Browsing by Author "Vural, K"

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    Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia- reperfusion injury in rats
    Mete, F; Tarhan, H; Celik, O; Akarken, I; Vural, K; Ekin, RG; Aydemir, I; Ilbey, YO
    We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone (O-P), and torsion/detorsion plus intratesticular ozone (O-IT). The O-IP ozone group received a 4 mg kg(-1) intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system. i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level. e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.
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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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    Selenium restores endothelial dysfunction and metabolic profile in type 2 diabetic rats
    Oztürk, Z; Gurpinar, T; Vural, K; Orenay, S; Korkmaz, M; Var, A
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    Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet
    Oztürk, Z; Gurpinar, T; Vural, K; Boyacioglu, SÖ; Korkmaz, M; Var, A
    Endothelial dysfunction develops as a result of oxidative stress and is responsible for diabetic vascular complications. We investigated the effects of selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats. Male Wistar rats were divided into five groups: controls, untreated diabetics, and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was induced by a single intraperitoneal injection of low dose streptozotocin to rats fed a high fat diet. Endothelium-dependent and -independent relaxations were measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase levels were measured in liver samples. RT-PCR showed that selenium reversed increased NADPH oxidase expression and decreased eNOS expression to control levels. Selenium also improved the impairment of endothelium-dependent vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant status in diabetic rats. Our findings suggest that selenium restores a normal metabolic profile and ameliorates vascular responses and endothelial dysfunction in diabetes by regulating antioxidant enzyme and nitric oxide release.
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    Cell division and cellular morphology of the chick retinal pigmented epithelial cells in culture - A time-lapse analysis
    Tuglu, I; Cezayirli, E; Vural, K; Gungor, K; Varol, T; Bekir, N
    Objective: To investigate the patterns of cell division, movement and shape during early stages of development of the chick embryo retinal pigmented epithelial (RPE) cells and to evaluate the morphology of dissociated embryonic cells with regard to their proliferation capacity. Methods: We conducted this study at the Department of Histology and Embryology, Celal Bayar University, Manisa, Turkey, between 2002 and 2003. We isolated the cells from chick embryos. We analyzed the images of the embryonic cells originated from neuroepithelia using a computer-based time-lapse acquisition system attached to a differential interference contrast microscope. Results: Retinal pigmented epithelial cells, despite being dissociated, depict a colony-type growth. Cells in the periphery of the colony and those outside the colony showed a tendency to proliferate and migrate and retained contact with the neighboring cells during division. Characteristics of cytokinesis were separation from the neighboring cell while retaining an attachment point, became rounded, moved up and started to shake and ascend to disseminate to the substrate to complete the division. The round-up stage was non-significantly shorter when the cell was closer to the center of the colony. Cells that were in the periphery of, or outside the colony had a round-up time of over one hour while cytokinesis-to-adhesion time was around 5 minutes. However, when we found the cells in the center of the colony, the times were half-an-hour and 1.5 hours for the daughter cells, a 2-fold difference between daughter cells with regard to the duration of attachment. Conclusion: Cell division, migration and proliferation are complex procedures influenced by growth factors, cell adhesion, matrix molecules underneath and the signal mechanisms and can be studied in detail using time-lapse microscopy, immunohistochemistry and confocal microscopy.
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    Pregnancy outcomes following the use of thiocolchicoside
    Ozturk, Z; Olmez, E; Gurpinar, T; Vural, K
    Thiocolchicoside is a commonly used muscle relaxant in orthopedic, rheumatologic or musculoskeletal disorders to treat painful muscle spasms. It is contraindicated in pregnancy and lactation. There is no previously published experience with thiocolchicoside exposure during pregnancy. In this observational study, we collected and evaluated 18 pregnancy outcomes of the women referred to our prenatal consultation service for thiocolchicoside exposure between 2007-2012, and offspring were followed up until 2 years of age. There were 16 live births, 1 spontaneous abortion and 1 elective termination of pregnancy. No major birth defect was observed. The mothers and their babies were free of perinatal complications. No growth or developmental abnormalities were found during follow-up period. Our findings add information on inadvertent use of thiocolchicoside in pregnancy. Further large prospective cohort studies are required to investigate this issue. (C) 2016 Elsevier Inc. All rights reserved.
