ALOE VERA PLANT'S POLYMERS ARE FOUND TO IMPROVE BLOOD FLOW

ALOE VERA PLANT'S POLYMERS ARE FOUND TO IMPROVE BLOOD FLOW PITT RESEARCHER'S RESULTS OFFERTANTALIZING IMPLICATIONS

For some people, cultivating an aloe vera plant is like having a first aid kit on the windowsill. In case of a minor burn or cut, they break off a leaf and use the clear, slick gel oozing from its center as an ointment. Surveying the array of aloe plants with broken, stubby leaves growing in the window of Marina Kameneva's laboratory, one might become concerned about the safety of the students working there. But her lab isn't an unusually hazardous place and her lab workers aren't particularly accident-prone. Rather, the plants are regularly harvested because the aloe gel contains polymers that Kameneva says improve blood flow. Adding a minute amount of these polymers to the blood makes it easier to pump and improves its ability to squeeze through the tiny arteries and capillaries where red blood cells do their work ---- supplying cells with oxygen and removing carbon dioxide. Kameneva, a bioengineer who directs the artificial blood program at the University of Pittsburgh's McGowan Institute for Regenerative Medicine, discovered these drag-reducing polymers in aloe gel several years ago. She believes they eventually might be used to treat a number of medical conditions, including heart attacks, stroke and circulation problems associated with chronic conditions such as diabetes and peripheral vascular disease. "It's quite a remarkable discovery," said Dr. Mitchell Fink, chairman of critical care medicine at the University of Pittsburgh School of Medicine. In a study published in this month's issue of the journal Shock, he and Kameneva found that rats that suffered severe blood loss were five times more likely to survive this hemorrhagic shock if treated with the aloe vera-derived polymer. "It's potentially applicable to a whole host of conditions," said Fink, who noted this small animal study in a relatively obscure journal already has generated a lot of buzz. "I've gotten e-mails from all over the place." As of yet, no one understands precisely how these polymers manage to improve blood flow. But the same thing also can be said for drag-reducing polymers in general. Reducing turbulence First described following World War II by British chemist B.A. Toms, drag-reducing polymers reduce turbulence when added to fluids. That allows fluids to be pumped with less pressure or, under constant pressure, to flow at a greater rate. This concept of cutting resistance by reducing turbulence is the same approach used by automobile designers, noted Guy Berry, a chemistry professor at Carnegie Mellon University. By streamlining or by adding airfoils, car designers smooth the flow of air over the vehicle, reducing turbulence and thus helping the vehicle slice through the air. "It was very exciting when it was first observed," Berry recalled of the discovery of drag-reducing polymers. They have been used to ease the flow of oil in the Alaskan pipeline, to increase well pressures for enhanced oil recovery and, in firefighting, to make water shoot farther from fire hose nozzles. The U.S. Navy has long been interested in using drag-reducing polymers to help submarines and surface ships move with greater stealth and less power. Charles McCormick, a polymer scientist at the University of Southern Mississippi, once worked on a project for the Defense Advanced Research Projects Agency to use the polymers to reduce friction on torpedoes. In a bit of serendipity, the British Navy once discovered that algae in water tanks it used to test ship models were producing a polysaccaride that was reducing turbulence, McCormick said. For a time, British scientists tried, without success, to get the algae to grow on ship hulls. But how turbulence is reduced is not fully understood. Drag-reducing polymers, whether naturally occurring or manmade, tend to be very long and relatively stiff molecules. Many polymers tend to coil back on themselves, Berry said, but drag-reducing polymers look more like uncooked spaghetti. It appears that the length of the polymers is related to the size of microturbulent eddies in liquids, McCormick said. This seems to keep waves from propagating from the eddies, reducing turbulence. At least that's one theory. But when it comes to how drag-reducing polymers work in blood, things get even murkier. Blood flowing through blood vessels is not turbulent, said Kameneva, who began studying drag-reducing polymers 30 years ago at Moscow State University in Russia. Kameneva and her mathematician husband, Boris Kushner, were among thousands of Soviet Jews who fled the foundering Soviet Union in the late 1980s. They moved to Pittsburgh in 1989 and Kameneva joined Pitt in 1991. She had suspected that aloe gel, known to be rich in polysaccarides, might contain drag-reducing polymers. An earlier researcher, she noted, had already shown that polysaccarides derived from okra improved blood circulation. She found the aloe-derived polymers made blood more slippery, helping it move from larger arteries to increasingly narrow pre-capillary vessels and capillaries. Also, as vessels continually branch off, the polymers seem to reduce the tiny vortexes that form at each bifurcation, she said. Normally, a very thin layer -- 4 to 5 microns -- of blood plasma coats the lining of the blood vessels, keeping the red blood cells away from the wall. But the drag-reducing polymers thin this plasma layer further, allowing the blood cells to come closer to the wall, making gas exchange easier. As the red blood cells get closer to the vessel walls, they experience more shear stress, stretching out the cells and exposing more of their surface to the vessel wall. The proximity of the cells to the vessels also triggers the production of nitric oxide, which causes the vessels to dilate. These effects would be important in the treatment of hemorrhagic shock, which occurs following the loss of blood. Standard treatment is to stop the bleeding and to restore blood volume by adding liquid called Ringer's solution and red blood cells. But even if blood volume is restored, the microcirculation at the capillary and pre-capillary level can remain impaired, particularly if the low blood volume has persisted for a long time. "That's why [hemorrhagic shock] patients die from organ failure," Kameneva said. The polymers improve microcirculation, by dilating the vessels, making the red blood cells work harder and by increasing blood pressure. "If you have higher blood pressure, it can push more blood cells through" the tiny vessels, she explained. Battlefield applications? The recent rat study of shock was sponsored by DARPA to test whether a small amount of polymer could keep battlefield victims alive another hour or two while they are evacuated. It's impossible for medics to carry sufficient fluids to infuse shock victims, but they could carry enough polymer to treat a number of patients. The study thus focused on whether the polymers could serve as an alternative to fluid infusions. But Fink said treatment for hemorrhagic shock remains problematic even when intravenous fluids are readily available, so further study of the polymers as an addition to standard therapy would be justified. Fink said the polymers don't seem to have any safety problems, but cautioned that the polymers have yet to undergo the sort of safety testing in animals that would be necessary before they could be considered for testing in humans. Also, Kameneva has yet to determine the exact composition of the drag-reducing polymer. That information would be necessary before the Food and Drug Administration would consider approving it as a drug and also would be needed to patent it, Fink said. Without a patent, he added, no pharmaceutical company would be willing to make the investment necessary to allow clinical trials, much less bring the drug to market. Kameneva said the composition of aloe gel has been widely studied, but which of the polysaccarides in the gel are incorporated in the polymer and in what sequence is not known. "I'm not a chemist," she explained. One of her graduate students, Joie Marhefka, is analyzing the polymer's structure, she said, but an expert in polysaccaride chemistry probably could determine the structure in two or three months. Kameneva hopes that as more people learn about the potential of her polymer she might find a chemist interested in collaborating or an industrial sponsor willing to bankroll such a study. Her experience thus far, however, has been that drag-reducing polymers are a concept that many medical researchers have a hard time comprehending. "It took me four years here to publish the first paper," she said, admitting she has been frustrated at times by the pace of her progress. "It's still in the laboratory and it's a shame."

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