Synchrotron Radiation-Based Three-Dimensional Visualization of Angioarchitectural Remodeling in Hippocampus of Epileptic Rats

Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation(SR)-based X-ray in-line phase-contrast imaging (ILPCI)and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.

Characterization and mapping of the multi-component release kinetics of a Traditional Chinese Medicine dosage form using a modified LC/MS/MS method and chemomic release kinetic theory

It is essential to develop effective methods for the quality control of the traditional medicine with multiple components.However,few researches on the quality control have been conducted to interpret the holistic characteristics of the traditional medicine in terms of dissolution/release.In this study,the multi-component release kinetics of Traditional Chinese Medicine(TCM)dosage forms was characterized and mapped by multivariate analysis techniques in the field of‘‘-omics’’.The Liuweidihuang pill was used as a model formulation.The multi-component release kinetics of the concentrated and water-honeyed Liuweidihuang pills at rotation speeds of 50 and 100 rpm were analyzed by chemomic release kinetic theory and modified LC/MS/MS method.Mass features of 103(concentrated pills)and 101(water-honeyed pills)were selected with a linear correlation coefficient Z0.99 between mass responses and concentrations.To compose the chemomic standard spectrum,the relative abundance of both mass features was no less than 1%as compared with an internal standard.The correlation coefficients between six samples of various solutions were in line with analytical requirements of precision(rZ0.985).The score plots of principal component analysis showed that the concentrated Liuweidihuang pills presented better chemomic release reproducibility than the water-honeyed pills.Conversely,the impact of rotation speed on the chemomic release was less obvious.The heat maps of hierarchical clustering analysis did not show significant changes in individual clusters of mass features along different time intervals,reflecting the release integrity of the mass features.Therefore,both multivariate analysis methods,the principal component analysis and the hierarchical clustering analysis,seemed to be effective techniques to demonstrate the multiple component release performance of TCM.The research provided the basis of a new strategy for the quality control procedures of the dissolution/release for the traditional medicine and multi-component natural products to address increasing regulatory requirements and scrutiny across the world.