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Öğe 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice(Pergamon-Elsevier Science Ltd, 2012) Ulugol, Ahmet; Oltulu, Cagatay; Gunduz, Ozgur; Citak, Cihad; Carrara, Roberto; Shaqaqi, Mohammad Reza; Mansilla Sanchez, AliciaThe role of 5-HT7 receptors in the nociceptive processing received most attention during the last few years. The involvement of 5-HT7 receptors in nerve injury-induced neuropathic pain states have been reported only recently; however, there are no reports on its contribution in diabetic neuropathic pain. We therefore planned to investigate the effect of 5-HT7 receptor activation on the changes of nociceptive threshold in diabetic mice. Diabetes was induced by a single intraperitoneal injection of streptozocin (150 mg/kg, i.p.). The nociceptive responses in normal and diabetic animals were tested in the hot-plate and tail-flick assays. Both hot-plate and tail-flick latencies significantly shortened at 1-3/4 weeks (thermal hyperalgesia) and prolonged at 6-7 weeks (thermal hypoalgesia) after streptozocin administration. At the dose of 10 mg/kg, systemic injections of AS-19, a selective 5-HT7 receptor agonist, reduced thermal hyperalgesia at early stage of diabetes, but did not influence thermal hypoalgesia at late stage. Co-administration of SB-258719, a selective 5-HT7 receptor antagonist, at a dose that had no effect on its own (10 mg/kg), reversed the anti-hyperalgesic effect of AS-19. Our results indicate that systemic administration of 5-HT7 receptor agonists may have clinical utility in treating diabetic neuropathic pain. (C) 2012 Elsevier Inc. All rights reserved.Öğe Akut ve Kronik Kanabinoid Uygulamasının Sıçan Beyin Bölgelerinde Nosiseptin/Orfanin FQ Düzeyleri Üzerine Etkisi ve Antinosiseptif Etkisine Tolerans Gelişimi ile İlişkisi(2014) Karadağ, Çetin Hakan; Todurga, Zeynep Gizem; Kızılay, Gülnur Özfidan; Topuz, Ruhan Deniz; Gunduz, Ozgur; Duvan, Kübra Aydemir; Ulugöl, Ahmet[Abstract Nıt Available]Öğe The alteration of asymmetric dimetilarginine (ADMA) levels in cardiac and gastrocnemius muscles following radioactive iodine application in guinea pigs and the effect of L-carnitine on this alteration(Taylor & Francis Ltd, 2011) Vardar, Selma Arzu; Gunduz, Ozgur; Altun, Gulay Durmus; Aydogdu, Nurettin; Karadag, Hakan; Torun, Nese; Kaya, OktayPurpose: Tissue levels of asymmetric dimetilarginine (ADMA) and symmetric dimetilarginine (SDMA) were investigated in cardiac ventricle and gastrocnemius muscles of guinea pigs treated with radioactive iodine (RAI) alone or in combination with L-carnitine (LC). Material and methods: Group 1 received no treatment (control group). Group 2 received a total dose of 30 mCi(-1)kg(-1) body weight iodine-131 alone. Group 3 received 200 mg(-1)kg(-1) of LC for 10 days alone. Group 4 received 200 mg(-1)kg(-1) of LC plus RAI therapy. Free thyroid hormones, ADMA and SDMA concentrations were measured. Results: Serum free thyroid hormone concentrations were found decreased in the RAI and LC-RAI groups after RAI application. A significant decrease in ADMA and SDMA concentration was observed in ventricle muscle following RAI application. The LC-RAI group had significantly decreased ADMA levels in ventricle muscle compared with those of the control group. Similarly, SDMA concentrations in ventricle and gastrocnemius muscles of the LC-RAI groups were significantly lower than those of the control groups. Conclusions: Our results indicated that RAI appears to exert an inhibitory effect on ADMA and SDMA levels of ventricular muscle. LC administration when given adjuvant to RAI therapy may cause a marked decrease in ADMA concentrations of both ventricular and gastrocnemius muscles.Öğe Anti-allodynic and anti-hyperalgesic effects of ceftriaxone in streptozocin-induced diabetic rats(Elsevier Ireland Ltd, 2011) Gunduz, Ozgur; Oltulu, Cagatay; Buldum, Dilek; Guven, Rabia; Ulugol, AhmetGlutamate is the principal excitatory neurotransmitter in the central nervous system. Recent evidence suggests that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Moreover, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids, and reduce visceral and nerve injury-induced neuropathic nociceptive responses. The aim of this study is to observe the effect of a beta lactam antibiotic, ceftriaxone, on mechanical allodynia and mechanical hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindpaws. Mechanical