Multidrug resistance of cancer cells is often accompanied by the (over)expression of integral plasma membrane P-glycoprotein, an ATP-dependent transport pump for diverse unrelated compounds. The glutathione detoxification system represents another mechanism that may be involved in multidrug resistance. In the multidrug-resistant L1210/VCR cell line obtained by long-term adaptation of parental L1210 cells to vincristine, an increased expression of P-glycoprotein has previously been established. In this paper, we investigated if the glutathione detoxification system is also involved in the multidrug resistance of these cells. L1210/VCR cells with resistance induced by adaptation to vincristine were also found to be cross-resistant to vinblastine, actinomycin D, mitomycin C, doxorubicin and cyclophosphamide. The resistance of the above cells to vincristine and doxorubicin was accompanied by a depression of drug accumulation (which has not yet been established for other drug). L1210/VCR cells are able to survive better than sensitive cells under conditions when glutathione was depleted by L-buthionine sulfoximine. Nevertheless, L-buthionine sulfoximine did not influence the resistance of L1210/VCR cells to vincristine. Moreover, the presence of sublethal concentrations of cytostatics neither changed the IC50 value of resistant cells to L-buthionine sulfoximine nor the cytoplasmic activity of glutathione S-transferase, the crucial enzyme of glutathione detoxification system. All the above findings indicate that the glutathione detoxification system is not involved in the mechanisms that ensure the multidrug resistance phenotype of L1210/VCR cells., V. Boháčová, J. Kvačkajová, M. Barančík, Z. Drobná, A. Breier., and Obsahuje bibliografii
The role of gossypol in the cumulus expansion of oocyte-cumulus complexes (OCC) isolated from large antral porcine follicles was investigated. Marked suppression of cumulus expansion stimulated with follicle-stimulating hormone (FSH) and epidermal growth factor (EGF) was observed in the presence of different concentrations of gossypol. Comparable inhibitory effects were obtained in the presence of NO donor, S-nitroso-N-acetylpenicillamine or sodium nitroprusside, suggesting that the inhibitory effect of gossypol may be mediated via NO generation. The inhibitory effect of gossypol on cumulus expansion of OCC was accompanied by inhibition of progesterone secretion of OCC and the decrease of [125I]EGF binding to granulosa cells., J. Kolena, S. Vršanská, E. Nagyová, M. Ježová., and Obsahuje bibliografii
The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF., M. Hofer, M. Pospíšil, J. Netíková, V. Znojil, J. Vácha., and Obsahuje bibliografii
The purpose of this study was to investigate the influence of heat treatment on glucocorticoid (GC) -induced myopathy. Eight -week - old Wistar rats were randomly assigned to the control, Dex, and Dex + Heat groups. Dexamethasone (2 mg/kg) was injected subcutaneously 6 days per week for 2 weeks in the Dex and Dex + Heat group. In the Dex + Heat group, heat treatment was performed by immersing hindlimbs in water at 42 °C for 60 min, once every 3 days for 2 weeks. The extensor digitorum longus muscle was extracted following 2 weeks of experimentation. In the Dex + Heat group, muscle fiber diameter, capillary/muscle fiber ratio, and level of heat shock protein 72 were significantly higher and atrogene expression levels were significantly lower than in the D ex group. Our results suggest that heat treatment inhibits the development of GC -induced myopathy by decreas ing atrogene expression and increasing angiogenesis., Y. Morimoto, Y. Kondo, H. Kataoka, Y. Honda, R. Kozu, J. Sakamoto, J. Nakano, T. Origuchi, T. Yoshimura, M. Okita., and Obsahuje bibliografii
In this study, lipoic acid and heat shock treatments were applied to C2C12 myotubes and Sprague-Dawley rats to investigate changes in the heat shock protein 70 (HSP70) and glucose transporter 4 (GLUT4) in 4 different skeletal muscle groups. The results of western blotting indicated that treatment of lipoic acid for 24 h, heat-shock and combined lipoic acid and heat-shock which all increased the level of HSP70 substantially in C2C12 myotubes. However, either lipoic acid or heat-shock did not increase the level of GLUT4 in C2C12 myotubes. In an in vitro migration assay, lipoic acid increased wound migration only when it was applied for 3 h. Moreover, our in vivo results revealed that lipoic acid did not increase HSP70 and GLUT4 in all 4 different skeletal muscles. Furthermore, heat-shock increased HSP70 in all 4 different muscle groups, and heat-shock treatment alone increased the GLUT4 in the soleus muscle only, suggesting that the GLUT4 increased by heat-shock was slow-twitch muscle specific. Collectively, our results indicated that heat-shock is critical factor that modulates GLUT4 and HSP70 in the skeletal muscle of rats., P.-F. Wu, S.-C. Luo, L.-C. Chang., and Obsahuje bibliografii
