PANCREATIC FUNCTION TESTING WITH LIPID ANALOGUES

使用脂质类似物进行胰腺功能测试

基本信息

批准号：
3151999
负责人：
HOWARD R SLOAN
金额：
$ 10.55万
依托单位：
CHILDREN'S HOSPITAL (COLUMBUS)
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1986-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151999
关键词：
acylation cystic fibrosis dietary constituent esterification gastrointestinal disorder diagnosis glycerol infrared spectrometry lipolysis noninvasive diagnosis nuclear magnetic resonance spectroscopy nutrition related tag orphan disease /drug p aminobenzoate palmitates pancreas triacylglycerol lipase triglycerides

项目摘要

I plan to develop a new, non-invasive technique to evaluate gastrointestinal lipolytic activity as a test of exocrine pancreatic function. The method involvs the synthesis of two types of esters of Rho-acid (PABA) in which the alcoholic moieties will be derived from glycerol and the acids will be palmitic acid and PABA; the esters will therefore be analgoues of triglycerides. In the first type, the amino group of PABA will be free and in the second type it will be acylated. Two of the compounds have been synthesized and their structures have been confirmed by n.m.r. and infrared spectroscopy. I will initially evaluate, In Vitro, the hydrolysis of these substrates by pancreatic lipase. I will then evaluate these compounds a indicators of pancreatic function in rats and dogs with spontaneous or experimentally induced pancreatic insufficiency. I will determine the optimal format for the test including the pre-test diet of the animals, the dose of the test substance, the timing of the sampling, nd the effects of the test of thedosage form of the test substance The lipid analogues will be administered orally or intraduodenally; PABA liberated from the compounds will be absorbed, conjugated in the liver and excreted in the urine. I will therefore determine, at intervals, the concentration of PABA in the blood and urine. The level of PABA in the blood or the extent of PABA excretion in theurine should provide an indirect index of exocrine pancreatic function. I will attempt to correlate the extent of PABA excreation with the degree of fat malabsorption. Should these studies be successful, they will form the basis for similar studies in humans with disorders such as cystic fibrosis or pancreatic insufficiency. The esters may also serve as the substrate for a sensitive assay of lipase activity.

我计划开发一种新的非侵入性技术来评估胃肠道脂肪性活性作为外分泌胰腺测试功能。该方法涉及两种类型的酯的合成 Rho-Acid（PABA），其中酒精部分将源自甘油和酸将是棕榈酸和PABA；酯会因此是甘油三酸酯的肛门。在第一种类型中，氨基 PABA组将是免费的，在第二种类型中，它将被酰化。二这些化合物已合成，它们的结构已经由N.M.R.确认和红外光谱。我最初会评估在体外，胰腺脂肪酶对这些底物的水解水解。我会然后评估这些化合物的大鼠胰腺功能指标和具有自发或实验诱导胰腺的狗不足。我将确定测试的最佳格式动物的预测试饮食，测试物质的剂量，抽样的时机，nd thedosage形式的测试的影响测试物质脂质类似物将口服或余生;从化合物中解放的PABA将被吸收，在肝脏中结合并在尿液中排泄。因此，我会的在血液和尿液中的paba浓度下确定。血液中的PABA水平或Theureine中的PABA排泄程度应提供外分泌胰腺功能的间接指数。我会尝试将PABA排泄程度与脂肪程度相关联吸收不良。如果这些研究成功，它们将形成在诸如囊性纤维化等疾病的人类中类似研究的基础或胰腺功能不全。酯也可以用作底物对于脂肪酶活性的敏感测定。