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Researchers identify new weapon to fight deadly bacterial sepsis

le that such an "aldose reductase inhibitor" could be used by physicians relatively quickly for "off-label" emergency use against sepsis in humans, the scientists said. When a drug is approved for one human use, individual doctors may try it out against other conditions where it appears warranted.

Srivastastava, senior author of a paper on the sepsis discovery to be published online Oct. 9 in the journal Circulation, explained that in this disease, "You can treat an infection and kill off all the bacteria, but there are still two things causing damage -- the inflammatory proteins released by the body's natural defenses, and the outer membranes of the dead bacteria, mainly composed of large toxic molecules called lipopolysaccharides, which go on inducing more inflammatory immune response even though the bacteria themselves are dead."

"This inflammatory response causes significant problems with cardiac contractility," Srivastava added, "and so instead of pumping blood properly, the heart just flutters, a condition leading to cardiomyopathy."

The drastic drop in the heart's ability to pump blood is dangerous in itself, the researcher continued, and it can also have disastrous effects on the lungs and kidneys, which depend on efficient blood circulation.

Srivastava, lead author Ramana and their collaborators injected mice with lipopolysaccharide (LPS) to produce the conditions of severe sepsis, leading to major declines in heart function and substantial increases in heart-damaging inflammatory signaling molecules. But when they treated the mice with an aldose reductase inhibitor, they found that blocking the enzyme's activity restored the heart's ability to pump blood normally and allowed mice injected with otherwise lethal levels of LPS to survive.

Other experiments conducted in cell cultures traced the specific biochemical pathways by which LPS triggers an inflammatory cycle that damages the cells of the heart. By
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Source:University of Texas Medical Branch at Galveston


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