, laboratory abnormalities should be evaluated in the clinical context of the individual patient. Neither does the presence of a laboratory abnormality necessarily signal the presence of an adverse clinical outcome, nor does the absence of a laboratory abnormality preclude the possibility of an adverse clinical outcome. Still, patients with acne who develop substantially high triglyceride levels are at risk for high cholesterol and the metabolic syndrome, which in turn may increase the risk for coronary artery disease; further study is needed regarding these side effects, the authors write.

Facial resurfacing treats precancerous skin lesions, may help prevent skin cancer

Mon, 21 Aug 2006 03:59:37 PST

( from http://www.rxpgnews.com ) A program that helps parents talk to their children about skin cancer risks may promote sun-safe behaviors, especially when parents and children have a high-quality relationship, according to a report in the August issue of Archives of Dermatology, one of the JAMA/Archives journals.

Approximately one in six individuals will develop skin cancer during his or her lifetime, according to background information in the article. The recent increase in skin cancer incidence has been attributed to various forms of high-risk sun exposure among young people, including sunbathing, inadequate use of sunscreen and other protective measures and the use of tanning beds or lamps. Recent preventive interventions have targeted children in school or community settings, but widespread rates of dangerous behaviors persist in young people.

Rob Turrisi, Ph.D., The Pennsylvania State University, University Park, and colleagues evaluated a parent-based intervention and assessed family characteristics that may contribute to the effectiveness of such a program in 469 parent-child pairs. Of those, 340 were assigned to the intervention group, in which parents received a handbook that encouraged them to communicate skin cancer risks, promote safe behaviors and discourage tanning, sunbathing and other high-risk activities. The other 129 were assigned to the control group. The children were all 9 to 12 years old, in fourth through sixth grade and from southern Idaho or eastern Tennessee. Forty-five days after parents in the intervention group received the handbook, children in both groups underwent an assessment in which they were asked questions about their sun-related habits and their family dynamics.

Among children who were in the intervention group, several family variables increased the effectiveness of the program. Children in the intervention who exhibited average levels of compliance--measured by how often they reported obeying their parents or following their parents' rules--had less frequent sunburns than those in the control group, but those with above-average compliance developed even fewer sunburns. Among children who reported that their parents had a low level of monitoring--for instance, that parents do not typically know where a child is or is going--the intervention had a larger effect on sunburn severity than among those who reported that their parents monitored them closely. The quality of the parent-child relationship, the child's level of compliance and the frequency of negative communication all affected sunbathing tendencies among those in the intervention group--the program was most effective in families with a high-quality parent-child relationship, a high level of compliance and a low level of negative communication.

The findings are consistent with current theories regarding effective parenting, the authors write. Since the intervention was parent based, it follows that if the child feels that the parent encompasses many general positive qualities (e.g., the parent is warm, loving, trusting and a good listener and shows respect for the child), the child will be more likely to listen to his or her parents about issues such as skin cancer risks, they continue. Furthermore, if the child is willing to comply with parental demands, the parent will have more influence in encouraging sun-safe behaviors and discouraging unsafe sun-related behaviors. Also, it is important that the parent does not exhibit negative communication patterns that can negate the effectiveness of positive communication.

Finally, when parents are already aware of their child's activities, they are more capable of making sure that their child is adequately protected from the sun, which can prevent severe burns, they conclude. Parents can be viable change agents for child behavior and the quality of the family relationship is critical to the success of such interventions.

With few factors, adult cells take on character of embryonic stem cells

Thu, 10 Aug 2006 03:59:37 PST

( from http://www.rxpgnews.com ) With the introduction of just four factors, researchers have successfully induced differentiated cells taken from mouse embryos or adult mice to behave like embryonic stem cells. The researchers reported their findings in an immediate early publication of the journal Cell.

The cells--which the researchers designate induced pluripotent stem cells (iPS)--exhibit the physical, growth, and genetic characteristics typical of embryonic stem cells, they reported. Pluripotent refers to the ability to differentiate into most other cell types.

Human embryonic stem cells might be used to treat a host of diseases, such as Parkinson's disease, spinal cord injury, and diabetes, said Shinya Yamanaka of Kyoto University in Japan. However, there are ethical difficulties regarding the use of human embryos, as well as the problem of tissue rejection following transplantation into patients.

Those problems could be circumvented if pluripotent cells could be obtained directly from the patients' own cells.

We have demonstrated that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors, Yamanaka said. Fibroblasts make up structural fibers found in connective tissue.

Embryonic stem cells are derived from inner cells of the mammalian blastocyst, a ball of cells that develops after fertilization and goes on to form a developing embryo. Cells from other parts of the body can also be reprogrammed by transferring their nuclear contents into egg cell precursors called oocytes or by fusion with embryonic stem cells, earlier studies showed.

Those findings provided evidence that unfertilized eggs and embryonic stem cells contain factors that can confer pluripotency to differentiated cells, Yamanaka said.

We hypothesized that the factors that play important roles in the maintenance of embryonic stem cell identity also play pivotal roles in the induction of pluripotency in other body cells, he explained.

The researchers selected 24 genes--all previously found to play a role in early embryos and embryonic stem cell identity--as candidate factors that might give body cells the ability to become other cell types.

The researchers found that four of those factors, known as Oct3/4, Sox2, c-Myc, and Klf4, could lend differentiated fibroblast cells taken from embryonic or adult mice the pluripotency normally reserved for embryonic stem cells.

They further reported that transplantation of the iPS cells under the skin of mice resulted in tumors containing a variety of tissues representing the three primary types found in mammalian embryos. Those primary germ layers in embryos eventually give rise to all an animal's tissues and organs.

Following injection into blastocysts, iPS cells also contributed to mouse embryonic development.

The finding is an important step in controlling pluripotency, which may eventually allow the creation of pluripotent cells directly from somatic cells of patients, Yamanaka said.

While the findings could have wide applications, stem cell experts caution that the study of embryonic stem cells has much further to go.

We still do not know whether the four factors can generate pluripotent cells from human somatic cells, Yamanaka said. Use of c-Myc, a gene implicated in many human cancers, may not be suitable for clinical applications, they added, and the process may require specific culture environments. It also remains unclear whether iPS cells can do everything that embryonic stem cells can.

Expression of 'Blimp1' gene leads to the discovery of cells responsible for skin's sebaceous gland

Thu, 10 Aug 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Mice may not get zits, but they do have oily skin. This week, new research on mice from Rockefeller University shows how the cells responsible for oil production develop, and uncovers clues about how stem cells renew and differentiate.

The research focuses on the skins sebaceous gland, which is linked to the hair shaft and secretes an oily mixture called sebum. But until today how the sebaceous gland is formed during development was a matter of debate: one group of scientists proposed that skin stem cells produce the gland and a second group suggested that it had its own progenitor cells. In new research, published in the August 11 issue of Cell, Elaine Fuchs, a Howard Hughes Medical Institute investigator at Rockefeller University, settles this argument, showing that at the site where the sebaceous gland adjoins the hair follicle, a unique population of cells exists whose sole job is to make, and maintain, the sebaceous gland.

We were exploring the expression of a transcription factor called Blimp1, which had surfaced in a genetic screen that we had conducted. explains Fuchs, who is the Rebecca C. Lancefield Professor and head of the Laboratory of Mammalian Cell Biology and Development at Rockefeller. We were surprised to find that Blimp1 was expressed in a small population of cells within the sebaceous gland. We knew these cells were skin keratinocytes but no one had ever described their existence and therefore, we had no clues about their relationship to the gland.

Valerie Horsley, a postdoc in the Fuchs lab and first author of the paper, had been interested in Blimp1s role in hair follicle development, and had engineered mice that were missing the Blimp1 gene in their skin. When the mice were born, they formed normal hair follicles, which was quite disappointing, says Horsley. But when they were around one month of age I noticed that the mice started getting very oily skin.

The sebaceous glands in mice missing Blimp1 were much larger than in normal skin. This happens in another genetically altered mouse, one overexpessing the c-myc gene, which has been implicated in many different kinds of cancers. Horsley found that Blimp1 usually acts to repress c-myc expression, and in mice without Blimp1 c-myc expression was increased, causing the sebaceous gland to contain cells that divide more frequently. When Horsley tagged the Blimp1 positive cells and tracked them, she found that the daughters of the Blimp1 cells contribute to the entire gland. Also, when grown outside in culture, the cells that make Blimp1 can divide and self-renew, as well as make the cell types important for generating the oils of the sebaceous gland.

The data show clearly that these cells are the progenitors for the entire sebaceous gland, says Horsley. And Blimp1 is somehow controlling this progenitor population, regulating how many cells are allowed into the gland. This is the first molecular characterization of these cells.

This study has implications for understanding sebaceous gland disorders ranging from acne to sebaceous cell cancers, says Fuchs. And it not only gives us a handle on these novel resident stem cells, but also clues to how stem cells can control the balance of proliferation and differentiation in tissues.

Skin Cells Found to Use a Coordinate System to Deduct their Positional Identity

Thu, 03 Aug 2006 17:52:37 PST

( from http://www.rxpgnews.com ) Global-positioning system aficionados know that it's possible to precisely define any location in the world with just three geographic coordinates: latitude, longitude and altitude. Now scientists at the Stanford University School of Medicine have discovered that specialized skin cells use a similar mapping system to identify where they belong in the body and how to act once they arrive.

These cellular cornerstones direct embryonic patterning and wound healing by sending vital location cues to their neighbors, and may help in growing tissue for transplant or understanding metastatic cancer.

"There is a logic to the body that we didn't understand before," said John Rinn, PhD, a postdoctoral scholar in the laboratory of Howard Chang, MD, PhD, assistant professor of dermatology. "Our skin is actively maintaining itself throughout our life, and these 'address codes' help the cells know how to respond appropriately." Rinn is the first author of the research, which is published in the current issue of Public Library of Science-Genetics.

Until now it's been a mystery as to how adult skin, which consists of basically the same components all over the body, knows to grow hair in some areas like the scalp, while manufacturing sweat glands, calluses and fingerprint whorls in others. In 1969, well-known developmental biologist Lewis Wolpert authored a famous treatise that described two possible ways for cells to know where they are in the body: Either they infer their location and adjust their behavior based on interactions with nearby cells, or they deduce their "positional identity" through the use of some type of coordinate system. The findings from the new Stanford study bolster the second possibility.

The scientists analyzed the gene-expression profiles of adult fibroblasts from more than 40 areas of the body. They found about 400 genes whose expression patterns varied with the cells' original location. Those from the top half of the body - arms, head and chest, for example - shared expression patterns that were markedly different from the patterns shared among cells from the bottom part of the body, such as the legs and feet. Similar patterns existed among cells originating close to or far from the center of the body, and those from the outer or the inner layer of the skin.

While these three rough anatomical divisions don't provide the precise coordinates of a global-positioning system, they do help explain similarities between the skin on the palms of the hands and the relatively distant soles of the feet. Like botanically similar areas of the world that share a latitude and altitude but differ in longitude, both the palms and soles are on the outer layer of the skin far from the center of the body and are more like one another than like their biological neighbors.

"Ideally, we can use this finding to develop a positional map that will allow us to correlate location with function in a way that will make it easier to regenerate certain parts of the body," said Rinn. "For example, if we need to grow skin in the laboratory to graft onto someone with badly burned palms, we'll know how to turn on the specific genes that make that type of skin." The implications are vast. Fibroblasts and other skin cells also comprise the lining of the lung and intestine as well as internal organs.

Not every kind of skin cell expresses gene patterns that can be correlated with their location in the body; the study found no such association in endothelial cells, which might depend on signals from surrounding cells.

"It's not like every cell has this code," said Rinn. "I like to think of the fibroblasts as wise, old parental cells who may tell the others how to behave." Their input is invaluable during embryogenesis, normal growth and wound healing, each of which requires location-specific responses by cells. Many of the genes identified by Rinn are known to be important in patterning the early embryo.

