MINIMAL ENTERAL NUTRIENT REQUIREMENT IN NEONATES

描述：长期目标是建立最低限度的肠道 维持肠道生长所需的营养物质 全胃肠外营养喂养的新生儿。拟议的研究将检验三个假设： 假设1：有一个强制性的和可量化的最低水平 必须通过肠道提供以维持营养的最佳营养成分 新生儿肠道发育正常。假设2：食物的营养效应 微量肠内喂养对肠道生长的影响是通过体液调节的 胃泌素，但胃泌素介导的作用依赖于最低水平的 肠内营养素。假设3：胃泌素和胃泌素的营养作用 肠内营养对肠道生长的影响是通过一种常见的 刺激粘膜鸟氨酸脱羧酶(ODC)活性。这些 假设将使用新生猪模型进行验证，该模型具有以下特性 具体目标：目标1：量化最低肠道营养需要量 通过a)直接在体内维持正常的肠道生长 浅谈肠内给药首过利用的措施 U-13C标记的氨基酸和碳水化合物在全饲喂猪和b)通过 确定是否提供肠道营养素水平，如 将维持新生猪的正常肠道生长。 否则由TPN喂养。目的2：描述相对肠道营养的特征 特定的常量营养素(氨基酸、碳水化合物和脂肪)在 以目标1中确定的最低肠内水平提供。确定 饮食的物理形式(基本配方与复杂配方)的影响。目标 3：在缺乏微量胃泌素的情况下，确定循环中胃泌素的作用 肠内营养，或通过抑制胃泌素的作用，使用胃泌素 受体拮抗剂丙谷胺在微量肠内注射时的应用 营养素。目的4：确定是否可以抑制ODC活性 长期服用二氟甲基鸟氨酸可阻断营养作用 胃泌素或微量肠道营养物质对小鼠肠道生长的影响 饲喂TPN的新生猪。用来量化肠道生长和 所有这些研究中的细胞增殖都将包括对细胞数量的估计 (蛋白质和DNA，体内蛋白质合成(2H3/13C1-Leu掺入)， 体内隐窝细胞增殖指数(BrdU标记)、绒毛形态计量学和 IFG-I基因表达。对TPN喂养的早产儿的护理强加了 美国的医疗保健成本很高。这项提议将 建立正常肠道生长所需的肠道营养需求 TPN喂养的新生猪，因此，在适当的比例下，提供了 为更合理地制定肠内喂养策略和 TPN喂养的早产儿的肠道营养需求。

DESCRIPTION: The long term goal is to establish the minimal enteral nutrient requirements for the maintenance of intestinal growth in the TPN-fed neonate. The proposed studies will test three hypotheses: Hypothesis 1: There is an obligatory, and quantifiable, minimum level and optimum composition of nutrients that must be provided enterally to maintain normal neonatal intestinal growth. Hypothesis 2: The trophic effect of minimal enteral feeding on intestinal growth is mediated humorally by gastrin, but gastrin-mediated effects are dependent on a minimum level of enteral nutrients. Hypothesis 3: The trophic effects of both gastrin and enteral nutrients on intestinal growth are medicated via a common stimulation of mucosal ornithine decarboxylase (ODC) activity. These hypotheses will be tested using a neonatal pig model with the following specific aims: Aim 1: Quantify the minimal enteral nutrient requirement for maintenance of normal intestinal growth by a) direct in-vivo measurements of the first pass utilization of enterally administered U-13C-labeled amino acids and carbohydrate in full-fed pigs and b) by determining whether the provision of the level of enteral nutrients, as defined in part a), will maintain normal intestinal growth in neonatal pigs otherwise fed by TPN. Aim 2: Characterize the relative intestinal trophic effect of specific macronutrients (amino acids, carbohydrate and lipid) when provided at the minimal enteral level determined in Aim 1. Determine the effect of the physical form of the diet (elemental vs complex formula). Aim 3: Determine the role of circulating gastrin, in the absence of minimal enteral nutrients, or by inhibition of gastrin action, using the gastrin receptor antagonist, proglumide, in the presence of minimal enteral nutrients. Aim 4: Determine whether inhibition of ODC activity with chronic administration of difluoromethylornithine blocks the trophic effect of either gastrin or minimal enteral nutrients on intestinal growth in TPN-fed neonatal pigs. Methods used to quantify intestinal growth and cellular proliferation in all of these studies will include mass estimates (protein and DNA, in vivo protein synthesis (2H3/13C1-Leu incorporation), in vivo crypt cell proliferation index (BrdU labeling), villus morphometry, and IFG-I mRNA expression. The care of TPN-fed preterm infants imposes a significant health care cost in the United States. This proposal will establish the enteral nutrient requirements for normal intestinal growth in the TPN-fed neonatal pig, and thus, with appropriate scaling, provide a basis for more rational development of enteral feeding strategies and enteral nutrient needs in TPN-fed preterm infants.