Browsing by Author "Gürpinar, T"

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    Effect of geldanamycin on the expression of the matrix molecules and angiogenetic factors in a gastric cancer cell line
    Gürpinar, T; Kosova, F; Kurt, FO; Cambaz, SU; Yücel, AT; Umur, N; Tuglu, MI
    Angiogenesis is the formation of new blood vessels. Angiogenesis affects cancer growth and is a useful target for cancer therapeutics. The effects of geldanamycin on angiogenesis in cases of gastric cancer are poorly understood. We investigated the effects of different doses of 17-allylamino-17-demethoxygeldanamycin (17-AGG), a semi-synthetic derivative of geldanamycin, on the interactions between cellular matrix proteins and angiogenesis factors in a gastric cancer cell line. We examined cancer cells on laminin and collagen I coated surfaces to determine their response to the angiogenic effect of these matrix molecules. We also evaluated the expression levels of VEGF, MMP-9, ES and TSP-1 using ELISA. We found that application of 17-AAG to the gastric cancer cell line on culture dish plastic decreased VEGF, TSP-1, ES and MMP-9 expression, whereas of all of these proteins were increased by laminin and collagen coating. 17-AAG currently is in clinical trial phase 2 and may be a promising drug for treatment of gastric cancer.
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    The Histologic Evaluation of Atorvastatin and Melatonin Treatment on Oxidative Stress and Apoptosis of Diabetic Rat Pancreas
    Gürpinar, T; Ekerbiçer, N; Uysal, N; Barut, T; Tarakçi, F; Tuglu, MI
    In the diabetic state, there is an enhanced oxidative stress due to excessive production of reactive oxygen compounds and decreased bioavailability of nitric oxide. Antioxidant treatment has been used to prevent oxidative damage in diabetes. The objective of the present study was to explore the effects of atorvastatin (AT) and melatonin (MLT) on oxidative stress in diabetic rat pancreas. We also assessed nitric oxide synthase (NOS) activity and apoptosis. Diabetes was induced by an alkylating agent steptozotocin (STZ, 55 mg/kg, IP). Six weeks later rats were divided into five groups: STZ-induced diabetic group received atorvastatin (STZ+AT), STZ-induced diabetic group received melatonin (STZ+MLT) and STZ-induced diabetic group received atorvastatin and melatonin (STZ+AT+MLT). The vehicle-treated non-diabetic (CT) and diabetic group (STZ-CT) served as normoglycemic and diabetic controls. AT was given 8 mg/kg orally and MLT was given 10 mg/kg/IP once a day for 2 weeks beginning from the sixth week. Pancreatic tissue was examined by immunohistochemical methods. Although no significant difference was observed with respect to antioxidant status, NOS activity was tended to be higher in the untreated diabetic rats than in the treated rats. We observed that AT and MLT treatment improved the histopathological changes including apoptosis and oxidative stress in diabetic pancreas.
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    Statin treatment reduces oxidative stress-associated apoptosis of sciatic nerve in diabetes mellitus
    Gürpinar, T; Ekerbiçer, N; Harzadin, NU; Barut, T; Tarakçi, F; Tuglu, MI
    Statins are lipid-lowering drugs that are widely used for treating hyperlipidemia, especially in diabetic patients. The aim of our study was to explore the effects of atorvastatin on oxidative stress and apoptosis in the sciatic nerve due to hyperglycemia. Diabetes was induced by streptozotocin. Atorvastatin was given orally for two weeks beginning from the sixth week. Microscopic examination of sciatic nerve revealed that normal tissue organization was disrupted in streptozotocin induced diabetic rats. Treatment with Atorvastatin reduced the histological damage and protected the morphological integrity of the sciatic nerve in streptozotocin induced diabetes. Increased expressions of transforming growth factor beta-1, endothelial nitric oxide synthase and TUNEL in sciatic nerve from streptozotocin induced diabetes were reduced by Atorvastatin. Atorvastatin could improve the effects of oxidative stress and apoptosis on the sciatic nerve due to diabetes.
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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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    The Effects of the Melatonin Treatment on the Oxidative Stress and Apoptosis in Diabetic Eye and Brain
    Gürpinar, T; Ekerbiçer, N; Uysal, N; Barut, T; Tarakçi, F; Tuglu, MI
    Oxidative stress plays an important role in the development of complications in diabetes mellitus. Antioxidant therapy has been thought to decrease oxidative stress. The objective of the present study was to explore the effects of melatonin (MLT) on oxidative stress in diabetic rat eye and brain tissue by using immunohistochemical methods. Diabetes was induced by streptozotocin, (STZ, 55 mg/kg/i.p) in adult rats. MLT was given 10 mg/kg/i.p once a day for 2 weeks beginning from the sixth week. Six weeks later, rats were divided into three groups: control (CR), STZ-induced diabetic (STZ), and STZ-induced diabetic group received melatonin (STZ+MLT). Although no significant difference was observed with respect to antioxidant status, NOS activity tended to be higher in the untreated diabetic rats than in the treated rats. It was observed that MLT treatment improved the histopathological changes including apoptosis and oxidative stress in brain and eye in diabetic rat.
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    Effects of acute treatment with dexamethasone on hemodynamic and histopathological changes in rats
    Ekerbiçer, N; Inan, S; Tarakçi, F; Barut, T; Gürpinar, T; Ozbek, M
    We assessed the time-dependent effects of intraperitoneal (i.p.) and intravenous (i.v.) application of dexamethasone (Dexa) on the mean arterial blood pressure (MAP), heart rate (HR) and total blood volume (TBV). We evaluated also the relation between the effects and immunoreactivities of transforming growth factor-beta (TGF-beta), epithelial nitric oxide synthase (eNOS), interleukin-1 beta (IL1-beta) and vascular endothelial growth factor (VEGF) in rat brain, lung and kidney tissues. Rats were anesthetized and while still breathing spontaneously, a tracheotomy and femoral vein and artery catheterizations were performed. To determine TBV using the hemodilution method, 2 ml albumin-electrolyte solutions were applied by i.v. injection. Group 1 (control group) received a 1 ml bolus injection of physiologic saline, Group 2 received 15 mg/kg and Group 3 received 75 mg/kg Dexa i.p. The hematocrit was measured at 10, 20, 60 and 120 min. For each animal, the values of MAP, HR and TBV were measured within 2 h. For immunohistochemical evaluation, anti-TGF-beta, anti-eNOS, anti-IL1-beta and anti-VEGF primary antibodies were tested using the avidin-biotin-peroxidase method. TBV was decreased in Group 1 and the increase in MAP was statistically significant. HR values increased slightly. None of the values changed significantly in Group 2. Although TBV was unchanged in Group 3, the decrease in MAP was statistically significant. HR values increased, but the increase was not statistically significant. Mild IL1-beta immunoreactivity and moderate TGF-beta, eNOS and VEGF immunoreactivities were observed in the brain, lung and kidney samples in Group 1. Increased eNOS immunoreactivity in the kidney samples were observed in Group 2. eNOS immunoreactivity was as strong in the brain and the kidney samples in Group 3. Decreased VEGF immunoreactivity was observed in the lung and kidney tissues in Group 3. Significantly decreased TGF-beta immunoreactivity was observed in all tissue samples in Group 3. The decreased MAP values in Group 3 differed from those in Groups 1 and 2. Despite increased eNOS immunoreactivity, especially in brain and kidney, the decrease in VEGF immunoreactivity in Group 3, especially lung and kidney, were consistent with a drop in blood pressure.