Rinn and his colleagues speculate that some of these processes may require more specific location indicators than the three they've currently identified. It's possible that additional cues may be provided by variations in gene expression levels too subtle to be detected in their current study. Alternatively, cell types other than fibroblasts or endothelial cells may express signals that further refine the current rough map. Finally, it's possible that adults simply don't need the same level of precision mapping as a developing embryo, and they stop broadcasting the finer points of the signal when it's no longer necessary.

UV-A therapy more effective than narrowband UV-B therapy in chronic plaque psoriasis

Mon, 31 Jul 2006 17:30:37 PST

( from http://www.rxpgnews.com ) UV-A therapy was found to be more effective than narrowband UV-B therapy in treating patients with chronic plaque psoriasis, according to an article in the July issue of Archives of Dermatology.

It is unclear whether narrowband UV-B (NB-UVB) therapy is as effective as psoralen-UV-A (PUVA) therapy in treating psoriasis, according to background information in the article. PUVA therapy includes the combination of 8-methoxypsoralen medication (taken orally) and exposure to UV-A (long-wave) radiation. NB-UVB involves exposure to UV-B (short-wave) radiation and is thought to be safer than PUVA.

Sami S. Yones, M.Sc., and colleagues from King's College London conducted a randomized, double-blind trial comparing the efficacy of PUVA and NB-UVB therapies in treating chronic plaque psoriasis. Ninety-three patients with moderate-to-severe cases of the disease were recruited to participate in the study. Two hours before receiving UV treatment, patients in the NB-UVB group took a placebo and those in the PUVA group took 10-mg of 8-methoxypsoralen. Patients in both groups attended sessions twice weekly until their skin cleared, up to a maximum of 30 sessions. Patients whose skin cleared were followed up until relapse or for 12 months.

In patients with skin types I through IV (skin more likely to burn), PUVA was more effective than NB-UVB at clearing skin, with respective 84 percent vs. 65 percent clearance. Patients in the PUVA group also achieved skin clearance in a significantly shorter number of treatments, a median of 17 treatments, compared to 28.5 treatments in the NB-UVB group. Nearly half of patients in the PUVA group experienced erythema (redness of the skin) at some point during treatment, compared to less than one-quarter in the NB-UVB group. Six months after skin clearance was achieved, 68 percent of patients in the PUVA group were still clear compared to 35 percent of patients in the NB-UVB group. Overall, patients with skin types V and VI had a lower rate of clearance than those with skin types I through IV (24 percent vs. 75 percent).

The authors write that despite the disadvantages of PUVA treatment (i.e., may cause nausea, has the potential to cause skin cancer, cannot be used during pregnancy), their results "suggest that PUVA compared with NB-UVB tends to clear psoriasis more reliably, with fewer treatments and for longer and should, therefore, still be used in appropriate patients."

Malignant melanoma cells secrete protein required for embryo formation

Sun, 30 Jul 2006 03:59:37 PST

( from http://www.rxpgnews.com ) A Northwestern University research group has discovered that aggressive melanoma cells secrete Nodal, a protein that is critical to proper embryo formation.

An article describing this research was published today in the advanced online issue of the journal Nature Medicine. The researchers identified the potent and highly unstable embryonic growth factor by injecting aggressive melanoma cells into developing zebrafish embryos, which were used as biosensors for tumor cell-derived signals, and were consequently able to induce ectopic (abnormal) embryonic skull and backbone (axes) formation.

This finding highlights the convergence of tumorigenic and embryonic signaling pathways. From a translational perspective, Nodal signaling provides a novel target for treatment of aggressive cancers such as melanomas, said Mary J. C. Hendrix, the corresponding author, of Children's Memorial Research Center where the discovery was made.

Hendrix is president and scientific director of the Children's Memorial Research Center, professor of pediatrics at Northwestern University Feinberg School of Medicine and a member of the executive committee of The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Jolanta M. Topczewska and Lynne-Marie Postovit, from Children's Memorial Research Center, co-led the study. Working with Brian Nickoloff of the Cardinal Bernardin Cancer Center at Loyola University Stritch School of Medicine, the investigators found that Nodal protein was present in 60 percent of cutaneous (skin) metastatic melanoma tumors but is absent in normal skin.

They also found that blocking Nodal signaling reduced melanoma cell invasiveness, as well as cancer cell colony formation and tumor-forming ability. Strikingly, nodal inhibition promoted the reversion of these cells toward a normal skin cell type. Like embryonic stem cells, malignant tumor cells similarly receive and send molecular cues during development that promote tumor growth and metastasis, or cancer spread.

The Northwestern study takes advantage of these similarities by using the developing zebrafish to detect tumor-derived chemical signals.

In addition, one of the hallmarks of aggressive cancer cells, including malignant melanoma, is their unspecified, plastic nature, which is similar to that of embryonic stem cells, expressing genes characteristic of multiple cell types, including endothelial, neural and stem cells.

The Hendrix lab has long hypothesized that the plastic nature of malignant melanoma cells serves as an advantage by enhancing the cells' ability to migrate, invade and metastasize virtually undetected by the immune system.

In this study, the researchers showed that aggressive tumor cells, particularly melanoma, are capable of responding to microenvironmental factors as well as influencing other cells via epigenetic (other than genetic) mechanisms, a quality known as bi-directional cellular communication. Bi-directional cellular communication is integral to both cancer progression and embryological development.

The significance of the research team's finding is profound in that it implies that through secretion of Nodal, aggressive melanoma cells maintain their plasticity and modulate the microenvironment, as exemplified by their ability to direct the formation of zebrafish tissues.

These results also highlight the propensity of tumor cells to communicate bi-directionally and survive within an embryonic microenvironment. Further, the findings illuminate the remarkable plasticity of melanoma cells and the utility of the developing zebrafish as a model for studying the epigenetic modulation of tumor cells.

Melanoma is one of the deadliest forms of cancer. The five-year survival rate for melanoma patients with widespread disease is between 7 percent and 19 percent.

NICE gives backing for the use of advanced biological therapies to treat severe psoriasis

Wed, 26 Jul 2006 03:59:37 PST

( from http://www.rxpgnews.com ) NICE's announcement comes as welcome relief to the thousands of UK patients who have exhausted current available treatment options and failed to sustain a long-term benefit. It is a positive sign for patients throughout Europe, whose healthcare systems are influenced by NICE decisions. Leeroy Blake in England was fortunate enough to be offered treatment with a biological therapy, after years of trying every other available psoriasis treatment: For many years, I tried every suitable treatment but nothing seemed to relieve the painful itching. As the itching got worse, I would get more stressed and this only made my condition worse. Following a treatment review with my doctor, I was prescribed a biological therapy and for the first time since developing psoriasis, my skin started to clear and my confidence came back. This treatment might not be suitable for everyone with severe psoriasis, but I think that it's important that patients at least discuss this option with their doctor.

Latest research has dismissed the preconception that psoriasis is merely a skin complaint, with recent data showing that severe psoriasis can affect a patient's quality of life to a similar extent as other prevalent chronic diseases such as diabetes and even heart diseases .

In addition to the impact on a patient's appearance, up to 30% of patients with psoriasis have been reported to have psoriatic arthritis, which causes pain, stiffness and swelling in and around the joints. Coinciding with its decision on the use of biological therapies in moderate to severe psoriasis, NICE has also given its backing for the NHS to use Enbrel and Remicade® (infliximab) to treat patients with severe, active psoriatic arthritis. Professor Robert Moots, Professor of Rheumatology at the University of Liverpool, UK welcomes this guidance commenting, the NICE guidance is a positive step forward for those patients whose condition is severe enough to warrant treatment with biologic therapies adding that the onus is now on NHS trusts to take note of this recent recommendation and ensure that the necessary funding is in place to allow patients access to these much-needed therapies.

This latest NICE guidance should now ensure that for adult patients with severe plaque psoriasis, who have failed on standard therapies, these new treatment options can now be made available. Lars Ettarp, President of the International Federation of Psoriasis Associations (IFPA) underlines that psoriasis is a systemic disease and that IFPA welcomes the new therapies in the treatment of severe psoriasis/psoriatic arthritis. The national healthcare providers must now make funding for these new drugs available in order to help these really sick persons.

Professor Knud Kragballe, Department of Dermatology, Århus University Hospital in Denmark, has echoed this call: Health care providers throughout Europe should take note of these recommendations and ensure that necessary funding is in place to allow access to biological therapies. Psoriasis can be highly debilitating and painful condition. If patients fulfill the criteria for a biological therapy then, I believe, it is important that treatment is started with minimal delay.5

Stevo Knezevic, MD, PhD, chief medical officer of Wyeth Europa commented: This endorsement of biological therapies is excellent news for psoriatic patients across Europe and the healthcare professionals who care for them. It is now vital that healthcare providers take note of the positive NICE decision, the opinion of dermatologists and the needs of psoriatic patients, and make funding for these therapies available as quickly as possible.

Patients who would like to find out more about biological therapy are advised to talk to their dermatologist.

In the European Union, Enbrel® is approved for the treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (Psoralen (a light-sensitizing medication) combined with exposure to ultraviolet light A (UVA).2 Enbrel is also approved for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate.2

Physicians in Europe have become familiar with the benefits and long-term tolerability profile of ENBREL since it became commercially available over six years ago. More than 400,000 patients have been treated worldwide across indications. Enbrel is a recombinant human tumour necrosis factor (TNF) receptor fusion protein that inhibits the activity of TNF. TNF is a cytokine that is released from T lymphocytes; it mediates inflammation and modulates the cellular immune response2. Enbrel is also indicated for treatment of the following: 2

Distress due to eczema very worrying

Wed, 19 Jul 2006 03:54:37 PST

( from http://www.rxpgnews.com ) Children with serious skin conditions feel their quality of life is impaired to the same extent as those with chronic illnesses such as epilepsy, renal disease and diabetes, according to research published in the July issue of British Journal of Dermatology.
A team of Scottish researchers surveyed 379 five to 16 year-olds, who had been suffering from skin diseases like acne, eczema and psoriasis for more than six months, together with their parents.

They asked the children and their parents how much the condition impaired the child's quality of life when it came to factors such as pain, loss of sleep, dietary restrictions, interference with school and play, friendships, teasing and bullying and medical treatment.

They then compared the quality of life scores given by the parents of 161 children with chronic diseases in the same age group.

Only six of the 546 parents approached by staff at Ninewells Hospital in Dundee and Perth Royal Infirmary preferred not to take part in the research. All the children included were attending outpatient clinics at the two hospitals.

Key findings included:

The children in the study said that psoriasis (red scaly patches) and eczema were the two skin conditions that caused them the greatest distress. Both resulted in a 31 per cent impairment in their quality of life score. This was followed by urticaria (itchy allergic skin rash) at 20 per cent impairment and acne at 18 per cent impairment.
From the parent's perspective, eczema was the biggest skin problem at 33 per cent, followed by urticaria at 28 per cent, psoriasis at 27 per cent and hair loss at 19 per cent.
When they compared the overall results for the children with skin diseases and chronic illnesses, the researchers found that the condition that had the worst affect on quality of life was cerebral palsy at 38 per cent. Generalised eczema and kidney disease both scored 33 per cent.
Cystic fibrosis also made the top five (32 per cent), followed by urticaria and asthma (28 per cent), psoriasis (27 per cent), epilepsy and bed wetting (24 per cent), diabetes, hair loss and localised eczema (19 per cent) and acne (16 per cent).
When children with psoriasis, and their parents, were asked to chose the factors that affected the child's quality of life most, parents rated bullying third and children rated bullying fourth.
Teasing or bullying was also a key concern for the 11 children with hair loss, with six of the children and nine of the parents putting it first on their list.
The biggest concerns for children with eczema, psoriasis and uticaria was itching or pain, while children with acne or warts said that embarrassment was their main worry.
"Our study shows that children with chronic skin diseases and their parents reported the same level of quality of life impairment as the parents of children with many other chronic illnesses" says lead author Dr Paula Beattie from the Royal Hospital for Sick Children in Glasgow.

