Sevtap Bakir

Examination of free radical metabolism and antioxidant defence system elements in patients with obsessive–compulsive disorder

Free radicals and oxidative stress are involved in the pathogenesis of various diseases. Malondialdehyde (MDA) is a natural product of lipid peroxidation in all mammalian cells. Vitamins C and E are nonenzymatic antioxidant structures. Our study investigated the role of free radicals in the obsessive-compulsive disorder (OCD). The participants were 30 patients with OCD that were drug-free at least for a month and a control group of 30 healthy subjects, matched with respect to age and sex. In both groups, the levels of erythrocyte malondialdehyde and the plasma vitamin C and E concentrations were measured. The levels of malondialdehyde were significantly higher in the patient group than in the control group (p<.01). The levels of plasma vitamin E were significantly lower in the patient than in the control group (p<.02). Although our patient group had slightly lower concentrations of plasma vitamin C compared to our control group, the difference between these two groups was not statistically significant. There was a significant correlation between increasing malondialdehyde levels and decreasing vitamin E concentrations. This study shows the presence of a significant relationship of OCD and oxidative stress, and consequently, an involvement of free radicals and of the antioxidant defence. Biochemical studies may contribute to the understanding of OCD and its treatment.

Comparison of oxidant/antioxidant, detoxification systems in various tissue homogenates and mitochondria of rats with diabetes induced by streptozocin.

Objective. Oxidative stress is considered to be the main factor in the development of diabetic complications and tissue injury. our objective was to investigate and compare the oxidant/antioxidant conditions and detoxification mechanisms of the liver, lung, kidney, cardiac tissues, and mitochondria of rats with diabetes induced by streptozocin (STZ). Methods. Rats with diabetes induced by streptozocin were anesthetized by administering 90 mg/kg ketamine hydrochloride and 3 mg/kg xylazine hydrochloride. Thoracic cavities were incised open; liver, lung, kidney, and cardiac tissues were removed and stored at −70°C. All samples were homogenized and mitochondrial fractions were separated. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Paraoxonase (PON), Arylesterase, Catalase (Cat), Malondialdehyde (MDA), and Glutathion-S-transferase were measured in each fraction. Results. MDA and TOS levels were significantly increased in liver tissues, and T OS and OSI were increased in the mitochondrial fractions of diabetic rats. These increases were not statistically significant compared to the control group. No significant differences were determined in the antioxidant and GST activities. Conclusion. According to our results, oxidative stress has not developed in rats with diabetes induced by streptozocin. The detoxification system was induced; however, this induction did not differ significantly from the controls.

Evaluation of the relationship between serum levels of VEGF and sVEGFR1 with mortality and prognosis in patients with Crimean–Congo hemorrhagic fever

The most accepted view to explaining the pathogenesis of Crimean–Congo hemorrhagic fever (CCHF) is endothelial damage. This study was conducted in a University hospital to investigate the serum levels and prognostic significance of the vascular endothelial growth factor (VEGF) and its receptor, soluble fms‐like tyrosine kinase‐1 receptor (sVEGFR‐1) in CCHF. Forty‐eight consecutive hospitalized CCHF patients (grouped into severe illness and non‐severe illness) and 40 healthy adults, as controls were enrolled. There was statistically significant difference for each of VEGF (P = 0.003), and sVEGFR1 (P = 0.0001) between the patients and controls. VEGF and sVEGFR1 levels in patients with severe CCHF were found to be higher than in the control group (P = 0.0001 and P = 0.0001, respectively). A significant difference was found in VEGF (P = 0.003) and sVEGFR1 (P = 0.0001) levels when compared to patients with CCHF who died and who recovered. In patients in the group with severe illness, the sensitivity, specificity, and the area underneath the ROC curve (AUROC) belonging to those cut‐off points of VEGF and sVEGFR1 were 66.7%, 76.2%, 0.747, and 77.8%, 81%, 0.849, respectively. In non‐survivors, the sensitivity, specificity, and the AUROC belonging to those cut‐off points of VEGF and sVEGFR1 defined as 77.8%, 76.9%, 0.813, and 88.9%, 97.4%, 0.912, respectively. In conclusion, high sensitivity, specificity, and the AUROC values were found in sVEGFR1 levels especially in the severely ill and non‐survivors. Therefore, sVEGFR1 may be an important biomarker for determining the risk of severity and death as result of infection with CCHF virus. J Med. Virol. 85:1794–1801, 2013.

