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 Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

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: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>