MINORITY INSTITUTION MENTORED RESEARCH SCIENTIST AWARD

描述 (改编自申请人的摘要)人们普遍认为孩子们 患有纯合子镰状细胞疾病的青少年在 儿童期和青春期的身体发育。营养一直是 考虑到可能是造成这一延误的原因。能量代谢， 蛋白质代谢，以及视黄醇、叶酸、锌和铁的状态 据报道，在镰状细胞病患者中存在缺陷。生长 然而，患有纯合子镰状细胞病的青少年发育迟缓 不能仅仅以摄入或吸收减少为基础来解释 营养和蛋白质。足够正常青少年生长的数量 可能不足以满足患有以下疾病的个人增加的代谢需求 镰状细胞性贫血[血红蛋白(Hb)SS基因型-HbSS]。氮平衡， 例如，在患有SCD的青少年中，对 饮食中的氮与健康的人相比。哈佛商学院是一家 红细胞破坏率较高的高分解代谢状态 并导致基础代谢率增加。这一增长 能量代谢率是由较高蛋白质的能量成本引起的 营业额。结果，静息能量消耗增加。其他 总能源支出的组成部分，如能量损失(EL)或热能 食物的影响(TEF)很可能保持不变，尽管没有证据 是存在的。年体力活动和工作的能量消耗(EEact) 患有糖化血红蛋白综合征的受试者尚未报告，因此尚不清楚。 在拟议的研究中。第一次，所有的能源成分 将同时测量支出和总24小时能量平衡 并持续地在HbSS青少年和成年人中生活在整个房间内 在半自然环境中的间接量热计与 用于测量蛋白质代谢的稳定同位素技术。第二个 这项提案的重点是确定提高利率的可能性 蛋白质合成、蛋白质分解和氨基酸氧化调节 糖化血红蛋白综合征患者的能量消耗。能量和营养摄入量 也将进行评估，并将测量所有 研究对象。此外，体力活动和工作对能量的影响 将对支出和余额进行评估。年龄、性别、体重和 高度匹配的健康个体。[血红蛋白(Hb)AA基因型-HbAA]。 来自相似的社会经济环境将成为所有 实验。这些研究的结果将加深我们对 能量摄入、能量消耗和蛋白质之间的关系 在纯合子镰状细胞疾病中的代谢，并可能有助于确定最佳 血瘀证患者的能量和氮摄入量。因此，这些研究可能 与HbSS患者的临床管理直接相关。 (摘要结束)

DESCRIPTION (Adapted from applicant's abstract) It is generally accepted that children and adolescents with homozygous sickle cell disease experience impairment in physical growth during childhood and adolescence. Nutrition has been con-sidered a possible contributor to this delay. Energy metabolism, protein metabolism, and retinol, folic acid, zinc, and iron status have been reported to be deficient in patients with sickle cell disease. Growth retardation in adolescents with homozygous sickle cell disease, however, cannot be explained solely on the basis of decreased intake or absorption of nutrients and protein. Amounts sufficient for growth in a normal adolescent may be insuf-ficient for the increased metabolic needs of individuals with sickle cell anemia [Hemoglobin (Hb) SS genotype - HbSS]. Nitrogen balance, for example, in adolescents with SCD responds differently to changes in dietary nitrogen when compared to healthy individuals. HbSS is a hypercatabolic condition in which rate of erythrocyte destruction is higher than normal and causing basal metabolic rate to increase. The increase in energy metabolism rate is caused by the energy cost of higher protein turnover. As a result, resting energy expenditure is elevated. Other components of total energy expenditure such as energy losses (EL) or thermal effect of food (TEF) most likely remain un-changed, although no proof exists. Energy expenditure for physical activity and work (EEact) in subjects with HbSS has not been reported and, therefore, is unknown. In the proposed studies. For the first time, all components of energy expenditure and total 24 h energy balance will be measured simultaneously and continuously in HbSS adolescents and adults living inside a whole-room indirect calorimeter in a semi-naturalistic environment in combination with stable isotope techniques to measure protein metabolism. The secondary focus of this proposal is to determine the potential of increased rates of protein synthesis, protein breakdown and amino acid oxidation to modulate energy expenditure in individuals with HbSS. Energy and nutrient intake will be also assessed, and nitrogen balance will be measured in all subjects. In addition, the effect of physical activity and work on energy expenditure and balance will be evaluated. Age-, sex-, weight-, and high-matched healthy individuals. [Hemoglobin (Hb) AA genotype - HbAA]. from similar socio-economic environments will serve as controls in all experiments. Findings from these studies will enhance our understanding of the relationship between energy intake, energy expenditure, and protein metabolism in homozygous sickle cell disease, and may help to define optimal energy and nitrogen intake in HBSS patients. As a result, these studies may be of immediate relevance to the clinical management of the HbSS patient. (End of Abstract)