RxPG News Feed for RxPG News

Medical Research Health Special Topics World
  Home
 
   Health
 Aging
 Asian Health
 Events
 Fitness
 Food & Nutrition
 Happiness
 Men's Health
 Mental Health
 Occupational Health
 Parenting
 Public Health
 Sleep Hygiene
 Women's Health
 
   Healthcare
 Africa
 Australia
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 UK
 USA
 World Healthcare
 
 Latest Research
 Aging
 Alternative Medicine
 Anaethesia
 Biochemistry
 Biotechnology
 Cancer
 Cardiology
 Clinical Trials
 Cytology
 Dental
 Dermatology
 Embryology
 Endocrinology
 ENT
 Environment
 Epidemiology
 Gastroenterology
 Genetics
 Gynaecology
 Haematology
 Immunology
 Infectious Diseases
 Medicine
 Metabolism
 Microbiology
 Musculoskeletal
 Nephrology
 Neurosciences
 Obstetrics
 Ophthalmology
 Orthopedics
 Paediatrics
 Pathology
 Pharmacology
 Physiology
 Physiotherapy
 Psychiatry
 Radiology
 Rheumatology
 Sports Medicine
 Surgery
 Toxicology
 Urology
 
   Medical News
 Awards & Prizes
 Epidemics
 Launch
 Opinion
 Professionals
 
   Special Topics
 Ethics
 Euthanasia
 Evolution
 Feature
 Odd Medical News
 Climate

Last Updated: Oct 11, 2012 - 10:22:56 PM
Research Article
Latest Research Channel

subscribe to Latest Research newsletter
Latest Research

   EMAIL   |   PRINT
New cancer fighter may help ICU patients beat infections

Aug 27, 2007 - 4:00:00 AM
He hopes to move ahead soon with clinical trials of HSP 90 inhibitors, used in conjunction with antibiotics, in intensive care patients.

 
[RxPG] HSP 90 inhibitors, which are finding favor in fighting cancer, may also help battle overwhelming infection in intensive care patients, researchers say.

Studies in an animal model of sepsis, a major cause of ICU patient death, indicate HSP 90 inhibitors help degrade proteins perpetuating inflammation, says Dr. John D. Catravas, director of the Medical College of Georgia Vascular Biology Center.

Results include restored lung function, reduced blood vessel leakage, which can lead to dangerous swelling in the lungs, and fewer byproducts of inflammation such as white blood cells, MCG researchers report in the American Journal of Respiratory and Critical Care Medicine, a journal of the American Thoracic Society.

They already have begun looking at the impact of HSP 90 inhibitors on the function of other organs, such as the liver and kidneys, also typically impacted by sepsis.

�We would die without an inflammatory response, but unreined inflammation is bad,� says Dr. Catravas. That�s just what happens with overwhelming infection; inflammation, which helps the body eliminate invaders, essentially keeps working after invaders are gone and the new target is the body.

�These are proteins that initially are useful in combating an invading bacteria but then, in some of us that develop sepsis for reasons that are poorly understood, the inflammatory response is amplified and stays much longer than it should,� says Dr. Catravas, the paper�s corresponding author.

Heat shock proteins carry proteins where they are needed and fold them up nicely so they do the correct job. Dr. Catravas compares their two-protein configuration to a lobster with its claws closed while tending to �client� proteins.

�The hypothesis we worked on is that these HSP 90 inhibitors take the heat shock protein and move it into a different conformation,� says Dr. Catravas. The published research indicates they were correct and that inhibitors, fortunately, readily target proteins that no longer have a useful function.

�The HSP 90 inhibitor binds to a little pocket in the dimer, the two identical proteins that make up HSP 90 complex, and forces the two claws open,� he says. �As soon as they open, as soon as the three-dimensional conformation of the HSP dimer and the client protein change, other proteins start attaching to the complex.� The client protein then becomes susceptible to degradation. It was their earlier finding that inducible nitric oxide synthase, a major mediator of sepsis, is a client protein of HSP 90 that led to the inhibitor study.

For the study, researchers used what would be considered lethal doses of endotoxin to create a worse-case infection and pretreated animals with smaller doses of HSP 90 than those currently under study for a wide range of cancers.

They have begun looking at more clinically relevant infection levels and identifying the best time after the insult to give the lowest dose. However, Dr. Catravas has not ruled out HSP 90 inhibitors� potential to preventively treat patients at risk because patients seem to tolerate it well in the cancer clinical trials.

He hopes to move ahead soon with clinical trials of HSP 90 inhibitors, used in conjunction with antibiotics, in intensive care patients.

These manmade HSP 90 inhibitors work by attaching where the protein pair�s energy source, called ATP, should be. The body appears to have an endogenous version, ADP, which has one less phosphate than ATP and binds at the same site, also opening the protein claws and sending the client protein toward degradation.




Publication: American Journal of Respiratory and Critical Care Medicine

Funding information and declaration of competing interests: National Institutes of Health

Advertise in this space for $10 per month. Contact us today.


Related Latest Research News


Subscribe to Latest Research Newsletter

Enter your email address:


 Feedback
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 
Contact us

RxPG Online

Nerve

 

    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)