Our interdisciplinary team will conduct studies in patients as well as in our experimental models of alcoholic injury in rats and baboons in which liver lesions seen in the alcoholic (including cirrhosis) were reproduced. We plan to assess biochemical differences between alcoholics and nonalcoholics and to apply these findings to the validation of a blood test for alcoholism. Alterations of alcohol metabolism and the role of protein retention, acetaldehyde toxicity and immunological reactions in the development of alcoholic liver diseases will be determined. The nature of the abnormality in collagen metabolism will be evaluated. We plan to study the pathogenesis of alcoholic fatty liver and to develop a blood test which might enable us, in a population of heavy drinkers, to detect those whose alcoholic intake has resulted in significant liver damage beyond the fatty liver stage. We will also try to define a precirrhotic lesion which might allow us to predict which alcoholics might develop cirrhosis, thereby enhancing our effectiveness in the prevention of this complication. Other attempts at prophylaxis will include the definition of nutritional and prexisting medical conditions that favor the development of cirrhosis and portal hypertension when associated with heavy drinking. Pathogenesis of alcohol induced muscle, intestinal and pancreatic lesions will be assessed, including the carcinogenic role of alcohol. Involvement of microtubular alterations in chromosomal abnormalities and their link to the fetal alcohol syndrome will be determined. Androgen and estrogen abnormalities associated with alcoholism will be evaluated through measurements of hormone levels and clearance rates in the blood enzyme activities in the liver. Our baboon model will be made available as a resource to other interested investigators. The ultimate goal is the application of the newly acquired knowledge to the successful prevention and treatment of alcohol related diseases.
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