Determination of serum adenosine deaminase and xanthine oxidase levels in patients with crimean-congo hemorrhagic fever

OBJECTIVE: Crimean–Congo hemorrhagic fever is an acute viral hemorrhagic fever with a high mortality rate. Despite increasing knowledge about hemorrhagic fever viruses, little is known about the pathogenesis of Crimean–Congo hemorrhagic fever. In this study, we measured serum adenosine deaminase and xanthine oxidase levels in Crimean–Congo hemorrhagic fever patients. METHODS: Serum adenosine deaminase levels were measured with a sensitive colorimetric method described by Giusti and xanthine oxidase levels by the method of Worthington in 30 consecutive hospitalized patients (mean age 42.6 ± 21.0). Laboratory tests confirmed their diagnoses of Crimean–Congo hemorrhagic fever. Thirty-five subjects (mean age 42.9 ± 19.1) served as the control group. RESULTS: There was a significant difference in adenosine deaminase and xanthine oxidase levels between cases and controls (p<0.05). However, neither adenosine deaminase nor xanthine oxidase levels varied with the severity of disease in the cases assessed (p>0.05). CONCLUSION: Adenosine deaminase and xanthine oxidase levels were increased in patients with Crimean–Congo hemorrhagic fever. Elevated serum xanthine oxidase activity in patients with Crimean–Congo hemorrhagic fever may be associated with reactive oxygen species generated by the xanthine/xanthine oxidase system during inflammatory responses. In addition, elevated lipid peroxidation may contribute to cell damage and hemorrhage. The association of cell damage and hemorrhage with xanthine oxidase activity should be further investigated in large-scale studies.

Relationship of plasma cell-free DNA level with mortality and prognosis in patients with Crimean–Congo hemorrhagic fever

Crimean–Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell‐free DNA (pcf‐DNA) is a novel marker indicating cellular damage. So far, the role of pcf‐DNA did not investigate in CCHF patients. In the current study, pcf‐DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf‐DNA level, virus load, and disease severity. Seventy‐two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf‐DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf‐DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf‐DNA levels in mild, intermediate, and severe patient groups was significant. The pcf‐DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non‐survivors had higher pcf‐DNA levels at admission (P = 0.001). A direct relationship was found between the pcf‐DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf‐DNA level of 0.42 as the optimal cut‐off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf‐DNA levels may be used as a biomarker in predicting CHHF prognosis. J. Med. Virol. 88:1152–1158, 2016.

INCREASED IRISIN CONCENTRATIONS IN PATIENTS WITH CRIMEAN-CONGO HEMORRAGIC FEVER

Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening viral infection. The pathogenesis of the disease is not well understood. The aim of this study was to determine the change in irisin concentrations in patients with CCHF. The study included a total of 30 patients with CCHF and 30 control participants. Irisin concentrations were determined using a commercial ELISA kit. Median irisin concentrations were 9.03 (5.81-12.22) μg/mL and 4.2 (3.39-7.62) μg/mL, respectively, in each group. There was no correlation between irisin and disease severity. Any correlations between irisin, and lactate dehydrogenase (LDH), international normalization ratio (INR), Alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, activated partial thromboplastin time (aPTT), D-dimer and hemoglobin, were also investigated. There were statistically significant positive correlations between the values of irisin, and platelet (p = 0.005, r: 0.369), ALT (p = 0.049, r: 0.261), INR (p = 0.006, r: 0.359) and aPTT values (p = 0.002, r: 0.405). A negative correlation was also found between the values of irisin and LDH (p = 0.008, r: －0.348). No correlations were determined between the values of irisin, and AST, hemoglobin and D-dimer. These results suggest that irisin may have a role in CCHF.

