DIETARY METHIONINE UPTAKE BY SPLANCHNIC REGION IN HEALTHY AND SICK CHILDREN

健康儿童和患病儿童内脏区域的膳食蛋氨酸摄取量

• 批准号: 8166704
• 负责人: Leticia Castillo
• 金额: $ 2.67万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166704
• 关键词: Adolescent; Affect; Amino Acids; Area; Arginine; Blood; Blood Circulation; Catabolism; Child; Childhood; Computer Retrieval of Information on Scientific Projects Database; Critical Illness; Cysteine; Data; Diet; Disease; Enteral; Essential Amino Acids; Funding; Glutamine; Grant; Homeostasis; Infant; Infusion procedures; Institution; Intestines; Intravenous; Leucine; Metabolism; Methionine; Newborn Infant; Nutritional; Organ; Pathologic; Patients; Pattern; Play; Population; Process; Protein/Amino Acids Nutrition; Protocols documentation; Research; Research Personnel; Resources; Role; Small Intestines; Source; Sulfur Amino Acids; Tissues; Tracer; United States National Institutes of Health; Venous; cystic fibrosis patients; uptake

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. The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism and selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. During critical illness the splanchnic area is profoundly affected, and may influence amino acid metabolism. There are limited data on inter-organ amino acid exchange and the role of splanchnic uptake and catabolism of amino acids in critically ill patients. To determine parenteral and enteral amino acid requirements, it is necessary to determine the extent of the first pass disappearance of amino acids in the splanchnic region. We plan to study a group of healthy adolescents who will serve as controls for our critically ill adolescent group. Sulfur amino acid splanchnic uptake in healthy adolescents has not been determined and needs to be define. Hence enteral requirement of sulfur amino acids in sick children need to be defined. The first objective of this protocol is to conduct studies of methionine and cysteine splanchnic uptake in healthy children adolescents. The studies in healthy children will serve as controls for our critically ill population. We are requesting GCRC support to conduct our studies in the healthy children. We aim to conduct primed, constant simultaneous intravenous and enteral infusions of L-[1-13C] and L[2H2 ]methionine in a first set of studies and of L-[1-13C] and L[2H2 ] cysteine in a second set of studies in healthy children and to use these data to estimate the contribution of splanchnic sequestration to methionine and cysteine requirements. Primary Endpoint: The fraction of methionine or cysteine tracer that disappears in a first-pass through the splanchnic area This protocol is a continuation of our studies on sulfur amino acid metabolism in sick children. We have already conducted studies of methionine splanchnic uptake in critically ill infants, children and adolescents (Please see preliminary data). The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism. The splanchnic area selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. Intestinal amino acid metabolism plays an important role in modulating the entry of absorbed dietary amino acids into the portal circulation. Thus, the pattern of amino acids in the diet differs markedly from that in portal venous blood and does not reflect their availability to extraintestinal tissues. This concept has important implications for protein and amino acid nutrition. The extensive catabolism of dietary essential amino acids in the first pass by the small intestine, a large organ in the body, results in decreased nutritional efficiency. Thus, intestinal amino acid metabolism will influence the utilization efficiency of dietary amino acids and therefore their requirements. Furthermore, it is not known how inter-organ amino acid exchange and splanchnic uptake are affected under pathologic conditions, and how these processes influence amino acid requirements under conditions of disease. There are data on the splanchnic uptake of leucine, arginine, glutamine and methionine in healthy subjects. In the pediatric population there are two studies on leucine splanchnic uptake, in a population of patients with cystic fibrosis and in the newborn period. These studies yield leucine splanchnic uptake values of 24% and 30% respectively. There are no data on methionine and cysteine splanchnic uptake in healthy or sick children. Therefore, the first objective of this proposal is to determine the rates of splanchnic uptake of methionine and cysteine in sick children.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 内脏区域在全身氨基酸代谢的稳态中起着重要作用，并选择性地影响随后释放到体循环中的吸收氨基酸的模式。危重疾病期间，内脏区域受到严重影响，并可能影响氨基酸代谢。关于危重患者的器官间氨基酸交换以及氨基酸的内脏摄取和分解代谢的作用的数据有限。为了确定胃肠外和肠内的氨基酸需求，有必要确定内脏区域氨基酸的首过消失程度。我们计划研究一组健康的青少年，他们将作为我们危重青少年组的对照。 健康青少年内脏摄取硫氨基酸尚未确定，需要确定。因此，需要确定患病儿童的含硫氨基酸的肠内需求量。 该协议的第一个目标是对健康儿童青少年的蛋氨酸和半胱氨酸内脏摄取进行研究。对健康儿童的研究将作为对危重人群的对照。我们请求 GCRC 支持在健康儿童中开展我们的研究。 我们的目标是在第一组研究中进行 L-[1-13C] 和 L[2H2] 蛋氨酸的预启动、持续同时静脉和肠内输注，并在第二组研究中进行 L-[1-13C] 和 L[2H2] 半胱氨酸的预启动、持续同步静脉和肠内输注。一组针对健康儿童的研究，并使用这些数据来估计内脏隔离对蛋氨酸和半胱氨酸需求的贡献。 主要终点：第一次通过内脏区域时消失的蛋氨酸或半胱氨酸示踪剂的分数 该方案是我们对患病儿童硫氨基酸代谢研究的延续。我们已经对危重婴儿、儿童和青少年的蛋氨酸内脏摄取进行了研究（请参阅初步数据）。 内脏区域在全身氨基酸代谢的稳态中起着重要作用。内脏区域选择性地影响吸收氨基酸的模式，随后将其释放到体循环中。肠道氨基酸代谢在调节吸收的膳食氨基酸进入门静脉循环方面发挥着重要作用。因此，饮食中的氨基酸模式与门静脉血中的氨基酸模式显着不同，并且不能反映它们对肠外组织的可用性。这个概念对蛋白质和氨基酸营养具有重要意义。膳食必需氨基酸首先经过小肠（人体的一个大器官），进行广泛的分解代谢，导致营养效率下降。因此，肠道氨基酸代谢将影响膳食氨基酸的利用效率及其需求量。此外，尚不清楚病理条件下器官间氨基酸交换和内脏摄取如何受到影响，以及这些过程如何影响疾病条件下的氨基酸需求。 有关于健康受试者内脏摄取亮氨酸、精氨酸、谷氨酰胺和蛋氨酸的数据。在儿科人群中，有两项关于囊性纤维化患者群体和新生儿期亮氨酸内脏摄取的研究。这些研究得出的亮氨酸内脏摄取值分别为 24% 和 30%。没有关于健康或患病儿童内脏摄取蛋氨酸和半胱氨酸的数据。因此，该提案的首要目标是确定患病儿童的内脏摄取蛋氨酸和半胱氨酸的比率。