ALCOHOL--DIRECT AND INDIRECT EFFECTS ON DRUG METABOLISM

酒精性肝病(ALD)是第四大死因 在居住在城市地区的24-65岁成年男性中，11%的人 是美国总体死亡的主要原因，并占 每年数十亿美元的医疗支出。调查人员 建立了一种大鼠模型，在该模型中注入含乙醇的饮食 胃内作为全肠内营养(TEN)系统的一部分 研究营养/酒精与酒精性肝病和酒精代谢的关系。 他们使用TEN模型进行了几个重要的观察。 首先，他们已经确定了一种预防酒精诱导的肝脏的饮食 伤害，即使在高酒精和高不饱和脂肪摄入期间也是如此 其他人报告的产生严重肝脏损伤的时期。 其次，研究人员已经确定了另一种饮食，它能产生 与第一次酒精摄入量相同的酒精性肝损伤 节食。他们觉得这两个观察结果结合在一起是令人兴奋的 因为对这些饮食之间的差异的研究可以揭示 酒精性肝损伤的重要机制 人类的ALD。第三，调查人员研究了他们认为 持续灌胃乙醇的一个有趣的后果是- 在含有食物的情况下，搏动性的BECs似乎是由于“循环” 乙醇代谢。他们不知道生物的意义。 这一现象在人类ALD的发生发展中起着重要作用。然而，它是 科学上的重要性有两个原因：a)乙醇代谢被认为 是酒精不良反应的一个促成因素；以及b) 大鼠胃内模型是唯一一种实用的 在合理的时间框架和费用范围内，酒精所致的肝损伤。 因此，理解乙醇在这个模型中是如何代谢的可能是 很重要。第四，啤酒的新陈代谢作用与纯啤酒不同 乙醇。这是一个重要的观察结果，因为57%的美国人。 饮酒者把酒精当做啤酒来喝，而不是纯乙醇 在大多数酒精研究中使用。他们的数据表明，有 对清除性、有效性和毒性的可能后果 可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) 乙醇与饮食在生化和细胞基础上的相互作用 通过提出新的营养和治疗方法治疗酒精性肝损伤 涉及碳水化合物调节和氧自由基的细胞机制- 分别调控基因表达；2)独特的脉动方面 慢性灌胃给药对乙醇代谢的影响 含乙醇的饮食；3)实验室的比较效果 乙醇和酒精饮料(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).