Pathobiology of the Enteric System

肠道系统病理学

• 批准号: 8685957
• 负责人: GIANRICO FARRUGIA
• 金额: $ 145.75万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2015-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8685957
• 关键词: Accounting; Animal Experimentation; Back; Caloric Restriction; Chronic; Clinical Trials; Computer software; Data; Development; Diabetes Mellitus; Disease; Eating Disorders; Electronics; Enteral; Event; Feedback; Functional disorder; Future; Gastric Emptying; HOI; Human; Image; In Vitro; Insulin-Like Growth Factor I; Knowledge; Leadership; Magnetic Resonance Imaging; Mediating; Molecular; Morbidity - disease rate; Motor; Normal Range; Patients; Physiological; Production; Regulation; Relaxation; Research; Research Personnel; Role; Stomach; System; Testing; Therapeutic; Translating; Work; base; data management; diabetic; diabetic gastroparesis; diabetic patient; effective therapy; energy balance; feeding; glycemic control; heme oxygenase-1; improved; in vivo; meetings; motility disorder; novel diagnostics; prevent; programs; tool

Disorders of gastric emptying in patients with diabetes, eating disorders and in idiopathic conditions are a significant cause of morbidity. Current approaches for effectively managing gastric emptying disorders are ineffective. The objective of this Program Project is to advance our understanding of the dystrophic changes in the gastric musculature and feed back mechanisms that are the cause of disorders of gastric emptying and gastric motor disturbances and develop strategies to prevent or reverse these changes and restore gastric emptying that are testable in human clinical trials. The scientific objectives are met through three highly Integrated projects and three cores. Project 1 (Pathobiology of Diabetic Gastroenteropathy) studies the role of HO1 in preventing the development of diabetic gastroparesis and the mechanisms that regulate HOI activity in diabetes. Project 2 (Mechanisms of Gastric Dysfunction in Chronic Caloric Restriction) studies the role of cellular dystrophy in the gastric musculature in dysmotilities associated with chronic or chronic intermittent caloric deficit and whether the dystrophic changes are mediated by reduced production of IGF-1 and HO-1. Project 3 (Neurohumoral Regulation in Diabetic Enteropathy) evaluates in clinical trials the effect of increasing HO1 expression on gastric emptying in patients with diabetes, assesses the Impact of glycemic control on gastric emptying in diabetic patients and determines the mechanism accounting for Impaired duodenal-gastric feedback responsible for impaired fundic relaxation and rapid gastric emptying. The Administrative Core A will provide leadership of all Program Project activities. The Imaging Core B will provide advanced software for rigorous quantitative analysis for in vivo and in vitro imaging, and dynamic MR imaging on the stomach in patients. The Physiological Characterization and Data Management Core C will develop and manage an Electronic Animal Research Record that makes available In a single electronic record all research data to all Program investigators. This highly-integrated Program will make significant progress toward understanding the pathobiology of the enteric system in gastric emptying disorders and translate this knowledge into new diagnostic tools and therapy.

糖尿病患者，饮食失调和特发性疾病患者的胃排空疾病是发病率的重要原因。当前有效管理胃排空疾病的方法无效。该计划项目的目的是促进我们对胃肌肉组织营养不良的变化的理解和反馈机制，这些机制是胃排空和胃运动障碍疾病的原因，并制定策略，以防止或逆转这些变化并恢复人类临床试验中可以测试的胃排空。科学目标通过三个高度集成的项目和三个核心实现。项目1（糖尿病性胃肠病病的病理学）研究HO1在防止糖尿病性胃轻瘫的发展和调节糖尿病中HOI活性的机制中的作用。项目2（慢性热量限制中胃功能障碍的机制）研究细胞营养不良在胃肌肉组织中的作用在与慢性或慢性间歇性热量缺陷有关的失调症中的作用以及营养不良的变化是否通过IGF-1和HO-1的产生降低而介导。 Project 3 (Neurohumoral Regulation in Diabetic Enteropathy) evaluates in clinical trials the effect of increasing HO1 expression on gastric emptying in patients with diabetes, assesses the Impact of glycemic control on gastric emptying in diabetic patients and determines the mechanism accounting for Impaired duodenal-gastric feedback responsible for impaired fundic relaxation and rapid gastric emptying.行政核心A将提供所有计划项目活动的领导。 Imaging Core B将为体内和体外成像进行严格的定量分析提供高级软件，并在患者的胃中进行动态MR成像。生理表征和数据管理核心C将开发和管理电子动物研究记录，该记录可在单个电子记录中提供所有研究数据，向所有计划研究者提供所有研究数据。这个高度综合的计划将在理解胃排空疾病中肠系统的病理生物学方面取得重大进展，并将这些知识转化为新的诊断工具和治疗。