|
||||||||
|
Axons Made to Sprout After InjuryUnder usual circumstances, nerve fibers cannot regenerate if damaged or cut—a fact that has consigned those with spinal cord injuries to a lifetime of paralysis or movement disorders. Against this grim background, researchers at Children's Hospital announced a promising finding: by applying a chemical normally found in small amounts in cells, they were able to get nerve fibers from the cerebral cortex to regrow into injured regions of the spinal cord in rats. The chemical, inosine, had previously been found to cause axonal sprouting in cultured cells. This is the first time inosine has been observed to induce sprouting in vivo. The research, headed by Larry Benowitz, HMS associate professor of neurosurgery at Children's, appears in the Nov. 9 Proceedings of the National Academy of Sciences. Benowitz and his colleagues severed one side of the corticospinal tract—the fiber pathways running from the cortex to the spinal cord—near the brainstem. Inosine was then infused directly into the opposite side of the brain, specifically, into the motor cortex—the region containing the nerve cells that give rise to the corticospinal tract. After 14 days of treatment, newly grown axon branches were traced by injecting a dye into the treated nerve cells. "The axon growth obtained in this model of corticospinal tract injury is unprecedented," Benowitz remarks. "Inosine's ability to stimulate regrowth of axons into the area of the spinal cord below a significant injury is a significant step forward in finding a treatment for spinal cord and other central nervous system injuries."
New Treatment Improves Blood Flow in Heart Attack PatientsResearchers at Brigham and Women's Hospital have developed a therapy that significantly improves blood flow to the heart in patients suffering from a myocardial infarction. The new therapy combines abciximab, an inhibitor of platelet function, with reduced doses of either reteplase or alteplase, drugs that dissolve blood clots. The treatment not only restores blood flow through large blocked arteries, but also improves the flow through small vessels in the injured portion of the heart muscle. This could minimize heart attack damage and potentially reduce the risk of mortality. The findings were presented by Elliott Antman, HMS associate professor of medicine and director of the Coronary Care Unit at BWH, at the scientific sessions of the American Heart Association in Atlanta on Nov. 6. The study is part of the Thrombolysis in Myocardial Infarction (TIMI) 14 trial, an international project testing different treatment regimens in patients with acute myocardial infarction. Run by investigators at BWH and the Leuven Coordinating Center in Belgium, the recent study looked at patients using reteplase alone, alteplase alone, abciximab and a reduced dose of alteplase, or abciximab and a reduced dose of reteplase. Patients receiving combination therapy with abciximab and reduced doses of either reteplase or alteplase had a 57 percent higher chance of having blood flow restored in large arteries within 90 minutes, compared with patients receiving standard clot-dissolving drugs. Complete heart muscle perfusion was observed in 58 percent of patients receiving the combination therapy, compared with 40 percent in those given a full dose of reteplase or alteplase alone. Significantly, the use of abciximab combined with a reduced dose of either thrombolytic was associated with a two-fold greater chance of improving the pattern of damage observed on these patients' electrocardiograms. Target Found for Autoimmune Response in ArthritisJoint destruction in rheumatoid arthritis is believed to be caused by an immune system attack against self-tissue, although the antigen that provokes this response has not been identified. Now scientists at Joslin Diabetes Center have found an endogenous protein that is the target of an autoimmune response in arthritic mice. The protein does not reside specifically in joints, as many researchers had suspected, but is a ubiquitously expressed enzyme—glucose-6-phosphate isomerase (GPI)—in the glycolysis pathway. The study, by Isao Matsumoto, HMS research fellow in medicine; Diane Mathis, HMS professor of medicine; and Christophe Benoist, HMS professor of medicine; appears in the Nov. 26 Science. To locate the self-antigen target, the researchers probed cell extracts from various mouse tissues with serum from either normal or arthritic mice. They visualized the antibodyantigen complexes that formed and consistently found a protein of a particular mass associated with antibodies from the sera of arthritic mice. To learn the protein's identity, they isolated it from the complex and performed a sequence analysis. Comparison of the sequences with those in a public database revealed it to be GPI. To confirm that arthritic mice produce antibodies to GPI, the researchers then engineered expression of the protein in bacteria, purified it, transferred it to a membrane, and probed the membrane with sera from either arthritic or control mice. GPI was recognized by antibodies from arthritic mice only. The researchers then tested whether anti-GPI antibodies could produce arthritis in non-arthritic strains of mice. Indeed, they did, and these were the only antibodies in the arthritic mice that caused disease. The results indicate that a joint-specific disease can result from an immune reaction to a protein that is expressed in all tissues. The researchers believe that "some unusual physiological feature of joints may be responsible for focusing the autoimmune destruction" in this area. —This and the brief above by Lorene Leiter Plasma Melatonin May Not Decline with AgeResearchers from the Program in Neuroscience and the Department of Medicine at HMS and the Circadian, Neuroendocrine and Sleep Disorders Section at Brigham and Women's Hospital are challenging popular ideas about lifelong endogenous melatonin patterns. Much previous research has suggested that plasma melatonin levels act as an "aging clock," decreasing naturally over time. These findings have prompted the development of melatonin replacement therapies used to combat sleep problems in the elderly. In this study, published in the Nov. 5 issue of The American Journal of Medicine, first author Jamie Zeitzer and colleagues report that healthy older adults exhibit plasma melatonin levels comparable to that of young adults. They conclude that a reduction in melatonin concentration is not a general characteristic of healthy aging. The study, conducted in the laboratory of Charles Czeisler, HMS professor of medicine at BWH, analyzed the plasma melatonin profiles of 34 older healthy adults (age 65 to 81) and 98 healthy young men (age 18 to 30). Participants were in good physical and mental health and did not use any prescription or nonprescription drugs that suppress melatonin secretion (such as aspirin, ibuprofen, beta-blockers, nicotine, alcohol, and caffeine). Because light levels and postural changes can affect plasma melatonin levels, the participants were kept under thoroughly controlled conditions throughout the study. After a baseline period was completed, the participants were monitored through constant, identical routines, and blood samples were collected every 20 to 60 minutes for 30 hours. Analysis of plasma melatonin levels showed there were no differences in the mean 24-hour plasma melatonin concentration, duration of the nocturnal peak of melatonin secretion, mean melatonin concentration during the nocturnal peak, or the integrated area of the nocturnal peak between groups. There was also no difference found between the variance of these parameters within the groups. The researchers believe the differences between their findings and previous results are due to the strict inclusion of healthy, drug-free older adults and controls for other factors that could affect melatonin levels. —Catherine Chu |
