The determination of the protective role of sildenafil administration in rats with sepsis-induced liver injury.

BACKGROUND: Sepsis is a complex syndrome which comes out after infection, characterized by activation of inflammation and infection and has a high morbidity and mortality. Sildenafil (SLD) is a selective phosphodiesterase Type 5 enzyme inhibitor and is used in the treatment of erectile dysfunction effectively all over the world. In this study, we investigated whether SLD had protective effect or not by studying the effect of SLD on reactive oxygen species and antioxidants in cecal ligation and puncture (CLP) polymicrobial sepsis model in rat liver histopathologically and biochemically. METHODS: Rats were divided into four groups: (1) 10 mg/kg SLD given CLP group; (2) 20 mg/kg SLD given CLP group; (3) CLP group; and (4) SHAM operated group. CLP polymicrobial sepsis model was applied to the rats. All rats in our study were sacrificed by overdose general anesthetic after 16 h (thiopental sodium, 50 mg/kg). Specimens of rat liver were analyzed histopathologically and biochemically. In the study, superoxide dismutase (SOD) and glutathione (GSH) parameters were measured to indicate the antioxidant activity in liver during sepsis. To evaluate the oxidant activity, myeloperoxidase (MPO) and lipid peroxidation (LPO) parameters were measured in liver tissue. RESULTS: SOD and MPO activities and GSH and LPO levels were high in CLP polymicrobial sepsis model when compared to SHAM group (p<0.05). In all SLD groups, GSH levels were high when compared to CLP group. In 20 mg/kg SLD given sepsis group, high GSH levels were observed according to SHAM group. In addition, while all SLD dose groups had a significant decrease versus CLP group in LPO levels (p<0.05), they had a significant increase in MPO activities. In 20 mg/kg SLD administrated rats, an improvement observed in biochemical parameters. In this study, SOD and MPO activities which were low in SHAM group increased in CLP polymicrobial sepsis model. When SLD administrated, MPO activity increased in both SHAM and CLP groups. In this study, GSH and LPO levels also increase in septic liver tissue. When SLD administrated to SHAM group, it increased VI protective GSH level and decreased detrimental LPO level. In histopathological examination, it was observed that 10 mg/kg SLD administration had a curative effect in liver tissue partly. CONCLUSION: It was shown that acute SLD administration decreased liver damage in septic rats dose-dependently in this study. In addition, it was observed that it corrected the broken oxidant-antioxidant balance. This might mediate the protective effect of SLD in liver. However, we believe that new experimental and clinical studies should be in the future to understand the protective effect of SLD in liver.

The frequency of complications and the etiology of disease in patients with liver cirrhosis in erzurum.

OBJECTIVE: This study included 100 patients diagnosed with liver cirrhosis who presented at Atatürk University Faculty of Medicine Gastroenterology clinic and polyclinic. MATERIALS AND METHODS: The etiology of liver cirrhosis and the incidence of its complications have been investigated. RESULTS: The etiological classification of liver cirrhosis in our patients was as follows: 47 hepatitis B virus hepatitis, 11 hepatitis C virus hepatitis, 5 HBV+HDV hepatitis, 4 Budd Chiari syndrome, 2 chronic alcohol abuse, 2 ischemic heart disease, 1 autoimmune hepatitis, 1 sclerosing cholangitis, 1 hydatid cyst. In 26 patients we could not find any etiological condition. These patients were called cryptogenic cirrhosis patients.When we examined the complications of liver cirrhosis, it appeared that there were ascites in 83 patient. In 56 patients, esophageal variceal bleeding occurred. There was spontaneous bacterial peritonitis in 42 patients. Hepatorenal syndrome occurred in 26 patients. Finally, in 3 patients we detected hepatorenal syndrome. CONCLUSION: The most common causes in the etiology of liver cirrhosis are viral, especially HBV. Many of the patients were in decompensated phase when diagnosed. We found that there was a close relation between the frequency of complications and mortality in liver cirrhosis.

Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study).

BACKGROUND/AIMS: Calcium channel blockers are increasingly used for the treatment of hypertension. Menopause and hypertension are both important risk factors for liver damage and several other circulatory abnormalities. The aim of this study was to determine the effects of amlodipine and lacidipine in an ovariectomy-induced postmenopausal period model and a deoxycorticosterone acetate-salt-induced hypertensive model in rats. METHODS: In this study, animals were divided into six groups as follows: control (Group 1), hypertension (Group 2), ovariectomy (Group 3), ovariectomy and hypertension (Group 4), ovariectomy, hypertension and amlodipine-treated (Group 5), and ovariectomy, hypertension and lacidipine-treated (Group 6). At the end of the experiment, the livers were removed and tissue samples were histologically and stereologically examined. RESULTS: The numerical densities of the hepatocytes according to group were 0.000422, 0.00329, 0.000272, 0.00259, 0.00374 and 0.000346 µm3, respectively. Significant differences were found between values of all groups (p<0.01, Mann-Whitney U test). According to histopathological investigation, Group 3 and particularly Group 4 showed some microscopic abnormalities such as dilatation in sinusoids central veins and branches of portal vein, irregularities of the hepatocyte columns, significant mononuclear cell infiltrations, and unstained vacuoles in the cytoplasm of the hepatocytes. Histological structure was protected from the destructive effects of ovariectomy and hypertension in Groups 5 and 6. CONCLUSIONS: Our experimental results show that both hypertension and the postmenopausal period have negative effects on the number of hepatocytes and histological structure of the liver. Both amlodipine and lacidipine appear to ameliorate the hypertension and/or postmenopausal period-related decrease in hepatocyte number. We thus suggest that lacidipine and particularly amlodipine have important protective and recovering effects on the liver.

