Drug-protein interaction studied by technique of microdialysis combined with high performance liquid chromatography

Drug-protein binding is an important process in determining the activity and fate of a pharmaceutical agent once it has entered the body. This review examines the method of microdialysis combined with high-performance liquid chromatography (HPLC) that has been developed;by ours to study such interactions, in which the microdialysis was applied to sample the free drug in the mixed solution of drug with protein, and HPLC to quantify the concentration of free drug in the microdialysate. This technique has successfully been used for determining various types of binding interactions between the low affinity drugs, high affinity drugs and enantiomers to HSA. For the case of competitive binding of two drugs to a protein in solution, a displacement equation has been derived and examined with four nonsteroidal anti-inflammatory drugs and HSA as model drugs and protein, respectively. Microdialysis with HPLC was adopted to determine simultaneously the free solute and displacing agent in drug-protein solutions. The method is able to locate the binding site and determine affinity constants even up to 10(7) L/mol accurately.

Application of liquid pre-column capillary electrophoresis technique to the study of interaction between drug enantiomers and human serum albumin

Based on the chiral separation of several basic drugs, dimetindene, tetryzoline, theodrenaline and verapamil, the liquid pre-column capillary electrophoresis (LPC-CE) technique was established. It was used to determine free concentrations of drug enantiomers in mixed solutions with human serum albumin (HSA). To prevent HSA entering the CE chiral separation zone, the mobility differences between HSA and drugs under a specific pH condition were employed in the LPC. Thus, the detection confusion caused by protein was totally avoided. Further study of binding constants determination and protein binding competitions was carried out. The study proves that the LPC technique could be used for complex media, particularly the matrix of protein coexisting with a variety of drugs.

认知电位时空模式研究

This report mainly focused on methodology of spatiotemporal patterns (STP) of cognitive potentials or event-related potentials (ERP). The representation of STP of brain wave is an important issue in the research of neural assemblies. This paper described methods of parametric 3D head or brain modeling and its corresponding interpolation for functional imaging based on brain waves. The 3D interpolation method is an extension of cortical imaging technique. It can be used with transformed domain features of brain wave on realistic head or brain models. The simulating results suggests that it is a better method in comparison with the global nearest neighbor technique. A stable and definite STP of brainwave referred as microstate may become basic element for comprehending sophisticated cognitive processes. Fuzzy c-mean algorithm was applied to segmentation STPs of ERP into microstates and corresponding membership functions. The optimal microstate number was estimated with both the trends of objective function against increasing clustering number and the decorrelation technique base don microstate shape similarity. Comparable spatial patterns may occur at different moments in time with fuzzy indices and thus the serial processing limit generated from behavioral methods has been break through. High-resolution frequency domain analysis was carried out with multivariate autoregressive model. Bases on a 3D interpolation mentioned above, visualization of dynamical coordination of cerebral network was realized with magnitude-squared partial coherence. Those technique illustrated with multichannel ERP of 9 subjects when they undertook Strop task. Stroop effects involves several regions during post-perception stage with technique of statistical parameter mapping based F-test [SPM(F)]. As SPM(F) suggested task effects occurred within 100 ms after stimuli presentation involved several sensory regions, it may reflect the top-down processing effect.