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Öğe Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice(Wiley-Blackwell, 2016) Gunduz, O.; Topuz, R. D.; Karadag, C. H.; Ulugol, A.BackgroundCombining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing -opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. MethodsPartial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. ResultsMechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p<0.05); therefore, cold allodynia was used in combination studies. As shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN 55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub-additive. ConclusionsOverall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.Öğe Asymmetric dimethylarginine levels in thyroid diseases(Editrice Kurtis S R L, 2007) Arikan, E.; Karadag, C. H.; Guldiken, S.Thyroid diseases may lead to endothelial dysfunction; however, the mechanism underlying the endothelial dysfunction in thyroid disease is not clear yet. Asymmetric dimethylarginine (ADMA), a novel inhibitor of endothelial nitric oxide synthase (eNOS), blocks nitric oxide (NO) synthesis from L-arginine. Symmetric dimethylarginine (SDMA) is the structural isomer of the eNOS inhibitor ADMA. SDMA does not directly inhibit eNOS but is a competitive inhibitor of arginine transport. Increased plasma ADMA, SDMA concentrations, and low Larginine/ADMA ratio were considered as possible contributing factors for endothelial dysfunction in hyperthyroid patients. On the other hand, plasma ADMA, SDMA levels and L-arginine/ADMA ratio in the hypothyroid group were unexpectedly found to be similar to those of the control subjects. The aim of this study is to evaluate and compare the plasma ADMA levels in hyperthyroid, hypothyroid and healthy subjects. Plasma ADMA, SDMA, and L-arginine levels were measured by high performance liquid chromatography. Plasma ADMA levels were significantly higher in both patients with hyperthyroidism and hypothyroidism than in the control group. SDMA concentrations were significantly increased in hypothyroid patients compared to control subjects. Patients with hyperthyroidism and hypothyroidism had significantly higher plasma L-arginine levels compared with healthy controls. L-arginine/ADMA ratio, which shows NO bioavailability, was significantly lower in hyperthyroid patients than in both hypothyroid and control subjects. In hyperthyroidism, plasma ADMA levels were related to age, L-arginine, and SDMA levels. SDMA was associated with age and L-arginine. L-arginine/ADMA ratio was negatively associated with freeT(4) levels. There was a relationship between ADMA and L-arginine in hypothyroid patients. SDMA was significantly related to L-arginine, total cholesterol, and LDL. In conclusion, not only hyperthyroidism but also hypothyroidism was associated with alterations of ADMA and SDMA metabolism.Öğe Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice(Springer, 2015) Gunduz, O.; Topuz, R. D.; Todurga, Z. G.; Duvan, K.; Karadag, C. H.; Ulugol, A.Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to the effect of this agent on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch.Öğe Evaluation of Iloprost to Prevent Vasospasm in Coronary Artery Bypass Grafts(Field House Publishing Llp, 2010) Ege, T.; Gur, O.; Karadag, C. H.; Duran, E.This study assessed the efficacy of iloprost in relieving vasospasm in coronary artery bypass grafts. Radial artery (RA), left internal thoracic artery (LITA) and saphenous vein (SV) grafts were taken from 20 patients (13 men and seven women, mean age 63.8 years [range 48 - 74 years]) scheduled to undergo coronary artery bypass grafting. Ten 3 mm vascular rings were cut from each graft and kept under tension for at least 60 min. They were kept alive with 37 degrees C oxygenated Krebs solution. Smooth muscle contraction was achieved with phenylephrine before iloprost was administered every 2 min, starting at a concentration of 10(-9) mol/l and increasing in logarithmic increments to a concentration of 10(-5) mol/l. The vasodilation response to iloprost started in all samples at a concentration of 10(-9) mol/l and increased with each incremental increase in iloprost concentration up to 10(-5) mol/l. These data suggest that local administration of iloprost has a role in relieving graft vasospasm during harvesting and preparation for coronary artery bypass grafting.