ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASE

通过物理化学原理和生物化学的应用， 我们将继续用生物物理技术来定义 健康和疾病中的消化道脂类和脂蛋白系统： 相的相关系、相的精细结构和性质 模型系统将与实际的病理生理相关 现象。这些实验将证明微妙的 多组分天然人群中脂质和蛋白质的物理化学平衡 系统，如胆汁、肠腔内容物、高密度脂蛋白(HDL) 在疾病状态下感到不安，并可能为他们的 更正。天然胆汁的物理状态将用 对胶束和非胶束粒子的具体引用，以及它们的 稀释后与胰酶和膳食脂肪混合后的命运 乳剂。胆汁中的胆固醇成核和结晶将是 特别参考胆汁蛋白、二价离子和 融合性胆盐。脂蛋白X的起源将被定义 采用离体肝灌流及其与细胞内的相关性 胆汁形成情况调查。聚合物的相平衡和胶束性质 鼠胆酸盐和熊胆酸盐，是潜在的亲水性胆汁盐 用于胆结石溶解和预防的试剂将被确定为 会不会改变钙胆盐的溶液性质。反转胆汁 盐/呋喃西德胶束和液晶相将被系统地 被检查为潜在的药物吸收载体。的影响 胆固醇对高密度脂蛋白重组体的相平衡和结构的影响 随着高密度脂蛋白-胆汁盐结合和肝脏高密度脂蛋白-胆汁盐摄取， 学习。用apo-AI的克隆片段合成盘状和囊状高密度脂蛋白 以及它们分泌到胆汁中的情况将被尽可能地调查 治疗方法，以加强反向胆固醇转运和 分别预防胆结石的发生。的物理化学性质 天然胆红素结合物在水体系、膜体系和 胆汁中的胆汁成分将被阐明，而胆汁中的物理化学异常 颜料致石胆汁将被鉴定。最后，使用一个组合 物理-化学和病理生理学方法，我们将确定 胶束与液体对肠道脂肪吸收的相对有效性 晶相，探索脂质渗透吸收的机制 细胞，并考察治疗多肽在肠道的吸收。 (胰岛素、胰岛素原、胰升糖素)来自反胶束系统和液体 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.