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Öğe Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats(Baishideng Publishing Group Inc, 2014) Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, ErmanAIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), p = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, p < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; p = 0.001, p = 0.001 and p < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) mu mol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) mu mol/g and 61.46 (58.27-67.75) U/g, p < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) mu mol/g and 69.22 (61.13-100.88) U/g, p < 0.05 and p < 0.01 vs model group respectively]. CONCLUSION: MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.Öğe Determination of dermatology life quality index, and serum C-reactive protein and plasma interleukin-6 levels in patients with chronic urticaria(Termedia Publishing House Ltd, 2013) Ucmak, Derya; Akkurt, Meltem; Toprak, Gulten; Yesilova, Yavuz; Turan, Enver; Yildiz, IsmailIntroduction: C-reactive protein (CRP) and interleukin-6 (IL-6), which is one of its most important simulators, were determined in great amounts in the sera of patients with chronic urticaria (CU). Aim: To determine the levels of IL-6 in patients with urticaria, and evaluate its relationship with urticaria activity scores and Dermatology Life Quality Index (DLQI). Material and methods: Fifty-three patients with CU were included in the study successively by determining their urticaria activity scores (0-3) and DLQI (0-5). The CRP and IL-6 were measured by immune assay methods. Thirty-two healthy subjects were included as a control group. Results: Serum levels of IL-6 and CRP were significantly higher in patients with CU compared to healthy controls (p < 0.001, p = 0.026 respectively). There was a statistically significant correlation among urticaria activity scores and IL-6 and CRP concentration (p = 0.004, p = 0.042). This correlation was more significant in patients who had moderate and severe disease activity scores than in those who had mild disease activity score (p < 0.001, p < 0.001, respectively). There was a statistically significant association between DLQI and IL-6 (p = 0.025). This correlation was very significant in patients who had severe and very severe disease activity scores (p < 0.001, p < 0.001, respectively). DLQI scores and serum levels of IL-6 were significantly different in the very severe group compared to healthy controls (p = 0.024). Conclusions: The levels of CRP and IL-6 are increased in patients with CU. A relationship of DLQI and urticaria activity scores with CRP and IL-6 was found. These findings support the relationship between the inflammatory process in CU and the clinical findings.Öğe Effects of antioxidant agents against cyclosporine-induced hepatotoxicity(Academic Press Inc Elsevier Science, 2015) Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Yalcin, Erhan; Otan, EmrahBackground: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. Methods: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. Results: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. Conclusions: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system. (C) 2015 Elsevier Inc. All rights reserved.Öğe Effects of Storage Temperature and Time on Stability of Serum Tacrolimus and Cyclosporine A Levels in Whole Blood by LC-MS/MS(Hindawi Ltd, 2015) Kaplan, Ibrahim; Yuksel, Hatice; Evliyaoglu, Osman; Basarali, M. Kemal; Toprak, Gulten; Colpan, Leyla; Sen, VelatTacrolimus and cyclosporine A are immunosuppressant drugs with narrow therapeutic windows. The aim of this study was to investigate the stability of tacrolimus and cyclosporin A levels in whole blood samples under different storage conditions. Whole blood samples were obtained from 15 patients receiving tacrolimus and 15 patients receiving cyclosporine A. Samples were immediately analyzed and then stored at different conditions (room temperature (24 degrees C-26 degrees C) for 24 hours, + 4 degrees C for 24 and 48 hours, and -20 degrees C for one month) and then analyzed again. For tacrolimus, there was a significant difference between samples analyzed immediately and those kept 24 hours at room temperature (P = 0.005) (percent change 32.89%). However, there were no significant differences between the other groups. For cyclosporine A, there was a significant difference between samples analyzed immediately and those kept 24 hours (P = 0.003) (percent change 19.47%) and 48 hours (P = 0.002) (percent change 15.38%) at + 4 degrees C and those kept 24 hours at room temperature (P = 0.011) (percent change 9.71%). Samples of tacrolimus should be analyzed immediately or stored at either + 4 degrees C or -20 degrees C, while samples of cyclosporine A should be analyzed immediately or stored at -20 degrees C.