RxPG News : Toxicology

Sandia Labs partners with UA Engineering to boost energy, water, climate research in the Southwest

Tue, 24 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) TUCSON, Ariz. and ALBUQUERQUE, N.M. (May 24, 2011) -- The University of Arizona and Sandia National Laboratories have agreed to collaborate on engineering aspects of four critical environmental research areas in a new partnership that will initially focus on research involving management of these resources in the Southwestern U.S.

The driving force behind the new collaboration is to increase investigations of the relationships between energy, water climate and sustainability -- especially in the Southwest -- through new research into the interrelationships between these areas. Under the agreement, research experts in these individual areas, plus materials science, will team to explore how strategies in one environmental area affect the other areas. By understanding these interrelationships, we can then engineer better materials, systems, devices and management strategies, said Jeff Goldberg, dean of the UA College of Engineering.

The initial stages of the plan involve research teams from the University of Arizona College of Engineering -- including faculty, students, grad students and staff -- collaborating with teams from the New Mexico-based Department of Energy national laboratories. Glenn Schrader, associate dean of research at the UA College of Engineering, says the unique aspect of this agreement is its focus on using teams of researchers to tackle these areas, rather than individuals or individual labs, providing additional research opportunities for UA students and faculty.

Joint proposals developed from the new partnership are expected to increase the amount of research funding opportunities at the UA, as well as increasing the amount of sponsored research awarded to the university as a whole. For Sandia, the partnership is expected to open up new research opportunities across many levels, including: allowing Sandia to capitalize on its core technical strengths; improving access to key university facilities, capabilities and ideas; identifying the next generation of research scientists and engineers; and providing a vehicle for addressing key sustainability issues affecting the nation's security. This is part of our technical strategy to partner with the best universities in the nation to address the most challenging technical problems facing the U.S., said Duane Dimos, director of engineering sciences at Sandia National Laboratories.

This new partnership with Sandia, led by the UA College of Engineering, is an excellent example of the world class interdisciplinary and collaborative research that characterizes work on the environment and energy across the University of Arizona, said Diana Liverman, co-director of the UA Institute of the Environment. It also demonstrates the university-wide commitment to finding solutions to local, national and international environmental challenges.

Other anticipated collaborations from the new partnership include exchanges allowing personnel from both institutions to serve on UA advisory panels and Sandia review panels, jointly-sponsored workshops, and courses which would be available at both institutions.

The partnership is also expected to raise the number of UA graduates and postdoctoral graduates at Sandia, increase the number of interns at Sandia from UA labs, and increase the number of fellowship program and Ph.D. candidates at Arizona. The collaboration will initially focus on the issues of utmost importance to the arid Southwestern U.S. that are common national security issues for both institutions, but other research themes may be partnered on as well, based on faculty interest and funding opportunities, Schrader said.

New robot system to test 10,000 chemicals for toxicity

Thu, 10 Mar 2011 05:00:00 PST

( from http://www.rxpgnews.com ) Several federal agencies, including the National Institutes of Health, today unveiled a new high-speed robot screening system that will test 10,000 different chemicals for potential toxicity. The system marks the beginning of a new phase of an ongoing collaboration, referred to as Tox21, that is working to protect human health by improving how chemicals are tested in the United States.

The robot system, which is located at the NIH Chemical Genomics Center (NCGC) in Rockville, Md., was purchased as part of the Tox21 collaboration. Tox21 was established in 2008 between the National Institute of Environmental Health Sciences National Toxicology Program (NTP), the National Human Genome Research Institute (NHGRI), and the U.S. Environmental Protection Agency (EPA), with the addition of the U.S. Food and Drug Administration (FDA) in 2010. Tox21 merges existing agency resources (research, funding, and testing tools) to develop ways to more effectively predict how chemicals will affect human health and the environment.

The 10,000 chemicals screened by the robot system include compounds found in industrial and consumer products, food additives, and drugs. A thorough analysis and prioritization process from more than 200 public databases of chemicals and drugs used in the United States and abroad was conducted to select the initial 10,000 chemicals for testing. Testing results will provide information useful for evaluating if these chemicals have the potential to disrupt human body processes enough to lead to adverse health effects.

Tox21 has used robots to screen chemicals since 2008, but this new robotic system is dedicated to screening a much larger compound library, said NHGRI Director Eric Green, M.D., Ph.D. The director of the NCGC at NHGRI, Christopher Austin, M.D., added The Tox21 collaboration will transform our understanding of toxicology with the ability to test in a day what would take one year for a person to do by hand.

The addition of this new robot system will allow the National Toxicology Program to advance its mission of testing chemicals smarter, better, and faster, said Linda Birnbaum, Ph.D., NIEHS and NTP director. We will be able to more quickly provide information about potentially dangerous substances to health and regulatory decision makers, and others, so they can make informed decisions to protect public health.

Tox21 has already screened more than 2,500 chemicals for potential toxicity, using robots and other innovative chemical screening technologies.

Understanding the molecular basis of hazard is fundamental to the protection of human health and the environment, said Paul Anastas, Ph.D., assistant administrator of the EPA Office of Research and Development. Tox21 allows us to obtain deeper understanding and more powerful insights, faster than ever before.

This partnership builds upon FDA's commitment to developing new methods to evaluate the toxicity of the substances that we regulate, said Janet Woodcock, M.D., director of the FDA Center for Drug Evaluation and Research.

Laboratories, universities unite to build radioecology expertise

Wed, 26 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) With the renewed and growing interest in nuclear energy, radioecology experts at the U.S. Department of Energy's Savannah River National Laboratory recognized an immediate need to build the pool of radioecology expertise both here and abroad. To address this need, they worked with partners from universities across the U.S. and laboratories in France and the Ukraine to form the National Center for Radioecology (NCoRE), a network of excellence for environmental radiation risk reduction and remediation.

Radioecology is the science that investigates the movement and effect of radionuclides released to the environment. It combines expertise in physics, chemistry, mathematics, biology, ecology, and radiation protection. The growth in new nuclear energy capacity is going to require the ability to realistically assess the health and environmental impacts of nuclear facilities, said SRNL's Dr. Wendy Kuhne, one of the lead researchers for NCoRE. With that knowledge, we can locate, design and operate the facilities in a way that meets our energy needs without increasing the risk to the population or the environment. Radioecology knowledge is also important for understanding, assessing and managing the impact of other potential sources of radionuclides, including contaminated sites managed by the Department of Energy (DOE), the military and others. In addition, it is an important contributor in preparing responses to acts of terrorism involving radioactive materials.

The increased need for radioecology, however, follows on the heels of many years' decline in educational opportunities in the field. There is currently no formal graduate program in radioecology in the United States since the retirement of Dr. Ward Whicker from Colorado State University (CSU), who is regarded as one of the founders of radioecology in the United States. Dr. Kuhne was Dr. Whicker's final PhD candidate to graduate from the program. One of the chief goals of NCoRE will be to work with key partners to establish a training and education program for radioecologists to develop future capability as the existing pool of experts reaches retirement age. NCoRE will serve as faculty for courses offered at some of the partner universities.

In addition to the education component, the NCoRE member institutions will seek out opportunities to collaborate in research projects and development of methods for risk reduction from human exposure to radionuclides and associated chemicals. The partners will leverage their resources and expertise through joint research proposals in areas that include molecular and genetic level effects, synergistic effects, individual and population level studies, ecosystem studies, sequestration and remediation, and homeland security issues related to urban radioecology. A core component of the program will be to make the fundamental connection between environmental health and human health risk assessment.

So far, two graduate students are pursuing projects at SRNL under the auspices of NCoRE. One is doing work in uncertainty analysis to determine potential errors or ways of enhancing current methods of measurement and analysis of radionuclides in liquid effluent and surface water samples taken at the Savannah River Site. The other, a PhD candidate, is performing work related to how non-radioactive and radioactive elements in contaminated soil are absorbed by specific plant species. .

Member organizations of NCoRE currently include:

Biodesign hosts international consortium on screening for lung cancer

Mon, 24 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) To address the latest issues on the early detection of lung cancer, the Biodesign Institute at Arizona State University will host an international research consortium in Scottsdale, Ariz., Feb. 25-26.

The International Early Lung Cancer Action Program, or I-ELCAP, is a lung cancer research organization with participation of cancer centers and medical institutions in 26 states and eight other countries whose mission is to reduce deaths from lung cancer by early detection and diagnosis through screening by computed tomography (CT).

Early screening is all about saving lives, said Claudia Henschke is a research scientist at the Biodesign Institute and a physician at Mount Sinai Medical Center in New York. Representatives from facilities participating in the screenings are eager to come to Arizona to compare notes and get updates on the joint effort.

Lung cancer is the No. 1 cancer killer in America, resulting in more than 160,000 deaths per year. An estimated 85 percent of patients diagnosed with lung cancer in the United States will die from it within 5 years, claiming more lives than breast, colon, and prostate cancers combined. But hope has been found in the early detection of lung cancer with annual CT screening of high-risk individuals. Annual screening with CT scans can find lung cancers in their earliest stage, when up to 92 percent can be cured. A recent study by the National Cancer Institute confirmed CT screening can significantly reduce the number of deaths from lung cancer.

Drs. Henschke and David Yankelevitz, who, like Henschke, also holds appointments as research scientist at the Biodesign Institute and physicians at Mount Sinai Medical Center in New York, will facilitate the 24th I-ELCAP event. They serve as the scientific and administrative leaders of the I-ELCAP study, collecting scientific data at each site, based on a common CT screening protocol. More than 54,000 at high risk for lung cancer have been screened thus far, making it the largest lung cancer screening study of its kind. The data is pooled with worldwide collaborators and contributes to their ongoing research regarding best practices for CT screening.

To explore possible synergies between two lung-cancer focused groups, the International Lung Cancer Consortium will hold its annual meeting concurrent to the I-ELCAP event. The consortium is an international group of lung cancer researchers, established in 2004 with the aim of sharing comparable data from ongoing lung cancer case-control and cohort studies. Organizers anticipate 150 lung cancer experts to attend.

Holding these conferences together for the first time should expand perspectives of both groups and catapult the research forward, said Dr. Yankelevitz.

The I-ELCAP effort is now part of a lung cancer demonstration project for the new ASU Biosignatures Initiative directed by former Fulton School of Engineering Dean Deirdre Meldrum. The Biodesign-led initiative will continue to be at the forefront of a multipronged strategy for the early detection of lung cancer to save lives.

This is ASU's second year as host to the prestigious biannual conference. Among the agenda topics for the 2011 conference are: minimizing harms related to screening, understanding the results of the National Lung Screening Trial, development of future collaborative research.

The main venue for the two-day meetings will be the Millennium Resort Scottsdale McCormick Ranch, 7401 N. Scottsdale Rd., Scottsdale, Ariz.

UCSF study identifies chemicals in pregnant women

Fri, 14 Jan 2011 05:00:00 PST

( from http://www.rxpgnews.com ) The bodies of virtually all U.S. pregnant women carry multiple chemicals, including some banned since the 1970s and others used in common products such as non-stick cookware, processed foods and personal care products, according to a new study from UCSF. The study marks the first time that the number of chemicals to which pregnant women are exposed has been counted.

Analyzing data for 163 chemicals, researchers detected polychlorinated biphenyls (PCBs), organochlorine pesticides, perfluorinated compounds (PFCs), phenols, polybrominated diphenyl ethers (PBDEs), phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate in 99 to 100 percent of pregnant women. Among the chemicals found in the study group were PBDEs, compounds used as flame retardants now banned in many states including California, and dichlorodiphenyltrichloroethane ( DDT), an organochlorine pesticide banned in the United States in 1972.

Bisphenol A (BPA), which makes plastic hard and clear, and is found in epoxy resins that are used to line the inside of metal food and beverage cans, was identified in 96 percent of the women surveyed. Prenatal exposure to BPA has been linked to adverse health outcomes, affecting brain development and increasing susceptibility to cancer later in life, according to the researchers.

Findings will be published in Environmental Health Perspectives on Jan. 14, and now are available on an embargoed basis.

The study was not designed to identify direct connections to adverse health outcomes.

It was surprising and concerning to find so many chemicals in pregnant women without fully knowing the implications for pregnancy, said lead author Tracey Woodruff, PhD, MPH, director of the UCSF Program on Reproductive Health and the Environment.

Several of these chemicals in pregnant women were at the same concentrations that have been associated with negative effects in children from other studies. In addition, exposure to multiple chemicals that can increase the risk of the same adverse health outcome can have a greater impact than exposure to just one chemical, said Woodruff, an associate professor in the UCSF Department of Obstetrics and Gynecology and Reproductive Sciences.

Exposure to chemicals during fetal development has been shown to increase the risk of adverse health consequences, including preterm birth and birth defects, childhood morbidity, and adult disease and mortality according to the research team. In addition, chemicals can cross the placenta and enter the fetus, and in other studies, a number of chemicals measured in maternal urine and serum have been found in amniotic fluid, cord blood and meconium, they state.

The researchers analyzed data for 268 pregnant women from the National Health and Nutritional Examination Survey (NHANES) 2003-2004, a nationally representative sample of the U.S. population.

Our findings indicate several courses of action. First, additional research is needed to identify dominant sources of exposure to chemicals and how they influence our health, especially in reproduction, said Woodruff. Second, while individuals can take actions in their everyday lives to protect themselves from toxins, significant, long-lasting change only will result from a systemic approach that includes proactive government policies.

2 studies present new data on effects of alcohol during pregnancy

Fri, 15 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Scientific data continue to indicate that higher intake of alcohol during pregnancy adversely affects the fetus, and could lead to very severe developmental or other problems in the child. However, most recent publications show little or no effects of occasional or light drinking by the mother during pregnancy. The studies also demonstrate how socio-economic, education, and other lifestyle factors of the mother may have large effects on the health of the fetus and child; these must be considered when evaluating the potential effects of alcohol during pregnancy.

A very large population-based observational study from the UK found that at the age of 5 years, the children of women who reported light (no more than 1-2 units of alcohol per week or per occasion) drinking did not show any evidence of impairment on testing for behavioral and emotional problems or cognitive ability. There was a tendency for the male children of women reporting heavy/binge drinking during pregnancy (7 or more units per week or 6 or more units per occasion) to have poorer behavioural scores, but the effects were less clear among female offspring.

A second study, published in Pediatrics, based on a population in Western Australia examined the associations between dose, pattern, and timing of prenatal alcohol exposure (PAE) and birth defects and found similar results, that there was no association between low or moderate prenatal alcohol exposure and birth defects.

Data from a randomly selected, population-based cohort of non- indigenous women who gave birth to a live infant in Western Australia (WA) between 1995 and 1997 (N = 4714) were linked to WA Midwives Notification System and WA Birth Defects Registry data. Information about maternal alcohol consumption was collected 3 months after birth for the 3 month period before pregnancy and for each trimester separately.

Low alcohol consumption was defined as less then 7 standard drinks (10g) a week, and no more than 2 drinks on any one day. Women who consumed more than 70g per week were classified as heavy drinkers and women consuming more than 140g were classified as very heavy drinkers.

The study results indicate that the prevalence of birth defects classified as ARBDs by the IOM was low. Compared with abstinence, heavy prenatal alcohol exposure in the first trimester was associated with increased odds of birth defects classified as ARBDs (adjusted odds ratio: 4.6 [95% confidence interval: 1.5-14.3]), with similar findings after validation through bootstrap analysis. There was no association between low or moderate prenatal alcohol exposure and birth defects.

Overall, current scientific data indicate that while drinking during pregnancy should not be encouraged, there is little evidence to suggest that an occasional drink or light drinking by the mother is associated with harm. Heavy drinking, however, is associated with serious developmental defects in the fetus.

Researcher awarded $2.27 million to study environmental effects on gene copy number

Mon, 04 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- The National Institute of Environmental Health Sciences has awarded $2.27 million to Indiana University researcher Joseph Shaw for a five-year study of how the environment alters genetic information through mutation and natural selection.

The project reflects a changing approach to environmental science, which is increasingly incorporating advances in molecular toxicology, computational sciences and information technology to learn how environmental factors produce genetic changes that influence health risks.

The grant comes from the NIEHS Outstanding New Environmental Scientist (ONES) program, which seeks to transform environmental research by identifying talented and creative scientists, encouraging and nurturing their innovative research, and supporting their long-term commitment to furthering the understanding of the impact of environmental exposures on human health.

Shaw, an assistant professor in the IU School of Public and Environmental Affairs, is the first Indiana University faculty member to be recognized by the ONES program.

He will lead studies that examine gene copy number variation (CNV) in the lake and pond dwelling crustacean Daphnia, commonly called the water flea, one of a handful of model organisms approved by the National Institutes of Health for biomedical research. Recent research has found that genetic differences between individuals of an animal population, including humans, are predominantly from genes that are duplicated or deleted from genomes, the full collection of DNA that prescribes the functions of a cell.

We have identified natural populations that have experienced substantial environmental stress for over a century, Shaw said, speaking of research that he and his colleagues have conducted on lakes near industrial-scale mining operations. The studies will now assess how some populations have adapted to cope with chemical changes to the environment, or have been harmed by effects linked to changes in the number of gene copies. Answers to these questions have profound implications for the long-term health of human populations that are living longer and doing so in the presence of a greater diversity of chemicals in our water that can modify DNA.

The award is unusual in that it funds basic research on how the environment can change an individual's susceptibility to disease rather than focusing on understanding the cause of a specific disease or the effects of a singular class of chemicals. Undergraduate and graduate students, research staff and postdoctoral investigators will be employed to work on the project.

We're pleased -- but not surprised -- that Joe was recognized as an outstanding new environmental scientist, said SPEA Dean John D. Graham. Joe's work has extraordinary long-term implications across several areas of research.

One consequence of the Human Genome Project and other genome sequencing studies that decode the genetic make-up of living organisms has been an awareness that the quantity of gene copies can vary from one individual to another. Furthermore, there are strong associations between gene copy number variation and a wide array of diseases, including autism, Alzheimer's disease, epilepsy, HIV susceptibility, lupus, Parkinson's disease and schizophrenia.

The impact of the environment on gene copy number remains unknown, however, in part because appreciation of the significance of CNV is so new. Also new is the toolbox needed for advancing environmental genomics research at an unprecedented pace. Researchers at Indiana University lead an international consortium, the Daphnia Genomics Consortium, devoted to obtaining high-throughput genetic data from natural populations of Daphnia. The toolbox they are developing is unique to the environmental sciences and now includes genome sequences, reagents, protocols and databases needed to simultaneously measure and interpret the condition specific action of all genes of the water flea.

The return on past investments by IU towards fostering cross-disciplinary genomics research is phenomenal, said John Colbourne, genomics director of the IU Bloomington Center for Genomics and Bioinformatics and co-founder of the Daphnia Genomics Consortium. This newly awarded project can potentially bridge two fields of research -- biomedical and environmental sciences -- that have traditionally worked apart.

The promise in studying the genetics of Daphnia populations is that we may better understand causal associations between environmental conditions, the composition and function of genomes, and disease, Colbourne added. Translating results from this research to humans rests on the great insight of the last 15-20 years in biology -- that fundamental genetic pathways are very similar in all organisms.

The IU studies will include working with Daphnia populations that developed tolerance to extreme exposure to toxic metals, including cadmium, in heavily polluted mining regions near Sudbury, Ontario, Canada. The unique biology of Daphnia will enable researchers to map genetic changes that took place in Daphnia populations in the past and associate the changes with changes in environmental exposure.

The grant builds on past training and support for Shaw's research career. He was an NIEHS Fellow while in graduate school at the University of Kentucky and an NIEHS-funded postdoctoral researcher with the Dartmouth College Superfund Basic Research Program. He has since 2004 been a summer research associate at Mt. Desert Island Biological Laboratory in Maine, and he came to IU Bloomington in 2007 with support from IU's Commitment to Excellence program, which funded the creation of faculty positions for research across its schools and departments in environmental sciences.

The ONES award supports not only a defined research project but also activities and training that enhance the long-term research goals of the investigator. Shaw will take advantage of this aspect by teaming with Michael Lynch, Distinguished Professor of biology at IU Bloomington, and Michael Pfrender, associate professor of biological sciences at the University of Notre Dame.

Lynch, a fellow of the National Academy of Sciences, will lend his expertise in assessing the spontaneous accumulation of mutations. Pfrender, faculty director of the Genomics Core Facility at Notre Dame, will provide assistance in producing genetic crosses of Daphnia that will help uncover the biological effects of CNV. These collaborations will enhance the environmental genomics toolbox to apply to future research on environmental health questions.

This project would not be possible without the resources and support provided by Indiana University and SPEA and the expertise available on this campus, especially the technical capabilities of the IU Center for Genomics and Bioinformatics, Shaw said. I'm also grateful for the NIEHS-funded training opportunities I have been afforded. Now we have some exciting work to do.

Prof. Xiaoguang Meng receives honorary master of engineering from Stevens

Mon, 27 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) For his significant and global contributions to clean water and environmental causes, his dedication as an outstanding educator, and his commitment to invention and the pursuit of discovery, Professor Xiaoguang Meng received an honorary Master of Engineering degree from Stevens Institute of Technology at the university's annual Convocation Ceremony on September 8, 2010.

Dr. Meng, a professor in the Charles V. Schaefer, Jr. School of Engineering and Science, has dedicated his career to teaching and research in physicochemical treatment of arsenic and heavy metals in water and solids. He has gained international recognition for research into the interaction of heavy metals, uranium, and inorganic compounds at the metal hydroxide-water interface and the fate and transport of arsenic and heavy metals in an aquatic environment. Through this work he has developed a number of patented technologies that have been successfully used to remove toxins from contaminated water, in the process saving lives around the world and protecting the environment.

Arsenic is a global problem, with up to 140 million people at risk due to arsenic contamination in drinking or irrigation water. Dr. Meng has been a pioneer in applying emerging nanotechnologies to create breakthrough filtration systems serving the worldwide need for clean and safe water. Due to nanomaterials' superior properties for reacting with or absorbing contaminants, Dr. Meng's filters are able to remove heavy metals and even radioactive elements from water quickly and effectively. As a result of Dr. Meng's research on metallic iron and co-precipitation filtration systems, full-scale water treatment units are currently operating at multiple locations around the United States. These units have been successfully restoring environmental remediation sites since the 1990s, treating contaminated groundwater that could have had disastrous, long-term effects on local communities.

At a Department of Defense site in California, Dr. Meng deployed material and chemical filtration units to reduce naturally-occurring elevated levels of fluoride and arsenic from groundwater. His work resulted in dramatically reduced well operation costs and a substantial reduction of waste water and other products associated with the purification process.

In Bangladesh, Dr. Meng's water purification technologies are utilized to address a national drinking water contamination crisis. Up to 20 percent of deaths in Bangladesh are caused by arsenic poisoning, and tens of millions of lives are at critical risk of death or illness due to arsenic. Under Dr. Meng's direction, household filtration units for removal of arsenic from well water have been effectively utilized in three established arsenic-free villages. Responding to this success, the Technical Advisory Group of Bangladesh Arsenic Mitigation Water Supply Project has recommended this particular filtration process for nationwide use.

Dr. Meng has also developed a system for real-time analysis of arsenic that can provide inexpensive and almost instant water quality testing for us around the world. As water quality issues occur more frequently in developing countries, Dr. Meng has always considered cost of testing and filtration when designing his technologies. The real-time arsenic test sensors and household filtration units for Bangladesh will be affordable for even the world's lowest-income families, fundamentally changing the ability of individuals to have access to safe drinking water.

As the co-director of the Center for Environmental Systems (CES) at Stevens, Dr. Meng has mentored a large number of students involved in various aspects of environmental research over the past 15 years. He has co-authored 59 journal articles, a book, and four patents. He has seen nearly 30 of his projects funded, most of them in the pursuit of purifying water. After raising more than $1 million in venture funding, HydroGlobe, a company co-founded by Dr. Meng to manufacture a patented water purification system, was profitably acquired by Graver Technologies.

Dr. Meng is a member of the American Chemical Society, American Water Works Association, and the Chinese American Association for Engineering.

In addition to his Bachelors of Science in chemistry and Masters of Science in Marine Chemistry from Shandong College of Oceanography in China, Dr. Meng holds a PhD in Civil Engineering from Syracuse University. He joined Stevens in 1993 and immediately began to contribute important research at CES.

NIH to launch Gulf oil spill health study

Tue, 07 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The National Institutes of Health will launch a multi-year study this fall to look at the potential health effects from the oil spill in the Gulf region. The Gulf Worker Study, announced by NIH Director Francis S. Collins, M.D., Ph.D., in June, is in response to the largest oil spill in U.S. history, caused by the explosion of the Deepwater Horizon offshore drilling oil rig in the Gulf of Mexico. Dr. Collins pledged $10 million in NIH funding for the study's initial phases.

To help expedite the launch of the study, BP will contribute an additional $10 million to NIH for this and other important health research. The BP funding will come through the Gulf of Mexico Research Initiative (GRI). The GRI is a ten-year, $500 million independent research program established by BP to better understand and mitigate the environmental and potential health effects of the Gulf spill. The NIH will have full autonomy regarding the distribution of the $10 million, with input from external scientific experts in environmental health and who are familiar with the Gulf region.

It was clear to us that we need to begin immediately studying the health of the workers most directly involved in responding to this crisis, said Collins. The donation from BP will help speed our work with CDC, EPA, and other federal agencies, academia, as well as state and local partners to carry out this important study. Collins asked the National Institute of Environmental Health Sciences (NIEHS), part of the NIH, to lead the research project.

The study will focus on workers' exposure to oil and dispersant products, and potential health consequences such as respiratory, neurobehavioral, carcinogenic, and immunological conditions. The study is also expected to evaluate mental health concerns and other oil spill-related stressors such as job loss, family disruption, and financial uncertainties.

Clean-up workers are likely to be the most heavily exposed of all population groups in the Gulf Coast region, said Dale Sandler, Ph.D., chief of the Epidemiology Branch at NIEHS and lead researcher on the study. We plan to enroll workers with varying levels of exposure. For example, we hope to recruit workers involved in oil burning, skimming and booming, equipment decontamination, wildlife cleanup, and also those with lower exposure such as shoreline clean-up workers. We'll also recruit some people who completed the worker safety training, but did not have the opportunity to do any clean-up work. They will be our study controls.

Sandler added, What we learn from this study may help us prepare for future incidents that put clean-up workers at risk.

The current focus of NIEHS is to ensure that the Gulf communities most affected by the oil spill have a say in the study's design and implementation, as well as input into future research directions. The NIEHS is hosting webinars and other community engagement activities to obtain input.

Community involvement and participation is critical to the success of this study, said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program.

NIH and the Department of Health and Human Services have had a continuous presence in the Gulf since the explosion occurred. The NIEHS Worker Education and Training Program (WETP) used its 24 years of experience preparing people for hazardous conditions to contribute to training more than 100,000 workers in the Gulf so they could safely clean up the oil spill. The WETP also distributed thousands of pocket-sized training booklets in English, Spanish, and Vietnamese, so workers have the information they need to protect themselves. The WETP materials are available at

EPA and other federal agencies collaborate to improve chemical screening

Mon, 19 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON - The U.S. Environmental Protection Agency (EPA), the National Institute of Environmental Health Sciences National Toxicology Program (NTP) and the National Institute of Health Chemical Genomics Center (NCGC) welcome the U.S. Food and Drug Administration (FDA) to the Tox21 collaboration. The Tox21 collaboration merges federal agency resources (research, funding and testing tools) to develop ways to more effectively predict how chemicals will affect human health and the environment. The collaboration was established in 2008 to develop models that will be able to better predict how chemicals will affect humans. FDA will provide additional expertise and chemical safety information to improve current chemical testing methods.

This collaboration is revolutionizing the current approach to chemical risk assessment by sharing expertise, capabilities and chemical information, which will lead to both a faster and deeper understanding of chemical hazards, said Dr. Paul Anastas, assistant administrator for EPA's Office of Research and Development. Through the Tox21 collaboration, 2,000 chemicals have already been screened against dozens of biological targets and we are working to increase the number of chemicals to 10,000 by the end of the year.

There are tens of thousands of chemicals currently in commerce and current chemical testing is expensive and time consuming.

This partnership builds upon FDA's commitment to developing new methods to evaluate the toxicity of the substances we regulate, said Dr. Janet Woodcock, director of FDA's Center for Drug Evaluation and Research.

FDA will collaborate with other Tox21 members to prioritize chemicals that need more extensive toxicological evaluation, and develop models that can better predict human response to chemicals.

EPA contributes to Tox21 through the ToxCast program and by providing chemicals and additional fast, automated tests to NCGC. ToxCast currently includes 500 chemical screening tests that have assessed over 300 environmental chemicals.

Using the best science to protect human health and the environment is the ultimate goal of this collaboration, said Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences and the NTP. The addition of FDA to this effort allows biomedical researchers and regulatory scientists to work together side by side to more rapidly screen chemicals and find more effective ways to protect the health of the public. The NTP is pleased to bring its toxicology and coordination expertise to bear on making Tox21 a reality.

A major part of the Tox21 partnership is the robotic screening and informatics platform at NCGC that uses fast, automated tests to screen thousands of chemicals a day for toxicological activity in cells.

Our robots screen in a day what would take one person a year to do by hand, allowing a fundamentally different approach to toxicology, which is comprehensive and based on molecular mechanisms, said Dr. Christopher Austin, director of the NIH NCGC.

Minilab can quickly identify antibiotic residues in milk, before it leaves the barn

Fri, 07 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) No one wants antibiotic residues in their milk. But antibiotics are sometimes used even in the dairy barn. The routine tests conducted nowadays take hours to produce a result and do not test for all of the typical antibiotics. This gap can now be closed, thanks to a fully automated minilab developed by scientists from the TUM in cooperation with the LMU Muenchen and gwk Praezisionstechnik GmbH.

Even at the best of farms, including organic farms, dairy cows can fall ill and require antibiotics. As drug residues in milk may be harmful, milk from sick animals must be kept out of the milk production chain. Meanwhile the European Community has established maximum residue values to protect consumers. However, the current method of testing for antibiotics in milk is laborious and fragmentary. Within the European dairy industry overall, loss of production and sanitation of dairy products due to milk contaminated with antibiotics add up to a loss of more than 200 million euros per year.

Dairies attempt to counteract the risk by conducting spot checks. Any milk sample that inhibits the growth of test bacteria comes under initial suspicion and is then tested on the basis of more extensive analyses. The disadvantage is that it takes hours and is very expensive to do so. If drug residues are not found until late in the production process, the lost output and disposal costs can reach business-critical dimensions. Companies in the dairy industry are therefore searching for a fast and simple way of establishing the presence of virtually all antibiotics that may be used on dairy cattle.

With this aim in mind, scientists from the Chair for Analytical Chemistry at the TUM and the Chair for Hygiene and Technology at the LMU developed a glass chip and an analysis unit that can identify the presence of residues from one or more of the 14 most important antibiotics with certainty and in parallel. To do this the scientists use what's known as an antigen/antibody reaction. A glass plate is marked with dots of the antibiotics; this is known as a microarray. Then they add antibodies to the milk sample that bind specifically to the antibiotics. If an antibiotic is present, most of the antibodies are bound depending on the concentration. The rest of the antibody molecules bind to the corresponding antibiotic on the glass chip.

Through a chemoluminescence reaction, such as that used to detect blood in forensic samples, the dots carrying the highest load of antibody light up most. If the milk sample contains antibiotics, the luminosity of the dot is correspondingly reduced, because the antibodies have been used up already. The light intensity is measured with an electronic camera, thus supplying proof, not only of whether there is an antibiotic in the milk, but also of how much of it is present.

Working with gwk Praezisionstechnik GmbH, the scientists developed a fully automated minilab, which, in conjunction with the microarray, precisely determines whether or not the maximum permitted limits are exceeded in raw, unpasteurized milk. These kinds of microarrays have long been in use in the medical sphere and in research labs, says Dr. Michael Seidel from the TUM's Institute of Analytical Chemistry. This milk chip is the world's first fully automated analysis system to employ the technique in practice with milk samples that have not been pretreated. It takes just under six minutes to achieve a result. And each microarray can be reused up to 50 times. This makes it the fastest and cheapest system of its kind in the world.

The scientists are hopeful that the analysis system will help avoid production losses and significant disposal costs. Not only the more than 100,000 milk-producing businesses and more than 36,000 people working in the milk-processing industry will benefit from our development, says Professor Reinhard Niessner, from the Chair for Analytical Chemistry at the TUM. Above all the consumers profit from the improved security of dairy products. They plan to have their sensor system ready for market by the end of this year.

Children living in apartments with nonsmoking adults still exposed

Sat, 01 May 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The majority of children living in apartments are exposed to secondhand smoke, even when they don't live with smokers. This study from the University of Rochester Medical Center is the first to examine whether housing type is a potential contributor to children's exposure to cigarette smoke. The abstract was presented this morning at the Pediatric Academic Society Meeting in Vancouver, Canada.

Among children who lived in an apartment, 84 percent had been exposed to tobacco smoke, according to the level of a biomarker (cotinine) in their blood that indicates exposure to nicotine found in tobacco, and this included more than 9 of 10 African-American and white children. Even among children who lived in detached houses, 70 percent showed evidence of exposure.

We are starting to understand the role that seepage through walls and through shared ventilation may impact tobacco smoke exposure in apartments, said Karen Wilson, M.D., MPH, author of the study and an assistant professor of Pediatrics at the University of Rochester Medical Center's Golisano Children's Hospital. We see that children are being exposed in ways we are not picking up, and it's important, for their health, that we figure out where this exposure is taking place, and work to eliminate it. Multi-unit housing is one potential source, but a very important one.

Previous studies have shown that children with cotinine levels indicating tobacco smoke exposure have higher rates of respiratory diseases, decreased cognitive abilities and decreased antioxidant levels.

The study analyzed data from almost 6,000 children between 6- and 18-years-old in a national database (National Health and Nutrition Examination Survey 2001-2006) to see if there was any relationship between their smoke exposure and their housing type. Apartment living was associated with a 45 percent increase in cotinine levels for African American children and a 207 percent increase for white children. About 18 percent of U.S. children live in apartments, and many of these children are living in subsidized housing communities where smoking is more prevalent.

Wilson said many parents are trying to limit their children's tobacco smoke exposure by not allowing smoking in their apartments, but they say they can smell tobacco smoke coming from other apartments or from common areas. Last summer, the U.S. Department of Housing and Urban Development released a memo recommending that their housing developments enact smoke-free policies. A smoking ban within multi-unit, subsidized housing could further reduce the tobacco smoke exposure for children and reduce smoking rates among residents.

K-State professor finds link between low oxygen levels in body and cancer-aiding protein

Tue, 09 Mar 2010 05:00:00 PST

( from http://www.rxpgnews.com ) What began as research into how diabetics could possibly preserve their eyesight has led to findings that could prolong the vision of children afflicted with retinoblastoma.