allodynia was detected with an electronic aesthesiometer, and mechanical hyperalgesia was studied using the method of Randall-Selitto. With its higher doses, ceftriaxone (100, 200 mg/kg, i.p.) reduced both mechanical allodynia and hyperalgesia. Dihydrokainic acid (10 mg/kg, i.p.), a selective GLT-1 transporter inhibitor, reversed the anti-allodynic and anti-hyperalgesic effects of ceftriaxone, at doses that produced no effect on its own. Our results indicate that ceftriaxone exerts an antinociceptive effect in streptozocin-induced diabetic rats and GLT-1 activation by beta lactam antibiotics may be a promising option in the treatment of diabetic neuropathy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.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 Anti-inflammatory effect of hydrogen sulfide donor sodium-sulfide in an experimental mouse model of contact hypersensitivity(Wolters Kluwer Medknow Publications, 2023) Ozlen, Nermin; Ercetin, Deniz; Sapmaz-Metin, Melike; Gunduz, OzgurBackground: Hydrogen sulfide (H2S), synthesized by most immune cells, has been shown to exert anti-inflammatory and antipruritic effects. The effect of H2S on allergic contact dermatitis (ACD), an inflammatory skin disease that negatively affects the quality of life, is unknown. Objectives: We planned to investigate the antipruritic and anti-inflammatory effects of the H2S donor sodium sulfide (Na2S) in the experimental mouse model of contact hypersensitivity (CHS), which is widely used for ACD research. Methods: CHS was created in Balb/c mice using 1-fluoro-2, 4-dinitrobenzene. Na2S was administered systemically (0.2-2-20 mg/kg/i.p.) and locally (1-3-10 nmol/both ear/i.d.) at 3 h and 25 h after the challenge. Ear thickness and the number of scratches were determined at 24 h and 48 h following the challenge. Ear tissue and serum interferon-gamma, interleukin (IL)-2, IL-4, and IL-5 cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). H and E staining was performed for histopathological studies. CD4(+) and CD8(+) T cells located in the skin were examined by immunohistochemical staining. Results: Locally (1-3-10 nmol/ear/i.d., P < 0.001, P < 0.0001, P < 0.0001, respectively) and systemically (2-20 mg/kg/i.p., P < 0.01, P < 0.0001, respectively), Na2S administration decreased ear thickness dose dependently. Local (1-3-10 nmol/ear/i.d.) Na2S treatment decreased serum IL-2 levels (P < 0.01, P < 0.05, and P < 0.01, respectively). Na2S administered locally (3-10 nmol/ear/i.d., P < 0.05) and systemically (20 mg/kg/i. p., P < 0.05) decreased the number of CD4(+) T lymphocytes. Conclusion: Locally and systemically administered Na2S reduces ear thickness, which is one of the symptoms of CHS, probably by preventing CD4(+) T lymphocyte infiltration and proliferation and decreasing IL-2 synthesis.Öğe Attenuation of serotonin-induced itch responses by inhibition of endocannabinoid degradative enzymes, fatty acid amide hydrolase and monoacylglycerol lipase(Springer Wien, 2015) Tosun, Nurcan Calimli; Gunduz, Ozgur; Ulugol, AhmetItch and pain are two irritating sensations sharing a lot in common. Considering the antinociceptive effects of blockade of endocannabinoid degrading enzymes in pain states, we attempted to reduce scratching behavior by endocannabinoid modulation, i.e. by inhibiting fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), or cellular uptake of endocannabinoids. Scratching behavior was induced by intradermal injection of serotonin to Balb/c mice. URB597 (10 mg/kg, i.p.), a FAAH inhibitor, JZL184 (16 mg/kg, i.p.), a MAGL inhibitor, and AM404 (10 mg/kg, i.p.), an endocannabinoid transport inhibitor, were given to evaluate the effects of endocannabinoid modulation on scratching responses. Then, the CB1 receptor antagonist, AM251 (1 mg/kg, i.p.), and the CB2 receptor antagonist, SR144528 (1 mg/kg, i.p.), were administered to determine whether cannabinoid receptors mediate these effects. URB597 and JZL184, but not AM404, attenuated serotonin-induced scratches. The inhibitory effect of URB597 was reversed by SR144528, but cannabinoid receptor antagonists had no other effects on modulation by the inhibitors. We propose that augmenting the endocannabinoid tonus by inhibition of degradative enzymes, FAAH and MAGL, but not cellular uptake, may be a novel target for the development of antipruritic agents.