Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Action of modern drug demonstrates how 2 ancient human systems interact

17.06.2010
Implications for Reducing Clotting in Kidney Disease Dialysis and Sepsis

The interaction of the drug compstatin with two ancient, co-evolved human systems points to new ways for reducing clotting during dialysis for end-stage kidney disease and multiple organ failure due to sepsis, a dangerous whole-body inflammatory response to infection.

“It has been suspected, but not demonstrated in vivo, until now, that these two systems are able to interact,” says study author John D. Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at the University of Pennsylvania School of Medicine. “Our basic research on these two human systems is helping us to come up with new ways to stop clotting problems.”

One system, called complement, an evolutionarily old arm of the immune system, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. The system serves as a rapid defense mechanism in most species from primitive sponges to humans.

The second system, coagulation, or blood-clotting, is also evolutionarily old and co-evolved with the complement system.

Penn researchers, along with an international team of collaborators, describe that inhibition of the complement system using compstatin helps to stop clotting problems during dialysis and in cases of sepsis, according to two recent articles published online in Blood.

Compstatin is a small molecule designed to specifically and maximally inhibit the complement harmful reactions by attaching to a complement molecule called C3.

Reaction to Dialysis Materials

Complement activation is often triggered by the tubing and filters used during dialysis itself, causing problems with blood clotting. However, the mechanism by which long-term dialysis causes clotting has not been clear. In the U.S. more than 500,000 receive treatment for end-stage renal disease annually.

In recent years, the adverse effects of dialysis have become a serious health and economic problem nationwide: The number of patients with end-stage renal disease has been steadily increasing in the U.S. over the past few decades, at a rate of approximately 9 percent per year, the highest increase in any developed country.

To solve this problem, Lambris reasoned that if the complement system was involved in triggering blood clotting, then inhibition of complement by compstatin binding to C3 would also stop the clotting. “We found that materials used in dialysis trigger the complement system and that the generation of certain complement molecules results in the expression of active tissue factor, a key initiator of clotting,” said Lambris. The Penn group found that compstatin blocks the generation of the complement molecules C5a, which stimulates the release of tissue factor from neutrophils.

These findings suggest that compstatin, or other drugs that target the complement system, might be therapeutic agents to prevent clotting in patients with renal failure who are maintained on long-term dialysis.

Staying Sepsis

During severe sepsis, which accounts for about 210,000 deaths annually in the US, the complement system is part of the primary response to an invading pathogen. However, both the complement and the coagulation systems can work overtime during sepsis, leading to multiple organ failure and death.

In a baboon model of severe sepsis caused by a sub-lethal dose of E. coli, Lambris and colleagues found that treating the animals with compstatin during the acute or secondary phase of sepsis reduced both blood and tissue markers of complement activation and blood coagulation.

“Similar to the dialysis study, this shows that there is an interplay between the complement and coagulation systems,” said Lambris.

Blocking the interplay between the two systems by compstatin, or a similar drug, may become a therapeutic strategy to prevent the devastating effects of sepsis.

“We are investigating several compstatin-related compounds that are one thousand times more active than compstatin, which was discovered in our lab 13 years ago,” said Lambris. Toxicity studies will be required before these newer compounds can move into human trials.

The Penn studies were done in collaboration with researchers at the Democritus University of Thrace, Greece; the University of Oslo, Sweden; the Oklahoma Medical Research Foundation; and the Oklahoma University.

These studies were supported by grants from the National Institute of Allergy and Infectious Diseases; the National Institute of General Medical Sciences; and the National Institute of Biomedical Imaging and Bioengineering.

This release can be found at: http://www.uphs.upenn.edu/news/News_Releases/2010/06/action-of-modern-drug/.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.

Penn Medicine’s patient care facilities include:

The Hospital of the University of Pennsylvania – the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report.
Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.
Pennsylvania Hospital – the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>