PIGMENT GALLSTONES: COMPOSITION AND FORMATION

色素性胆结石：成分和形成

• 批准号: 3225595
• 负责人: ROGER DAVID SOLOWAY
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225595
• 关键词: bile pigments; bilirubin; chemical structure; cholelithiasis; cholesterol; crystallization; gallbladder; gel filtration chromatography; human tissue; interferometry; mucopolysaccharides; phosphates; secretion

Cross-section analysis of most gallstones shows repeated cyclic patterns in stone composition suggesting that bile composition undergoes fluctuations during stone nidation and growth. The overall aim of this study is to examine the thesis that some proteins act consistently or intermittently as traps for calcium salts and cholesterol and provide a skeleton for stone nidation and growth. Biliary protein fractions will be identified, characterized and correlated with proteins in stones to identify mechanisms by which stone components precipitate. Biliary components that control this process will be assessed for their effect on protein binding of calcium salts in vitro and on stone composition in animals. This process will be examined in man to provide a relevent framework and in animals to provide reproducible and controllable conditions. The specific aims are to: 1. Determine the influence of biliary pH on stone growth by examining the distribution of the acidic and neutral salts of calcium bilirubinate in stone using Fourier Transform Infrared Spectroscopy (FTIR). 2. Examine, using FTIR, the composition of gallstone surfaces in comparison with the surrounding bile. Identify the microstructure and composition of cholesterol-calcium salt crystals using scanning electron microscopy-energy dispersive x-ray analysis (SEM-EDXA). Identify the distribution of proteins in stones using FTIR. 3. Use SEM-EDXA to examine stone microstructure and composition, stone porosity and protein-crystal interactions. 4. Use a gallbladder explant system to determine the effects of ionized calcium, bilirubinate and phosphate on mucin production and secretion. 5. Examine the effects of graded biliary stasis on gallbladder function, bile secretion and brown pigment stone formation and to examine the hypothesis that an acid microenvironment exists in bile during stone nidation and intermittently during stone growth. 6. Quantitate and characterize the calcium salt binding properties of proteins in bile and through mixing experiments to examine the nidation inhibition and promation properties of other biliary proteins separated using Fine performance liquid chromatography on gel filtration columns. The results of these studies will test the theory that a variety of proteins of different binding affinities, together with other protein acting as inhibitors or promoters, explains the unique proportions of cholesterol and calcium salts found in sets of gallstones from different patients.

大多数胆结石的横截面分析显示， 结石成分表明胆汁成分经历波动 在结石形成和生长过程中。 本研究的总体目标是 研究一些蛋白质持续或间歇地作为 钙盐和胆固醇的陷阱，并为石头提供骨架 nidation和growth. 将鉴定胆汁蛋白组分， 表征并与结石中的蛋白质相关联，以确定机制 由此使结石成分沉淀。 胆道成分控制 将评估该过程对蛋白结合的影响， 钙盐在体外和对结石成分的动物。 这个过程 将在人身上进行检查，以提供相关的框架，并在动物身上进行检查， 提供可再现和可控的条件。 具体目标是 至：1.通过检查确定胆汁pH值对结石生长的影响 琥珀酸钙的酸性盐和中性盐在 使用傅里叶变换红外光谱（FTIR）对石材进行分析。 2.检查， 使用FTIR，胆结石表面的组成与 周围的胆汁 确定的微观结构和组成 胆固醇-钙盐晶体的扫描电子显微镜能量法 色散X射线分析（SEM-EDXA）。 确定的分布 用傅里叶变换红外光谱分析石头中的蛋白质。 3. SEM-EDXA在结石检查中的应用 显微结构和组成，结石孔隙度和蛋白质晶体 交互. 4.使用胆囊外植系统来确定 离子钙、胆红素和磷酸盐对粘蛋白产生的影响， 分泌物 5.观察不同程度胆汁淤积对胆囊的影响 功能，胆汁分泌和棕色色素结石的形成，并检查 结石形成过程中胆汁中存在酸性微环境的假设 在结石生长过程中， 6.定量和 表征胆汁中蛋白质的钙盐结合特性， 通过混料实验考察其对成巢的抑制和促进作用 使用Fine Performance分离的其他胆汁蛋白的性质 凝胶过滤柱上的液相色谱法。 的结果予以 研究将验证一种理论，即各种不同的蛋白质 结合亲和力，与其他蛋白质一起作为抑制剂，或 促进者，解释了胆固醇和钙盐的独特比例 在不同病人的胆结石中发现。