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.
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