DEVELOPMENTALLY IMPAIRED MOTOR ACTIVITY IN THE CYSTIC FIBROSIS SMALL INTESTINE

囊性纤维化小肠运动活动发育受损

• 批准号: 8167987
• 负责人: ROBERT C DE LISLE
• 金额: $ 5.87万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167987
• 关键词: Age; Behavior; Cessation of life; Childhood; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Development; Enzymes; Exhibits; Experimental Models; Failure; Failure to Thrive; Functional disorder; Funding; Gastrointestinal Motility; Goals; Grant; Growth; Health; Hereditary Disease; Human; Inflammatory disease of the intestine; Institution; Intestinal Motility; Intestines; Life; Measures; Metabolic; Metabolism; Motor Activity; Muscle; Nutritional; Outcome; Prostaglandins; Research; Research Personnel; Resources; Small Intestines; Source; Time; United States National Institutes of Health; cystic fibrosis mouse; cystic fibrosis patients; design; improved; motility disorder; novel therapeutics; nutrition; postnatal

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. Background: Small intestinal motility protects against bacterial overgrowth and is important for proper nutrition. Cystic fibrosis (CF) is one of the most common lethal genetic diseases and about half of CF patients have dysfunction of gastrointestinal motility and small intestinal bacterial overgrowth. Childhood failure-to-thrive and life-long nutritional problems are common in CF. Rationale: Poor nutrition is strongly correlated with the progression to airway failure and death in CF. At what age intestinal dysmotility develops in CF, and by what mechanisms, are not known. The long term goal is to understand intestinal dysfunction in CF in order to provide new therapeutic directions to improve health. Questions: The goal is to determine the relationships between bacterial overgrowth, inflammation, and intestinal muscle dysfunction during postnatal development. Design: The CF mouse model exhibits similar intestinal problems as human CF patients and will be used as an experimental model for this project. The objectives in this application are to determine the temporal relationships between altered metabolism of prostaglandins, intestinal muscle dysfunction, and bacterial overgrowth during development of the CF mouse small intestine. Outcomes: (1) Determine when prostaglandin metabolism is altered, by measuring expression of prostaglandin metabolic enzymes and levels of prostaglandins; (2) Determine when circular muscle activity is impaired, by measuring muscle behavior; and (3) Determine when abnormal bacterial growth occurs. The developmental time courses of these changes will be revealing about the causes of intestinal dysfunction in CF.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 背景：小肠运动能够防止细菌过度生长，对于适当的营养很重要。囊性纤维化（CF）是最常见的致命遗传疾病之一，大约一半的CF患者患有胃肠道运动和小肠细菌过度生长功能障碍。 CF中常见于童年的衰竭和终身营养问题。理由：营养不良与CF中气道失败和死亡的进展密切相关。在CF中，肠道运动障碍的年龄较高，以及通过哪些机制出现的。长期目标是了解CF中的肠道功能障碍，以提供新的治疗方向以改善健康。问题：目的是确定产后发育过程中细菌过度生长，炎症和肠肌功能障碍之间的关系。设计：CF小鼠模型表现出与人类CF患者相似的肠道问题，并将用作该项目的实验模型。本应用中的目标是确定前列腺素的代谢改变，肠肌肉功能障碍和细菌过度生长的时间关系。结果：（1）通过测量前列腺素代谢酶的表达和前列腺素水平来确定何时改变前列腺素代谢； （2）通过测量肌肉行为来确定何时会损害循环肌肉活动； （3）确定何时发生异常细菌生长。这些变化的发展时间课程将揭示有关CF中肠道功能障碍的原因。