Zafer Bayraktutan

Relationship of Asymmetrical Dimethylarginine, Nitric Oxide, and Sustained Attention during Attack in Patients with Major Depressive Disorder

We investigated the relationship of serum nitric oxide (NO) and asymmetrical dimethylarginine (ADMA) levels with cognitive functioning in patients with major depressive disorder (MDD). 41 MDD patients (Beck depression scale scores >16) and 44 controls were included in the study. Rey verbal learning and memory test, auditory consonant trigram test, digit span test, Wisconsin card sorting test, continuous performance task (TOVA), and Stroop test scores were found to be impaired in patients with major depressive disorder when compared to healthy controls. There was no significant difference between patient and control groups in terms of serum NO and ADMA. Serum NO levels were correlated with TOVA test error scores and Stroop test time scores, whereas serum ADMA levels were negatively correlated with TOVA test error scores. Metabolic detriments especially in relation to NO metabolism in frontal cortex and hypothalamus, psychomotor retardation, or loss of motivation may explain these deficits.

The Ocular Endothelin System: A Novel Target for the Treatment of Endotoxin-Induced Uveitis With Bosentan

PURPOSE We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.

High serum HTATIP2/TIP30 level in serous ovarian cancer as prognostic or diagnostic marker

BackgroundHuman HIV-1 TAT interactive protein 2 (HTATIP2/TIP30) is an evolutionarily conserved gene that is expressed ubiquitously in human tissues and some tumor tissues. This protein has been found to be associated with some gynecological cancers; as such, this study aimed to investigate blood HTATIP2/TIP30 levels in patients with ovarian cancer.MethodsTwenty-three women with ovarian cancer and 18 patients with various non-cancerous gynecological complaints (for example, dysfunctional uterine bleeding, fibroids, and urinary incontinence) were included in the study. The pathological diagnosis of ovarian cancer was adenocarcinoma. HTATIP2/TIP30 concentration in the patients’ blood samples was determined using ELISA kits.ResultsThe HTATIP2/TIP30 level was significantly higher in the cancer group than in the control group (1.84 ± 0.82 versus 0.57 ± 0.13 ng/ml, mean ± SD).ConclusionsWe demonstrated the potential role of HTATIP2/TIP30 in ovarian cancer for the first time, thereby enlightening future studies targeting HTATIP2/TIP30 in ovarian cancer treatment, diagnosis, and prevention.

Is There a Relationship between Obstructive Sleep Apnea Syndrome Severity and Nesfatin-1?

Background: Obstructive sleep apnea syndrome (OSAS) and obesity frequently occur together. The relationship between increased appetite and obesity is well known; however, despite existing knowledge about the relationship between OSAS and obesity, it is not fully understood. Objectives: This study aimed to evaluate the relationship between OSAS and the appetite-suppressing hormone nesfatin-1 independent of body mass index (BMI). Methods: A total of 134 cases were included in the study; 102 with OSAS (OSAS group) and 32 healthy controls (control group). All cases underwent polysomnography, and nesfatin-1 levels were determined. Results: Nesfatin-1 levels were significantly lower in the OSAS group compared to the control group (3,776.5 ± 204.8 and 4,056.2 ± 101.5 pg/ml, respectively; p < 0.001). In addition, there was a statistically significant negative correlation between nesfatin-1 and the apnea hypopnea index (r = -0.543; p < 0.001). The statistically significant relationship persisted after adjusting for confounding intergroup factors such as age, gender and BMI (p < 0.001). In the OSAS group, there was a statistically significant correlation between nesfatin-1 and neck circumference (r = -0.304; p = 0.02) but not between nesfatin-1 and BMI and waist circumference. There was no statistically significant difference in nesfatin-1 levels between the sexes. Conclusion: OSAS patients have lower nesfatin-1 levels compared to controls, and a greater nesfatin-1 deficit corresponds to an increased severity of OSAS and an increased neck circumference. Replacement therapy may be a potential treatment for obese OSAS patients who have lower nesfatin-1 levels, which may have additional benefits through appetite suppression and weight loss.

Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain.

Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non‐diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)‐1 in brain damage formed in a streptozocin (STZ)‐induced diabetes model, and the effect of bosentan, which is the non‐specific ET1 receptor blocker in the prevention of the diabetes‐induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes‐induced cerebral complications.

Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage*

Background: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. Objective: So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. Method: Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. Results: During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± 1.89 pg/ml in the survival group. Furthermore, it was 10.22 ± 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.01 for all). Conclusion: The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management.

