RESUMEN
Hydrogen sulfide (H2S) is a significant physiologic inhibitory neurotransmitter. The main goal of this research was to examine the contribution of diverse potassium (K+) channels and nitric oxide (NO) in mediating the H2S effect on electrical field stimulation (EFS)-induced neurogenic contractile responses in the lower esophageal sphincter (LES). EFS-induced contractile responses of rabbit isolated LES strips were recorded using force transducers in organ baths that contain Krebs-Henseleit solutions (20 ml). Cumulative doses of NaHS, L-cysteine, PAG, and AOAA were evaluated in NO-dependent and NO-independent groups. The experiments were conducted again in the presence of K+ channel blockers. In both NO-dependent and NO-independent groups, NaHS, L-cysteine, PAG, and AOAA significantly reduced EFS-induced contractile responses. In the NO-dependent group, the effect of NaHS and L-cysteine decreased in the presence of 4-AP, and also the effect of NaHS decreased in the NO-dependent and independent group in the presence of TEA. In the NO-independent group, K+ channel blockers didn't change L-cysteine-induced relaxations. K+ channel blockers had no impact on the effects of PAG and AOAA. In addition, NaHS significantly relaxed 80-mM KCl-induced contractions, whereas L-cysteine, PAG, and AOAA did not. In the present study, H2S decreased the amplitudes of EFS-induced contraction responses. These results suggest that Kv channels and NO significantly contribute to exogenous H2S and endogenous H2S precursor L-cysteine inhibitory effect on lower esophageal sphincter smooth muscle.
Asunto(s)
Sulfuro de Hidrógeno , Sulfuros , Animales , Conejos , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Esfínter Esofágico Inferior/metabolismo , Canales de Potasio , Cisteína/farmacología , Óxido Nítrico/metabolismoRESUMEN
Objectives: Endocannabinoids and nicotine regulate the neurotransmitter release in different central and peripheral synapses. Various studies in the literature demonstrate the interaction between endocannabinoid and nicotinic systems, especially in the central nervous system. The interaction between nicotinic and endocannabinoid systems was investigated in this study. We aimed to show the effects of cannabinoid and vanilloid receptor antagonists on nicotine-induced relaxation response increases in rabbit corpus cavernosum. Materials and Methods: From a total of seven male albino rabbits, three or four equal strips were cut from each corpus cavernosum and inserted in isolated organ baths. Tissues were contracted with phenylephrine (3×10-5 M). After contraction reached a plateau, strips were stimulated with EFS, and with the stabilization of EFS relaxation responses, 10-4 M of nicotine was administered to tissues. After that, in order to investigate the effects of AM251 (CB1 antagonist), AM630 (CB2 inverse agonist) or capsazepine (a vanilloid receptor antagonist) were given to different tissues, after the resting period. Results: Nicotine (10-4 M) increased the EFS-induced relaxation responses (14.60%±2.94%, P<0.05). AM630 decreased the enhancement of nicotine-induced EFS relaxation responses (nicotine 10-4 M enhancement: 17.16%±3.19%; nicotine 10-4 M enhancement in the presence of AM630 10-6 M: 4.44%±3.43% P<0.05; n=6), whereas effects of AM251 and capsazepine were not significant. Conclusion: In the present study, nicotine increased the amplitudes of EFS-induced relaxation responses probably via nicotinic acetylcholine receptors located on the nitrergic nerves of the corpus cavernosum. We showed the role of cannabinoid-like endo-ligands in nicotine-induced enhancement via CB2 receptors but not CB1 and VR1 receptors.
RESUMEN
BACKGROUND: Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system. METHODS: The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs-Henseleit solution. After obtaining EFS-induced contractile responses, 10-4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10-6 M), AM630 (a cannabinoid CB2R antagonist, 10-6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10-6 M). RESULTS: Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines' effect. DISCUSSION: These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines' effect.
Asunto(s)
Cannabinoides , Nicotina , Animales , Conejos , Nicotina/farmacología , Cannabinoides/farmacología , Canales Catiónicos TRPV/farmacología , Endocannabinoides/farmacología , Vejiga Urinaria , Contracción Muscular , Músculos , Estimulación Eléctrica/métodosRESUMEN
OBJECTIVE: Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. METHODS: Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. RESULTS: The TAS (p=0.001), total thiol, and native thiol levels (pï¼0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (pï¼0.001). CONCLUSION: These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs.
RESUMEN
Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening viral infection. The pathogenesis of the disease is not well understood. The aim of this study was to determine the change in irisin concentrations in patients with CCHF. The study included a total of 30 patients with CCHF and 30 control participants. Irisin concentrations were determined using a commercial ELISA kit. Median irisin concentrations were 9.03 (5.81-12.22) µg/mL and 4.2 (3.39-7.62) µg/mL, respectively, in each group. There was no correlation between irisin and disease severity. Any correlations between irisin, and lactate dehydrogenase (LDH), international normalization ratio (INR), Alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, activated partial thromboplastin time (aPTT), D-dimer and hemoglobin, were also investigated. There were statistically significant positive correlations between the values of irisin, and platelet (p = 0.005, r: 0.369), ALT (p = 0.049, r: 0.261), INR (p = 0.006, r: 0.359) and aPTT values (p = 0.002, r: 0.405). A negative correlation was also found between the values of irisin and LDH (p = 0.008, r: ï¼0.348). No correlations were determined between the values of irisin, and AST, hemoglobin and D-dimer. These results suggest that irisin may have a role in CCHF.
Asunto(s)
Fibronectinas/sangre , Fiebre Hemorrágica de Crimea/patología , Adulto , Análisis Químico de la Sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. METHODS: Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group I), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. RESULTS: Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. CONCLUSION: We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Deformación Eritrocítica/efectos de los fármacos , Ibuprofeno/farmacología , Riñón/fisiopatología , Hígado/fisiopatología , Piroxicam/análogos & derivados , Circulación Renal/efectos de los fármacos , Anestesia General , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Ibuprofeno/administración & dosificación , Infusiones Intravenosas , Inyecciones Intravenosas , Piroxicam/administración & dosificación , Piroxicam/farmacología , Ratas , Ratas WistarRESUMEN
Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 µM against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.