Dolores Takemoto, a Kansas State University professor of biochemistry who was researching protein kinase C gamma in the lens of the human eye, found her work taking a fascinating turn when she discovered a correlation between the protein Coonexin46 and hypoxia -- a deficiency of oxygen which kills normal tissue cells.

According to the data, Coonexin46, or Cx46, appears in the body during these levels of low oxygen. Besides the eye, which is one of the body's only naturally occurring hypoxic tissue, Cx46 also is present in cancer cells since the cells seal themselves off from the oxygen carried by the blood vessels, thus creating a hypoxic environment.

Takemoto believes the findings will lead to serious advancements in treating retinoblastoma, a cancer that forms in the tissue of the retina -- the light-sensitive layers of nerve tissue on the back of the eye. It occurs in 300 U.S. children under the age of 5 each year, according to the National Cancer Institute.

When a child comes in with retinoblastoma in one eye it's usually too late in the process to save that eye, and, it will spread to the other eye, Takemoto said.

Once an eye becomes cancerous, it has to be removed to prevent the tumor from spreading. Too often, though, Takemoto said, by the time the tumor is noticed in one eye, it has already spread to the second, resulting in a child being permanently blind.

Through her research, Takemoto believes a siRNA medication can be invented which can be injected monthly into the noncancerous eye, preventing tumor growth. siRNA, or small interfering ribonucleic acid, is a class of double-stranded RNA molecules that can be used to interfere with the expression of a specific gene. In this case, the siRNA would suppress Cx46, which allows a tumor to exist in a hypoxic environment. In this manner, the tumor can be prevented from growing at the early hypoxic stage.

Using a mouse model for retinoblastoma, the Takemoto lab has found that use of siRNA to lower the levels of Cx46 will prevent tumor formation.

An international application has been filed with the Patent Cooperation Treaty regarding the findings.

During her trials with Cx46, Takemoto collaborated with Thu Annelise Nguyen, associate professor of toxicology at K-State. The two examined biopsies of MCF-7 breast cancer, where they also found Cx46 present. Takemoto said the same was true for samples of colon cancer.

Any time there's a drop in oxygen within the body, Cx46 appears, Takemoto said.

While Takemoto's research into Cx46 is focused on the eye, Nguyen is studying Cx46 in breast cancer. She is currently exploring drug discovery and drug testing related to breast cancer.

Besides treating tumors, Takemoto said she believes these findings could help with treatment in acute or chronic heart disease, heart attacks, retinal ischemia, ischemia of the brain, blood pressure problems and glaucoma, as well as for health applications in animals.

NIEHS awards Recovery Act funds to focus more research on health and safety of nanomaterials

Thu, 19 Nov 2009 05:00:00 PST

( from http://www.rxpgnews.com ) The National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, is increasing its investment in understanding the potential health, safety and environmental issues related to tiny particles that are used in many everyday products such as sunscreens, cosmetics and electronics. The NIEHS will award about $13 million over a two-year period, through the American Recovery and Reinvestment Act, to bolster the NIEHS's ongoing research portfolio in the area of engineered nanomaterials (ENMs).

Engineered nanomaterials are very tiny materials about 100,000 times smaller than a single strand of hair. They represent a significant breakthrough in material design and development for industry and consumer products, including stain-resistant clothing, pesticides, tires, and electronics, as well as in medicine for purposes of diagnosis, imaging and drug delivery.

We currently know very little about nanoscale materials' effect on human health and the environment, said Linda Birnbaum, Ph.D., director of the NIEHS and the National Toxicology Program (NTP), an interagency program for the U.S. Department of Health and Human Services. Nanomaterials come in so many shapes and sizes, with each one having different chemical properties and physical and surface characteristics. They are tricky materials to get a handle on. The same properties that make nanomaterials so potentially beneficial in drug delivery and product development are some of the same reasons we need to be cautious about their presence in the environment.

The NIEHS has awarded 13 new two-year grants through the Recovery Act to develop better methods to assess exposure and health effects associated with nanomaterials. Ten of the grants were awarded through the NIH Grand Opportunities program announced in March 2009 http://www.niehs.nih.gov/recovery/nanomaterial-go.cfm, and three were funded from the NIH Challenge Grants program. All 13 are aimed at developing reliable tools and approaches to determine the impact on biological systems and health outcomes of engineered materials.

The new awards focus on ensuring that we have reliable and reproducible methods and models to assess exposure, exposure metrics, and biological response to nanomaterials. This research is also essential for the harmonization of research results and forming a scientifically sound basis for hazard assessment, as well as the safe design and development of ENMs.

There are inconsistencies in the biological effects of ENMs reported in the scientific literature, and a major reason for this is lack of detailed characterization of the physical and chemical properties of the ENMs used in these studies, said Sri Nadadur, Ph.D., program administrator at the NIEHS. One of our goals is to identify three or four reliable and reproducible test methods using the same ENMs by investigators across different labs.

To accomplish this, the NIEHS brought 36 investigators together on Oct. 20, 2009 in North Carolina, where the NIEHS is headquartered, to identify ENMs, assays and test systems to be utilized in these investigations in a more coordinated and integrated effort.

The NIEHS is establishing an integrated program that will narrow its focus to identify the best methods to evaluate the health effects of nanomaterials through use of cell cultures and animal systems. After the initial meeting, grantees will meet face-to-face twice a year to share information, evaluate progress and determine next steps.

Recovery Act funds have allowed us to expand our efforts in this important area, said Sally Tinkle, Ph.D., senior science sdvisor at the NIEHS. We want to be sure that we come away with some better tools to assess the health and safety of nanomaterials. This NIEHS effort focused on nanomaterials supports the goals identified by the National Nanotechnology Initiative Strategy for Nanotechnology-related Environmental, Health, and Safety Research.

In addition to Recovery Act funding, the NIEHS supports grantees across the country working on issues related to nanotechnology. The NIEHS extramural activities are focused on three main areas:

Natural Orifice Transluminal Endoscopic Surgery (NOTES)

Tue, 03 Nov 2009 04:59:36 PST

( from http://www.rxpgnews.com ) A recent review in Faculty of 1000 Medicine Reports, a publication in which clinicians highlight advances in medical practice, suggests regional pain relief could be used during abdominal surgery. In this review, Michael Schaefer recommends a new approach that can be performed without the need for general anaesthetics.

Currently, abdominal surgery is often carried out through laparoscopy, in which surgical tools are manoeuvred through several small incisions in the abdominal wall under general anaesthetics. But in an emerging technique, Natural Orifice Transluminal Endoscopic Surgery (NOTES), the organs are reached through a natural opening in the body, such as the mouth or the vagina.

This type of surgery is not yet a mainstream procedure. NOTES procedures in patients have been reported worldwide in only about 30 cases, Schaefer emphasizes. Patients may prefer it because of low postoperative pain discomfort and because of a lack of visible scarring. Schaefer points out that NOTES may also be beneficial from an anaesthetic point of view. The small perforations of the gastric or vaginal wall that are needed to accommodate the surgical tools and the low intra-abdominal pressure that is needed for best visibility may only require spinal or epidural anaesthesia.

Combined with a quick recovery time, low pain levels after surgery and complete absence of visible scars, this may eventually make NOTES the preferred method for abdominal surgeries. NOTES has the potential to further improve the advantages of laparoscopy, writes Schaefer, but advises that these findings need to be corroborated by further randomized controlled clinical trials.

NIEHS awards Recovery Act funds to address bisphenol A research gaps

Wed, 28 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) For Immediate ReleaseWednesday, October 28, 2009

Contact:Robin Mackar, NIEHS(919) 541-0073

NIEHS Awards Recovery Act Funds to Address Bisph

Researchers studying the health effects of the chemical bisphenol A (BPA) gathered in North Carolina to launch an integrated research initiative to produce data that will allow for a comprehensive assessment of its possible human health effects.

Researchers who just received funds from the American Recovery and Reinvestment Act to study BPA were brought together to meet with scientists from academia and government already working on the compound. The meeting was held Oct. 6, 2009 at the National Institute of Environmental Health Sciences (NIEHS).

The meeting is part of an effort to support human and animal research that will help determine if current exposures to BPA in the general population pose a potential health risk. NIEHS is part of the National Institutes of Health (NIH) and has the lead in supporting research to study the potential effects that chemicals, such as BPA, may have on human health. President Obama allocated $5 billion in Recovery Act funds to the NIH, with about $14 million going to NIEHS for research on BPA.

We know that many people are concerned about bisphenol A and we want to support the best science we can to provide the answers, said Linda Birnbaum, Ph.D., who serves as director of the NIEHS and the National Toxicology Program (NTP), an interagency program for the U.S. Department of Health and Human Services. Bringing the key BPA researchers together at the onset of new funding will maximize the impact of our expanded research effort.

NIEHS will invest approximately $30 million over two years on BPA-related research. This includes existing grants, the newly awarded Recovery Act grants and supplements, in-house research and NTP projects. The NTP effort is part of a larger five-year commitment to collaborate with the U.S. Food and Drug Administration's National Center for Toxicological Research to examine long-term health outcomes resulting from developmental exposures.

BPA is a chemical used primarily in the production of polycarbonate plastics and epoxy resins. People, including children, are exposed to BPA in food and beverages when it leaches from the internal epoxy resin coatings of canned foods and also from consumer products such as polycarbonate tableware, food storage containers, water bottles and baby bottles. In 2008, NTP and NIEHS concluded that there is evidence from animal studies that BPA may be causing adverse effects. But researchers are uncertain about whether the changes seen in the animal studies would result in human health problems. For this reason, NIEHS identified BPA as a priority area.

The innovative two-year grants provided through the Recovery Act will support human and animal studies that address many of the research gaps identified by expert scientific panels, and provide a better understanding of how this chemical may impact human health.

We want the new grantees to be able to hit the ground running, said Jerry Heindel, health scientist administrator at the NIEHS who oversees much of the institute's portfolio on BPA. Having the key players talking to one another as they begin new research efforts will stimulate collaboration, create opportunities to share resources, and encourage researchers to develop reliable and reproducible methods that will allow for a comprehensive assessment of the human health effects of BPA.

In animal studies, there is some evidence linking BPA exposure with infertility, weight gain, behavioral changes, early onset puberty, prostate and mammary gland cancer and diabetes. For the newly funded research, two-year animal and human studies will focus on either developmental exposure or adult chronic exposures to low doses of BPA. Researchers will be looking at a number of health effects including behavior, obesity, diabetes, reproductive disorders, development of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects. The 10 Recovery Act NIH Grand Opportunities grants focusing on BPA research have been awarded to:

EPA reviews Univ. of Michigan dioxin study

Thu, 01 Oct 2009 04:00:00 PST

( from http://www.rxpgnews.com ) (CHICAGO - Sept. 30, 2009) U.S. Environmental Protection Agency's Office of Research and Development has completed its review of a dioxin exposure study conducted by the University of Michigan in the Midland-Saginaw, Michigan area. EPA found the study was conducted well and provided useful, scientifically credible information. However, the study is of limited value to help EPA fully evaluate human exposure to levels of dioxin in the Tittabawassee River and Saginaw River and Bay.

EPA's review was conducted under the dioxin science plan announced by Administrator Lisa P. Jackson this past May. The University of Michigan Dioxin Exposure Study (UMDES) was conducted in response to community concerns that dioxin compounds from the Midland-based Dow Chemical Co. had contaminated the city and surrounding areas. The University received financial support for the UMDES from Dow through an unrestricted grant. Primary data collection was completed in 2004-2005 and the analysis of study results continues.

EPA's review identified several significant issues that limit the utility of the UMDES results:

The study did not include children, who tend to have higher exposures to contaminants because they have more contact with, and ingestion, of soils and dusts.

It is unclear if the study included a sufficient number of properties with highly-contaminated soils. Such properties can be found in the Midland-Saginaw area.

It is uncertain how well the study represented people who participate in activities that could lead to elevated dioxin exposures, such as eating local fish and game with elevated dioxin levels.

Additionally, the UMDES included no health status information on the people surveyed. Thus, the UMDES data do not support analysis of the association between dioxin blood levels and possible health effects. Understanding these issues is critical when evaluating associations between exposure and blood dioxin levels in sensitive populations, including children. Also, the site specific data collected by the study will not be relevant as EPA revises its national interim preliminary remediation goals for dioxin in soil.

The study included more than 900 participants and provided estimates of the distributions of dioxin concentrations in blood, soil and dust in the Midland-Saginaw area as well as a reference area for comparison 100 miles to the south. EPA's review found that the UMDES was well-suited to identify patterns of serum dioxin, furan and PCB levels among adults. Among the study's other findings: people living the Midland-Saginaw area have higher blood dioxin levels than those in the reference area and national averages, and that properties in Midland-Saginaw tend to have higher soil dioxin levels than in the reference area. As has been found in other studies, it also found that higher blood dioxin levels were associated with demographic factors such as increased age, dietary choices and being overweight.

Representatives from EPA's Office of Research and Development and Office of Solid Waste and Emergency Response will hold a public meeting in the Midland-Saginaw area in late October to discuss the UMDES review. More information will be announced soon.

NOAA announces an experimental harmful algal bloom forecast bulletin for Lake Erie

Thu, 17 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Predicting harmful algal blooms, or HABs, in the Great Lakes is now a reality as NOAA announces an experimental HAB forecast system in Lake Erie. HABs produce toxins that may pose a significant risk to human and animal health through water recreation and may form scum that are unsightly and odorous to beach visitors, impacting the coastal economy. Forecasts depicting current and future locations of blooms, as well as intensity, will alert scientists and managers to possible threats to the Great Lakes beaches and assist in mitigation efforts.

When a harmful bloom in Lake Erie is detected by the experimental system, scientists issue a forecast bulletin to nearby scientists and community managers. The bulletin depicts the HABs' current location and future movement, as well as categorizes its intensity on a weekly basis.

With this new forecast, we now have an idea of when and where blooms are predicted to occur and can share products with on-the-ground local managers to reduce the human health threats associated with algal toxins, said Sonia Joseph, Michigan Sea Grant outreach coordinator for the NOAA Center of Excellence for Great Lakes and Human Health.

Having a forecast bulletin for Lake Erie will allow us to study the impacts of excess nutrients on beaches and coastal waters, including impacts of harmful algal blooms, said Jill Lis, environmental health services supervisor for Cuyahoga County, Ohio's Board of Health.

HABs, such as the blue green algae Microcystis, occur in the waters of almost every coastal state and cost in excess of $82 million annually, including public health, fisheries, and tourism losses. Microcystis blooms are increasing in frequency and duration in the Great Lakes, in part due to the invasive zebra mussel that filters Great Lakes water and removes other algae competitors. These blooms can produce a toxin that can cause skin rashes, liver damage, fish kills, and taste and odor issues in drinking water.

The experimental forecast incorporates data from various ocean-observing systems, including commercial and government satellite imagery obtained by NOAA's National Ocean Service, coastal forecast modeling and field data by NOAA Great Lakes Environmental Research Laboratory scientists, and reports received from resource managers in the field. The information is then synthesized and interpreted to determine the current and future location and intensity of Microcystis blooms.

The HAB forecasts for Lake Erie are applying the latest science and technology, said Rick Stumpf, NOAA oceanographer. Feedback from the Ohio environmental managers and drinking water utilities will allow us to better forecast these blooms, develop useful tools for our end users, and begin to monitor and forecast blooms in other parts of the country.

New research to unravel how nutrients drive toxic 'brown tides' on East Coast

Wed, 16 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) NOAA has awarded Massachusetts-based Woods Hole Oceanographic Institution $120,000 as part of an anticipated three-year, nearly $500,000 project, to determine how nitrogen and phosphorus promote brown tides on the East Coast. Funds were awarded through the interagency Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) program.

The project will focus on brown tides, a type of algae along the East Coast that causes tremendous damage to coastal habitats and scallop and hard clam fisheries from Rhode Island to Virginia. Researchers plan to use genome technology to examine how these nutrient pollutants may cause a brown tide event and influence its duration.

In the late 1980s, brown tide caused the collapse of the multi-million dollar scallop industry on eastern Long Island and mass die-offs of seagrass in its bays, said Christopher Gobler, Ph.D, a brown tide expert from the State University of New York at Stony Brook who is involved in the project. Blooms have continued since then with damage extending to New York's largest fishery which harvests the northern quahog, or hard clam. Unfortunately, these blooms were so damaging, the fisheries and resources have never recovered.

Brown tides are unusual since they grow when a certain type of inorganic nitrogen is in low supply. As such, it is suspected that an excess of other nutrient types, mainly organic phosphorus and nitrogen, in aquatic ecosystems contributes to the development of brown tides. Determining which nutrient conditions trigger these blooms will help predict and prevent brown tides. Knowing the genome sequence of the brown tide organism also allows researchers to observe changes in the cell's genes as conditions change.

The ability to monitor individual genes from brown tide cells that are 'turned on or off' in response to nutrients is a breakthrough that can show us precisely which nutrient conditions foster the growth of brown tide cells in nature, said principal investigator Sonya Dyhrman, Ph.D., of the Woods Hole Oceanographic Institution. It is difficult to track how nutrient type and supply influence harmful algal blooms because most of the approaches examine all species in the environment, rather than one specific harmful species.

This project is timely as the state of New York is currently developing a nutrient management strategy for our estuaries, said Karen Chytalo, Section Chief of Marine Habitat Protection of the New York State Department of Environmental Conservation. The type of detailed information this project will provide is exactly what we need to develop estuarine nutrient criteria so that, ultimately, we can prevent these damaging events and improve the overall health of our estuaries.

ISU researchers study insecticide-free method for control of soybean aphids

Tue, 15 Sep 2009 04:00:00 PST

( from http://www.rxpgnews.com ) AMES, Iowa - Two Iowa State University researchers are examining a new method of controlling soybean aphids without the use of chemical pesticides.

Bryony Bonning, professor of entomology, and Allen Miller, professor of plant pathology and director of the Center for Plant Responses to Environmental Stresses, are looking at a way to genetically modify soybeans to prevent damage from aphids.

If the research is successful, soybeans will carry in-plant protection from aphids, similar to the way genetically modified corn now keeps the European Corn Borer from destroying corn yields, but using a different molecular tool. Modified corn technology has been in use for about 12 years.

The study is being funded by a Grow Iowa Values Fund Grant. The goal of the grant program is to support development of technologies with commercial potential and to support the growth of companies using those technologies.

The researchers are working with Pioneer Hi-Bred, a DuPont business, as their corporate partner.

Previous research at Iowa State University indicated that if major soybean aphid outbreaks were left untreated, the loss in yield could exceed $250 million in Iowa. The annual cost to prevent the yield loss with insecticides can reach $64 million for Iowa soybean growers.

Soybean aphid outbreaks have become an annual phenomenon in Iowa, according to Miller.

The current research focuses on introducing a gene into soybeans that is harmless to mammals, but creates a toxin that is lethal to aphids that feed on soybean plants.

In order to be effective, the toxin needs to be taken intact into the body cavity of the aphid, not broken down by the digestive system in the bug.

Miller and Bonning identified a plant virus coat protein eaten by soybean aphids that doesn't break down and goes into the aphid body cavity intact.

They know the virus coat protein remains intact because the aphids often spread the virus from plant to plant while they are feeding.

Coat proteins make up the outer shell of a virus particle.

The researchers devised a method to use virus coat proteins to their advantage. The researchers have fused their toxin to the virus' protein coat. Since the protein coat is only part of the virus to be used, there is no risk of an infectious virus. Also, the coat protein is from a virus that normally doesn't infect soybeans.

When the hybrid toxin coat protein is eaten by the aphid, the fatal toxin should get into the aphid body cavity intact.

What we thought was, if this (virus) protein has this ability to be taken up into the aphid (intact), let's take advantage of that specialization and fuse that to other proteins that are toxic, said Miller.

In addition to possibly curbing the aphid problem and the yield loss it causes, there are other benefits to the farmers and the ecosystems.

The (potential) economic impact overall is huge, said Bonning. There will be less insecticide use, and also less fossil fuel used to apply the insecticides.

Also, spraying soybeans with insecticides doesn't just control the aphids, according to Bonning.

When you spray, you also control beneficial insects, said Bonning. Lady beetles are affected, for example, and they are a natural enemy of the aphids. So when the aphids come back to a field after spraying, there won't be any lady beetles to naturally control the aphid populations.

Miller adds that if growers spray for aphids and don't eliminate them all, the aphids simply disperse to other fields, making the problem worse.

There are many reasons not to spray, but you can't tell the growers to stop spraying until you give them an alternative for soybean aphid management, said Bonning.

A child's IQ can be affected by mother's exposure to urban air pollutants

Tue, 21 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A mother's exposure to urban air pollutants known as polycyclic aromatic hydrocarbons (PAHs) can adversely affect a child's intelligence quotient or IQ, a study reports. PAHs are chemicals released into the air from the burning of coal, diesel, oil and gas, or other organic substances such as tobacco. In urban areas motor vehicles are a major source of PAHs.

The study, funded by the National Institute of Environmental Health Sciences (NIEHS), a component of the National Institutes of Health, the U.S. Environmental Protection Agency and several private foundations, found that children exposed to high levels of PAHs in New York City had full scale and verbal IQ scores that were 4.31 and 4.67 points lower than those of less exposed children. High PAH levels were defined as above the median of 2.26 nanograms per cubic meter (ng/m3). A difference of four points, which was the average seen in this study, could be educationally meaningful in terms of school success, as reflected, for example, in standardized testing and other measures of academic performance. However, the researchers point out that the effects may vary among individual children.

This research clearly shows that environmental PAHs at levels encountered in an urban setting can adversely affect a child's IQ, said Linda Birnbaum, Ph.D., director of NIEHS. This is the first study to report an association between PAH exposure and IQ, and it should serve as a warning bell to us all. We need to do more to prevent environmental exposures from harming our children.

The study was conducted by scientists from the Columbia University Center for Children's Environmental Health. It included children who were born to non-smoking black and Dominican-American women age 18 to 35 who resided in Washington Heights, Harlem or the South Bronx in New York. The children were followed from utero to 5 years of age. The mothers wore personal air monitors during pregnancy to measure exposure to PAHs and they responded to questionnaires.

At 5 years of age, 249 children were given an intelligence test known as the Wechsler Preschool and Primary Scale of the Intelligence, which provides verbal, performance and full-scale IQ scores. The test is regarded as a well validated, reliable and sensitive instrument for assessing intelligence. The researchers developed models to calculate the associations between prenatal PAH exposure and IQ. They accounted for other factors such as second-hand smoke exposure, lead, mother's education and the quality of the home caretaking environment. Study participants exposed to air pollution levels below the average were designated as having low exposure, while those exposed to pollution levels above the median were identified as high exposure.

The decrease in full-scale IQ score among the more exposed children is similar to that seen with low-level lead exposure, said lead author Frederica P. Perera, Dr.P.H., professor at Columbia's Mailman School of Public Health and director of the Columbia Center for Children's Environmental Health.

This finding is of concern, said Perera. IQ is an important predictor of future academic performance, and PAHs are widespread in urban environments and throughout the world. Fortunately, airborne PAH concentrations can be reduced through currently available controls, alternative energy sources and policy interventions.

Researchers consider herd movements to help eradicate bovine TB

Fri, 10 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) In 2008, the U.S. Department of Agriculture spent $31 million to depopulate herds of cattle affected by bovine tuberculosis (TB), even though the risk of the disease has been significantly reduced in the U.S. over the past several decades. Worldwide, especially in developing countries, the disease persists, which could threaten the U.S. cattle industry in terms of international trade.

The development of new tools to better understand bovine TB and to help disease eradication efforts by the USDA was the focus of a workshop held at the National Institute for Mathematical and Biological Synthesis (NIMBioS), July 7-9, on the University of Tennessee, Knoxville, campus.

The workshop brought together experts from around the world to share ideas about how mathematical modeling approaches for cattle movements in the United States may influence disease transmission models as well as inform policies and programs for reducing the spread of bovine TB. Scientists attending the workshop include those with expertise in mathematical network and disease spread models, as well as scientists with expertise in cattle movements, livestock industry practices, and the bovine TB agent.

NIMBioS is uniquely situated to foster such collaborations such as this one because one of its specific priorities is bringing together mathematics and biology researchers to address problems that are important to the animal industry, said Agricola Odoi, workshop co-organizer and an assistant professor in the department of comparative medicine at the University of Tennessee School of Veterinary Medicine.

One of the primary goals of the workshop is to assist the USDA in identifying new and novel methods for evaluating control options for bovine TB.

There is a lot we don't know or understand about cattle movement across the U.S., said USDA veterinarian Katie Portacci. I think the expertise that NIMBioS is bringing to the workshop will help us better understand bovine TB transmission dynamics through cattle movement,

In terms of controlling the spread of the disease, one of the goals of the USDA is to move away from the use of depopulation as a management tool, Portacci said. I think the NIMBioS meeting will help us come up with alternative ways of dealing with the problem of bovine TB.

Bovine TB is a slow, progressive bacterial disease and is difficult to diagnose in the early stages. As the disease progresses, animals may exhibit emaciation, lethargy, weakness, anorexia, low-grade fever, and pneumonia with a chronic, moist cough. It usually is transmitted through contact with respiratory secretions from an infected animal.

Mostly found in cattle, bovine TB can also infect other domesticated and wild animals. The U.S. State and Federal Cooperative Bovine TB Eradication program, which began in 1917, has made significant progress in decreasing the prevalence of the disease in humans and cattle. However, small pockets of the M. bovis infection still exist in cattle and wildlife in the United States.

Researchers consider herd movements to help eradicate bovine TB

Fri, 10 Jul 2009 04:00:00 PST

Chemicals in common consumer products may play a role in pre-term births

Mon, 06 Jul 2009 04:00:00 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---A new study of expectant mothers suggests that a group of common environmental contaminants called phthalates, which are present in many industrial and consumer products including everyday personal care items, may contribute to the country's alarming rise in premature births.

Researchers at the University of Michigan School of Public Health found that women who deliver prematurely have, on average, up to three times the phthalate level in their urine compared to women who carry to term.

Professors John Meeker, Rita Loch-Caruso and Howard Hu of the SPH Department of Environmental Health Sciences and collaborators from the National Institute of Public Health in Mexico and the U.S. Centers for Disease Control and Prevention analyzed data from a larger study directed by Hu, which follows a cohort of Mexican women recruited during pre-natal visits at one of four clinics of the Mexican Institute of Social Security in Mexico City.

Meeker and colleagues looked at data from 60 women: 30 who carried to term and 30 who delivered prematurely (defined as less than 37 weeks gestation). They analyzed urine samples collected during the third trimester and compared them to the control group who carried to term. They found significantly higher phthalate metabolite levels in the women who delivered prematurely.

Premature birth is a significant risk factor for many health problems in childhood that can persist into adulthood, Meeker says. In the United States, premature births have increased by more than 30 percent since 1981 and by 18 percent since 1990. In 2004, premature births accounted for 12.8 percent of live births nationwide.

Premature births, he says, account for one-third of infant deaths in the United States, making it the leading cause of neonatal mortality. Being born too early can also lead to chronic health problems such as blindness, deafness, cerebral palsy, low IQ and more.

Phthalates are commonly used compounds in plastics, personal care products, home furnishings (vinyl flooring, carpeting, paints, etc.) and many other consumer and industrial products. The toxicity varies by specific phthalates or their breakdown products, but past studies show that several phthalates cause reproductive and developmental toxicity in animals.

A couple of human studies have reported associations between phthalates and gestational age, but this is the first known study to look at the relationship between phthalates and premature births, Meeker says.

We looked at these commonly used compounds found in consumer products based on the growing amount of animal toxicity data and since national human data show that a large proportion of the population are unknowingly exposed, Meeker said. One of the problems for consumers is that you don't know exactly which products contain phthalates because the products do not have to be labeled accordingly.

Meeker says the U-M study is a stepping stone to larger and more detailed studies examining the role of phthalates and premature births. The researchers hope to examine a larger population of pregnant women to corroborate these initial study findings, and conduct experimental lab studies to further explore the biological mechanisms of how phthalates work in the body.

NOAA forecast predicts large 'dead zone' for Gulf of Mexico this summer

Thu, 18 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) A team of NOAA-supported scientists from the Louisiana Universities Marine Consortium, Louisiana State University, and the University of Michigan is forecasting that the dead zone off the coast of Louisiana and Texas in the Gulf of Mexico this summer could be one of the largest on record. The dead zone is an area in the Gulf of Mexico where seasonal oxygen levels drop too low to support most life in bottom and near-bottom waters.

Scientists are predicting the area could measure between 7,450 and 8,456 square miles, or an area roughly the size of New Jersey. However, additional flooding of the Mississippi River since May may result in a larger dead zone. The largest one on record occurred in 2002, measuring 8,484 square miles.

Dead zones are caused by nutrient runoff, principally from agricultural activity, which stimulates an overgrowth of algae that sinks, decomposes, and consumes most of the life-giving oxygen supply in the water.

The dead zone size was predicted after researchers observed large amounts of nitrogen feeding into the Gulf from the Mississippi and Atchafalaya Rivers. The rivers experienced heavy water flows in April and May that were 11 percent above average.

The high water volume flows coupled with nearly triple the nitrogen concentrations in these rivers over the past 50 years from human activities has led to a dramatic increase in the size of the dead zone, said Gene Turner, Ph.D., a lead forecast modeler from Louisiana State University.

This forecast helps coastal managers, policy makers, and the public better understand and combat the sources of the dead zones. For example, the models that generate this forecast have been used to determine nutrient reduction targets required to reduce the size of the dead zone. This hypoxic, or low-to-no oxygen area, is of particular concern because it threatens valuable commercial and recreational Gulf fisheries by destroying critical habitat.

As with weather forecasts, this forecast uses multiple models to predict the range of the expected size of the dead zone. The strong track record of these models reinforces our confidence in the link between excess nutrients from the Mississippi River and the dead zone, said Robert Magnien, Ph.D., director of NOAA's Center for Sponsored Coastal Ocean Research. This advanced warning is just one example of NOAA's growing ecological forecasting capabilities that allow managers to protect valuable resources and coastal economies in a proactive manner.

NOAA has been funding investigations and forecast development for the dead zone in the Gulf of Mexico since 1990 and currently oversees the two national hypoxia programs authorized by the Harmful Algal Bloom and Hypoxia Research and Control Act. Data from the U.S. Geological Survey on river flow and nutrient concentrations this spring was critical information required by the models to produce the forecasts.

An announcement of the official size of the 2009 hypoxic zone, which is an annual requirement of the Gulf of Mexico Task Force Action Plan, will follow a NOAA-supported monitoring survey led by the Louisiana Universities Marine Consortium on July 18-26.

In addition, NOAA's Southeast Area Monitoring and Assessment Program currently is providing near real-time data on the hypoxic zone during a five-week NOAA Fisheries Service summer fish survey in the northern Gulf of Mexico between June 8 and July 18.

The information is available on the NOAA's Gulf of Mexico Hypoxia Watch Web page. The objective of Hypoxia Watch is to develop new near-real-time data and map products using shipboard measurements of bottom-dissolved oxygen and to disseminate them over the Internet. These products form the basis for summertime advisories to fishermen in the North-central Gulf of Mexico, indicating where fish and other living marine resources may not be found due to low or non-existent oxygen levels.

Common chemotherapy drug triggers fatal allergic reactions

Mon, 08 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- A chemotherapy drug that is supposed to help save cancer patients' lives, instead resulted in life-threatening and sometimes fatal allergic reactions.

A new study from the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program at Northwestern University Feinberg School of Medicine identified 287 unique cases of hypersensitivity reactions submitted to the FDA's Adverse Event Report System between 1997 and 2007 with 109 (38 percent) deaths in patients who received Cremophor-based paclitaxel, a solvent-administered taxane chemotherapy.

Adverse event reports generally only represent from 1 to 10 percent of actual incidence, so the number of hypersensitivity reactions and deaths is likely significantly higher. The severe allergic reactions are believed to be caused by Cremophor, the chemical solvent - a derivative of castor oil -- that is used to dissolve some insoluble drugs before they can be injected into the blood stream.

Two patients who died from an allergic reaction had early-stage breast cancer, which had been surgically removed, and were being treated with Cremophor-containing paclitaxel to prevent the cancer from coming back. Both of these patients had received medications before the chemotherapy to reduce the risk of hypersensitivity reactions.

The study was led by Charles Bennett, M.D., RADAR program coordinator and a professor of hematology/oncology at Northwestern's Feinberg School, and Dennis Raisch, a professor of pharmacy at the University of New Mexico.

The deaths of women with early-stage breast cancer are particularly disturbing because without the adverse reaction, they could have likely had 40 years of life ahead of them, Bennett said.

RADAR investigators also found that 22 percent of all fatalities occurred in patients despite patients having received premedication to prevent hypersensitivity reactions, while another 15 percent of such patients experienced life-threatening respiratory arrest.

The report was presented at the 45th Annual Meeting of the American Society of Clinical Oncology held recently in Orlando, Fla.

Cremophor-containing paclitaxel has been associated with hypersensitivity reactions, with responses ranging from mild skin conditions to more severe effects, including anaphylaxis and cardiac collapse. Current U.S. product labeling for Cremophor containing paclitaxel includes a black-box warning alerting physicians and patients of potential toxicity and recommending the use of corticosteroids and other medications before chemotherapy administration to reduce the risk of hypersensitivity reactions.

The results of our review suggest that physicians should be vigilant in monitoring the safety of their patients undergoing chemotherapy treatment, said Bennett, who also is the A.C. Buehler Professor in Economics and Aging at the Feinberg School and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Patients receiving Cremophor-based paclitaxel should be given medications to prevent hypersensitivity reactions, but what is sobering, as the study has shown and as the black-box warning indicates, women suffer anaphylaxis despite receiving steroid premedication, Bennett said. Physicians should be diligent in reporting adverse events to regulatory agencies to better monitor the impact of Cremophor on patient safety. Physicians may also want to consider exploring other alternative chemotherapy options that do not include Cremophor.

In addition to the two women with early-stage breast cancer who died after treatment with the Cremophor-based paclitaxel, four other women with early-stage breast cancer experienced life-threatening anaphylaxis reactions. Each of them had received prior medications to prevent the reactions.

The fatal outcomes observed in patients with early-stage breast cancer were particularly striking as this is a patient population with a good prognosis that is generally treated with curative intent, said Raisch.

For the report, Bennett and Raisch reviewed adverse event reports submitted to regulatory agencies in the U.S., Europe and Japan. The most common cancer diagnosis for these patients with allergic reactions was lung cancer followed by breast cancer and ovarian cancer.

Estrogen linked to lowered immunity in fish

Wed, 03 Jun 2009 04:00:00 PST

( from http://www.rxpgnews.com ) Exposure to estrogen reduces production of immune-related proteins in fish. This suggests that certain compounds, known as endocrine disruptors, may make fish more susceptible to disease.