Öğe Blockade of cannabinoid CB1 and CB2 receptors does not prevent the antipruritic effect of systemic paracetamol(Springer Heidelberg, 2014) Saglam, Gulis; Gunduz, Ozgur; Ulugol, AhmetCannabinoid CB1 receptors have been shown to mediate the antinociceptive, but not the hypothermic, action of the worldwide used analgesic, paracetamol. Since itch and pain sensations share many similarities, the purpose of the present study was to investigate whether blockade of cannabinoid CB1 and CB2 receptors participates in the antipruritic activity of paracetamol in mice. Scratching behavior was induced by intradermal serotonin injection into the rostral part of the back of the mice. After serotonin administration, scratching of the injected site by the hind paws were videotaped and counted for 30 min. Serotonin-induced scratching behavior was attenuated with high-dose paracetamol (300 mg/kg). The CB1 receptor antagonist, AM-251 (1 mg/kg), and the CB2 receptor antagonist, SR-144528 (1 mg/kg), did not alter the anti-scratching behavioral effect of paracetamol. Our results indicate that, in contrast to its antinociceptive action, but similar to its hypothermic effect, cannabinoid receptors are not involved in the antipruritic activity of paracetamol.Öğe Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance(Wiley-Blackwell, 2016) Ulugol, Ahmet; Topuz, Ruhan D.; Gunduz, Ozgur; Kizilay, Gulnur; Karadag, Hakan C.It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/OFQ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/OFQ receptor (NOP) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/OFQ levels in pain-related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague-Dawley rats. N/OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212-2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC-801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212-2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212-2 was combined with JTC-801. We hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception.Öğe Contribution of nociceptin/orphanin FQ receptors to the anti-nociceptive and hypothermic effects of dipyrone(Cambridge Univ Press, 2015) Ertin, Ismet Hande; Gunduz, Ozgur; Ulugol, AhmetBackground Dipyrone is one of the most commonly used non-opioid analgesic and antipyretic drug. Its anti-nociceptive and hypothermic effects have long been suspected to be centrally mediated. The involvement of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ), and its receptor (NOP) in pain transmission is controversial. It appears to be pro-nociceptive when administered supra-spinally, but exerts anti-nociceptive effects when injected spinally or systemically. Objective Investigation of the role of the N/OFQ system in paracetamol-induced anti-nociception and hypothermia led us to determine its role in the anti-nociceptive and hypothermic effects of dipyrone. Material and Methods Hot-plate and tail-flick tests were used to assess nociception, and a rectal thermometer was used to measure rectal temperature in mice. Results Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) displayed dose-related anti-nociception and hypothermia. The NOP receptor antagonist JTC-801 (3 mg/kg, i.p.), at a dose that exerted no effect when used alone, alleviated dipyrone-induced anti-nociception but did not reverse dipyrone-induced hypothermia. Conclusion We conclude that NOP receptors participate in the anti-nociceptive, but not in the hypothermic, effects of dipyrone.Öğe Contribution of spinal 5-HT5A receptors to the antinociceptive effects of systemically administered cannabinoid agonist WIN 55,212-2 and morphine(Canadian Science Publishing, Nrc Research Press, 2018) Aksu, Ahmet Goktan; Gunduz, Ozgur; Ulugol, AhmetThe antinociceptive effects of cannabinoids and opioids have been known for centuries. Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied. We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids. Hot plate and tail fl(i)ck tests were used to assess the antinociceptive activity in Balb/c mice. WIN 55,212-2, a nonselective CB1 and CB2 agonist, and morphine exerted significant antinociceptive effects at 1, 3, and 10 mg/kg doses administered intraperitoneally in both hot plate and tail flick tests. The selective 5-HT5A receptor antagonist SB-699551 (10 nmol/mouse) was administered intrathecally 10 min before the agonists. SB-699551 significantly reduced the antinociceptive effect of both WIN 55,212-2 and morphine. In the rotarod test, WIN 55,212-2 disrupted the motor coordination at a dose of 10 mg/kg, while morphine did not affect this function at any dose. Our findings show that spinal 5-HT5A receptors are involved in the antinociceptive effects of WIN 55,212-2 and morphine.