Decreased Chitotriosidase Activity and Levels in Familial Mediterranean Fever

Different studies have demonstrated changes in chitotriosidase (ChT) activity and concentrations in multiple diseases. However, changes in ChT activity and concentrations have not been concurrently evaluated in patients with Familial Mediterranean Fever (FMF). In this study, we analyzed the changes in serum ChT activity and concentrations in patients with FMF. The study included a total of 80 patients with FMF and 80 healthy controls. ChT enzyme activity and concentrations were measured and then compared between the groups. ChT activity was measured by using fluorometric ELISA and ChT concentrations were measured by using colorimetric ELISA methods. The median ChT activity was 10.00 (6.00–15.00) nmol/mL/hr in the patients and 14.00 (6.25–20.75) nmol/mL/hr in the controls. There was a statistically significant difference in the ChT activity between the controls and patients (P = 0.027). The median ChT concentrations were 65.40 (46.20–84.92) pg/mL and 125.00 (75.72–143.95) pg/mL in the patients and controls, respectively (P < 0.001), which were expressed as median percentiles (25th–75th). Additionally, we found no correlation between C-reactive protein and ChT activity (P = 0.978, r = 0.003) and concentrations (P = 0.446, r = −0.87). Serum ChT enzyme activity and concentrations may not be considered as a biomarker in FMF patients taking colchicine. New studies are needed to evaluate the changes of enzyme activity and concentration in colchicine-negative 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.

Evaluation of the associations between endothelial dysfunction, inflammation and coagulation in Crimean-Congo hemorrhagic fever patients

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease. The aim of this study was to evaluate the association between inflammation, coagulation and endothelial dysfunction in CCHF. The study population consisted of 40 patients and 50 healthy controls. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), endocan, high sensitive C-reactive protein (hsCRP), international normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets values were determined in blood samples. Median hsCRP (p < 0.0001), ALT (p < 0.001), AST (p < 0.001) and aPTT (p < 0.001) values were found to be higher in CCHF patients than in the healthy control subjects. In contrast, median endocan (p = 0.0006) and platelet (p < 0.001) concentrations were found to be lower in CCHF patients than in healthy controls. Serum hsCRP concentrations positively correlated with PT, aPTT and INR in CCHF patients, whereas serum endocan levels were not correlated with hsCRP, PT, aPTT and INR. In conclusion, endothelial dysfunction is one of the key steps in CCHF disease development and serum endocan may be used as a biomarker to evaluate endothelial dysfunction in patients. There is no relationship between increased inflammation and endothelial dysfunction. Coagulation abnormalities might be related to the impaired hepatic synthetic function of coagulation factors. Increased hsCRP concentrations may have a compensatory role in restoring impaired hemostasis in CCHF. Further research is needed to confirm these findings and to examine possible explanations.

Comparison of sulfur transferases in various tissue and mitochondria of rats with type 1 diabetes mellitus induced by streptozotocin

This study aims to investigate the relationship between sulfurtransferase (STS) activities [rhodanese (TST), mercaptopyruvate sulfurtransferase (MST)] involved in the catalysis of several biochemical reactions including detoxification of cyanide (CN−), restructuring of Fe-S cluster in proteins, and detoxification of oxygen radicals. Rats with type 1 diabetes mellitus induced by streptozotocin (STZ) were anesthetized at 14th day, and liver, lung, kidney, and heart tissues were extracted. All samples were homogenized, and mitochondrial parts were separated. Same processes were performed also in the control group, and TST and MST activities were measured in each part. The homogenate MST (MSTHomo.) activities of the type 1 diabetes mellitus group were compared with the control group, and a decrease was observed in the lung, liver, and kidney, respectively; at the same time, an increase was seen in the heart tissue. The mitochondrial MST (MSTMito.) activities of rats with type 1 diabetes mellitus group were compared with the control group, and a decrease was found in all tissues. The highest decrease in the TSTMito. level of rats with type 1 diabetes mellitus was observed in kidney tissue. The TST activities of the type 1 diabetes mellitus group were compared with the control group, and a decrease was observed in the liver, lung, and kidney, respectively; at the same time, an increase was seen in the heart tissue. It is demonstrated in the present study that decreases occur both in enzyme levels of tissue homogenates and in mitochondria, of rats with induced type 1 diabetes mellitus. However, these results were not statistically significant. In the presence of these findings, we think that kidney, liver, lung, and heart tissue can be affected by type 1 diabetes in the long term.