The research may provide new clues for why intersex fish, fish kills and fish lesions often occur together in the Shenandoah and Potomac rivers. The tests were conducted in a lab by scientists from the U.S. Geological Survey.

The study, led by USGS genomics researcher Dr. Laura Robertson, revealed that largemouth bass injected with estrogen produced lowered levels of hepcidin, an important iron-regulating hormone in mammals that is also found in fish and amphibians. This is the first published study demonstrating control of hepcidin by estrogen in any animal.

Besides being an important iron-regulating hormone, researchers also suspect that hepcidin may act as an antimicrobial peptide in mammals, fish and frogs. Antimicrobial peptides are the first line of defense against disease-causing bacteria and some fungi and viruses in vertebrate animals.

Our research suggests that estrogen-mimicking compounds may make fish more susceptible to disease by blocking production of hepcidin and other immune-related proteins that help protect fish against disease-causing bacteria, said Robertson.

USGS researchers Drs. Vicki Blazer and Luke Iwanowicz have previously found intersex occurring in fish in the Potomac and Shenandoah rivers. Intersex is primarily revealed in male fish that have immature female egg cells in their testes. Because other studies have shown that estrogen and estrogen-mimicking compounds can cause intersex, the co-occurrence of fish lesions, fish kills and intersex in these two rivers suggested to USGS scientists that estrogen-mimicking compounds could be involved in the fish lesions and fish kills in addition to being a possible cause of intersex traits.

That caused Robertson and her colleagues to investigate how estrogen could be affecting the immune system in these fish. The study showed that largemouth bass produced two different hepcidin proteins. Production of the first hepcidin protein was turned down by estrogen. Production of the second hepcidin protein by fish exposed to bacteria was blocked by estrogen. The fact that estrogen blocked production of hepcidins in fish exposed to bacteria gives more weight to the theory that estrogen or estrogen-mimicking chemicals could be making fish more susceptible to diseases, Robertson added.

Hepcidin could protect against bacterial infection in two ways. First, said Robertson, hepcidin could be an antimicrobial peptide that actually kills pathogens. Or it could be more complex. To live, a microbe must have iron, so when a microbe invades a person or animal, that microbe must obtain iron from its host. To 'fight' the microbe, a host can 'suck up iron' and store it in places inaccessible to the microbe. In mammals, hepcidin is a key player in how the host takes up and stores iron.

Codeine use and accident risk

Tue, 24 Mar 2009 04:00:00 PST

( from http://www.rxpgnews.com ) The risk of being involved in a traffic accident with personal injury is significantly higher among codeine users than non-users. However, sporadic or moderate use of codeine alone does not carry an increased risk, according to a newly published study from the Norwegian Institute of Public Health.

Codeine and tramadol are painkillers in the opiate group, used for mild to moderate pain. In Norway, codeine is included in Paralgin forte and Pinex forte, and tramadol, amongst others, in Nobligan. Norway has a higher consumption of codeine preparations than other European countries.

Earlier studies have given conflicting results when evaluating traffic accident risk linked to the use of codeine and tramadol. In this new study from the Norwegian Institute of Public Health, anonymised data from the Norwegian Prescription Database and Road Traffic Accident Register was used to study whether codeine- or tramadol users have an increased risk of being involved in a traffic accident with personal injury.

During the 33 months of the study, 181 road traffic accidents were registered with personal injury where the driver had been exposed to codeine and 20 after exposure to tramadol. Exposure is defined as the first 7 days after the dispensing of a prescription for a codeine- or tramadol preparation.

The study showed that the risk of being involved in a road traffic accident with personal injury was twice as high in the period after having a prescription for codeine dispensed. For those who had used more than approximately 400 tablets per year, the risk of being involved in a traffic accident was 3 times as large. When the use of other potential impairing medicines was excluded, the risk of accident sank significantly. For sporadic codeine users there was no increased risk of accident. There was not a significantly higher risk for tramadol.

- We have previously seen that large users of codeine preparations often use benzodiazepines (anxiolytics- and hypnotics) or carisoprodol (muscle relaxants /painkillers) in addition. This is an important contributory factor when evaluating the accident risk, says the study's leader Liliana Bachs.

98 of the 181 drivers exposed to codeine who were included in the study had also been dispensed other medicines with abuse potential in the week prior to the accident.

- One can conclude that sporadic or moderate use of codeine alone to a small degree increases the chance of being involved in accidents with personal injury. Simultaneous use of benzodiazepines or carisoprodol gives a clear increase in the risk of accidents, explains Bachs.

Nanoparticle toxicity doesn't get wacky at the smallest sizes

Sat, 14 Feb 2009 05:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO -- The smallest nano-sized silica particles used in biomedicine and engineering likely won't cause unexpected biological responses due to their size, according to work presented today. The result should allay fears that cells and tissues will react unpredictably when exposed to the finest silica nanomaterials in industrial or commercial applications.

Nanotoxicologist Brian Thrall and colleagues found that, mostly, size doesn't matter, by using total surface area as a measure of dose, rather than particle mass or number of particles, and observing how cultured cells responded biologically.

If you consider surface area as the dose metric, then you get similar types of responses independent of the size of the particle, said Thrall, a scientist at the Department of Energy's Pacific Northwest National Laboratory in Richland, Wash. That suggests the chemistry that drives the biological responses doesn't change when you get down to the smallest nanoparticle.

Nanoparticles are materials made up of spherical particles that are on average 100 to 1,000 times smaller than the width of a human hair. They are being used in tires, biomedical research, and cosmetics. Researchers are exploring these tiny spheres because their physical and chemical properties at that size offer advantages that standard materials don't, such as being able to float through blood vessels to deliver drugs.

But whether these materials are safe for human consumption is not yet clear. Previous work suggested in some cases, nanoparticles become more toxic to cells the smaller the particles get.

Thrall presented this toxicology data on amorphous silica nanoparticles today at the 2009 American Association for the Advancement of Science's annual meeting. He also presented data on which cellular proteins the nanoparticles use to get inside cells.

One difficulty in measuring toxicity is that not everyone agrees which kind of dose unit to compare. Some researchers measure the dose by total weight, some by the number of particles. Neither method distinguishes whether a nanomaterial's toxicity is due to the inherent nature of the material or the particle size under scrutiny.

Different dose metrics give different impressions of which particles are more toxic, he said.

To find out, Thrall and his colleagues at PNNL measured the dose at which the particles caused a biological response. The biological response was either death of the cell, or a change in which genes the cell turned on and off. They found that when calculating doses by particle number or mass, the amount needed to generate a biological response was all over the map.

They found that the best way to pinpoint how toxic the particles are to cells was to calculate the dose based on the total surface area of the nanomaterial. Only when they considered the surface area of the dose could they predict the biological response.

And the biological response, they found, was very similar regardless of the size of the nanoparticles. Inside cells, some genes responded to nanoparticles by ramping up or down. More than 76 percent of these genes behaved the same for all nanoparticle sizes tested. This indicated to the researchers that, for these genes, the nanoparticles didn't pick up weird chemical properties as they shrunk in size.

The big fear is that you'd see unique biological pathways being affected when you get down to the nanoscale. For the most part, we didn't see that, said Thrall.

However, the team found some genes for which size did matter. A handful of genes, these fell into two categories: smaller particles appeared to affect genes that might be involved in inflammation. The larger particles appeared to affect genes that transport positively charged atoms into cells. This latter result could be due to metals contaminating the preparation of the larger particles, Thrall suggested.

Overall, the results contribute to a better understanding of what goes on at the nanoscale.

Inspection technology by Louisiana Tech researchers to examine buried infrastructure

Fri, 09 Jan 2009 05:00:00 PST

( from http://www.rxpgnews.com ) An innovative underground scanning technology developed by Louisiana Tech researchers is the cornerstone of a technology development and commercialization project that has secured one of only nine Technology Innovation Program (TIP) grants awarded nationally by the National Institute of Standards and Technology (NIST).

$3.2 million has been secured for this project, of which nearly $900,000 will flow to Louisiana Tech over the next three years, says Dr. Erez Allouche, associate professor of civil engineering and associate director of Louisiana Tech's Trenchless Technology Center.

Allouche, along with Drs. Arun Jaganathan, Neven Simicevic and Klaus Grimm, is partnering with Elxsi Corporation of Orlando to develop a deep-penetrating scanning system, based on a new technology called ultrawideband (UWB) pulsed radar. This technology will allow for the inspection of buried pipelines, tunnels, and culverts to detect fractures, quantify corrosion, and determine the presence of voids in the surrounding soil.

The project, called FutureScan, incorporates leading-edge simulation, electronics, robotics, signal processing, and three-dimensional (3-D) rendering technologies in a package that can be mounted on existing pipe-inspection robots.

A patent on this new technology is currently pending. This is the first attempt to commercialize UWB for the inspection of municipal pipes around the world.

Using highly directional electromagnetic pulses and special signal-processing algorithms derived from mine and bomb detection technology, the technique can see through solid objects and measure both surface and internal structural integrity.

Our project will greatly increase the ability of municipalities and DOTs to detect developing sink holes around buried pipes before they propagate to the surface and cause collapse of the roadway, explains Allouche.

The consequences of pipeline failure range from disease-causing water pollution to sometimes fatal highway accidents. The United States has over one million miles of buried pipes carrying water to cities, towns, and homes.

In addition to the federal funding [Louisiana Tech] receives, this award will also mean the establishment of new technical positions, the creation of a new start-up company in Tech's incubator, and the potential for a leading-edge technology, developed at Louisiana Tech, getting into markets around the world, adds Allouche.

TIP was created to support innovative, high-risk, high-reward research in areas of critical national need where there is a clear interest because of the magnitude of the problems and their importance to society.

Allouche appreciates the prestige and exclusivity that this program carries.

The high dollar value attracts proposals from the best academic institutions in the nation. This award is another example of the growing ability of Louisiana Tech to develop innovative technologies and bring them to a market-ready status.

Cutting the cord to determine babies' health risk from toxic exposure

Wed, 03 Dec 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Despite the well-known dangers of first- and secondhand smoke, an estimated ten percent of pregnant women in the U.S. are smokers. Exposure of a developing baby to harmful cigarette byproducts from mothers who smoke affects an estimated 420,000 newborns each year and poses a significant health care burden.

Now, in the first study of its kind, a team of researchers has completed a global assessment of newborns' umbilical cord blood to better understand the fetal health risks from smoking mothers. The research was led by Johns Hopkins University and included Rolf Halden, a researcher from the Biodesign Institute at Arizona State University.

Cigarette smoking is a massive onslaught on human physiology, said Halden, who works in the institute's Center for Environmental Biotechnology. Cigarette smoke is known to contain more than 4,000 chemicals, potentially affecting the health of a newborn baby on multiple levels, including low birth weight, premature delivery and small size for gestational age. The exact cause of these health effects continues to be the subject of investigation.

Unfortunately, maternal cigarette smoking puts babies at risk of adverse birth outcomes and increases susceptibility to other diseases later in life, said Halden.

The research team's goal was to provide the first assessment of proteins detectable in infant blood and to identify possible molecular predictors, or biomarkers, of fetal health risks.

The emergence of improved analytical tools allowed the researchers to address newborn health risks and explore the environmental effects of a well-known toxin in a level of detail not previously available. These tools include high-speed DNA sequencing, a powerful instrumental analysis called proteomic mass spectrometry to enhance the detection of proteins in complex samples, and bioinformatics, or the raw computing power to perform massive data crunching to tease out and identify biomarkers.

In doing so, the team described over 200 serum proteins contained in umbilical cord blood, the vital link between mother and developing baby that shares between the pair both essential nutrients as well as unwanted toxins absorbed by the mother.

Modern tools in mass spectrometry and bioinformatics have enabled us to obtain a first view of proteins contained in fetal cord blood serum and to single out among these more than a dozen interesting ones whose concentrations change as a function of chemical exposure. These biomarkers of exposure and early effect are the gold of protein mining, said Halden, who is also an associate professor in the Ira A. Fulton School of Engineering.

Halden, who joined ASU's Biodesign Institute in 2008, initiated the study while at Hopkins along with lead author David R. Colquhoun, and colleagues Lynn R. Goldman, Frank R. Witter, Robert N. Cole, Marjan Gucek, Malini Mansharamani, and Benjamin J. Apelberg. The results were published in the early online edition of the journal

FSU researcher's discovery leads to $1.5 million grant, potential new treatment of liver fibrosis

Fri, 17 Oct 2008 04:00:00 PST

( from http://www.rxpgnews.com ) TALLAHASSEE, Fla. -- The discovery of a protein involved in the life-threatening mechanism of liver fibrosis has helped a researcher at the Florida State University College of Medicine attract a $1.5 million grant from the National Institutes of Health.

Branko Stefanovic, associate professor in the department of biomedical sciences at the College of Medicine, hopes his discovery could lead to treatment methods that may stem the process of liver fibrosis. Cirrhosis, the terminal phase of the disease, kills 26,000 Americans each year -- the ninth leading cause of death in the United States.

Liver fibrosis refers to the accumulation of excess scar tissue in the liver through excess deposits of collagen, a fibrous protein found in skin, bone, and other connective tissues. The formation of scar tissue is a normal bodily response to injury, but in fibrosis the scarring begins to accumulate to unacceptable levels. The process can result from one of multiple causes, the most frequent of which are alcohol abuse and hepatitis C infection.

Fibrosis is difficult to detect until collagen deposits reach a point where the scarring has severely impaired organ function, meaning individuals suffering from the disease typically do not receive any treatment until it's too late.

The capacity of liver cells to regenerate is great, so therefore normally the primary diseases that can lead to fibrosis do not kill the patient, Stefanovic said. What kills the patient is secondary scarring and the replacement of normal liver tissue with scar tissue. Once this happens a liver cannot regenerate anymore.

Stefanovic and his research team made the important discovery of a protein involved in the scar formation process while working on a previous NIH grant. The RNA-binding protein, which Stefanovic has successfully cloned in his lab at the College of Medicine, is found at the place and specific time when the body is making collagen as part of the normal wound healing resulting from the body's efforts to repair injured tissue.

We had evidence of its existence, but we didn't have the protein, Stefanovic said. We had been looking for this particular protein for several years until we used some very sophisticated methods of cloning. When I saw the results of the binding of the protein to our target I knew immediately we had found the right one.''

Stefanovic said he doesn't believe there will ever be a cure for liver fibrosis but that research and development will one day lead physicians to be able to slow down the progress of the disease.

At least if we slow down the chronic process, instead of dying in five years the patient will live 15 years or more,'' he said.

The goal is to suppress excessive collagen synthesis. In order to do that we have to know the molecular mechanisms that regulate manufacture of the protein and then see what has gone wrong when the liver is creating excess collagen.

Then we will be able to find specific points in this process where we can intervene, by designing either a drug of some kind or a therapeutic agent that will allow us to block these key points and slow down the scarring. Cloning of this protein is a major step toward this goal.

Bacteria stop sheep dip poisoning fish and bees

Tue, 09 Sep 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Bacteria can be used to break down used sheep dip, preventing bees and fish from dying because of soil and river contamination, scientists heard today (Wednesday 10 September 2008) at the Society for General Microbiology's Autumn meeting being held this week at Trinity College, Dublin.

Most modern sheep dips are based on natural insecticides found in chrysanthemum flowers that have been manufactured synthetically since the 1970s called pyrethroids. These pyrethroids are commonly used in household products like head lice shampoo, ant powders and fly sprays as well as agricultural products designed to control insects.

Synthetic pyrethroid compounds are far less toxic to humans than other insecticides, such as the organophosphates formerly used for removing disease-causing insects from sheep but they are actually a thousand times more toxic to fish, said Dr Mairin Cannon from University College Dublin, Ireland. They may also cause cancer in people, according to the US Environmental Protection Agency.

Just one cupful of used sheep dip could wipe out all the fish in an entire river, said Dr Cannon. The current advice is to dilute sheep dip with two parts of water to one part dip, then spread it on a designated area of land well away from water courses. This allows specialised bacteria in the soil to degrade the sheep dip over the next couple of months, hopefully before it can get into rivers or streams.

However in rural economies in Ireland, where agriculture provides over 10% of employment and economic turnover, and in upland Wales or Devon where sheep are a major farming activity and sheep dips are routinely used to control parasites, heavy rainfall can cause used sheep dip to leach out into waterways and sediments where it can kill huge quantities of fish.

Synthetic pyrethroids are also extremely toxic to aquatic invertebrates such as leeches, water snails and beetles and are particularly toxic to bees which can lead to problems with pollination. Once the poison is absorbed by these animals it can move up the food chain, accumulating as it goes. In order to prevent pollution of this kind, we looked at bacteria taken from sheep dip contaminated soils in the hope that they could degrade the pyrethroids in the sheep dip before it is spread on land, said Dr Cannon.

30 different bacteria were isolated from sheep dip polluted soil and dipping tanks. Previously, similar bacteria had been found to degrade synthetic pyrethroids at low concentrations. Dr Cannon tested the bacteria to see if they could degrade the pyrethroids at higher concentrations before the sheep dip was diluted. They found 8 different bacteria that could break down the pyrethroid compounds in the sheep dip tank under laboratory conditions.

One type of bacteria originally taken from a sheep dip tank degraded 75% of the compound, which is unprecedented said Dr Cannon. We think these bacteria could be added into sheep dip tanks to break down the insecticides prior to land disposal. We know they can survive because they originally came from inside a sheep dip tank.

It is vital that we do our utmost to prevent fish kills in the future, said Dr Cannon. Most recently there have been several reports of fish kills as a result of sheep dip pollution in the UK. The best way to degrade synthetic pyrethroids in an environmentally friendly manner is to use these naturally occurring bacteria before the dip gets out into the environment. This could prevent a cascade of detrimental effects to fish, bees, aquatic invertebrates and ultimately humans.

NTP finalizes report on Bisphenol A

Wed, 03 Sep 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Current human exposure to bisphenol A (BPA), a chemical used in many polycarbonate plastics and epoxy resins, is of some concern for effects on development of the prostate gland and brain and for behavioral effects in fetuses, infants and children, according to a final report released today by the National Toxicology Program (NTP).

The report provides the NTP's current opinion on BPA's potential to cause harm to human reproduction or development. The conclusions are based primarily on a broad body of research involving numerous laboratory animal studies. The report is part of a lengthy review of the scientific literature on BPA and takes into consideration public and peer review comments received on an earlier draft report. The final report is available at

There remains considerable uncertainty whether the changes seen in the animal studies are directly applicable to humans, and whether they would result in clear adverse health effects, said NTP Associate Director John Bucher, Ph.D. But we have concluded that the possibility that BPA may affect human development cannot be dismissed.

About the impact that these findings may have on consumers, CERHR Director Michael Shelby, Ph.D., said, Unfortunately, it is very difficult to offer advice on how the public should respond to this information. More research is clearly needed to understand exactly how these findings relate to human health and development, but at this point we can't dismiss the possibility that the effects we're seeing in animals may occur in humans. If parents are concerned, they can make the personal choice to reduce exposures of their infants and children to BPA.

The NTP, an interagency federal research program at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, uses a five-level scale ranging from negligible to serious, with some concern being the midpoint.

We are expressing this level of concern because we see developmental changes occurring in some animal studies at BPA exposure levels similar to those experienced by humans, Bucher said.

The report also expresses minimal concern that BPA exposure will affect development of the mammary gland or accelerate puberty in females. The NTP expressed negligible concern that exposure of pregnant woman to BPA will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring.

The NTP also expressed negligible concern that exposure to BPA causes reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings.

The literature on experimental animal studies is large and filled with many conflicting findings. There are a number of remaining uncertainties in the scientific information on BPA, said Bucher. The report discusses many of the uncertainties, including the very limited data from studies in humans and the difficulty in relating the often subtle developmental endpoints in animal studies to human health risks.

The NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted the BPA evaluation. The CERHR follows a formal process for review and evaluation of nominated chemicals that includes convening panels of scientific experts to review the world's scientific literature on the chemical being studied and a peer review process, as well as numerous opportunities for public input. For a summary of the NTP evaluation of BPA, please see

Queen's researchers provide solution to world's worst mass poisoning case

Thu, 28 Aug 2008 04:00:00 PST

( from http://www.rxpgnews.com ) A solution to the world's worst case of ongoing mass poisoning, linked to rising cancer rates in Southern Asia, has been developed by researchers from Queen's University Belfast.

Currently over 70 million people in Eastern India and Bangladesh, experience involuntary arsenic exposure from consuming water and rice; the main staple food in the region. This includes farmers who have to use contaminated groundwater from minor irrigation schemes.

It is estimated that for every random sample of 100 people in the Bengal Delta, at least one person will be near death as a result of arsenic poisoning, while five in 100 will be experiencing other symptoms.

Now, researchers at the Belfast-based University have created new low-cost technology to provide arsenic-free water to millions of people in South Asia currently exposed to high levels of the poison in groundwater.

Leading an international team, Queen's researchers have developed a trial plant in Kasimpore, near Calcutta, which offers chemical-free groundwater treatment technology to rural communities for all their drinking and farming needs.

The technology is based on recharging a part of the groundwater, after aeration, into a subterranean aquifer (permeable rock) able to hold water. Increased levels of oxygen in the groundwater slow down the arsenic release from the soil. At higher dissolved oxygen levels, soil micro organisms, as well as iron and manganese, reduce the dissolved arsenic level significantly.

Dr Bhaskar Sen Gupta of Queen's, co-ordinator of the project said: Arsenic poisoning is behind many instances of ill-health in Southern Asia, including a rising number of cancer cases. Developing a low cost method of decontaminating ground water that is laced with high levels of arsenic is a key challenge for sustainable agriculture there.

While there are some techniques available for treating relatively small quantities of water, there has, until now, been no viable technology available for decontaminating groundwater on a large scale that can ensure safe irrigation and potable water supply.

This project developed by Queen's is the only method which is eco-friendly, easy to use and deliverable to the rural community user at an affordable cost.

The project is part of the EU-funded Asia Pro Eco Programme which is dedicated to the improvement of environmental performance in Asian economic sectors. Known as TiPOT (Technology for in-situ treatment of groundwater for potable and irrigation purposes), a key part of the project is the establishment of sustainable technology partnerships.

Explaining further, Dr Sen Gupta said: From its inception we have had the vital support of Indian-based stakeholders, such as village councils and local financial institutions. This has been vital as they are the authorities who monitor the water supply and distribution in rural areas and provide micro-credit to the local farmers.

With their help, we now have a solution which is transferable to many areas in need across Asia.

The new plant will be maintained and operated by local village technicians. To help apply the technology to other areas in the South Asian region, the World Bank has given a grant of $200,000 to the TIPOT consortium to set up six more subterranean water treatment plants in the Gangetic plains of West Bengal.

Researchers probe geographical ties to ALS cases among 1991 Gulf War veterans

Mon, 21 Jul 2008 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Researchers from Duke University, the University of Cincinnati (UC) and the Durham Veterans Administration Medical Center are hoping to find a geographical pattern to help explain why 1991 Gulf War veterans contracted the fatal neurological disease amyotrophic lateral sclerosis (ALS) at twice the normal rate during the decade after the conflict.

By layering military records of troop locations onto Gulf-area maps, we've found there were some areas of service where there appears to be an elevated risk, said Marie Lynn Miranda, an associate professor at Duke's Nicholas School of the Environment whose group uses geographic information systems (GIS) to study environmental health problems.

Also known as Lou Gehrig's Disease because it crippled and ultimately killed that baseball great in 1941, ALS causes cellular degeneration in the central nervous system. Its cause is unknown.

There are no reports on the occurrence of ALS among veterans of other conflicts, the researchers wrote. There is only a single report that suggests ALS may arise from environmental exposures associated with military service, per se. The cases assessed by Miranda and her colleagues occurred within a group of people who are expected to be at low risk for ALS, because they're mostly under the age of 45.

Miranda is the first author of a report on an initial analysis now published online in the research journal NeuroToxicology. The work was funded by the Department of Veterans Affairs Cooperative Studies Program.

The report's senior author is Ronnie Horner, professor and director of the department of public health at Cincinnati, who led research that first documented twice-normal ALS rates among vets of the first Persian Gulf War in an article published in the September 2003 issue of the journal Neurology.

Horner's group is now assessing possible exposures vets might have had in the Gulf region that could explain the higher ALS rates its 2003 study found.

As one of the largest contemporary set of cases, it presents a real opportunity to identify clues as to the cause of ALS not only for veterans of the first Gulf War but, perhaps, for ALS generally, Horner said. UC researchers are coordinating their investigations with those of researchers at the Durham, N.C. Veterans Medical Center and nearby Duke Medical Center.

Another UC-led study, published in the July 2008 issue of the journal Neuroepidemiology, found that the risk for developing ALS has now decreased among 1991 Gulf War vets. That suggests that the cause or causes of the ALS had something to do with their deployment in the region between August 1990 and July 1991.

Of the 135 cases diagnosed among the vets within 11 years after the war, only three had a family history of the disease. The small numbers might indicate that there is an environmental cause for ALS, the authors added.

In the one-year period of military operations, some deployed military personnel experienced numerous exposures to multiple, potentially neurotoxic agents, Miranda and coauthors wrote in the new report. If the array of possible candidate environmental exposures could be reduced, it may be possible to identify or at least focus inquiry on specific potential causative agents.

To narrow down the possibilities, Miranda and fellow investigators used GIS analysis, which allows researchers to layer different kinds of information onto maps to deduce potential risks.

They began by searching Department of Veterans Affairs and Department of Defense records as well as other sources to identify military personnel diagnosed with ALS after 1991. Department of Defense data also allowed the researchers to identify the military units these veterans with ALS served in during their deployment to the Persian Gulf region.

In a separate analysis, the researchers identified troop units known to have been exposed to emissions from a munitions storage area at Khamisayah, Iraq. Those munitions were destroyed by U.S. forces in March 1991, and a United Nations commission later found many rockets there had been loaded for chemical warfare.

A previous Defense Department modeling study deduced that some 90,000 veterans may have been exposed to low levels of nerve agent at Khamisayah, the new report said.

The GIS mapping revealed that there were some areas where there appeared to be an elevated risk, Miranda said. To narrow down the possibilities, she and co-investigators then used statistical methods that assess the best guess about the likelihood that space matters for each grid of Gulf territory, she added.

Applying those statistics, the likelihood of a spatial connection with ALS development climbed as high as 91 percent in some grid cells, she said, most notably in a region southeast of Khamisayah. But Miranda cautioned that she will need to do additional analyses that add time to place before she can be more specific.

For instance, the researchers will want to know whether the ALS victim's units were in the path of emissions from Khamisayah on a specific day. Miranda and her colleagues are also interested in examining environmental exposures that may be associated with smoke plumes from oil well fires.

Study shows quantum dots can penetrate skin through minor abrasions

Wed, 02 Jul 2008 04:00:00 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.

Newly approved ocular safety methods reduce animal testing

Mon, 23 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Federal regulatory agencies have accepted recommendations of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) for two methods that can reduce live animal use for ocular safety testing, the committee announced today. ICCVAM is a permanent interagency committee composed of representatives from 15 federal regulatory and research agencies, including the National Institutes of Health (NIH) that use, generate or disseminate toxicology testing information.

The two alternative test methods, the bovine corneal opacity and permeability (BCOP) assay and the isolated chicken eye (ICE) assay, do not involve the use of live animals. These are the first scientifically valid alternative methods to gain regulatory acceptance for ocular safety testing.

The Consumer Product Safety Commission (CPSC), the Environmental Protection Agency (EPA), and the Food and Drug Administration (FDA) concurred with the ICCVAM recommendations for the BCOP and ICE tests. CPSC will now accept these tests instead of the conventional ocular toxicity test for the purpose of classification for labeling under the Federal Hazardous Substance Act (15 U.S.C. 1261-1278).

Based on an extensive database of product test results, the use of these two alternative test methods will likely reduce the use of live animals for eye safety testing by 10 percent or more, stated William Stokes, D.V.M., the executive director of ICCVAM and director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods NICEATM). More importantly, the use of these tests will eliminate the testing in animals of most substances likely to cause the most severe pain and discomfort.

If a positive response is obtained using either of the two new approved alternative methods, the product can be labeled as causing irreversible or severe eye damage and no live animal testing will be required. If the response is negative, the product is then tested in an animal to confirm that it does not cause severe or irreversible damage.

The NIH and other federal agencies are committed to the welfare of animals used in research. All animals used in federally funded research are protected by laws, regulations and policies to ensure they are used in the smallest number possible and with the greatest commitment to their comfort. ICCVAM is working to promote the development and validation of alternative test methods. Alternative test methods are those that accomplish one or more of the 3Rs of reducing the number of animals used in testing, or refining procedures so animals experience less pain and distress, or replacing animals with non-animal systems.

Marilyn Wind, Ph.D., chair of ICCVAM and principal ICCVAM representative for the CPSC said, The use of these alternative methods will help reduce animal use while ensuring the proper identification and hazard labeling for substances that may cause severe or permanent eye damage.

Before certain new products such as drugs and pesticides can be marketed in the United States, they must be tested for their potential to adversely affect the health of consumers. Currently, the FDA, the CPSC and the EPA require that these and other products such as cosmetics, shampoos, detergents and household chemical products be labeled with information on hazards for human health. Tests that use animals are among the tests used by these federal agencies to evaluate potential damage to the eye that may result from exposure to these products. ICCVAM conducted a comprehensive scientific review of four alternative test methods and concluded that the BCOP and ICE methods can be useful for identifying products that may cause permanent or severe damage to an exposed eye. ICCVAM's evaluation report and recommendations were forwarded to federal agencies for their consideration in October 2007.

The ICCVAM Test Method Evaluation Report: In Vitro Ocular Toxicity Test Methods for Identifying Severe Irritants and Corrosives (NIH Publication 06-4511) contains the ICCVAM recommendations for these two alternative eye test methods and how results can be used to determine appropriate warning labels and special packaging requirements. The report also includes proposals for new studies that might further increase the usefulness of alternative test methods for detecting products that cause severe eye damage.

ICCVAM's recommendations were made after consideration of public comments and a report from an independent scientific peer review panel. The full report is available at the ICCVAM-NICEATM Web site (

Arsenic and new rice

Mon, 09 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Amid recent reports of dangerous levels of arsenic being found in some baby rice products, scientists have found a protein in plants that could help to reduce the toxic content of crops grown in environments with high levels of this poisonous metal. Publishing in the open access journal BMC Biology, a team of Scandinavian researchers has revealed a set of plant proteins that channel arsenic in and out of cells.

Arsenic is acutely toxic and a highly potent carcinogen, but is widespread in the earth's crust and easily taken up and accumulated in crops. Contaminated water is the main source of arsenic poisoning, followed by ingestion of arsenic-rich food, especially rice that has been irrigated with arsenic-contaminated water. According to the WHO, arsenic has been found approaching or above guideline limits in drinking water in Argentina, Australia, Bangladesh, Chile, China, Hungary, India, Mexico, Peru, Thailand, and the US.

Until now, scientists have been unable to identify which proteins are responsible for letting arsenite, the form of arsenic that damages cellular proteins, into plant cells. Now Gerd Bienert and his colleagues from the University of Copehangen, Denmark and the University of Gothenburg, Sweden, are the first to show that a family of transporters, called nodulin26-like intrinsic protein (NIPs), can move arsenite across a plant cell membrane. NIPs are related to aquaglyceroporins found in microbes and mammalian cells and which have already been shown to function as arsenite channels in these other organisms. Bienert's team put the plant genes coding for different NIP transporters into yeast cells in order to test the cells for arsenic sensitivity. The researchers found that the growth of yeast containing certain plant NIPs was suppressed when arsenite, one of the predominant forms of arsenic found in soil, was added to the mix. They showed that the arsenite was channelled by NIPs and accumulated inside the yeast cells. Further investigations showed that only a subgroup of NIPs had arsenite transport capabilities, and have now been identified as metalloid channels in plants.

More surprisingly, the researchers also found that when they added arsenate some yeast, cells actually grew better and arsenite was released out of the cells. It appears that some NIPs don't just transport arsenite in one direction, says Bienert. They are bidirectional and, given the right conditions, can clear cells of toxic arsenite as well as accumulate it. This striking exit of the accumulated arsenite in cells could have an important role to play in the detoxification of plants, especially coupled with possibility of engineering a transporter that discriminates against arsenite uptake in the first place.

Long-term pesticide exposure may increase risk of diabetes

Wed, 04 Jun 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Licensed pesticide applicators who used chlorinated pesticides on more than 100 days in their lifetime were at greater risk of diabetes, according to researchers from the National Institutes of Health (NIH). The associations between specific pesticides and incident diabetes ranged from a 20 percent to a 200 percent increase in risk, said the scientists with the NIH's National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI).

The results suggest that pesticides may be a contributing factor for diabetes along with known risk factors such as obesity, lack of exercise and having a family history of diabetes, said Dale Sandler, Ph.D., chief of the Epidemiology Branch at the NIEHS and co-author on the paper. Although the amount of diabetes explained by pesticides is small, these new findings may extend beyond the pesticide applicators in the study, Sandler said. Some of the pesticides used by these workers are used by the general population, though the strength and formulation may vary. Other insecticides in this study are no longer available on the market, however, these chemicals persist in the environment and measurable levels may still be detectable in the general population and in food products. For example, chlordane, which was used to treat homes for termites, has not been used since 1988, but can remain in treated homes for many decades. More than half of those studied in the National Health and Nutrition Examination Survey in 1999-2002 had measurable evidence of chlordane exposure. This is not cause for alarm, added Sandler since there is no evidence of health effects at such very low levels of exposure.

Overall, pesticide applicators in the highest category of lifetime days of use of any pesticide had a small increase in risk for diabetes (17 percent) compared with those in the lowest pesticide use category (0-64 lifetime days). New cases of diabetes were reported by 3.4 percent of those in the lowest pesticide use category compared with 4.6 percent of those in the highest category. Risks were greater when users of specific pesticides were compared with applicators who never applied that chemical. For example, the strongest relationship was found for a chemical called trichlorfon, with an 85 percent increase in risk for frequent and infrequent users and nearly a 250 percent increase for those who used it more than 10 times. In this group, 8.5 percent reported a new diagnosis of diabetes compared with 3.4 percent of those who never used this chemical. Trichlorfon is an organophosphate insecticide classified as a general-use pesticide that is moderately toxic. Previously used to control cockroaches, crickets, bedbugs, fleas, flies and ticks, it is currently used mostly in turf applications, such as maintaining golf courses.

This is one of the largest studies looking at the potential effects of pesticides on diabetes incidence in adults, said Freya Kamel, Ph.D., a researcher in the intramural program at NIEHS and co-author in the paper appearing in the May issue of the American Journal of Epidemiology. It clearly shows that cumulative lifetime exposure is important and not just recent exposure, said Kamel. Previous cross-sectional studies have used serum samples to show an association between diabetes and some pesticides.

