Serpil Erdogan

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.

The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis.

Abstract Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.

The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: An in-depth analysis

Abstract The underlying mechanism of the central nervous system (CNS) injury after acute carbon monoxide (CO) poisoning is interlaced with multiple factors including apoptosis, abnormal inflammatory responses, hypoxia, and ischemia/reperfusion-like problems. One of the current hypotheses with regard to the molecular mechanism of CO poisoning is the oxidative injury induced by reactive oxygen species, free radicals, and neuronal nitric oxide. Up to now, the relevant mechanism of this injury remains poorly understood. The weakening of antioxidant systems and the increase of lipid peroxidation in the CNS have been implicated, however. Accordingly, in this review, we will highlight the relationship between oxidative stress and CO poisoning from the perspective of forensic toxicology and molecular toxicology.

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.

Insulin resistance is a well-documented risk factor for the development of endometrial cancer. Adiponectin and vaspin are insulin-sensitizing proteins that are secreted from adipose tissue. A clear association between serum levels of adipokines and endometrial cancer has yet to be established. The study group consisted of postmenopausal women with confirmed endometrial cancer, whereas patients with benign endometrial conditions constituted the control group. The two groups were compared in terms of insulin resistance and serum levels of adiponectin and vaspin. A total of 60 patients with confirmed endometrial cancer and 70 controls with benign endometrial conditions (polyps and atrophy) were enrolled. Median homeostasis model assessment of insulin resistance value was significantly higher in the study group compared with the control group (2.93 vs 1.27, P<0.0001), whereas mean quantitative insulin sensitivity check index value was significantly lower (0.33 ± 0.02 vs 0.37 ± 0.37, P<0.0001). Median values for both adiponectin and vaspin were significantly lower in patients with endometrial cancer compared with the control group (4.09 vs 17.13 μg/ml, P<0.0001 and 0.21 vs 0.39 ng/ml, P<0.0001 respectively). Low levels of both adiponectin and vaspin were found to be significantly associated with an increased risk for endometrial cancer. Following adjustment for confounding factors, the respective odds ratios for endometrial cancer in patients in the first tertile compared with those in the third tertile were 10.80 (2.76-42.24; P=0.001) and 13.23 (2.94-59.64; P=0.001). Our results show that lower levels of circulating adiponectin and vaspin levels are associated with an increased risk of developing endometrial cancer.

The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients

Abstract Background. Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. Methods. The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Loks model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. Results. Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Loks model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. Conclusions. Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

Background: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). Methods: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (–SH+–S–S–), native thiol (thiol) (–SH), and disulfide (–S–S–) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (–SH/–S–S–) ratio was also calculated. Results: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. Conclusion: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.

Augmentation of ADAMTS9 gene expression by IL-1β is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐κB (NF‐κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF‐κB in IL‐1β‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1β. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1β. For the effects of NF‐κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1β. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.

Serum vaspin and adiponectin levels in patients with prolactinoma

Abstract Background: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. Methods: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. Results. Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621–12.035; p > 0.05) and 5.041 (1.191–21.339; p < 0.05). Conclusion: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs

Objective Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. Methods Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. Results The TAS (p=0.001), total thiol, and native thiol levels (p<0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p<0.001). Conclusion These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs.

Assessment of macroprolactinemia rate in a training and research hospital from Turkey

Abstract Objective: Macroprolactinemia detection is important to avoid unneccessary tests and overtreatment. High prolactin levels require routine screening and clinicians must be aware of macroprolactinemia frequency encountered with the method in use. In this study we aimed to determine the macroprolactinemia rate in our laboratory. Methods: Prolactin results of different patients analysed on two different immunoassay systems within two consecutive years were evaluated. Analyses were performed on Beckman Coulter UniCel® DxI800 and Roche Cobas® e601 immunoassay systems. Samples for macroprolactin analysis were precipitated using polyethylene glycol (PEG) 6000. Post-PEG recovery <40% was defined as positive, 40–60% as gray-zone and >60% as negative for macroprolactin. Results: For the samples analysed on DxI800 (n=14,958) hyperprolactinemia frequency was 8.1% (n=1208). One of 138 samples submitted for macroprolactin analysis was positive, while three of them were in the gray-zone. For the samples analysed on Cobas® e601 (n=14,040) hyperprolactinemia frequency was 13.9% (n=1954). Eighteen of 238 samples submitted for macroprolactin analysis were positive, while 21 of them were in the gray-zone. Conclusion: A difference was found between two immunoassay systems used in our laboratory in terms of macroprolactinemia rate. However, inability of simultaneous analyses on both systems, lack of evaluation with gel filtration chromatography, and heterophile antibody blocking tube were the limitations.