Toxokinetics of Swainsonine--Nutrient Metabolism Effects

目标和宗旨：本计画的长期目标包括：1）训练学生了解毒理学与营养代谢的原理; 2）确定苦马豆素吸收的动力学与模式; 3）确定苦马豆素对营养代谢的影响。为了实现这些目标，本项目将涉及四个具体目标。具体目标#1是定义苦马豆素的吸收动力学具体目标#2是定义苦马豆素对营养消化和通过消化道的流动的影响。具体目标#3是定义苦马豆素的spanchnic组织通量。具体目标#4是确定苦马豆素对所选营养素的spanchnic组织通量的影响。Swainsonine是一种天然植物。临床上，苦马豆素已显示出作为抗肿瘤剂的前景。因此，苦马豆素已显示出作为抗肿瘤剂的前景。因此，苦马豆素正在积极探索作为癌症的治疗方法。虽然苦马豆素的化学治疗性质已被广泛研究，很少或没有数据存在有关苦马豆素的药代动力学性质已被广泛研究，很少或没有数据存在有关苦马豆素的药代动力学或苦马豆素的作用或对营养代谢的影响，如果我们要开发口服给药方案和营养支持策略使用苦马豆素作为癌症治疗。将对动物进行手术插管/导管插入术，以便于采集消化物和血液样本，用于苦马豆素分析和营养代谢物分析。此外，将收集相同的肠上皮细胞用于微泡转运研究。这些研究将提供有关苦马豆素的吸收及其对营养代谢的影响的一些第一批数据。

Goals and Aims: The long term goals of this project include: 1) training students in the principles of toxicology and nutrient metabolism, 2) defining the kinetics and mode of swainsonine absorption, and 3) defining the effects of swainsonine on nutrient metabolism. In order to accomplish these goals, four specific aims will be addressed in this project. Specific Aim #1 is to define the absorption kinetics of swainsonine Specific Aim #2 is to define the effects of swainsonine on nutrient digestion and flow through the digestive tract. Specific Aim #3 is to define the spanchnic tissue flux of swainsonine. Specific Aim #4 is to define the effects of swainsonine on spanchnic tissue flux of selected nutrients. Swainsonine is a naturally occurring plant. Clinically, swainsonine has shown promise as an anti-tumor agent. As such, swainsonine has shown promise as an anti-tumor agent. As such, swainsonine is actively being explored as a treatment for cancer. Although the chemotherapeutic properties of swainsonine have been extensively studied, little or no data exists concerning the pharmacokinetics properties of swainsonine have been extensively studied, little or no data exists concerning the pharmacokinetics of swainsonine or the effects of swainsonine or the effects on nutrient metabolism if we are to develop oral dosing protocols and nutritional support strategies for the use of swainsonine as a cancer treatment. Animals will be surgically cannulated/catheritized to facilitate the collection of digest and blood samples for swainsonine analysis and nutrient metabolite analysis. In addition, same intestinal epithelia will be collected for microvesicle transport studies. These studies will provide some of the first data concerning the absorption of swainsonine and its effects on nutrient metabolism.