Browsing by Author "Gok, S"

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    Contribution of RhoA kinase and protein kinase C to weak relaxant effect of pinacidil on carbachol-induced contractions in sensitized guinea-pig trachealis
    Gok, S; Izanli-Paksoy, A; Vural, K
    The exact mechanisms underlying the weak bronchodilator effect of K(ATP) channel openers on cholinergic stimulations is unknown. The present study was designed to examine the relaxant efect of pinacidil in guinea-pig trachea stimulated with carbachol by the presence of calcium sensitizer inhibitors; HA 1077, a rhoA kinase inhibitor, and chelerythrine, a protein kinase C inhibitor. Adenosine (10 mu M) was used as other contractile agent for comparison. Tracheal tissues were isolated from ovalbumin sensitized guineapigs and changes in tension were recorded isometrically. Pinacidil (1-100 mu M, cumulatively) and HA 1077 (0.01-30 mu M, cumulatively) produced concentration-dependent relaxations in unstimulated tisues. The relaxant response to pinacidil decreased in carbachol contracted tissues, but increased in adenosine-stimulated tissues. Pretreatment of the tissues with HA 1077 (0.1 mu M) and chelerythrine (10 mu M) increased the pinacidil-induced relaxations by similar to%100 and %40, respectively. Glibenclamide, a KATP channel blocker, partially antagonized the pinacidil response in contracted tissues. Glibenclamide also inhibited the carbachol and adenosine induced contractions. These results suggest that diminish effect of pinacidil may have related to the enhanced calcium sensitization by cholinergic stimulation. Rho kinase inhibitors appear more effective than PKC inhibitors to achieve of this failure.
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    Apoptosis of colon cancer cells under the effect of geldanamycin derivate
    Kosova, F; Kasar, Z; Tuglu, I; Kurt, FO; Gok, S; Ari, Z; Imren, T
    AIM: The apoptotic effect of geldanamycin derivative may be important for the colorectal cancer therapy. The mechanisms of apoptosis require understanding of the behavior of colon cancer cell line Colo-205 which mimics colon adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for its anti-apoptotic activity. METHOD: Apoptotic ratio of the Colo-205 cells was determined after 17-AAG application with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and apoptosis related genes. Apoptosis signal path related key mitochondria! proteins, cytochrome c, bcl-2, caspase 9 and Apaf-1 expression were examined with RT-PCR method. RESULTS: 17-AAG caused induction of cell death. Apoptotic related genes such as cytochrome-c, Apaf-1 and caspase-9 protein expressions were increased significantly (p < 0.05) and anti-apoptotic bcl-2 expression was decreased significantly (p < 0.05). Our results indicated that the application of 17-AAG on Colo-205 cells showed anticancer effect by the apoptosis due to alteration of apoptotic genes. CONCLUSION: The apoptotic effect of 17-AAG as an natural product for alternative medicine would be very important for the success and quality of life during the treatment of colon carcinoma with the combination of anticancer drugs (Tab. 1, Fig. 2, Ref. 32). Text in PDF www.elis.sk.
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    Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet
    Olmez, E; Vural, K; Gok, S; Ozturk, Z; Kayalar, H; Ayhan, S; Var, A
    Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low-density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium-dependent relaxations in cholesterol-fed rats. For this purpose, rats were fed by 2% cholesterol-enriched or standard chow for 8weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100mg/kg/day. Atorvastatin at dose of 20mg/kg of body weight daily was also given as positive control. After 8weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium-dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL-cholesterol levels were found to be increased in cholesterol-fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis. Copyright (c) 2015 John Wiley & Sons, Ltd.
