IN VIVO MICRODIALYSIS SAMPLING FOR METABOLISM STUDIES

该项目的主要目标是开发新技术， 持续监测体内生化过程， 生物系统的扰动。 方法将是设计一个 基于微透析技术的“生物传感器”。 微透析是 通过将一小段透析纤维植入 通过其灌注测试溶液的兴趣。 小分子可以 扩散通过膜，以被递送到膜或从膜取样。 靶组织。 这种“生物传感器”探针直接类似于毛细管 血管 这个系统将保持有机体的完整性， 细胞和器官的区室化以及其他生理学上的 条件 没有液体的净流量，也最小化了扰动 从实验中。 因此，实际的生理途径将是 研究没有人为刺激的替代路径。 的 微透析取样将与液相色谱分析相结合。 这提供了对每个样品中的几种物质的选择性检测 在体内实验中。 将采样步骤与 分析步骤相对于其他体内方法提供了几个优点。 特别是苯和9-氨基-1，2，3，4- 四氢吖啶（THA）将被研究。 苯最简单 芳香，但其代谢的信息可以外推到更多 复杂的分子。 这些都是非常感兴趣的，因为 人类广泛接触酚类化合物， 和药物来源。 由于已经有很多关于 苯的代谢，它作为一个很好的测试化合物的方法 发展 关于苯还有几个重要的问题 代谢，所提出的方法将有助于回答。 很少 报道了THA的代谢。 据报道， 治疗阿尔茨海默病的有希望的疗法，但已表现出肝毒性 在临床试验中，这一信息极为重要。

The primary goal of this project is to develop new techniques to continuously monitor biochemical processes in vivo with minimal perturbation of the biological system. The approach will be to design a "biosensor" based on the technique of microdialysis. Microdialysis is performed by implanting a small length of dialysis fibre at the site of interest through which a test solution is perfused. Small molecules can diffuse through the membrane to either be delivered to or sampled from the target tissue. This "biosensor" probe is directly analogous to a capillary blood vessel. This system will maintain the integrity of the organisms, both cell and organ compartmentation as well as other physiological conditions. There is no net flow of liquid, also minimizing perturbations from the experiment. Thus the actual physiological pathways will be studied without artificial stimulation of alternative paths. The microdialysis sampling will be coupled to liquid chromatographic analysis. This provides for selective detection of several species in each sample during the in vivo experiment. Decoupling the sampling step from the analysis step offers several advantages relative to other in vivo methods. In particular the metabolism of benzene and 9-amino-1,2,3,4- tetrahydroacridine (THA) will be investigated. Benzene is the simplest aromatic but information on its metabolism may be extrapolated to more complicated molecules. These are of great interest because of the widespread human exposure to phenolic compounds from dietary, environmental and pharmaceutical sources. As much information already exists on the metabolism of benzene, it serves as a good test compound for method development. There remain several important questions about benzene metabolism that the proposed methods will help answer. Little has been reported on the metabolism of THA. As THA has been reported to be a promising therapy for Alzheimer's disease but has exhibited liver toxicity in clinical trials this information is extremely important.