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.
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