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Öğe Anti-Inflammatory and Antipruritic Effects of Remote Ischaemic Postconditioning in a Mouse Model of Experimental Allergic Contact Dermatitis(Mdpi, 2023) Gunduz, Ozgur; Sapmaz-Metin, Melike; Topuz, Ruhan Deniz; Kaya, Oktay; Karadag, Cetin Hakan; Ulugol, AhmetBackground and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4(+) and CD8(+ )T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8(+ )T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.Öğe Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids(Cambridge Univ Press, 2016) Todurga, Zeynep Gizem; Gunduz, Ozgur; Karadag, Cetin Hakan; Ulugol, AhmetBackground: For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common. Objective: The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2. Material and methods: Scratching behaviour was induced by intradermal injection of serotonin (50 mu g/50 mu l/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 mu g/mouse) and 6-hydroxydopamine (6-OHDA, 20 mu g/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2. Conclusion: Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.Öğe Does dipyrone produce anxiolytic-like effects in mice?(Cukurova Univ, Fac Medicine, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Dokmeci, Dikmen; Karadag, Cetin Hakan; Ulugol, AhmetPurpose: Paracetamol has been shown to exert anxiolytic-like effects mediated by endocannabinoids via cannabinoid CB1 receptors. Dipyrone is an analgesic with similar effects to paracetamol rather than non-steroidal anti-inflammatory drugs. Involvement of central structures to its effects are long under debate, whereas recent findings suggesting contribution of cannabinoid CB1 receptors to its antinociceptive effect support this argument. Taken together, the purpose of this study was to investigate whether dipyrone possesses anxiolytic-like behavior; contribution of cannabinoid CB1 and CB2 receptors and TRPV1 receptors will be determined in case of observing any effect of dipyrone in anxiety tests. Material and Methods: Balb-c mice effects of dipyrone (150, 300, 600 mg/kg, i.p) were assessed in three-chamber social interaction, open-field, elevated plus-maze and rota rod tests. The cannabinoid CB1 antagonist AM251 (1 mg/kg i.p.), the CB2 antagonist SR 144528 (1 mg/kg i.p.) and the TRPV1 antagonist capsazepine (3 mg/kg i.p) were going to be administered before dipyrone injections if any effect of dipyrone occurs. Results: Dipyrone had no effect at any dose in behavioral tests (three-chamber social interaction, open-field, elevated plus-maze and rota rod tests). Therefore, dipyrone is not tested together with the cannabinoid CB1 and CB2 antagonists and the TRPV1 receptor antagonist. Conclusion: Unlike paracetamol, dipyrone did not possess anxiolytic-like effects in mice. Discrepancies in experimental models and methodologies may be the reason of our results.Öğe The Effect of Intrauterine Antipsychotic Drug Exposure on Learning and Memory in Adult Rats(Kure Iletisim Grubu A S, 2016) Oltulu, Cagatay; Karadag, Cetin HakanObjective: The effects of antipsychotic drugs, of whose different classes can be used in the treatment of patients with resistant to schizophrenia, on the fetus and the benefits of the treatment to the mother should be taken into consideration before making a decision about initiating treatment. This study aimed to examine the effects of prenatal exposure to various antipsychotic agents on learning and memory in adult rats. Method: In this study, antipsychotic drugs from different chemical classes (2 mg/kg haloperidol, 100 mg/kg thioridazine, 200 mg/kg sulpiride, 20 mg/kg chlorprothixene, 40 mg/kg clozapine, 10 mg/kg fluphenazine, 20 mg/kg chlorpromazine) and water for the control group were administered to pregnant Sprague-Dawley dams through gavage during the pregnancy period. In total, 16 groups were created and tested in the Morris water maze by dividing offspring of eight mother rats into male and female rat groups (n=10) on postpartum day 60. Learning was tested with hidden platform task and memory was tested with probe test. Results: