A Killer Turned Kind: Carbon Monoxide Protects Transplanted Kidneys In Rats
Carbon monoxide, a highly toxic gas often called the "silent killer," may prove useful for extending the life of transplanted organs, suggests a University of Pittsburgh study that found prolonged, low-dose exposure to be protective against chronic rejection in a rat kidney transplant model. Chronic rejection is the primary reason that patients require second or third transplant operations.
In the study, to be published in an upcoming issue of the American Journal of Physiology-Renal Physiology and available now as an online publication, the researchers report minimal signs of inflammation and tissue damage indicative of chronic rejection following kidney transplantation in rats housed for 30 days in cages with air consisting of 20 parts per million of carbon dioxide. In contrast, the kidneys transplanted into rats maintained in normal air conditions began to deteriorate almost immediately, and microscopic examination revealed progressive rejection. Both groups were given a six-day course of the anti-rejection drug tacrolimus.
Although carbon monoxide is toxic at high concentrations, at low concentrations it appears to function as a signaling molecule that protects cells against bombardment by the inflammatory immune response, says senior author Noriko Murase, M.D., associate professor of surgery at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine. The idea to study the effects of carbon monoxide in the transplant setting came from co-author Augustine Choi, M.D., professor of medicine and chief of the division of pulmonary, allergy, and critical care medicine, who is a leading expert on the effects of carbon monoxide.
Contact: Lisa Rossi, (412) 647-3555, RossiL@upmc.edu
Two Out Of Three Is The Key: Measuring Several Inflammatory Markers Rather Than a Single Marker Offers Better Prediction of Cardiovascular Disease Risk
Measuring levels of several inflammatory markers rather than a single marker can substantially improve assessment of cardiovascular disease (CVD) risk, according to a study published in the November issue of the American Heart Journal by University of Pittsburgh researchers and others.
Currently, medical guidelines recommend measuring a particular inflammatory marker, called C-reactive protein, along with cholesterol levels, for assessing CVD risk. In this study, researchers from the University of Pittsburgh Medical Center's Cardiovascular Institute and the University of Pittsburgh Graduate School of Public Health (GSPH) analyzed blood samples taken from 580 women age 31 to 85 looking for multiple inflammatory markers. The investigators also performed coronary angiographies to detect any blockage of blood vessels in the heart and then followed the women for an average of almost five years. Of interest to the researchers was whether the women experienced any heart attacks (both nonfatal and fatal), strokes, or episodes of congestive heart failure.
Women with significantly elevated levels of at least two of three markers (interleukin-6, serum amyloid A, and C-reactive protein) had a more than four-times greater risk of dying compared to women who had no elevated markers. According to the lead author, Kevin E. Kip, Ph.D., assistant professor of epidemiology, GSPH, this was a higher conferred risk than any single marker alone, all of which were roughly equally predictive.
Surprisingly, the authors, which also included researchers from the American Cardiovascular Research Institute, the University of Florida College of Medicine and Cedar-Sinai Medical Center, suggest the negative effects of inflammation on CVD may be largely due to other mechanisms than the most widely accepted theory of the effects of inflammation on CVD -- promoting the buildup of plaques in the inner linings of arteries. Rather, they said inflammation may potentially lead to the destabilization of vulnerable plaques.
Contact: Jim Swyers, (412) 647-3555, SwyersJP@upmc.edu
Passing on Prevention: Large Percentage of African Americans and Diabetics Not Using Aspirin to Ward Off Heart Disease
In recent years, regular aspirin use by older adults to prevent heart disease has increased, particularly among those at high risk, according to a recent study conducted by researchers at the University of Pittsburgh Graduate School of Public Health (GSPH) and others. However, the study, published in the November issue of the American Journal of Medicine, found that African Americans and diabetics -- two groups that could benefit most from preventive aspirin therapy -- are under-represented in this trend.
The University of Pittsburgh investigators, along with collaborators from medical centers around the U.S. and in Europe, measured regular aspirin use among 2,163 African American and Caucasian older adults without cardiovascular disease in the late 1990s and again between 2002 and 2003. They also determined 10-year heart disease risk scores for all participants.
During 1997 and 1998, 17 percent of the participants were regular aspirin users. Aspirin use increased with their risk of heart disease, from 13 percent in those with a 10-year low-risk profile to 23 percent in those with a 10-year high-risk profile. However, blacks were less likely to use aspirin (13 percent) than whites (20 percent). Between 1997 and 1998 and 2002 and 2003, aspirin use almost doubled (from 17 percent to 32 percent) among those still free of coronary heart disease. However, despite their particularly high heart disease risk, diabetics were not more likely to use aspirin than nondiabetic individuals, even in 2002 and 2003.
According to lead author, Anne B. Newman, M.D., M.P.H., professor of epidemiology and medicine, GSPH, aspirin therapy should be better targeted to high-risk individuals. This would decrease the incidence of side effects of aspirin therapy, such as gastrointestinal bleeding and hemorrhagic stroke, among those who are at low risk for heart disease.
Contact: Jim Swyers, (412) 647-3555, SwyersJP@upmc.edu
Mind Over Bladder
Millions of people have the sudden urge to go, often at the most inconvenient times -- a condition called overactive bladder. Although little is known about the causes of overactive bladder in otherwise healthy people, new research reported in a recent issue of the Journal of Urology and at a recent meeting of the International Continence Society suggests part of the answer can be found in a certain area of the brain.
Using functional magnetic resonance imaging, or fMRI technology, researchers at the University of Pittsburgh scanned the brains of six people with good bladder control and six people with poor bladder control while filling and withdrawing liquid from their bladders.
Those with good bladder control had increased activity in the orbitofrontal cortex, a region of the brain associated with deciding between alternative courses of action. In contrast, fMRI showed that those with poor bladder control had little activity in this part of the brain, even when their bladders were full. Instead, other parts of their brains were activated.
According to lead author, Derek Griffiths, Ph.D., professor of geriatric medicine, University of Pittsburgh School of Medicine, finding that poor bladder control is associated with weak activation of the orbitofrontal cortex is consistent with clinical observations that stroke and other types of injury to this part of the brain can cause bladder problems. This study suggests that treatment strategies for overactive bladder should target the brain rather than the bladder, adds Dr. Griffiths.
Contact: Jocelyn Uhl Duffy, (412) 647-3555, UhlJH@upmc.edu
The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the University of Pittsburgh Medical Center. Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease, and participate in the delivery of outstanding patient care. In fiscal year 2004, Pitt and its institutional affiliates ranked 7th nationally among educational institutions in grant support from the National Institutes of Health (NIH). Approximately 93 percent of this $396 million in NIH support went to the Schools of the Health Sciences and their affiliates.
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