Exacerbation of hypoxic injury after reoxygenation is a crucial mechanism mediating organ injury in transplantation, and in myocardial, hepatic, gastrointestinal, cerebral, renal, and other ischemic syndromes. The occlusion and reperfusion of the splanchnic artery is a useful animal model to elucidate the mechanism of gastrointestinal injury induced by ischemia-reperfusion (I/R). Although xanthine oxidase is a major source of reactive oxygen species (ROS), which plays an important role in the I/R-induced intestinal injury, there are many other sources of intracellular ROS. Various treatment modalities have been successfully applied to attenuate the I/R injury in animal models. This review focuses on the role of oxidant stress in the mechanism of I/R injury and the use of antioxidant agents for its treatment.
The etiology of esophageal mucosal injury is complex, since it may involve the reflux of gastric acid, bile acid, and pancreatic juice, external factors such as drugs and alcohol, or functional factors such as esophagogastric motility. The mechanism of esophageal mucosal injury has gradually been understood at the molecular biological level. It is particularly important that pro-inflammatory factors, such as inflammatory cytokines (interleukin-6 and -8), leukocytes and oxidative stress, have been demonstrated to be involved in the development of gastroesophageal reflux disease (GERD) including nonerosive reflux disease (NERD). In addition, nociceptors such as acid-sensitive vanilloid receptors, protease-activated receptors and substance P have also been implicated in the pathogenesis of neurogenic inflammation in NERD patients with esophageal hypersensitivity. The development of new therapy with anti-inflammatory and anti-oxidant effects is expected to assist in the treatment of intractable NERD/GERD and the prevention of carcinogenesis.
Although atopic dermatitis is known to be closely associated with food antigens, the actual changes in the gastrointestinal tract have not been clarified. The aim of this study was to investigate the macroscopic and histological features of the large intestine in patients with atopic dermatitis. We studied 15 outpatients who had generalized atopic dermatitis. Eight non-dermatitis subjects of a similar age without inflammatory bowel disease were also enrolled as controls. Total colonoscopy, pathological evaluation of biopsy specimens, and detection of Candida albicans were performed in all subjects. Four patients were re-examined after 6 months of treatment with an antifungal drug. Among the 15 patients with atopic dermatitis, 4 patients had melanosis coli. On pathological examinations, prominent infiltration of eosinophils and fragmentation of granulocyte nuclei were observed. There were no changes after an antifungal therapy. In the patients with melanosis coli, lipofuscin deposits were observed in the lamina propria. Candida albicans was not detected in any of the subjects. In conclusion, patients with atopic dermatitis may have a predisposition to develop chronic inflammation of the large intestine.
We examined whether Saikokeishito extract (TJ-10), a traditional Japanese herbal medicine, exerts a therapeutic effect on α-naphthylisothiocyanate (ANIT)-induced liver injury in rats through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. In rats treated once with ANIT (75 mg/kg, i.p.), liver injury with cholestasis occurred 24 h after treatment and progressed at 48 h. When ANIT-treated rats orally received TJ-10 (0.26, 1.3 or 2.6 g/kg) at 24 h after the treatment, progressive liver injury with cholestasis was significantly attenuated at 48 h after the treatment at the dose of 1.3 or 2.6 g/kg. At 24 h after ANIT treatment, increases in hepatic lipid peroxide and reduced glutathione contents and myeloperoxidase activity occurred with decreases in hepatic superoxide dismutase and glutathione reductase activities. At 48 h after ANIT treatment, these changes except for reduced glutathione were enhanced with decreases in catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. TJ-10 (1.3 or 2.6 g/kg) post-administered to ANIT-treated rats attenuated these changes found at 48 h after the treatment significantly. These results indicate that TJ-10 exerts a therapeutic effect on ANIT-induced liver injury in rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue.
