MODERATE ALCOHOL AND THE HEMOSTATIC SYSTEM

适量酒精与止血系统

• 批准号: 2606276
• 负责人: ADAM K MYERS
• 金额: $ 11.01万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2606276
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; biomarker; blood tests; cardiovascular disorder epidemiology; clinical research; cyclic AMP; cyclic GMP; dosage; hemostasis; human subject; plasminogen activator; plasminogen activator inhibitors; platelet activation; platelets; substance abuse epidemiology; thromboxanes

DESCRIPTION: Interest in effects of alcohol on blood platelets has grown due to reports that moderate drinking reduces cardiovascular mortality. Alcohol consumption may affect the incidence of disorders involving platelets, including stroke an(f myocardial infarction. Despite the popular view, studies on platelet function have had mixed results. Generally, platelet function is inhibited by alcohol, but other studies show stimulation, particularly of early events in the activation cascade. During withdrawal in alcoholics, platelets undergo a rebound, becoming hypersensitive. Thus a complex, incomplete picture emerges. In particular, few epidemiological studies of how moderate drinking affects platelet reactivity in normal individuals have been performed, and in fact, key preliminary data are still needed before such studies can be effectively proposed. Our hypothesis is that moderate drinking will reduce platelet activity, potentially protecting against thrombosis-related cardiovascular accidents. The long range goal is to conduct a well-controlled epidemiological study of the effects of drinking behavior on platelet function in normal men and women. The goals of the present application are to complete preliminary studies necessary before the performance of such an epidemiological study. Our specific aims are to 1) establish, in normal men and women, the dose-response relationship between alcohol consumption and inhibition of platelet function, including agonist specificity; 2) evaluate time-dependency of responses of platelets to alcohol consumption; 3) determine the most appropriate preparation (whole blood/platelet rich plasma/washed platelets) for measurement of effects of drinking; 4) determine the best-suited mechanistic studies for alcohol's effects on the hemostatic system, for application to later epidemiological studies, including effects on thromboxane production, cyclic nucleotides, and the plasminogen activator system. These studies will address, in a clinically relevant manner, a deficit in our knowledge of how alcohol consumption alters incidence of disease states involving platelets, and lay the groundwork for meaningful epidemiological investigations in this area.

描述：酒精对血小板影响的兴趣越来越大 因为有报道称适量饮酒可以降低心血管疾病的死亡率。 饮酒可能会影响以下疾病的发病率： 血小板，包括中风和心肌梗塞。 尽管人们普遍 然而，关于血小板功能的研究结果喜忧参半。 一般而言， 酒精会抑制血小板功能，但其他研究表明， 刺激，特别是激活级联中的早期事件。 期间 戒酒后，血小板会反弹， 过敏 因此，一个复杂的、不完整的画面出现了。 特别是， 关于适度饮酒如何影响血小板的流行病学研究很少 在正常人的反应已经进行，事实上，关键 在这些研究能够有效地 提出了 我们的假设是适度饮酒会减少血小板 活性，可能保护免受血栓形成相关的心血管疾病 事故为重点 长期目标是进行一个控制良好的 饮酒行为对血小板影响的流行病学研究 在正常的男人和女人身上。 本申请的目的是 在执行这一任务之前完成必要的初步研究， 流行病学研究。 我们的具体目标是：1）在正常人中建立 和女性，饮酒量与 抑制血小板功能，包括激动剂特异性; 2）评价 血小板对酒精消耗的反应的时间依赖性; 3） 确定最合适的制备（全血/富含血小板 血浆/洗涤的血小板）用于测量饮用的影响; 4） 确定最适合的机制研究酒精的影响， 止血系统，用于以后的流行病学研究， 包括对血栓素产生、环核苷酸和 纤溶酶原激活物系统 这些研究将在临床上解决， 相关的方式，在我们的知识赤字如何酒精消费 改变涉及血小板的疾病状态的发生率， 为在这一领域进行有意义的流行病学调查奠定基础。