Diabetes occurs when the body fails to produce enough insulin to regulate blood sugar levels or when tissues stop responding to insulin. Nearly 21 million Americans have diabetes. The cause of diabetes continues to be a mystery, although genetics and environmental factors such as obesity and lack of exercise appear to play roles.

To conduct the study, the researchers analyzed data from more than 30,000 licensed pesticide applicators participating in the Agricultural Health Study, a prospective study following the health history of thousands of pesticide applicators and their spouses in North Carolina and Iowa. The 31,787 applicators in this study included those who completed an enrollment survey about lifetime exposure levels, were free of diabetes at enrollment, and updated their medical records during a five-year follow-up phone interview. Among these, 1,171 reported a diagnosis of diabetes in the follow-up interview. The majority of the study participants were non-Hispanic white men.

Repeated methamphetamine use causes long-term adaptations in brains of mice, researchers find

Wed, 09 Apr 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.

The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.

Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.

They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal -- the equivalent of years in humans -- did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.

The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.

What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.

After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.

What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that, said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children's Hospital. We think these changes in the brain may account for at least some of the physiological components of meth addiction.

If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.

Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction, explained Bamford. We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals.

Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.

How do infections and toxins launch a cell's self-destruct and alarm system?

Mon, 10 Mar 2008 04:00:00 PST

( from http://www.rxpgnews.com ) Cells are coded with several programs for self-destruction. Many cells die peacefully. Others cause a ruckus on their way out.

Some programmed cell death pathways simply and quietly remove unwanted cells, noted a team of University of Washington (UW) researchers who study the mechanisms of cell destruction.

Then there is the alarm-ringing death of a potentially dangerous cell, such as a cell infected with Salmonella, they added. These dying cells spill chemical signals and get a protective response. The resulting inflammation, which the body launches in self-defense, can at times backfire and damage vital tissues.

A research team lead by Dr. Brad T. Cookson, an associate professor of microbiology and laboratory medicine, named this type of cell death pyroptosis, Greek for going down in flames. Cell death that doesn't cause inflammation is called apoptosis: to drop gently like leaves from a tree.

An enzyme inside cells, called caspase-1, plays a critical role in both harmful inflammation and in resistance to infection, Cookson and his colleagues noted. It's not just responsible for cell death, but also for the production of inflammatory proteins that are released from the dying cell. Mice deficient in caspase-1 are susceptible to infection, yet resistant to toxic shock, tissue injury from lack of oxygen, and inflammatory bowel disease.

The Cookson lab has done many studies of caspase-1 and how it mediates the pathway of pro-inflammatory programmed cell death. The lab's most recent study will be published the week of March 10 to March 14 in the online Early Edition of the Proceedings of the National Academy of Sciences. The study looked at how two different noxious stimuli, anthrax toxin and Salmonella infection, trigger the caspase-1-mediated cell death pathway. UW graduate students Susan Fink and Tessa Bergsbaken conducted this study.

The researchers found that each of these stimuli took an independent route to activate caspase-1; however, these two distinct mechanisms of activation eventually converged on a common pathway of cell death. This common pathway featured cleavage of the cell's DNA, activation of inflammatory chemical messengers, and the final jettison of the cells contents. The spillage occurs after nano-scale pores form in the cell membrane, much like punctures in a water balloon.

According to Cookson, these findings are helping to create research models for studying a broadly important pathway of pro-inflammatory programmed cell death. The findings also support the notion that diverse disease agents can use different mechanisms to elicit this pathway.

Examining this system provides insight into mechanisms of both beneficial and pathological cell death, and the strategies that infectious disease agents employ to manipulate the body's responses, Cookson said. His group's previous studies of Yersinia, the plague pathogen, revealed that cell death mechanisms can be re-directed from a passive, non-inflammatory pathway, to a more beneficial inflammatory pathway. This finding suggests the possibility of treating diseases by modulating cell death pathways.

In addition to its protective role in fighting infection, Cookson added, caspase-1 also plays a role in many medical conditions characterized by cell death and inflammation. These conditions include organ damage in the heart, brain, lungs, nerves, and kidneys. Understanding pro-inflammatory cell death pathways may lead to new therapies against fatal or disabling diseases, such as serious infections, heart attack, cancer and stroke.

Cookson is part of the National Institutes of Health-funded Microscale Life Sciences Center, a collaboration among scientists and engineers from the UW, the University of Arizona, the Fred Hutchinson Cancer Research Center, and Brandeis University. The scientists work to discover basic mechanisms in the formation, growth, and decline of human cells. Their aim is to develop biotechnology to combat widespread diseases and environmental threats to human health.

Gene expression differences between Europeans and Africans affect response to drugs, infections

Thu, 28 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) Differences in gene expression levels between people of European versus African ancestry can affect how each group responds to certain drugs or fights off specific infections, report researchers from the University of Chicago Medical Center and the Expression Research Laboratory at Affymetrix Inc. of Santa Clara, CA.

In the March 7, 2008, print issue of American Journal of Human Genetics, and published early online, the researchers used Affymetrix exon arrays to show that expression levels for nearly five percent of the 9,156 human genes they studied varied significantly between individuals of European and African ancestry. The research team took an unbiased whole genome approach and found significant differences in several unrelated processes, especially among genes involved in producing antibodies to potential microbial invaders.

The researchers used lymphoblastoid cell lines derived from blood from 180 healthy individuals. They studied 60 nuclear families, including mother, father and child. Thirty of the families were Caucasians from Utah and 30 were Yorubans from Ibadan, Nigeria.

Our primary interest is the genes that regulate how people respond to medicines, such as cancer chemotherapy, said cancer specialist Eileen Dolan, PhD, professor of medicine at the University of Chicago and senior author of the study. We want to understand why different populations experience different degrees of toxicity when taking certain drugs and learn how to predict who might be most at risk for drug side effects.

But in the process they saw several other differences. Some, including variation in the immune system's response to microbial invaders, were expected. Previous studies have found that African Americans may be more susceptible than Caucasians to infection by certain bacteria, such as Porphyromonas gingivalis that causes periodontitis.

Others were unanticipated, including significant differences in expression levels among genes involved in fundamental cellular processes such as ribosomal biogenesis, transfer RNA processing, and Notch-signaling--part of a complex system of communication that governs basic cellular activities and coordinates cell actions.

Population differences in gene expression have only recently begun to be investigated, said Dolan, We believe they play a significant role in susceptibility to disease and in regulating drug response. Our current research focuses on how these genetic and expression differences play a role in sensitivity to adverse effects associated with chemotherapy.

Understanding at the genetic level how individuals within and among populations vary in their response to drugs could improve treatment. The University of Chicago team worked closely with Affymetrix on new technology that enabled them to perform a very comprehensive study including evaluation of expression levels of every known gene.

Federal toxics disclosure law could help inform public of nanotechnology risks

Tue, 26 Feb 2008 05:00:00 PST

( from http://www.rxpgnews.com ) The Project on Emerging Nanotechnologies (PEN) is releasing a first-time legal analysis that finds a key federal toxics reporting statute could be applied to production and commercialization of nanotechnology, providing the public with more information about these revolutionary -- yet still potentially risky -- technologies.

But before the Toxics Release Inventory (TRI) authorities can be applied to nanomaterials, in most cases more toxicological data must be developed to better understand the potential human health and environmental impacts of these cutting-edge technologies. The analysis, conducted by two noted environmental law experts, finds that federal authorities may need to be amended to address reporting thresholds that may not apply effectively to nanomaterials because of their unique characteristics.

There needs to be development of additional toxicological data on nanomaterials, but in theory TRI could be applied to nanomaterials. The key question is whether EPA will make any determinations about whether particular nanomaterials constitute toxic chemicals, says Linda Breggin, one the authors of the analysis and Senior Attorney at the Environmental Law Institute.

The landmark analysis comes as over 40 environmental, consumer, labor and other groups are calling for regulation and disclosure of products containing nanomaterials, and as congressional lawmakers are considering legislation to expand reporting requirements for environmental pollutants under TRI. Although currently proposed legislation does not specifically address nanomaterials, a public dialogue about the benefits and costs of TRI is underway that could include discussion of the program's application to nanomaterials, the new PEN analysis says.

At the local level the City of Berkeley, Calif., adopted in 2006 a disclosure ordinance that requires nanomaterial manufacturers to disclose the known risks of their products. Now Cambridge, Mass., is considering a similar ordinance, and other local governments may follow suit.

If Cambridge passes an ordinance similar to Berkeley's, who knows how many other cities or other municipalities will follow says PEN Director David Rejeski. Soon we could have a patchwork of cities across the country with nanotech disclosure ordinances, which is why environmental law experts should take the time now to make the decision as to whether TRI is a tool that can be used at the federal level to disclose nanomaterials' potential risks.

The report also emphasizes the importance of recognizing that several additional right-to-know or disclosure-related laws and initiatives should be explored as possible disclosure vehicles for environmental, health, and safety risks that could be associated with nanomaterials. The report also highlights the fact that additional research is required to determine whether application of TRI to nanomaterials should be pursued as a policy priority in the near term.

Iowa State researchers look for smaller, cheaper, 1-dose vaccines

Tue, 15 Jan 2008 05:00:00 PST

( from http://www.rxpgnews.com ) A team of Iowa State University researchers is examining a new vaccine method that may change the way we get vaccinations.

Michael Wannemuehler and his team of researchers is hoping to find a way to produce vaccines that work better, use smaller doses and require only one trip to the doctor's office.

Traditionally, injectable vaccines have often been prepared from killed bacteria. The vaccinated person's immune system then learns to recognize the bacteria as a threat and consequently builds up defenses against it. Then, if the individual is exposed to the live version of the infectious agent, his or her body is already prepared to defend itself.

Wannemuehler's research is focused on the use of just a part of the bacteria -- a protein -- as a vaccine, instead of the entire bacteria, coupled with novel polymers that will be used to deliver these vaccines. This combination of new approaches will allow vaccines doses to be smaller, safer and induce fewer side effects.

As we move away from using whole bacteria, we're going to more molecular approaches with purified proteins or portions of proteins, said Wannemuehler, a professor of veterinary microbiology and preventative medicine. What these technologies should allow us to do is, instead of injecting 100 units to get protection, we can inject one unit, for example.

Wannemuehler's research targets the bacteria that causes plague, a disease that's rare in the United States, but is still found in other parts of the world.

Using select proteins of the bacteria coupled with unique polymers can reduce the amount of vaccine needed as well as costs for shipping and storage. That makes the vaccine economically feasible for areas at a great distance, such as Africa, where vaccines can be difficult to obtain.

Also, vaccinating a large population can be difficult if more than one dose or injection is required. In places where doctors are scarce, locating and vaccinating patients can be difficult. In addition, having the same patients return for their booster vaccinations can be even more complicated.

Another aspect is the hope that this would be single dose, said Wannemuehler. We hope we can get a robust response with one dose.

And there will likely be uses beyond the plague.

If this technology works here, said Wannemuehler, it's completely transferable to any protein, with minor changes.

Wannemuehler is working with BioProtection Systems Corp. of Ames on this research. BPSC hopes to supply lower-cost vaccines to government agencies for use where the plague is still a threat.

We are thankful that the Iowa Values Fund supports our collaboration with Iowa State University and allows us to combine our broadly applicable vaccine technology with theirs for the development of more effective vaccines, said Joe Lucas of BPSC, located at the Iowa State University Research Park.

Biochip mimics the body to reveal toxicity of industrial compounds

Mon, 17 Dec 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Troy, N.Y. - A new biochip technology could eliminate animal testing in the chemicals and cosmetics industries, and drastically curtail its use in the development of new pharmaceuticals, according to new findings from a team of researchers at Rensselaer Polytechnic Institute, the University of California at Berkeley, and Solidus Biosciences Inc.

The team's most recent discovery will be featured in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) on Dec. 17.

The researchers have developed two biochips, the DataChip and the MetaChip, that combine to reveal the potential toxicity of chemicals and drug candidates on various organs in the human body, and whether those compounds will become toxic when metabolized in the body, all in one experiment without the use of live animals.

Traditional toxicity testing involves the use of animals to predict whether a chemical or drug candidate is toxic. However, with the large number of compounds being generated in the pharmaceutical industry, and new legislation stipulating that chemicals undergo toxicity analysis, there is a rapidly emerging need for high-throughput toxicity testing.

We looked at the issues facing companies and realized that we needed to develop something that was low-cost, high-throughput, easily automatable, and did not involve animals, said co-lead author Jonathan S. Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer and co-founder of Solidus Biosciences Inc., the company that is working to commercialize the chips. We developed the MetaChip and DataChip to deal with the two most important issues that need to be assessed when examining the toxicity of a compound -- the effect on different cells in our body and how toxicity is altered when the compound is metabolized in our bodies.

When the biochips are used together the result is a promising and affordable alternative to animal-based toxicology screening and a direct route to developing safe, effective drugs, according to Dordick, who is also a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.

Currently, detailed toxicity screening does not come into the drug discovery process until later in the development, when significant time and money have been invested in a compound by a company. And animal testing does not always provide information that translates to predicting the toxicity of a compound or its metabolites in a human, Dordick said.

The collaborative team sees the combined chips as an efficient, more accurate way to test drug compounds for toxicity earlier in the discovery process. But, co-lead author and Solidus Biosciences co-founder Douglas S. Clark, professor of chemical engineering at the University of California at Berkeley, views pharmaceutical companies as only one potential user, and not necessarily the first.

The initial market will not necessarily be pharmaceuticals, Clark said. He further explains that the initial market will likely be chemical and cosmetic companies that are being pushed to eliminate animal testing or cannot afford such testing. In fact, by 2009 cosmetics companies in Europe will be restricted from using animals in testing for chemical toxicity. Obviously cosmetics need to be safe, and ensuring the safety of new compounds without testing them on animals presents a new challenge to the industry, especially as the number of compounds increases. These chips can meet this challenge by providing comprehensive toxicity data very quickly and cheaply.

The team's most recent achievement outlined in PNAS is the DataChip, a biochip comprising up to 1,080 three-dimensional human cell cultures. The three-dimensional structure is more closely in line with how the cells would be arranged in organs of the human body. The DataChip can provide companies or academic labs with an extremely fast screen of potential toxicity of chemicals and drug candidates on different types of human cells.

In an earlier paper published in a Jan. 25, 2005, edition of PNAS, the team introduced the MetaChip. The biochip mimics the metabolic reactions of the human liver, where chemicals and drugs are processed in the body. Depending on the compound, a seemingly benign chemical like acetaminophen can become highly toxic when metabolized by the liver. Because of differences in the type and amount of their drug-metabolizing enzymes, most of which are in the liver, individuals can metabolize a drug or other chemical compound differently. What is harmless to one person may be toxic to another. By arranging the ratio of enzymes on the MetaChip, scientists could develop a personalized chip to determine how toxic a drug might be to different people.

We are still a ways off from personalized medicine, but the MetaChip offers that future possibility, Dordick said. When coupled with the new DataChip, the two chips could someday be used to determine the levels and combinations of drugs that are safe and effective for each individual patient, Clark explains.

Even minute levels of lead cause brain damage in children

Tue, 20 Nov 2007 05:00:00 PST

( from http://www.rxpgnews.com ) Even very small amounts of lead in children's blood -- amounts well below the current federal standard -- are associated with reduced IQ scores, finds a new six-year Cornell study.

The study examined the effect of lead exposure on cognitive function in children whose blood-lead levels (BLLs) were below the Centers for Disease Control and Prevention (CDC) standard of 10 micrograms per deciliter (mcg/dl) -- about 100 parts per billion. The researchers compared children whose BLLs were between 0 and 5 mcg/dl with children in the 5-10 mcg/dl range.

Even after taking into consideration family and environmental factors known to affect a child's cognitive performance, blood lead played a significant role in predicting nonverbal IQ scores, says Richard Canfield, a senior researcher in Cornell's Division of Nutritional Sciences and senior author of the study in the journal Environmental Health Perspectives. We found that the average IQ scores of children with BLLs of only 5 to 10 mcg/dl were about 5 points lower than the IQ scores of children with BLLs less than 5 mcg/dl. This indicates an adverse effect on children who have a BLL substantially below the CDC standard, suggesting the need for more stringent regulations, he said.

In the United States over the last several months, nearly 50 specific products, including millions of toys for young children, have been recalled due to excessive lead in the paint, plastics and metal. Our findings emphasize the very real dangers associated with low-level exposures, to which lead in toys can contribute, Canfield said.

U.S. children are exposed to lead primarily from household dust contaminated by deteriorating interior lead-based paint. In addition to toys, other potential sources include contaminated soil, imported food stored in lead-glazed pottery and certain plastic, metallic and painted products.

This most recent finding builds on the same research team's influential 2003 study, published in the New England Journal of Medicine, that reported adverse effects of BLLs below 10 mcg/dl in a group of children followed from infancy to age 5. Our new findings are based on follow-up testing of the same children at age 6, using a more comprehensive IQ test to assess cognitive function. The results provide compelling evidence that low-level lead exposure has effects into the school-age years, said Todd Jusko '01, a University of Washington Ph.D. candidate in epidemiology and co-author on both reports.

Children living in poverty disproportionately suffer from elevated BLLs, said statistician and co-author Charles Henderson, a Cornell senior researcher in human development. He also noted that even a small decline in an IQ score is likely to be reflected in aptitude test scores such as the SAT.

According to the CDC, about one out of every 50 children in the United States between ages 1 and 5 has a BLL above 10 mcg/dl and about 10 percent of children have BLLs of 5 mcg/dl or higher; about 25 percent of U.S. homes with children under age 6 have a lead-based paint hazard.

The bottom line, according to Canfield, is that lead is a persistent neurotoxin that causes brain damage. The fact that lead has been found in millions of toys, even toys specifically designed for children to put into their mouths, presents an unacceptable risk. Our findings suggest the need to re-evaluate the current federal standards for lead in consumer products and the current definition of an elevated BLL in children.

Contamination from depleted uranium found in urine 20 years later

Wed, 24 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Inhaled depleted uranium (DU) oxide aerosols are recognised as a distinct human health hazard and DU has been suggested to be responsible in part for illness in both military and civilian populations that may have been exposed.

University of Leicester geologist, Professor Randall R Parrish will be giving this message to the 119th annual meeting of the Geological Society of America at the Colorado Convention Center in Denver on 28 October 2007 at 10.05-10.25am.

In his talk entitled: �Depleted uranium (DU): its environmental dispersion and human uptake� he will outline his research findings on a new method of tracing DU.

The issue has been the subject of investigations by the Royal Society (UK), the National Academy of Science (US) and other bodies, but studies of individuals who have been clearly exposed to environmental contamination are lacking.

Professor Parrish commented: �Our objective was to develop a high sensitivity method of EU detection in urine, using MC-ICP mass spectrometry that would be capable of detecting an individual�s exposure to DU up to 20 years after the event.

�We developed this method and applied it to individuals, either known or likely to have had a DU aerosol inhalation exposure, and to a large voluntary cohort of 1991 Gulf conflict veterans to assess DU exposure screening reliability and accumulate data on exposure.�

Using his method, Professor Parrish and his research team have found traces of DU in urine more than 20 years later, in those cases where exposure to DU aerosol has been unambiguous and in sufficient quantity. This is true even when the U concentration is at the low end of the normal range.

Most such samples would return a negative screening result with other, less sensitive, methods.

Professor Parrish added: �Our method has been used to show that it is capable of resolving legal cases based on a claim of DU exposure. Also it shows that the occurrence of DU in 1991 Gulf Conflict veterans is likely to be uncommon to rare, but if a significant inhalation exposure occurred then it can be detected in urine for decades to come.

�It offers a way to resolve debates about DU and health and provide perspective on the issue. Resolving the potential implications of DU to health in contaminated populations is best done by properly testing exposed cohorts. The cohorts in need of study are those living in DU-contaminated areas of Iraq, or those living in the vicinity of DU munitions factories with large DU contamination footprints.�

NAS report offers new tools to assess health risks from chemicals

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Determining how thousands of chemicals found in the environment may be interacting with the genes in your body to cause disease is becoming easier because of a new field of science called toxicogenomics. A new report issued today by the National Academies of Sciences (NAS) recognizes the importance of toxicogenomics in predicting effects on human health and recommends the integration of toxicogenomics into regulatory decision making. The NAS report was commissioned by the National Institute of Environmental Health Sciences (NIEHS) part of the National Institutes of Health (NIH) and a leader in the development of toxicogenomic technologies.

Toxicogenomic technologies provide tools to better understand the mechanisms through which environmental agents initiate and advance disease processes. They can also provide important information to help identify individuals that are more susceptible to disease risks posed by certain environmental agents than the general population.

�Using toxicogenomic technologies will open the door for public health decision makers who need to decide in a timely and accurate manner what chemicals are safe and which ones are not,� says Christopher Portier, Ph.D., Associate Director, NIEHS and Director, Office of Risk Assessment Research.

The report from the NAS National Research Council (NRC) entitled �Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment� states that the technological hurdles that could have limited the reproducibility of data from toxicogenomic technologies have been resolved and recommends ways for the field to move forward.

�NIH and others have invested in the development of these tools and have already tackled many of the tough technical questions. We are now ready to move to the next phase of technology development, refined standardization and validation, so these tools can be even more useful to regulatory agencies,� says Portier.

�The NIEHS and NTP have been steadily increasing the use of toxicogenomic and other technologies derived from the molecular biology revolution,� said Samuel H. Wilson, M.D., NIEHS Acting Director. The research and initiatives supported through the National Center for Toxicogenomics and the Toxicogenomics Research Consortium, for example, were at the forefront of these technologies and were leaders in the development of many of the standards for quality and reproducibility that are used today.

The report, which was prepared by a panel of 16 scientists assembled by the NRC, provides a broad overview of the potential benefits arising from toxicogenomic technologies, describes challenges regarding use of new technologies, and provides 14 recommendations to achieve the potential benefits of these technologies.

UT researcher earns $1.3M grant to study toxic cleanup at DOD sites

Wed, 10 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) KNOXVILLE -- Decades of weapons production and base operations have left the U.S. Department of Defense (DOD) with a legacy of as many as 3,000 sites contaminated with highly toxic substances.

University of Tennessee Research Professor Jack Parker and Peter Kitanidis of Stanford University have been awarded $1.3 million over three years to find the best methods to analyze and clean up the sites effectively while keeping costs to a minimum.

Parker is a member of UT's Institute for a Secure and Sustainable Environment (ISSE) and Department of Civil and Environmental Engineering.

Their work will look specifically at substances known as dense non-aqueous phase liquids (DNAPLs). DNAPLs are among the more troublesome -- and costly -- toxic substances to remediate, and contamination may be linked to human health effects, including birth defects and cancer.

Parker and Kitanidis received the award from DOD�s Strategic Environmental Research and Development Program. The methodology will be field-tested at Hill and Dover Air Force bases, located in Utah and Delaware, respectively.

Aleisa Bloom, group leader of the DOD Base Technical Support Group at Oak Ridge National Laboratory, and Kyle Gorder, project manager with the Hill Air Force Base Environmental Restoration Branch, will assist with the project.

Once the project is completed, the research group's cost-optimization methods can be applied at the nation's other DNAPL-contaminated sites, which include more than half of the Environmental Protection Agency's Superfund sites.

The history of DNAPL site remediation over the last 30 years can best be described as the history of serial underestimation of cleanup costs, said Parker.

The project aims to produce comprehensive methods and computational tools for making cost-effective decisions on how to understand a polluted site -- a process called characterization -- and meet the DOD's cleanup goals.

This project will focus specifically on optimal management of DNAPL-contaminated sites, which pose a major problem at many DOD facilities, said Way Kuo, dean of the UT College of Engineering. The ability to apply and evaluate these methods and computational tools at Hill and Dover Air Force bases will be of direct and immediate benefit.

Kuo said the study also may lead to conclusions applicable to other national policy issues, such as which approaches make most sense in the real world of complex and hard-to-characterize sites.

Costs for cleaning up these sites easily can run in tens of millions of dollars, with larger sites costing many times more, said Randall Gentry, ISSE director and associate professor in UT's Department of Civil and Environmental Engineering.

If Parker's methodology achieves even modest cost reductions, cumulative savings to the federal government can run into the billions of dollars, said Gentry.

Current remediation technologies for DNAPL contamination of soil and water include, among other approaches, chemical and thermal treatment, enhanced microbial degradation, extraction with surfactants, treatment of extracted groundwater, monitored natural attenuation and use of various containment methods to limit further migration.

DNAPLs, which include well-known chemicals such as creosote, coal tar and PCBs, saw widespread use beginning in the mid-20th century and continuing until the 1980s, when monitoring revealed significant contamination of groundwater.

Love Canal, a neighborhood of the city of Niagara Falls, N.Y., has become synonymous with DNAPL contamination. The 10-square-block residential area -- home to nearly 1,000 families -- surrounded an abandoned landfill used by a chemical company as a dumping ground for thousands of tons of various hazardous wastes. The neighborhood, contaminated with DNAPLs and other toxic substances, ultimately was declared a Superfund site and evacuated.

Scripps research scientists develop innovative dual action anthrax vaccine-antitoxin combination

Thu, 04 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The immune response generated in rats by the new agent protects against lethal toxin exposure after only one injection, and is faster and stronger than any currently available vaccine.

The new study, led by Scripps Research scientists Anette Schneemann and Marianne Manchester, and Salk Institute Professor John A.T. Young, was published in the October 5 issue of the journal PLoS Pathogens (Volume 3, Issue 10).

�The new anti-anthrax agent that we developed is an important and potentially critical development for anyone who works with the bacterium or those who might be exposed to it in a bioterrorism attack,� Schneemann said. �While other strategies are being pursued to develop improved anthrax vaccines, none of these offer the distinct advantage of combining the function of a vaccine with a potent antitoxin.�

Concerns about anthrax-a potentially fatal disease caused by the spore-forming, gram-positive bacterium Bacillus anthracis-as a weapon of bioterrorism has prompted increased efforts to develop better antitoxins and vaccines. The current vaccine, which was developed in the 1950s, is safe and effective, but requires multiple injections followed by annual boosters. Current anthrax treatment involves antibiotics such as ciprofloxacin and doxycycline that attack the bacteria but provide no protection against the dangerous toxins secreted by the bacteria.

The new study introduces a highly effective dual-action compound that leapfrogs current efforts to develop a second-generation anthrax vaccine. In the research, the scientists created a �multivalent display,� with several sites of attachment for recombinant protective antigen protein (PA), the primary component of the current anthrax vaccine, rather than only one. Virus-like particles coated with PA were found to produce a potent toxin-neutralizing antibody response that protected rats from the lethal anthrax toxin after only a single immunization.

The antitoxin strategy arose from the discovery of the anthrax toxin receptor, ANTXR2, in the Young lab. �The new anti-anthrax agent is based on a multivalent display of ANTXR2 on the surface of an insect virus,� explains Schneemann. �Our approach was based on the assumption that a multivalent display of recombinant protective antigen protein would induce a far more potent immune response. That turned out to be correct.�

Specifically, the new vaccine-antitoxin combination is based on the multivalent display (180 copies) of the PA-binding von Willebrand A (VWA) domain of the ANTXR2 cellular receptor on the Flock House virus. The chimeric virus-like particle platform, which produces protective immunity and has been shown to be safe, inhibited lethal toxin action in in vitro and in vivo models of anthrax infection.

In fact, rats survived exposure to the toxin four weeks after a single injection of the new double-acting agent. This result suggests an extremely rapid production of neutralizing antibodies without the use of an adjuvant, a secondary agent that helps stimulate the immune system and is often used to increase the vaccine response-key goals for the development of third-generation anthrax vaccines.

In addition to its use against anthrax, Schneemann notes that creating a multivalent platform may also have the potential to work against other infectious agents.

�One important reason for the success of this project is that it arose from the multidisciplinary and highly collaborative efforts of our team of microbiologists, structural biologists, and immunologists,� said Manchester, who headed a National Institutes of Health (NIH)-funded program project grant that supported the work.

New test could help consumers avoid surprise headaches from chocolate, wine

Mon, 01 Oct 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers in California are reporting development of a fast, inexpensive test suitable for home use that could help millions of people avoid those �out of the blue� headaches that may follow consumption of certain red wines, cheese, chocolate, and other aged or fermented foods.

The test is designed to detect the presence of so-called biogenic amines, naturally occurring toxins that can trigger a wide range of symptoms in sensitive individuals �from nasty headaches to life-threatening episodes of high-blood pressure.

Existing tests for biogenic amines can take several hours, are cumbersome and require large, expensive instruments found only in laboratories, the researchers say. The new test, based on lab-on-a-chip technology, could produce results within five minutes, they state. It will be described in the Nov. 1 issue of ACS� Analytical Chemistry, a semi-monthly journal.

�These toxins can be a serious health problem and are more common than people think,� says study leader Richard A. Mathies, Ph.D., a chemist with the University of California, Berkeley. �They are hidden in a wide variety of foods. Having a quick, convenient way to identify them will help consumers avoid them or at least limit their intake.�

Biogenic amines include tyramine, histamine, and phenylethylamine, which have been known to cause nausea, headaches, and respiratory disorders. These toxins can be particularly dangerous in people with reduced monoamine oxidase (MAO) activity or those taking MAO inhibitors, an older class of antidepressant medications, because they can potentially interact and cause dangerously high blood pressure. Having a quick testing kit could ultimately save lives in these individuals, Mathies suggests.

The new technique, called portable microchip capillary electrophoresis, involves labeling the sample with a fluorescent dye, separating the components by applying an electric field on a special microchip, and analyzing the pattern of light produced by the sample upon exposure to a laser beam. In the study, Mathies and colleagues used a prototype device to analyze tyramine and histamine concentrations in a variety of wines (both red and white), beer and sake. They found that the device accurately measured the biogenic amines present in the beverages in less than five minutes.

The highest levels of tyramine were found in red wine, and the highest levels of histidine were found in sake, the researchers note. The beer tested contained only small amounts of these biogenic amines, they say.

�Some foods have more biogenic amines than others, but you can�t tell because they aren�t listed on the food labels,� Mathies says. Even a single glass of wine has been known to trigger elevated blood pressure, heart rate and headaches in some people, he notes. �I think that certain foods, especially wines, should indicate their biogenic amine content.�

Besides beverages, the test can be used for a wide range of food products, including cheese, chocolate, fish and even sauerkraut. In addition to being used by consumers in the home, the device could be used by industry as a quick method to monitor or limit the biogenic amine content of foods and beverages, according to the researchers. It can also be used to screen foods that have been deliberately contaminated, they say.

Mathies envisions that the test will eventually be engineered into a PDA or other handheld device that consumers can use at home or in a restaurant to instantly screen a food or beverage sample for the presence of these toxins. More research is needed before this occurs, he says.

The study was funded, in part, by the National Aeronautics and Space Administration. The analyzer was originally developed to look for organic molecules, particularly amino acids, on future explorations of Mars. A version of the sensor has been developed for use in the European Space Agency�s 2013 ExoMars mission, Mathies says.

Study shows lead-based paint problem isn't isolated to China

Thu, 27 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CINCINNATI�A multinational team of environmental and occupational health researchers has found that consumer paints sold in Nigeria contain dangerously high levels of lead.

Increased globalization and outsourcing of manufacturing has drastically increased the likelihood that products with unacceptably high levels of lead are being traded across borders�including between China and Africa as well as into regulated countries like the United States.

Researchers at the University of Cincinnati (UC) and University of Ibadan in Nigeria report these findings in an early Sept. 12 online edition of the journal Science of the Total Environment. Researchers believe the study�to be published in the December print issue of the journal�is the first report of new consumer paint lead levels in Africa.

�Nigeria�s recent economic recovery may lead to increased activity in the building industry and Nigeria�like other African countries�is increasing trade with Asia, particularly in China,� explains Eugenious Adebamowo, of the University of Ibadan and lead author of the study.

�It�s important that international regulations be in place to supplement local efforts to ensure that paints have lower than recommended lead levels, with the ultimate goal of eventually eliminating all lead from paint,� she adds.

For this study, researchers analyzed lead levels in five colors of paint, from each of five brands, marketed and sold in Ibadan, a city of more than 2 million people in southwestern Nigeria. Each paint sample was applied in a single layer to a wood block, left to dry and then removed and analyzed in UC laboratories for lead content.

They found that 96 percent of the consumer paints available in Nigeria contained higher than the recommended levels of lead. Bright-colored paints�particularly yellow, red, and green contained the highest levels. Respectively, lead levels in yellow, red and green paint were 10, six and three times higher when compared with basic white paint

�The extent of domestic lead exposure, and its resulting health hazards has been understudied in developing countries, though its importance in cognitive dysfunction related to early exposure is well established in countries such as the United States,� says Scott Clark, PhD, professor of environmental health at UC and study collaborator.

Researchers compared the Nigerian paint samples with those sold in some Asian countries, using data obtained by Clark and his collaborators in previous studies. In the September 2006 issue of the journal Environmental Research, Clark reported that more than 75 percent of consumer paint tested from countries without lead-content controls��including India, Malaysia and China�had levels exceeding U.S. regulations. Collectively, these countries represent more than 2.5 billion people.

Although the median lead levels on Nigerian consumer-based paints did not substantially differ from those in Asian countries, nearly all still exceeded U.S. safety guidelines.

Sandy Roda, a study coauthor who oversaw sample analysis, stressed the international nature of the problem. She noted that one paint manufacturer in Nigeria sold high-lead paint in India, but offered a low-lead version in Singapore, a country that enforces a lead standard similar to the United States.

�It�s very likely that many existing Nigerian homes contain dangerously high levels of lead, so it�s absolutely critical from a health standpoint that immediate efforts be made to assess the presence of lead in homes,� adds Clark. Lead is a malleable metal previously used to improve the durability and color luster of paint applied in homes and on industrial structures such as bridges. Now scientifically linked to impaired intellectual and physical growth in children, lead is also found in some commonly imported consumer products, including candy, folk and traditional medications, ceramic dinnerware and metallic and wooden toys and trinkets. Researchers say exposure to environmental health hazards is a continuing concern in developing countries, where the United Nations has identified lead as a primary problem.

�When it comes to public awareness of lead and its detrimental health effects, Nigeria and many other large, developing countries are 25 years behind,� says Clement Adebamowo, corresponding author of the study. �Intervention programs could eliminate the risk for exposure and improve the overall health of the Nigerian people.�

Training and research programs to increase public and professional awareness of lead exposure are being developed at the University of Ibadan in collaboration with other centers in Nigeria.

Previous studies conducted by Jos University Teaching Hospital in Nigeria and several international collaborators have shown that 70 percent of children, aged 6 to 35 months, had elevated blood-lead levels and that flaking house paint was a primary determinant of this exposure.

