PROTEIN TURNOVER AND ANABOLIC INTERVENTIONS IN AIDS

艾滋病中的蛋白质周转和合成代谢干预措施

• 批准号: 2150132
• 负责人: KEVIN E YARASHESKI
• 金额: $ 25.3万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2150132
• 关键词: PROTEIN; TURNOVER; ANABOLIC; INTERVENTIONS; AIDS

DESCRIPTION: Body protein wasting is an important physical and clinical problem in patients with AIDS. However, the metabolic basis for this protein wasting is unknown and no acceptable anabolic intervention currently exists. This project has 3 objectives. First, the investigator will evaluate the alterations in whole body and skeletal muscle protein synthesis and breakdown rates that occur in three subject populations infected with HIV and referred to the ACTU at Washington University: a) HIV without weight loss or opportunistic infection and CD4>200; b) HIV with involuntary unexplained weight loss (>10 percent body weight within previous year) and CD4<200; and c) HIV with weight loss, non-life-threatening opportunistic infections and CD4 <200.Second, they will evaluate whether short-term (2 week) treatment with GH or resistance exercise training increase whole body and skeletal muscle protein anabolism in patients with HIV, weight loss, and CD4<200. Each subject will be studied during a two week control period that immediately precedes the two week treatment period. This short-term (within subject design) will minimize the potential confounding effects of different antiviral therapies in these subjects, and permit a rapid assessment of the potential muscle anabolic effects of the interventions. Third, they will evaluate whether long-term treatment (eight week) with either GH or resistance exercise training continues to enhance whole body and skeletal muscle protein anabolism, and results in increments in lean body mass, muscle cross-sectional area, and strength in these patients. Only the most anabolic short-term intervention will be studied in these long-term experiments. Whole body and skeletal muscle protein metabolism will be determined using an intravenous infusion of tracer quantities of stable isotopically labeled amino acids. The metabolic fate of these tracers is assessed by measuring the appearance rate of exhaled labeled CO2, their dilution with naturally occurring leucine and glutamine in the plasma, and their in vivo incorporation rate into vastus lateralis muscle protein during 12-13 hour tracer infusion. Alterations in body composition will be assessed with DXA, MRI of thigh muscle and fat cross-sectional area, and by measuring total body water. Knee extensor and flexor maximum voluntary muscle strength will be assessed on an isokinetic dynamometer.

描述：身体蛋白质浪费是重要的物理和临床 艾滋病患者的问题。 但是，代谢基础 蛋白质浪费是未知的，没有可接受的合成代谢干预措施 目前存在。 该项目有3个目标。首先， 研究者将评估全身和骨骼的变化 肌肉蛋白的合成和三个受试者发生的分解率 感染了艾滋病毒并转介华盛顿的ACTU的种群 大学：a）艾滋病毒没有体重减轻或机会性感染和 CD4> 200; b）艾滋病毒具有非自愿性无法解释的体重减轻（> 10％ 上一年的体重）和CD4 <200; c）体重的艾滋病毒 损失，非生命威胁的机会感染和CD4 <200.second，第二 他们将评估GH的短期（2周）治疗 抵抗运动训练增加了全身和骨骼肌肉 HIV，体重减轻和CD4 <200的患者的蛋白质合物。 每个 主题将在为期两周的控制期内研究 紧接在两个星期的治疗期之前。 这个短期 （在主题设计中）将最大程度地减少潜在的混杂效果 这些受试者的不同抗病毒疗法的允许快速 评估干预措施的潜在肌肉合成代谢作用。 第三，他们将评估是否长期治疗（八周） GH或抵抗运动训练继续增强 身体和骨骼肌肉蛋白合成代谢，并增加 在瘦体重，肌肉横截面区域和强度 患者。 只有最合成代谢的短期干预才是 在这些长期实验中进行了研究。 全身和骨骼肌肉 蛋白质代谢将通过静脉输注确定 示踪剂量的稳定同位素标记的氨基酸。 这 通过测量外观来评估这些示踪剂的代谢命运 呼出的标记二氧化碳的速率，它们自然发生的稀释 血浆中的亮氨酸和谷氨酰胺及其体内掺入速率 在12-13小时的示踪剂输注过程中进入巨大的外侧肌肉蛋白。 人体成分的改变将用DXA，大腿MRI评估 肌肉和脂肪横截面区域，并通过测量全身水。 膝盖伸肌和屈肌最大自愿性肌肉力量将是 评估在等力测功机上。