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    Safety of Psychotropic Medications in Pregnancy: An Observational Cohort Study
    Ozturk, Z; Olmez, E; Gurpinar, T; Gok, S; Vural, K
    Objective: The question of harmfulness of the psychiatric drugs creates a major dilemma for pregnant women. The risks associated with prenatal psychotropic drug exposure are often overestimated. It is unclear that psychotropic medication or disorders themselves increase the risk of adverse pregnancy outcomes. The purpose of this study is to generate data about the safety of psychotropic drugs in pregnancy and maternal characteristics of the pregnant women exposed to these drugs. Method: An observational cohort study was performed. Pregnancy outcomes of 135 pregnancies after psychotropic drug exposure are compared to a control group of 275 pregnancies. Results: There were no statistically significant differences in rates of major malformations, miscarriages, and preterm deliveries between the two groups. However, the rate of elective abortions was higher in the exposed group compared to the control group (11.1% vs. 5.1%, respectively; RR 2.18; 95% CI: 1.09-4.39), and most of them were nulliparous (45.2%). The majority of the pregnant women did not smoke cigarettes and no alcohol consumption was reported in both groups. Conclusion: Our study showed that there was a tendency to terminate pregnancy among women exposed to psychotropic drugs. An accurate risk assessment about drug safety and informing pregnant women would help to prevent unnecessary terminations of pregnancies.
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    Evaluation of antidepressant-like effect of 2-pyrazoline derivatives
    Gok, S; Demet, MM; Özdemir, A; Turan-Zitouni, G
    Many studies have shown that pyrazoline derivatives have therapeutic potential as antidepressant drugs. In this study, we aimed to investigate the antidepressant-like effect of eight new 1-[(N,N-disubstituted thiocarbamoylthio)acetyl]-3-(2-thienyl)-5-aryl-2-pyrazolines that have previously been synthesized in our laboratory. Antidepressant-like activity was investigated in mouse forced swimming test (FST). Drug-induced effects on motor function were also tested by using digitized motor activity monitoring system. Shortened immobility time in FST was accepted as indicator of antidepressant-like activity. Results showed that three of eight pyrazoline compounds (1b, 1d, 1g) significantly shortened immobility time compared with control. Compound 1b was found to be more effective in FST than were clomipramine and tranylcypromine, used as reference antidepressant drugs. This compound also significantly increased horizontal motor activity, like clomipramine, compared with control mice. These results suggest that the N,N-disubstituted dithiocarbamate moiety of pyrazoline derivatives may have therapeutic antidepressant potential.
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    Effects of a lipoxygenase inhibitor on digoxin-induced cardiac arrhythmias in the isolated perfused guinea-pig heart
    Gok, S; Ulker, S; Huseyinov, A; Evinc, A
    1. The effects of a lipoxygenase inhibitor, BW A4C, on digoxin-induced arrhythmias and cardiac dynamics (contractile force, perfussion pressure, heart rate) were investigated in Langendorff perfused isolated guinea pig hearts. In the control group, arrhythmias were induced by 25 mu g/ml digoxin at a perfusion rate of 0.5 ml/min. In the treated groups, BW A4C (1 and 0.3 mu M) perfused continuously from 15 min prior to digoxin until cardiac arrest occurred. Digoxin exposure (mu g/g wet weight of heart) for the occurrence of arrhythmias and cardiac arrest were the parameters evaluated to assess cardiotoxicity. 2. Digoxin caused a marked increase in leukotriene Bq release in the coronary effluent, and was collected during tachyarrhythmias. BW A4C markedly inhibited the digoxin-induced elevation of LTB4. 3. BW A4C (1 and 0.3 mu M) did not prevent the onset of ventricular fibrillation and ventricular tachycardia despite a slight delay in the occurrence of ventricular fibrillation and cardiac arrest at the 0.3 mu M concentration. 4. Contractile force increased significantly after digoxin infusion which was concomitant with the time of onset of arrhythmias. In the presence of BW A4C, the contractile force increased, but not significantly. Perfusion pressure increased initially after digoxin infusion in the absence and the presence of BW A4C, but not significantly. 5. These findings show that the lipoxygenase inhibitor lacked any protective action on digoxin-induced arrhythmias despite its effective suppression of digoxin-induced elevation of LTB4 in coronary effluent. (C) 1997 Elsevier Science Inc.