Distribution of HLA Tissue Groups in Patients with Gastric Cancer.

OBJECTIVE: Gastric cancer is an important disease that is seen all over the world and that threats public health. At the same time, gastric cancer is a heterogeneous disorder with multifactorial etiologies. Recent studies have shown a significant association between HLA antigens and gastric adenocarcinoma. The aim of the present study was to determine the distribution of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) antigens in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: HLA alleles or HLA haplotypes associated with gastric cancer were established in the Turkish population using PSR-SSP analysis in 71 unrelated patients with gastric cancer and in 82 unrelated healthy controls. The statistical significance of differences in allele frequencies between patients and controls was measured by the Chi-square test with Yates's correction. RESULTS: The study revealed that the HLA-Cw5 antigen is more prevalent in patients with gastric cancer (p=0.042) and that the HLA-DRB1*15 antigen is more prevelent in the control group (p=0.021). CONCLUSION: It is probable that HLA-Cw5 is a risk factor for gastric cancer whereas HLA-DRB1*15 plays a protective role for this disease. The results show that different loci on HLA may control resistance to or tendency for any disease in different societies; each society should determine its own tissue group.

Effects of cirrhosis on bone mineral density and bone metabolism.

OBJECTIVE: The present study was undertaken to examine the correlation between the severity of liver disease and the presence and severity of bone disease in patients with hepatic cirrhosis. MATERIALS AND METHODS: Between January 2005 and February 2006, 40 patients with cirrhosis and 22 healthy controls were enrolled in a cross-sectional study. All subjects underwent standard laboratory testing and bone densitometric studies of the lumbar spine and femoral neck using dual X-ray absorptiometry (DEXA). RESULTS: Cirrhotic patients had lower serum follicle-stimulating hormone (FSH) levels than controls. Male patients had lower serum free testosterone (fT) levels than male controls. 25-hydroxyvitamin D (25-OHD3) levels were significantly higher in the controls as compared to patients with cirrhosis. In the cirrhotic group, 25-OHD3 concentrations did not differ significantly between patients with Child B and C class cirrhosis. As compared to the control group, cirrhotic patients had significantly elevated levels of urinary deoxypyridinoline (DPD). The cirrhotic patients also had a significantly lower mean spinal (SD) bone mineral density (BMD) than the control group. BMD of the lumbar spine (LS) was noted to be significantly lower in the Child C group than in the Child B group. In the cirrhotic patients, there was a positive correlation between the BMD T score of the femoral neck (FN) and albumin levels whereas there was a negative correlation between BMD T scores of the FN and age, bilirubin and prothrombin time (PT). CONCLUSION: Osteopenia and osteoporosis are highly prevalent in individuals with liver cirrhosis. Cirrhotic patients should undergo routine bone densitometric assessment and, if necessary, be treated for osteoporosis.

Prevalence patterns of gastric cancers in Turkey: model of a developing country with high occurrence of Helicobacter pylori.

AIM: In developed countries, there has been a recent increase in the prevalence of adenocarcinoma of the esophagus and cardia, along with a decrease in distal gastric cancers. Little is known regarding the prevalence of these diseases in developing countries. The aim of the present study was to evaluate changes in the prevalence of gastric adenocarcinomas in Turkey as a function of anatomic location. METHODS: Data were retrospectively collected from 16 centers from January 1990 to December 2000. Owing to the exclusion criteria, a total of 4065 cases of tumors of the stomach and distal esophagus were included. Tumors localized to the body, the antrum and pyloric channel were considered distal cancers. Helicobacter pylori (H. pylori) was also detected. RESULTS: Patients' mean age was 60.7 +/- 9 years, with a male : female ratio of 68:32. The ratio of distal/proximal adenocarcinoma was 2,1 [corrected] for the western part of Turkey and 3,8 [corrected] for the eastern part of the country (P < 0.0001), and this did not change during the 11 years. H. pylori was detected significantly less in the west compared to the east for distal tumors (65.7 vs 38.7%, respectively, P = 0.02). CONCLUSION: In Turkey, a developing country with a high H. pylori prevalence, contrary to the state of developed countries, the ratio of distal versus proximal gastric adenocarcinomas has not changed. Geographical distribution should be taken into the account in projecting the changing patterns of gastric cancers.

Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy in H pylori infected or noninfected gastroduodenal disease.

AIM: To investigate the relationship between myelo-peroxidase polymorphisms as a host-related factor and atrophy caused by H pylori. METHODS: Our study enrolled 77 patients. Biopsy materials obtained during gastrointestinal endoscopies were evaluated for the presence of H pylori. Polymerase chain reaction-restriction fragment length polymorphism assay was used to characterize myeloperoxidase genotypes. RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1 (1.29%) had AA genotype. The change in atrophy in relation to neutrophil infiltration was significant in Hp (+) patients (P = 0.0001). The change in atrophy in relation to neutrophil infiltration in patients with GG genotype was significant (P = 0.002). However, the change in atrophy in relation to neutrophil infiltration was not significant in patients with Hp (+) GG genotype (r = 0.066, P = 0.63). CONCLUSION: Myeloperoxidase genotype is critical for development of atrophy in relation to the severity of inflammation. However, it is interesting to note that, H pylori does not show any additive effect on development of atrophy.