It has been observed that learning was impaired in the male and female groups that received haloperidol, sulpiride, chlorprothixene, clozapine, and chlorpromazine, as well as in the female groups receiving fluphenazine and thioridazine. Thigmotaxis is the time spent on 10 cm perimeter of the walls of the pool. Thigmotaxis values of all groups were still higher except for the male group of thioridazine on fifth day. Conclusion: These results show that when prenatal exposure to antipsychotics occurs, it causes impairment in the realization of task of finding escape platform properly, rather than affecting learning and memory functions, specifically in their adulthood so that high thigmotaxis may be the reason for deterioration in escape latency parameter.Öğe Effects of hippocampal histone acetylation and HDAC inhibition on spatial learning and memory in the Morris water maze in rats(Wiley, 2020) Topuz, Ruhan Deniz; Gunduz, Ozgur; Tastekin, Ebru; Karadag, Cetin HakanIn recent years, it has been pointed out that epigenetic changes affect learning and memory formation. Particularly, it has been shown that histone acetylation and DNA methylation work in concert to regulate learning and memory formation. We aimed to examine whether acetylation of H2B within the rat hippocampus alters by trainings in the Morris water maze test. Male, 2-3 months old, Sprague Dawley rats were trained in Morris water maze task. Animals were given four trials per day for five consecutive days to locate a hidden platform. On the sixth day, the platform was removed and the animals were swum for 60 s. The effects of sodium butyrate, histone deacetylase inhibitor, were tested on normal and scopolamine-induced memory-impaired rats. The histone deacetylase inhibitor, sodium butyrate, increased histone H2B acetylation in normal rats. Sodium butyrate had no effect on learning and memory performance of normal rats; however, it partially ameliorated learning and memory disruption induced by scopolamine. So, the histone deacetylase inhibitors can be new treatment agent for cognitive disorders.Öğe Effects of in vitro Amitriptyline, Fluoxetine, Tranylcypromine and Venlafaxine on Saphenous Vein Grafts(Soc Brasil Cirurgia Cardiovasc, 2019) Akinci, Melek; Karadag, Cetin Hakan; Huseyin, Serhat; Oltulu, Cagatay; Canbaz, Suat; Gunduz, Ozgur; Topuz, Ruhan DenizObjective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3x10(-6)M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10(-11)-3x10(-5)M, while venlafaxine was added in the range of 10(-9)-3x10(-5)M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.Öğe Effects of Losartan on Glycerol-induced Myoglobinuric Acute Renal Failure in Rats(Kafkas Univ, Veteriner Fakultesi Dergisi, 2013) Kaya, Oktay; Aydogdu, Nurettin; Tastekin, Ebru; Karadag, Cetin Hakan; Gunduz, Ozgur; Sut, NecdetMyoglobinuric acute renal failure (mARF) is an uremic syndrome which develops due to damage of skeletal muscle. It was demonstrated that free radicals and nitric oxide (NO) play an important role in pathogenesis of mARF. Our aim was to investigate the effect of losartan, a drug known for its antioxidant effect, on mARF. In our study, a total of 34 male Spraque Dawley rats were divided into four groups. 1st and 2nd groups were injected with saline, 3rd and 4th groups were injected with intramuscular glycerol. One and 24 hours later, 1st and 3rd groups received saline orally and 2nd and 4th groups have taken 10 mg/kg losartan. Urine was collected; the blood samples and kidneys of the rats were taken under the anesthesia. The levels of NO, arginine, asymmetric dimethylarginine (ADMA), glutathione (GSH) and malondialdehyde (MDA) were determined, renal functions and histopathological changes examined. In our study, we found that levels of urea, creatinine, and potassium, in serum samples and MDA and ADMA in renal tissue were increased in 3rd group when it's compared with the 1st group. Levels of sodium, arginine in serum samples and arginine in renal tissue were reduced 3rd group when compared with the 1st group. When 3rd and 4th groups were compared, serum creatinine was higher in the latter group whereas ADMA level in renal tissue was lower in the same group. We think that there is no positive effect of losartan on the pathogenesis of mARF.