"Skin diseases are often more obvious to other children than chronic diseases such as asthma or diabetes and are more likely to lead to alienation, name calling, teasing and bullying.

"Some skin conditions can also disturb children's sleep and cause lack of self-confidence, embarrassment and poor self-esteem, especially as they get older.

"Although skin diseases may not shorten life in the same way as serious conditions like cystic fibrosis, they can cause children as much, if not more, distress in their everyday lives."

"Measuring quality of life can be a powerful political tool as it provides the patient's perspective on the health impact of different diseases" adds co-author Dr Sue Lewis-Jones from Ninewells Hospital, Dundee.

"This is particularly important when arguing for vital resources, especially in dermatology, as skin diseases are not considered to have as much of an impact on people's lives as other illnesses.

"Our study clearly shows the profound effect skin diseases can have on children's quality of life and we hope that our findings will raise awareness of the problems they face and encourage greater sensitivity towards them."

Glucosamine can stop formation of new age spots

Sat, 01 Jul 2006 16:18:37 PST

( from http://www.rxpgnews.com ) For many women, accumulated sun exposure has already permanently damaged their skin cells, causing them to overproduce pigment that shows up as unsightly dark splotches and uneven skin tone over time. But new research indicates that glucosamine - a compound best known for treating arthritis can actually help stop the formation of new age spots, and help fade existing ones.

"These findings on glucosamine may impact the way dermatologists treat UV-related skin damage in the future. Right now we have prescription and surgical options, which some people aren't willing to try," says Alexa Kimball, M.D., assistant professor of dermatology, Harvard Medical School and lead researcher on one of the studies testing glucosamine. "It's exciting to see this level of research being done on topical cosmetic applications of glucosamine, and the promising results."

An International Consensus on Glucosamine Skin Benefits In early 2006, a group of leading dermatologists from around the world and Procter & Gamble Beauty scientists convened in Rome to review and discuss the glucosamine data. The panel determined that n-acetyl glucosamine, a more stable form of glucosamine, reduced the amount of melanin in skin cells, meaning there was less excess pigment in the skin to cause age spots. Additionally, the panel concluded that a formulation of n-acetyl glucosamine and niacinamide, a vitamin B derivative, significantly reduced the amount and appearance of hyperpigmentation, age spots and uneven melanin distribution. Researchers paired n-acetyl glucosamine with niacinamide because they knew that niacinamide had similar effects on slowing down pigment production and hypothesized that the two might work better together.

The panel reviewed data from three studies involving the n-acetyl glucosamine /niacinamide formulation. Tissue studies showed a reduction in melanin and an increase in collagen a key structural protein in skin. Three double-blinded placebo- controlled clinical studies involving more than 200 subjects, including a study supervised by Dr. Kimball, showed improvement in hyperpigmentation and skin tone and a decrease in the size of age spots. The research is set to be presented in July at the "Academy '06" meeting of the American Academy of Dermatology (AAD), and was first presented at the AAD annual meeting in March 2006.

Skin Biology Gives Researchers Clues for Developing New Treatments The interest in glucosamine as a possible treatment comes in part from what scientists already know happens on a cellular level when skin is exposed to UV radiation. Chronic UV exposure can damage melanocytes, cells in the skin responsible for producing melanin, in a variety of different ways. Often, this damage can lead to a loss of cellular control, and the production of chemicals that allow the cells to keep producing more and more melanin which eventually leads to age spots and uneven discoloration. Additionally, as skin ages, cell turnover slows down and melanin "dust" microscopic particles of melanin can become trapped in the upper layers of skin, resulting in a duller appearance.

Researchers are familiar with these processes and that has helped them focus on substances - such as n-acetyl glucosamine - that are known to interrupt the UV-triggered chemical signals that turn on melanin production. Skin care products that utilize signal-blocking ingredients currently exist in the marketplace, but products with n-acetyl glucosamine/niacinamide - which block melanin at two different points in the pigment producing process - are among the newest and most studied.

"Pigmentation is an appearance issue that strikes an emotional chord for women, and even though we're constantly telling our patients about the importance of UV-protection, once the damage is done, we need to be able to provide them with ways to help," says Dr. Kimball. "The level of research and validation on topical cosmetic application of glucosamine will help it stand apart from other ingredients when it comes to improving tone and treating hyperpigmentation."

Mouse model aids discovery of novel melanoma metastasis gene

Thu, 29 Jun 2006 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON--Researchers from Dana-Farber Cancer Institute have identified a novel gene that facilitates the spread of malignant melanoma, a life-threatening skin cancer, using a technique they say can speed the discovery of hard-to-find cancer genes.

In the June 30 issue of Cell, scientists led by Lynda Chin, MD, report that the gene, NEDD9, is abnormally abundant in more than a third of melanomas that have metastasized, but not in primary melanomas that have not spread.

The protein made by the NEDD9 gene allows the cancer cells to migrate beyond the initial skin tumor, to invade surrounding tissues and ultimately to metastasize to distant organs. While the protein itself does not lend itself to targeting by cancer drugs, say the researchers, insights gained in this study suggest that disrupting genes and proteins associated with NEDD9 may be fruitful in halting spread of melanoma.

This is clinically important, said Chin, because primary skin melanoma doesn't kill patients metastases are the major problem. So understanding the events that drive metastasis may lead to identifying the most relevant targets for therapy, and potentially, for preventing metastasis.

More than 62,000 cases of melanoma will be diagnosed in the United States this year, according to American Cancer Society estimates, and about 7,900 people will die of the cancer.

Chin and her group at Dana-Farber use genome-scanning methods such as array-CGH (comparative genomic hybridization) to uncover structural abnormalities of the chromosomes of cancer cells. In one common form of abnormality, bits of DNA have been overcopied (amplified) or, conversely, have been lost (deleted), and these copy number alterations are key events in the development and progression of cancers.

If the alterations are confined to a very small part of the chromosome, it is relatively easy to identify the likely culprits involved in the cancer. But in some cancers, including metastatic melanoma, scientists have discovered large regions of chromosomal DNA that have been amplified or deleted. In such cases, it would be a daunting task to pinpoint the actual gene culprit among a large number of bystander gene abnormalities that may not be relevant to the cancer.

For example, scientists had previously shown that the entire short arm of Chromosome 6, referred to as 6p, is amplified in more than 35 percent of cells from melanoma tumors that had metastasized. But the 6p region is only rarely amplified in primary, non-spreading melanomas. There are hundreds of genes on 6p, making the task of narrowing down to a few candidate culprits nearly impossible. Chin had previously created transgenic mice in which melanoma could be induced by turning cancer genes on or off. When tumors from these mice were transplanted into normal mice lacking an immune system, the cancers grew and a few of them became metastatic. Genome scans of the metastatic tumors -- known as escapers -- revealed an amplified region on Chromosome 13 that was not present in the primary (non-metastatic) tumor cells. That region, presumably, reflected a genetic change that promoted metastasis.

Although it is located on Chromosome 13 in the mouse, the amplified region was similar to the amplified region on Chromosome 6 in human melanoma cells, but, fortunately, it contained only eight genes. Therefore it was possible to pinpoint the NEDD9 gene in the mouse tumors and verify that the same gene in humans, when overactive, drives metastasis of melanoma tumors.

This is a demonstration of the principle, that the mouse has similar genomic changes that are important for cancer, and we can use the mouse model as a 'filter' to help us identify which gene is responsible for the cancer development and metastasis, said Chin, who is also an associate professor of dermatology at Harvard Medical School.

Microscopic scaffolding offers a 'simple' solution to treating skin injuries

Tue, 27 Jun 2006 03:59:37 PST

( from http://www.rxpgnews.com ) This ultra-fine, 3-dimensional scaffold, which is made from specially developed polymers, looks similar to tissue paper but has fibres 100 times finer. Before it is placed over a wound, the patient's skin cells (obtained via a biopsy*) are introduced and attach themselves to the scaffold, multiplying until they eventually grow over it. When placed over the wound, the scaffold dissolves harmlessly over 6 to 8 weeks, leaving the patient's skin cells behind.

This new approach to skin reconstruction has been developed by a team of chemists, materials scientists and tissue engineers at the University of Sheffield, with funding from the Engineering and Physical Sciences Research Council. It is designed primarily for cases involving extensive burns where surgeons are unable to take enough skin grafts from elsewhere on the body to cover the damaged areas. Currently, bovine collagen** or skin from human donors is used in these cases, but these approaches have potential health and rejection risks.

Simplicity is the key, says Professor Tony Ryan, who is leading the team. Previous attempts to find better ways of encouraging skin cell growth have used chemical additives and other elaborate techniques to produce scaffolds, but their success has been limited. We've found that skin cells are actually very 'smart' it's in their DNA to sort themselves into the right arrangement. They just need a comparatively uncomplicated scaffold (and each other) to help them grow in a safe, natural way.

The polymers used in the scaffold are biodegradable materials already approved for medical applications. Because the team has recognised that skin cells are 'smart' and the scaffold can therefore be 'dumb' (i.e. not overly sophisticated), simple polymers can be used.

The process for making the scaffolds is based on the well-known technique of electrospinning***. However, the team has made a key advance by developing a new method of making, from the same biodegradable polymers, aligned-fibre 'mats' of potential use in promoting nerve or tendon growth. This method is currently being patented.

The next step in the research is to develop the skin reconstruction technology for clinical use, hopefully in the next few years. The technology also offers possibilities for testing the toxicity of cosmetic and similar products, using materials grown in the laboratory that closely resemble natural skin.

Ultimately, we can envisage treatment of burns victims and the undertaking of reconstructive surgery using the scaffold and the patient's own skin to produce bespoke skin for that patient, says Professor Ryan. As an accident-prone mountain biker, I find that prospect very attractive!

Hispanics and blacks with melanoma more likely to be diagnosed at a later stage

Mon, 19 Jun 2006 03:59:37 PST

( from http://www.rxpgnews.com ) The skin cancer melanoma has become increasingly more common, with incidence rates increasing 2.4 percent annually in the United States over the past decade, according to background information in the article. Because light-skinned individuals are at higher risk for melanoma, much of the prevention and early detection efforts have targeted white populations; this may help explain improving survival rates (up to 92 percent from 68 percent in the 1970s) among whites. However, similar progress has not been seen among black and Hispanic populations.

Shasa Hu, M.D., University of Miami Miller School of Medicine, and colleagues reviewed 1,690 melanoma cases reported in Miami-Dade County between 1997 and 2002. Of those, 1,176 occurred in white patients, 485 in Hispanic patients and 29 in non-Hispanic black patients.

Hispanic and black patients were both more likely to have advanced-stage melanomas than white patients. Of the melanoma patients, 16 percent of Hispanics and 31 percent of blacks had cancer that had already metastasized (spread to other organs and tissues) at the time it was diagnosed, compared with 9 percent of whites. Black patients had the highest rate, 52 percent, of regional- or distant-stage melanoma, the two most severe stages that indicate the cancer has spread to other lymph nodes or organs; this compares to 26 percent for Hispanics and 16 percent for whites. White patients were more likely to be diagnosed with earlier stages of melanoma, including melanoma in situ, or cases in which the cancer cells are found only in the outer layer of skin, and local melanoma, in which cancer has spread to the lower layers of skin but not to the surrounding lymph nodes. Twenty-seven percent of white patients, 10 percent of black patients and 22 percent of Hispanic patients were diagnosed with melanoma in situ; 57 percent of white, 38 percent of black and 52 percent of Hispanic cases were diagnosed at the local stage.

This disparity in stage at diagnosis may contribute to lower survival rates among blacks and Hispanics, the authors write. According to previously published studies, the five-year survival rate for melanoma diagnosed in the local stage is 98 percent. The rate drops to 64 percent for regional stage melanoma and 16 percent for distant stage.

