Gülen Akyol

Effects of vitamin E treatment on peroxisome proliferator-activated receptor-α expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study

Background: Insulin resistance (IR) is commonly associated with non‐alcoholic steatohepatitis (NASH). Peroxisome proliferator‐activated receptor‐α (PPAR‐α) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR‐α expression and IR in patients with NASH.

Hepatitis B virus infection in allogeneic bone marrow transplantation

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(−) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1=0.007, p2=0.003 and p3=0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

Expression of Transforming Growth Factor β1 in Bronchial Biopsies in Asthma and COPD

The role of transforming growth factor β1 (TGF β1) in airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) has not been fully described. To evaluate the possible pathogenetic role of TGF β1 in asthma and COPD, immunohistochemical expression of TGF β1 was described in bronchial biopsies from patients with asthma and COPD compared with healthy individuals. Twelve subjects with asthma, 13 subjects with COPD, and 10 healthy individuals enrolled in the study. Bronchial biopsies were stained with hematoxylin and eosin and anti‐TGF β1 antibody. As a result, immunoreactive TGF β1 was mainly localized in association with connective tissue in all groups. The staining intensity was not statistically different among the groups in bronchial epithelium, whereas it was significantly higher in the group of asthma in the submucosa. Because there is evidence showing a significant increase of staining intensity in the submucosa from asthmatics but not from subjects with COPD, we may conclude that TGF β1 may play a significant role in pathogenesis of asthma but not in COPD.

Effects of topical vitamin E on keratocyte apoptosis after traditional photorefractive keratectomy.

Purpose: To evaluate the keratocyte apoptosis and effects of topical vitamin E on keratocyte apoptosis after photorefractive surgery. Methods: Rabbits were divided into 7 groups, and all groups were compared with controls after epithelial scraping, epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK), transepithelial PRK, production of a corneal flap with microkeratome and laser-assisted in situ keratomileusis (LASIK). The effects of topical Vitamin E treatment were investigated in the traditional PRK group. The terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy have been used to detect apoptosis in rabbit cornea. Results: Transepithelial PRK induced minimal keratocyte apoptosis, less than in all other refractive surgical procedures. The greatest amount of keratocyte apoptosis was observed after traditional PRK (p = 0.001), therefore we tested the effects of topical vitamin E in this group. The number of apoptotic keratocytes significantly reduced after vitamin E therapy (p < 0.005). Conclusion: Keratocytes undergo apoptosis after refractive surgery in response to mechanical epithelial removal, preparing of corneal flap and excimer laser stromal photoablation. The topical application of vitamin E immediately after surgery can prevent keratocyte apoptosis, and this result suggests that free radicals may be partly responsible for keratocyte apoptosis after excimer laser keratectomy.

Expression of MUC1 and MUC2 mucins in gastric carcinomas: Their relationship with clinicopathologic parameters and prognosis

The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.

Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery.

Purpose Refractive corneal surgery induces keratocyte apoptosis and generates reactive oxygen radicals (ROS) in the cornea. The purpose of the present study is to evaluate the correlation between keratocyte apoptosis and corneal antioxidant enzyme activities after different refractive surgical procedures in rabbits.Methods Rabbits were divided into six groups. All groups were compared with the control group (Group 1), after epithelial scraping (Group 2), epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK: Group 3), transepithelial PRK (Group 4), creation of a corneal flap with microkeratome (Group 5) and laser-assisted in situ keratomileusis (LASIK, Group 6). Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy were used to detect apoptosis in rabbit eyes. Glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities of the corneal tissues were measured with spectrophotometric methods.Results Corneal Gpx and SOD activities decreased significantly in all groups when compared with the control group (P<0.05) and groups 2, 3 and 6 showed a significantly higher amount of keratocyte apoptosis (P<0.05). Not only a negative correlation was observed between corneal SOD activity and keratocyte apoptosis (cc: −0.3648) but Gpx activity also showed negative correlation with keratocyte apoptosis (cc: −0.3587).Conclusion The present study illustrates the negative correlation between keratocyte apoptosis and corneal antioxidant enzyme activities. This finding suggests that ROS may be partly responsible for keratocyte apoptosis after refractive surgery.

Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: Comparison with traditional clinicopathologic variables

&NA; We investigated the relation of expression of tumor‐suppressor gene product p53, apoptosis‐regulator gene product bcl‐2, and CD34 (as a measure of microvessel density [MVD]) with traditional clinicopathologic prognostic variables in endometrial carcinoma (histologic type, grade, depth of myometrial invasion, angiolymphatic invasion, lymph node involvement). In specimens from 63 patients with endometrial carcinoma, the mean MVD (64.38±28.71 microvessels per 200× field) was not related to any clinicopathologic variables. Nuclear p53 expression was detected in 15 (23.8%) patients and was higher in nonendometrioid carcinomas (p<0.05) and in tumors with increasing histologic grade (p<0.001). Cytoplasmic bcl‐2 staining was seen in 79.3% of the tumors. There was a negative correlation between bcl‐2 expression and histologic type and tumor grade (p<0.05). In survival analysis, patient age, FIGO stage, high expression of p53, low expression of bcl‐2, and high and intermediate MVD values were found to be the most significant prognostic indicators of survival (p<0.05). In multivariate regression analysis, FIGO stage and low bcl‐2 expression were found to be the only independent indicators of prognosis (p<0.05).

Is increased red cell distribution width an indicating marker of nonalcoholic steatohepatitis and fibrotic stage

AIM To evaluate the red cell distribution width (RDW) as an indicator of the presence of non-alcoholic steatohepatitis (NASH) and its association with fibrotic scores. METHODS A retrospective study was carried out that included sixty-two biopsy proven NASH, 32 simple steatosis patients and 30 healthy controls. The correlation between the clinical and histopathological features of NASH patients and RDW values was evaluated. Liver fibrosis scores were measured using a 0 to 4 point scale and were divided in to two groups; fibrosis scores 0-1 were termed mild and fibrosis scores 2-4 were termed advanced fibrosis. RDW values were compared between NASH, simple steatosis and healthy controls. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver fibrosis caused by NASH. RESULTS Patients with NASH had higher RDW values compared with simple steatosis and healthy control groups [14.28% ± 0.25% vs 13.37% ± 0.12%, 12.96% ± 0.14% (P < 0.01), respectively]. Patients with advanced fibrosis had higher RDW values than the mild fibrosis group (15.86% ± 0.4% vs 13.63% ± 0.67%, P < 0.01, respectively). RDW also correlated with fibrotic scores (r = 0.579 and P < 0.01). The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and RDW was an independent predicting factor of NASH (OR = 1.75, 95%CI: 1.129-2.711, P < 0.05). CONCLUSION RDW a new non-invasive marker that can be used to demonstrate the presence of NASH and indicate advanced fibrotic scores.

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34