Improved Understanding Of The Very Early Stages In The Development Of Inflammatory Diseases Such As Atherosclerosis And Rheumatoid Arthritis

Main Category: Heart Disease
Also Included In: Immune System / Vaccines;  Arthritis / Rheumatology
Article Date: 06 Jul 2012 - 1:00 PDT Current ratings for:
Improved Understanding Of The Very Early Stages In The Development Of Inflammatory Diseases Such As Atherosclerosis And Rheumatoid Arthritis

Scientists at the University of East Anglia (UEA) have discovered a 'constant cloud' of potent inflammatory molecules surrounding the cells responsible for diseases such as thickening of the arteries and rheumatoid arthritis.

Published online by The Journal of Cell Science, the findings could eventually lead to new treatments for chronic inflammatory diseases. Cardiovascular disease arising from atherosclerosis (thickening of the arteries) kills around 17 million people worldwide each year, including 120,000 people in England and Wales, while rheumatoid arthritis affects around 400,000 people in the UK.

The UEA team studied a type of white blood cell called monocytes. Monocytes play an important role in the human immune system and help protect our bodies against infection. But they can also invade tissue, triggering the early stages of common inflammatory diseases.

The researchers detected for the first time that monocytes were surrounded by a constant cloud. This cloud was found to be made up of potent inflammatory molecules called adenosine triphosphate, or ATP. Further study showed that the ATP molecules were being propelled through the cell wall by the actions of lysosomes. Lysosomes are sub-cellular compartments within blood cells which had previously been thought to only break down cell waste.

"These unexpected findings shed light on the very early stages in the development of inflammatory diseases such as atherosclerosis and rheumatoid arthritis," said lead author Dr Samuel Fountain of UEA's School of Biological Sciences.

"We found that lysosomes are actually highly dynamic and play a key role in the way inflammatory cells function. This is an exciting development that we hope will lead to the discovery of new targets for inflammatory drugs in around five years and potential new treatments beyond that."

Dr Fountain said further study was now needed to investigate how to control the release of ATP by lysosomes in monocytes and other white blood cells, and to understand how inflammation may be affected in patients with inherited diseases involving lysosomes.

Dr Fountain is a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellow and recently received £0.9m from the BBSRC to study how cells use ATP as a signalling molecule.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our heart disease section for the latest news on this subject. 'Constitutive lysosome exocytosis releases ATP and engages P2Y receptors in human monocytes' by V Sivaramakrishnan (UEA), S Bidula (UEA), H Campwala (UEA), D Katikaneni (UEA) and S Fountain (UEA) is published online on July 5 by the Journal of Cell Science. The paper will be available here: http://jcs.biologists.org/content/early/recent
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University of East Anglia. (2012, July 6). "Improved Understanding Of The Very Early Stages In The Development Of Inflammatory Diseases Such As Atherosclerosis And Rheumatoid Arthritis." Medical News Today.

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Restricting Calories Early on Does Not Help Acute Lung Injury Patients on Ventilators

For Immediate Release
Monday, February 6, 2012

Acute lung injury patients on ventilators who require a feeding tube have a similar number of ventilator-free hospital days and similar mortality rates if they receive a low-calorie feeding program initially followed by a full-calorie program compared to a full-calorie program right away. These results are part of a new clinical study funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

The patients in the low-calorie, or delayed, feeding program received about 400 calories per day for the first six days before advancing to a full feeding program. The patients enrolled in the full feeding program were advanced as quickly as they could tolerate to a full daily calorie and protein goal based on weight (averaging about 1,300 calories per day).

"The appropriate feeding protocol for mechanically ventilated patients is an important practical question that has been debated in intensive care units for decades," said Susan B. Shurin, M.D., acting director of the NHLBI. "Nutrition is important for healing, but feeding may lead to bowel complications in acutely ill patients. This study suggests that in cases of acute lung injury, physicians can take into account the patient's tolerance to feeding in reaching caloric goals."

Results of this study will be presented Feb. 5 at the Society of Critical Care Medicine Congress in Houston, Tex. The results will also appear online in the Journal of the American Medical Association.

Previous clinical studies that enrolled small numbers of patients have produced conflicting results on the amount of feeding to provide ventilated patients. Some studies indicate that full feeding as soon as possible can improve patient health and their outcomes. Other findings, however, have suggested that starting out with lower calories could improve patient recovery by reducing gastrointestinal problems such as vomiting or constipation.

This new study enrolled 1,000 mechanically ventilated adult patients with acute lung injury who required a feeding tube. The primary clinical outcomes measured were the number of days alive and off the ventilator each patient had in the first 28 days, as well as overall mortality after 60 days.

Patients on the delayed feeding program had an average of 14.9 ventilator-free days and 23.2 percent mortality. Patients on the full feeding program had an average of 15.0 ventilator-free days and 22.2 percent mortality. The researchers noted that patients in the full feeding group showed slightly higher rates of vomiting and constipation, although this was a secondary outcome of the study.

The researchers noted that since these findings were in adult patients ventilated for acute lung injury from largely medical causes, such as pneumonia or sepsis, extrapolation to surgical patients or children must be done cautiously.

The study was carried out at 44 hospitals and medical centers across the country as part of the NHLBI Acute Respiratory Distress Syndrome Clinical Research Network.

To schedule an interview with an NHLBI spokesperson, contact the NHLBI Communications Office at 301-496-4236 or NHLBI_News@nhlbi.nih.gov.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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