�Recent massive recalls of toys from China for lead-based paint content offer further evidence of the public health threat lead-based paint marketing in foreign countries can pose in the United States,� adds Clark. �A consistent, global ban against lead-based paint is urgently needed to protect people not just in the United States�but across the world.�

Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage

Wed, 26 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) WASHINGTON, Sept. 26 2007 -- Consuming large amounts of caffeine while taking acetaminophen, one of the most widely used painkillers in the United States, could potentially cause liver damage, according to a preliminary laboratory study reported in the Oct. 15 print issue of ACS� Chemical Research in Toxicology, a monthly journal. The toxic interaction could occur not only from drinking caffeinated beverages while taking the painkiller but also from using large amounts of medications that intentionally combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions, the researchers say.

Health experts have warned for years that consuming excess alcohol while taking acetaminophen can trigger toxic interactions and cause liver damage and even death. However, this is the first time scientists have reported a potentially harmful interaction while taking the painkiller with caffeine, the researchers say.

While the studies are preliminary findings conducted in bacteria and laboratory animals, they suggest that consumers may want to limit caffeine intake -- including energy drinks and strong coffee -- while taking acetaminophen.

Chemist Sid Nelson, Ph.D., and colleagues, of the University of Washington in Seattle, tested the effects of acetaminophen and caffeine on E. coli bacteria genetically engineered to express a key human enzyme in the liver that detoxifies many prescription and nonprescription drugs. The researchers found that caffeine triples the amount of a toxic byproduct, N-acetyl-p-benzoquinone imine (NAPQI), that the enzyme produces while breaking down acetaminophen. This same toxin is responsible for liver damage and failure in toxic alcohol-acetaminophen interactions, they say.

In previous studies, the same researchers showed that high doses of caffeine can increase the severity of liver damage in rats with acetaminophen-induced liver damage, thus supporting the current finding.

�People should be informed about this potentially harmful interaction,� Nelson says. �The bottom line is that you don�t have to stop taking acetaminophen or stop taking caffeine products, but you do need to monitor your intake more carefully when taking them together, especially if you drink alcohol.�

Nelson points out that the bacteria used in the study were exposed to �megadoses� of both acetaminophen and caffeine, much higher than most individuals would normally consume on a daily basis. Most people would similarly need to consume unusually high levels of these compounds together to have a dangerous effect, but the toxic threshold has not yet been determined, he says.

Certain groups may be more vulnerable to the potentially toxic interaction than others, Nelson says. This includes people who take certain anti-epileptic medications, including carbamazepine and phenobarbital, and those who take St. John�s Wort, a popular herbal supplement. These products have been shown to boost levels of the enzyme that produces the toxic liver metabolite NAPQI, an effect that will likely be heightened when taking both acetaminophen and caffeine together, he says.

Likewise, people who drink a lot of alcohol may be at increased risk for the toxic interaction, Nelson says. That�s because alcohol can trigger the production of yet another liver enzyme that produces the liver toxin NAPQI. The risks are also higher for those who take large amounts of medications that combine both acetaminophen and caffeine, which are often used together as a remedy for migraine headaches, arthritis and other conditions.

The researchers are currently studying the mechanism by which this toxic interaction occurs and are considering human studies in the future, they say. The National Institutes of Health funded the initial animal and bacterial studies.

PETA awards $120,000 to Duluth Foundation for advancing non-animal tests

Mon, 24 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Duluth, Minn. � Tomorrow, PETA will donate $120,000 to the Duluth-based International QSAR Foundation to Reduce Animal Testing to further its important work aimed at improving toxicity testing and saving the lives of millions of animals who are routinely maimed and killed in laboratory experiments. PETA will present the check at the McKim Conference tomorrow, September 25, at the Inn on Lake Superior in Duluth. The annual McKim Conference provides a stimulating environment for scientists, regulators, and other stakeholders to identify scientific barriers to intelligent testing paradigms and to discuss critical pathways of research to overcome those barriers. The International QSAR Foundation then facilitates special projects to develop the proposed solutions.

Under the direction of founder Dr. Gilman Veith�a pioneer of a technology known as quantitative structure-activity relationship (QSAR)�the foundation's work holds promise for greatly reducing the number of animals used in chemical safety testing by developing databases and computer modeling tools that increase the accuracy of QSAR models. QSAR methodology uses mathematical modeling of the structure of chemicals to determine their levels of toxicity. This virtual testing will also improve the development of in vitro methods�producing results that are faster, more accurate, less expensive, and far more humane than animal tests.

The foundation�s work is being applied to major testing methods required by the Food and Drug Administration, the Environmental Protection Service, and international regulatory testing agencies and include acute and chronic oral, dermal, and inhalation toxicity, all of which cause extreme pain and suffering to the animals used. This work is fundamental to enacting the vision for a more intelligent and humane toxicity testing strategy that was set forth recently in a landmark report by the National Academy of Sciences.

Minimizing animal testing is an important national goal, much like putting a man on the moon was in the 1960s, said Veith. While we committed public money to create the technology for flying to the moon, there has been little public funding for the QSAR technology that eliminates the need for the animal tests used back in the 1960s. The Foundation is grateful to PETA for supporting this science and hopes the chemical industry and our government will do likewise.

In recent years, PETA has donated $760,000 toward the development of alternatives to animal testing. This award is funded by the estate of former Memphis resident Lavelle Shaw Brooks, who made a bequest dedicated to the development of alternatives to animal testing.

Not only is testing toxic substances on animals cruel, it's also bad science, says PETA Director Jessica Sandler. We hope that our gift to the International QSAR Foundation will be an incentive for others in the scientific community to move away from outdated, ineffective, and cruel animal testing.

Scientists decipher mechanism behind antimicrobial 'hole punchers'

Thu, 20 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CHAMPAIGN, Ill. � In the battle against bacteria, researchers have scored a direct hit. They have made a discovery that could shorten the road to new and more potent antibiotics.

The rapid development of bacterial resistance to conventional antibiotics (such as penicillin or vancomycin) has become a major public health concern. Because resistant strains of bacteria can arise faster than drug companies can create antibiotics, understanding how these molecules function could help companies narrow their focus on potential antibiotics and bring them to market sooner.

As reported in a paper accepted for publication in the Journal of the American Chemical Society and posted on its Web site, researchers have now deciphered the molecular mechanism behind selective antimicrobial activity for a prototypical class of synthetic compounds.

The compounds, which mimic antimicrobial peptides found in biological immune systems, �function as molecular �hole punchers,� punching holes in the membranes of bacteria,� said Gerard Wong, a professor of materials science and engineering, physics, and bioengineering at the U. of I., and a corresponding author of the paper. �It�s a little like shooting them with a hail of nanometer-sized bullets � the perforated membranes leak and the bacteria consequently die.�

The researchers also determined why some compounds punch holes only in bacteria, while others kill everything within reach, including human cells.

�We can use this as a kind of Rosetta stone to decipher the mechanisms of much more complicated antimicrobial molecules,� said Wong, who also is a researcher at the university�s Beckman Institute.

�If we can understand the design rules of how these molecules work, then we can assemble an arsenal of killer molecules with small variations, and no longer worry about antimicrobial resistance.�

In a collaboration between the U. of I. and the University of Massachusetts at Amherst, the researchers first synthesized a prototypical class of antimicrobial compounds, then used synchrotron small-angle X-ray scattering to examine the structures made by the synthetic compounds and cell membranes.

Composed of variously shaped lipids, including some that resemble traffic cones, the cell membrane regulates the passage of materials in and out of the cell. In the presence of the researchers� antimicrobial molecules, the cone-shaped lipids gather together and curl into barrel-shaped openings that puncture the membrane. Cell death soon follows.

The effectiveness of an antimicrobial molecule depends on both the concentration of cone-shaped lipids in the cell membrane, and on the shape of the antimicrobial molecule, Wong said. For example, by slightly changing their synthetic molecule�s length, the researchers created antimicrobial molecules that would either kill nothing, kill only bacteria, or kill everything within reach.

�By understanding how these molecules kill bacteria, and how we can prevent them from harming human cells, we can provide a more direct and rational route for the design of future antibiotics,� Wong said.

Keck Foundation funds study of biological interactions with nanomaterials

Tue, 11 Sep 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The University of Oregon has received a $1.6 million grant from the W.M. Keck Foundation to explore the biological effects of exposure to precisely engineered nanoparticles that are being designed for diagnostic and therapeutic uses.

The three-year grant from the Keck Foundation�s medical research program will involve six researchers: Mark Lonergan, Jim Hutchison and Andy Berglund, all UO professors of chemistry; UO biology professors Karen Guillemin and Eric Johnson; and Robert Tanguay, a professor of environmental and molecular toxicology at Oregon State University.

All are members of the Safer Nanomaterials and Nanomanufacturing Initiative (SNNI), directed by Hutchison and part of the Oregon Nanoscience and Microtechnologies Institute (ONAMI).

�This award from the Keck Foundation puts us at the forefront of this quickly developing and promising field of nanotechnology,� said UO President Dave Frohnmayer. �Nanotechnology has been described as being in its discovery phase. This newly funded project means the University of Oregon, Oregon State University and the state, through ONAMI � Oregon�s first Signature Research Center � can help build a green roadmap for the field.�

The interdisciplinary project is designed to help researchers understand potential biological interactions of engineered nanomaterials and develop design rules for the development of nanoparticles with enhanced biological properties. The researchers will produce specific structures of nanomaterials, investigate their interactions with biological systems and then design new materials and nanoparticle libraries that have specific biological responses.

The biological testing will involve laboratory experiments using zebrafish, an invertebrate animal model system that was first developed for research at the University of Oregon. With zebrafish, researchers can monitor tissue-specific interactions with nanoparticles, developmental and acute toxicity, and the impacts of exposure on gene regulation.

The researchers will address existing gaps in the field, from the basic construction of nanoparticles to how they interface with biological cells. As the foundation for the project, the group will build upon the library of gold nanoparticles created by Hutchison using his patented green-chemistry approach.

�Our goal is to define the important interactions at the bio-nano interface, as well as the ground rules for producing nanoparticles that have very fine-tuned objectives,� Hutchison said. �The end results could lead to a variety of future therapeutics that specifically seek out and destroy cancer cells or promote desired cell growth for tissue regeneration.�

The Keck Foundation funds will cover just under $1 million in graduate and faculty research, with the remainder going toward the purchase of equipment and space for housing it. The instruments will go into the Lorry I. Lokey Laboratories, the underground portion of the Integrated Science Complex, where some of the project�s research will be conducted.

Collaborative cross attracting diverse genetics experiments

Wed, 29 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) OAK RIDGE, Tenn., Aug. 29, 2007 -- Mice that are part of the Collaborative Cross project at Oak Ridge National Laboratory are helping scientists around the world learn more about possible causes of drug abuse, diabetes, sleep disorders, stress and pain, kidney disease and a number of other conditions that affect millions of people.

The Collaborative Cross, begun in 2005 with a grant from the Ellison Medical Foundation, represents a fundamentally new way of conducting genetics research and aims to create 1,000 strains of mice that feature the genetic diversity of the world population. When completed in about five years, the research community will have access to an extremely versatile resource plus data that is the click of a mouse away. There will be other benefits as well.

�With our new facility at ORNL, we offer economies of scale for the production of populations of mice,� said Elissa Chesler, leader of the systems genetics group in the Biosciences Division. �Without having to maintain their own mouse colonies, researchers will have access to mice that will enable them to do experiments that cannot be done anywhere else.�

While conventional genetics studies have primarily involved stand-alone experiments aimed at discovering single gene variants, the Collaborative Cross represents the new approach that researchers say is necessary to develop a community resource for understanding the genetic and environmental complexity of human diseases. With this approach, using a reference population that allows for high genetic diversity and large sample size, researchers can more effectively examine combinations of genes responsible for diseases. This combination is what makes the Collaborative Cross special.

�We can stop blaming single genes for causing diseases,� Chesler said. �We now know that bad combinations of normal genes are at fault, and this mouse population will make it possible to determine complex causes and to develop drugs to treat those diseases.�

In one experiment at ORNL, William Lariviere of the University of Pittsburgh School of Medicine hopes to find genes that cause some people to be more sensitive to pain than others and to identify new drugs for treatment of different types of pain. The study involves collecting a standard set of thermal, chemical, inflammatory and mechanical sensitivity measures in groups of mice from 80 different lines in a genetic reference population called the BXD lines.

Data from Lariviere�s study will form an important foundation for integrative genomic analysis of pain. The results will be placed in the public domain through Web resource www.genenetwork.org.

�The BXD lines are a powerful tool for integration, but they do not have maximum precision and genetic diversity,� Lariviere said. �For that, we will collect additional trait data in the Collaborative Cross mouse population being created at ORNL.�

One area of specific interest to Lariviere is variations in the amount of messenger RNA (mRNA) produced by different individuals. This often determines how much of a particular protein is made, and that in turn might be related to biological pathways that are involved in processes such as pain perception.

�Because we will measure both the mRNA levels and the sensitivity levels in the same strains of mice, we will be able to efficiently not only study the genes that cause individual differences in pain sensitivity, but also identify the pathway of genes that make ideal targets for new pain drugs,� Lariviere said.

In another study, Michael Miles of Virginia Commonwealth University leads a team that hopes to learn more about the connection between anxiety and alcoholism. Working with Alex Putman and Chesler, the researchers have identified a region of a mouse chromosome that appears to significantly alter the effects of alcohol on anxiety.

�Understanding the basic mechanisms connecting brain events in anxiety and alcoholism could lead to better treatments for both disorders,� Miles said.

In this study, researchers used special strains of mice being raised and maintained at ORNL. Miles noted that the strains of mice used for his study are not available through any commercial source and offer a �great advantage to genetic studies of complex diseases.�

In upcoming months the researchers hope to identify the actual genes in this chromosome region that alter the response to alcohol.

In another study, Bruce O�Hara of the University of Kentucky is working to identify sleep- and wake-related genes. In addition to gaining a more thorough understanding of the sleep process, this research could lead to better drugs to help people with sleep disorders.

O�Hara�s study takes advantage of noninvasive piezoelectric sensors instead of conventional techniques that use electroencephalogram and eletromyogram recordings, which require surgical implants and cables that tether the mouse to a recording device. This limitation has made it impractical to study large numbers of animals, which is necessary in genetic screening, according to O�Hara.

These and other experiments are housed in ORNL�s Laboratory for Comparative Functional Genomics, a pathogen-free 36,000-square-foot facility that is home to approximately 30,000 mice. The lab, completed in 2004, boasts accommodations for 80,000 mice, cryogenic storage and other state-of-the-art features.

Safe water: simpler method for analyzing radium in water samples cuts testing time

Tue, 28 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A simpler technique for testing public drinking water samples for the presence of the radioactive element radium can dramatically reduce the amount of time required to conduct the sampling required by federal regulations. The U.S. Environmental Protection Agency (EPA) has approved use of the new testing method.

The technique � developed by Bernd Kahn, director of the Georgia Tech Research Institute�s (GTRI) Environmental Radiation Center (ERC), and GTRI senior research scientist Robert Rosson � became advantageous when the EPA established new radionuclide drinking water standards in 2000.

While radium is found at low concentrations in soil, water, plants and food, the greatest potential for human exposure to radium is through drinking water. Research shows that inhalation, injection, ingestion or body exposure to relatively large amounts of radium can cause cancer and other disorders. Since radium is chemically similar to calcium, it has the potential to cause harm by replacing calcium in bones.

As a result, drinking water systems are now required to sample and report on the amounts of two isotopes, radium-226 and radium-228, that are sometimes found in drinking water supplies.

�The Georgia Department of Natural Resources recognized the applicability and benefits of our method because of the new rules and proposed it to the EPA in 2002,� said Kahn.

The new method developed at GTRI requires only two steps. First, hydrochloric acid and barium chloride are added to a sample of water and heated to boiling. Then concentrated sulfuric acid is added and the radium precipitate is collected, dried and weighed. The samples are then counted with a gamma-ray spectrometry system to determine the content of radium-226 and radium-228.

A gamma-ray spectrometer determines the energy and the count rate of gamma rays emitted by radioactive substances. When these emissions are collected and analyzed, an energy spectrum can be produced. A detailed analysis of this spectrum is used to determine the identity and quantity of radioisotopes present in the source.

�The old method took four hours for each type of radium you needed to test�totaling eight hours for radium-226 and radium-228,� said Rosson. �Our method does the two tests simultaneously and it takes about half an hour of actual technician time.�

Previously approved EPA methods for measuring radium required several isolation and purification steps involving sequential precipitations from large sample volumes and sometimes liquid-liquid extractions. They all ended with a complicated final preparation step before measurement with an alpha scintillation detection system. The scintillation detector detects and counts the flashes of light that are produced when a radioactive substance interacts with a special coating on the inside of the detection container.

The EPA�s December 2007 deadline requiring every water supply be tested for radium-228 and gross alpha radioactivity greatly increased the number of radium-228 measurements required, as well as the likelihood both radium-226 and radium-228 must be measured in the same sample, also increasing the number of measurements required.

If the total radium concentration measured is above five picocuries per liter, then the water supply is out of compliance and radium-226 and radium-228 must be measured quarterly. This may require the water source to be replaced or treated to reduce the radium concentration. If the amount of radioactivity measured is less than five picocuries per liter, samples may be collected at three-, six- or nine-year intervals.

Since the EPA approved this new testing procedure in July 2006, GTRI�s ERC has been able to use the testing method they developed to analyze water samples from Georgia�s Department of Natural Resources.

�We analyze about 1,200 samples per year for them. With 3,000 to 6,000 water supply entry points in Georgia, we�re not done yet,� noted Rosson.

Survey finds elevated rates of new asthma among WTC rescue and recovery workers

Mon, 27 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Findings released today by the Health Department shed new light on the health effects of exposure to dust and debris among workers who responded to the World Trade Center disaster on September 11, 2001. The data, drawn from the World Trade Center Health Registry, show that 3.6% of the 25,000 rescue and recovery workers enrolled in the Registry report developing asthma after working at the site. That rate is 12 times what would be normally expected for the adult population during such a time period. The paper was published today in the journal Environmental Health Perspectives and is available online at www.ehponline.org.

The rescue and recovery workers are a subset of the 71,000 people enrolled in the registry. The survey, conducted in 2003 and 2004, found that arriving soon after the buildings collapsed, or working on the WTC pile over a long period, increased the workers� risk of developing asthma. Workers who arrived on September 11, 2001, and worked more than 90 days reported the highest rate of new asthma (7%).

Though respirator use increased as the clean-up progressed, many workers did not wear respiratory protection at the outset. Certain respirators can reduce exposure to hazardous dust when used correctly, but the survey could not distinguish among different types of masks or respirators, nor could it gauge correct usage. Workers who wore them on September 11th and September 12th reported newly-diagnosed asthma at lower rates (4.0% and 2.9%, respectively) than those who did not (6.3% and 4.5%). The longer the period of not wearing masks or respirators, the greater the risk, the survey found. Workers who went months without respiratory protection reported two to three times more asthma incidence than those who wore respirators from the outset. Though respirators were shown to be protective, all worker groups, including those who reported wearing masks, had elevated levels of newly reported asthma.

�The dust from the World Trade Center collapse appears to have had significant respiratory health effects at least for people who worked at the site,� said Dr. Thomas R. Frieden, New York City Health Commissioner. �These findings reflect the critical importance of getting appropriate respiratory protection to all workers as quickly as possible during a disaster, and making every effort to make sure workers wear them at all times. The events of 9/11 were unprecedented, and with the urgency of rescue operations and the difficulty of prolonged physical exertion with most types of respirators, there are no easy answers, even in retrospect.�

Rescue and recovery workers were a diverse group that included firefighters, police officers, construction workers and volunteers, among others. The study found no significant differences among people of different occupations, but workers� locations did affect their risk. Those who were caught in the dust cloud or worked on the debris pile reported asthma at higher rates (4.9% and 4.5% respectively), presumably because they inhaled more dust.

Asthma can be controlled with the right care and medications. Inhaled corticosteroids are a very effective treatment for people with frequent symptoms. By learning what triggers asthma and developing a plan to manage it, people can stay healthy for work, school, and other activities. The Health Department has collaborated with clinicians from WTC Centers of Excellence to develop and distribute treatment guidelines for WTC-related respiratory condition. The guidelines are available at

Field Museum gives Parker/Gentry Award to environmental activist, attorney, author Judith Kimerling

Thu, 23 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO�In recognition of her courageous and unrelenting efforts on behalf of indigenous peoples of Amazonia and Alaska, and their natural resources, Judith Kimerling has won The Field Museum�s prestigious Parker/Gentry Award.

�For the past 12 years, The Field Museum has given the award to inspiring environmental innovators who, in the spirit of Ted Parker and Al Gentry, have made a profound difference in conservation,� said Debby Moskovits, senior vice president of The Field Museum for Environment, Culture, and Conservation. �This year we are extremely pleased to acknowledge Judith Kimerling�s courageous efforts on behalf of indigenous peoples and vast forests in the headwaters of the Amazon and wilderness of Alaska. Kimerling�s work to establish independent verification of the environmental impact of transnational corporations� practices is fundamental in a world that is becoming increasingly dominated by oil concessions.�

As an Assistant Attorney General for New York State during the 1980s, Kimerling litigated environmental cases, including Love Canal. In 1989, she became concerned about degradation and loss of the rainforests and began asking herself what a North American lawyer could do to help save the rainforests. She decided that to be effective she would need to work with the people who live in the rainforests so she moved to Ecuador and learned Spanish. She soon discovered that oil production was the driving force behind rainforest destruction in Ecuador, so she began to study the problem.

�I was appalled by what I saw,� Kimerling said. �It was as if everything we had learned in this country at Love Canal was being ignored in Ecuador.

�I felt ashamed that U.S. companies would come into someone else�s country and behave in this way,� she added. �I didn�t think that the American public or the Ecuadorian government would approve of this if they knew about it.�

To shine an international spotlight on what she had observed, Kimerling wrote Amazon Crude (Natural Resources Defense Council, 1991). The book exposed the exploitation of the Amazon basin by transnational oil corporations as well as their disregard for the well-being of local peoples. It prompted a $1.5 billion class action lawsuit in the United States, Aguinda v. Texaco.

Kimerling is currently an Associate Professor of Law and Policy at The City University of New York, with a joint appointment at Queens College and CUNY Law School. Also, she is the international representative of Makarik �ihua, an alliance of 38 Huaorani and Lower Napo Kichwa communities working to remedy environmental and cultural injuries caused by Chevron Texaco�s operations in Ecuador.

�I am honored to receive this award especially because The Field Museum�s conservation work is not just based on advocacy from afar but also based on the realities on the ground,� Kimerling said. �Field Museum scientists understand that conservation in the Amazon depends most of all on the people who live there.�

Frog plus frying pan equals better antibiotic

Mon, 20 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) By creating Teflon versions of natural antibiotics found in frog skin, a research team led by biological chemist E. Neil Marsh has made the potential drugs better at thwarting bacterial defenses, an improvement that could enhance their effectiveness. Marsh will discuss the work Aug. 20 at the 234th national meeting of the American Chemical Society in Boston.

Marsh and collaborators work with compounds called antimicrobial peptides (AMPs), which are produced by virtually all animals, from insects to frogs to humans. AMPs are the immune system's early line of defense, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces. They're copiously produced in injured or infected frog skin, for instance, and the linings of the human respiratory and gastrointestinal tracts also crank out the short proteins in response to invading pathogens. In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications.

Scientists have been interested in exploiting these natural antibiotics since their discovery in the 1980s, but they haven't been able to overcome some limitations. In particular, AMPs are easily broken down by protein-degrading enzymes (proteases) that are secreted by bacteria and are also naturally present in the body. Increasing the concentration of AMPs in an effort to get around that problem can cause toxic side effects, such as the destruction of red blood cells---those critical carriers of oxygen in the bloodstream. That seems to happen because sticky parts of the AMP molecule interact with the cell membrane in a harmful way.

Marsh had the idea of replacing sticky portions of the peptides with nonstick analogs. His inspiration came from the kitchen as much as the chemistry lab: nonstick cookware is coated with fluorinated polymers, plastic-like compounds composed of chains of carbon atoms completely surrounded by fluorine atoms. The fluorine not only makes Teflon slippery, it also makes the coating inert to almost every known chemical.

When Marsh and co-workers swapped sticky parts of their AMP molecule with nonstick, fluorinated versions, the molecules became much more resistant to proteases.

The difference was quite striking, said Marsh, a U-M professor of chemistry. When we treated them with purified proteases, the nonfluorinated AMPs were all degraded within 30 minutes. Under the same conditions, the fluorinated AMP was completely intact after 10 hours. We think that should make them more effective, as they'll stay around longer in the body.

We also showed that they seem to be at least as good at killing bacteria as their nonfluorinated counterparts, and for some bacteria they're actually significantly better.

Next, the researchers plan experiments to learn whether Teflon AMPs are also less toxic than their stickier equivalents. If they are, and if further studies continue to point to their promise, eventually producing large enough quantities of fluorinated AMPs for clinical trials should be quite feasible, Marsh said.

Though the research now has obvious practical applications, it started as an exploration in basic science.

We were just interested in translating useful properties of man-made materials into biological molecules, Marsh said. But fairly immediately we saw the potential for applying our fundamental science to a very important clinical problem, which is the way that more and more bacteria are becoming resistant to more and more conventional antibiotics.

PFOS and PFOA exposure associated with lower birth weight and size

Fri, 17 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in the womb is statistically associated with lower weight and head circumference at birth, according to an analysis of nearly 300 umbilical cord blood samples led by researchers at the Johns Hopkins Bloomberg School of Public Health. The results are published in the July 31, 2007, online edition of the journal Environmental Health Perspectives. Some of the studys findings were previously reported at a Society of Toxicology workshop held in February.

PFOS and PFOA are polyfluoroalkyl compounds (PFCs)ubiquitous man-made chemicals used in a variety of consumer products, including as a protective coating on food-contact packaging, textiles and carpets and in the manufacturing of insecticides and other industrial products.

The study, conducted in Baltimore, Md., found small decreases in head circumference and body weight in association with concentrations of PFOS and PFOA among infants born vaginally. The study also reported a negative association with PFOS and PFOA concentrations and the infants ponderal index, which is a measurement of weight for length similar to the body mass index (BMI). For unknown reasons, the reductions in birth weight and head circumference were not observed among 65 infants born by caesarian section. The researchers also did not find any associations between PFOS and PFOA concentrations and length at birth or gestational age.

These small, but significant, differences in head circumference and body weight provide the first evidence for a possible association between exposures to PFOS and PFOA and fetal growth. However, the differences are small and their impact on health is uncertain, said Benjamin Apelberg, PhD, lead author of the study and a research associate in the Bloomberg School of Public Healths Department of Epidemiology.

The health impact from exposure to PFOS and PFOA is not fully known, but previous studies found these compounds could cause tumors and developmental toxicity in laboratory animals at doses much higher than those observed in the Hopkins study.

The researchers analyzed cord serum from 293 newborns delivered at Johns Hopkins Hospital in Baltimore between 2004 and 2005. The samples were tested for the presence of PFOS and PFOA and eight other polyfluoroalkyl compounds. The samples were then matched to anonymous patient records, which included measurement of height, weight and head circumference of infants and other health information.

PFOA was detected in all of the samples and PFOS in all but two of the samples. The concentrations for both compounds were lower than those typically detected in adults in the United States and lower than those known to cause tumors and developmental problems in laboratory animals; more study is needed to understand health effects at these lower exposure levels.

Our study population has a large proportion of mothers at greater risk for adverse birth outcomes. Because of this, and also because this is the first study to report these associations, we need to be cautious in interpreting these findings until they can be replicated in other populations, said Lynn Goldman, MD, co-author of the study and a professor in the Department of Environmental Health Sciences at the Bloomberg School of Public Health.

SRMs track fire retardants in humans and environment

Thu, 16 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) If only the flame retardant chemicals routinely added to consumer products from carpets to cell phones just did their job and nothing more. Health officials, however, are concerned that one class of these chemicals called polybrominated diphenylethers (PBDEs), may be doing more than reducing fire-related injuries and property damage.

After several decades of use, PBDEs are widely distributed in the environment as contaminants, and trace levels of these chemicals can be measured in animal tissues and in the food chain (they can be found, for example, in bird eggs and human breast milk). To help scientists evaluate the risks of PBDEs by improving measurements of these pollutants in the environment, the National Institute of Standards and Technology (NIST) has re-evaluated several of its environmental reference materials to report PBDE concentrations in them.

Different commercial PBDE flame retardant formulations have been used, including pentaBDE in furniture foam; decaBDE in plastics for television cabinets, consumer electronics, draperies and upholstery; and octaDBE in plastics for personal computers and small appliances. Although human data on health effects are limited, the U.S. Environmental Protection Agency (EPA) cites animal tests as evidence that PBDEs are neurodevelopmental toxins, disruptors of thyroid functions, and liver toxins. The doses used in animal studies were slightly higher than PBDE levels found in some people in the United States.

U.S. production of pentaBDE and octaBDE formulations ended in 2004. DecaBDE (formulations which do not seem to be easily accumulated in humans, but can degrade to octaBDEs and pentaBDEs) are not banned. Pathways by which PBDEs enter the environment and humans are not yet known. Human exposure might come from food, manufacturing, or even from use of consumer product such as furniture.

To help investigators get a handle on the source and degree of PBDE contamination, NIST measured concentrations of selected PBDEs and other brominated flame retardants including hexabormocyclododecane (HBCD) in seven of the agencys existing Standard Reference Materials (SRMs) that are considered benchmarks for measurements of environmental pollutants.

Concentration values for PBDEs are now available for NISTs reference materials for house dust (SRM 2585), cod liver oil (SRM 1588b) and human blood serum (SRM 1589a). Newly certified values for PBDE concentrations in four other SRMs for whale blubber, mussel tissue and two types of fish tissue are expected to be available soon.

In collaboration with the Centers for Disease Control and Prevention (CDC), NIST also is developing four new SRMs based on human blood and milk. Two of these SRMs will have certified values for current PBDE concentrations to record the level of current human exposure. PBDEs will be added at higher levels for the other two materials to facilitate comparability of measurements among laboratories.

Negative effects of plastic's additive blocked by nutrient supplements

Mon, 30 Jul 2007 04:00:00 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. Experiments in animals have provided additional and tantalizing evidence that what a pregnant mother eats can make her offspring more susceptible to disease later in life.

This susceptibility is the result of a process that alters how a gene is expressed without actually changing or mutating the gene itself. Appreciation of this phenomenon has spawned a new avenue of genetic research known as epigenetics, a name which refers to changes happening over and above the gene sequence without altering its code.

In their most recent experiments, Duke University Medical Center investigators demonstrated that exposure within the womb to bisphenol A (BPA), an ubiquitous chemical used in the production of plastics, caused noticeable changes in the offspring without altering any of the offsprings genes. Additionally, the researchers discovered that administration of folic acid or genistein, an active ingredient in soy, during pregnancy protected the offspring from the negative effects of BPA.

The results of the study, which was supported by the National Institutes of Health and the Department of Energy, were published early online by the Proceedings of the National Academy of Science July 30.

In their experiments, the Duke team studied a well-documented strain of animals known as agouti mice. Normally, these mice tend to be slender and brown. While past epigenetic research at Duke has focused on nutrients given to pregnant agouti mice, the current experiments represented the first tests of a potential environmental toxin.

The researchers found that when the mouse mothers received BPA, a statistically significant increase in the number of their offspring were born with a yellow coat. Previous studies with these mice have shown that yellow agouti mice are at a much greater risk for diabetes, obesity and cancer.

The fact that the mice fed BPA had a yellow coat and likely would grow to be obese as adults demonstrates that this single substance had a system-wide effect, said Dana Dolinoy, Ph.D., postdoctoral fellow in the laboratory of Randy Jirtle, Ph.D., senior member of the research team. A comparison between the large yellow mice and the normal brown mice showed identical genetic makeup, yet strikingly different appearances.

Just as importantly, when pregnant mothers were also given folic acid or genistein, the epigenetic influence of BPA was counteracted, she added.

BPA is a synthetic estrogen first synthesized in the 1890s and is used in the manufacturing process from such everyday products as plastic water bottles, food containers and baby bottles. While laboratory studies have uncovered possible health concerns in animals, there has been considerable debate in the United States and Europe about what levels are considered safe for human consumption. Attempts have been made in Canada, California, Maryland and Minnesota to ban its use.

Jirtle, one of the leaders of epigenetics research, said that it is difficult at this point to determine what the levels of maternal BPA in humans would equal those that caused epigenetic changes seen in the mice. The levels of BPA used in the current experiments were five times lower than that considered harmful for mice, showing that even a low exposure was able to cause noticeable effects in the offspring.

Since BPA can be detected at some level in almost all humans, the current findings could hold the promise of reducing disease susceptibility by using nutritional approaches, Jirtle said. The ability of some agents to counteract the epigenetic effects of a toxin, in this case BPA, with maternal supplements has the potential to protect present and future generations.

Genistein, which is readily available in health food stores, is an active ingredient in soy. It is possible, Jirtle said, that the reason Asians have much lower rates of obesity and certain cancers is that their diet typically includes greater use of soy products than Western diets. However, he pointed out, it is not known at what doses genistein would be protective or harmful in humans. Future studies would be needed to determine optimal doses.

Its like the findings that have suggested that one glass of red wine a day may be good for your cardiovascular system, Jirtle said. That may be true, but we certainly know a gallon of red wine a day is not good for you.

Mouse genome will help identify causes of environmental disease

Sun, 29 Jul 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Research on the DNA of 15 mouse strains commonly used in biomedical studies is expected to help scientists determine the genes related to susceptibility to environmental disease. The body of data is now publicly available in a catalog of genetic variants, which displays the data as a mouse haplotype map, a tool that separates chromosomes in to many small segments, helping researchers find genes and genetic variations in mice that may affect health and disease. The haplotype map appearing online in the July 29th issue of Nature is the first published full descriptive analysis of the Mouse Genome Resequencing and SNP Discovery Project conducted by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

These data allow researchers to compare the genetic makeup of one mouse strain to another, and perform the necessary genetic analyses to determine why some individuals might be more susceptible to disease than another. This puts us one step closer to understanding individual susceptibility to environmental toxins in humans. We also hope that pharmaceutical companies developing new treatments for environmental diseases will find these data and this paper as a valuable resource, said David A. Schwartz. M.D., NIEHS Director.

The paper describes in detail the laborious and technology-driven approaches that were used to identify 8.27 million high quality SNPs distributed among the genomes of 15 mouse strains. Single Nucleotide Polymorphisms, or SNPs (known as snips), are single genetic changes, or variations, that can occur in a DNA sequence.

Much of the project was conducted through a contract between the National Toxicology Program at NIEHS and Perlegen Sciences, Inc. of Mountain View Calif.

The database of mouse genetic variation should facilitate a wide range of important biological studies, and helps demonstrate the utility of this array technology approach, said David R. Cox, M.D., Ph.D., chief scientific officer at Perlegen Sciences, Inc.