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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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    Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk?
    Öztürk, Z; Ölmez, E; Gürpinar, T; Vural, K
    Drugs contraindicated in pregnancy are medicines that should be avoided by pregnant women, since they carry a concern for teratogenicity or there is no indication for their use during pregnancy. It does not mean that exposures to these drugs always cause harm. The aim of the present study was to investigate the risk of adverse outcomes following maternal exposure to the drugs contraindicated in pregnancy. We retrospectively analyzed prenatal drug exposure records of the pregnant patients referred to the clinical pharmacology consultation service in a tertiary-level university hospital from January 2007 until December 2012. Exposures to category X drugs (CXD) contraindicated in pregnancy were evaluated. After the expected date of delivery, we collected data about pregnancy complications and the outcomes. For comparison the women in the exposed group (N=52) were matched with a control group (N=162) of pregnant women without teratogenic exposure. We observed only one baby born with a birth defect (congenital cryptorchidism) in CXD group (2.6%) and four in control group (RR 0.91; 95% CI 0.10-7.94). The rates of adverse pregnancy outcomes including miscarriage, preterm birth and congenital abnormality were not significantly different from controls. However, the rate of elective termination of pregnancy was higher in women exposed to CXD while pregnant (RR 2.54; 95% CI 1.11-5.80, p = 0.027). Contraceptive failure and unintended pregnancy are the reasons for inadvertent drug exposure and choosing abortion. The high perception of teratogenic risk among pregnant women may cause terminations of pregnancies. Individual risk assessment and avoiding the phrase 'CXD' or 'contraindicated in pregnancy' in counseling may help to reduce maternal concerns about medication use in pregnancy.
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    Effects of Oxytocin on Glutamate Mediated Neurotoxicity in Neuroblastoma Cell Culture
    Özgür, BG; Vural, K; Tuglu, MI
    Introduction: We aimed to investigate the effects of oxytocin on neurite growth, cell viability, cell proliferation and apoptosis to demonstrate its neuroprotective effect on glutamate induced neurotoxicity in human neuroblastoma SH-SY5Y cell culture. Method:The effect of oxytocin on the toxic effects of glutamate in human neuroblastoma SH-SY5Y cell line with the Neurotoxicity Screening Test (NTT), apoptotic effects by Terminal Transferase dUTP Nick End Labeling (TUNEL) method and cell viability test by 3-(4.5-dimethylthiazol-2yl)-2.5-diphenyltetrazolium bromide (MTT) method. In the NTT test; Neurotoxicity was induced by adding glutamate at a concentration of 32 uM to the cell culture. Oxytocin was added at 1, 3, 10, 30 and 100 uM concentrations and its effect on neurite elongation was investigated. It was demonstrated by TUNEL method that application of glutamate caused apoptosis. Afterwards, when glutamate and different doses of oxytocin were given, antiapoptotic effect was evaluated with the apoptotic index. Results: Glutamate was found to have a dose -dependent neurotoxic effect and reduced neurite elongation by 50% at a concentration of 32 mu M. It was shown that the inhibition of neurite elongation caused by glutamate decreased in a dose -dependent manner by applying oxytocin. Especially oxytocin was found to significantly reduce neurite inhibition and show a neuroprotective effect starting from 10 uM concentrations. The concentration at which glutamate reduces cell proliferation by 50% was determined as 54 uM in MTT. Subsequently, it was observed that the adverse effect of glutamate on cell proliferation significantly decreased with oxytocin administration, depending on the dose. Conclusion: It was found that different concentrations of glutamate have a significant toxic effect on cell proliferation and viability, glutamate inhibits neurite elongation in a dose -dependent manner; oxytocin reduces neurite inhibition caused by glutamate, has a neuroprotective effect, increases cell viability and has antiapoptotic effects.
