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 At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History

nachricht New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>