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 platelet-rich plasma in inactive form on the burn zone of stasis in rats(Taylor & Francis Ltd, 2019) Orhan, Erkan; Sapmaz-Metin, Melike; Tarladacalisir-Topcu, Yeter; Gunduz, Ozgur; Kaya, OktayThe protection of the burn stasis zone tissues (BSZT) reduces the width and depth of the burn injury. In this study, it is aimed to show the effect of platelet-rich plasma (PRP) on the burn zone of stasis. Seventy-two Wistar rats were used in the study. PRP was obtained from the blood taken from eight rats. The remaining 64 rats were divided into four groups. In Group 1, only the burn procedure was performed. In Group 2, 0.3 cc of physiological saline solution, in Group 3, 0.3 cc of platelet-poor plasma and in Group 4, 0.3 cc of PRP were intradermally injected into BSZT after burn procedure. 21.5% of the tissues in Group 1, 20.8% in Group 2, 27.0% in Group 3, and 69.6% in Group 4 were found to be alive. The autophagic cell number average was calculated as 340 in Group 1, 340 in Group 2, 335 in Group 3 and 450 in Group 4, while the average number of cells stained with Nrf2 was calculated as 225 in Group 1, 245 in Group 2, 250 in Group 3 and 370 in Group 4. When the groups were compared in terms of the living tissue ratio, autophagy and number of cells stained with Nrf2, the values in Group 4 were found to be statistically significantly higher compared to Group 1, Group 2 and Group 3, while there was no difference between Groups 1, 2 and 3. This study has shown that PRP has a protective effect on BSZT.Öğe Effects of Cannabinoid Modulation on Hypothalamic Nesfatin-1 and Insulin Resistance(Wolters Kluwer Medknow Publications, 2019) Kaya, Oktay; Yilmaz, Makbule Elif; Bayram, Sinasi; Gunduz, Ozgur; Kizilay, Gulnur; Ozturk, LeventBoth nesfatin-1 and cannabinoid systems involved in the regulation of sleep, metabolism, and food intake. The relationship between cannabinoid system and nesfatin-1 levels remains to be elucidated. This study investigated nesfatin-1 and insulin resistance in 72-h rapid eye movement (REM) sleep-deprived mice under the effects of cannabinoid, and cannabinoid receptors CB1R and CB2R blocking. Sixty mice were exposed to 72-h sleep deprivation. Groups and drug administrations were as follows: Group 1 (control) received injection of vehicle. Group 2 received WIN 55,212,2. Group 3 received AM251 (CB1R antagonist) followed by WIN 55,212,2 injection. Group 4 received SR144528 (CB2R antagonist) followed by WIN 55,212,2 injection. Group 5 received only AM251. Group 6 received only SR144528. Blood samples were collected 1 h after drug administration and prepared for biochemical measurements. Glucose levels were measured by glucometer, whereas insulin and nesfatin-1 levels were measured by ELISA. Central nesfatin-1 was also assessed using immunohistochemistry. One-way analysis of variance together with post hoc Tukey's test was used for inter-group comparisons. Serum nesfatin-1 levels were comparable in all study groups. Brain nesfatin-1 immune-positive cell count was lower in WIN group compared to controls. The administration of CB1R or CB2R antagonist prevented reduction in nesfatin-1-positive cell count. Insulin resistance was higher in WINCB2 and CB2 groups than in control and WINCB1 groups. Cannabinoid treatment reduced nesfatin-1 immunoreactivity in the central nervous system and this effect was prevented by either CB1R or CB2R antagonist pretreatment. Insulin resistance might be related to CB2 receptor activation which was independent from central nesfatin-1 immunoreactivity.Öğe The Effects of Cannabinoid Receptor Agonist and Antagonist in Experimental Myoglobinuric Acute Kidney Injury(Wiley, 2022) Erge, Ummuhan; Arslan, Enver; Metin, Melike Sapmaz; Deger, Ecem Busra; Gunduz, Ozgur; Kaya, Oktay[Abstract Not Available]Öğe Effects of Cannabinoid Receptor Blockers on Serum Nesfatin-1/Nucb2 Levels in REM sleep Deprived Mice(Wiley-Blackwell, 2016) Kaya, Oktay; Yilmaz, M. Elif; Bayram, Sinasi; Gunduz, Ozgur; Ozfidan, Gulnur Kizilay; Ozturk, Levent[Abstract Not Available]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.