Öğe Effects of Sublethal Doses of Thiacloprid, a Neonicotinoid Insecticide, on Learning and Memory Performance of Mice(Asian Network Scientific Information-Ansinet, 2020) Akkoc, Hasan; Acar, Abdullah; Toprak, Gulten; Uyar, EmreBackground and Objective: Thiacloprid (THI), a neonicotinoid insecticide, currently one of the most preferred insecticides worldwide. Although they are claimed to be less hazardous on mammals, late studies revealed the harmful effects of this kind of insecticides. However, there are few studies examining the effect of THI on learning and memory performance in the literature. This study was conducted to investigate the effects of sublethal doses of THI on learning and memory functions and to determine the effect of the protocol on biochemical parameters. Materials and Methods: In this outcome, 50, 100 and 200 mg kg(-1) THI were administered by oral gavage for 3 weeks in mice (n:7). At the end of this process, a novel object recognition (NOR) and passive avoidance (PA) tests were conducted to measure learning and memory functions. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) levels were measured biochemically. Results: In the NOR test, reductions in the discrimination index values were observed with THI applications. The step-through latencies of the mice to enter the dark compartment in the retention trial of the PA test was reduced similarly in THI applied groups. The biochemical investigations revealed that BDNF and GPx levels in the brain tissue were significantly reduced in all groups compared to the control group, while a significant reduction in NGF levels was observed only in 200 mg kg(-1) applied group. There was no significant difference in SOD and CAT levels between test groups. Conclusion: These results indicated that sublethal, chronic THI application degenerates the learning and memory functions with affecting BDNF, NGF and GPx levels.Öğe Evaluation of testosterone levels in men with metabolic syndrome(Turkish Soc Cardiology, 2005) Iltumur, Kenan; Karabulut, Aziz; Toprak, Gulten; Yokus, Beran; Toprak, NizamettinObjectives: Low plasma levels of testosterone in men are associated with increased risk for atherosclerosis. In this study, we assessed plasma testosterone levels in patients with metabolic syndrome (MS) and its relationship with MS parameters. Study design: The study consisted of 36 men (mean age 50.2 +/- 7.2 years) with a diagnosis of MS according to the NCEP (National Cholesterol Education Program) criteria. An age-matched control group comprising 39 healthy volunteers (mean age 48.3 +/- 8.1 years) was also included. Plasma testosterone levels were determined by electro-chemiluminescence immunoassay on the Roche Elecsys 2010 analyzer. Fasting blood samples were analyzed for glucose and insulin levels, and lipid profiles (total cholesterol, triglyceride, LDL, and HDL). In addition, HOMA (Homeostasis Model Assessment) index was calculated. Results: The mean plasma testosterone level was significantly lower in the patient group (3.6 +/- 0.8 vs 4.8 +/- 1.9 ng/ml, p=0.001). There was a significant correlation between the levels of testosterone and HDL cholesterol (r=0.25, p<0.05). Testosterone levels were inversely correlated with the following: body mass index (r=-0.41, p<0.001), waist circumference (r=-0.40, p<0.001), HOMA index (r=-0.31, p=0.008), insulin (r=-0.28, p<0.05), glucose (r=-0.29, p<0.05), triglyceride (r=-0.28, p<0.05), and very low density lipoprotein (r=-0.28, p<0.05). Multivariate analysis identified only body mass index as an independent correlate of testosterone (beta=-0.36, p=0.038). Conclusion: Our results show that plasma testosterone levels are significantly decreased in MS. This may be of clinical importance for the assessment of cardiovascular risks in male patients with MS.Öğe Investigating the Effects of Trolox on Behaviour and Biochemical Parameters in Mice Exposed to Immobilization Stress(Asian Network Scientific Information-Ansinet, 2019) Toprak, Gulten; Akkoc, Hasan; Uyar, EmreBackground and Objective: Stress is known to play a causal role in several neuropsychiatric disorders. Trolox has been reported to show potent antioxidant activity against reactive oxygen species. The aim of this study was to investigate the effect of trolox on the behaviour and biochemical parameters of mice exposed to immobilization stress. Materials and Methods: The mice were subjected to 6 h of immobilization stress daily for 7 consecutive days. The 48 mice were randomly divided into 6 groups with 8 mice each: (I) Control, (II) Immobilization (IM), (III) Immobilization+Trolox (IM+T), (IV) Immobilization+Fluoxetine (IM+F), (V) Immobilization+Trolox+Fluoxetine (IM+T+F) and (VI) Trolox (T). At the end of day 7, open field test (OFT) and forced swimming test (FST) were performed to assess the locomotor activity and anxiety-like behaviour in mice. After the completion of these tests, brain tissue samples were removed for biochemical analysis. Results:The OFT and FST results indicated that the incidences of anxiety-like and depression-like behaviour were significantly lower in the IM+T group compared to the IM group. A significant improvement was observed in the groups treated with trolox for the catalase, total oxidant status, total antioxidant status and oxidative stress index values deteriorated by immobilization. Conclusion:The results implicated that antioxidant molecules such as trolox can lead to favourable outcomes in the treatment of oxidative damage either in isolation or in combination with classic treatment methods.