Evidence suggests that secondary prevention efforts such as skin cancer examination are suboptimal in Hispanic and black populations, the authors conclude. Although varying cultural values may account for some differences in health care use, public education regarding melanoma risk in black and Hispanic persons and delivery of skin cancer screening and examinations represent the main potential areas of intervention to improve the stage at diagnosis of melanoma in these populations. We hope that earlier diagnosis of melanoma at a more favorable stage will ultimately improve melanoma survival rates in minority populations.

Low-dose Arsenic in drinking water increases risk of premalignant skin lesions

Thu, 15 Jun 2006 17:18:37 PST

( from http://www.rxpgnews.com ) Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, up until now estimates of the health effects associated with low-dose exposure had been based on research from high-dose levels. In a study of more than 11,000 people in Bangladesh, research conducted by Columbia University's Mailman School of Public Health clearly provides evidence that a population exposed to well water with arsenic concentrations of as little as 50 ug/l is at risk for skin lesions. The report also concludes that older, male, and thinner participants were more likely to be affected by arsenic exposure.

The Mailman School team of researchers evaluated the relationship between arsenic exposure from drinking water and premalignant skin lesions over the course of three years. Participants were evaluated for arsenic exposure based on well-water arsenic concentration and usage. "Because of the wide range of arsenic exposure in the study population and the relatively large sample size, we were able to estimate and report dose-response relations even at the very low end of the arsenic exposure range. In particular, arsenic exposure seems to increase the risk of skin lesions at the low end of exposure in this population," said Habibul Ahsan, M.D., MMedSc, associate professor and director of the Center for Genetics in Epidemiology in the Department of Epidemiology at the Mailman School of Public Health and principal investigator.

The researchers indicate that a unique opportunity exists in Bangladesh to study chronic arsenic exposure measured at the individual level, because the majority of the population uses a single well as their primary source of drinking water, while, for example, in the United States, people usually drink water from multiple sources. However, up until now even assessments at the individual level were extremely difficult because exposures measurements were from years past or the Bangladeshi population drank water from multiple sources.

Another obvious difference between the rural population of Bangladesh and other studied populations is that this population consumes a large amount of water, as much as 2.53 liters per day on average vs. 1 liter in the United States. Moreover, almost 100 percent of the drinking water for this population comes from one or two wells with relatively stable concentrations of arsenic.

The team of researchers note that skin lesions were less of a factor in the study for females in the study, and this may be due to the tendency of women in rural Bangladesh tend to cover their bodies more extensively than men. "It also is possible that hormonal and other biologic differences between men and women also could be responsible for part of the gender differences in the skin lesion risks," observed Joseph Graziano, Ph.D., Mailman School associate dean for research, professor of Pharmacology & Public Health, and professor of Environmental Health Sciences.

The study also found some evidence that participants with a higher body mass index were at lower risk of skin lesions than participants with a lower body mass index. "Lower body mass index reflects poorer nutritional status in rural Bangladesh, which could directly or indirectly influence the effect of arsenic. In particular, poor nutritional status may be associated with lower intake of the antioxidants, folates, and/or dietary proteins necessary for metabolism and detoxification of arsenic in the body, said Dr. Ahsan." The influence by gender, age and body mass should be considered in future research and policy decisions."

Skin cancer is the most common arsenic-related cancer. Nearly 100 million people in the world are chronically exposed to arsenic and, therefore, are at increased risk of skin and other arsenic-induced cancers.

The most common route of human exposure to arsenic is through ingesting drinking water that is naturally enriched with arsenic. With an estimated 57 million people in Bangladesh having been exposed to high levels of arsenic from drinking water, starting in the 1970s, UNICEF and the Bangladeshi government installed a large number of hand-pumped tube-wells to provide pathogen-free drinking water to the population of Bangladesh.

The study builds on some of the activities developed in coordination with the NIEHS-funded Superfund Basic Research Program, led by Dr. Joseph Graziano, whose primary goal is to elucidate the health effects and geochemistry of arsenic. The work of the Superfund involves studies at four sites in the U.S., and also focuses on carcinogenic, reproductive and childhood effects of arsenic exposure in drinking water in Bangladesh.

Atorvastatin may increase new blood vessel formation

Thu, 25 May 2006 12:39:37 PST

( from http://www.rxpgnews.com ) Systemic sclerosis (SSc), also known as scleroderma, is an uncommon and confounding disease characterized by excessive fibrous tissue formation and vascular abnormalities. Primarily affecting the small arties, SSc decreases blood flow to the body's extremities. This can lead to Raynaud's phenomenon, a condition that causes the hands and feet to feel extremely cold and numb; ulcers on the fingers and toes; and gangrene. SSc can also restrict blood flow to internal organs, resulting in lung, kidney, and heart damage. While its cause and cure have yet to be found, SSc is generally viewed and treated as an autoimmune inflammatory disorder.

Researchers in Japan recently proposed a different theory: the root of SSc may be defective vasculogenesis, the process of forming new blood vessels by producing new cells in the blood vessel lining. In the June 2006 issue of Arthritis & Rheumatism, Dr. Masataka Kuwana and colleagues at the Keio University School of Medicine in Tokyo share the results of an experiment to affirm their hypothesis and test a novel treatment strategy. Their objective: to determine the effectiveness of one of the most popular and potent cholesterol-lowering drugs atorvastatin, marketed under the brand name Lipitor for increasing blood flow and improving the symptoms of SSc.

The study focused on 14 women, between ages 36 and 75, with a confirmed diagnosis of SSc. Disease duration ranged from 13 months to 21 years. All the patients were treated with 10 milligrams of atorvastatin per day for 12 weeks; all but one participated in a follow up 4 weeks after. At the time of entry, all the patients had active Raynaud's phenomenon, and 2 had digital ulcers. For the study's duration, all patients continued their routine course of treatment, from low-dose aspirin to low-dose prednisolone.

At pre-treatment, at weeks 4, 8, and 12 during treatment, and at 4 weeks post-treatment, all the patients were evaluated for SSc symptoms. What's more, and most significant, each patient was assessed, using rigorously developed assay systems, for their absolute number of circulating endothelial precursors (CEPs). Vasculogenesis requires the recruitment of CEPs from bone marrow to form blood vessels when there are no pre-existing ones. This study's ultimate goal was to evaluate whether statins work to treat SSc by increasing patient's production of strong, blood vessel-building CEPs.

For the 13 patients who completed the 12 weeks of therapy, atorvastatin yielded a 1.7 to 8-fold increase in the number of CEPs. However, for 8 patients, 62 percent of the group, CEP levels peaked during treatment, either at week 4 or week 8, and gradually decreased thereafter. Even for the 5 patients who experienced continual gains in CEP levels while taking atorvastatin, the numbers did not reach the levels seen in healthy individuals. For all patients, CEP counts returned to within baseline counts by the follow up session. All the patients experienced improvements in Raynaud's phenomenon activity while taking atorvastatin. Symptoms generally returned to within baseline levels after discontinuation of the drug.

As this study demonstrates, atorvastatin is capable of stimulating CEP production in SSc patients. But its effects are limited. "Although the results of this preliminary study are encouraging," Dr. Kuwana notes, "further multicenter, placebo-controlled trails involving a large number of SSc patients are necessary to confirm the clinical benefit of statins in SSc patients."

Gene first linked to rare disease may trigger skin cancer, other tumors

Thu, 18 May 2006 03:59:37 PST

( from http://www.rxpgnews.com ) The disease familial cylindromatosis results from the loss of a gene called CYLD, causing tumors known as cylindromas to develop in hair-follicle cells. Earlier studies indicated a role for CYLD in inflammation, but the mechanism behind the gene's control over tumor growth had remained uncertain.

A team led by Reinhard Fässler of the Max Planck Institute of Biochemistry in Germany and his colleagues has now found that CYLD has a second role that explains its ability to keep tumors at bay.

The enzyme chemically modifies the cancer-promoting protein Bcl-3, first identified in connection with some forms of leukemia. That modification bars the oncogenic protein's entry into the cell nucleus, the central command center and storehouse for DNA, where it would otherwise drive the uncontrolled increase in cell numbers characteristic of tumor growth.

The researchers first showed that mice lacking CYLD were highly sensitive to developing skin tumors. Mutant mice exposed to particular chemicals all developed skin tumors compared to half of normal mice experiencing the same exposures. Moreover, the CYLD-deficient mice developed 7-fold more and significantly larger tumors than their control littermates.

Further examination of tumors taken from the mutant mice suggested that the defect stemmed from an increase in cell proliferation rather than cell survival. Isolated CYLD-deficient skin cells, when treated with the tumor-inducing chemicals, began to proliferate due to an accumulation of Bcl-3 in the nucleus, they found. Treatment with a single dose of ultraviolet light--thought to be a trigger of cylindromas--sparked the same reaction in the mutant cells, they found.

In the absence of CYLD, it is the accumulation of Bcl-3 that is the problem, Fässler said. Bcl-3 is normally under tight regulation; it is primarily found out in the cytoplasm, with very little in the nucleus. Cytoplasm is the clear, jelly-like material in which all the cell's components are suspended.

In animals deficient for CYLD, much too much Bcl-3 makes it into the nucleus where it activates genes leading to the growth of tumors.

In normal skin cells, chemical treatment or UV light prompts the transport of CYLD out into the cytoplasm, they reported. Once there, the protein binds and modifies the cancer promoter Bcl-3 to prevent its nuclear accumulation.

In addition to elucidating the cause of cylindromas, the findings might have important implications for understanding the events underlying skin cancer, and perhaps also tumors in other body tissues, the researchers said.

Indeed, the group noticed an intriguing trend--most of the tumors found in the mutant mice developed from cells of the epidermis rather than the hair-follicle cells thought to be involved in cylindromatosis. They therefore conducted a preliminary analysis of CYLD levels in human skin cancers originating from the epidermis, including basal cell carcinomas (BCC) and squamous cell carcinomas (SCC).

BCC and SCC represent the two most common forms of skin cancer, which together affect an estimated one million Americans each year.

Interestingly, we observed reduced or absent expression of CYLD in more than ten samples of BCC and SCC, respectively, the researchers wrote. This strongly suggests that CYLD plays a general role as a tumor suppressor, which is in agreement with its ubiquitous expression pattern and with a recent observation showing that CYLD levels are downregulated in several other tumors such as kidney, liver, and uterine cervix.

The researchers are now further examining their CYLD-deficient mice to find out whether the animals also show an increased prevalence of colon tumors. Early indications suggest that they do, according to Fässler.

We think the CYLD tumor suppressor involved in cylindromas is likely to be important to many, many other tumors, he said.

Studies shed new light on why exercise can protect against skin and bowel cancers

Fri, 12 May 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Published in the journal Carcinogenesis, one study found that female mice that had 24-hour access to running wheels and were exposed to ultraviolet B light (UVB) took longer to develop skin tumours, developed fewer and smaller tumours, and had decreased amounts of body fat compared to mice that did not have access to running wheels. The second study looked at the development of pre-cancerous polyps in the intestines of male mice and discovered that voluntary exercise and a restricted diet reduced the number and size of polyps and improved survival.

Dr Allan Conney, Garbe Professor of Cancer and Leukemia Research and Director of the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers University, New Jersey, USA, is one of the authors of the skin cancer study. He said that programmed cell death (apoptosis), triggered by exercise, might explain why the running wheel mice did better.

Preliminary indications from follow-up work in the laboratory suggest that voluntary exercise enhances UVB-induced apoptosis in the skin, and that it also enhances apoptosis in UVB-induced tumours. So, although UVB is triggering the development of tumours, exercise is counteracting the effect by stimulating the death of the developing cancer cells.

