MINORITY INSTITUTION MENTORED RESEARCH SCIENTIST AWARD

描述 （摘自申请人摘要）一般认为， 患有纯合子镰状细胞病的青少年， 儿童和青少年时期的身体发育。 营养一直 考虑了可能导致这种延迟的因素。 能量代谢， 蛋白质代谢，以及视黄醇，叶酸，锌和铁的状态已经被 据报道，镰状细胞病患者缺乏。 增长 然而，患有纯合子镰状细胞病的青少年的发育迟缓， 不能仅仅解释为摄入或吸收减少， 营养素和蛋白质。 足够正常青少年生长的量 可能不足以满足个体增加的代谢需求， 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， 与健康人相比， HbSS是一种 红细胞破坏率较高的一种过度分解代谢状态 导致基础代谢率增加。 的增加 能量代谢率由较高蛋白质的能量消耗引起 周转 结果，静息能量消耗增加。 其他 总能量消耗的组成部分，如能量损失（EL）或热 食物效应（TEF）很可能保持不变，尽管没有证据表明 存在. 体力活动和工作的能量消耗（EEact） 尚未报告HbSS受试者，因此未知。 在拟议的研究中。 这是第一次，所有的能量成分 将同时测量消耗和24小时总能量平衡 在HbSS青少年和成人中， 间接量热计在半自然环境中， 稳定同位素技术来测量蛋白质代谢。 次级 该提案的重点是确定提高 蛋白质合成、蛋白质分解和氨基酸氧化来调节 HbSS患者的能量消耗。 能量和营养摄入 也将进行评估，氮平衡将在所有 科目 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 高匹配的健康个体。 [血红蛋白（Hb）AA基因型- HbAA]。 来自类似社会经济环境的人将作为所有人的对照。 实验 这些研究的结果将加强我们对 能量摄入、能量消耗和蛋白质之间的关系 纯合子镰状细胞病的代谢，并可能有助于确定最佳的 HBSS患者的能量和氮摄入。 因此，这些研究可能 与HbSS患者的临床管理直接相关。 (End摘要）

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)