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$1,780,000 grant to SLU aims to buy time for those with sepsis

Chlorinated lipids may hold key to quick diagnosis

Saint Louis University

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IMAGE: Saint Louis University's David Ford, Ph.D., professor of biochemistry and molecular biology, and Jane McHowat, Ph.D., professor of pathology, are collaborating on a research study they hope will lead to... view more

Credit: Saint Louis University

ST. LOUIS -- With a new $1,780,000 grant from the National Institutes of Health (NIH), Saint Louis University researchers aim to develop a biomarker that will buy precious time for sepsis patients.

Sepsis is a dangerous immune response to an infection in which the whole body becomes inflamed. Most of the body's infections are local, sealed off and kept within the boundaries of an organ or part of the body, like the lungs or sinuses. In some cases, however, an untreated infection spreads and causes overwhelming systemic inflammation throughout the body.

Though older and immunocompromised patients are at greatest risk, sepsis strikes and kills adults and children of every age. It carries a high mortality rate as well as high risk of complications from massive drops in blood pressure, endothelial damage and organ failure. The Centers for Disease Control and Prevention (CDC) estimates that over a million people are hospitalized for sepsis each year.

One of the challenges with sepsis is that it is crucial to treat it quickly. As organs begin to shut down, treating sepsis becomes a game of beating the clock. The infection itself is treated with broad spectrum antibiotics. Doctors also try to manage extreme drops in blood pressure and limit tissue damage.

To improve doctors' ability to identify sepsis early, the NIH has funded researchers at SLU who may have already discovered a solution: chlorinated lipids.

In 2002, David Ford, Ph.D., professor of biochemistry and molecular biology at Saint Louis University, made a discovery of a type of lipid that had not previously been identified in people.

"My lab discovered chlorinated lipids," Ford said. "We performed a chemical reaction to mimic what we believed could be formed in the human body. Next we showed that they, indeed, could be made in the body. They are made under conditions where there is inflammation."

Because chlorinated lipids appear under circumstances where the body is inflamed, they might be able to serve as a "canary in the coal mine" for sepsis. If doctors had a reliable biomarker, something that could be measured that signaled sepsis, they could diagnose the condition more quickly.

This is Ford's aim for the research.

"I hope that we find a valid biomarker," Ford said. "We could improve therapy for sepsis before detrimental outcomes occur."

The grant funds several arms of research. In addition to Ford's work, Jane McHowat, Ph.D., professor of pathology at SLU, will conduct cell culture research and a collaborator at the University of Missouri -- Columbia, Ron Korthuis, Ph.D., will conduct research in an animal model. The three are co-principal investigators on the multi-pronged project.

McHowat studies the endothelial cells that line the blood vessels, and she believes it is crucial to understand how chlorinated lipids affect these cells.

"Microcirculation governs overall cardiovascular health," said McHowat. "Every tissue has a microcirculatory system that manages oxygen and nutrients. It's critical that it be intact. It is lined by endothelial cells. It is our hypothesis that endothelial cells are altered by chlorinated lipids.

"We need to know: What affect do chlorinated lipids have on microcirculation? And, how does that relate to end organ damage?"

Beyond serving as a biomarker, it may be that chlorinated lipids also are the culprits causing tissue damage.

"If we can determine that chlorinated lipids cause cell damage and develop targets, we might develop a great drug," Ford said. "Part of the research will be trying to determine the mechanisms by which the cells are injured."

The scientists hope to improve the odds of survival and limit the debilitating effects of this illness that can take a surprising toll on even the otherwise healthy.

"Anyone is at risk for sepsis, although the risk increases with age" McHowat said. "For example, people with untreated sinus infections can develop sepsis. Once it has developed, the big challenge is to manage the dangerous drop in blood pressure. There is only so much you can do. And, even once the infection has cleared, patients may have damaged blood vessels and organs.

"If we can catch it earlier, we are in a much better position to treat sepsis before it gets too bad," McHowat said. "This a case where 12 or 24 hours can make a big difference."

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Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.

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