![]() First, MALDI-MS requires the careful coating of the tissue with a matrix compound prior to the MS analysis. (3-5) While this technique continues to mature, some lingering limitations are apparent. While this conventional procedure might be fully automated, a direct surface sampling, ionization, and analysis method by mass spectrometry of such thin tissue sections, including the same tissues used for WBA study, would save time and other resources by shortening the sampling and extraction steps of a quick first pass look for drug and metabolite distributions.Ĭurrently, the most widely used technique for molecular identification of drug related materials directly from animal thin tissue sections is matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Currently, the particular molecular forms and quantity of the drug-related material present must be determined from punched samples for areas of interest in the same tissue sections (e.g., radioactive “hot spots”) or from whole organ tissue homogenates from separate animals, which are analyzed with conventional sample extraction, cleanup and high-performance liquid chromatography−mass spectrometry (HPLC−MS) or tandem mass spectrometry (MS/MS). (1, 2) Inherently, WBA cannot distinguish between the parent drug and the metabolites of that drug. In the area of drug discovery, the distribution of total drug related compounds in thin tissue sections is often determined using whole-body autoradiography (WBA) employing radiolabeled drugs. The ability to directly and efficiently sample from thin tissue sections via a liquid extraction and then perform a subsequent liquid phase separation increases the utility of this liquid extraction surface sampling approach. ![]() These drug and metabolite data obtained using the LMJ surface sampling/HPLC−MS method and the results achieved by analyzing similar samples by conventional extraction of the tissues and subsequent HPLC−MS analysis were consistent. Confirming the presence of one or the other or both of these glucuronides in the extract from the various organs was not possible without the separation. In addition, two isomeric phase II metabolites of propranolol (an aliphatic and an aromatic hydroxypropranolol glucuronide) were observed in the chromatograms of the extracts from lung, kidney, and liver. The parent drug was observed in the chromatograms of the surface sampling extracts from all the organs of the dosed mouse examined. To illustrate the utility of coupling a separation with this direct liquid extraction based surface sampling approach, four different organs (brain, lung, kidney, and liver) from whole-body thin tissue sections of propranolol dosed and control mice were examined. A calcium-rich diet inhibits lipogenesis in the fat tissue thus additionally improving the cardiovascular risk profile.In this work, a commercially available autosampler was adapted to perform direct liquid microjunction (LMJ) surface sampling followed by a high-pressure liquid chromatography (HPLC) separation of the extract components and detection with electrospray ionization mass spectrometry (ESI-MS). This positive effect is due to parathormone suppression with a subsequently decreased calcium content in the vascular smooth muscle cells. A calcium-rich diet (> 1000 mg calcium daily) slightly decreases blood pressure. Moreover, patients with essential hypertension have high parathormone levels already before hypertension is diagnosed. There is a positive correlation between parathormone and blood pressure, present in primary as well as secondary hyperparathyroidism. Parathormone plays a permissive role since it regulates the calcium-influx into the cells and thus increases the vasoconstrictive effect. Intracellular calcium plays a crucial role in the regulation of cardiovascular functions: An increased influx of calcium into the vascular smooth muscle cells leads to an augmental muscular tone and therefore to an increased vascular resistance and rise in blood pressure. ![]() ![]() The regulation of blood pressure is complex with several organs being involved.
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