Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blocking Digestive Enzymes May Reverse Shock, Stop Multiorgan Failure

25.01.2013
New research from the University of California, San Diego published in the Jan. 23 issue of Science Translational Medicine moves researchers closer to understanding and developing treatments for shock, sepsis and multiorgan failure.

Collectively, these maladies represent a major unmet medical need: they are the number one cause of mortality in intensive care units in the United States, with hundreds of thousands of deaths annually. There is currently no treatment for these conditions in spite of many clinical trials.

Most researchers agree that organ failure in shock and sepsis involves the intestine – and that it arises when the mucosal barrier of the small intestine becomes permeable. However, the mechanism by which this disrupted membrane is tied to vastly different kinds of shock, as well as multiorgan failure and death has not been understood.

In the case of sepsis (septic shock), for example, some researchers speculate that bacteria in the intestine and their toxins are responsible for organ failure. However, interventions against bacteria that are aimed at reducing mortality in patients undergoing septic shock have been unsuccessful in clinical trials.

Looking more broadly than bacteria, a team of researchers led by Geert W. Schmid-Schönbein in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering has carried out several years of careful analysis of the events in shock. That research led them to investigate the powerful, concentrated digestive enzymes in the intestine, the same enzymes that are part of daily digestion.

These digestive enzymes need to be restricted to the inside of the small intestine by the mucosal barrier. Once this barrier is disrupted, which can occur for a variety of reasons including dramatic loss of blood, physical puncture or opening (as in shrapnel injury or appendicitis), or degradation by bacterial toxins, digestive enzymes leak into the wall of the intestine and begin digesting it, a phenomenon the UC San Diego researchers call “autodigestion”. Once beyond the mucosal barrier of the small intestine, the UC San Diego researchers believe the digestive enzymes damage other organs by indiscriminately starting to degrade them, which can lead to multiorgan failure and death.

The new research, published in the Jan. 23 issue of Science Translational Medicine, provides novel results linking digestive enzymes to shock, sepsis and multiorgan failure. In particular, by administering digestive enzyme blockers directly into the small intestines of rats an hour after the onset of different types of shock, the researchers led by Schmid-Schönbein reversed the often fatal conditions, reduced injury to the heart and lungs, and greatly increased long-term survival of the animals from about 16 percent to 86 percent.

* The animals that received the digestive enzyme blockers in the lumen of the intestine regained their health and survived for long periods of time after shock. (Past experimental shock studies have been limited to relatively short observation periods.)

* The researchers showed a clear connection between direct inhibition of pancreatic digestive enzymes after the onset of three different shock models in rat, reduced organ damage and long-term survival of the animals. They demonstrated improved survival with three very different inhibitors of the digestive enzymes.

* All three of the pancreatic enzyme inhibitors, when delivered directly into the small intestine, but not when delivered intravenously, stopped autodigestion brought on by shock. (One of these enzyme inhibitors is already approved for use in the United States for other purposes).

* Blockade of the digestive enzymes was successful in three widely different forms of shock. The researchers studied hemorrhagic shock, septic shock and endotoxic shock.

For the first time, these studies specifically indicate that it is possible to stop autodigestion by blocking the digestive enzymes in animals with induced shock. “We saw far less damage to organs, faster recovery of the animals, and a reduction of mortality in shock,” said Research Associate Frank DeLano, who carried out the studies with Schmid-Schönbein.

Autodigestion
The UC San Diego bioengineers have described aspects of autodigestion, as well as the potential for stopping it (and treating shock) by blocking the powerful digestive enzymes that have breached the intestine barrier, in numerous papers in the scientific literature.

This research has the potential to lead to therapies that greatly reduce fatalities, morbidity, and length of stay in intensive care units in patients undergoing various forms of shock.

“Organisms rely on full containment of the digestive enzymes in the small intestine. The moment the intestinal mucosal barrier is compromised, the digestive enzymes escape and then we are no longer digesting just our food, but we may be digesting our organs,” said Schmid-Schönbein.

A Phase 2 clinical pilot study is under way to test the efficacy and safety of a new method of administering an enzyme inhibitor for critically ill patients such as those with new-onset sepsis and septic shock, post-operative complications, and new-onset gastrointestinal bleeding.

In addition, a published clinical report points to successful treatment of a patient with severe septic shock with digestive enzyme inhibitors delivered directly into the intestine.

In shock, there is a major failure of the mucosal barrier
in the small intestine. There may also be other conditions in which the failure of this barrier is less severe, and digestive enzymes leak more slowly into the blood stream. The effect on human health of slow leakage of digestive enzymes into the body with low level of autodigestion remains to be explored, Schmid-Schönbein explained.
Funding
This research was supported by an unrestricted gift from Leading BioSciences Inc. and by National Institutes of Health (NIH) grants HL 67825 and GM 85072.
Competing interests
Geert W. Schmid-Schönbein is a scientific advisor to Leading BioSciences Inc.
David B. Hoyt, Frank A. DeLano and Geert W. Schmid-Schönbein own equity in InflammaGen, a company by Leading BioSciences Inc., which develops therapy for shock patients.

“Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock,” by Frank A. DeLano from the Department of Bioengineering, and The Institute of Engineering in Medicine at University of California, San Diego; David B. Hoyt from the American College of Surgeons; and Geert W. Schmid-Schönbein from the Department of Bioengineering, and The Institute of Engineering in Medicine at University of California, San Diego. Published in the 23 Jan. issue of Science Translational Medicine.

Daniel Kane | Newswise
Further information:
http://www.ucsd.edu

More articles from Health and Medicine:

nachricht Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

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: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>