METABOLIC CONSEQUENCE OF SICKLE CELL ANEMIA IN ADOLESCENCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设：纯合子镰状细胞病（HbSS），也被称为镰状细胞性贫血，是由于父母双方遗传了镰状细胞Bs-glabin基因，通常以显著的临床严重程度为特征。许多患有HbSS的儿童生长和性发育迟缓。生长迟缓和体重增加缓慢的原因尚不清楚，但这可能与能量需求增加有关。这种增加的潜在生理机制可以部分解释为新红细胞（rbc）的合成加速和不可逆镰状红细胞的代谢改变。然而，在HbSS青少年加速生长过程中，这些代谢事件是如何发生和进展的尚不清楚。该GCRC提案的中心假设是，HbSS青少年全身蛋白质周转增加和心输出量增加，导致基础需求和身体活动的能量消耗增加，转移了正常生长途径中的能量和蛋白质。具体目的：1)确定患有HbSS的青少年需要多少能量和蛋白质才能达到最佳生长。根据将在“初步研究”中提出的工作，工作假设是HbSS的生长速度将取决于青春期HbSS增加了多少能量消耗和全身蛋白质周转率。2)解释HbSS青少年的生长速率是如何被更高的全身蛋白质周转和心输出量增加引起的能量需求增加所改变的。我们假设，再次基于初步数据，心输出量、红细胞生成活动和骨转换的变化是影响全身蛋白质转换和增加能量需求的潜在生理机制。我们假设这种增长限制了青春期生长所需的能量。3)量化HbSS青少年每日体力活动所需的能量和蛋白质。我们的工作假设是，由于自愿体力活动较少，HbSS青少年体力活动所需的能量和蛋白质量与HbAA对照组相似。

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. HYPOTHESIS: Homozygous sickle cell disease (HbSS), known also as sickle cell anemia, results from inheritance of the sickle cell Bs-glabin gene from both parents and is characterized usually by marked clinical severity. Many childen w/HbSS have delayed growth and sexual development. The reason for the delayed growth and associated poor weight gain is not well understood but it might be associated w/the increased requirement for energy. The underlying physiological mechanism of this increase could be in part explained by the accelerated synthesis of new red blood cells (RBCs) and the altered catablolism of irreversibly sickled RBCs. However, how these metabolic events develop and progress during the accelerated growth occurring in HbSS adolescents is unknown. The central hypothesis of this GCRC proposal is that increased whole-body protein turnover and increased cardiac output, resulting in increased energy expenditure for basal needs and physical activity, divert energy and protein from normal growth pathways in HbSS adolescents. SPECIFIC AIMS: 1) To determine how much energy and protein is needed for optimal growth in adolescents w/HbSS. Based on work that will be presented under Preliminary Studies, the working hypothesis is that the growth rate in HbSS will depend on how much energy expenditure and whole-body protein turnover are increased during adolescence by HbSS. 2) To explain how growth rate in HbSS adolescents is altered by increased demands for energy caused by higher whole-body protein turnover and increased cardiac output. We postulate, anain based on preliminary data, that changes in cardiac output, erythropoietic activity, and bone turnover, are the underlying physiological mechanisms affecting whole body protein turnover and increase the demand for energy. We hypothesize that this increase limits the amount of energy available for grwoth during adolescence. 3) To quantify how much energy and protein is required for daily physical activity in adolescents w/HbSS. Our working hypothesis is that because of lower voluntary physical activity, the amount of energy and protein required for physical activity in HbSS adolescents is similar to HbAA controls.