D-galactosamine is a hepatotoxic agent, which induces diffuse injury of liver tissue followed by the regeneration process. Our data showed a high increase of serum aminotransferases after D-galactosamine administration, which indicates a high extent of liver injury. When lipid emulsion was applied immediately after D-galactosamine, the increase of serum aminotransferases was greatly reduced. In addition, the decrease of the cytochrome c oxidase activity induced by D-galactosamine was not observed after lipid emulsion administration and the increase of total liver oxidative capacity in the regeneration period due to activated mitochondrial biogenesis was accelerated. All these findings indicate a protective effect of lipid emulsion administration against D-galactosamine toxicity., R. Ferenčíková, Z. Červinková, Z. Drahota., and Obsahuje bibliografii
Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and/or oxidant mechanisms. Gum arabic (GA) is a complex po lysaccharide that acts as an anti-oxidant which can modulate inflammatory and/or immunological processes. Therefore, we tested here the effect of GA treatment (15 % in the drinking water for 4 weeks) in plasma and urine of rats, on a novel cytokine that has been shown to be pro-inflammatory, viz, DNA-binding high-mobility group box-1 protein (HMGB1). Adenine (0.75 % in the feed, 4 weeks) significantly increased indoxyl sulphate, urea and creatinine concentrations in plasma, an d significantly decreased the creatinine clearance. GA significantly abated these effects. The concentrations of HMGB1 in urine before the start of the experiment were similar in all four groups. However, 24 h after the last treatment, adenine treatment increased significantly the concentration of HMGB1 when compared with the control. GA treatment did not affect the HMGB1 concentration in urine. Moreover, the concentration of HMGB1 in plasma obtained 24 h after the last treatment in rats treated with adenine was drastically reduced compared with the control group. This may explain its significant rise in urine. In conclusion, HMGB1 can be considered a potentially useful biomarker in adenine induced CRF and its treatment., B. H. Ali, M. Al Za'abi, A. Al Shukaili, A. Nemmar., and Obsahuje bibliografii
In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute’s breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists., V. Lobellová, E. Brichtová, T. Petrásek, K. Valeš, A. Stuchlík., and Obsahuje bibliografii
We studied hsBAFF activity in in vitro mouse splenic B cells. hsBAFF effects on intracellular free Ca 2+ concentration ([Ca 2+ ] i ) were assayed, using a laser scanning confocal microscope with fluorescent probe, Fluo-3/AM. We showed that treatment of B cells with 0.5-5 μ g/ml hsBAFF resulted in significantly higher [Ca 2+ ] i levels in a dose-dependent fashion at 12 and 24 h, respectively (p<0.05 or p<0.01 vs. control). Furthermore, we noticed that 2.5 μ g/ml hsBAFF-treated cells were significantly resistant to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca 2+ -ATPase inhibitor (p<0.05 hsBAFF plus Tg group vs. Tg group). Thus hsBAFF may promote B cell survival by direct upregulation of [Ca 2+ ] i physiological homeostasis contri buting to prevention of [Ca 2+ ] i dysfunction. Using immunocytochemistry and Western blot analysis, we found that the activation of ERK1/2 due to hsBAFF was triggered by a [Ca 2+ ] i -dependent pathway, leading to elevation of B cell proliferation. This is supported by the findings that intracellular Ca 2+ chelator BAPTA/AM attenuated phosphorylated ERK1/2 expression and cell proliferation in hsBAFF-stimulated B cells. hsBAFF-stimulated B cell proliferation was obviously reduced by mitogen extracellular kinase 1/2 (MEK1/2, upstream of ERK1/2) inhibitor U0126. Taken together, the main finding of this study is that hsBAFF elicits higher but homeostatic [Ca 2+ ] i levels, which regulates ERK1/2 activity and cell proliferation in in vitro B cells., J. Q. Liang, W. Zhang, L. Wen, W. Gao, S. Q. Zhang, L. Chen., and Obsahuje bibliografii