Öğe Investigation of dermatology life quality index and serum prolactin and serum dehydroepiandrosterone sulphate levels in patients with chronic urticaria(Allergy Immunol Soc Thailand,, 2014) Ucmak, Derya; Akkurt, Meltem; Ucmak, Feyzullah; Toprak, Gulten; Acar, Gurbet; Arica, MustafaBackground: Chronic urticaria (CU) is known to be one of the most disturbing diseases which significantly affect the quality of life. Prolactin (PRL) and DHEA-S (dehydroepiandrosterone sulfate) are stress-associated hormones in chronic urticaria. Objective: In the present study, we measured DHEA-S and prolactin levels of CU patients, compared them with healthy subjects and evaluated the association between disease status and serum levels. Methods: Plasma DHEA-S and serum PRL concentrations were measured in 48 CU patients and 31 healthy subjects. CU activity was assessed with the use of the symptom scores recommended with EAACI/GALEN/EDF guidelines. All the patients participating in this study were evaluated by means of Dermatology Life Quality Index (DLQI). With respect to DLQI and clinical activity scores, plasma DHEA-S and serum prolactin levels were compared. Results: Median plasma concentration of DHEA-S was significantly lower in CU patients as compared with healthy subjects (p = 0.026). DHEA-S levels of females were significantly lower than males (p = 0.001). Mean PRL values of the patients were higher than the controls, but not statistically significant (p = 0.619) and there was a statistically signifcant inverse correlation with DHEA-S levels (p = 0.04, r = -0.298). There was a significant correlation between DLQI and clinical disease activity (p < 0.001, r = 0.748). Conclusions: The exact relation of hormones to CU pathogenesis remains to be determined by further clinical studies. In addition, therapies aiming to increase DHEA-S and decrease PRL may be subject to trial in CU.Öğe An investigation of the effect of placental growth factor on intrapartum fetal compromise prediction in term-induced high risk pregnancies(Via Medica, 2018) Budak, Mehmet Sukru; Toprak, Gulten; Akgol, Sedat; Obut, Mehmet; Oglak, Cemil; Bagli, Ihsan; Kahramanoglu, IlkerObjectives: To date, there is no available test to predict the risk of intrapartum fetal compromise (IFC) during labor, either starting spontaneously or induced due to obstetrics indications. The aim of this study was to examine the effectiveness of placental growth factor (PIGF) in identifying cases that develop intrapartum fetal compromise (IFC) in term high-risk pregnancies induced for labor. Material and methods: This prospective cross-sectional study was conducted on 40 IFC+ cases and 40 IFC- cases with high-risk term pregnancy and labor induction started in the Health Sciences University Gazi Yasargil Training and Research Hospital, between January 2018 and April 2018. Comparisons were made between the groups in respect of placental growth factor (PIGF) levels, and obstetric and neonatal outcomes. Results: The PIGF level was found to be statistically significantly lower in the IFC+ cases compared to the IFC- cases. For a PIGF cutoff value of 32 pg/mL for the prediction of IFC+ cases, sensitivity was 74.4%, specificity 73.2%, NPV 75% and PPV 72.5%, with a statistically significant difference determined between the groups. The IFC+ development risk increased 7.91-fold in patients with PIGF <= 32 pg/mL. Conclusions: The PIGF levels in cases of IFC+ high risk pregnancies were found to be statistically significantly lower than those of IFC-cases. However, further, large-scale randomized controlled research is necessary to demonstrate this relationship better.Öğe Oxytocin Ameliorates Remote Liver Injury Induced by Renal Ischemia-Reperfusion in Rats(Korean Journal Of Physiology & Pharmacology, 2013) Hekimoglu, Askm Tas; Toprak, Gulten; Akkoc, Hasan; Evliyaoglu, Osman; Ozekinci, Selver; Kelle, IlkerRenal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT (500 mu g/kg) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.Öğe A questionnaire study among nurses: awareness of blood and urine sample collection procedures(Walter De Gruyter Gmbh, 2014) Yuksel, Hatice; Kaplan, Ibrahim; Toprak, Gulten; Evliyaoglu, Osman; Kus, Seyit; Azizoglu, Mustafa; Mete, Nuriye[Abstract Not Available]