The Perlegen scientists used C57BL/6J the first mouse strain to undergo DNA sequencing as their standard reference to conduct the re-sequencing on the four wild-derived and eleven classical mouse strains. The technology used, the oligonucleotide array, was also used to discover common DNA variation in the human genome.

The arrays looked at about 1.49 billion bases (58 percent) of the 2.57 billion base pair of their standard reference strain. The data were then used to develop the haplotype map which contains 40,898 segments.

The data will be a valuable resource to many, including the National Toxicology Program, Schwartz says. The National Toxicology Program (NTP) is an interagency program, headquartered at NIEHS, with the mission to coordinate, conduct and communicate toxicological research across the U.S. government.

The NTP is looking forward to exploring the responses of these strains of mice to various environmental agents, said John Bucher, Ph.D., the new associate director of the NTP.

Frank M. Johnson, Ph. D., an NTP research geneticist and one of the authors of the Nature paper, adds that systematically characterizing even more mouse strains for susceptibility to toxins will not only help with genetic analysis, but better position researchers to do intervention studies.

MIT, BU team builds viruses to combat harmful 'biofilms'

Mon, 09 Jul 2007 04:00:00 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, Mass.--In one of the first potential applications of synthetic biology, an emerging field that aims to design and build useful biomolecular systems, researchers from MIT and Boston University are engineering viruses to attack and destroy the surface biofilms that harbor harmful bacteria in the body and on industrial and medical devices.

They have already successfully demonstrated one such virus, and thanks to a plug and play library of parts believe that many more could be custom-designed to target different species or strains of bacteria.

The work, reported in the July 3 Proceedings of the National Academy of Sciences, helps vault synthetic biology from an abstract science to one that has proven practical applications. Our results show we can do simple things with synthetic biology that have potentially useful results, says first author Timothy Lu, a doctoral student in the Harvard-MIT Division of Health Sciences and Technology.

Bacterial biofilms can form almost anywhere, even on your teeth if you don't brush for a day or two. When they accumulate in hard to reach places such as the insides of food processing machines or medical catheters, however, they become persistent sources of infection.

These bacteria excrete a variety of proteins, polysaccharides, and nucleic acids that together with other accumulating materials form an extracellular matrix, or in Lu's words, a slimy layer, that encases the bacteria. Traditional remedies such as antibiotics are not as effective on these bacterial biofilms as they are on free-floating bacteria. In some cases, antibiotics even encourage bacterial biofilms to form.

Lu and senior author James Collins, professor of biomedical engineering at BU, aim to eradicate these biofilms using bacteriophage, tiny viruses that attack bacteria. Phage have long been used in Eastern Europe and Russia to treat infection.

For a phage to be effective against a biofilm, it must both attack the strain of bacteria in the film and degrade the film itself. Recently, a different group of researchers discovered several phages in sewage that meet both criteria because, among other things, they carry enzymes capable of degrading a biofilm's extracellular matrix.

This discovery led Lu and Collins to consider engineering phages to carry enzymes with similar capabilities. Why Finding a good naturally occurring combination for a given industrial or medical problem is difficult. Plus, people don't want to dig through sewage to find these phages, says Lu.

So Collins and Lu defined a modular system that allows engineers to design phages to target specific biofilms. As a proof of concept, they used their strategy to engineer T7, an Escherichia coli-specific phage, to express dispersin B (DspB), an enzyme known to disperse a variety of biofilms.

To test the engineered T7 phage, the team cultivated E. coli biofilms on plastic pegs. They found that their engineered phage eliminated 99.997% of the bacterial biofilm cells, an improvement by two orders of magnitude over the phage's nonengineered cousin.

The team's modular strategy can be thought of as a plug and play library, says Collins. The library could contain different phages that target different species or strains of bacteria, each constructed using related design principles to express different enzymes.

Creating such a library may soon be feasible with new technologies for synthesizing genes quickly and cheaply. We hope in a few years, it will be easy to create libraries of phage that we know have a good chance of working a priori because we know so much about their inner-workings, says Lu.

Synthetic biology also makes it possible to control the timing of when a gene is expressed in an organism. For instance, Lu inserted the DspB genes into a precise location in the T7 genome so that the phage would strongly express it during infection rather than before or after. Such control was possible because T7 was extremely well characterized by other researchers such as MIT synthetic biologist Drew Endy, an assistant professor of biological engineering.

Though phages are not approved for use in humans in the United States, recently the FDA approved a phage cocktail to treat Listeria monocytogenes on lunchmeat. This makes certain applications, such as cleaning products that include phages to clear slime in food processing plants, more immediately promising. Another potential application: phage-containing drugs for use in livestock in exchange for or in combination with antibiotics.

New $1.16 million study investigates how dietary iron is used by cells

Thu, 21 Jun 2007 04:00:00 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- A four-year study on iron metabolism within cells, an essential process that impacts both iron deficiency and iron toxicity, conditions responsible for a multitude of human diseases, is underway at the University at Buffalo funded by a $1.16 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Daniel Kosman, Ph.D., professor of biochemistry in the UB School of Medicine and Biomedical Sciences, is lead researcher on the study.

The concern about how iron is managed in our cells has never been more acute, said Kosman. The reasons for this are three-fold. First is the endemic problem of iron deficiency that the World Health Organization estimates afflicts 80 percent of the worlds population, or more than 5 billion people.

Iron deficiency is not confined to developing nations. In the U.S., 5 percent of newborns and 7 percent of new mothers have clinical symptoms of iron deficiency. Reducing the incidence of this nutritional deficit is one of the objectives of the U.S. Department of Health and Human Services Healthy People 2010 program.

Second is the broad recognition that the corrosive chemistry associated with iron and oxygen interactions is a major factor in a multitude of human diseases.

Too much iron in tissues, called iron-loading, is thought to increase the risk of tumor development, infection, cardiomyopathy, joint disorders and several endocrine and neurodegenerative disorders.

And third, we now have an increasingly sophisticated knowledge and understanding of iron metabolic pathways, the proteins involved in these pathways and how these pathways are regulated in all organisms, making this issue ripe for investigation, he said.

Kosman proposes that a general mechanism of cellular iron metabolism requires that iron-handling proteins involved in sequential steps in the pathway must be architecturally arranged contiguously in the cells membranes, at the interfaces between membranes and soluble compartments or within soluble compartments.

The researchers will test this form-function model of ionic iron metabolism by focusing on three steps critical to maintaining the proper balance of iron in cells: 1) the reduction of ferric to ferrous iron and the subsequent transport of ferrous iron into a cell; 2) the hand-off of this ferrous iron from a membrane protein to iron chaperones in the cells cytoplasm; and 3) the utilization of this ionic iron for the activation of essential iron-containing enzymes.

These three components of cellular iron metabolism are relatively under-investigated, said Kosman, yet they represent the essence of cell iron metabolism in all organisms.

Understanding the intermediary metabolism of iron is one of the primary objectives of a program announcement from NIH titled Metals In Medicine, he noted. This announcement encourages studies that lead to the identification and characterization of the macromolecular players and vesicular compartments involved in metal ion homeostasis and metal trafficking.

Children of smokers have more than 5 times higher levels of a nicotine toxin

Wed, 20 Jun 2007 16:00:00 PST

( from http://www.rxpgnews.com ) Children who have at least one parent who smokes have 5.5 times higher levels of cotinine, a byproduct of nicotine, in their urine, according to a study by researchers from Warwick Medical School at the the University of Warwick, and the University of Leicester, published online ahead of print in Archives of Disease in Childhood.

Having a mother that smokes was found to have the biggest independent effect on cotinine in the urine quadrupling it. Having a smoking father doubled the amount of cotinine, one of chemicals produced when the body breaks down nicotine from inhaled smoke to get rid of it.

Sleeping with parents and lower temperature rooms were also associated with increased amounts of cotinine.

Cotinine was measured in 100 urine samples taken from infants aged 12 weeks. Seventy one of the babies had at least one parent that smoked and the parents of the other 33 were non-smokers.

The authors say: "Smoking babies tend to come from poorer homes, which may have smaller rooms and inadequate heating."

"Higher cotinine levels in colder times of year may be a reflection of the other key factors which influence exposure to passive smoking, such as poorer ventilation or a greater tendency for parents to smoke indoors in winter."

Sleeping with a parent is a know risk factor for cot death and the authors suggest that one reason for this could be inhalation of, or closeness to clothing or other objects contaminated with, smoke particles during sleep.

Nearly 40% of under-fives are believed to be exposed to tobacco smoke at home, and smoke may be responsible for up to 6,000 deaths per year in young children.

The authors say: "Babies and children are routinely exposed to cigarette smoking by their carers in their homes, without the legislative protection available to adults in public places."

But they acknowledge that there are practical difficulties in preventing smoking in private homes because it relies on parents or carers being educated about the harmful effects of passive smoking on their children and then acting on that knowledge.

Helping chlorine-eating bacteria clean up toxic waste

Wed, 20 Jun 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Cornell researchers hope to learn how certain bacteria that break down pollutants do their job and then to make them more effective in cleaning up toxic wastes.

Bacteria called Dehalococcoides ethenogenes, discovered in Ithaca sewage sludge in 1997 by James Gossett, Cornell professor of civil and environmental engineering, and isolated and studied by Stephen Zinder, Cornell professor of microbiology, are now in wide use to detoxify such carcinogenic chemicals as perchloroethylene (PCE) and trichloroethylene (TCE). They do this by removing chlorine atoms from molecules and leaving less-toxic compounds behind.

But D. ethenogenes strains work well at some sites and not so well at others, and nobody knows for sure why. In fact, very little is understood about how these organisms live and breathe. Normal laboratory procedures haven't provided enough answers, because the bacteria are hard to grow in a petri dish, said Ruth Richardson, Cornell assistant professor of civil and environmental engineering, who is following up on Gossett's and Zinder's work, in continued collaboration with them.

She is partnering with Gene Network Sciences (GNS), a firm specializing in computer simulation of biochemical processes, to create computer models of the inner workings of the bacterium. The project is funded by a three-year, $381,000 grant from the Department of Defense, which has some 6,000 toxic-dump sites of its own to clean up.

Richardson explained that in the field the bacteria sometimes start and then stop. We might improve conditions for the organisms. For example, she said, it has been found that Dehalococcoides needs vitamin B-12, so the vitamin is added to cultures that are injected into cleanup sites. The bacterium also grows better in a mixed community with other kinds of bacteria. There are some factors it needs from other organisms, and we don't know yet what they are, she said.

Her laboratory will test the D. ethenogenes strains under a variety of different conditions, such as exposing them to different chlorinated compounds one at a time, varying the environment or the nutrients supplied, and then observing which genes are expressed and what proteins are manufactured. The data will go to GNS, which will try to build computer models of how the bacteria's proteins work together under each condition and whether the pathway for each condition is the same for PCE and TCE, and if not, what steps they have in common.

It will be an iterative process, Richardson said. If a model shows that changing a particular condition produces a particular result, the lab will try it out and see if the result matches the model. Eventually, Richardson said, some commonalities should appear.

There will be a suite of models, and we can highlight features that are common across several models, she said. As we develop the model, we can begin to look at the genomes of other strains of Dehalococcoides. If genes that are important in our strain are found in others ... then we can do the same experiments with the others. Finding which genes are at work with which pollutants might lead to understanding how to remediate other kinds of pollutants, such as PCBs, dioxins, chlorobenzenes or chlorophenols.

Richardson, who grew up in the Hudson River Valley, notes that such pollutants are common in the river's harbors. There are still thousands of sites around the country that need to be cleaned up, she said. Ithaca has three or four, and that's not atypical.

Researchers call for investigation into links between khat use and psychiatric disorders

Mon, 04 Jun 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers investigating the evidence for a potential causal link between khat use and mental illness - in the first ever systematic review of the topic - have called for improved research on the stimulant plant, and its possible association with psychiatric disorders.

In light of ongoing international concern about a contributory association between use of khat and ill mental health, Dr Nasir Warfa - lecturer in Transcultural Psychiatry at Queen Mary, University of London - has reviewed clinical case reports, alongside qualitative and quantitative articles on khat use and mental illness, dating back over 50 years. The work was undertaken in partnership with colleagues at the Institute of Psychiatry, University College London, and the University of Kent.

The findings, which appear online in the social science journal, Social Science and Medicine, show that whilst khat use appears to exacerbate existing psychological problems, there is not currently, any clear evidence which indicates that khat use is a catalyst for the development of mental illness.

Commonly used by around 10 million people in east Africa and countries in the Arabian peninsula, chewing khat for its stimulant properties has also become popular in the UK among immigrants of the Somali, Yemeni and Ethiopian communities. Whilst it is reported to have cultural functions, it is also increasingly reported to be associated with social and medical problems including anti-social behaviour, unemployment, psychoses, depression, and self-neglect.

Crucially, there is also a link between poverty and widespread misuse of khat. In east Africa, 60 per cent of the population live below the poverty line, yet sizeable numbers of khat users borrow money to obtain the drug, exacerbating poverty levels and eroding the quality of life of khat users and their communities. It is in this context, that researchers are planning to undertake a new study to examine khat as a cause of poverty and a failure of regeneration and economic prosperity.

Whilst anecdotal evidence does point towards there being a consequence of mental illness via excessive use of khat, particularly where there is a pre-existing mental illness or vulnerability to psychological distress, Dr Warfa and his team argue that there are many other alternative hypotheses to a causal relationship between khat use and mental illness including the use of khat for self-medication. The researchers suggest that only by improving the quality of future research, and integrating social, medical and pharmacological studies, can a more incisive understanding of the psychological and social impact of khat on individuals and communities be gained.

Further, the researchers recommend that any future policy developments in the UK should feature health and social care which is culturally and socially appropriate. Dr Axel Klein, lecturer in the Study of Addictive Behaviour, University of Kent, also warns that potential legislators should consider the repercussions of criminalising large sections of the community such as the evolution of new organised crime groups based on khat trafficking, and the perverse consequence of increased risk behaviour among khat users.

Dr Warfa said: We need to revisit existing theories of addiction and substance use to include a new model to understand consumption of khat not only among migrant communities in the West but also in conflict and post conflict settings. This will take account of the cultural context, and the socio-economic and psychological implications of khat use. This would allow the formulation of appropriate and contextualised social policy and harm reduction strategies, particularly in the context of maximising impacts from campaigns against global poverty.

An 'elegant' idea proves its worth 25 years later

Wed, 30 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The simple notion of copying the bodys own natural waste disposal chemistry to mop up potentially toxic nitrogen has saved an estimated 80 percent of patients with urea cycle disorders --- most of them children according to a report in this weeks New England Journal of Medicine summarizing a quarter century of experience with the treatment.

The effectiveness of sodium phenylacetate and sodium benzoate, two chemicals the body already makes to carry nitrogen for disposal in urine just knocked my socks off from the moment we first tried them, recalls Saul Brusilow, M.D., professor emeritus of pediatrics at Hopkins who first had the notion to use the drugs. In all my years I never came across another disease where patients come in near-comatose and you stick a needle in them and lo and behold, they wake upjust like that. It was just astonishing, he says.

His elegant idea was to give patients chemicals they already make in small amounts in large doses to make up for the missing urea cycle enzyme they inherited, says Ada Hamosh, M.D., M.P.H, clinical director of the McKusick-Nathans Institute of Genetic Medicine. Sodium phenylacetate and sodium benzoate already know how to eliminate nitrogen in urine, so having more in the body carries more nitrogen out and reduces the toxic effects of excess nitrogen accumulation.

Excess nitrogen yields ammonia, which is poisonous and in the case of urea cycle disorders, causes brain damage, retardation, coma and even death.

Despite the immediate clinical success of the treatment, the drug combination was finally approved by the U.S. Food and Drug Administration only in 2005.

Brusilow, Hamosh, and colleagues at Stanford University, University of Minnesota, Thomas Jefferson University and the Medical College of Wisconsin looked back at 299 urea cycle disorder patients with a total of 1,181 hyperammonemia episodes from 118 hospitals around the United States from August 1980 until March 2005.

The regimen consisted of high-dose intravenous sodium phenylacetate and sodium benzoate for two hours followed by maintenance infusions until blood ammonia levels were normal. The patients overall survival rate was 84 percent, and 96 percent survived episodes of severe ammonia poisoning.

An estimated one in 40,000 live births is a child with a urea cycle disorder, according to Hamosh, who says early and accurate detection can now assure prompt treatment.

Were teaching all medical students at Hopkins to consider hyperammonemia and immediately do blood tests when they see a combative, lethargic or comatose newborn or child, she says. The longer the hyperammonemia lasts, the higher the risk for brain damage.

This is a happy story, says Brusilow. It isnt too often in genetic medicine that we can intuitively develop a treatment with already available chemicals and save lives.

Mercury's link to heart disease begins in blood vessel walls

Wed, 30 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio Heavy metals and other toxins have been linked to many human diseases, but determining exactly how they damage the body remains a mystery in many cases. New research focusing on a relatively obscure, misunderstood protein suggests mercury's link to heart disease can be traced to activation of this enzyme, which triggers a process leading to plaque buildup in blood vessel walls.

The study examined three forms of mercury, matching its characteristics in the environment. Each form of mercury caused changes in the behavior of cells that line the blood vessel walls and that can lead to cardiovascular diseases.

The study also suggests that chelation therapy, a process that removes metals from the body, and antioxidants both show signs of suppressing this activity and might be key to reducing the damage caused by mercury, and possibly other heavy metals.

The research was published in a recent issue of the International Journal of Toxicology.

Mercury has been implicated as a risk factor in cardiovascular disease because of environmental concerns both from contamination and the atmosphere. But no one has looked at heavy metal regulation of this enzyme, said Narasimham Parinandi, director of the lipidomics and lipid signaling laboratory at Ohio State University Medical Center and senior author of the study. If we understand this regulation and know how to block it, we can come up with proper ways to prevent the activity.

Parinandi and colleagues focused on activation of an enzyme called phospholipase D, or PLD, in cells that line arteries in the lung. They exposed the cells to the inorganic, environmental and pharmaceutical forms of mercury, and observed that all three forms activated the enzyme.

The activation of the enzyme involves a complex sequence of events in the cell membranes that in turn releases phosphatidic acid, which can damage cells in the vessel lining called endothelial cells and is believed to contribute to vascular disorders.

To further test the enzyme's role in blood vessel lining damage, the scientists then showed that metal chelators and antioxidants lessen the mercury-induced activation of the enzyme in endothelial cells. This portion of the study showed that different types of mercury affect the cells in different ways.

In the three forms of mercury methylmercury chloride, (environmental form), thimerosal (pharmaceutical form) and mercuric chloride (inorganic form) the enzyme activation was prevented by metal chelators, which are organic chemicals that bind with and remove free metal ions from substances.

The power of methylmercury chloride to activate the enzyme was also affected by antioxidants, including vitamin C, suggesting that this form of the metal generates free radicals. This is the form of mercury most closely associated with the food supply.

Chelators overall did a better job than antioxidants at protecting against mercury activation of the enzyme, said Thomas Hagele, first author of the study and an undergraduate researcher in Parinandi's lab. This shows that activation of the enzyme is not isolated to one location in the cell. Since we can protect against the enzyme activation with both chelators and antioxidants, that means a few different types of activation are likely to occur, depending on the toxin.

This research is not just about mercury, noted Parinandi, also an assistant professor of pulmonary, critical care and sleep medicine. Mercury in this case acts as a model for other toxins that have similar effects on blood vessel walls, pointing to what happens in the body when toxic substances are a factor in causing diseases.

Genome of Clostridium botulinum reveals the background to world's deadliest toxin

Fri, 25 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) The genome of the organism that produces the worlds most lethal toxin is revealed today. This toxin is the one real weapon in the genome of Clostridium botulinum and less than 2 kg the weight of two bags of sugar is enough to kill every person on the planet. Very small amounts of the same toxin are used in medical treatments, one of which is known as Botox®.

The genome sequence shows that C. botulinum doesnt have subtle tools to evade our human defences or tricky methods of acquiring resistance to antibiotics. It lives either as a dormant spore or as a scavenger of decaying animal materials in the soil, and doesnt interact with human or other large animal hosts for prolonged periods of time.

Occasionally it gets into a living animal, via contaminated food or open wounds, leading to infant botulism or wound botulism, both of which are serious human infections. The host can be quickly overpowered and, in some cases, killed by the toxin, and C. botulinum has a new food source.

Although in the same group as Clostridium difficile the Cdiff superbug C. botulinum has a genome that is remarkable because it is so stable, commented Dr Mohammed Sebaihia, lead author on the paper from the Wellcome Trust Sanger Institute. Unlike Cdiff, in which more than 10 per cent of genes have been acquired from other bacteria, there is almost no footprint of these in C. botulinum.

There are several types of C. botulinum: although described as variants of a single species, they are really very different organisms linked simply because they have the deadly toxin. For each type, there is also a near-identical but harmless relative that lacks the toxin. C. sporogenes is the non-malignant, near twin of the organism sequenced.

Professor Mike Peck, from the Institute of Food Research, commented that It is astonishing that 43 per cent of the predicted genes in the C. botulinum genome are absent from the other five sequenced clostridia, and only 16 per cent of the C. botulinum genes are common to all five. Our findings emphasise just how different clostridia are from each other.

C. botulinum toxin stops nerves from working the basis of its use in medicine to control tremors and in cosmetic treatments. For the prey of its opportunistic attacks, death is swift. Perhaps the most important tool it has to act out its stealth attacks is its ability to hibernate when times are hard by forming dormant spores.

More than 110 of its set of almost 3700 genes are used to control spore formation and germination when opportunity arises.

C. botulinum shows us one extreme of the ways that bacteria can make the most of animal hosts, explained Dr Julian Parkhill of the Wellcome Trust Sanger Institute. Some organisms use subtle approaches, elegantly choreographing their interaction with us and our defences.

C. botulinum takes the opposite approach. It lies in wait and, if it gets the opportunity, it hits its host with a microbial sledgehammer. It then eats the remains and lays low until the next host comes along.

The genome sequence is peppered with genes that produce enzymes to digest proteins and other animal material in the soil. Also found, uniquely in this species, is a range of genes that allow it to attack the many insect and other small creatures that live in the soil. The chitinases produced by these genes can degrade the casing of insects and small crustaceans.

It is not only animals that can feel the wrath of C. botulinum, explains Dr Sebaihia: The soil can be a harsh environment and food can be scarce. To see off the competition, C. botulinum comes with its own antibiotic a chemical called boticin that kills competing bacteria.

Genome sequences can tell us a lot about the biology of the organism, but research into clostridia has been hampered by the lack of a good genetic system. Professor Nigel Minton, Professor of Applied Molecular Microbiology at The University of Nottingham, has developed new methods to knock out genes in clostridia.

Even after decades of research, only a handful of mutants had been made in clostridia, and none in C. botulinum, Professor Minton explains. We have developed a highly efficient system, the ClosTron, with which we have, in a few months, knocked out over 30 genes in four different clostridial species, including eight in C. botulinum. The availability of this tool should revolutionise functional genomic studies in clostridia.

This remarkable, stable genome demonstrates the wide range of strategies used by bacteria to enhance their chances of survival. For the Clostridia, these range from the approach used by Cdiff long-term interaction with hosts, which involves evading the immune system and countering antibiotics to the single-minded opportunistic approach of C. botulinum.

Pointing a finger at the source of fecal bacteria

Wed, 23 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) MADISON, WI, MAY 23, 2007 -- Excessive levels of fecal bacteria were to blame for almost 60 percent of Nebraska streams deemed impaired by federal and state environmental laws in 2004. In order to develop effective pollution-control strategies, it is important for researchers to identify the source of the contamination. By using multiple methods, or a toolbox approach, to determine the origin of fecal pollution in streams, researchers were able to identify the source of fecal bacteria with greater certainty than if testing with a single method.

In collaboration with the Nebraska Department of Environmental Quality, the U.S. Environmental Protection Agency (EPA), and the University of Cincinnati, U.S. Geological Survey (USGS) scientists used a toolbox approach when investigating the sources of fecal bacteria within the Plum Creek watershed in south-central Nebraska. The scientists report their findings in the May-June 2007 issue of the Journal of Environmental Quality.

This research was funded by the Nebraska Department of Environmental Quality, the U.S. Geological Survey Cooperative Water Program, and the U.S. Environmental Protection Agency.

In 2001, monitoring studies by the Nebraska Department of Environmental Quality named Plum Creek the most contaminated tributary to the middle reaches of the Platte River. The researchers used two fecal source-tracking tools to analyze contaminated water and stream-sediment samples in the Plum Creek watershed.

The source-tracking tools use genetic material from bacteria collected in water and sediment samples to determine their source, either by comparing the genetic material with that of known fecal bacteria sources, or by looking for a marker within the genetic material that is associated with a specific fecal source. The results of the study revealed that cattle and wildlife were the dominant sources of fecal bacteria found in water and stream sediment samples at the main study site located in an upper reach of the creek.

While the two methods led to similar overall interpretations, using both methods together gave us a clearer picture of potential sources and the strengths and weaknesses of the methods used, said USGS Hydrologist Jason Vogel, lead author of the study. Additionally, results from bacteria found in stream-bottom sediment also suggest that different tools for tracking fecal contamination may have varying relevance to the more specific goal of tracking the sources of E. coli in water or soil within the watershed.

Ongoing studies at the USGS and EPA are testing the use of microorganisms as tools for tracking fecal contamination. Fecal bacteria can enter watersheds from specific sources such as wastewater treatment outfalls, and diffuse sources such as runoff from fields where livestock waste has been applied as fertilizer. Determining the source of the bacteria is necessary to implement appropriate pollution-control practices and comply with water-quality standards required by the Clean Water Act. Further research is needed to continue to develop and refine existing and new tools for identifying the sources of fecal contamination in water and sediment.

Engineered protein effective against Staphylococcus aureus toxin

Mon, 21 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A research team led by the University of Illinois has developed a treatment for exposure to enterotoxin B, a noxious substance produced by the Staphylococcus aureus bacterium. The team engineered a protein, which was successfully tested in rabbits, that could one day be used to treat humans exposed to the enterotoxin.

S. aureus enterotoxin B (SEB) is a common cause of food poisoning, but if it is inhaled or produced during an infection it can elicit a systemic and sometimes fatal immune response in humans. In purified form, SEB is listed as a potential bioterrorism agent. Other potent S. aureus enterotoxins include the toxic shock syndrome toxin.

These enterotoxins are classed as superantigens because they set off a massive immune response in humans and other animals. They bind to variable regions of T-cell receptors, stimulating a cascade of events, including the systemic release of inflammatory cytokines. In some cases the powerful immune response leads to toxic shock and death.

The research team, led by University of Illinois professor of biochemistry David M. Kranz, included scientists and clinicians from the Boston Biomedical Research Institute and the University of Minnesota Medical School. Their findings appear today in the online edition of Nature Medicine.

The team began by engineering a protein with the same structure as the binding site of the T-cell receptor targeted by SEB. The researchers expressed the engineered protein on the surface of yeast cells (using a process they helped develop, called yeast display) and generated mutations meant to increase the protein's ability to bind SEB. After several rounds of mutagenesis and screening, graduate student Rebecca A. Buonpane developed a soluble protein with an affinity for SEB that was over a million times that of the original.

Our approach was to take these receptors that bind to the toxins and to try to make them higher affinity and therefore act as effective neutralizing agents when delivered in soluble form, Kranz said. It's the binding of the toxin to T-cells that is critical. If you can prevent the toxin from binding to the T-cell receptor then you can prevent it from initiating that cascade.

The engineered protein prevented the onset of symptoms in rabbits exposed to SEB and reversed the course of the illness in those treated two hours after exposure.

We were very pleasantly surprised that it showed effectiveness in every rabbit tested, Kranz said.

He noted that the protein has some potential advantages and disadvantages when compared to antibodies, which might also be used to fight infection with SEB. One advantage is that the engineered protein is small, about one-tenth the size of an antibody. Its size may allow it to penetrate deeper into tissues, and may make it less likely to spark an immune response in animals. The protein can also be produced in large quantities using the bacterium, Escherichia coli.

E. coli is the cheapest source for making proteins, Kranz said. Whenever you can express a protein in E. coli you do so because it is inexpensive, easy and fast.

Antibodies, on the other hand, can remain in the body for days or weeks, whereas the new protein is cleared within hours. This may make antibodies a better treatment option in some circumstances, said Kranz.

No antibody has yet been developed, however, that has a comparable affinity for SEB.

Hexavalent chromium in drinking water causes cancer in lab animals

Wed, 16 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers announced today that there is strong evidence a chemical referred to as hexavalent chromium, or chromium 6, causes cancer in laboratory animals when it is consumed in drinking water. The two-year study conducted by the National Toxicology Program (NTP) shows that animals given hexavalent chromium developed malignant tumors.

Previous studies have shown that hexavalent chromium causes lung cancer in humans in certain occupational settings as a result of inhalation exposure, said Michelle Hooth, Ph.D., NTP study scientist for the technical report. We now know that it can also cause cancer in animals when administered orally.

The study findings were announced at the National Institute of Environmental Health Sciences (NIEHS) after the NTP Board of Scientific Counselors Technical Reports Review Subcommittee completed its independent peer review of the sodium dichromate dihydrate research report. Sodium dichromate dihydrate is an inorganic compound containing hexavalent chromium that was used in the NTP studies. The NTP is located at the NIEHS, part of the National Institutes of Health.

Hexavalent chromium compounds are often used in electroplating, leather tanning, and textile manufacturing and have been found in some drinking water sources.

Male and female rats and mice were given four different doses of sodium dichromate dihydrate in their drinking water ranging from 14.3 mg/l to 516 mg/l for two years. The lowest doses given to the animals in the study were ten times higher than what humans could consume from the most highly contaminated water sources identified in California.

The researchers report finding significant increases in tumors at sites where tumors are rarely seen in laboratory animals. Male and female rats had malignant tumors in the oral cavity. The studies conducted in mice found increases in the number of benign and malignant tumors in the small intestine, which increased with dose in both males and females.

We found that hexavalent chromium is absorbed from the gastrointestinal tract, said Hooth. After it is orally administered, it is taken up by the cells in many tissues and organs.

Hexavalent chromium has been brought to the publics attention in many ways, most notably in the movie Erin Brockovich. Eleven members from the California Congressional Delegation sent a letter to the NTP Director requesting the NTP conduct the studies. Nominations for studying this compound also came from the California Environmental Protection Agency and the California Department of Health Services. The NTP began work on this compound after gaining input from the public and a panel of scientific experts about the study design.

Agent protects cells from lethal effects of radiation even if given after exposure

Tue, 08 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) No drugs exist to protect the public from the high levels of radiation that could be released by a dirty bomb or nuclear explosion. Such excessive exposure typically causes death within weeks as the radiation kills blood cells vital to clotting and fighting infection, along with the stem cells needed to replenish their supply. But now researchers at Washington University School of Medicine in St. Louis report they have developed an agent that protects cells from the lethal effects of radiation, regardless of whether it is given before or after exposure.

Using this agent in mice, the investigators found that the treatment helped shield rapidly dividing cells that are most vulnerable to radiation-induced death, providing proof in principle that it is possible to fend off radiation damage, according to a study published in the April issue of Biochemical and Biophysical Research Communications.

Current treatments for severe radiation exposure, also called acute radiation syndrome, are limited to drugs that boost the production of blood cells and platelets, but this approach is futile if underlying stem cells are also killed off. Moreover, there are no available treatments that can be given after exposure to limit damage to cells.

We are using an entirely different approach, says Clayton Hunt, Ph.D., of the Department of Radiation Oncology. Rather than ramp up the production of blood cells, we are trying to prevent radiation-induced cell death from occurring in the first place.

The researchers developed the agent by attaching a portion of the Bcl-xL protein already known to block cell death - a snippet called BH4 - to the HIV protein TAT, which can deftly carry other molecules into cells. They gave the agent intravenously to mice exposed to 5 Grays of radiation. In humans, this level of exposure would cause a sharp drop in blood cells, leaving individuals with an increased risk of infection and bleeding.

They found the treatment helped protect rapidly dividing T cells and B cells in the spleen - immune system cells that are prone to radiation damage - whether it was given 30 minutes before radiation exposure or 30 minutes afterward.

As part of the research, the investigators monitored the levels at which old or damaged cells in the spleen were dying, a process called apoptosis. In a group of control mice that were not exposed to radiation, the researchers determined that 4.7 percent of T cells and 5.1 percent of B cells in the spleen were undergoing apoptosis. This level is considered normal as cells naturally die and are replaced by new ones. After the mice received 5 Grays of whole body radiation, apoptosis increased to 15.6 percent of T cells and 38.7 percent of B cells.

But when the researchers gave TAT-BH4 to the mice prior to whole body radiation, levels of apoptosis dropped significantly, to 8.6 percent of T cells and 16.9 percent of B cells. In mice given TAT-BH4 after radiation exposure, the proportion of cells undergoing apoptosis dropped even further, to 5.7 percent of T cells and 12.3 percent of B cells.

The Washington University approach appears to halt apoptosis by targeting pathways within cells that are far removed, or downstream, from the initial radiation insult. In particular, BH4 is thought to block a release of the electrical charge across the membrane of mitochondria - the powerhouses of cells - a key event in initiating cellular self-destruction. This gives us a window of opportunity to treat patients and still prevent cells from undergoing programmed cell death, said Richard Hotchkiss, M.D., professor of anesthesiology, medicine and surgery. We have a lot more work to do, but we are encouraged by these early findings.

Follow-up data suggest that TAT-BH4 is still effective when it is given to irradiated mice one hour after exposure, and the researchers plan further studies to determine how long after exposure the agent can prevent radiation-induced apoptosis.

In the past several years, the federal government has devoted increasing resources to the development of countermeasures that protect the public from chemical, biological, radiological or nuclear attack. TAT-BH4 may one day be a viable candidate because theoretically it could be given after radiation exposure, administered in pill form, and synthesized and stored in large quantities - all properties that would be desirable for treating large groups of individuals exposed to high levels of radiation, Hotchkiss said.

The researchers contend that developing such a drug would be less challenging than finding a way to protect healthy cells from radiation therapy aimed at destroying cancer cells. In radiation therapy, you want to give a dose of radiation to a tumor and reduce the exposure to surrounding, healthy tissues, Hunt said. This is difficult because a drug has to distinguish between tumor and normal tissue. But with people exposed to a large dose of radiation over the entire body, you want to protect all the cells in the body. To me, that is an easier problem to solve.

Prenatal toxicity linked to immune dysfunctions in later life

Wed, 02 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A Cornell researcher and his wife have conducted the first comprehensive review of later-life diseases that develop in people who were exposed to environmental toxins or drugs either in the womb or as infants. They have found that most of the diseases have two things in common: They involve an imbalanced immune system and exaggerated inflammatory reactions (at the cellular level).

