Gulsen Ozbay

DNA damage and antioxidant defense in peripheral leukocytes of patients with Type I diabetes mellitus

We determined relationship among DNA damage, nitric oxide (NO) and antioxidant defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G-Px) activity of the leukocytes were measured by spectrophotometric kits. Serum glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients, as expected. Differences in measured parameters between controls and patients were assessed in men and women separately. There was no significant difference between patient and control groups in neither men nor women for nitrite level. Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px activities of the leukocytes were found to be decreased in both men and women of patient group as compared to their respective controls. Significant correlations were determined between strand breakage and HbA(1c) (r = 0.37, P<0.05); Fpg-sensitive sites and HbA(1c) (r = 0.59, P<0.01); Fpg-sensitive sites and glucose (r = 0.45, P<0.02); Fpg-sensitive sites and SOD (r = -0.48, P<0.02); HbA(1c) and SOD (r = -0.50, P<0.02). In conclusion, impaired antioxidant defense in leukocytes of patients with Type 1 DM may be one of the responsible mechanisms for increased DNA damage in those patients.

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats

Abstract:  Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)‐induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

Prevalence of Hepatic Granulomas in Chronic Hepatitis B

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.

Relationship between aminotransferase levels and histopathological findings in patients with nonalcoholic steatohepatitis.

Relationship between aminotransferase levels and histopathological findings in patients with nonalcoholic steatohepatitis

Shear wave elastography in the evaluation of liver fibrosis in children.

Background: Shear-wave elastography (SWE) is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. In this study, our goal was to assess the performance of SWE in the staging of liver fibrosis in children with chronic liver disease. Methods: The study involved measuring SWE values in the right lobe of the liver in a patient group of 76 children with chronic liver disease and a control group of 50 healthy subjects. In the patient group, the shear elastic modulus values were correlated with biopsy results according to the Brunt scoring system (F0: portal fibrosis, F1: perisinusoidal or portal/periportal fibrosis, F2: both perisinusoidal and portal/periportal fibrosis, F3: bridging fibrosis, and F4: cirrhosis). Performance of SWE in estimating liver fibrosis in children was determined based on a receiver-operating characteristics (ROC) analysis. Results: Mean SWE values of the control group and F0 group were not statistically significantly different (P = 0.106). The mean SWE values of the F1, F2, F3, and F4 groups were higher than that of the control group (all P < 0.001). Based on kiloPascal measurement values, the area under the ROC curve was 95.2% (95% confidence interval [CI] 92.1–99.5), with a sensitivity for diagnosing liver fibrosis of 91.5%, a specificity of 94.0%, a positive predictive value of 93.1%, and a negative predictive value of 92.6%. Based on meter-per-second measurement values, the area under the ROC curve was 96.3% (95% CI 92.7–99.8), with a sensitivity for diagnosing liver fibrosis of 93.2%, a specificity of 94.0%, a positive predictive value of 93.2%, and a negative predictive value of 94.0%. Mean SWE values for patients with nonalcoholic steatohepatitis were higher than those in the remainder of the study group. Conclusions: Although liver fibrosis can be detected using SWE, differentiation of fibrosis stages could not be achieved. The presence of steatosis significantly increased the mean SWE values on elastography and so care should be taken when assessing children with nonalcoholic steatohepatitis.

Losartan-induced hepatic injury.

Losartan, an angiotensin II receptor antagonist, is widely used for the treatment of hypertension. Clinical experience with this drug has demonstrated that it is safe. Losartan-induced hepatic toxicity is extremely rare. We report a case of severe hepatic toxicity and fibrosis caused by losartan use, and we review four previously reported cases. Drug-induced hepatic injury may be seen during the treatment of hypertension by losartan and the clinician should be aware of this toxicity, especially during the initial phase of treatment.

Efficacy of interferon α‐2b and lamivudine combination treatment in comparison to interferon α‐2b alone in chronic delta hepatitis: A randomized trial

Background and Aim:  Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN‐α 2b and lamivudine combination treatment in comparison to IFN‐α 2b alone in patients with chronic delta hepatitis.

Therapeutic vaccination in chronic hepatitis B.

Aims: The aim was to test the efficacy of a pre‐S2‐containing vaccine (Genhevac‐B) in chronic hepatitis B (CHB). Twenty‐five naive patients (22 male, three female; median age 35; range: 6–69 years) with CHB were recruited. The inclusion criteria were: hepatitis B e antigen (HBeAg) positive or HBV‐DNA detectable with liquid hybridization; alanine aminotransferase (ALT) is at least 1.5‐fold the upper normal limit and histological evidence of chronic hepatitis.

Urinary N-acetyl-β-D-glucosaminidase and β2-microglobulin excretion in primary nephrotic children

Enzymuria and low molecular weight proteinuria reflect tubular damage and dysfunction, respectively. We examined urinary N-acetyl-β-. D -glucosamini-dase (U-NAG) and β2-mic

Management of Marked Liver Enzyme Increase during Clozapine Treatment: A Case Report and Review of the Literature

Objective: Clozapine-induced hepatotoxicity is not infrequent and usually transient. It mostly causes asymptomatic elevation of liver transaminases. “Elevation in liver enzymes to what extent should preclude further treatment?” or “Is only a dose-reduction sufficient?” are questions yet to be answered. The present article uses a case report to discuss the treatment alternatives when liver enzymes reach three times the upper normal limits during the clozapine therapy. Methods: In the following case report, the authors describe a 27-year-old male patient diagnosed with schizophrenia, resistant to different atypical and typical antipsychotics. Based on the pathological findings of our patient and a review of the literature, the author summarizes the reasons for the liver enzymes increase and treatment alternatives during clozapine treatment. Results: Substantial improvement was achieved with clozapine therapy. Increase in liver enzymes at the beginning of the clozapine treatment was successfully managed with a multidisciplinary approach: the treatment was initially withdrawn, afterwards restarted, and carefully continued. Conclusion: The authors demonstrate that clozapine may be cautiously continued in selected patients who showed marked psychiatric improvement with clozapine in the face of liver enzyme elevation.