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    The Neuroprotective Effect of Pioglitazone on NB2a Mouse Neuroblastoma Cell Culture
    Vural, K; Seyrek, O
    Pioglitazone (PGT) is a PPAR-gamma activator that has neuroprotective properties via different mechanisms. It is thought to be neuroprotective in both acute and chronic use. Chlorpyrifos (CPS) is an Organophosphate insecticide that leads to attention deficit and cognitive problems in children and its neurotoxic effects are well known. This study aims to investigate the neuroprotective effects of PGT on CPS neurotoxicity in NB2a cell in the culture medium. We investigated the cell viability and proliferation using MTT assay and the percentage of neurite inhibition was analysed by measuring neurite outgrowth. Apoptosis was evaluated using the apoptotic index in TUNEL staining. Cell proliferation was found to be significantly reduced by CPS (25 mu M), and this concentration-based reduction was prevented by PGT. Neurite outgrowth was inhibited by CPS (25 mu M), whereas PGT significantly reversed neurite inhibition at and above 10 mu M concentrations. The apoptotic index, which was increased using CPS (25 mu M), was observed to reduce using PGT, depending on the concentration. Organophosphate is harmful to human health, and to our knowledge, there is no treatment. In individuals exposed to chlorpyrifos toxicity, acute toxic effects on neurons may be prevented or treated by PGT.
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    Neurotoxic effect of statins on mouse neuroblastoma NB2a cell line
    Vural, K; Tuglu, MI
    Objective: Evidences from cell culture experiments suggest a link between cholesterol and nervous system disease. Statins may have neurotoxic or neuroprotective effects, but these effects remain controversial. Therefore, the present study was aimed to investigate the possible toxicity of statins on a neurite outgrowth in mouse neuroblastoma NB2a cell line. Materials and Methods: We have utilized d-cAMP-induced terminally differentiated NB2a cells in culture as an experimental model to study the effects of statins. The cell survival and proliferation were studied by MTT. Measurement of neurite outgrowth was done by neurotoxicity screening test. NB2a cell differentiation was achieved by serum free medium plus 0.5 mM dibutyryl cAMP. Cells were incubated for 24 hours at 37 C. After this period, lovastatin, mevastatin and atorvastatin were added to wells at different concentrations (1, 3, 10, 100 mu M). Approximately 100 cells were chosen for each sample and examined randomly 24 hours later, from 10 different fields. Total length of neurite was photographed microscopically and measured by image analyze software. Changes in neurite lengths were expressed as % inhibition compared to that of the control group. Results: Results showed that three statins at high concentrations induced neurite inhibition, inhibited proliferation and reduced the viability of differentiated neuroblastoma NB2a cells. Conclusions: Our results suggest that statins could act as a neurotoxic agent at high doses depending upon their concentrations. These results require further investigation at ultra structural and molecular levels to understand long term side effects for clinical safety of statins.
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    In Vitro Effects of Culture Medium and Serum on Germ Cells in Testis and Epididymis of Male Wistar Rats
    Cezayirli, E; Tuglu, MI; Vural, K; Varol, T
    The present study was designed to examine the influence of culture media and serum on survival of in vitro rat sperms. The effects of different culture media with or without 10% fetal bovine serum (FBS) on spermatids and spermiums of Wistar rats were assessed in vitro between 2004 and 2005. Spermatozoa were cultured in Gamete-20, RPMI-1640, alphaMEM (AMEM), Dulbecco's modified Eagle's medium (DMEM) and Eagle's MEM (MEM). The number and morphology of cells was recorded at 4 and 24 h. Under all conditions the number and the viability of the cells decreased with time but parameters were positively affected by the presence of FBS. Viability rates of spermatids and spermatozoa reduced at 24 h of culturing. The survival and morphology were the best in RPMI with serum and worst in MEM without serum. These results indicate that different composition of culture media and FBS are important for maturation and survival of spermatozoa. Carefully selected culture media can play important roles in the generation of functional sperms as well as in the success of in-vitro fertilization (IVF) procedures.