In an invited, peer-reviewed article on developmental immunotoxicity (DIT), published in a recent issue of Current Medicinal Chemistry, Rodney Dietert, professor of immunotoxicology at Cornell's College of Veterinary Medicine, and Janice Dietert of Performance Plus Consulting in Lansing, N.Y., found that almost all the chronic diseases that are associated with DIT share the same type of immunological damage.

The diseases linked to DIT include asthma, allergy, suppressed responses to vaccines, increased susceptibility to infections, childhood neurobehavioral conditions, autoimmunity, cancer, cerebral palsy, atherosclerosis, hypertension and male sterility.

Toxins that are known to cause developmental immune problems in fetuses and neonates, according to the Dieterts, include herbicides, pesticides, alcohol, heavy metals, maternal smoking, antibiotics, diesel exhaust, drugs of abuse and PCBs.

Antidotes to DIT, the researchers note, could come from a variety of sources, including herbal and fungal chemicals -- from mushrooms to clover -- which appear to have promise.

Two immune processes -- T helper (Th) cell balances and dendritic cell maturation -- are both compromised in ways that disrupt the regulation of inflammatory cell function, which leads to exaggerated inflammatory responses.

Most therapeutic approaches have looked at specific disease outcomes from DIT, rather than focusing on the underlying immune dysfunction that creates the increased disease risk, said Rodney Dietert, who also presented his findings March 28 at the annual Society of Toxicology meeting in Charlotte, N.C. Instead, we looked at the common immune dysfunction that is related to a host of diseases.

Knowing the most common immune dysfunction patterns from DIT allows researchers to consider more seriously those medicinals with the capacity to restore inflammatory cell regulation, promote dendritic cell maturation and restore desirable Th balance that would be the most likely candidates to combat the problems resulting from DIT.

Focusing on studies of herbal and fungal chemicals, the Dieterts scoured the literature and found that some of the chemicals appear to be particularly promising when taken at appropriate doses. These include: Astragalus; Echinacea (purple coneflower); sang-hwang shiitake, reishi, maitake and snake butter mushrooms, black seed, Asian ginseng, milk vetch root, wild yam, Sophoro root and Greek clover (all of these also go by various other names).

In their paper, the Dieterts also list a multitude of substances that have been found to have an uncertain impact on DIT as well as several found to exacerbate immune dysfunction (including marijuana).

We hope that these findings of persistent immune dysfunction from gestational exposure will provide encouragement for additional research. Furthermore, that researchers will look at these categories of medicines that have the possibility of correcting inflammatory and immune balance problems resulting from DIT rather than focusing solely on individual disease symptoms, Rodney Dietert said.

He noted that until recently toxin-testing guidelines predicted only risk in adults, but that the Environmental Protection Agency has announced it will issue new guidelines to take into account the increased immune sensitivity of fetuses and young children.

New treatments have major impact on heart failure rates

Tue, 01 May 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Deaths from severe heart attacks following admission to hospital have nearly halved in six years as a result of advances in medical treatment.

In the largest study of its kind, research led by the University of Edinburgh, analysed hospital treatment and outcomes for 44,372 patients admitted to 113 hospitals in 14 countries with heart attacks or unstable angina (threatened heart attacks).

As well as a significant reduction in death rates, the study published in the Journal of American Medical Association also established a decline in heart failure a progressive disorder when damage to the heart weakens the cardiovascular system and poor heart muscle function causes fluid in the lungs.

This is the first time such findings relating to heart failure, a chronic condition often requiring specialised nursing care in the community, have been made.

In patients admitted with a severe heart attack, where the arteries were completely blocked, death rates reduced from 8.4 to 4.5 per cent. Their risk of heart failure also nearly halved with a reduction from 20 to 11 per cent. For every 1,000 patients presenting themselves to hospital this means 39 fewer death and 90 less patients with new heart failure.

Patients who suffered from severe heart attacks also saw subsequent rates of critical heart failure cardiogenic shock reduce from 7.1 to 4.7 per cent. This is important as 70 per cent of patients with cardiogenic shock die.

Professor Keith Fox, British Heart Foundation professor of cardiology at the University of Edinburgh, said: We know that advances in medical treatments have improved outcomes due to large scale trials of therapies but there has been a substantial gap in knowing how this relates to how new drugs and procedures are being used and implemented in hospitals.

Our study enables us to look at differences in practice in a clinical setting over time and it has reflected significant changes in how patients with heart attacks are treated, showing that guidelines are being followed. As a result there is a major reduction in death rates.

Deaths in patients admitted with milder forms of heart attacks, where the artery was not completely blocked, also reduced (from 2.9 to two per cent).

Both patients with severe and milder heart attacks were less likely to suffer from strokes and further heart attacks in the following six months.

For those who suffered from severe heart attacks, their risk of having a stroke reduced from 1.3 to 0.5 per cent and also more than halved for heart attacks (down from 4.8 to 2 per cent).

For those who had suffered a milder heart attack, the risk of stroke reduced from 1.26 to 0.67 per cent and the risk of having another heart attack reduced from 3 to 1.9 per cent.

Professor Fox, said: There have been many advances in medical treatment for heart attacks over recent years which includes the use of beta-blockers, statins or angiotensin-converting enzyme inhibitors (ACE) and anti-clotting agents.

However, these long-term prevention methods do not account for improved outcomes while patients are in hospital, which must be down to the acute treatments given after admission. We have taken into account risk factors and the improved outcomes are not because patients are less unwell when they arrive at hospital.

Our study supports the fact that hospitals are using new treatments effectively. Patients now have a much reduced risk of dying or having another stroke while being treated in hospital and are also less likely to suffer a stroke or further heart attack once they have been discharged.

The study looked at patients between July 1999 and the end of 2006. Countries involved in the study included Britain, the United States, Canada, France, Germany, Belgium, Spain and Poland.

Professor Peter Weissberg, Medical Director at the British Heart Foundation (BHF), said: This is a great example of why long-term investment in heart research is vital. The study shows that fewer people are dying, and fewer are developing debilitating heart failure thanks to research evidence prompting these hospitals to improve the way they treat people with heart disease.

Every day, heart patients are benefiting from research made possible partly by generous public donations to the BHF.

Researchers call for national database of epidural complications

Mon, 02 Apr 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have called for a national database to be set up to identify major complications arising from epidural pain relief after a small number of serious problems were identified during a six-year UK study, according to the April issue of Anaesthesia.

They discovered that 12 of the 8,100 people studied developed major complications after receiving epidural pain relief following an operation. Six developed epidural abscesses, three suffered from meningitis and three had blood clots in the epidural space.

Twelve different anaesthetists sited the epidural catheters and the patients were managed on five different wards after surgery. All the epidural insertions met recommended aseptic techniques to minimise infection.

Although relatively rare, these complications are serious and point to the need for regular surveys to be carried out after epidural pain relief to identify risk factors and the scale of the problem says consultant anaesthetist Dr Iain Christie from Derriford Hospital, Plymouth, UK.

For example, epidural abscesses can cause neurological damage and paralysis of the lower limbs if left untreated.

The survey which took place between 2000 and 2005 gathered information from four key sources.

Researchers looked at the hospitals patient information system to identify patients undergoing surgery and the acute pain service to identify all patients receiving epidural pain relief after surgery.

They also looked at any patients who had received a spinal MRI scan or undergone relevant microbiological investigations within 60 days of surgery.

Before they carried out the survey clinicians were aware of seven patients who had suffered major complications after epidural pain relief during the study period. The survey identified a further five.

Patients have a much better outcome if they are diagnosed and treated before neurological symptoms develop stresses Dr Christie. It is particularly important to monitor leg weakness as this is an important measure of spinal cord health and ensure that patient information systems pick up any infections following discharge from hospital.

The authors point out that other reported cases of epidural abscesses following epidural pain relief indicate that it is not just a local problem.

We would strongly recommend that all acute pain services supervising epidural pain relief after surgery perform a regular survey to identify patients who have suffered one of these complications stresses Dr Christie.

The results should then be stored in a national database to provide a more accurate estimate of the risk of these complications. This register might also identify other relevant risk factors such as MRSA infections.

The Royal College of Anaesthetists started its 3rd National Anaesthesia Audit in September 2006 and says that it plans to report the findings in 2008. We hope that the outcome of this project will be a national register.

NJIT professor obtains patent to uncover trace elements of airborne pollutants

Tue, 20 Mar 2007 04:00:00 PST

( from http://www.rxpgnews.com ) A breakthrough patent awarded to a New Jersey Institute of Technology (NJIT) researcher will enable manufacturers to create a device to uncover miniscule amounts of airborne pollutants. Using computer chip technology, Somenath Mitra, PhD, professor and chair of NJIT's Department of Chemistry and Environmental Sciences, has developed and patented what could eventually become a simple keychain device to detect tiny, though potentially lethal, amounts of airborne carcinogens.

Calling the invention a microconcentrator, Mitra said his NJIT research team has created a novel, cost-effective and efficient method to concentrate pollutants. By doing so, pollutants can then be introduced onto a sensor to identify trace pollutants.

Our chip has a polymer enabling it to concentrate the pollutants and a tiny built-in heater that drives them onto the sensor, Mitra said. It works like a bicycle pump. First our chip accumulates the pollutants as a pump fills with air. Then, the chip directs the tiny heater to send a large enough sampling of pollutantsif they exist-- to the sensor's head. With a large sample, the sensor can recognize that pollutants exist.

A Microfabricated Microconcentrator For Sensors and Gas Chromatography, US Patent 7147695B2, was awarded to Mitra in December of 2006. Research about the invention was previously published in Sensors and Materials (Design and Fabrication of Microheaters for Microfluidic Channels) in 2006 and The Journal of Chromatography A (A Microfabricated Microconcentrator for Sensors and Gas Chromatography) in 2003.

The value of our sensing system is that it can see pollutants even when they are present at very low concentrations, said Mitra. Down the road, we hope to see this technology pave the way for developing a small, inexpensive device to fit on a key chain. These devices would do the same job as larger instruments used in chemical laboratories for monitoring organic and other pollutants in air and water.

Although many advances have been made in science, it is still not as simple as many people imagine for scientists to monitor pollutants. The consequences from automobile exhaust, the dilution of cleaning solvents in air or the problems that occur when tankers spill gasoline, remain of concern to scientists.

Typical concentrations of many pollutants can be small--only a few molecules of pollutants in every part per billion of air or water molecules, Mitra said. But even at these levels, these pollutants pose a threat to human and public health.

For example, we know that benzene, a by-product of automobile exhaust, causes cancer, Mitra said. The organics from auto exhaust fumes also lead to smog formation in urban areas like Los Angeles. Measuring benzene and similar chemicals, though, is costly and difficult. One must have access to large instruments that cost thousands of dollars. But using the microconcentrator, this will no longer be the case.

Although the market currently features affordable miniature sensors, the technology is not there yet for the tiniest amounts of pollutants, said Mitra. I'm talking about creating an instrument sensitive enough to measure concentrations of pollutants such as benzene, which may range in just a few parts per million or even billion.

Mitra's research interests are two-pronged. He looks for novel analytical techniques and sensors to discover low-level trace elements in air, water and soil. His current projects include developing instrumentation and methods for continuous, on-line analysis of trace levels of organic pollutants in air and water. These methods range from using gas chromatography or mass spectrometry to micro-scale, lab-on-a-chip devices.

Mitra also looks for new ways to assemble and modify carbon nanotubes to create novel and new materials to be used in applications ranging from tennis rackets to rocket ships. Other uses might include developing smaller nano chips for electronics (also known as nano-electronics) and inexpensive, high-performance throw-away chemical sensors. The latter might range from sensors for clinical diagnostic purposes to using sensors to find toxic chemicals in air, food or water.

Mitra has published 70 journal papers and is the coauthor of Environmental Chemical Analysis (CRC Press, New York, 1998). He also edited Sample Preparation Techniques in Analytical Chemistry (John Wiley, New York, 2003). Mitra holds five patents and has made more than 150 presentations conferences.

Mitra received his PhD from Southern Illinois University in 1988.

Studies force new view on biology of flavonoids

Mon, 05 Mar 2007 05:00:00 PST

( from http://www.rxpgnews.com ) CORVALLIS, Ore. Flavonoids, a group of compounds found in fruits and vegetables that had been thought to be nutritionally important for their antioxidant activity, actually have little or no value in that role, according to an analysis by scientists in the Linus Pauling Institute at Oregon State University.

However, these same compounds may indeed benefit human health, but for reasons that are quite different the body sees them as foreign compounds, researchers say, and through different mechanisms, they could play a role in preventing cancer or heart disease.

Based on this new view of how flavonoids work, a relatively modest intake of them the amount you might find in a healthy diet with five to nine servings of fruits and vegetables is sufficient. Large doses taken via dietary supplements might do no additional good; an apple a day may still be the best bet.

A research survey, and updated analysis of how flavonoids work and function in the human body, were recently published in Free Radical Biology and Medicine, a professional journal.

What we now know is that flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant, said Balz Frei, professor and director of the Linus Pauling Institute. The body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile.

Flavonoids are polyphenolic compounds with some common characteristics that are widely found in fruits and vegetables and often give them their color they make lemons yellow and certain apples red. They are also found in some other foods, such as coffee, tea, wine, beer and chocolate, and studies in recent years had indicated that they had strong antioxidant activity and because of that, they might be important to biological function and health.

If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants, Frei said. Based on laboratory tests of their ability to scavenge free radicals, it appears they have 3-5 times more antioxidant capacity than vitamins C or E. But with flavonoids in particular, what goes on in a test tube is not whats happening in the human body.

Research has now proven that flavonoids are poorly absorbed by the body, usually less than five percent, and most of what does get absorbed into the blood stream is rapidly metabolized in the intestines and liver and excreted from the body. By contrast, vitamin C is absorbed 100 percent by the body up to a certain level. And vitamin C accumulates in cells where it is 1,000 to 3,000 times more active as an antioxidant than flavonoids.

The large increase in total antioxidant capacity of blood observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, Frei said, but most likely is the result of increased uric acid levels.

But just because flavonoids have been found to be ineffectual as antioxidants in the human body does not mean they are without value, Frei said. They appear to strongly influence cell signaling pathways and gene expression, with relevance to both cancer and heart disease.

We can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them, Frei said. But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention.

Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion, Frei added.

It also appears that flavonoids increase the activation of existing nitric oxide synthase, which has the effect of keeping blood vessels healthy and relaxed, preventing inflammation, and lowering blood pressure all key goals in prevention of heart disease.

Both of these protective mechanisms could be long-lasting compared to antioxidants, which are more readily used up during their free radical scavenging activity and require constant replenishment through diet, scientists say.

However, Frei said, its also true that such mechanisms require only relatively small amounts of flavonoids to trigger them conceptually, its a little like a vaccine in which only a very small amount of an offending substance is required to trigger a much larger metabolic response. Because of this, there would be no benefit and possibly some risk to taking dietary supplements that might inject large amounts of substances the body essentially sees as undesirable foreign compounds.

Numerous studies in the United States and Europe have documented a relationship between adequate dietary intake of flavonoid-rich foods, mostly fruits and vegetables, and protection against heart disease, cancer and neurodegenerative disease, Frei said.

MIT engineer works toward clean water, more

Mon, 05 Mar 2007 05:00:00 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, Mass.--An MIT engineer working toward clean drinking water in Nepal describes in a recent issue of the Journal of International Development how people from developed and developing countries can work together to solve key humanitarian problems, ultimately meeting the basic human needs for security, broadly defined.

Such a collaboration begins with a relationship among partners in the global village, taking into consideration the specific conditions of the local culture, environment and location, said Susan Murcott, a senior lecturer in MIT's Department of Civil and Environmental Engineering (CEE).

Murcott has personal experience of a global engineering partnership of this kind--she calls it co-evolutionary engineering design-through her work in developing countries.

She and students in MIT's CEE master of engineering program have worked for years with citizens of Nepal and, since 2005, of Ghana, to design, test and distribute inexpensive household water filters that simultaneously remove arsenic and microbial contamination from the available water supply. Murcott notes that some 150 million people worldwide are affected by arsenic-tainted water, while an estimated 1 to 5 billion people worldwide lack access to microbially safe water.

As of December 2006, more than 5,000 such filters are operating across Nepal, serving some 40,000 people. An additional 5,000 filters are slated for sales and distribution in 2007 in Nepal, with further outreach into Vietnam, Cambodia and Bangladesh underway.

The students and I are trying to make a positive contribution to people's lives and to improve our collective chances of development and security, said Murcott.

With co-evolutionary design, technical designers from developed countries become partners with the user communities, who are experts in their local conditions. With the MIT Nepal Water Project, Murcott points out, Our team's partners have included university-educated people and illiterate peasant farmers. We have identified a common need-safe, clean drinking water for all-and we have worked together successfully for seven years so far.

Any system to provide clean water should consider factors such as sustainability, green engineering and World Health Organization guidelines. In addition, the system must meet the requirements of the local women who typically haul and store water, as well as being affordable to people earning one dollar a day. The same general principles also apply to other co-evolutionary design projects.

Murcott is currently focusing her energies in the northern region of Ghana, thanks to a two-year grant from the Conrad N. Hilton Foundation. Here, a social enterprise-Pure Home Water, initiated by Murcott with Ghanian partners-is marketing ceramic water filters in one of the poorest regions of Ghana, where cholera, typhoid, guinea worm and other waterborne diseases are rampant. Two Ghanaian social entrepreneurs, together with MIT engineering and Sloan School of Management students, hope to spread ceramic filters to reach more than a million people in northern Ghana in the coming years.

Murcott is also leading MIT teams to Nicaragua, Haiti, Peru and Kenya to address water and sanitation issues in those countries.

She concludes, We hope to increase awareness of health and safe water issues among the least educated people in remote areas of Nepal and Ghana, subsidize filters for the very poorest people, insure that locally made units are built correctly, and make sure that future teams will effectively and passionately carry the work forward.

We are confident that this work provides a model of engaged, cross-cultural cooperation that builds self-reliant solutions, at the same time providing a renewed understanding that security for most people in the world relates not to armed conflict but to 'common good' social, environmental and economic challenges, for example, the simple need for safe water.

Biodesign Institute takes part in $14.4M NIH chemical defense grant

Mon, 12 Feb 2007 05:00:00 PST

( from http://www.rxpgnews.com ) The Biodesign Institute at Arizona State University has been awarded one of six research projects as part of a $14.4 million National Institutes of Health (NIH) effort to develop improved antidotes for civilian populations vulnerable to chemical agent poisoning by a terrorist attack.

The overall effort is dubbed the CounterACT (Countermeasures Against Chemical Threats) Center of Excellence. The program is led by David Lenz, PhD, of the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD).

Tsafrir Mor, a researcher at ASU's Biodesign Institute and assistant professor in the School of Life Sciences, will be the lead investigator of the five-year, $2.67 million ASU portion of the award.

Nerve agents, such as sarin, are among the most lethal chemical weapons ever developed. They have been used in wars as recently as the 1980s and by terrorist organizations such as the subway attacks in Japan in the mid 1990s said David Moore, DVM, PhD, Director, Strategic Research Program Development, USAMRICD, at Aberdeen Proving Ground, Maryland. The work of this new center will lead to a paradigm shift in how to treat nerve agent exposure.

Besides the terrorist threat, Biodesign's Mor points out that the active chemical ingredient contained in nerve agents, organophosphates, can be found in many pesticides, leading to the accidental death of an estimated one to two million individuals worldwide who don't properly handle pesticides.

Mor's project is based on two interlocking themes, one focused on the design of human enzymes with new activities to neutralize nerve agents and a second utilizing plants to express proteins of human origin in high quantities.

The project, Rapid and Large Scale Plant-Derived Production of Catalytic Nerve-Agent Bioscavengers is a natural progression of Mor's previous work that was supported by the Defense Advance Research Project Agency (DARPA)

In our DARPA project, said Mor, we engineered plants to express the natural target of these toxins, the enzyme acetylcholinesterase, and proved that the plant-derived protein is effective in protecting against pesticide poisoning.

Preclinical studies have shown that a family of human proteins, called cholinesterases (ChEs), is an effective antidote against nerve agents. The enzymes act like molecular sponges, soaking up and neutralizing the harmful organophosphates before they do damage.

The new project focuses on developing next-generation antidotes, called bioscavengers.

The new candidate bioscavengers we hope to develop are human enzymes that not only bind to nerve agents to neutralize them, but also destroy them, said Mor,We can use plants and new technologies developed at ASU to scale-up production to make large amounts of antidote material in a cost-effective manner.

Nerve agents achieve their lethal effects by shutting down the control of the body's peripheral nervous system, including control of glands, internal organs and skeletal muscles. This nervous system has a vital, sweeping scope, from the dilation of the pupil in the eye, through excretion of tears and saliva to powerful muscle contractions in the gut, heart and lungs. Consequently, nerve agent poisoning can lead to more severe symptoms like involuntary excretion, tremor, paralysis and death.

The trigger behind the muscle contractions is a chemical messenger, acetylcholine, which communicates and transmits signals between nerves, and between nerves and target cells like muscles. Many steps are necessary for proper nerve signaling, but a key step is to whisk acetylcholine away from the nerve by an enzyme called acetylcholinesterase (AChE). Otherwise, the body's cholinergic system can quickly spiral out of control.

Mor is most interested in a chemical cousin of AChE, called butyrylcholinesterase (BChE), which is found in serum plasma and the liver. BChE can also degrade acetylcholine, but it also seems to play a role as the body's vacuum cleaner, degrading drugs and natural products and eliminating them from the body. Another enzyme, paraoxonase (PON1) is a constituent of HDL, the body's good cholesterol and has a role in prevention of atherosclerosis.

If we can catalytically neutralize these poisons using BChE or PON1, the real advantage will be that we won't need as much of the enzymes, said Mor. Plus, there may be benefits to conditions such as heart disease through gaining an increased knowledge of how BChE works to clear potentially harmful items from the body.

ChEs can be purified from the blood to use as a nerve agent antidote. However, large amounts are needed for full protection, and the only source is outdated blood-banked plasma.

But using blood banks as the main source of ChEs is out of the question.

According to Mor, ChEs are present in such tiny quantities that he estimates it would take the entire blood supply of the U.S. just to produce one kilogram of material.

Therefore, Mor, a protein engineering and plant-based therapeutics expert, will initially adapt plants as protein production factories to develop a novel means to biomanufacture catalytic bioscavengers based on the human proteins BChE and PON1.

Mor recently completed his four-year award from the Defense Applied Research Projects Administration (DARPA) to develop ideas of using plants as a bioproduction system for countermeasures against chemical warfare agents. His plant of choice is tobacco, because it is a non-food crop. According to his calculations, he can create enough ChEs with the system and scale it up accordingly to supply the entire U.S. in about 100-1000 acres, depending on the protein yield per plant.

At the end of the new grant period, Mor is hopeful that his approach will lead to new effective and safe countermeasures to protect humans from the toxic effects of pesticides and nerve agent exposure at a fraction of the current dose of human BChE and at a fraction of the costs.

Study reveals molecular basis of botulism toxin's deadly activity

Thu, 14 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) In the study, the scientists reveal the mysterious structural basis of the remarkably strong interaction that botulinum toxins form with nerve cells, a union so robust that a single toxin molecule can completely incapacitate a nerve cell. Because of this action, even in minute quantities these toxins are potentially deadly, leading to muscle weakness, paralysis, and sometimes respiratory failure.

The structure finally helps to answer part of the mystery of how a very large protein can search through the body and locate the neuromuscular junction with such high affinity and specificity, says Scripps Research Professor Raymond Stevens, an author of the paper who has studied botulinum toxins for many years.

The toxins responsible for botulism are produced by the bacterium Clostridium botulinum. Humans can get the toxins from tainted food, certain wounds, and gastrointestinal tract colonization by the bacteria, the latter being particularly dangerous for infants. There is also growing concern that botulinum toxins might be used as weapons, with the Centers for Disease Control ranking them as one of the six highest-risk threats for bioterrorism.

Scientists had suspected for many years that botulinum toxins bind with nerve cells through a two-step process, but the details were unknown. Using x-ray crystallography on type B (there are seven structurally and functionally related botulinum neurotoxins, serotypes A through G) in action with receptors, the Scripps Research investigators took a molecular snapshot of regions critical to the process. Analyzing the data along with colleagues at the University of Wisconsin, Madison, and the Howard Hughes Medical Institute led to the discovery of just how the binding proceeds.

Botulinum toxins first attach to a portion of a protein found on the surface of nerve cells that mates with two parallel, narrow grooves on the toxin. Because this protein receptor is only exposed on active cells, the toxins target those nerves that are most important to a victim, such as muscles needed for breathing that are constantly in use.

The team was also able to model the structure of the second step in the process, where a separate region of a botulinum toxin binds with a sugar known as a ganglioside that acts as a second receptor. The gangliosides are found on the nerve cell surface close to the protein receptor. This double binding to the nerve cell orients the toxin in such a way that it can penetrate the nerve cell and break apart proteins that are essential to proper transmission of nerve signals.

Solving the structures opens the possibility of developing new botulism treatments, including improved small molecule drugs, vaccines, and antibody therapies.

Currently, botulism treatment rests on a cocktail of antibodies derived from horses. Because the antibodies are not human, rejection is a pervasive problem with severe potential side effects, including anaphylactic shock. The development of new types of antibodies could be a boon for treatment, and this possibility is explored by Stevens and colleagues in a paper to be published in Nature Biotechnology later this week.

In addition, the structure will help the development of other types of therapeutics to treat botulism infection. You could essentially design smaller compounds that mimic those interactions, says Joseph Arndt, a Scripps Research postdoctoral fellow in the Stevens lab, who conducted the x-ray crystallography work for the study along with Qing Chai, another Scripps Research postdoctoral fellow. If you block that step of recognition of the receptor, the toxin can't be internalized into the nerve cell, so it's basically shut down.

Another application for the new understanding of botulinum toxins is equally intriguing. Although botulinum toxins can have devastating effects, in very small concentrations injected directly into a specific muscle they can actually be a beneficial treatment for diseases such as cerebral palsy and multiple sclerosis that are caused by overactive nerve signaling, which the toxins can reduce. However, for reasons not completely clear, some patients do not respond to current treatments. This could be due to variations in their nerve cells that prevent the toxins from binding. If that is the case, researchers may be able to engineer toxins that bind to these variant receptors.

CU study reveals pros and cons of therapy for lead exposure

Wed, 13 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Lead chelation therapy -- a chemical treatment to remove lead from the body -- can significantly reduce learning and behavioral problems that result from lead exposure, a Cornell study of young rats finds.

However, in a further finding that has implications for the treatment of autistic children, the researchers say that when rats with no lead in their systems were treated with the lead-removing chemical, they showed declines in their learning and behavior that were similar to the rats that were exposed to lead.

Chelating drugs, which bind to lead and other metals in the blood, are increasingly being used for the treatment of autism in children.

Although these drugs are widely used to treat lead-exposed children, there is remarkably little research on whether or not they improve cognitive outcomes, the major area of concern in relation to childhood lead poisoning, said Barbara Strupp, Cornell associate professor of nutritional sciences and of psychology and the senior author of the study, which was published in a recent issue of Environmental Health Perspectives.

Studies on the safety or effectiveness of the drugs for treating autism are similarly lacking, Strupp said.

Strupp added that to her knowledge this is the first report that shows that chelation therapy can reduce behavioral and learning problems due to lead exposure as well as the first to show that this type of treatment can have lasting adverse effects when administered in the absence of elevated levels of heavy metals.

The study used succimer (brand name, Chemet), the most widely prescribed drug for the treatment of lead poisoning. Doctors prefer succimer to other such drugs because it can be given orally on an outpatient basis, and it leaches less zinc, iron and other essential minerals out of the body. Although the Centers for Disease Control recommends chelation therapy only for children whose blood lead levels exceed 45 micrograms per deciliter, such drugs as succimer are commonly administered at much lower levels of exposure, due to concerns about lasting complications with even slightly elevated blood lead levels.

It is important to remove lead from the body as quickly as possible to prevent or lessen lasting damage to the developing brain. High-lead exposure from peeling lead-based paint can lead to coma, convulsions and even death. At lower levels, lead exposure causes attention deficits, delinquency and difficulty regulating emotions and can lower IQ scores at a rate of about one IQ point per microgram/deciliter of exposure.

The study used rats -- whose mental and behavioral responses to lead exposure are similar to humans' -- and exposed them to moderate- and high-lead levels (administered via mothers' milk). A third group -- the control -- was not exposed. Exposures were followed by a treatment with succimer or placebo. Immediately thereafter, the researchers conducted automated tests over six months on the rats' attention, memory and abilities to learn and regulate emotions.

The rats with moderate-lead exposure benefited greatly from the succimer: Their test results were indistinguishable from the control test results. Rats exposed to higher lead levels showed benefits in the emotional domain: After succimer treatment, they behaved similarly to the control group. However, the treatment only slightly improved their learning deficit.

In the group that had no lead exposure but were given succimer, we found lasting cognition and emotion-regulation [deficits] that were as pervasive and large as rats with high lead exposure, said Strupp. She added that one possibility is that succimer, in the absence of lead, may disrupt the balance of such essential minerals as zinc and iron. These findings raise concerns about the use of chelating agents in treating autistic children, she said.

Study helps explain why botulinum toxin is so deadly

Wed, 13 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) MADISON - A pilot without a map can locate an airport by first finding a nearby landmark, like a big river, and then searching for the airport.

New research from the University of Wisconsin School of Medicine and Public Health (SMPH) and Scripps Research Institute shows how the astonishingly powerful botulinum toxin uses a similar strategy to latch onto nerve cells, the first step in inactivating them.

The research helps explain how the toxin first attaches to a receptor on the surface of a nerve cell, then looks for a second type of receptor that is nearby. Once the toxin links to this second receptor, it can enter the nerve cell and break a protein needed to deliver molecules that can signal other nerve cells.

By blocking this signaling molecule, tiny amounts of botulinum toxin can cause paralysis and even death through respiratory failure. The bacteria that makes this toxin grows in soil, and can be found inside cans of food that were improperly processed. Botulinum toxin is the reason for the extreme danger from bulging cans of food.

Researchers have been working on the unique nerve-blocking ability of the seven individual botulinum toxins for decades, says botulinum expert Edwin Chapman, UW-Madison professor of physiology and a Howard Hughes Medical Institute investigator. A major question is how the toxin enters neurons, he says.

The research was a close collaboration with Ray Stevens of Scripps, who crystallized the structure that forms when botulinum toxin links to the protein receptor on a nerve cell.

This is the first paper to show in atomic detail the structure of botulinum neurotoxin touching the receptor on the surface of the neuron, Chapman says. The toxin has to bind to the neuron it wants to poison. This is a snapshot of the first stage of that poisoning.

The report on the work, in the journal Nature this week, identified a short section on the protein receptor as the exact spot where botulinum toxin grips the cell immediately before entering it.

UW-Madison has long been a center of botulism research. In 2003, Min Dong, a post-doctoral fellow in Chapman's lab, showed that a known protein receptor for one botulinum toxin was a key point of entry into the nerve cell. Dong shares first authorship on the current study along with Qing Chai and Joseph Arndt of Scripps.

The Nature paper is an elaboration on that 2003 discovery, which was published in The Journal of Cell Biology. Stevens's lab bombarded a crystal of the toxin bound to a small sub-region of the primary receptor with X-rays, then measured the reflections to portray the toxin and the receptor bound in deadly embrace.

The research could have several practical applications. Botulinum toxin is a potential biological weapon, so the U.S. military is interested in finding anti-toxins to protect soldiers -- molecules that attach to the binding site on the toxin or on the cell. The search for such a blocking molecule becomes easier now that the exact structure of the link between the toxin and the nerve cell are known.

Better knowledge of botulinum toxin's structure could also enhance the growing number of treatments that use the toxin to block nerve signals. The medical treatments are not just for wrinkles, Chapman says. People with paralysis get spasms in the muscles that are shut off, and this could solve that. In a wide variety of dystonias, where spasms can cause really severe pain, this can relax the muscles.

A third potential benefit is further down the line. After the researchers found the binding site on the protein receptor, they varied it until the toxin could no longer bind to it. If a mutated toxin was made to attach to the mutated receptor, the combination might target botulinum toxin against over-active cells in the body, Chapman suggests.

Using genetic engineering, you might be able to sensitize whatever cell you want to the toxin, he says. Theoretically, such a treatment could be used to slow mucus production in the lungs of cystic fibrosis patients, or to attack hyperactive cells in a wide range of other disorders.

Overall, the research improves our knowledge of a devilishly clever toxin, says Dong. Botulinum is an enzyme - a biological catalyst -- that can move through a cell, breaking one protein molecule and quickly attacking another. Botulinum toxin attacks communications between nerve cells, one of the most sensitive parts of the animal physiology, Dong says. That provides an efficient way to immobilize an animal, far easier than targeting muscles directly.

Another reason for botulinum toxin's extraordinary power becomes clear from this study, Dong says. The toxin is only able to attach to a nerve cell that is working. If the synapse between two nerve cells is not active, all the receptors will be hiding inside the cells. But a synapse that controls a very important muscle must be firing all the time, and it will be exposing more receptors, and the toxin will therefore target them.

Botulinum toxin, he says, Only goes where it can be effective. It's like a smart bomb.

Nano design adjustment may help find, clear some water contaminants

Wed, 13 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Experiments designed to test discrepancies in theoretical computational chemistry have turned up a barely two-angstrom difference that may lead to a new approach to locate and remove dangerous toxins such as perchlorate and nitrates from the environment.

The research targets toxic groundwater contaminants that contain negatively charged ions known as anions (a-NI-ens), which are historically difficult to remove. Perchlorate, a rocket fuel additive recently linked to thyroid deficiency in women, has contaminated more than 450 wells in California alone. Nitrate contamination, which results mainly from the use of nitrogen fertilizer, is a leading cause of shutdowns of wells and public water supplies in the United States.

There is a need for improved materials that are effective at removing anions from the environment, said Darren W. Johnson, a University of Oregon chemist and co-principal investigator of a study appearing online Dec. 13 ahead of regular publication in the Journal of the American Chemical Society. A current leading strategy is anion exchange, which uses a polymeric resin to exchange an anion for one thats not a problem. (Two other currently used methods aimed at anions are biochemical denitrification and reverse osmosis.)

In the new study, led by UO doctoral student Orion B. Berryman, researchers focused on anion-pi interaction, in which a negatively charged species is attracted to a neutral electron-deficient aromatic ring, which could be incorporated into a specifically designed receptor.

Anion-pi interactions have been the focus of recent theoretical work, in which electronic structure calculations predicted that anion binding between halides and electron-deficient aromatic rings will occur over the center of a ring. However, the lab experiments on crystalline material found that the binding occurs as much as 2 angstroms, or 0.2 nanometers from the center.

It's very important to consider these off-centered anion-interactions occurring through a charge-transfer interaction, Berryman said. We looked at solid-state structures and the geometry of the interaction involved in a simple system. In these initial studies we noted significant color changes due to this off-center binding geometry found in the crystal structures.