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    Vasodilator effects of cromakalim and HA 1077 in diabetic rat aorta
    Gurpinar, T; Gok, S
    BACKGROUND: Impairment of the vasorelaxant responses have been reported in diabetes mellitus. In this study, the roles of the K-ATP channel and rho kinase pathway were evaluated by using the K-ATP channel opener cromakalim and Rho-kinase inhibitor HA 1077 in diabetic rat aorta. METHODS: Adult male Wistar rats weighing (250-300 g) were divided into diabetic and control groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg/i.p). RESULTS: Vasodilator responses induced by cromakalim ;(10(-7) to 10(-3)M) and HA 1077 (10(-6) to 10(-4)M) were significantly less in diabetic rings compared with control rings (p<0.01). The decrease in the relaxant effect of cromakalim was more in endothelium-denuded rings compared to the endothelium-intact rings (p<0.05). There were no significant differences between endothelium intact and non-intact rings in the presence of HA 1077. When two drugs were administered together, relaxation was significantly less than with seperate administration of each drug in the diabetic group (p<0.01). Pre-treatment with N omega-nitro-L-arginine methylester (L-NAME) (10(-6) to 10(-4) M), an NO synthase inhibitor, significantly decreased the relaxant response to cromakalime and HA 1077 in both the control and diabetic groups (p<0.05). CONCLUSIONS: These results suggest that the impaired relaxant effects were further decreased depending on KATP channel activity but the effects of Rho-kinase enzyme inhibitors on relaxation responses were not significantly changed in diabetes mellitus.
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    The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion-induced apoptosis
    Gok, S; Vatansever, S; Vural, K; Sekuri, C; Izanli, A; Tezcan, A; Cilaker, S
    During ischemia, ATP-sensitive K+ channels (KATP channels) open, and this triggers necrotic processes and apoptosis. In this study, we investigated whether selective sarcoplasmic and mitochondrial KATP channel blockers affected myocardial apoptosis and nitric oxide synthase (NOS) activity in a rat model of myocardial ischemia/reperfusion in vitro. Isolated rat hearts were subjected to 30 min of coronary artery occlusion followed by 30 min of reperfusion. A selective sarcKATP channel blocker, HMR1098 and a selective mitoKATP channel blocker, 5-hydroxydecanoate, were added to the perfusion fluid 10 min before occlusion. Myocardial apoptosis was detected immunohistochemically using the TUNEL method. Myocardial inducible NOS (iNOS) and endothelial NOS (eNOS) were determined immunohistochemically. In control hearts, apoptosis induction was associated with a greater immunoreactivity of iNOS than eNOS. Treatment with HMR1098, at a concentration of 3 mu mol/l, significantly reduced the TUNEL-positive cardiomyocytes and this was associated with decreased iNOS and increased eNOS immunoreactivity. When this drug was administered at a higher concentration, at 30 mu mol/l, a more marked reduction in apoptosis was observed but, in contrast to the effects observed at the lower drug concentration, eNOS immunoreactivity was almost completely abolished while iNOS was strong. Moreover, ischemia-induced cardiac dysfunction (e.g. contractile force and recovery of coronary flow) was increased by the higher concentration of HMR 1098. In hearts treated with 5-hydroxydecanoate, myocyte apoptosis was slightly reduced, and this was associated with an almost equal increase in both iNOS and eNOS immunoreactivity. These findings suggest that iNOS appears to be more important than eNOS in the reduction of apoptosis. However, the further inhibition of apoptosis by the higher concentration of HMR 1098 was associated with poorer cardiac function. (C) 2006 Elsevier GmbH. All rights reserved.
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    The Effect of Nicotine among Active, Passive Smoker Health Personnel
    Temel, O; Coskun, AS; Gok, S; Celik, P; Yorgancioglu, A
    Objective: It is aimed to evaluate the effect of environmental tobacco smoke among active and passive smoker and nonsmoker health staff. Material and Method: 209 volunteers were included; age, gender, occupation and smoking habits were recorded. Exhaled air carbon monoxide ( CO), urinary cotinine levels and Fagerstrom Nicotine Tolerance Questionnaire were performed. Results: 106 (55%) of 117 active, 66 (32%) passive smokers and 26 (13%) non-smokers were male and the mean age was 30.3+6.6 (18-55). 56 (27%), 33 (16%), 80 (38%), and 40 (19%) were doctors, nurses, assistant staff and officers respectively. Mean CO level was higher in active smokers (18 ppm) than passive smokers (1.9 ppm) and non-smokers (1.5 ppm) (p=0.001). Mean urinary cotinine level was higher in active smokers (949.5 ng/ml), than passive smokers (11.3 ng/ml) and non-smokers (0.00 ng/ml) (p=0.000). Nicotine consumption in active smokers was positively and significantly related with CO, urine cotinine levels and nicotine dependency (<0.05). Conclusion: It is concluded that environmental tobacco smoke has been found to be very high in hospitals and smoke-free hospital programs should ibe started immediately.
