The overall goal of this proposal is to continue my studies that have employed gases as probes to study human physiology.
The specific aims of this proposal are as follows. 1) Quantitate the efficiency of luminal stirring in the normal human small intestine via measurements of the hydrolysis of disaccharides. this stirring determines the thickness of the unstirred layer that covers the mucosa and provides a diffusion barrier to the absorption of all solutes. In addition, the influence of the viscosity and nutrients of luminal contents on luminal stirring will be investigated. As a related project, the efficiency of stirring of the intervillous space of dogs and rats will be studied to assess the role of villous surface area on absorption and surface hydrolysis. Data from these studies can be compared to that from subjects with intestinal disease to determine if inadequate luminal stirring plays a role in the malabsorption of patients with bowel disease. 2) Separately identify the role of H2 producing the H2 consuming organisms: a) in subjects with very high or very low H2 production and b) in subjects adapting to a high fiber diet or lactase deficient subjects adapting to a high lactose diet. H2 is a major component of flatus and hence understanding of the factors regulating H2 accumulation in the gut is important to understanding the pathogenesis and potential approaches to therapy of flatulence. Subjects ingesting high dose of fiber or lactose initially have severe flatulent symptoms that improve with continued ingestion of the foodstuff. This improvement seemingly reflects an adaptation of the gas producing flora and these studies will determine if changes in H2 producing or H2 consuming organisms are involved in this adaptation. 3) Utilize measurements of carbon monoxide (CO) in alveolar air to assess red blood cell (RBC) turnover. At present there is no simple, rapid test for RBC turnover and it is proposed that the assessment of alveolar PCO corrected for environmental PCO will provide a clinically useful test for RBC survival. 4) Utilize measurements of CO release from substrates as a measure of oxidant injury. The proposed studies will use fructose as a test compound to: a) identify the carbons involved in this oxidation and b) test the oxidant-antioxidant activity of various biological fluids. Oxidant injury has widespread implications for health, and CO release appears to be a unique marker of this injury.
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