Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Restoring mortality as a measure of community health

In the last several decades traditional community health indicators have become ambiguous and lost some of their relevance. During this same period national and international health agencies adopted new expanded definitions of Health that include underlying social determinants. These two influences are responsible for a proliferation of new health indicators and many are constructed from a combination of older mortality measures and available information on morbidity. Problems inherent in attempting to combine these sources of information have produced a situation where some indicators are difficult to calculate at the national level and may not function at all for small communities. What is needed is a relevant measure of the burden of ill health appropriate for smaller populations that is accessible to local health planners. ^ Death records are still the best available population health information. In Europe the burden of health problems is often portrayed using 'premature' death. Health agencies in the United States have moved to adopt Years of Potential Life Lost. Both these regions are also developing systems of 'avoidable' or 'preventable' death as health indicators. This research proposes a method combining these methodologies to produce a relevant indicator portraying the burden of ill health in communities. ^