Experiments have shown that hemoglobin associated acetaldehyde (HBAA) and plasma associated acetaldehyde (PAA) as measured by a fluorigenic high performance liquid chromatographic assay normalized to protein concentration can serve as markers in humans for ethanol intake with different biological kinetics. Additional experiments in animal models (C57 mice and miniature swine) have confirmed these observations and indicated that use of the same assay system to measure platelet associated acetaldehyde (PLTAA) and whole blood associated acetaldehyde (WBAA) provides assessments of ethanol intake as well. The present proposal is designed to define the clinical utility of the above four assays as markers for ethanol intake. Ongoing studies with Schick Health Services assure availability of samples such that assays can be evaluated in well characterized groups of teetotallers, social drinkers, alcoholics, and pregnant women. We have also applied for and received over 10,000 plasma samples from the NICHD-Diabetes and Early Pregnancy Study to help in the definition of the utility of these assays in this latter population. Thus it will be possible to determine norms for the assays involved by age and gender, the statistical significance of discrimination for each assay between drinkers, nondrinkers, and alcoholics as well as correlation with another measure of drinking behavior (the SAAST), and also evaluate special subgroups. Specific studies are designed to determine the chemical nature of the adducts measured by the assay, the biological on and off rates of each assay, as well as precision, recovery, optimum conditions for sample storage and shipping. The development of two animal models will be continued in our own laboratories (the C57 mouse) and in collaboration with investigators at the University of Missouri (miniature swine). The availability of these animal models will allow definition of questions concerning the assays which are difficult to perform in humans including gender differences in response to quantified intakes of ethanol, tolerance, on and off rates, and responses of recidivist drinkers.
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