Our studies may be the first to suggest an apoptotic mechanism for the effect of voluntary exercise in the development of cancer. In addition, we found that voluntary exercise decreased body fat and that the number of tumours decreased with decreasing amounts of fat. This effect may also play an important role in the mechanism and warrants further investigation, bearing in mind the growing rates of obesity in the Western world, particularly in the USA and UK, he said.

Dr Lisa Colbert, Assistant Professor at the University of Wisconsin-Madison, USA, lead author of the bowel cancer study, said that her study was the first to suggest that a negative energy balance, produced by increasing the mice's energy output (by use of a running wheel) while maintaining a restricted calorie intake, appeared to be the important factor in inhibiting the growth of polyps (the fore-runners of bowel tumours).

Negative energy balance was indicated by a lower body weight among the exercising mice, although they retained more body fat at the end of the study than the non-exercising mice an observation that might be due to the fact that the exercising mice were healthier, while the health of the non-exercising mice was beginning to decline due to higher numbers of polyps. There were higher levels of hormones known to be associated with the onset of cancer insulin-like growth factor-1 (IGF-1) and corticosterone amongst the exercising mice, but this did not correlate with higher total polyp numbers. These data suggest that voluntary exercise that induces a negative energy balance protects against the onset of cancer in these mice, but that the mechanism is unlikely to be related to body composition, IGF-1 or corticosterone.

Dr Conney emphasised that it was not known yet whether exercise decreased the risk of sunlight-induced skin cancer in humans, and clinical trials were needed to investigate this further. However, in bowel cancer, evidence from population studies already suggests that physically active people have a reduced risk of developing the disease, but the mechanisms remain unclear.

The skin cancer study involved two experiments. In a high risk model, mice were exposed to UVB three times a week for 16 weeks, and then for the subsequent 14 weeks, in the absence of further UVB treatment, half the mice had access to running wheels in their cages while the other half did not. In a second, complete carcinogenesis model, mice were exposed to UVB twice a week for 33 weeks and, from the beginning, half had access to a running wheel and half did not. Mice not exposed to UVB acted as controls for the study. In both models, the exercising mice increased their food intake and maintained their normal body weight.

The exercising mice in the high risk model had an average of seven weeks without tumours after the UVB exposure ceased, while the non-exercising mice only had an average of 3.5 tumour-free weeks.

Dr Conney said: In both the no running wheel and running wheel groups, the number of tumours per mouse increased with time, but throughout the 14 weeks of tumour development, animals with access to running wheels had a decreased number of tumours per mouse compared to animals with no running wheels. At all times, the tumour size in the no running wheel group was greater than in the running wheel group; on average, the tumour size per mouse for the no wheel group was just over three times more than for the exercise group.

In the complete carcinogenesis model, mice with no running wheel started to develop tumours 20 weeks after the start of UVB exposure, while tumours in the running wheel group started after 23 weeks. The average tumour-free time was 25 weeks for the no running wheel group and 27 weeks for the running wheel group.

Dr Conney said: The rate of increase in tumour numbers per mouse for the no running wheel group was significantly greater than that for the running wheel group. On average, the tumour size per mouse for the no running wheel group was about 3.5 times more than in the exercise group.

In both models, voluntary running decreased the number of non-malignant tumours per mouse by 34%. Exercise substantially decreased the size of non-malignant tumours and malignant tumours: in the high risk model, the non-malignant tumour size per mouse was decreased by 54% and the malignant tumour size per mouse by 73%, and in the complete carcinogenesis model, tumour size per mouse was decreased by 75% and 69% respectively.

For the bowel cancer study, Dr Colbert and her co-authors used mice (APC Min mice) that had a genetic mutation that predisposed them to develop intestinal polyps. Our studies are relevant for humans in that these Min mice have a mutation in one of the same genes, APC, that is also mutated in human colon cancer, she explained. The protective effect of exercise and lower body weight in our mice is consistent with epidemiological evidence in humans that suggests higher levels of activity and lower body weight reduces the risk of colon cancer.

Mutations in the APC gene in humans are responsible for an inherited condition called familial adenomatous polyposis (FAP). FAP affects about one in 10,000-15,000 people worldwide, 95% of whom will develop numerous polyps in the bowel which eventually develop into colon cancer, usually before the age of 40. The gene is mutated in sporadic forms of colon cancer as well.

The researchers randomly assigned seven-week-old male mice to either voluntary wheel running or to no exercise for 10 weeks. For the first three weeks both groups had the same amount of food and water, but after that the exercising mice were fed the amount that the non-exercising mice had eaten the week before so that their food consumption was unable to rise with their increased activity, thereby producing a negative energy balance.

By the end of the ten weeks, six of the 23 control mice had died due to the number of polyps that had grown and the resulting anaemia, while all the 24 exercising mice were still alive.

The exercising mice ran an average of 3.8 km a day, and the further they ran the fewer polyps they had. Exercise significantly reduced total polyp number and polyp size, as well as prolonging survival, said Dr Colbert. On average there were 16 polyps per mouse in the exercising mice compared to 22 polyps in the control mice a decrease of 25%.

Ineffective skin barrier may trigger immune reaction, illness

Tue, 25 Apr 2006 20:10:37 PST

( from http://www.rxpgnews.com ) A genetic finding by researchers at the National Institutes of Health provides new insight into the cause of a series of related, common and complex illnesses including hay fever and asthma as well as the skin disorders eczema and psoriasis and suggests a novel therapeutic approach. These illnesses are essentially inflammatory disorders of the tissues that separate the inside of the body from the outside world, such as the skin and the linings of the throat and lungs.

In the May issue of The Journal of Clinical Investigation, researchers from the National Human Genome Research Institute, the National Eye Institute, and the National Institute of Child Health and Human Development, all part of the National Institutes of Health, report that excessive production of a specific protein disrupts the protective properties of the skin barrier. Once the skin barrier is compromised, immune-system-stimulating chemicals allergens can enter the body and cause an inflammatory reaction that, in turn, stimulates skin cells to grow rapidly, further diminishing the protective function of the skin. The compromised barrier, in turn, becomes more porous to allergens that then stimulate more inflammation in a cycle that eventually produces common skin conditions such as psoriasis and eczema.

It may, however, be possible to break the cycle by creating a temporary, artificial barrier on the skin that blocks incoming allergens. The solution could be as simple as developing a lotion that effectively blocks allergens from getting through damaged skin. Keeping allergens out of the skin would keep the immune system from over-stimulating cell growth, giving the skin time to re-create a normal barrier. Current therapies for these skin conditions principally focus on suppressing the immune system, but the medicines used can produce undesired side-effects.

"The human body is an incredibly complex system," said Elias A. Zerhouni, M.D., director of the National Institutes of Health. "Only by conducting this kind of basic research can we hope to understand the causes of complex diseases. And only by understanding disease can we produce a future in which we can predict who is at risk, pre-empt the illness from ever occurring and personalize the treatment when it does."

Several recent studies have suggested that defects in the skin barrier may be as important to eczema and psoriasis as the hyperactive response of the immune system. In addition, doctors have observed that individuals with eczema are also likely to develop hay fever and asthma, suggesting a common mechanism for both disorders. The other risk factor for these conditions is having a relative with the disorder, suggesting a genetic connection.

To test whether a defective skin barrier can actually produce these diseases, a team of NIH researchers focused on a specific gene called connexin 26, which makes a protein that forms connections between skin cells that create the normal barrier. When the skin is intact, the production of connexin 26 is turned off once there is enough to hook all the skin cells together. When skin is damaged by a cut or a scrape, connexin 26 is produced while new skin cells reproduce and heal the wound. Researchers have shown that connexin 26 production is turned on in the sore skin of people with psoriasis, but it wasn't clear what role connexin 26 played in the disorder.

To determine connexin 26's role in psoriasis, NIH researchers created a line of transgenic mice that over-produce connexin 26. The resulting mice develop psoriatic-type skin sores, just like humans with psoriasis.

"This discovery demonstrates the power of animal models to unravel complex conditions of medical importance," said Eric D. Green, M.D., Ph.D., NHGRI's scientific director and the director of the institute's Division of Intramural Research, where the research was conducted. "Our current abilities to rapidly create new genetically altered animal models allow researchers to move from conception of an idea to its implementation at an incredible pace."

The discovery broadens the basic understanding of the causes of skin disorders such as psoriasis and eczema, and may well contribute to the basic understanding of asthma and hay fever, conditions that arise when allergens penetrate the tissue barrier in the lungs and nose, respectively.

"Hopefully, this will help us understand the complex genetics of psoriasis," said Julia A. Segre, Ph.D., an investigator in NHGRI's Genetics and Molecular Biology Branch and the senior author on the paper. "Previous genetic studies have focused on the genes that regulate immune response. We are now examining the effect of genes that are involved in both regulating the growth of skin cells and signaling to the immune cells."

The problem causing these related disorders may simply be the body over-reacting to an allergen getting through the barrier that is supposed to block it. "The skin goes into a stress response and overcompensates by trying to rebuild the barrier too fast, actually becoming less effective," Dr. Segre said. "The skin cells grow so fast that they fail to make a normal barrier, and the body is stimulating the immune response because of material (chemicals and allergens) coming through the barrier."

Understanding the genetics of skin disorders may well have important implications for more serious illnesses, such as asthma. It is not uncommon for a family doctor to face the dilemma of a child who has eczema and then having to decide how aggressively to treat the disease. Eczema is not particularly dangerous, but children presenting with eczema commonly go on to develop asthma, which severely compromises quality of life and in rare cases can be lethal. Treating eczema with immune-suppressing drugs, which may also prevent asthma from developing, may cause undesirable side effects.

The genetic studies suggest that researchers now need to focus on both turning down the immune response, as well as restoring a normal skin barrier to keep the outside world out of the body.

"The barrier function of epithelial surfaces is important in all tissues that have contact with the outside world. In addition to the skin and respiratory tract, it includes the gastrointestinal tract, and the ocular surface," said Ali Djalilian, M.D., formerly a research fellow and medical officer at the National Eye Institute but now at the University of Illinois in Chicago, and the lead author of the paper. "These findings underline the importance of this barrier function and suggests a new strategy for restoring it in human diseases."

Recurrent melanoma may be more common than previously thought

Tue, 18 Apr 2006 14:22:37 PST

( from http://www.rxpgnews.com ) Approximately 8 percent of patients with melanoma skin cancer may develop an additional melanoma within two years of their initial diagnosis, and those with atypical moles appear to be at higher risk, according to an article in the April issue of Archives of Dermatology, one of the JAMA/Archives journals.

Cutaneous (skin) melanoma begins in cells known as melanocytes, which produce the pigment that gives skin its color. Previous studies have evaluated the recurrence of melanoma among patients already diagnosed with the disease; most have estimated that less than 4 percent of them will develop additional tumors in the year following diagnosis, according to background information in the article.

Linda Titus-Ernstoff, Ph.D., Dartmouth Medical School, Lebanon, N.H., and colleagues assessed the frequency of and risk factors for recurring cancer among 354 New Hampshire residents with a first diagnosis of cutaneous melanoma. Participants completed a 40-minute telephone interview, during which they answered questions about medical history, demographics, eye and hair color, sun exposure and whether their skin tanned, burned or freckled in the sun. They then underwent a skin examination, during which a physician identified and catalogued benign and atypical moles. Atypical moles have at least three of the following features: a diameter larger than 5 millimeters, redness, an irregular or ill-defined border, a variety of colors or a portion that is flat.

By examining pathology records, the researchers found that 20 (6 percent) of the participants developed an additional melanoma within one year of diagnosis and 27 (8 percent) developed an additional melanoma within two years. Sixty-three percent of those who developed additional tumors and 37 percent of those who did not had at least one atypical mole. The more atypical moles an individual had, the more likely he or she was to develop additional melanomas--three or more atypical moles indicated four times the risk. Lifetime history of sun exposure did not appear to influence the risk of recurring melanoma. However, those with a history of sunburn were less likely to develop a second melanoma than those without, a finding that "must be viewed cautiously," the researchers write. Those who are predisposed to develop multiple melanomas may be less susceptible to sunburn than those with one melanoma, or they may be more likely to avoid sun exposure. "In any case, the association should not be construed as suggesting that sunburn protects patients with melanoma from developing additional tumors," the authors continue.

