Sare Altas

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.

The role of ischemic neurodegeneration of the nodose ganglia on cardiac arrest after subarachnoid hemorrhage: an experimental study.

BACKGROUND The heart is innervated by several systems that contribute to the control of the hearts rhythm. The cardiac fibers of the vagus nerve have an important role in the regulation of heart rhythm under many emotional and physical conditions. Severe electrocardiographic disturbances have been reported following subarachnoid hemorrhage (SAH), but ischemic neuronal degeneration of the nodose ganglion of the vagus nerve has not been previously investigated. We examined if there is a relationship between ischemic injury of the nodose ganglion of the vagus nerve and the severity of heart rhythm disorders after subarachnoid hemorrhage. METHODS This study was conducted on 20 rabbits. Four rabbits were used as a baseline group. Experimental subarachnoid hemorrhage was applied to half of the remaining animals (n = 8) by injecting homologous blood into the cisterna magna, and the others (SHAM group, n = 8) were injected with isotonic saline solution in the same manner. For 20 days after the injection, heart rhythm changes were observed daily. After the experiment, normal and ischemic neuron densities in the nodose ganglia of the vagus nerves were examined stereologically. The number of heart rhythm irregularities and the number of degenerated neurons in the nodose ganglia were compared statistically. RESULTS The normal heart rhythm rate was 280 ± 45/min. At the beginning of the SAH, the average heart rate was 220 ± 30/min; about 10 hours later, it decreased to 189 ± 30/min, indicating severe bradycardia. However, after 7 days, the average heart rate had increased to 350 ± 30/min. Six animals died due to irregularities in cardiac function and respiration. Histopathological examinations showed that the average density of normal neurons in the nodose ganglion was 10,500 ± 2500 in the baseline animals and the SHAM group, but the normal neuron density was 8250 ± 1500 in survivors and 6450 ± 1330 in dead animals. The ischemic neuronal degeneration in the nodose ganglia was more severe in the dead animals than in the survivors (p < 0.0001). CONCLUSION Afferent vagus nerves originating from the nodose ganglia have an important role in regulating heart rhythm via their afferent fibers and efferent connections. If neurons of the nodose ganglia are lesioned due to ischemic insult during subarachnoid hemorrhage, heart rhythm regulation by vagus afferent reflexes is disturbed. Vagus pathway paralysis may result in indirect sympathetic overactivity. The development of tachycardia causes depletion of the hearts reserves, and cardiac arrest may be inevitable following extensive subarachnoid hemorrhage.

Anti-inflammatory effect of erythromycin on histamine-induced otitis media with effusion in guinea pigs

In this study, the anti-inflammatory effect of erythromycin was investigated in a model of histamine-induced otitis media with effusion (OME). OME was induced in guinea pigs by the transtympanic injection of histamine solution into the middle-ear cavity. Guinea pigs were randomly assigned to one of three groups: control, erythromycin treatment, or methylprednisolone treatment. After histamine injection, the animals were treated with intraperitoneal medication for five days consecutively. Afterwards, the animals were sacrificed and the temporal bones were removed. The samples were examined stereologically. In the erythromycin-treated group, it was observed that neutrophil infiltration was significantly inhibited when compared to the control group. This result shows that erythromycin may produce a significant anti-inflammatory effect in this model of OME.

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.

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

Objectives: Helicobacter pylori (H pylori) infection induces chronic inflammation that can progress to gastric atrophy, intestinal metaplasia, and gastric adenocarcinoma. We have examined oxidative damage caused by Helicobacter pylori, metaplasia, and atrophy of gastric mucosal cells in patients with chronic gastritis by measuring their urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Methods: We recruited 77 outpatients with chronic gastritis, confirmed by endoscopic examination. H pylori status was evaluated by histology (modified Giemsa staining), the H pylori stool antigen test (n=20), and the 13C urea breath test (n=27), as described in the Maastricht consensus report. Results: The mean amount of 8-OHdG (&mgr;g/g creatinine) in 77 subjects was 18.07 ± 13.49 x 10-3 &mgr;g/g creatinine. The levels of urinary 8-OHdG in the H pylori-positive gastritis patients were also significantly higher than those in the H pylori-negative gastritis patients (P=0.003, respectively, 20.42 ± 13.33 x 10-3 &mgr;g/g creatinine, 13.16 ± 12.71 x 10-3 &mgr;g/g creatinine). The level of urinary 8-OHdG was markedly higher in patients with gastric atrophy and intestinal metaplasia than in those without (P=0.000, P=0.002, respectively). There were significant correlations between levels of urinary 8-OHdG and both the atrophy score (r=0.441, P=0.000) and the intestinal metaplasia score (r=0.436, P=0.000). Conclusions: Urinary 8-OHdG levels could be investigated in every patient with chronic gastritis, since it is a simple and completely noninvasive procedure. In patients with high levels of urinary 8-OHdG, endoscopic procedures or even pathological investigation may then be carried out, with the consideration that there is a high risk of intestinal metaplasia or atrophy.

The Contribution of Chemoreceptor-Network Injury to the Development of Respiratory Arrest Following Subarachnoid Hemorrhage

OBJECTIVE Respiratory arrest following brainstem herniation has been attributed to injuries resulting from compression of the respiratory centers. While it is widely perceived that the chemoreceptor network, consisting of the glossopharyngeal nerve and carotid body (GPN-CB), is essential for the modulation of respiration, its contribution to the development of respiratory arrest has not been investigated. Therefore, the aim of this study was to investigate whether injury to the GPN-CB occurs in animals with respiratory arrest caused by experimentally-induced subarachnoid hemorrhage. MATERIALS AND METHODS Eighteen hybrid rabbits were used in this study. Four rabbits (n=4) were used to determine the normal structure of the GPN-CB. The remaining rabbits (n=14) received an autologous blood injection into the cisterna magna to produce a subarachnoid hemorrhage, after which they were observed for 20 days. The number of axons and the neuron density in the glossopharyngeal nerve and carotid body, respectively, were counted by stereological methods. The Mann-Whitney U test was used to analyze the results. RESULTS Six of 14 rabbits died within the first week, likely due to brain swelling and crushing injuries that were observed in the brain stem and related structures. In control rabbits, the average neuronal density of the carotid body was 4250 ±1250/mm(3), while the axonal density in the glossopharyngeal nerve was 18000±5100 mm(2). Conversely, in the dead rabbits, the degenerated neuron density of the carotid body was 2100±500/mm(3), while the degenerated axon density in the glossopharyngeal nerve was 8500±2550 mm(2). In addition, histopathological lesions were more severe in the dead rabbits in terms of their glossopharyngeal nerve and carotid body. CONCLUSION There is an important relationship between neurodegeneration in the GPN-CB and mortality rates following experimentally-induced hemorrhage. This relationship suggests that injury to the GPN-CB network disrupts the breathing reflex and results in respiratory arrest following a subarachnoid hemorrhage (SAH).