ALCOHOL--DIRECT AND INDIRECT EFFECTS ON DRUG METABOLISM

酒精引起的肝病（ALD）是第四大死亡原因 在居住在城市地区的24-65岁成年男子中， 在美国死亡的主要原因，并占 每年数十亿美元的医疗支出。 调查人员 开发了一种大鼠模型， 作为全肠内营养（TEN）系统的一部分， 研究营养/乙醇与ALD和乙醇代谢的关系。 他们使用TEN模型进行了几次重要的观察。 首先，他们已经确定了一种饮食，防止乙醇诱导的肝脏 损伤，即使在高乙醇和高不饱和脂肪的摄入， 其他人报告的产生显著肝损伤的时期。 其次，研究人员已经确定了另一种饮食， 在与第一次相同的乙醇摄入量下乙醇诱导的肝损伤 饮食. 他们觉得这两个观测结果放在一起令人振奋 因为对这些饮食差异的研究可以揭示 乙醇诱导的肝损伤的重要机制 ALD在人类 第三，调查人员研究了他们的感受 一个有趣的结果，不断胃内注入乙醇， 含有饮食，搏动的BEC似乎是由于“循环” 乙醇代谢 他们不知道生物学意义 这种现象在人类ALD的发展中。 但委员 科学的重要性有两个原因：a）乙醇代谢被认为是 是乙醇不利影响的促成因素;和B） 胃内大鼠模型是唯一能产生 在合理的时间范围和费用内，乙醇诱导的肝损伤。 因此，了解乙醇在该模型中的代谢方式可能是 重要. 第四，啤酒比纯的有不同的代谢作用 乙醇 这是一个重要的观察结果，因为57%的美国人 饮酒者将乙醇作为啤酒而非纯乙醇 用于大多数酒精研究。 他们的数据表明， 对清除率、有效性和毒性的可能后果 可能与酒精饮料同时服用的药物。 这次更新的主要目的是详细研究：1） 乙醇和饮食在生化和细胞基础上的相互作用 乙醇诱导的肝损伤，提出了新的营养和 涉及碳水化合物调节和氧自由基的细胞机制- 调节基因表达; 2）一个独特的脉动方面 慢性胃内灌注的乙醇代谢 含乙醇的饮食;和3）实验室的比较效果 酒精饮料（尤其是啤酒）。

Alcohol induced liver disease (ALD) is the fourth leading cause of death among adult men 24-65 years of age residing in urban areas, the eleventh leading cause of deaths overall in the United States, and accounts for billions of dollars annually in medical expenditures. The investigators developed a rat model in which an ethanol-containing diet is infused intragastrically as part of a total enteral nutrition (TEN) system to study the nutrition/ethanol relationships to ALD and ethanol metabolism. They have made several important observations using the TEN model. First, they have identified a diet that prevents ethanol-induced liver injury, even during high ethanol and high unsaturated fat intake for periods reported by others to produce significant hepatic injury. Second, the investigators have identified another diet that produces ethanol-induced liver injury at the same ethanol intake as the first diet. They feel that these two observations together are exciting because study of the differences between these diets could reveal important mechanism underlying ethanol-induced liver injury leading to ALD in humans. Third, the investigators have studied what they feel is an interesting consequence of constant intragastric infusion of ethanol- containing diets, the pulsatile BECs that appear to be due to "cyclic" ethanol metabolism. They do not know the biological significance of this phenomenon in the development of human ALD. However, it is of scientific importance for two reasons: a) ethanol metabolism is thought to be a contributing factor in adverse effects of ethanol; and b) the intragastric rat models are the only practical models that produce ethanol-induced liver injury within a reasonable time frame and expense. Thus, understanding how ethanol is metabolized in this model may be important. Fourth, beer has different metabolic effects than pure ethanol. This is an important observation, because 57 percent of U.S. alcohol drinkers consume their ethanol as beer, not the pure ethanol used in most alcohol research. Their data suggest that there are possible consequences upon the clearance, efficacy and toxicity of medications that may be taken concomitantly with alcoholic beverages. The principal aims of this renewal are to study in detail: 1) the interactions of ethanol and diet on the biochemical and cellular basis of ethanol induced liver injury by proposing novel nutritional and cellular mechanisms involving carbohydrate-regulated and oxygen radical- regulated gene expression, respectively; 2) a unique pulsatile aspect of ethanol metabolism revealed by chronic intragastric infusion of ethanol-containing diets; and 3) the comparative effects of laboratory ethanol and alcoholic beverages (especially beer).