ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASE

通过物理化学原理和生物化学的应用， 生物物理技术，我们将继续定义相行为 健康和疾病中的消化道脂质和脂质-蛋白质系统： 相关系、精细结构和相的性质 模型系统将与实际的病理生理学 现象。 这些实验将证明 多组分天然脂质和蛋白质的物理化学平衡 系统，例如胆汁、肠腔内容物、高密度脂蛋白（HDL） 在疾病状态中受到干扰，并可能建议他们的策略 纠正一下 天然胆汁的物理状态将通过以下方法进行研究： 具体涉及胶束和非胶束颗粒，其 当稀释并与胰酶和膳食脂肪混合时 乳剂 胆汁中的胆固醇成核和结晶将 研究特别涉及胆汁蛋白、二价离子和 促融合胆汁盐 脂蛋白X的起源将被定义 采用离体灌注肝脏，及其与细胞内 研究胆汁形成。 的相平衡和胶束性质 盐酸盐和熊胆酸盐，亲水性胆汁盐， 用于胆结石溶解和预防的药物，将被确定为 将影响胆汁酸钙盐的溶液性质。 逆胆汁 盐/夫西地酸盐胶束和液晶相将系统地 作为药物吸收的潜在载体进行检查。 的影响 胆固醇对HDL重组体的相平衡和结构的影响， 由于HDL-胆盐结合和肝HDL-胆盐摄取， 研究了 用克隆的apo-AI片段合成盘状和囊泡状HDL 和AII及其分泌到胆汁中的情况将尽可能进行研究 增强胆固醇逆向转运的治疗方法， 胆结石预防，分别。 理化性质 水系统、膜系统中的天然胆红素缀合物，和 将阐明胆汁中的理化异常， 将鉴别色素性结石性胆汁。 最后，使用组合 物理化学和病理生理学方法，我们将确定 胶束与液体的肠脂肪吸收的相对功效 结晶相，探索脂质渗透到吸收的机制， 细胞，并研究治疗肽的肠道吸收 （胰岛素，胰岛素原，胰高血糖素）从反胶束系统和液体 结晶相

Through the application of physical-chemical rationale and biochemical, biophysical techniques we will continue to define the phase behavior of alimentary tract lipids and lipid-protein systems in health and disease: Phase relations, fine structures and properties of phases encountered in model systems will be correllated with actual pathophysiological phenomena. Those experiments will demonstrate how the delicate physical-chemical balance of lipids and proteins in multicomponent native systems, e.g. bile, gut luminal contents, high density lipoproteins (HDL) are perturbed in disease states and may suggest strategies for their correction. The physical state of native bile will be studied with specific reference to micellar and non-micellar particles, as will their fate when diluted and mixed with pancreatic enzymes and dietary fat emulsions. Cholesterol nucleation and crystallization from bile will be investigated with particular reference to bile proteins, divalent ions and fusogenic bile salts. The origin of lipoprotein X will be defined employing the isolated perfused liver, and its relevance to intracellular bile formation investigated. Phase equilibria and micellar properties of muricholates and ursocholates, hydrophilic bile salts that are potential agents for gallstone dissolution and prevention, will be determined, as will the solution properties of calcium bile salts. Reverse bile salt/fusidate micelles and liquid crystalline phases will be systematically examined as potential vehicles for drug absorption. The influence of cholesterol on phase equilibria and structures of HDL recombinants, as well as HDL-bile salt binding and hepatic HDL-bile salt uptake, will be studied. Synthetic discoid and vesicle HDL with cloned fragments of apo-AI and AII and their secretion into bile will be investigated as possible therapeutic approaches to enhance reverse cholesterol transport and gallstone prevention, respectively. Physical-chemical properties of natural bilirubin conjugates in aqueous systems, in membrane systems, and in bile will be elucidated, and the physical-chemical abnormalities in pigment lithogenic biles will be identified. Finally, using a combination of physical-chemical and pathophysiological methods, we will determine the relative efficacy of intestinal fat absorption from micellar vs. liquid crystalline phases, explore mechanisms of lipid penetration into absorptive cells, and investigate intestinal absorption of therapeutic peptides (insulin, proinsulin, glucagon) from reverse micellar systems and liquid crystalline phases.