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    Assessment of lung toxicity caused by bleomycin and amiodarone by Tc-99m HMPAO lung scintigraphy in rats
    Gumuser, G; Vural, K; Varol, T; Parlak, Y; Tuglu, I; Topal, G; Sayit, E
    The purpose of the study was to determine the lung toxicity caused by amiodarone (AD) and bleomycin (BLM) in rats, by means of Tc-99m HMPAO lung scintigraphy. Thirty albino rats were randomly divided into five groups. After AD or BLM was dissolved with isotonic saline (SF), a 0.5 ml solution was applied to the right bronchus via a catheter. Group 1 (n = 5 rats) received a single dose of AD, group 2 (n = 5) received two doses of AD, group 3 (n = 9) received BLM, group 4 (n = 3) received hydrochloric acid (HCl), and group 5 (n = 8) received SF. Rats in groups 1, 2, 3 and 5 were given 37 MBq Tc-99m HMPAO from the tail vein on days 7, 14, 21 and 28, and at 4 and 24 h in group 4. Static images of 10 min duration were obtained at 30 and 60 min by a double-headed gamma camera (Infinia, GE, Tirat Hacermel, Israel) on 256 x 256 matrix. Regular regions of interests were drawn over the right lung (RL), left lung (LL) and the liver (Li), and lung/liver (L/Li) ratios were calculated. After the scintigraphic imaging procedures were completed, rats were killed. Lung tissues were evaluated on a scale of (+) to (+++++) for edema, alveolar structural integrity and infiltration by inflammatory cells. Groups 2 and 3 showed statistically significant differences in RL/Li and LL/Li ratios, whereby RL/Li was higher than LL/Li (p < 0.05). There were no significant differences in RL/Li and LL/Li ratios in group 5 (p > 0.05). In histopathological examination, minimal damage or artifacts were observed in group 5. In group 4, almost all pathological findings were present in the right lung. Statistically significant (p < 0.01) histological differences were found when groups 1 and 5 were compared. More significant (p < 0.001) pathological effects were noted when groups 2 and 3 were compared to both groups 5 and 1. Injury was more prominent in the lung tissues of the control rats that were given HCl. Increased RL/Li ratios and histopathological findings were consistent. Tc-99m HMPAO lung scan are found to be useful in the identification of patients with lung toxicity. The simplicity of the procedure and lower radiation exposure are the advantages of Tc-99m HMPAO lung scan.
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    Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats
    Salmanoglu, DS; Gurpinar, T; Vural, K; Ekerbicer, N; Dariverenli, E; Var, A
    Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ), HFD+STZ diabetic group received melatonin (10 mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6 g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5 mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes. (C) 2015 The Authors. Published by Elsevier B.V.
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    Comparison of blood brain barrier permeability in normal and ovariectomized female rats that demonstrate right or left paw preference
    Kutlu, N; Mutlu, F; Vural, K; Cezayirli, E
    We explored the relations among paw preference, cerebral asymmetry and asymmetrical disruption of blood-brain barrier (BBB) permeability in normal and ovariectomized female rats with known paw preference. A high dose of pentylenetetrazol was used to disrupt the BBB and induce acute hypertension. To determine the areas of macroscopic infarct, samples were stained with 2,3,5-triphenyltetrazolium chloride. Histological staining techniques were used to show the areas of infarct microscopically on paraffin sections. Sixty-two percent of the rats demonstrated right paw preference, 24% demonstrated left paw preference and 14% were ambidextrous. Areas of infarct, which indicated destruction of the BBB, were determined microscopically and macroscopically in rats that demonstrated right and left paw preference. We found a relation between permeability of the BBB and paw preference. There may be a relation between paw preference, cerebral asymmetry and asymmetrical destruction of the BBB in rats. Asymmetrical destruction of the BBB in experimental rats was similar to the control group, which had asymmetrically disrupted BBB with respect to paw preference. Like the control rats, asymmetrical areas of infarct consistent with cerebral asymmetry were observed in ovariectomized rats.