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

OBJECTIVE To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drugs action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. METHODS The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media--iohexol 10 ml kg(-1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncans multiple comparison test. RESULTS Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. CONCLUSION Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). ADVANCES IN KNOWLEDGE CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats.

Levels of endothelial cell-specific molecule-1 (ESM-1) in overt hypothyroidisim

ABSTRACT Purpose: Endothelial cell-specific molecule-1, endocan, is a proteoglycan that is expressed by the vascular endothelium. Endocan can be a biomarker of endothelial dysfunction caused by endothelial cell-dependent disorders. Endothelial dysfunction is an early step of atherosclerosis and is developed in hypothyroid patients, which indicates an association between hypothyroidism and atherosclerosis. Therefore, we aimed to investigate whether circulating endocan levels are associated with endothelial dysfunction in overt hypothyroid patients. Materials and methods: Forty patients with hypothyroidism diagnosed in the last 5 years and 30 healthy subjects were recruited. Results: The mean endocan value in all patients was 0.63 ± 0.26 pg/ml, which was higher than that in controls (0.36 ± 0.10 pg/ml, p < 0.05). When we subgrouped the patients as hypothyroid and euthyroid, all groups demonstrated significantly different endocan levels, and hypothyroid patients had the highest endocan levels. A correlation analysis demonstrated that endocan levels were positively correlated with body mass index (BMI), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin and negatively correlated with free thyroid hormone 4 (FT4) and vitamin D levels. In addition, in the patient group, endocan levels were correlated with FT4 levels independently in a covariance analysis. Conclusions: The circulating endocan level increased in hypothyroid patients, suggesting that endocan levels may be an early biomarker of the development of endothelial dysfunction in patients with hypothyroidism. They may also prove useful in the prediction of cardiovascular diseases after further studies using cardiovascular disease biomarkers. In addition, targeting endocan levels to decrease cardiovascular risk may be a new treatment strategy in these patients.

The comparison of two glucose measurement systems: POCT devices versus central laboratory

Abstract Background: Glucose meters are used for two purposes: point-of-care testing and the self-monitoring of glucose, both of which are very important in the management of diabetes, hypoglycemia, or hyperglycemia and in therapeutic decisions. Objective: The aim of this study was to determine the test reliability of glucose meters and to compare their results with those of the clinical laboratory method. Material and methods: Evaluation was made of five different types of glucose meters which are generally used for hospitalized patients. Capillary and venous specimens were obtained concurrently from each patient. The former were analyzed in the glucose meters, and the latter in the laboratory analyzer. Results: Of 1837 glucose meters read-outs, 1748 capillary and venous comparisons were evaluated. The majority of the glucose meter measurements were within acceptable limits. The error percentage distribution of glucose meters indicated that the accuracy of glucose meters is higher in the prediabetic/diabetic measurement range than at normo-/hypoglycemic levels. Conclusion: In general, the glucose meters and laboratory method were observed to be compatible. However, health care professionals and self-monitoring diabetic patients should be aware of the evaluation of glucose meter results, and should cross-check, as frequently as possible, with laboratory values.

Is there any correlation between levels of serum ostepontin, CEA, and FDG uptake in lung cancer patients with bone metastasis?

OBJECTIVE In this study, an evaluation was made of the relationship between the serum levels of carcinoembryonic antigen (CEA), osteopontin (OPN), and the semi-quantitative parameters of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in lung cancer patients with bone metastasis. MATERIAL AND METHODS The evaluation included 42 non-small cell lung cancer (NSCLC) and 31 small cell lung cancer (SCLC) patients who were referred to our institution for staging by (18)F-FDG PET/CT. The biochemical parameters measured included CEA and OPN serum levels. RESULTS Serum levels of OPN in NSCLC patients with and without bone metastasis were 21.20±4.97 ng/ml and 13.33±4.53 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum OPN levels were 23.95±4.78 ng/ml and 17.30±3.09 ng/ml, respectively (p<0.05). Serum levels of CEA in NSCLC patients with and without bone metastasis were 33.79±6.49 ng/ml and 11.74±2.96 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum levels of CEA were 28.93±4.59 ng/ml and 13.88±4.47 ng/ml, respectively (p<0.05). There were no correlations between primary tumor SUVmax, and serum levels of CEA and OPN. CONCLUSIONS Bone metastasis can be detected in patients with lung cancer by measuring CEA and OPN levels. Increased levels of CEA and OPN levels may be considered an early warning sign in patients needing accurate imaging, as they are at higher risk of bone metastasis.