"The importance of studying risk for additional primary tumors within a defined population-based study group is underscored by our findings," they conclude. "These findings, which indicate a higher frequency of second primary melanomas than suggested by previous studies, also underscore the importance of close surveillance of patients with melanoma."

Recurrent melanoma may be more common than previously thought

Mon, 17 Apr 2006 03:59:37 PST

( from http://www.rxpgnews.com ) Cutaneous (skin) melanoma begins in cells known as melanocytes, which produce the pigment that gives skin its color. Previous studies have evaluated the recurrence of melanoma among patients already diagnosed with the disease; most have estimated that less than 4 percent of them will develop additional tumors in the year following diagnosis, according to background information in the article.

Linda Titus-Ernstoff, Ph.D., Dartmouth Medical School, Lebanon, N.H., and colleagues assessed the frequency of and risk factors for recurring cancer among 354 New Hampshire residents with a first diagnosis of cutaneous melanoma. Participants completed a 40-minute telephone interview, during which they answered questions about medical history, demographics, eye and hair color, sun exposure and whether their skin tanned, burned or freckled in the sun. They then underwent a skin examination, during which a physician identified and catalogued benign and atypical moles. Atypical moles have at least three of the following features: a diameter larger than 5 millimeters, redness, an irregular or ill-defined border, a variety of colors or a portion that is flat.

By examining pathology records, the researchers found that 20 (6 percent) of the participants developed an additional melanoma within one year of diagnosis and 27 (8 percent) developed an additional melanoma within two years. Sixty-three percent of those who developed additional tumors and 37 percent of those who did not had at least one atypical mole. The more atypical moles an individual had, the more likely he or she was to develop additional melanomas--three or more atypical moles indicated four times the risk.Lifetime history of sun exposure did not appear to influence the risk of recurring melanoma. However, those with a history of sunburn were less likely to develop a second melanoma than those without, a finding that must be viewed cautiously, the researchers write. Those who are predisposed to develop multiple melanomas may be less susceptible to sunburn than those with one melanoma, or they may be more likely to avoid sun exposure. In any case, the association should not be construed as suggesting that sunburn protects patients with melanoma from developing additional tumors, the authors continue.

The importance of studying risk for additional primary tumors within a defined population-based study group is underscored by our findings, they conclude. These findings, which indicate a higher frequency of second primary melanomas than suggested by previous studies, also underscore the importance of close surveillance of patients with melanoma.

Dark skin needs more sun exposure for Vitamin D

Wed, 05 Apr 2006 14:20:37 PST

( from http://www.rxpgnews.com ) Dark-skinned people need up to six times as much sunlight as those with fair skin to produce the same levels of Vitamin D, says a new study.

Researchers at the Australian National University found that fair-skinned people need over four minutes in the summer sunshine to produce enough Vitamin D whereas dark-skinned people need more, reported online edition of Daily Mail.

Acceptable levels of sunbathing also depends on geography and the amount of solar ultraviolet radiation, says the study.

Between two and 14 minutes of midday summer sun three or four times a week on the face and arms will produce an adequate dose of the vitamin for those living in Australia, they said.

But people living in Britain would need twice the exposure because the sun's rays are not as intense.

Vitamin D is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralisation of bone.

Sunlight is the most abundant natural source that helps our bodies make vitamin D. About 10 percent of Vitamin D comes from food, such as oily fish.

Lack of sunlight can lead to Vitamin D deficiency, which can cause rickets in children, osteoporosis in adults, and also contribute to cancer, diabetes and hypertension, the study said. Scientists have also said excess exposure could cause harm.

Addictive effects of frequent tanning - Study

Wed, 29 Mar 2006 06:35:37 PST

( from http://www.rxpgnews.com ) Frequent users of tanning beds may be getting more out of the experience than darker skin, according to researchers from Wake Forest University Baptist Medical Center. New evidence suggests that ultraviolet light has "feel-good" effects that may be similar to those of some addictive drugs.

"We had previously shown that ultraviolet light has an effect on mood that tanners value," said Mandeep Kaur, M.D., lead author. "Now, in this small study, we've shown that some tanners actually experience withdrawal symptoms when the 'feel-good' chemicals are blocked."

The research reported in the April issue of the Journal of the American Academy of Dermatology involved eight frequent tanners and eight infrequent tanners. Frequent tanners were those who tan eight to 15 times a month, or more than necessary to maintain a tan. Infrequent tanners were those who use tanning beds no more than 12 times a year.

The research was designed to test the hypothesis that exposure to ultraviolet (UV) light may produce endorphins, brain chemicals that are linked to pain relief and euphoric feelings, and could play a role in tanning behavior. UV light occurs naturally in sunlight and is responsible for the tanning and burning effects of the sun. Artificial UV light is used in tanning beds and sunlamps.

In 2004, the Wake Forest researchers reported on a study in which participants had tanning sessions in two identical-looking tanning beds. Tanners spent half of each session in one bed, which used UV light, and half in the other, which didn't. Mood was measured before and after each tanning exposure. The results revealed greater relaxation and lower tension after UV exposure compared to non-UV exposure.

In the current study, the researchers hoped to discover whether endorphins could be driving the tanning behavior. Half of tanners were given an inactive drug and half were given a drug to block the effects endorphins and other opioids, which include narcotics such as morphine. Participants then tanned in both the UV and non-UV beds.

At higher doses of the opioid-blocking medication (15 mg. of naltrexone), frequent tanners showed a reduced preference for UV tanning. And, four of the eight frequent tanners reported nausea or jitteriness. None of the infrequent tanners who took the drug reported these symptoms.

"The finding was unexpected and is consistent with the hypothesis that frequent tanning is may be driven in part by a mild dependence on opioids, most likely endorphins," said Steven Feldman, M.D., Ph.D., senior researcher and a professor of dermatology. "The nausea and jitteriness induced by the medication are consistent with symptoms of mild opiate withdrawal."

The researchers said that while the study is small, it supports the hypothesis that tanning behavior may be driven by endorphins in much the same way that the so-called "runner's high" helps to motivate runners.

Kaur said the finding is significant because, like other risky behaviors, it is important to understand why frequent tanners choose the activity. Exposure to UV through tanning has been shown to damage the genetic information in cells and is linked to the development of skin cancer. Despite this, there was a 300 percent increase in the number of indoor tanners in the United States between 1986 and 1996.

Eczema Producing Gene Discovered

Wed, 22 Mar 2006 11:07:37 PST

( from http://www.rxpgnews.com ) Experts on genetic skin disorders at the University of Dundee, with collaborators in Dublin, Glasgow, Seattle and Copenhagen, have discovered the gene that causes dry, scaly skin and predisposes individuals to atopic dermatitis (eczema). Some of these individuals also develop a form of asthma that occurs in association with eczema.

Currently, only symptomatic treatment of ichthyosis vulgaris and eczema is possible, using emollients and ointments to try to prevent the skin drying out or anti-inflammatory drugs to treat the inflamed skin in eczema. Now that the underlying gene defect behind this disorder is known, it will be possible to design new more effective therapies to tackle the root cause of the problem, rather than treating the symptoms. The Dundee group is already working on developing methods to treat and even prevent these diseases.

The gene in question produces a protein called filaggrin which is normally found in large quantities in the outermost layers of the skin. This protein is essential for skin barrier function, helping to form a protective layer at the surface of the skin that keeps water in and keeps foreign organisms out.

Reduction or complete absence of this important protein leads to impaired formation of the skin barrier. As a result, the skin dries out too easily and in addition, the outer layers of the skin are poorly formed and constantly flake off. As well as keeping water in, the skin barrier normally keeps foreign substances out of the skin. In people with filaggrin mutations, foreign substances can easily enter the skin and be seen by the immune system. This explains the development of inflamed skin (eczema). In some people, priming of the immune system through the "leaky" skin appears to lead to asthma when foreign substances later enter the lungs.

The first study, led by geneticists Professor Irwin McLean and Dr Frances Smith in Dundee and their dermatology colleague, Dr Alan Irvine, Our Lady's Hospital for Sick Children, Dublin, discovered that about 10% of European people carry a type of genetic mutation that switches off the filaggrin gene and this causes a very common dry, scaly skin condition, known as ichthyosis vulgaris. About 5 million people in the UK alone make only 50% of the normal amount of filaggrin protein and have a milder form of the disorder where the skin is dry and flaky. About 1 in 500 people, or 120,000 people in the UK, have both copies of the gene knocked out by genetic mutations and have no filaggrin protein whatsoever in the skin. These individuals have a severe and persistent form of the disease, often requiring specialist treatment.

A second study showed that many people with ichthyosis vulgaris also have eczema. Further research then showed a link between ichthyosis vulgaris, eczema and asthma. McLean, Smith and Irvine, in collaboration with Drs Colin Palmer and Somnath Mukhopadhyay of the Dundee BREATHE study, and Professor Hans Bisgaard in Copenhagen, showed in four independent experiments that these common mutations in the filaggrin gene are a major predisposing factor in the development of eczema and the form of asthma associated with eczema.

* A significant association between filaggrin mutations and eczema was shown in familes affected by ichthyosis vulgaris.
* About two-thirds of Irish children with eczema examined were found to carry one or more filaggrin mutations.
* In a study of Scottish children with asthma, there was a very strong association between filaggrin mutations in those children who had both eczema and asthma.
* In a study of Danish babies whose medical history was followed for the first years of life, there was again a strong association between filaggrin mutations and eczema.
* The Danish study also showed that more than 60% of the children carrying filaggrin mutations get eczema within the first couple of years of life.

About 5 million people in the UK carry one of the filaggrin mutations and consequently, have dry skin and are predisposed to eczema and to a lesser extent, asthma.

Worldwide, about 60 million people are estimated to carry these particular gene defects and more than 1 million are predicted to have the severe form of the disease as a consequence of these mutations alone.

Defective immune system response to smallpox vaccine detailed in new study

Tue, 21 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com ) The investigators are part of NIAID's Atopic Dermatitis and Vaccinia Network, which was created in 2004 to integrate clinical and animal research aimed at reducing the risk of eczema vaccinatum, a potentially deadly complication of smallpox vaccination. Eczema vaccinatum occurs almost exclusively in people who have a history of atopic dermatitis, a common, non-contagious skin disorder also known as eczema.

This new research, the first to be published by Atopic Dermatitis and Vaccinia Network scientists, illuminates one potential mechanism leading to eczema vaccinatum and improves our understanding of the immune responses to smallpox vaccine of people with atopic dermatitis, says NIAID Director Anthony S. Fauci, M.D.

Published in this month's issue of Immunity, the study details how the overproduction in skin cells of inflammation-promoting molecules called interleukin-4 and interleukin-13 (IL-4 and IL-13) hampers LL-37 activity in people with atopic dermatitis. LL-37, a small protein produced in skin cells, is part of the body's first line of defense against invaders. Earlier research by Dr. Leung and his colleagues suggested that LL-37 is critical in controlling the spread of vaccinia virus.

In the current study, the investigators used skin samples taken from people with atopic dermatitis (as well as samples taken from healthy volunteers without skin disease and from people with another skin condition called psoriasis) to further investigate how dysfunctions in the immune response of people with eczema set the stage for eczema vaccinatum. When exposed to vaccinia virus, the skin samples from healthy volunteers and from those with psoriasis reacted by producing more LL-37. As a result, the replication of the virus was controlled and eventually halted. In contrast, LL-37 production was minimal in skin samples from people with atopic dermatitis and vaccinia replication was poorly controlled. Next, the scientists exposed skin samples from people with atopic dermatitis to vaccinia, and then added LL-37. With the LL-37 supplement, the skin cells successfully controlled the viral replication.

