Hakan Dursun

Is HMGB1 a new indirect marker for revealing fibrosis in chronic hepatitis and a new therapeutic target in treatment

In chronic hepatitis B virus (HBV) infection, inflammation-associated cytokines including proinflammatory cytokines are involved in the development and progression of liver fibrosis. The liver is a source of many cytokines that may influence liver function. High-mobility group box 1 (HMGB1) was identified as an inflammatory cytokine. HMGB1 is present in nuclei of all mammalian cells and is released both through active secretion from various cells and by passive release from necrotic cells. Here we explore the relationship between HMGB1 plasma levels and liver fibrosis. HMGB1 serum levels, HBV-DNA, and ALT values were significantly higher in patients with chronic HBV than in controls. In addition, HMGB1 serum levels were significantly higher in patients with low fibrosis (fibrosis score 1-2) compared to those with high fibrosis (fibrosis score 3-4). In the present study, we have shown that HMGB1 is a noninvasive, repeatable, and convenient marker for distinguishing advanced fibrosis from low fibrosis in chronic HBV patients. We believe that the inhibition of HMGB1 may reduce inflammation, apoptosis, and fibrosis, and may stop the progression of chronic liver disease. Furthermore, we are of the opinion that fibrotic progression in chronic liver patients may be prevented by the inhibition of HMGB1, and that this substance can be a new means of following chronic HBV treatment.

Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue

BackgroundAlthough many drugs are available for the treatment of gastric ulcers, often these drugs are ineffective. Many antidepressant drugs have been shown to have antiulcer activity in various models of experimental ulcer. One such drug, the antidepressant mirtazapine, has been reported to have an antiulcer effect that involves an increase in antioxidant, and a decrease in oxidant, parameters. To date, however, there is no information available regarding the antiulcer activity for a similar antidepressant, fluvoxamine. This study aimed to investigate the antiulcer effects of fluvoxamine and to determine its relationship with antioxidants.MethodsGroups of rats fasted for 24 h received fluvoxamine (25, 50, 100 and 200 mg/kg), ranitidine (50 mg/kg) or distilled water by oral gavage. Indomethacin (25 mg/kg) was orally administered to the rats as an ulcerative agent. Six hours after ulcer induction, the stomachs of the rats were excised and an ulcer index determined. Separate groups of rats were treated with the same doses of fluvoxamine and ranitidine, but not with indomethacin, to test effects of these drugs alone on biochemical parameters. The stomachs were evaluated biochemically to determine oxidant and antioxidant parameters. We used one-way ANOVA and least significant difference (LSD) options for data analysis.ResultsThe 25, 50, 100 and 200 mg/kg doses of fluvoxamine exerted antiulcer effects of 48.5, 67.5, 82.1 and 96.1%, respectively, compared to the control rat group. Ranitidine showed an 86.5% antiulcer effect. No differences were observed in the absence of indomethacin treatment for any dose of fluvoxamine or for ranitidine. The levels of antioxidant parameters, total glutathione and nitric oxide, were increased in all fluvoxamine groups and in the ranitidine group when compared with the indomethacin-only group. In addition, fluvoxamine and ranitidine decreased the levels of the oxidant parameters, myeloperoxidase and malondialdeyhyde, in the stomach tissues of the rats when compared to indomethacin group.ConclusionWe conclude that fluvoxamine has antiulcer effects, and that these occur by a mechanism that involves activation of antioxidant parameters and inhibition of some toxic oxidant parameters.

Antioxidant Enzyme Activities and Lipid Peroxidation Levels in Erythrocytes of Patients with Oesophageal and Gastric Cancer

In this study, levels of lipid peroxidation and antioxidant enzyme activities were investigated in the erythrocytes of patients with oesophageal and gastric cancers. Erythrocytes were obtained from 17 patients with oesophageal cancer, 37 patients with gastric cancer and 20 healthy controls. Levels of malondialdehyde (MDA), a lipid peroxidation marker, and activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined using spectrophotometric methods. MDA levels and CuZn-SOD activity were significantly higher and GPx and CAT activities significantly lower in patients with oesophageal and gastric cancer than in controls. There were no statistically significant differences in the parameters measured in relation to disease stage in either patient group. These results indicate significant changes in the antioxidant defence system in patients with oesophageal and gastric cancer. It is postulated that this may lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

Can Helicobacter pylori invade human gastric mucosa?: an in vivo study using electron microscopy, immunohistochemical methods, and real-time polymerase chain reaction.

