Biomedical subjects

Martin Kopecky

Publications and source records attributed to Martin Kopecky.

8 recordsLinked to original sources

PubMed2005

MDOC and atorvastatin have potential antiinflammatory effects in vascular endothelium of apoE-/- mouse model of atherosclerosis.

Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherogenesis. The aim of this study was to detect and quantify the changes of endothelial expression of VCAM-1, and ICAM-1 in the vessel wall after the short-term administration of simvastatin, atorvastatin, and micro dispersed derivatives of oxidised cellulose (MDOC) in apolipoprotein-E-deficient (apoE(-/-)) mice atherosclerotic model. Hyperlipidemic apoE(-/-) mice (n = 32) received normal chow diet or diet containing simvastatin or atorvastatin 10 mg/kg/day or MDOC 50 mg/kg/day. Total cholesterol, VLDL, LDL, HDL and TAG were measured and the endothelial expression of VCAM-1 and ICAM-1 was visualized and quantified by means of immunohistochemistry and stereology, respectively. Total cholesterol levels was insignificantly lowered only in MDOC treated mice but not in mice treated with statins. ICAM-1 endothelial expression was not affected by neither simvastatin nor MDOC treatment. However, significant diminution of VCAM-1 endothelial expression was observed in both atorvastatin and MDOC treated mice. These results provide new information of potential hypolipidemic substance MDOC and its potential anti-inflammatory effects. Furthermore, we have confirmed anti-inflammatory effects of atorvastatin independent of plasma cholesterol lowering. Thus, the results of this study show potential benefit of both MDOC and atorvastatin treatment in apoE(-/-) mouse model of atherosclerosis suggesting their possible combination might be of interest.

Administration, Oral↗

PubMed2005

Vimentin expression during altered spermatogenesis in rats.

The collapse of vimentin caused by some xenobiotics correlates with the loss of structural integrity of the seminiferous epithelium. In this study, we investigated the effect of busulphan (an anticancer drug with toxic effects on dividing germ cells) on vimentin filament distribution in rat seminiferous epithelium and compared it with changes found in testes of unilaterally cryptorchid rats. In the seminiferous epithelium, the vimentin labelling was observed only in the Sertoli cells, showing a stage-specific arrangement of the filaments. Both busulphan treatment and cryptorchism caused altered distribution of vimentin filaments in the Sertoli cells. In both models, the apical vimentin filaments collapsed towards the nuclei and were disorganized in the basal region of the Sertoli cells while the germ cells were diminished in the epithelium. After the busulphan effect subsided (4 weeks after administration), spermatogenesis began to restore and vimentin filaments began to organize in basal and perinuclear regions of Sertoli cells among the spermatogonia and spermatocytes. Vimentin labelling of the sloughed material in the lumen of cryptorchid testes (but not in busulphan treated animals) was observed. We conclude that the Sertoli cell vimentin filaments play an important role in the maintenance of spermatogenesis, their damage is associated with the seminiferous epithelium disintegration and their restoration with a recovery of spermatogenesis after the unfavourable conditions subside.

Animals↗

PubMed2005

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

BACKGROUND AND METHODS: In 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. RESULTS: Rapid 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. CONCLUSION: 99mTc 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.

Animals↗

PubMed2005

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 shortterm 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 immunohistochemical 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.

Animals↗

PubMed2004

Analysis of accumulation of 99mTc-octreotide and 99mTc-EDDA/HYNIC-Tyr3-octreotide in the rat kidneys.

The aim of this study was to compare renal handling and distribution of (99m)Tc-octreotide and (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide (HYNIC-TOC) in rats. In kidney perfusion experiments, the renal clearance value of (99m)Tc-octreotide was three times lower than that of (99m)Tc-EDDA/HYNIC-TOC. The predominant renal excretion of (99m)Tc-EDDA/HYNIC-TOC was associated with a high and long-term renal accumulation up to 48 hrs. Microautoradiographic results indicated that (99m)Tc-EDDA/HYNIC-TOC was retained mainly in the renal medulla within the cells of the collecting ducts and in the surrounding tissue. Lower positivity was found in the proximal and distal tubular cells. We conclude that the mechanism of renal accumulation of somatostatin analogues renal accumulation is complex and that proximal tubular reabsorption is probably not the main mechanism for uptake of (99m)Tc-EDDA/HYNIC-TOC in the kidneys. The presence of the somatostatin receptors, differences in the tonicity level within kidneys and other possible mechanisms could participate in their renal accumulation.