Dr. Leung and his group then looked more closely at why vaccinia infection fails to induce LL-37 production in atopic dermatitis skin. Comparing immune responses of skin cells grown in the lab from healthy volunteers and from people with atopic dermatitis, the researchers found that the latter skin samples produced excessive amounts of IL-4 and IL-13. Adding IL-4 and IL-13 to skin cells from healthy volunteers prior to vaccinia exposure reduced levels of LL-37 production. Conversely, when the scientists applied IL-4- and IL-13-neutralizing antibodies to skin samples from people with atopic dermatitis, LL-37 production increased significantly.

Together, these findings suggest a rationale for new treatment approaches to eczema vaccinatum, notes Dr. Leung. One approach involves developing drugs to mimic the action of LL-37 or developing LL-37-containing creams that could be applied to the skin in order to boost its ability to contain vaccinia virus infection. Another approach could be to develop agents to neutralize IL-4 and IL-13. Although no such drugs are currently marketed, compounds that can neutralize IL-4 and IL-13 are under study as possible asthma and allergy treatments, Dr. Leung says, and might also be applied to eczema vaccinatum treatment.

Smallpox vaccine, which is made with live vaccinia virus (a close relative of the virus that causes smallpox), has not been routinely given in the United States since the early 1970s. But recent concerns about the possibility of a bioterrorist attack using smallpox virus prompted authorities to reinstate voluntary smallpox vaccination for specific groups, such as military personnel. In the first five months of 2003, the U.S. Department of Defense vaccinated more than 450,000 personnel against smallpox. During this period, the majority of those who deferred vaccination cited atopic dermatitis or other skin conditions as the main reason.

Injection of synthetic polymer may improve facial wasting syndrome associated with HIV

Mon, 20 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Advances in treatments for HIV, including combination antiretroviral therapy, have enabled patients with the disease to live longer and healthier lives, according to background information in the article. Because of their longer lifespans, some patients with HIV are now experiencing additional complications. Changes in body fat distribution, including loss of subcutaneous fat in the face, may be a side effect of antiretroviral therapy and affect somewhere between 10 and 62 percent of individuals with HIV, the authors write. This facial lipoatrophy or facial wasting may lead to anxiety, depression, self-image problems and difficulties in social or sexual relationships.

Anna Maria Cattelan, M.D., University of Padua, Italy, and colleagues studied the efficacy, safety and tolerability of polylactic acid injections on 50 HIV¬¬¬infected patients (42 men, 8 women) with moderate to severe facial lipoatrophy who visited an outpatient clinic between January and June 2002. Participants were given a full physical examination and questionnaire about the degree of their facial lipoatrophy and their overall health status when they enrolled in 2002. Facial photographs were taken and they underwent ultrasound evaluation, which recorded the thickness of the skin over their cheeks. The researchers then administered four sets of injections at the beginning of the study and again after 30, 45 and 60 days. The 16 patients with the most severe facial wasting received two additional injections after 75 and 90 days.

The patients' facial atrophy began to improve after the second injection and remained visibly improved through the end of the follow-up period (12 months). Twelve months after the end of the treatment period, the total thickness of skin and fat increased an average of 3.4 millimeters over the right cheek and 3.3 millimeters over the left cheek. More than half of the patients had rated their facial lipoatrophy as severe at the beginning of the study; after finishing treatment none did so, and 12 months later two patients (4 percent) rated their condition as severe and more than half rated it as absent to moderate. Fifteen (30 percent) of the participants experienced adverse reactions to the injections, but none were severe and none interrupted treatment because of them. Questionnaire results also revealed an improvement in self-perceptions of well-being after treatment.

The results of our study show that the correction of facial lipoatrophy with polylactic acid applications is safe and effective in increasing dermal thickness after a complete cycle of four to six injections, with a durability of response lasting until month 12 of follow-up, the authors conclude. These benefits were confirmed by ultrasonographic study, with a significant increase in dermal thickness that persisted at 36 to 40 weeks after the last injection. Our patients did not need either hospitalization or chemoprophylaxis [preventive medications] and were treated using an outpatient regimen, without affecting their daily activity.

Corrective cosmetics may not boost quality of life for women with severe facial blemishes

Wed, 08 Mar 2006 04:59:37 PST

( from http://www.rxpgnews.com )

Using makeup to cover a severe facial blemish may not improve the quality of a woman's life, a new study suggests.

It did not matter how severe or what kind of blemish she had, whether it was a case of severe acne, a noticeable facial scar or pronounced dark spots covering the face.

The women who used foundations to cover these kinds of marks reported having a lower health-related quality of life than did the women who didn't wear the same kind of makeup, said Rajesh Balkrishnan, the study's lead author and the Merrell Dow professor of pharmacy at Ohio State University.

While it may seem obvious that anyone with a severe blemish on their face contends with psychological issues, until this study, no one had systematically evaluated how such blemishes affect women psychologically, said Balkrishnan.

Though they may not have much effect on physical health, severe facial marks may have a significant impact on self-image and over time, that could adversely affect a woman's health, he said. In this case the psychological impact often outweighs the physical aspects of the problem the women in our study reported having more problems with social and sexual functioning than with physical functioning.

The study appears in a recent issue of the International Journal of Dermatology.

Of the 73 women in the study, 66 used what Balkrishnan calls corrective cosmetics while seven did not. Corrective cosmetics are skin-colored foundations meant to conceal serious blemishes. It's not the kind of makeup that would typically be found in the cosmetics aisle of a drug store, and a dermatologist usually recommends these foundations to her patient.

The women who used foundation to cover blemishes may have had a tougher time psychologically dealing with their blemishes than did the women who didn't use corrective makeup, Balkrishnan said. Although it's difficult to say why this is, it may be that the women who didn't wear makeup to cover their blemishes felt more confident in their appearance.

These kinds of cosmetics are also fairly expensive one company sells a 1-ounce jar of its corrective foundation for $27.50.

The majority of women that Balkrishnan and his colleagues surveyed had severe facial scarring, acne, melasma a pronounced pigmentation of the upper cheeks, bridge of the nose, forehead and upper lip or hyperpigmentation, a condition in which patches of facial skin become very dark. Most of the women had only one type of blemish. Participants' average age was 37.

The overwhelming majority of women (90 percent) reported that they used some type of corrective foundation to cover the blemish, although the researchers did not record the brands of makeup that the women wore. Overall, the women were in good physical health.

The researchers used the Blemish Area and Severity Index (BASI) to quantify the area of the face covered by the blemish and to rate the severity of the blemish. Included in the BASI survey were questions that measured health-related quality of life issues, as well as questions that measured each woman's fear of negative evaluation by others.

The researchers asked each woman to rate their health in general answer choices ranged from excellent to poor. The women were also asked questions about any recent problems with physical or mental health, and how often poor physical or mental health kept them from doing their usual activities.

The survey also asked women to describe what they thought life would be like if they didn't have to contend with the blemishes.

Not surprisingly, having a severe facial blemish negatively affected how most of the women perceived the quality of their lives. But the women who wore foundations to conceal their blemishes reported having a lower health-related quality of life than did the seven women who said that they did not wear this kind of makeup.

The women who didn't wear makeup did not necessarily have less severe blemishes, either, Balkrishnan said.

Overall, the women who used foundation treatments felt that they were worse off physically and mentally than the women who weren't using these treatments, Balkrishnan said.

Whether or not they wore makeup, participants overwhelmingly felt that without their blemish other people would see them in a less negative light, and that the overall quality of their lives would improve.

Interestingly, the researchers found no difference in health-related quality of life scores based on the type and size of a blemish. For example, a woman with bad acne did not feel any worse or any better than a woman with melasma.

But the more fearful a woman was of being negatively evaluated in public, the lower she rated her health-related quality of life.

Researchers aren't certain exactly how severe blemishes affect a woman's mental health, and a study like this one may help in designing better treatments, including corrective cosmetics, for women, Balkrishnan said.

He conducted the study with researchers from the departments of dermatology, psychiatry and public health services at Wake Forest University School of Medicine in Winston-Salem, N.C.; the division of management and policy sciences at the University of Texas School of Public Health in Houston; and Vichy Laboratoires and Tarnier Hospital, both in Paris.

Imiquimod cream reduces fine lines and wrinkles

Mon, 06 Mar 2006 17:28:37 PST

( from http://www.rxpgnews.com ) Results from a new study show that Aldara (imiquimod) Cream, 5%, a topical skin cancer treatment, improved the structure and appearance of prematurely aged skin, including fine lines, wrinkles, dyspigmentations and texture. The findings, from researchers at S.K.I.N. Incorporated, a dermatology research facility, are presented as a poster this weekend at the 64th Annual Meeting of the American Academy of Dermatology in San Francisco.

Aldara Cream is an immune response modifier used to treat precancerous skin lesions called actinic keratoses (AK) as well as superficial basal cell carcinoma (sBCC), a nonmelanoma skin cancer. It works by stimulating the body's immune system. AK and sBCC are the result of a lifetime of exposure to ultraviolet rays of the sun. Long-term exposure to the ultraviolet rays of the sun can also cause structural and cosmetic damage to the skin commonly referred to as photodamage. Photodamaged skin is characterized by fine lines and wrinkles, roughness, dryness, lack of firmness and irregular pigmentation.

"Our results indicate that Aldara Cream may offer patients cosmetic benefits in addition to its important therapeutic role in treating precancerous and cancerous skin lesions," said Albert Kligman, MD, PhD, Professor Emeritus of Dermatology at the University of Pennsylvania and lead investigator in this study. "We initiated this study after anecdotal finding that some AK patients treated with Aldara Cream reported cosmetic improvements to their skin. Further exploration of the cosmetic uses for Aldara Cream is clearly warranted."

The open-label study included ten healthy females with visible signs of photoaging. Volunteers received Aldara Cream five times per week for four weeks. At predetermined intervals, the subjects were evaluated for both visible and microscopic-level changes to the underlying skin structures.

According to the results of this small study, treatment with Aldara Cream corrected the structural changes associated with photodamage caused by sun exposure. Additionally, use of Aldara visibly reduced fine lines and wrinkles, improved skin texture and resulted in more uniform skin color. At the end of the study, 80 percent of the subjects rated these improvements as "moderate" or "great." According to subjects' assessments, 90 percent expressed strong approval of the cosmetic benefits. The visible improvement in appearance was also documented by histological study of biopsies. Aldara Cream was well tolerated in the study and no volunteers reported irritation with redness, stinging, or discomfort.

Journal article validates the coming of age of hair replacement surgery

Mon, 06 Feb 2006 04:59:37 PST

( from http://www.rxpgnews.com ) Published in the January 2006 issue of Dermatologic Surgery, the article examines a study piloted by Dr. Harris to determine the efficacy of the SAFE Surgically Advanced Follicular Extraction (SAFE) System. The SAFE System SM, developed and patented by Dr. Harris in 2004, utilizes a small, self-contained device to isolate, extract and transplant singular units of hair without the trauma associated with other types of hair transplantation surgery.

Twenty-two patients were enrolled in this pilot study, followed by an additional 37 based on the success of the first group. Final results of the study indicate lower follicular transection rates, the cutting or damaging of hair follicles, than traditional follicular unit extraction.

The results of Dr. Harris' study are positive news for the roughly 40 million Americans experiencing hair loss. Lower transection rates mean increased accessibility for African-American and elderly patients who may not have qualified for the procedure due to particular hair qualities. Other benefits of the SAFE System methodology include virtually pain-free surgery, faster recovery time and increased efficiency for physicians performing the procedure.

These results are very exciting for anyone who has considered hair replacement, explained James Harris, MD. I feel strongly that this is the future of our specialty offering excellent options for every candidate.

