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SDF-1 and its receptor in the ventricles of rat with monocrotaline-induced pulmonary hypertension

Abstract

Aim: Chemokine stromal cell derived factor-1 (SDF-1) plays an important role in many processes such as apoptosis, proliferation, migration and angiogenesis, and these effects are mediated mostly by the receptor CXCR4. The aim of this study was to determine the expression of SDF-1 and CXCR4 in the ventricles of rats with monocrotaline-induced pulmonary hypertension.

Methods: 10–12 weeks old male Wistar rats were injected with monocrotaline (s. c., 60mg/kg; MON) or vehicle (CON). Rats were sacrificed 1 week (1W-MON, 1W-CON), 2 weeks (2W-MON, 2W-CON) and 4 weeks after monocrotaline administration (4W-MON, 4W-CON). Gene expression of SDF-1 and CXCR4 was determined by qRT-PCR.

Results: We observed a decrease in the SDF-1 expression on mRNA level in the right ventricle in 2W-MON and 4W-MON rats without any changes in the left ventricles and a decrease in CXCR4 expression in 1W-MON in both ventricles with an increase of CXCR4 expression in 4W-MON in the left ventricle (*P ˂ 0.05).

Conclusion: SDF-1/CXCR4 axis is affected in both ventricles of rats with monocrotaline model of pulmonary hypertension.

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The Transcription Factor Creb is Involved in Sorafenib-Inhibited Renal Cancer Cell Proliferation, Migration and Invasion

Abstract

Our previous reports showed that the cyclic-AMP-response element-binding protein (CREB) served as a proto-oncogene in the process of tumorigenesis and mediated the growth and metastatic activity of renal cancer cells. Our study, therefore, explored the role of CREB in sorafenib- -inhibited cell proliferation, migration and invasion. Renal cancer cells were cultured in medium containing sorafenib for 12, 24, 48 and 72 h. The MTT assay was used to study the cytotoxic effects of sorafenib. Cell invasion and migration were assayed in wound healing and transwell experiments, respectively. Protein expression levels were evaluated by western blotting. The results show that sorafenib treatment decreased cell viability in a dose- and time-dependent manner. Sorafenib inhibited cell migration and invasion and decreased the expression of MMP-2 and MMP-9. Moreover, addition of the recombinant plasmid pCI-neo/ CREB (PN) reversed the sorafenib-induced inhibition of cell proliferation, migration and invasion. These results show that CREB is associated with the sorafenib-induced inhibition of proliferation, migration and invasion.

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The Modulation Of Detrusor Contractility By Agents Influencing Ion Channel Activity

Abstract

Background: This study specified the role of several significant ion channels regulating the metabolism of calcium ions in contraction and relaxation of human detrusor muscle in order to identify possible target for future drugs that are capable of treating diseases resulting from impaired detrusor activity, e.g. overactive bladder. Although this disease can be successfully treated with muscarinic receptor antagonists or β3 agonist, many patients may not be suitable for chronic therapy, especially due to the relatively high side effects of the treatment.

Material and Methods: The study used the isolated detrusor tissue samples, which were obtained from the macroscopic healthy tissue of urinary bladder from 19 patients undergoing a total prostatectomy because of localized prostate cancer. Each biological sample was prepared into 8 strips. We used oxybutynin and mirabegron as control drugs and several blockers of specific subtypes calcium and potassium ion channels as tested substances. The contractility of bladder was investigated by an organ tissue bath method in vitro and contraction was induced by carbachol.

Results: The amplitude of contraction was successfully decreased by positive control drugs and, from tested agents, the comparable effect had the substance capable of influencing IP3 receptors and Orai-STIM channels and combination consisting of drugs possessing an inhibitory effect on IP3 receptors, L- and T-type voltage-gated calcium channels and Orai-STIM channels.

Conclusion: The present work represents a new finding about handling Ca2+ in urinary bladder contraction and pointed to a dominant role of IP3 receptor-mediated pathway in the regulation of Ca2+ metabolism, which may represent a future strategy in pharmacotherapy of impaired detrusor activity.

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Stimulatory effect of repeated treatment with lipopolysaccharide on a key enzyme of the kynurenine pathway in both genders in rats

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Preliminary studies on the effect of rebamipide against the trypsin and egg-albumin induced experimental model of asthma

inflammatory bowel disease, Mediators Inflamm.   7 (1998) 157-162; DOI: 0962-9351/98/030157-06. C. D. Kim, Y. K. Kim and S. H. Lee, Rebamipide inhibits neutrophil adhesion to hypoxia/re-oxygenation stimulated endothelial cells via nuclear factor-κB dependent pathway, J. Pharmacol. Exp. Ther.   294 (2000) 864-869; DOI: 0022-3565/00/2943-0864. J. Y. Ro, J. Y. Kim and K. H. Kim, The inhibitory mechanism of rebamipide on the mediator release in the guinea pig lung mast cells activated with specific antigen

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Effect of quercetin on the transport of ritonavir to the central nervous system in vitro and in vivo

. DeArmond and S. B. Prusiner, Pharmacokinetics of quinacrine efflux from mouse brain via the P-glycoprotein efflux transporter, PLoS One 7 (2012) e39112; DOI: 10.1371/journal.pone.0039112. 4. D. Pal, D. Kwatra, M. Minocha, D. K. Paturi, B. Budda and A. K. Mitra, Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals, Life Sci. 88 (2011) 959–971; DOI: 10.1016/j.lfs.2010.09.012. 5. A. Antinori, G. Arendt, J. T. Becker, B. J. Brew, D. A. Byrd, M. Cherner, D. B. Clifford, P. Cinque, L. G. Epstein, K

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Lipoxygenase in Condition of Experimental Hypertriacylglycerolaemia

] Radmark O, Werz O, Steinhilber D. 5-Lipoxygenase: regulation of expression and enzyme activity. Trends Biochem. Sci. 2007;32:332–341. [15] Riccioni G, Zanasi A, Vitulano N, Mancini B, D’orazio N. Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives. Mediators of Inflamm. 2009;Article ID 737282, 6 pages. [16] Romano M. Lipid mediators: lipoxin and aspirin-triggered 15-epi-lipoxins. Inflamm. Allergy Drug Targets 2006;5: 81–90. [17] Schindler CH. The metabolic

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Sesquiterpenes α-humulene and β-caryophyllene oxide enhance the efficacy of 5-fluorouracil and oxaliplatin in colon cancer cells

bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction, Molecules 18 (2013) 1418–1433; https://doi.org/10.3390/molecules18021418 11. Y. S. Sun, L. X. Lv, Z. Zhao, X. He, L. You, J. K. Liu and Y. Q. Li, Cordycepol C induces caspase-independent apoptosis in human hepatocellular carcinoma HepG2 cells, Biol. Pharm. Bull . 37 (2014) 608–617. 12. T. C. Chou, Drug combination studies and their synergy quantification using the Chou-Talalay method, Cancer Res . 70 (2010) 440–446; https://doi.org/10.1158/0008-5472.CAN-09

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Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats

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Induction of xenobiotic-metabolizing enzymes in hepatocytes by beta-naphthoflavone: Time-dependent changes in activities, protein and mRNA levels

, Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism, Cancer Res. 63 (2003) 5513-5520. 15. M. D. Burke and R. T. Mayer, Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene, Drug Metab. Dispos. 2 (1974) 583-588. 16. A. Untergasser, I. Cutcutache, T. Koressaar, J. Ye, B. C. Faircloth, M. Remm and S. G. Rozen, Primer3 - new capabilities and interfaces, Nucleic Acids Res. 40 (2012) e

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