Animals↗

PubMed2004

Application of stereological methods for the quantification of VCAM-1 and ICAM-1 expression in early stages of rabbit atherogenesis.

Early stages of atherogenesis are characterized by the overexpression of cell adhesion molecules with the subsequent accumulation of macrophages, smooth muscle cells and proliferation of extracellular matrix in arterial intima. The quantification of atherogenic changes is necessary for the objective evaluation of the atherogenic process. The purpose of this study was to introduce stereological methods that may be used for the quantification of immunohistochemical staining, namely intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Twenty-four New Zealand White rabbits were subdivided into the three groups. Eighteen rabbits received a 0.4% cholesterol diet for 1, 2 and 3 months, respectively. Stereological principles of the systematic uniform random sampling and the point-counting method were applied for the quantification. Stereological analysis showed that VCAM-1 and ICAM-1 were upregulated during the consumption of high cholesterol diet and that VCAM-1, but not ICAM-1, has a considerable role in the formation of early atherosclerotic lesions. Stereological methods proved to be useful for the quantification of immunohistochemistry and can be used for an objective characterization of atherogenic changes in atherosclerosis.

Animals↗

PubMed2003

Examination of the functional activity of P-glycoprotein in the rat placental barrier using rhodamine 123.

Rhodamine 123 (Rho123), a model substrate of P-glycoprotein (P-gp), was used to evaluate the functional activity of P-gp efflux transporter in the rat placental barrier. The dually perfused rat-term placenta method was used. In our experiments, the materno-fetal transplacental passage of Rho123 did not meet the criteria of the first-order pharmacokinetics, suggesting an involvement of transporter-mediated process. Inhibitors of P-gp, such as [3'-keto-Bmt1]-[Val2]-cyclosporine (PSC833), cyclosporine (CsA), quinidine, and chlorpromazine, increased significantly the materno-fetal transplacental passage of Rho123 in the experiments under steady-state conditions. On the other hand, PSC833, CsA, and quinidine decreased the feto-maternal passage of Rho123. Similarly, in the experiments carried out under nonsteady-state conditions, CsA accelerated the passage of Rho123 in the materno-fetal direction and decreased its passage in the opposite direction. Feto-maternal transplacental clearances of Rho123 were found to be considerably higher than those in the materno-fetal course. Potent P-gp inhibitors, such as PSC833 or CsA, partially canceled the asymmetry. Negligible metabolism of Rho123 into its major demethylated metabolite rhodamine 110 was observed in the rat placenta. Expression of P-gp genes was detected using immunohistochemical, Western blotting, and reverse transcription-polymerase chain reaction methods preferentially in the second rat syncytiotrophoblast layer. In conclusion, these data suggest that P-gp limits the entry of Rho123 into fetuses and at the same time it accelerates the feto-maternal elimination of the model compound. Therefore, it seems plausible that pharmacokinetics of xenobiotics in the rat placental barrier could be controlled by P-gp in both directions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

P-glycoprotein expression and distribution in the rat placenta during pregnancy.

P-glycoprotein (P-gp) is a drug efflux transporter that limits the entry of various potentially toxic drugs and xenobiotics into the fetus and is thus considered a placental protective mechanism. In this study, P-gp expression was investigated in the rat chorioallantoic placenta over the course of pregnancy. Three methods have been employed: real-time RT-PCR, western blotting and immunohistochemistry. The expression of mdr1a and mdr1b genes was demonstrated as early as on the 11th gestation day (gd) and increased with advancing gestation. Western blotting analysis revealed the presence of P-gp in the rat placenta starting from gd 13 onwards. P-gp was localized in the developing labyrinth zone of the placenta on gd 13; from gd 15 up to the term P-gp was seen as a dot like continuous line in the syncytiotrophoblast layers. Our data confirm the presence of P-gp in the rat chorioallantoic placenta starting soon after its development, which may signify the involvement of P-gp in transplacental pharmacokinetics during the whole period of placental maturing.

ATP Binding Cassette Transporter, Subfamily B↗