XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
  Anti-Inflammatory
  Antivirals
  Antihypertensives
  Anticholesterol
  Anti-Clotting Drugs
  Anti Cancer Drugs
  Hypnotics
  PPI
  Antibiotics
  Analgesics
  Surfactants
  Fatty Acids
  Adrenergics
  Metals
  Varenicline
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
 
 India
Search

Last Updated: Nov 18, 2006 - 12:32:53 PM

Pharmacology Channel
subscribe to Pharmacology newsletter

Latest Research : Pharmacology

   DISCUSS   |   EMAIL   |   PRINT
NRTIs limits the atherogenic side effect of the protease inhibitors
Sep 5, 2006 - 6:20:00 PM, Reviewed by: Dr. Rashmi Yadav

"The combination prevented the negative cardiovascular effect, hardening of the arteries, of the protease inhibitors without reducing the effectiveness of the protease inhibitors on HIV."

 
Physiologists may have found a way to decrease the risk of hardening of the arteries that accompanies the long-term use of protease inhibitors, a class of drugs that has emerged as the most effective treatment against HIV and AIDS.

Writing in the American Journal of Physiology�Cell Physiology, researchers from the University of Kentucky found that when mice were given a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor in combination, it prevented hardening of the arteries often associated with long-term use of protease inhibitors alone. The mice received ritonavir, a common protease inhibitor, in combination with d4T or didanosine, which are common NRTIs.

"The combination prevented the negative cardiovascular effect, hardening of the arteries, of the protease inhibitors without reducing the effectiveness of the protease inhibitors on HIV," said the study's senior author, Eric J. Smart. "To our knowledge, these are the first data that indicate that nucleoside reverse transcriptase inhibitors can limit the atherogenic (tendency to form lipid deposits in the arteries) effects of ritonavir," the authors wrote.

The study also found:

-Although protease inhibitors alone caused cholesterol to build up in mouse arteries, the increased cholesterol could not be detected in the blood. "This means that when doctors test for cholesterol on human patients who are using protease inhibitors, their cholesterol levels may look normal even when they are not," Smart said. "In other words, the accumulation of cholesterol within the arteries is a silent problem."

-Although Vitamin E, an antioxidant, has been shown to prevent the negative effects of protease inhibitors in vitro (in the test tube), the vitamin provided no benefit to the mice in this study.

The study, entitled "Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C," was carried out by Emily L. Bradshaw, Xian-An Li, Theresa Guerin, William V. Everson, Melinda E. Wilson, Annadora J. Bruce-Keller, Richard N. Greenberg, Ling Guo, Stuart A. Ross and Eric J. Smart. The researchers are from the University of Kentucky and the Veterans Administration Medical Center in Lexington. The American Physiological Society published the study.

Long-term side effects a concern

Protease inhibitors have been effective in prolonging the lives of people with AIDS, so much so that patients now survive long enough to develop side effects that are years in the making. One such side effect is atherosclerosis, the accumulation of cholesterol and foam cells in the arteries, causing the vessels to narrow and harden.

Atherosclerosis is a problem in the general population, but protease inhibitors accelerate the process by increasing production of the protein CD36 within macrophages, which fight infections by consuming unwanted materials. CD36 spurs macrophages to eat cholesterol: The more CD36 the body produces, the more cholesterol the macrophages consume.

The problem occurs when cholesterol-laden macrophages get stuck in artery walls. Over time, they accumulate, block the arteries and can result in heart attacks. Because protease inhibitors prompt the CD36-rich macrophages to accumulate more cholesterol, the cholesterol and foam cells build faster and thus lead the arteries to harden more quickly, Smart explained.

Ritonavir produces greater blockage

The researchers examined macrophages isolated from mice receiving ritonavir, a protease inhibitor, and d4T and didanosine, both NRTIs. "NRTIs completely prevented the upregulation of CD36 and the development of atherosclerosis," the authors wrote. Their results also suggest that the NRTIs prevented the increase in CD36 by decreasing protein kinase C, an enzyme that changes the function of proteins.

What's more, NRTI reduced the negative effect of macrophages and cholesterol without reducing the effectiveness that ritonavir had against HIV. "So by giving both drugs at the same time, you get the positive effects of the protease inhibitors without the negative effect of hardening of the arteries," Smart concluded.

The researchers are now beginning a short-term study with healthy human volunteers to see if the protease inhibitor/NRTI drug combination will help control the production of CD36 in humans as well, Smart said.

"We'll try to find out if the NRTI regimen can keep the CD-36 protein in check in the non-infected volunteers," Smart said. If the drug combination works, the researchers will move to further clinical trials.
 

- American Journal of Physiology '�Cell Physiology
 

 
Subscribe to Pharmacology Newsletter
E-mail Address:

 

Funding

The National Institutes of Health funded the study.

The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.



Related Pharmacology News

Phase Ib Trial Is Evaluating Bavituximab Administered With Common Chemotherapy Regimens
Two-component lantibiotic with therapeutic potential discovered
Prescription pain medication abuse on rise
Antibiotic inhibits cancer gene activity
NRTIs limits the atherogenic side effect of the protease inhibitors
Cyclin-dependent kinase inhibitors: The latest anti-inflammatory
FDA requested to promptly approve 17-P to prevent premature birth
Rapamycin shown to inhibit angiogenesis
Tigecycline, world�s first glycylcycline expanded broad-spectrum antibiotic, launched in UK
Ibuprofen - worsening cognitive function


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

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us