RESUMO
BACKGROUND: Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. METHODS: Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. RESULTS: The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. CONCLUSIONS: D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.
RESUMO
BACKGROUND: It is known that some opioids protect the myocardial tissue from myocardial ischemia-reperfusion (I/R) injury. The aim of this study was to investigate whether remifentanil, at a clinically relevant concentration that's during the peri-ischemic period, has a protective effect against a regional I/R injury in an in vivo rat heart model. METHODS: Rats were subjected to 25 minutes of coronary artery occlusion and this was followed by 24 hours of reperfusion. A microcatheter was advanced into the left ventricle and the hemodynamic function was evaluated after 24 hours of reperfusion. The infarct size was determined by triphenyltetrazolium staining. The serum level of cardiac troponin-I (cTnI) was determined by ELISA (enzyme-linked immunosorbent assay). RESULTS: Remifentanil administration during the peri-ischemic period didn't show any identifiable protective effects for the hemodynamic function or to reduce the infarct size. In the control group, the peak rate of the ventricular pressure increase (+dP/dt(max)) (P < 0.05) and the peak rate of the intraventricular pressure decline (-dP/dt(max) P < 0.05) were significantly decreased as compared to those values for the sham group. In the remifentanil group, the +dP/dt(max) and -dP/dt(max) were not improved compared to those values of the control group. The infarct size was 45.6% of the area at risk in the control group, and the infarct size was reduced by administration of remifentanil to 43.2% in the remifentanil group. The I/R-induced serum level of cTn-I was not reduced by remifentanil infusion during the peri-ischemic period. CONCLUSIONS: Remifentanil, at a clinically relevant concentration that's infused during the peri-ischemic period, has no myocardial protective effect after regional myocardial I/R injury in an in vivo rat heart model.
RESUMO
1. The aims of the present in vitro study were to examine the roles of pathways associated with arachidonic acid metabolism in dexmedetomidine-induced contraction and to determine which endothelium-derived vasodilators are involved in the endothelium-dependent attenuation of vasoconstriction elicited by dexmedetomidine. 2. Dexmedetomidine (10(-9)-10(-6) mol/L) concentration-response curves were constructed in: (i) aortic rings with no drug pretreatment; (ii) endothelium-denuded aortic rings pretreated with either 2 x 10(-5) mol/L quinacrine dihydrochloride, 10(-5) mol/L nordihydroguaiaretic acid (NDGA), 3 x 10(-5) mol/L indomethacin or 10(-5) mol/L fluconazole; and (iii) endothelium-intact aortic rings pretreated with either 5 x 10(-5) mol/L N(G)-nitro-l-arginine methyl ester (l-NAME), 10(-5) mol/L fluconazole, 10(-5) mol/L indomethacin, 10(-5) mol/L glibenclamide, 5 x 10(-3) mol/L tetraethylammonium or 5 x 10(-5) mol/L l-NAME plus rauwolscine (10(-5), 10(-6) mol/L). The production of nitric oxide (NO) metabolites was determined in human umbilical vein endothelial cells treated with dexmedetomidine. 3. Quinacrine dihydrochloride, NDGA and indomethacin attenuated the dexmedetomidine-induced contraction of endothelium-denuded rings. Dexmedetomidine (10(-7)-10(-6) mol/L)-induced contractions of endothelium-denuded rings were enhanced compared with those of endothelium-intact rings, as were dexmedetomidine-induced contractions of endothelium-intact rings pretreated with l-NAME or tetraethylammonium. Rauwolscine attenuated dexmedetomidine-induced contractions in endothelium-intact rings pretreated with l-NAME. Dexmedetomidine (10(-6) mol/L) was found to activate NO production. 4. Taken together, the results indicate that dexmedetomidine-induced contraction of aortic rings involves activation of the lipoxygenase and cyclo-oxygenase pathways and is attenuated by increased NO production following stimulation of endothelial alpha(2)-adrenoceptors by dexmedetomidine.
