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Project Title:
Intestinal Perfusion and Permeability in Sepsis
Funding Agency:
National Inst of Gen Med Science
Total Project Period:
Apr 01, 1987 - Jun 30, 2008
Principal Investigator:
Mitchell Fink
Project Summary:
Our long-term goal is to elucidate the fundamental mechanisms responsible for intestinal barrier dysfunction in states associated with acute tissue hypoxia and/or inflammation. Our unifying hypothesis is that derangements in cellular energy metabolism cause or contribute to alterations in epithelial barrier function in critical illness. Aim I is to study cytokine mediated repression of hypoxia-inducible factor-1 (HIF-1)-dependent adaptive epithelial responses in hypoxia during sepsis. Aim II is to evaluate one potential way that an increase in cytosolic ionized calcium concentration, [Ca2+], could act to increase intestinal epithelial paracellular permeability. Aim III is to investigate the effect of cytokines, hypoxia, or metabolic inhibition on the polarized basolateral-to-apical transport of complex carbohydrates and other hydrophilic compounds across the intestinal epithelium.
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