Background-Goals We used transmission electron microscopy and immunohistochemistry (IHC) to investigate how Helicobacter pylori affects the gastric mucosa of humans. Study Gastric biopsy specimens were obtained from 15 patients with gastric discomfort. The samples were processed using both microscopic examinations and a real-time polymerase chain reaction to detect H. pylori DNA. IHC staining was performed with an avidin-biotin complex immunoperoxidase kit for paraffin-embedded tissue sections. Polyclonal rabbit anti-H. pylori was used as a primary antibody. Results IHC-applied slides with brown-stained spiral bacteria on the luminal surface and in the intercellular spaces of the gastric epithelium; electron-dense spiral H. pylori of approximately 200 to 300 nm in diameter both in the gastric lumen and between the gastric epithelial cells; coccoid or ellipsoid H. pylori attached to the epithelial cells through egg-cup-like pedestals; coccoid H. pylori within the endocytotic vesicles in the apical cytoplasmic part of the epithelial cells, thus suggesting their internalization by phagocytosis; electron-dense spiral H. pylori within the membrane-bounded vacuoles of both the gastric epithelial cells, and the lamina propria; a prominent vacuolization of gastric epithelial cells invaded by H. pylori; and swollen and lytic gastric epithelial cells that suggest a mucosal erosion and may lead to peptic ulcer. All of these microscopic findings were not present in the H. pylori DNA-negative specimens that were used as the control group. Conclusion This is the first histomicrobiologic study to show gastric cells invaded by H. pylori in patients with H. pylori infection confirmed by real-time polymerase chain reaction.

Antiulcerative effect of dexmedetomidine on indomethacin-induced gastric ulcer in rats

A gastroprotective effect occurs when α(2) receptors are innervated. The dextro isomer of medetomidine, dexmedetomidine, is a highly selective α(2)-adrenoreceptor agonist. The aim of this study was to investigate whether dexmedetomidine has an antiulcerative effect and to show whether the antiulcer mechanism of dexmedetomidine is linked with oxidant/antioxidant parameters. The antiulcerative effect of dexmedetomidine was studied in an indomethacin-induced ulcer model, and some oxidant/antioxidant parameters were measured in these gastric tissues. Whereas the average ulcerous areas for the groups that received 10, 25, 50, and 100 μg/kg dexmedetomidine doses were 29 ± 4.2, 8 ± 2.1, 0 ± 0 and 0 ± 0 mm(2), respectively, the ulcerous area was 52.1 ± 4.5 mm(2) in the indomethacin control group and 0.5 ± 0.2 mm(2) in the famotidine group. In conclusion, the α(2)-adrenoreceptor agonist dexmedetomidine showed a significant antiulcerative effect in rat gastric tissue at all doses. This antiulcerative effect is stronger with increasing dosage; at the 50 and 100 μg/kg doses, no ulcerous areas were observed. In light of these results, we conclude that there is a correlation between antiulcer mechanisms and α(2)-receptor activation. In rats given dexmedetomidine, all of the investigated antioxidant parameters increased, except for catalase (CAT). Conversely, aside from myeloperoxidase (MPO), all oxidant parameters decreased. Therefore, oxidant/antioxidant parameters play a role in the antiulcer mechanism of dexmedetomidine.

Inflammatory myofibroblastic tumor of the stomach in an adult woman: a rare intermittent cause of gastric outlet obstruction.

BACKGROUND Inflammatory myofibroblastic tumor is a neoplasm of intermediate biological potential that frequently recurs and rarely metastasizes. CASE REPORT We report a rare case of intermittent gastric outlet obstruction by an inflammatory myofibroblastic tumor of the cardia. RESULTS A 56-year-old woman presented at the gastroenterology department with a two-day history of hematemesis and melena. She had intermittent nausea and vomiting complaints, which had manifested periodically for about five months. Upper gastrointestinal endoscopy demonstrated a mass of 6 cm in diameter, which was resected. Histological examination revealed ulcerated mucosal granulation-like tissue with myofibroblastic spindle cell proliferation in a storiform pattern. CONCLUSIONS In order to avoid unnecessary aggressive therapy, gastric IMT should be taken into account when a gastric mass accompanied by the various clinical manifestations of IMT is found in an adult.

Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine levels in patients with active Behcet’s disease

Behcet’s disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to examine the effects of nitric oxide synthase activity (NOS), nitric oxide

Should increased levels of urinary 8-hydroxydeoxyguanosine in chronic gastritis imply intestinal metaplasia or gastric atrophy?

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