Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify new weapon to fight deadly bacterial sepsis

11.10.2006
One of the most dangerous risks of contracting a serious bacterial infection is that the victim may develop sepsis--an overreaction by the immune system causing destructive inflammation throughout the body, often leading to heart and other organ failure and death.

Even the best hospital intensive care units may be helpless to save patients stricken by severe sepsis. According to a 2003 study by Emory University and the Centers for Disease Control and Prevention, sepsis killed 120,491 hospitalized people in 2000. The same study found cases of sepsis in the U.S. have risen dramatically in recent decades, nearly tripling from 82.7 cases out of every 100,000 Americans in 1979 to 240.4 cases per 100,000 in 2000. Muppets creator Jim Henson died of the disease in 1990 at age 53.

Epidemiologists blame this large increase on the explosive rise in antibiotic-resistant bacteria caused by overuse of antibiotics as well as on the increasing numbers of people living with immune systems weakened by HIV, using immune-suppressive therapy for organ and bone marrow transplants, and receiving high-dose chemotherapy for cancer. Young children and elderly people are also at a higher risk for the condition because of their weaker immune systems.

Now, Assistant Professor Kota V. Ramana and Professor Satish Srivastava of the University of Texas Medical Branch at Galveston (UTMB) and their collaborators have discovered that in laboratory mice, blocking the activity of a single enzyme known as aldose reductase can short-circuit sepsis, protecting heart function and greatly reducing sepsis deaths. Moreover, the scientists have accomplished this feat using a chemical compound very similar to a diabetes drug already in stage three clinical trials in the United States, the final level of human experimentation before a drug is considered for federal licensing approval.

If those diabetes trials prove successful and the drug is approved for use in diabetics, it's possible 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 blocking aldose reductase activity with pharmacological inhibitors or using small interfering RNAs (pieces of genetic material that specifically stop the production of particular cellular proteins) to prevent the cells from producing the enzyme in the first place, the researchers demonstrated that aldose reductase is essential to that cycle.

Previous work by Srivastava and his UTMB collaborators (including research described in a paper published Oct. 1 in Cancer Research) has demonstrated that blocking aldose reductase similarly can dramatically reduce the inflammation-driven processes of colorectal cancer and complications of diabetes.

"There are so many inflammatory signaling processes that depend on this enzyme, and so it made sense to look into with regard to sepsis, which we knew was a runaway inflammatory process," Srivastava said. "We're hoping that when an aldose reductase inhibitor is approved as a drug in the U.S. -- one is already in use in Japan for diabetes, by the way -- we can interest clinicians in studying its use against sepsis."

Jim Kelly | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>