INFANTILE DIARRHEA: IMPROVED ORAL REHYDRATION SOLUTIONS

婴儿腹泻：改进的口服补液解决方案

• 批准号: 2025377
• 负责人: RAUL A WAPNIR
• 金额: $ 18.43万
• 依托单位: NORTH SHORE UNIVERSITY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2025377
• 关键词: body fluid balance therapy; body water dehydration; brush border membrane; diarrhea; dietary fiber; disease /disorder model; electrolyte balance; fluid flow; fluidity; gastrointestinal nutrient absorption; intestinal mucosa; laboratory rat; malnutrition; molecular polarity; nonblood rheology; nonhuman therapy evaluation; nutrition related tag; osmotic pressure; perfusion; polymers; polysaccharides; small intestines; sodium; viscosity; water solution

Oral rehydration solutions (ORS) presently in use are effective for the treatment of diarrhea, especially early in life. Current ORS reverse dehydration and sodium (Na) losses, although they do not shorten the duration of the disease. This revised proposal is designed to extend preliminary investigations which showed that certain viscous agents improved ORS capacity for rehydration and Na uptake. We now aim to broaden our observations and substantiate the general hypothesis that the effectiveness of ORS can be enhanced by soluble fibers or gums which alter the rheological characteristics of the intestinal lumen contents. To achieve this goal we will study the role of viscosity, net charge and polymer chain organization at different Na concentrations. We will also examine whether water absorption improvement is due to a reduction of fluid recirculation into the lumen associated with changes in the architecture of the mucosal brush border. An important component of the project is the use of several animal models of childhood gastrointestinal disease and malnutrition which mimic presentations of diarrheal disease in human populations. They include: (1) secretory diarrhea induced by stable E. coli toxin; (2) in situ exposure of the small intestine to theophylline, which acts by the same mechanisms as cholera toxin; (3) protein-energy malnutrition (PEM); (4) a combination of PEM and toxin-induced secretion. The basic experimental technique will be an intestinal perfusion procedure in anesthetized rats. Nonabsorbable markers and labeled tracers will enable us to calculate net and unidirectional flows of water and other ORS components. We will also evaluate the effectiveness of soluble fiber- enhanced ORS in reversing the effects of secretagogues on the intestinal villi and the brush border vicinity by histologic and electron microscopic methods. Quantitative data obtained with intestinal perfusions in rats under anesthesia have been shown to parallel results reported in children with diarrhea treated with the same ORS. This proposal should provide the basis for a new approach intended to make ORS a more effective and economically accessible therapy in the treatment of diarrhea and dehydration, particularly in infancy and childhood.

目前正在使用的口服补液解决方案（ORS）对 腹泻的治疗，尤其是生命的早期。当前的ORS反向 脱水和钠（NA）损失，尽管它们不缩短 疾病的持续时间。该修订的建议旨在扩展 初步研究表明某些粘性剂 改善了ORS补液和NA吸收能力。我们现在旨在扩大 我们的观察结果并证实了一个总体假设 可溶性纤维或牙龈可以增强OR的有效性 肠腔内容物的流变特征。到 实现这一目标，我们将研究粘度，净充电和 聚合物链组织以不同的NA浓度。我们也会 检查吸水的改善是否是由于减少 流体再循环与与变化有关的管腔 粘膜刷边界的建筑。 该项目的重要组成部分是使用几种动物模型 儿童胃肠道疾病和营养不良的 人群中腹泻病的介绍。其中包括：（1） 由稳定的大肠杆菌毒素诱导的分泌性腹泻； （2）原位暴露 小肠到茶碱的小肠，通过相同的机制起作用 作为霍乱毒素； （3）蛋白质 - 能源营养不良（PEM）； （4）组合 PEM和毒素诱导的分泌。 基本的实验技术将是肠道灌注过程 在麻醉大鼠中。不可吸收的标记和标记的示踪剂将 使我们能够计算水和其他OR的净和单向流动 成分。我们还将评估可溶性纤维的有效性 增强的OR在逆转促分子对肠的影响 绒毛和刷边界附近通过组织学和电子显微镜 方法。用大鼠肠道灌注获得的定量数据 在麻醉下已显示在儿童中报告的结果 用相同的OR处理腹泻。 该建议应为一种新方法提供基础 在治疗中更有效，更经济的治疗 腹泻和脱水，特别是在婴儿期和童年时期。