Martin Kopecky

The changes in the endothelial expression of cell adhesion molecules and iNOS in the vessel wall after the short-term administration of simvastatin in rabbit model of atherosclerosis

Cell adhesion molecules P‐selectin, VCAM‐1 and ICAM‐1 play an important role in the pathogenesis of atherosclerosis. High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerotic processes. Simvastatin is an HMG‐CoA reductase inhibitor responsible for many clinical benefits. The aim of this study was to detect and quantify changes in endothelial expression of P‐selectin, VCAM‐1, ICAM‐1 and iNOS in the vessel wall after the short‐term administration of simvastatin in a rabbit model of atherosclerosis. Eighteen New Zealand White rabbits were randomly divided into three groups (n = 6). In the cholesterol group, rabbits consumed an atherogenic diet (0.4% cholesterol) for eight weeks. In the simvastatin group, rabbits consumed an atherogenic diet for six weeks and then consumed an atherogenic diet supplemented with simvastatin (10 mg kg−1) for two weeks. Biochemical analysis showed that administration of simvastatin led to an almost two‐fold lowering of the total serum cholesterol, VLDL, LDL and HDL, but not triglycerides, compared with the cholesterol‐fed rabbits only. Stereological analysis of the immuno‐histochemical staining revealed that administration of simvastatin (10 mg kg−1 daily) in an atherogenic diet decreased the endothelial expression of P‐selectin, ICAM‐1 and iNOS in both aortic arch and carotid artery compared with the cholesterol fed‐rabbits only. We conclude that simvastatin has beneficial effects on endothelial function by decreasing expression of P‐selectin, ICAM‐1 and iNOS in endothelial cells in the very early stages of atherogenesis.

Reciprocal changes in maternal and fetal metabolism of corticosterone in rat during gestation.

Objective. The objective of this study was to investigate the role of 11β-hydroxysteroid dehydrogenases (11HSD1 and 11HSD2) in determining the fetal concentration of glucocorticoids. Methods. The expression patterns for mRNA abundance, protein level, and enzyme activities of placental and fetal 11HSD1 and 11HSD2 were assessed from embryonic day 13 (E13) to day 21 (E21; term E22). The transplacental passage of maternal corticosterone and its contribution to fetal glucocorticoids was also studied. Results. Placental 11HSD1 mRNA decreased between days E13 and E14 and then remained at much lower values up to E21. Similarly, NADP+-dependent 11β-oxidation and 11-reduction were lower in late gestation. In contrast, placental 11HSD2 mRNA and protein decreased between E13 and E21. Dithiothreitol increased the activity of 11HSD2 and the output of 11-dehydrocorticosterone into fetal circulation.The fetal activity of 11HSD1 increased and 11HSD2 decreased between E16 and E21. Conclusions. The final third of gestation is accompanied by reciprocal changes in placental and fetal metabolism of corticosterone due to changes in 11HSD1 and 11HSD2 not only at the level of transcription but also at a posttranslational level.

99mTc demotate 1: biodistribution and elimination characteristics in rats.

Background and methodsIn this study, we investigated the biodistribution and elimination characteristics of a new radiolabelled somatostatin analogue, 99mTc demotate 1, in rats by in-vivo biodistribution and elimination experiments, perfused rat liver and kidney experiments and micro-autoradiography of renal tissue. ResultsRapid clearance from blood and most organs was found. High and long-term uptake in organs with high density of somatostatin receptors (the adrenals and pancreas) and in stomach and intestine was reduced in non-radiolabelled octreotide pretreated animals. The predominant urine excretion was associated with an accumulation of 99mTc demotate 1 in the kidney, mainly in the renal cortex. This uptake was not affected by non-radiolabelled octreotide pretreatment. Conclusion99mTc demotate 1 is a prospective radiopharmaceutical for use in human medicine in somatostatin receptor-positive tumour imaging and its potential should be confirmed in further experiments and clinical trials.