MINIMAL ENTERAL NUTRIENT REQUIREMENTS IN NEONATES

描述：长期目标是建立最小的肠内 维持肠道生长的营养需求 TPN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、可量化的最低水平， 必须通过肠道提供的营养物质的最佳组成， 正常的新生儿肠道生长 假设2： 最低限度的肠内喂养对肠道生长的作用是通过体液介导的， 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：胃泌素和胃蛋白酶的营养作用 肠内营养素对肠道生长的作用是通过一种常见的 刺激粘膜鸟氨酸脱羧酶（ODC）活性。 这些 将使用新生猪模型检验假设， 具体目标：目标1：量化最低肠内营养需求 通过a）直接体内 肠内给药的首过利用率的测量 全喂猪中的U-13 C标记的氨基酸和碳水化合物，和B）通过 确定是否提供肠内营养物的水平，如 在a）部分中定义的，将维持新生猪的正常肠道生长 否则由TPN喂养。 目的2：表征相对肠营养 特定常量营养素（氨基酸、碳水化合物和脂质）的影响， 以目标1中确定的最低肠内水平提供。 确定 饮食的物理形式的影响（元素与复杂的公式）。 目的 3：确定循环胃泌素的作用，在缺乏最小的 肠内营养物，或通过使用胃泌素抑制胃泌素作用 受体拮抗剂，丙谷胺，在存在最小肠 营养素 目的4：确定是否用抗氧化剂抑制ODC活性。 二氟甲基鸟氨酸的长期给药阻断了营养效应 胃泌素或最小肠内营养素对肠道生长的影响， TPN喂养的新生猪。 用于量化肠道生长的方法， 所有这些研究中的细胞增殖将包括质量估计 （蛋白质和DNA，体内蛋白质合成（2 H3/13 C1-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 mRNA表达。 对TPN喂养的早产儿的护理要求 在美国，医疗保健成本很高。 这项建议会 建立正常肠道生长的肠内营养需求， TPN喂养新生猪，因此，适当缩放， 更合理地制定肠内喂养策略的基础， TPN喂养早产儿的肠内营养需求

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.