Öğe Endocannabinoid and N-acylethanolamide levels in rat brain and spinal cord following systemic dipyrone and paracetamol administration(Canadian Science Publishing, 2019) Topuz, Ruhan Deniz; Gunduz, Ozgur; Karadag, Cetin Hakan; Dokmeci, Dikmen; Ulugol, AhmetThe cannabinoid system has been suspected to play a role in the mechanisms of action of dipyrone and paracetamol. Our purpose was to measure the local endocannabinoid and N-acylethanolamide levels in the brain and spinal cord of rats following dipyrone and paracetamol administration. Nociception was assessed 1, 5, and 12 h following drug injections in Wistar rats, using tail-flick and hot-plate tests. The antinociceptive effects of dipyrone (150, 300, and 600 mg/kg, i.p.) and paracetamol (30, 100, and 300 mg/kg, i.p.) were observed. After administration of the highest doses of dipyrone and paracetamol, endocannabinoid (N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG)) and N-acylethanolamide (palmitoylethanolamide (PEA), oleoylethanolamide (OEA)) levels were measured in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cords of rats using tandem mass spectrometry with liquid chromatography. Increased 2-AG levels were observed in the PAG and the RVM 12 h after paracetamol injection; dipyrone exerted no action on 2-AG levels. Analgesic administrations led to a reduction in AEA levels in the RVM and spinal cord; similar decreases in PEA and OEA levels were observed in the RVM and the spinal cord. Dipyrone and paracetamol administrations appear to exert complicated effects on endocannabinoid and N-acylethanolamide levels in rats.Öğe In vitro effects of amiodarone on coronary artery bypass grafts(Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2015) Karaca, Okay Guven; Ege, Turan; Canbaz, Suat; Gur, Ozcan; Karadag, Cetin Hakan; Ecevit, Ata Niyazi; Kalender, MehmetBackground: This study aims to investigate the effects of amiodarone on the most commonly used grafts, internal thoracic artery (ITA), saphenous vein (SV), and radial artery (RA) in organ bath. Methods: Twenty patients (16 males, 4 females; mean ages 58.4 +/- 9.9 years; range 38 to 80 years) who underwent isolated coronary artery bypass graft (CABG) surgery between May 2008 and October 2008 were included in this study. Internal thoracic artery, saphenous vein, and radial artery grafts were harvested. Specimens were taken to laboratory in +4 degrees C Krebs solution. Specimens were suspended in 10 ml organ bath containing Krebs solution. Results: Amiodarone caused relaxation in all grafts (ITA, RA, SV) between 10(-9)-10(-3,5) M concentration in a dose dependent manner (p<0.01). Maximum relaxation rates (mean) induced by amiodarone were 78.9%, 74.9% and 66.5% for ITA, RA and SV, respectively. Conclusion: Although we did not evaluate the endothelium-independent relaxation response in this study, higher rates of relaxation response were observed with ITA grafts comparing to other grafts, and these results were compatible with literature. According to the results of this study, amiodarone-class III antiarrhythmic agent- caused vasodilation in all three grafts in vitro. Vasodilator effect of amiodarone on grafts may help to increase patency rates.Öğe In Vitro Effects of Dopamine on Internal Thoracic Artery Graft Used in Coronary Artery Bypass Surger(Aves Yayincilik, Ibrahim Kara, 2010) Halici, Umit; Ege, Turan; Karadag, Cetin Hakan; Duran, EnverObjective: The aim of this study was to investigate in vitro effects of dopamine on internal thoracic artery (ITA) graft. Material and Methods: Between December 2003- June 2005, 32 patients (2 women and 30 men, mean age; 59.26+/-8.34, range 37-75 years old) who were subjected to coronary artery bypass grafting (CABG) operation in our clinic were enrolled in this study. ITA remnants were suspended in an isolated organ bath. Constrictor or relaxant responses to dopamine were recorded isometrically. Results: Dopamine in the concentration range of 10(-9) M-10(-7) M