THE ALTERED PROTEIN METABOLISM OF PEDIATRIC PATIENTS WITH HIV INFECTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尽管高效抗逆转录病毒疗法（HAART）显著降低了艾滋病毒感染儿童的发病率和死亡率，但预期寿命的延长与一部分患者的一系列复杂的代谢紊乱有关。这些疾病包括生长障碍与较低的瘦体重（LBM）。虽然这种代谢紊乱的临床特征描述，其机制的基础是未知的。重要的是要阐明这些机制，以建立新的治疗儿童患者，因为生长障碍将导致发育迟缓。在这个项目中，我们计划测试的假设，艾滋病毒感染的儿童有一个较低的LBM由于净蛋白质合成的赤字，因为上调蛋白质catenin。为了验证这一假设，我们建议进行稳定同位素示踪实验，以实现以下具体目标：测量瘦体重（LBM）和蛋白质动力学在HIV感染的青春期前儿童与年龄和性别匹配的HIV暴露的儿童，并确定饮食能量和蛋白质补充对LBM和蛋白质动力学在HIV感染组的影响。 尽管有足够的膳食蛋白质摄入量，艾滋病毒感染的儿童有一个较低的LBM由于缺乏内源性蛋白质的可用性，以支持LBM合成。 这种蛋白质可用性的降低是继发于相对于摄入的蛋白质催化剂的慢性上调。 我们进一步提出，这种情况可以通过膳食补充更多的能量和蛋白质来改善。 测量青春期前HIV感染儿童与年龄和性别匹配的HIV暴露儿童的身体成分和蛋白质动力学，并确定饮食能量和蛋白质补充对HIV感染组蛋白质动力学的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although highly active anti-retroviral therapy (HAART) has markedly reduced the morbidity and mortality of HIV-infected children, the improved life expectancy is associated with a complex set of metabolic disorders in a subset of patients. These disorders include growth failure with lower lean body mass (LBM). Although the clinical features of this metabolic derangement is described, its mechanistic underpinnings are unknown. It is important to delineate these mechanisms in order to establish new therapies for pediatric patients because growth failure will lead to stunting. In this project we plan to test the hypothesis that HIV-infected children have a lower LBM due to a deficit in net protein synthesis because of upregulated protein catabolism. To test this hypothesis we propose to conduct stable isotope tracer experiments to achieve the following specific aim: measure lean body mass (LBM) and protein kinetics in HIV-infected prepubertal children versus age-and gender-matched HIV-exposed children and determine the effect of dietary energy and protein supplementation on LBM and protein kinetics in the HIV-infected group. Despite an adequate dietary protein intake, HIV-infected children have a lower LBM due to a deficit in the availability of endogenous protein to support LBM synthesis. This decreased protein availability is secondary to a chronic upregulation of protein catabolism relative to intake. We further propose that this condition can be ameliorated by dietary supplementation with more energy and protein. Measure body composition and protein kinetics in prepubertal HIV-infected children versus age and gender matched HIV-exposed children and determine the effect of dietary energy and protein supplementation on protein kinetics in the HIV-infected group.