Co-principal investigator Benjamin P. Hay, a chemist at the Pacific Northwest National Laboratory in Richland, Wash., where Berryman studied last fall as part of UO's National Science Foundation-funded internship program, said the study has important ramifications in anionophore design, crystal engineering and other aspects of supramolecular chemistry. In fact, he said, the findings indicate that prior designs may be flawed, incomplete or even misleading. We discovered an unexpected bonding motif that involves the transfer of charge from the anion to the arene -- in other words, a covalent bonding motif, Hay said. This is the first theoretical characterization of what we have termed an off-center, weak charge-transfer interaction.

Anions, of which notable examples include DNA, nitrate, pertechnetate, cyanide and chromate, play indispensable roles in biological and chemical processes, but they also can contribute significantly to environmental pollution that threatens aquatic life cycles and human health.

Johnson, in collaboration with UO chemist Michael M. Haley, now is seeking to design receptors that aim to the off-center location, with a goal of developing sensors for anion detection. Because Berryman's research produced sometimes intense color changes at binding sites, such an approach could lead to developing materials that sense the presence of these toxins and remediate them.

While 0.2 nanometers seems an insignificant distance, it could mean there's a 100 percent chance that binding cannot occur, Johnson said. We're finding that from a design standpoint, that 0.2 nanometers is a big difference.

He noted that estimating or calculating the binding distances when optimizing a receptor for positively charged binding, or cation, such as the chelation of metals by EDTA (ethylenedinitrilotetraacetic acid), is done almost exactly --s (0.01 nanometers). EDTA is widely used in industrial cleaners, detergents and textile production.

AVN944 inhibits IMPDH and induces apoptosis-related biomarkers in patients with hematologic cancers

Mon, 11 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Germantown, Md., December 11, 2006 -- Avalon Pharmaceuticals, Inc. (NASDAQ and NYSE Arca: AVRX), presented a poster detailing the effect of AVN944 on a comprehensive set of genetic and biochemical biomarkers at the American Society of Hematology 48th Annual Meeting. AVN944 demonstrated a statistically meaningful impact on IMPDH and other proteins that are critical to activities in cancer cells, including nucleotide biosynthesis, energy and metabolism, DNA replication, apoptosis and cell cycle control. The data were collected in an ongoing Phase I open-label, repeat dose-escalation study designed to evaluate the safety and tolerability of AVN944 in patients with advanced hematologic malignancies and to determine the optimal dose for Phase II efficacy trials. Further data from an interim analysis of the trial is expected to be available shortly.

IMPDH is highly upregulated in most hematological cancers and in many solid tumors, said Beverly S. Mitchell, M.D., Deputy Director of the Stanford Comprehensive Cancer Center and George E. Becker Professor of Medicine at Stanford University. IMPDH plays an essential role in cancer cell synthesis of DNA and RNA, and the inhibition of IMPDH represents a new and potentially important approach to the treatment of cancer.

Analysis of the selected markers in patient samples from the Phase I trial showed a correlation of changes in the expression of these genes to dose level and duration of exposure. Importantly, several of these markers have been shown to reflect a durable, sustained stress response indicative of cancer cell death, particularly in cancer cells from AML patients. Specifically, it was found that the gene HspA1A, a marker of stress response found to correlate with depleted GTP pools in cancer cell lines, is induced within hours upon the first treatment of the drug in patients, even at the trial's lowest doses. Following continued dosing of AVN944, this marker of disease cell stress was elevated even in the absence of circulating levels of the drug between doses. Other genes directly related to IMPDH inhibition showed similar response characteristics.

AvalonRx®, our proprietary gene expression platform, enabled us to identify a set of 34 genes that reflect the mechanism-based activity of AVN944, said David Bol, Ph.D., Senior Vice President of Product and Pharmaceutical Development at Avalon. These gene markers correlate with the biochemical effects of AVN944 on protein function, which we believe will result in tumor cell apoptosis at the right doses. Our goal for the current Phase I study is to achieve those dose levels in patients. It is very encouraging that we have not seen any drug related adverse events even though we are already seeing biomarker movements consistent with significant inhibition of the IMPDH enzyme. This indicates the potential for a good therapeutic window. Additionally, these data showcase the power of the AvalonRx® technology in understanding the pharmacologic, pharmacodynamic and biologic activity of a drug on patients in early clinical studies.

This analysis of the trial data was intended to describe how these biomarkers correlate with biologic activity of the drug in patients as the doses escalate. When comparing patients with different hematologic cancers, examination of the complete set of markers clearly demonstrated the utility of comprehensive gene expression analysis in clinical trials by distinguishing individuals with similar diseases, as well as patients with different malignancies, based on the makeup of their disease prior to drug administration as well as the different nature of the cellular response following drug administration.

Consumers neutral on risks, benefits of nano

Tue, 05 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) HOUSTON, Dec. 5, 2006 -- The largest and most comprehensive survey of public perceptions of nanotechnology products finds that U.S. consumers are willing to use specific nano-containing products even if there are health and safety risks when the potential benefits are high. The study also finds that U.S. consumers rate nanotechnology as less risky than everyday technologies like herbicides, chemical disinfectants, handguns and food preservatives.

The study, which was conducted by researchers at Rice University's Center for Biological and Environmental Nanotechnology (CBEN), University College London (UCL) and the London Business School, is the largest survey yet conducted on public willingness to use commercial nanotechnology products. It appears in the December issue of Nature Nanotechnology.

By some estimates, products containing nanotechnology already account for more than $30 billion in annual global sales, but there is concern that the public's fixation with nanotechnology's risks either real or imaged will diminish consumers' appetite for products, said lead researcher Steven Currall, a management and entrepreneurship expert who conducted the research while a faculty member at Rice and while at UCL and London Business School, where he currently holds academic appointments. Measuring public sentiment toward nanotechnology lets us both check the pulse of the industry right now, and chart the growth or erosion of public acceptance in the future.

The research was based on more than 5,500 survey responses. The authors of the article developed the surveys, which were administered by Zogby International. The surveys defined nanotechnology as involving human-designed materials or machines at extremely small sizes that have unique chemical, physical, electrical or other properties.

One survey polled consumers about how likely they would be to use four specific, nano-containing products: a drug, skin lotion, automobile tires and refrigerator gas coolant. This is the first large-scale study to experimentally gauge the public's reaction to specific, nano-containing products, and Currall said the use of scenarios about plausible, specific products yielded results that challenge the assumption that the public focuses narrowly on risk.

It was clear that people were thinking about more than risk, he said. The average consumer is pretty shrewd when it comes to balancing risks against benefits, and we found that the greater the potential benefits, the more risks people are willing to tolerate.

Study co-author Neal Lane, who helped craft the U.S.'s National Nanotechnology Initiative during his tenure as director of the White House's Office of Science and Technology Policy, said the public is likely to become more aware of nanotechnology's risks as environmental health and safety research is completed and as nanomaterials find their way into more products. What remains to be seen is whether the public's budding perceptions of the benefits of nanotechnology will also grow, he said.

We propose that academic bodies like the UK's Royal Society and the US's National Academies set up interagency clearinghouses to coordinate public education and synthesize the latest scientific findings, said Lane, senior fellow in science and technology at Rices Baker Institute for Public Policy. Transmitting the latest information about both risks and benefits, in a timely, thorough and transparent way, will minimize the likelihood of a polarized public debate that turns on rumor and supposition.

Dartmouth researchers find that low doses of arsenic have broad impact on hormone activity

Mon, 04 Dec 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Dartmouth Medical School investigators are learning more about how low doses of arsenic, such as the levels found in drinking water in many areas of the United States, affect human physiology. In a paper published online on Dec. 2 in the journal Chemical Research in Toxicology, the researchers report that three different steroid hormones all show similar responses to arsenic, suggesting a broader effect and a common mechanism of arsenic on how these hormones function.

Since most of the health consequences of exposure to arsenic - various cancers, diabetes, heart and vascular disease, reproductive and developmental effects, etc. - involve these same steroid receptors, we think that disruption of their normal function could explain, in large part, how arsenic can influence so many disease risks, says Joshua Hamilton, one of the authors on this study and the director of the Center for Environmental Health Sciences at Dartmouth and Dartmouth's Superfund Basic Research Program on Toxic Metals.

Hamilton's laboratory had earlier found that arsenic disrupts the activity of the glucocorticoid receptor, and this follow up study considered the progesterone and mineralocorticoid receptors, which regulate a wide range of biological processes. This current work was done in collaboration with Jack Bodwell, the lead author on this paper and a research associate professor of physiology at Dartmouth Medical School.

Hamilton, Bodwell, and their team found that arsenic appears to suppress the ability of all three of these critical receptors to respond to their normal hormone signals. Chemicals that disrupt steroid hormone receptor signaling are called endocrine disruptors, and this study provides further evidence that arsenic, a metal, does not behave like other endocrine disruptors such as pesticides.

Arsenic does not activate these receptors, as some endocrine disruptors do, by mimicking the natural hormone, nor does it block the ability of the normal hormones to activate their specific receptor, as most other endocrine disruptors do, says Hamilton, who is also a professor of pharmacology and toxicology at Dartmouth Medical School. Nor does it affect the ability of the hormone-activated receptor to move to the nucleus of the cell or to bind to DNA to initiate gene expression. Yet, somehow arsenic still strongly affects the ability of these hormone-activated receptors to regulate gene expression. There's still a lot more to learn.

The study also looked into the effects of different levels of arsenic on these receptors. At very low doses (comparable to what is found in drinking water at the current and previous U.S. regulatory limits, in the range of 5-50 ppb) arsenic enhances hormone-stimulated gene expression, by two- to three-fold. At slightly higher doses (in the range of 50-200 ppb, commonly found in drinking water from contaminated wells in New Hampshire and elsewhere in the U.S.) arsenic has the exact opposite effect, strongly and almost completely inhibiting hormone-stimulated gene expression by these receptors. This non-conventional dose-response suggests that arsenic might have very different biological effects at the lower and higher doses.

Elucidating these complex biological effects of arsenic on hormone signaling at different doses will be critical to our overall understanding of how arsenic influences human health, and should be considered as an important component of determining the overall disease risk of people who are exposed to arsenic in their drinking water, says Hamilton.

'Nanorust' cleans arsenic from drinking water

Thu, 09 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) HOUSTON, Nov. 9, 2006 -- The discovery of unexpected magnetic interactions between ultrasmall specks of rust is leading scientists at Rice University's Center for Biological and Environmental Nanotechnology (CBEN) to develop a revolutionary, low-cost technology for cleaning arsenic from drinking water. The technology holds promise for millions of people in India, Bangladesh and other developing countries where thousands of cases of arsenic poisoning each year are linked to poisoned wells.

The new technique is described in the Nov. 10 issue of Science magazine.

Arsenic contamination in drinking water is a global problem, and while there are ways to remove arsenic, they require extensive hardware and high-pressure pumps that run on electricity, said center director and lead author Vicki Colvin. Our approach is simple and requires no electricity. While the nanoparticles used in the publication are expensive, we are working on new approaches to their production that use rust and olive oil, and require no more facilities than a kitchen with a gas cooktop.

CBEN's technology is based on a newly discovered magnetic interaction that takes place between particles of rust that are smaller than viruses.

Magnetic particles this small were thought to only interact with a strong magnetic field, Colvin said. Because we had just figured out how to make these particles in different sizes, we decided to study just how big of magnetic field we needed to pull the particles out of suspension. We were surprised to find that we didn't need large electromagnets to move our nanoparticles, and that in some cases hand-held magnets could do the trick.

The experiments involved suspending pure samples of uniform-sized iron oxide particles in water. A magnetic field was used to pull the particles to out of solution, leaving only the purified water. Colvin's team measured the tiny particles after they were removed from the water and ruled out the most obvious explanation: the particles were not clumping together after being tractored by the magnetic field.

Colvin, professor of chemistry, said the experimental evidence instead points to a magnetic interaction between the nanoparticles themselves.

Co-author Doug Natelson explains, As particle size is reduced the force on the particles does drop rapidly, and the old models were correct in predicting that very big magnetic fields would be needed to move these particles.

In this case, it turns out that the nanoparticles actually exert forces on each other, said Natelson, associate professor of physics and astronomy and in electrical and computer engineering. So, once the hand-held magnets start gently pulling on a few nanoparticles and get things going, the nanoparticles effectively work together to pull themselves out of the water.

Colvin said, It's yet another example of the unique sorts of interactions we see at the nanoscale.

Because iron is well known for its ability to bind arsenic, Colvin's group repeated the experiments in arsenic-contaminated water and found that the particles would reduce the amount of arsenic in contaminated water to levels well below the EPA's threshold for U.S. drinking water.

Colvin's group has been collaborating with researchers from Rice Professor Mason Tomson's group in civil and environmental engineering to further develop the technology for arsenic remediation. Colvin said Tomson's preliminary calculations indicate the method could be practical for settings where traditional water treatment technologies are not possible. Because the starting materials for generating the nanorust are inexpensive, she said the cost of the materials could be quite low if manufacturing methods are scaled up. In addition, Colvin's graduate student, Cafer Yavuz, has been working for several months to refine a method that villagers in the developing world could use to prepare the iron oxide nanoparticles. The primary raw materials are rust and fatty acids, which can be obtained from olive oil or coconut oil, Colvin said.

Heavy smoking cuts women's chance of pregnancy -- even with donated oocytes

Wed, 08 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) Heavy smoking may reduce female fertility by directly affecting the uterus making it less receptive and reducing the chances the embryo will implant, according to research published on line (Thursday 9 November) in Europe's leading reproductive medicine journal Human Reproduction[1].

The finding, from a team of fertility experts in Portugal and Spain, comes as a result of comparing the pregnancy rates between non-heavy smokers[2] and heavy smokers, all of whom received donated oocytes.

Smoking has long been known to affect female fertility, but this study is believed to be the first to examine the impact of smoking in women who have received donated oocytes the situation that allows the most objective assessment of the role of the uterus in the outcome of IVF.

The researchers studied all the first cycles of oocyte-donated IVF treatments carried out at the IVI-Valencia Foundation between the start of 2002 and June 2005 741 in non-heavy smokers (under 10 cigarettes a day) and 44 in heavy smokers (over 10 a day). None of the women's partners were smokers and none of the oocyte donors were heavy smokers. The two groups of recipients were comparable and the number of embryos transferred in each cycle (between one and three) was also comparable between the groups.

Lead researcher Dr Sérgio Soares, Director of the IVI Clinic in Lisbon, said: The non-heavy smokers had a significantly higher pregnancy rate, with over half becoming pregnant (52.2%), compared with just over a third (34.1%) of the heavy smokers.

This means we have confirmed previous data that show light smoking has no significant impact on IVF cycles, either through affecting the ooctye or the uterus. But, heavy smokers have a much lower chance of achieving pregnancy. The fact that we see this result in a situation in which the oocytes were donated by other women demonstrates that cigarette smoking negatively affects the receptiveness of the uterus independently of its effect on ovarian function, and this is a new finding.

Although the pregnancy rate was much lower in heavy smokers, for those that did become pregnant the multiple pregnancy rate was much higher, with 60% of the heavy smokers expecting twins against 31% of the non-heavy smokers.

This is counter-intuitive, said Dr Soares, and although we controlled for all known interfering variables, it is possible this is not a real association. What would confirm it as a real association is to find it still applies in a large number of cases. However, if it is confirmed as a real association it suggests that, paradoxically, tobacco constituents affect the uterus in different ways in different women, impairing implantation in some and having the opposite effect in others.

It is already known that there is paradoxical dose-dependent effect of nicotine on ovarian tissue. Maybe the same effect is happening in uterine tissue. The effect of a certain molecule depends, not only on its concentration, but also on the concentration of its receptors and all the other molecules present in the cell. It could be that heavy smoking disrupts the stability of cells in the lining of the uterus differently in some women to others or triggers a response in the embryo itself, resulting in a reduced general pregnancy rate overall, but an increased chance of multiple pregnancy in those who do become pregnant.

Dr Soares said, that as well as confirming these findings in higher numbers of heavy smokers who use donated oocytes, it would be worthwhile studying differences in gene expression in the lining of the uterus of heavy smokers who fail to get pregnant and those whose have twins.

But, for now, the clinical implications of the findings were clear. Tobacco makes the uterus less likely to accept an embryo.

In spite of all the noise generated about the effects of smoking in a series of health areas, its possible effect on uterine receptiveness has never been evaluated until now, he said.

Our study is just the first step on this path, and certainly not the last, but it means that we should now be telling patients, if they are heavy smokers, that even if fertilisation takes place they have less chance of achieving a successful pregnancy, whether they are trying to conceive naturally, or through IVF, and particularly with donated ooctyes. Furthermore, we should also warn them of the risks of multiple births, as multiple births are less safe for mothers or babies.

Lungs try to repair damaged elastic fibers

Fri, 03 Nov 2006 05:00:00 PST

( from http://www.rxpgnews.com ) FORT LAUDERDALE, Fla. (Nov. 3, 2006) -- The lungs of patients suffering chronic obstructive pulmonary disease (COPD) attempt to repair damaged elastic fibers, a new finding that contradicts the conventional wisdom on the capabilities of the adult lung.

The study Evidence for attempted regional elastic fiber repair in severe emphysema, was done by Jason Woods, Kristin Castillo, Alexander Patterson and Richard Pierce of Washington University, St. Louis, Mo.; Joel Cooper of the University of Pennsylvania, Philadelphia; and James Hogg of St. Paul's Hospital, Vancouver, British Columbia. The authors will be present their findings Nov. 3 at The American Physiological Society conference Physiological Genomics and Proteomics of Lung Disease.

The researchers found that synthesis of elastin, a gene linked to elastic fiber growth, is increased in the moderately diseased tissue of COPD patients. Elastic fibers allow the lung to expand and contract with breathing.

We've found elastin synthesis to increase in the air sacs (alveoli) and airways of the lungs of patients suffering severe or end-stage COPD, Woods explained. This shows that the lung may be attempting to repair itself.

The finding is important because it could pave the way to develop a drug to 'turn on' key genes to allow the lung to grow new alveoli, he said. Alveoli play a role in the exchange of oxygen and carbon dioxide between the lungs and the circulatory system.

A 2-year-old could do it

Very young children who suffer lung injuries increase elastin expression and produce new elastic fibers inside the alveoli, Woods said. Adults do not have that ability and that has led physiologists to conclude that the elastin gene must shut off after we reach a certain age, ending elastin fiber production.

Physiologists want to understand this process in the hope that it could be harnessed to repair the diseased adult lung. In particular, Woods and his colleagues looked at three genes associated with elastic fiber assembly: Emilin-1, MFAP2 and elastin. They found the expression of elastin consistently increased in the diseased lungs they studied.

In a preliminary study, the researchers examined two diseased lungs removed from end-stage COPD patients undergoing lung transplants. COPD develops as a result of exposure to toxins such as cigarette smoke, resulting in inflammation to the small airways and destruction of elastic fibers within alveoli. The patients suffered from emphysema.

The team used hyperpolarized magnetic resonance imaging (MRI) to characterize the regions of the lung showing moderate emphysema and regions showing severe emphysema. They found that new elastin synthesis was initiated in moderately diseased specimens.

The researchers did a second study using 10 lungs from end-stage COPD patients who had undergone transplants. Again, they found the greatest amount of elastin gene expression in the moderately diseased areas of the lungs, Woods said. There was no variability in elastin levels within the control lungs.

Further, the team found that the increase in elastin expression occurred on the alveolar walls, the same area where elastin occurs during the lung's development in children. This shows the lung is attempting to repair the elastic fibers in end-stage emphysema, the authors concluded.

Mouse DNA to aid biomedical research

Wed, 25 Oct 2006 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers announced today that they have successfully resequenced the DNA of 15 mouse strains most commonly used in biomedical research. More than 8.3 million single nucleotide polymorphisms (SNPs) were discovered among the genomes of the 15 mouse strains and the data are now publicly available. These new data will help researchers better understand complex genetic traits, such as why some individuals are more susceptible to certain diseases, and will serve as a valuable resource in determining how environmental agents influence the development of disease.

Single Nucleotide Polymorphisms, or SNPs (known as snips), are single genetic changes, or variations, that can occur within a DNA sequence. Because mice and humans share many of the same fundamental biological and behavioral processes, including gene functions, these data will help researchers understand human genetic susceptibility to almost 200 diseases such as Parkinson's, cancer, diabetes, heart and lung diseases, reproductive diseases, and asthma and other childhood diseases, which are affected by exposure to environmental substances.

Making this wealth of data freely available to the research community is a significant milestone, said David A. Schwartz. M.D., director of the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, which funded the research. Each mouse strain is genetically unique. Now that we know the DNA variations for these mouse strains, we can compare the genetic makeup of one strain that acquires a certain disease to another strain that does not get the same disease. In this way researchers gain insight into the same processes that may cause one human to get a disease while another human in the same environment remains disease-free.

The Resequencing and SNP Discovery Project began less than two years ago through a contract between the National Toxicology Program at NIEHS and Perlegen Sciences, Inc. of Mountain View CA. Perlegen scientists conducted the project using as a standard reference the 2003 DNA sequencing of the C57BL/6J mouse strain -- the very first mouse strain to undergo DNA sequencing. The mouse models included in the resequencing project are: 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, C3H/HeJ, CAST/EiJ, DBA/2J, FVB/NJ, MOLF/EiJ, KK/HlJ, NOD/LtJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ. The 15 mouse strains were carefully chosen because of their routine use as research models and their genetic diversity. The project used the same high-density oligonucleotide array technology that was used to discover common DNA variation in the human genome.

Perlegen Sciences was excited to perform this scientific work, because it promised to provide an extremely valuable resource. We believe the data will generate a lot of knowledge about complex genetic traits, said Kelly Frazer, Vice President of Genomics at Perlegen Sciences, Inc.

This project was highly anticipated by scientists. Now, we can go to our computer, click on the mouse strain we want to use, see the sequence variations for that strain and compare it to the others, said David Threadgill, Ph.D., an expert in mouse models of disease at the University of North Carolina, Chapel Hill. If we use multiple strains, we can then look at the data after the animals are exposed to an environmental substance and compare the genetic differences between the strains that acquired a disease and those that did not. This will help us begin to identify causes of differential susceptibility to disease.

These mouse data will aid in our understanding of 'counterpart' genes in humans, the corresponding molecular and biological pathways the lead to disease susceptibility, and the environmental agents that trigger the development of disease in susceptible people, said David Christiani, M.D., Professor of Medicine at Harvard Medical School and Professor of Occupational Medicine and Epidemiology at Harvard School of Public Health. The data will also be a great resource for pharmaceutical companies that are developing new treatments for disease.

Drug combo improves survival in patients with COPD

Mon, 23 Oct 2006 04:00:00 PST

( from http://www.rxpgnews.com ) A combination of two common medications may help patients with chronic obstructive pulmonary disease (COPD) live longer. New research presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP), shows that when used in combination, inhaled salmeterol (SAL) and fluticasone propionate (FP) reduced the risk of dying by up to 17.5 percent in patients with COPD. Currently, FP, an inhaled corticosteroid, and SAL, a long-acting B2-agonist bronchodilator, are used alone and in combination to treat both asthma and COPD.

The combination therapy of salmeterol and fluticasone is the first intervention since oxygen therapy or smoking cessation to show improved survival in patients with COPD, said study author Bartolome R. Celli, MD, FCCP, of Caritas-St. Elizabeth's Medical Center, Boston, MA. The improvement was comparable with that produced by statins in cardiovascular mortality. This represents an important step forward in the management of COPD.

As part of the TOwards a Revolution in COPD Health (TORCH) study, researchers from the United Kingdom, Denmark, Australia, and the United States investigated whether the combined therapy of salmeterol and fluticasone (FSC) would significantly impact survival in patients with COPD. Patients (n=6,112) with moderate to severe COPD from 42 countries were included in the 3-year, double-blind trial. Of the patients (76 percent men, mean age 65 years), 1,534 received FP; 1,521 received SAL; 1,533 received FSC; and the remaining patients received a placebo. Results were clinically significant, showing that FSC reduced the risk of dying at any time by 18 percent compared with placebo over the 3-year period, with absolute reduction rates being 15.2 percent and 12.6 percent, respectively. Secondary endpoints also were significant, including reduction in exacerbations, improvement in quality of life, and lung function. Furthermore, there was a trend in the reduction in COPD-related mortality with FSC vs placebo (6.0% vs 4.7%). Overall, survival was better for patients on combined therapy than for FP alone. Mortality for the active combination also was lower than for SAL, but the difference was not statistically significant.

We do not know the exact mechanism by which this combined therapy works better than the separate therapies. We speculate that synergistic action on cell receptors may lead to less muscle contraction or inflammation, said Dr. Celli. Although we do not expect the combination therapy to replace existing therapies, it will allow greater room for intervention for health-care providers treating patients with COPD.

COPD is a progressive and debilitating lung disease most often caused by smoking, said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. There is no cure for COPD, but smoking cessation and other effective treatments can slow the damage brought about by smoking. Physicians should encourage their patients who smoke to quit in order to avoid further lung damage.

Biodegradable 'napkin' could help quickly detect, identify biohazards

Mon, 11 Sep 2006 04:00:00 PST

( from http://www.rxpgnews.com ) SAN FRANCISCO, Sept. 11 - Detecting bacteria, viruses and other dangerous substances could soon be as simple as wiping a napkin or paper towel across a table, according to Cornell University researchers. Once fully developed, the new absorbent wipe, embedded with nanofibers containing antibodies to numerous biohazards, could be used by virtually anyone to rapidly uncover pathogens in meat packing plants, hospitals, cruise ships, airplanes and other commonly contaminated areas, the researchers say.

The materials for this new process, which is still being tested in the laboratory, were described today at the 232nd national meeting of the American Chemical Society, the world's largest scientific society.

It's very inexpensive, it wouldn't require that someone be highly trained to use it, and it can be activated for whatever you want to find, said Margaret Frey, Ph.D., Lois and Mel Tukman assistant professor of textiles and apparel at Cornell. So if you're working in a meat packing plant, for instance, you could swipe it across some hamburger and quickly and easily detect E. coli bacteria. If biohazards were detected, she added, the area could be scoured and re-tested to confirm the contaminants were destroyed.

In their experiments, Frey and her colleagues formed nanofibers with diameters between 100 nanometers and 2 microns (a human hair is about 80,000 nanometers wide). On these nanofibers, the researchers created platforms made of biotin, a B-vitamin and the protein streptavidin to hold the antibodies. The nanofibers, which are made of polyactide (PLA) - a polymer compound made from corn - can be used to make non-woven wipers or swabs. To reduce costs, the nanofibers also could be incorporated into conventional paper products.

The fabric basically acts as a sponge that you can use to dip in a liquid or wipe across a surface, Frey said. As you do that, antibodies in the fabric are going to selectively latch onto whatever pathogen that they match. Using this method we should, in theory, be able to quickly activate the fabric to detect whatever is the hazard of the week, whether it is bird flu, mad cow disease or anthrax.

For now, identifying the collected pathogens requires a separate analytical step. But Frey and colleagues are working on methods, such as color changes in the fabric, which would instantly identify the contaminant.

We're probably still a few years away from having this ready for the real world, Frey said, but I really believe there is a place for this type of product that can be used by people with limited training to provide a fast indication of whether a biohazard is present.

New methods for screening nanoparticles

Mon, 21 Aug 2006 04:00:00 PST

( from http://www.rxpgnews.com ) UPTON, NY - Scientists at the U.S. Department of Energy's Brookhaven National Laboratory have developed a screening method to examine how newly made nanoparticles -- particles with dimensions on the order of billionths of a meter -- interact with human cells following exposure for various times and doses. This has led to the visualization of how human cells interact with some specific types of carbon nanoparticles. The method is described in a review article on carbon nanoparticle toxicity in a special section of the August 23, 2006, issue of the Journal of Physics: Condensed Matter devoted to developments in nanoscience and nanotechnology, now available online.

Nanoparticles may have different physical, chemical, electrical, and optical properties than occur in bulk samples of the same material, in part due to the increased surface area to volume ratio at the nanoscale. Many scientists believe that understanding these nanoscale properties and finding ways to engineer new nanomaterials will have revolutionary impacts -- from more efficient energy generation and data storage to improved methods for diagnosing and treating disease. Brookhaven Lab is currently building a Center for Functional Nanomaterials (CFN) with state-of-the-art facilities for the fabrication and study of nanomaterials, with an emphasis on atomic-level tailoring of nanomaterials and nanoparticles to achieve desired properties and functions.

Nanomaterials show great promise, but because of their extremely small size and unique properties, little is known about their effects on living systems, said lead author Barbara Panessa-Warren, a Brookhaven biologist who has been developing a nanoparticle cytotoxicity-screening model for the past five years. Our experiments may provide scientists with information to help redesign nanoparticles to minimize safety concerns, and to optimize their use in health-related applications. They may also lead to effective screening practices for carbon-based materials.

A variety of studies conducted in living animals, which are described in the review article, have found a range of toxic effects resulting from exposure to carbon-based nanoparticles. All of these in vivo studies clearly show that multiple factors interact following nanoparticle exposure to produce acute and chronic changes within individual cells and the organism itself. In vitro laboratory studies, such as the cell-culture method developed by the Brookhaven team, are an attempt to simplify the research by eliminating many of the variables found in animal studies, giving researchers greater control over experimental conditions.

By combining techniques of molecular biology with sophisticated imaging methods, we can rapidly gather information about the response of specific cell types to specific nanoparticles, making in vitro testing an inexpensive and immediate tool for screening and fine-tuning nanoparticle design to maximize safety and target specificity, Panessa-Warren said.

In the Brookhaven team's studies, the scientists used lung and colon epithelial cells -- chosen to represent two likely routes of nanoparticle exposure (inhalation and ingestion) -- grown as cell monolayers, where the individual cells join together to form a tight layer with many of the characteristics of lung and colon cells growing in the body as an epithelial layer. These monolayers of living cells are then exposed to varying doses of carbon nanoparticles over differing amounts of time, and the cells are studied at each time period and dose.

The scientists also tested the response of the cells to different types of nanoparticles (a raw nanotube preparation containing mostly single-walled carbon nanotubes, nanoropes, graphene and trace elements; partially cleaned air-oxidized carbon nanotubes; as well as, carbon-nanotube-derived loops used to carry antibodies). They assessed cell viability (did the cells live or die?) and growth characteristics of the monolayer, and examined any alterations within the cells using various microscopy techniques. These techniques enabled them to visualize the first contact of the nanoparticles with the cells and follow this process ultrastructurally so they could see how the cells responded and determine whether the nanoparticles entered the cells or caused specific changes to the cell surfaces of those cells that did not die.

Using this in vitro screening, the scientists found that a type of engineered carbon nanoparticle called a 'nanoloop,' which was made at Brookhaven, did not appear to be toxic to either cell type regardless of dose and time. In contrast, both colon and lung cells exposed to carbon nanoparticles from the raw nanotube preparation showed increased cell death with increased exposure time and dose. Microscopic studies revealed losses of cell-to-cell attachments in the monolayers, and changes in cell-surface morphology on cells where carbon nanotubes and other carbon nanoparticles had attached. Damage was severe for both the low and higher doses at three hours, suggesting that exposure time may be even more predictive of damage than nanoparticle concentration.

Using electron microscopy, the scientists found that areas in which the carbon nanoparticles, and especially carbon nanotubes, touched or attached to the cell surface, the plasma membranes became damaged and were microscopically interrupted. Images of the cell surfaces with attached carbon nanoparticles showed membrane holes that exposed the underlying cell cytoplasm. Transmission electron microscopy revealed that small carbon particles could pass into the cells and become incorporated into the cell nuclei. Neighboring cells with no attached carbon nanoparticles appeared normal and continued to grow, suggesting that direct contact with untreated nanoparticles is required for damage to occur. These findings agree with recent biochemical studies in the literature that reported the production of reactive oxygen species (free radicals) and lipid peroxidation of cell membranes following living cell contact with other forms of carbon nanoparticles called fullerenes, also known as buckyballs.

Although our screening method gives us a quick way to analyze human cell responses to nanoparticles at a visual macro- and micro- scale, we are now taking this to a molecular and genetic level to see whether the cells are stressed, said Pannessa-Warren.

Ultimately any new nanomaterials intended for large-scale production or use would also have to be tested in vivo -- where the combined reactions of many cell types and tissues, as well as the blood, immune, and hormonal factors, are all taken into account to assess biocompatibility and assure safety, she added. Still, our methods give us a way to screen-out those nanoparticles that shouldn't even make it that far, or identify ways to improve them first.

New Queen's study offers environmentally friendly solution to oil industry needs

Thu, 17 Aug 2006 04:00:00 PST

( from http://www.rxpgnews.com ) KINGSTON, Ont. -- Queen's University researchers have devised a green chemistry solution to one of the oil industry's biggest problems in a cost-effective way.

Their findings will be published in the international journal Science on Friday August 18.

The study addresses the recurring problem of separating oil and water mixtures, and targets diverse applications including cleaning up oil spills, and extracting oil deposits from tar sands and reservoirs. Other potential beneficiaries are plastics manufacturers, chemical and pharmaceutical companies, mining companies and makers of cleaning products.

The new process can be used whenever industry requires an emulsion (the mixture of two liquids in which droplets of one are suspended evenly throughout the other), explains lead researcher and Queen's Chemistry Professor Philip Jessop. This might occur when cleaning spills, extracting oil from the ground, de-greasing metal equipment or metal surfaces, and manufacturing chemical products such as plastics.

Since oil and water don't normally mix, it's necessary to add a surfactant (surface active agent) in the layer between them before you can create an emulsion. The problem is that in many situations, you later want the water and oil to separate again, he continues. But of the 'switchable' surfactants known so far, one is very expensive and contains metals, another is extremely toxic, and the third type is activated by light which doesn't work well with opaque emulsions.

Old-fashioned soap can be made to switch but that requires large amounts of acid to be added, which is not desirable, says Dr. Jessop, Canada Research Chair in Green Chemistry. The surfactant developed by the Queen's team is also completely reversible and does not require metals, acid, or light. Exposure to carbon dioxide (CO2) activates it, while bubbling air through the liquid turns it off again. CO2 and air were chosen because they are cheap, non-toxic and environmentally benign: the CO2 can be recycled material from power plants.

You can do this over and over, timing it for exactly when you want the switch to occur, Dr. Jessop notes. And when the surfactant is turned off, causing oil and water to separate, the now-clean water may be returned to its source or recycled.

The new surfactant builds on Dr. Jessop's discovery last year of switchable solvents that change their properties when alternately exposed to carbon dioxide and nitrogen, making it possible to re-use the same solvent for multiple steps in a chemical process.

Right now there are big separation problems causing enormous headaches in the oil industry, says Dr. Jessop. If 'green chemistry' can solve these problems, then the environment benefits and companies profit financially as well. It's very much a win-win situation.