PROTEIN AND ENERGY METABOLISM IN PEDIATRIC CROHN'S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 克罗恩病的急性加重会导致能量和蛋白质的负平衡，这可能会导致营养不良、生长迟缓和愈合不良。英夫利昔单抗是一种抗肿瘤坏死因子抗体，对克罗恩病儿童有效。这项应用的目的是描述这些儿童在禁食和喂养状态下营养的系统利用及其对皮质类固醇和抗肿瘤坏死因子治疗的反应。这一应用的中心假设是，克罗恩病中存在的炎性细胞因子，包括肿瘤坏死因子-，增加了净蛋白质分解代谢和能量消耗，抗肿瘤坏死因子治疗将导致这些代谢测量比传统的皮质类固醇治疗有更大的改善。我们的长期目标是优化克罗恩病儿童的营养和生长结果。 计划接受英夫利昔单抗或皮质类固醇治疗的复发克罗恩病儿童将被纳入这项研究。为了实现我们的目标，这些儿童将在首次服用英夫利昔单抗或开始皮质类固醇治疗前、后2周和14周进行研究。使用稳定同位素技术，我们将测量禁食状态和肠内营养输注期间的蛋白质动力学和平衡。采用间接量热法，测定空腹和肠内营养输注期间的静息能量消耗。这项拟议的工作是创新的，因为它扩大了我们对营养在克罗恩病中的利用的了解。我们期望这一方法将更清楚地描绘出克罗恩病儿童生长障碍的根本原因。

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. Acute exacerbations of Crohn's disease lead to negative energy and protein balances, which may contribute to malnutrition, growth retardation and poor healing. Infliximab, an anti-tumor necrosis factor (TNF)- antibody, has been efficacious in children with Crohn's disease. The objective of this application is to characterize the systemic utilization of nutrition and its response to corticosteroid and anti-TNF- therapies in these children in both the fasting and fed states. The central hypothesis of this application is that inflammatory cytokines present in Crohn's disease, including TNF- , increase net protein catabolism and energy expenditure, and that anti-TNF- therapy will result in a greater improvement in these metabolic measurements than traditional corticosteroid therapy. Our long-range goal is to optimize the nutritional and growth outcomes of children with Crohn's disease. Children with recurrent Crohn's disease who have been scheduled for either infliximab or corticosteroid therapy will be recruited for this study. To accomplish the objectives of our aims, these children will be studied just prior to, and two and fourteen weeks following their initial dose of infliximab or beginning of corticosteroid therapy. Using stable isotope techniques, we will measure protein kinetics and balance during both the fasting state and enteral nutrition infusion. Using indirect calorimetry, resting energy expenditure will be determined during fasting and enteral nutrition infusion. The proposed work is innovative, because it expands our knowledge of the utilization of nutrition in Crohn's disease. It is our expectation that this approach will more clearly delineate the underlying causes of growth disturbance in children with Crohn's disease.