Prior to the development of the SAFE System, hair transplant surgeons had to rely on traditional, invasive surgical procedures that required the surgeon to surgically remove strips of scalp from the sides or back of the head, resulting in a linear scar and a lengthy healing time. In recent years, technological advancements have led to the development of Follicular Unit Extraction. Follicular Unit Extraction (FUE) involves the removal of singular follicular units of hair. While less invasive than traditional transplants, traditional FUE is time consuming, more expensive and only appropriate for a small percentage of patients. The SAFE System was developed to improve upon the difficulties associated with this system of FUE.

A survey by the International Society of Hair Restoration Surgery underscores the growing popularity of hair replacement surgery. The survey found that more than 168,000 hair transplant procedures were performed worldwide in 2004, with about half of those procedures being performed in the United States. The survey found that 40 is the average age of men and women seeking these procedures.

Dr. Harris will present the SAFE System and further advancements in hair tranplantation as the host of the first-ever International Society of Hair Replacement Surgery Regional Workshop. Physicians from around the world will gather in Denver on April 21-23 to participate in live surgery demonstrations and listen to lectures by leaders in the area of FUE.

Antibiotics For Acne May Increase Risk Of Common Infectious Illness

Fri, 23 Sep 2005 15:25:38 PST

( from http://www.rxpgnews.com ) Individuals treated with antibiotics for acne for more than six weeks were more than twice as likely to develop an upper respiratory tract infection within one year as individuals with acne who were not treated with antibiotics, according to an article in the September issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Although there is considerable concern that the overuse of antibiotics will lead to resistant organisms and an increase in infectious illness, there have been few studies on people who have actually been exposed to antibiotics for long periods, according to background information in the article. Patients with acne, for which long-term antibiotic use is standard and appropriate therapy, represent a unique and natural population in which to study the effects of long-term antibiotic use, the authors suggest.

Using statistical models and controlling for possible confounding variables including how often individuals were likely to see a physician, the researchers compared the incidence of a common infectious illness, upper respiratory tract infection (URTI), in individuals with acne who were treated with antibiotics to those whose acne was not treated with antibiotics.

Of 118,496 individuals with acne, 84,977 (71.7 percent) received either topical or oral antibiotic for more than six weeks for treatment of their acne and 33,519 (28.3 percent) did not. "Within the first year of observation, 18,281 (15.4 percent) of the patients with acne had at least one URTI, and within that year, the odds of a URTI developing among those receiving antibiotic treatment were 2.15 times greater than among those who were not receiving antibiotic treatment," the authors report.

"In this study, we have shown that the odds of a URTI developing among individuals who use an antibiotic to treat acne is about two times greater compared with those who do not use an antibiotic," the authors conclude. "The true clinical importance of our findings, in which patients and practitioners need to balance the risk of these infections with the benefits that patients with acne receive from this therapy, will require further investigation. However, patients with acne represent an ideal model in which to study the long-term effects of antibiotic therapy, the risks associated with colonization, and the risks of increasing resistance among bacterial pathogens exposed to antibiotics during treatment."

"Margolis and coworkers should be congratulated on a well-designed study, albeit with stated limitations and the need for further analysis," the authors conclude. "We can all hope that their findings will stimulate further research to strengthen or dispel the observed association between URTIs and antibiotic use in patients with acne. Large prospective clinical studies will be required, ideally as part of a randomized trial.

Dithranol may hold more hope for psoriasis sufferers

Tue, 06 Sep 2005 00:19:38 PST

( from http://www.rxpgnews.com ) Scientists at the University of Newcastle upon Tyne, studying the effects of a drug used in the treatment of a distressing skin condition, have found that it is actually killing off the cells which are the cause of the problem.

The team believe the discovery represents a major step towards enabling the design of better treatments for psoriasis, which affects up to a million people in the UK alone (figures from the Psoriasis Association).

Dithranol, which is widely used in the treatment of psoriasis, is derived from a natural compound, called chrysarobin. Chrysarobin is prepared from the araroba tree found in the rain forests of the Amazon. In India, the same substance is known as Goa powder.

Psoriasis is a genetic condition which, when triggered by certain factors such as injury or throat infection, leads to an over-production of skin cells ¬¬ called keratinocytes which causes a thickening of the skin, resulting in the raised red, scaly patches characteristic of psoriasis.

The team of scientists, led by Professor Nick Reynolds and Dr Mark Birch-Machin, of the Skin and Environmental Interactions Research Group in the School of Clinical and Laboratory Sciences at Newcastle University, studied the effects of dithranol an ointment applied to the surface of the skin which is used in the treatment of severe cases of psoriasis.

Professor Reynolds says: 'Psoriasis is what is known as a relapsing/remitting condition, which means that sufferers don't display the symptoms all of the time. Dithranol is a very effective treatment for episodes of psoriasis and it has been around for a long time, since the early 1900s. By studying the action of the drug, we wanted to gain a better understanding of how it works, to give us an insight into the mechanism of the condition.'

Laboratory studies showed that dithranol very quickly targeted skin cells' mitochondria the part of a cell from which it draws its energy causing the cells to die within 24 48 hours of the application of the drug, through a process of programmed cell death.

Professor Reynolds continued: 'Although dithranol is a very effective and safe treatment for psoriasis, its widespread use is limited because it is quite difficult to use and causes dark brown stains on clothing and bedding. Also, if it is not used properly, it can cause irritation or burning to the skin around the affected area, so it is most commonly used in hospitals, where the application of the ointment can be overseen by a nurse.'

Most people suffering an episode of psoriasis that requires treatment with dithranol therefore have either to attend hospital as an outpatient five days a week for a six week course of treatment, or be admitted for a three-week period.

'In modern life, this is far from ideal', says Professor Reynolds. 'These findings represent an important step towards the development of better-designed treatments for psoriasis sufferers'.

Gladys Edwards, Chief Executive of the Psoriasis Association said: 'The Psoriasis Association welcomes these new research findings. It is so important to develop new, effective and safe treatments for psoriasis and this research is clearly a positive step forward'.

Immune protection factor (IPF) in sunscreens is essential in determining cancer prevention ability

Mon, 29 Aug 2005 22:09:38 PST

( from http://www.rxpgnews.com ) Immune protection factor (IPF) in sunscreens and its relation to sun protection factor (SPF) is essential in determining skin cancer prevention ability, researchers found.

In this paper, published in the September issue of the Journal of Investigative Dermatology , researchers discuss the problems associated with the evaluation of IPF of sunscreens, different techniques for the assessment of IPF in human skin, and propose development of standard techniques for IPF assessment.

Based on past discussion by experts convened by L'Oréal Recherche in Paris in 2002, five groups of immunosuppresion researchers met to discuss the status of IPF in human skin for this study. The researchers tested different sunscreens, methods and factors on volunteers from Australia, Austria, France, UK and USA to establish a standard method for determining IPF.

According to the researchers, the relationship between a sunscreen's SPF and its ability to protect against immunosuppression is not presently known. A sunscreen with high SPF but a low protection against immunosuppression, or IPF, could in fact increase skin cancer risk. The paper describes progress in assessing sunscreen immune protection and demonstrates that much work is still needed to define a standard method to do this.

Immunotherapy Used Successfully to Treat Warts

Wed, 18 May 2005 16:58:38 PST

( from http://www.rxpgnews.com ) Injection of skin test antigens (preparations used in skin tests for immunity) into warts appears to stimulate the immune system and successfully treat the injected wart and also helps to treat distant non-injected warts, according to a study in the May issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Warts are unsightly and often tender or painful, causing most patients with warts to seek treatment. Primary treatment usually involves destruction of the wart using one of a number of different techniques, including cutting it out, applying salicylic acid, freezing it with liquid nitrogen and laser vaporization, according to background information provided in the article. Because wart proliferation is controlled by the immune system, various methods have been tried to stimulate an immune response to the human papillomavirus (HPV), the cause of skin warts. Previous studies have shown that injecting a wart with an antigen preparation of mumps, Candida (a cause of yeast infections) or Trichophyton (a cause of fungal infections) clears the wart and other distant and distinct warts. These skin test antigens, although they can not cause or promote infection themselves, cause a reaction on the skin if a person has been previously exposed to mumps, Candida or Trichophyton, and are used to test for immunity.

Thomas D. Horn, M.D., of the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a randomized, clinical trial to determine the effectiveness of wart treatment with injection of skin test antigen. Warts were injected with antigen alone, antigen plus interferon alfa-2b (a chemical produced by the immune system), interferon alfa-2b alone or normal saline. Patients who had more than one wart were also tested for an immune response to HPV. Because interferon alfa-2b had no impact on the results, the patient data were analyzed in two groups, those who had received antigen and those who did not.

Of the 201 patients enrolled in the study, 95 received injections of antigen and 106 received injections of either saline or interferon alfa-2b alone. "Fifty-seven subjects injected with antigen were judged to have 100 percent resolution of warts at study conclusion, 21 of whom had more than one wart and experienced 100 percent resolution of all distant warts," the authors report. "In the interferon alfa-2b and saline groups, these numbers were 25 and 11, respectively." The researchers also found that patients who responded to treatment were much more likely to have an immune response to HPV.

"Our repeated observation that untreated warts resolve after injection of only one wart prompts the speculation that intralesional [injection into the wart] immunotherapy induces HPV-directed immunity," the authors write. "Indeed we have observed resolution of hundreds of flat warts in individual patients after injection of only one lesion. ...It is possible that local and distant responses of warts in subjects who received saline or interferon alfa-2b alone develop by the same mechanism as when antigen is injected and that many triggers of an immune response to HPV exist. While injection of saline is an appropriate control, it is not a true placebo. That noted, local and systemic responses to saline injection in this study were far less likely than when antigen was used."

"Intralesional immunotherapy for common warts is effective and safe," the authors conclude. "It is unique in affording many patients a therapeutic response in untreated warts and may, through stimulation of HPV-directed immunity, provide fewer recurrent warts. While useful in any patient with warts, intralesional immunotherapy may be particularly useful in patients with numerous lesions or lesions covering large surface areas."

Increased levels of estrogen may improve psoriasis

Wed, 18 May 2005 16:58:38 PST

( from http://www.rxpgnews.com ) Increased levels of estrogen that occur during pregnancy may be associated with improvement in psoriasis, according to a study in the May issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Anecdotal reports have suggested that psoriasis tends to improve during pregnancy, according to background information in the article. The current study investigated prospectively how psoriasis fluctuates in pregnancy and correlated progesterone and estrogen levels in pregnancy with psoriatic change.

Jenny E. Murase, M.D., of the University of California, Irvine, and colleagues compared changes over the course of one year in psoriatic body surface area in women with psoriasis in a group of 47 pregnant women and a control group of 27 non-pregnant pre-menopausal women. The women reported on their stress level, perceived psoriatic severity and the extent of their body surface affected by psoriasis five times over the course of the year: pregnant women at 10, 20 and 30 weeks gestation, and six and 24 weeks after birth and the control group at baseline, 10, 20, 36 and 54 weeks following enrollment. Hormone levels at each assessment were determined for 19 of the pregnant women.

During pregnancy, 55 percent of the patients reported improvement in psoriasis, 21 reported no change and 23 percent reported worsening. Only nine percent of patients reported improvement post partum, 26 reported no change and 65 percent reported worsening. Psoriatic body surface area decreased significantly from 10 to 20 weeks' gestation compared to controls and increased significantly six weeks post partum. Although 65 percent of the pregnant patients reported worsening, their psoriatic body surface area only returned to pre-pregnancy levels, the authors report. In pregnant women with 10 percent or greater psoriatic body surface area, lesions decreased by 83.8 percent during pregnancy. Psoriatic body surface area levels in the controls remained the same throughout the year.

"High level of estrogen correlated with improvement in psoriasis, whereas progesterone levels did not correlate with psoriatic change," the authors write. "We believe that further examination of how estrogen may improve psoriasis is warranted. ...Whether estriol [a form of estrogen] can improve psoriasis or can prevent worsening of psoriasis in menopause should be explored."