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    Levosimendan Attenuates Reperfusion Injury in an Isolated Perfused Rat Heart Model
    Ozturk, T; Gok, S; Nese, N
    Objectives: The aim of this study was to investigate the effect of levosimendan on apoptosis and infarct size when administered before ischemia in an isolated rat heart model. Design: An in vitro experimental study. Setting: Animal laboratory. Participants: Isolated perfused rat heart preparation (n = 22). Interventions: Perfusion with Krebs-Henseleit solution was performed for 30 minutes and then 0.1 mu mol/L of levosimendan was added to the perfusion fluid for 10 minutes before global ischemia; the control hearts received no levosimendan. Hearts underwent global ischemia for 30 minutes and then were reperfused for 30 minutes before specimens were obtained for testing. Measurements and Main Results: Infarct sizes were measured at the end of the reperfusion period and expressed as a percentage of the area at risk. Myocardial apoptosis was detected by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) method. Bcl-2 expression was determined to detect antiapoptotic activity. Infarct size was significantly less in the levosimendan group (26% +/- 3% v 40% +/- 4%, respectively; p = 0.009). Levosimendan significantly reduced the proportion of TUNEL-positive cardiomyocytes (3 1 v 20 4, respectively; p < 0.001) and increased Bcl-2 expression compared with control hearts (44% +/- 3% v 31% +/- 3%, respectively; p = 0.01). Recovery of left ventricular developed pressure 30 minutes after reperfusion in ischemic hearts pretreated with levosimendan was significantly better than that of placebotreated hearts (53% +/- 3% v 38% +/- 3% of baseline, respectively; p = 0.004). Conclusions: Levosimendan has a cardioprotective effect when administered before ischemia in ischemia-reperfusion injury. This effect may be useful in elective cardiac surgery for protecting myocytes from ischemia-reperfusion induced apoptosis. (C) 2010 Elsevier Inc. All rights reserved.
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    Effects of the blockade of cardiac sarcolemmal ATP-sensitive potassium channels on arrhythmias and coronary flow in ischemia-reperfusion model in isolated rat hearts
    Gok, S; Vural, K; Sekuri, C; Onur, R; Tezcan, A; Izanli, A
    Activation of ATP-sensitive K+ channels (K-ATP) during ischemia leads to arrhythmias and blockade of these channels exert antiarrhythmic action. In this study, we investigated the effects of HMR1098, a sarcolemmal K-ATP channel blocker and 5-hydroxydeconoate (5-HD), a mitochondrial K-ATP channel blocker on cardiac function and arrhythmias in isolated rat hearts. The hearts were subjected to 30 min coronary occlusion, followed by 30 min reperfusion. In the preischemic period, both HMR 1098 and 5-HD slightly increased coronary perfusion pressure. Coronary occlusion increased the perfusion pressure and decreased the left ventricular developed pressure (LVDP) in both control and drug-treated hearts. However, inhibition of LVDP was greater and recovery of the perfusion pressure was lower in 30 mu mol/l HMR1098 and 100 mu mol/l 5-HD-treated hearts compared to control (P < 0.05). HMR1098, at 3 mu mol/l, but not at 30 mu mol/l, significantly reduced the ratio of bigeminis, couplets and salvos (P < 0.05). Ventricular tachycardia and ventricular fibrillation were not prevented by HMR1098,. at both concentrations, and with 5-HD (100 mu mol/l). These results suggest that blockade of sarcK(ATP) and mitoK(ATP) channels exert weak antiarrhythmic action, but reduce the recovery of coronary perfusion and contractile force, implying that both types of K-ATP channels have beneficial role in the recovery of ischemic rat myocardium. (c) 2005 Elsevier Inc. All rights reserved.