produced a mild relaxant effect on phenylephrine-precontracted ITA, and at higher concentrations than 10(-7) M it produced a constrictor response. Ther relaxant effect of dopamine was partially antagonized by L-NAME (nitric oxide synthase inhibitor, 10(-6) M), propranolol (10(-6) M), and cis-alpha-flupenthixol (dopaminergic receptor antagonist, 10(-6) M), but not by metoclopramide (D-2-dopaminergic receptor antagonist). The constrictor effect of dopamine was partially antagonized by phentolamine, prazosin and, yohimbine. Conclusion: It was concluded that, while dopamine produces a vasodilator response at the lower concentrations, it causes a constrictor effect on ITA at the higher concentrations. Both a beta-adrenergic and a nitric oxide mediated mechanism (via D-1-dopaminergic receptor) may play a role in the relaxant effect of dopamine on ITA at the lower concentrations. Constrictor response to dopamine at the higher concentrations on ITA may be produced by the activation of alpha(1)- and alpha(2)-adrenergic receptors.Öğe Modulatory role of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), in morphine tolerance and dependence in mice(Springer Wien, 2010) Gunduz, Ozgur; Karadag, Cetin Hakan; Ulugol, AhmetElevated plasma asymmetric dimethylarginine (ADMA) levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that peripheral ADMA is an important contributor to opioid tolerance and dependence, by determining plasma ADMA levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to male mice, divided into groups of 3-, 6-, 9- and 10-day injection duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from carotid artery. The plasma levels of ADMA, symmetric dimethylarginine (SDMA), l-homoarginine and l-arginine in morphine-tolerant and -dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma ADMA and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous plasma ADMA, SDMA, l-homoarginine and l-arginine levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena.Öğe The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats(Galenos Publ House, 2012) Ozgen, Seher Cimen; Dokmeci, Dikmen; Akpolat, Meryem; Karadag, Cetin Hakan; Gunduz, Ozgur; Erbas, Hakan; Benian, OmerObjective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.Öğe The role of endocannabinoid system and TRPV1 receptors in the antidepressant and anxiolytic effects of dipyrone in chronic unpredictable mild stress in mice(Elsevier, 2021) Topuz, Ruhan Deniz; Cetinkaya, Mehmet Zahid; Erumit, Dilsat; Aydemir, Kubra Duvan; Gunduz, Ozgur; Karadag, Cetin Hakan; Ulugol, AhmetAlthough dipyrone is a widely used analgesic and antipyretic, its mechanism of action is not fully clarified. Recent studies have drawn attention to its central effects and its relationship with the endocannabinoid system. The endocannabinoid system plays important roles in processes such as anxiety, depression, fear, and learningmemory. In this study, we aimed to investigate whether endocannabinoid levels change in the amygdala in chronic unpredictable mild stress model in mice and whether cannabinoid and TRPV1 receptors mediate antidepressant and anxiolytic effects of dipyrone. Mice were submitted to chronic unpredictable mild stress protocol of 6-weeks, then behavioral test were performed. In the first part of the study, dipyrone was injected at doses of 150, 300, and 600 mg/kg (i.p.) during behavioral tests. In the second part, the CB1 antagonist AM 251 (1 mg/kg, i.p.), the CB2 antagonist AM630 (1 mg/kg, i.p.), and the TRPV1 antagonist capsazepine (3 mg/kg, i.p.) were administered alone or in combination with 300 mg/kg dipyrone to observe if these receptors mediate dipyrone effects. Endocannabinoid and N-acylethanolamines levels were measured by LC-MS/MS in amygdala. Our results showed that there were no changes in AEA, 2-AG, PEA, OAE levels in the amygdala in mice exposed to chronic unpredictable mild stress model; dipyrone exerted antidepressant and anxiolytic effects at doses of 300 and 600 mg/kg; its anxiolytic effect appears to be mediated via CB1 receptors, whereas TRPV1 receptors seems to mediate its antidepressant action.