Tugba Gurpinar

Relationship between circulating IGF-1 levels and traumatic brain injury-induced hippocampal damage and cognitive dysfunction in immature rats.

It is well known that traumatic brain injury (TBI) induces the cognitive dysfunction resulting from hippocampal damage. In the present study, we aimed to assess whether the circulating IGF-I levels are associated with cognition and hippocampal damage in 7-day-old rat pups subjected to contusion injury. Hippocampal damage was examined by cresyl violet staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Spatial memory performance was assessed in the Morris water maze. Serum IGF-1 levels decreased in both early and late period of TBI. Decreased levels of serum IGF-1 were correlated with hippocampal neuron loss and spatial memory deficits. Circulating IGF-1 levels may be predictive of cognitive dysfunction resulted from hippocampal damage following traumatic injury in developing brain. Therapy strategies that increase circulating IGF-1 may be highly promising for preventing the unfavorable outcomes of traumatic damage in young children.

The Effects of the Melatonin Treatment on the Oxidative Stress and Apoptosis in Diabetic Eye and Brain

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.

Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats.

AIM It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. MATERIAL AND METHODS Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days. RESULTS Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period. CONCLUSION These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.

Serum IGF-1 levels correlate negatively to liver damage in diabetic rats

Abstract Diabetes and insulin resistance frequently cause liver damage. Diabetes also causes reduction in liver and blood IGF-1 levels. We investigated the relation between liver damage and IGF-1 levels in diabetic rats. Fourteen Wistar albino rats were divided into control and diabetic groups. Diabetes was induced by streptozotocin. Rats were sacrificed for biochemical and histologic examinations 2 weeks after streptozotocin injection. Serum and liver IGF-1 levels were decreased, liver malondialdehyde (MDA) levels were increased, glutathione peroxidase (GPx) enzymes activities were decreased and serum alanine aminotransferase (ALT) levels were increased in diabetic group. Microscopic examination of liver revealed that normal tissue organization was disrupted in streptozotocin-induced diabetic rats. There was a strongly positive correlation between blood glucose levels and liver injury, and blood and liver IGF-1 levels. There was a strongly negative correlation between blood IGF-1 levels and hepatic injury. Our results suggest that reduction of blood IGF-1 levels correlates with hepatic injury and circulating IGF-1 levels may have predictive value for determining hepatic damage that results from diabetes. In addition, circulating IGF-1 levels are correlated with glutathione levels and the oxidative stress status of diabetic rat liver.

Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats

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.

Statin treatment reduces oxidative stress-associated apoptosis of sciatic nerve in diabetes mellitus.

Abstract 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.

A possible perianesthetic serotonin syndrome related to intrathecal fentanyl

Serotonin syndrome occurs with selective serotonin reuptake inhibitors, opioids, and other serotonergic agents. We describe a possible serotonin syndrome related to intrathecal fentanyl in a patient taking multiple drugs and substances such as ergot alkaloids, marijuana, methylenedioxy-N-methylamphetamine, and ephedrine.

Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet

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.

The effects of gender and menopause on serum lidocaine levels in smokers

SummaryIt has been established that human cytochrome P450 (CYP) enzymatic activity is affected by gender, or by hormonal factors such as the menopause in women. Gender differences have a more pronounced effect on cytochrome (CYP) 3A4 isoenzyme activity, whereas cytochrome (CYP) 1A2 isoenzyme activity is mainly induced by chronic smoking. Lidocaine is frequently used in the treatment of hemodynamic changes following laryngoscopy and tracheal intubation during general anesthesia, and is metabolized by CYP3A4 and CYP1A2 isoenzymes in the liver.The aim of this study was investigate the effects of gender and menopause on serum lidocaine levels in smokers under general anesthesia. Six men, six premenopausal women and six postmenopausal women were enrolled in the study and received i.v. lidocaine (1 mg/kg) 1 minute before they underwent general anesthesia. Serum lidocaine concentrations were measured using the EMIT® method at 1, 5, 10, 20, 40 and 60 minutes post-administration. Statistical analyses were performed using the Mann-WhitneyU-test.No statistically significant differences were found regarding the area under curve (AUC(0−60) μg/mL/min), elimination half-life (t1/2 [min]) of lidocaine and in the measured levels of serum lidocaine at any time point between the study groups (p>0.05). These results suggest that gender and menopause may have no significant effect on serum lidocaine levels in smokers.

Effects of acute treatment with dexamethasone on hemodynamic and histopathological changes in rats

Abstract 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-β), epithelial nitric oxide synthase (eNOS), interleukin-1 beta (IL1-β) 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-β, anti-eNOS, anti-IL1-β 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-β immunoreactivity and moderate TGF-β, 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-β 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.