Various radical-scavenging activities of thiamin and thiamin diphosphate (TDP) were found in some in vitro experiments. Thiamin and TDP caused considerable suppressive effects on superoxide generation in hypoxanthine and xanthine oxidase system which was measured by a sensitive chemiluminescence method using 2-methyl-6-[p-methylphenyl]-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA), and their 50% inhibition (IC50) values were estimated to be 158 and 56 μM, respectively. They also showed the significant suppression against hydroperoxide generation derived from oxidized linoleic acid which was estimated by aluminum chloride method and their IC50 values were calculated to be 260 and 46 μM. They further prevented the oxygen radical generation in opsonized zymosan-stimulated human blood neutrophils which was shown by chemiluminescence method using luminol, and their IC50 values were calculated to be 169 and 38 μM. In contrast, they caused weak but significantly suppressive effects on the hydroxyl radical generation by Fenton reaction which was measured by electric spin resonance (ESR) method, their IC50 values were calculated to be 8.45 and 1.46 mM respectively. These results strongly suggest a possibility that thiamin and TDP play as radical scavengers in cell-free and cellular systems.
Oxidative stress is one of the mechanisms with a central role involved in the pathogenesis of myocardial infarction. The protective effect of glutamine on myocardial antioxidant defense system was investigated during isoprenaline-induced myocardial infarction, an animal model of myocardial infarction of human beings. Levels of diagnostic marker enzymes in plasma, reduced glutathione (GSH) and lipid peroxides and the activities of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase in heart tissue were determined. Injection of isoprenaline caused significant increases in the levels of diagnostic marker enzymes in plasma and lipid peroxidation in heart tissue. A parallel decline in the levels of ATP (Adenosine triphosphate) and GSH and the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes in heart tissue was also observed. Prior oral administration of glutamine significantly prevented isoprenaline-induced adverse effects and maintained myocardial antioxidant status at near normal status. The cardioprotective effect of glutamine is probably related to a strengthening of the myocardial membrane by its membrane stabilizing action, or to a counteraction of free radicals by its antioxidant property, or to its ability to maintain near to normal status the activities of free radical scavenging enzymes and the level of GSH, which protect myocardial membrane against oxidative damage by decreasing lipid peroxidation.
This study was undertaken to determine humoral immune response to the presence of anti-immunoglobulin antibodies in children with newly diagnosed type 1 diabetes mellitus, using as a target cow immunoglobulins, in an attempt to elucidate further complex immuno-pathogenetic interactions of the disease. Serum immunoglobulin G (IgG) concentrations were measured by ELISA in 30 children with type 1 diabetes mellitus and 30 healthy matched normal children. It was found that normal children had a mean IgG level of 7.41 mg/ml while diabetic individuals had a mean IgG level of 8.52 mg/ml (p<0.00004). On the contrary, the mean level of IgG in diabetic sera after purification from anti-cow immunoglobulins was determined to be 7.52 mg/ml. Therefore, there was no significant difference in IgG level in patients with type 1 diabetes mellitus after removal of anti-cow immunoglobulin antibodies compared to normal children (p<0.58). Visualization of IgG and immuno-precipitation confirm that anti-cow immunoglobulins antibodies, which were unrelated to antigen, were co-precipitated with the antigen-antibody complex. A circulating immunoglobulin reacting with other immunoglobulins is thus present in children with type 1 diabetes and may well play a part in the complex immuno-pathogenetic interactions.
Host genetic factors may play a key role in determining the long-term outcome of the Helicobacter pylori (H. pylori) infection. Toll-like receptor 4 (TLR4) mediated recognition of lipo-polysaccharide (LPS) is required for efficient recognition of gram-negative bacterial infections. The aim of this study is to investigate the effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile in patients with gastroduodenal diseases in Japanese population. The study was performed in 149 gastric cancer (GC) cases (mean age 64.0 ± 12.4, M:F = 109:40) and 94 patients without evidence of GC (mean age 64.1 ± 12.3, M:F = 65:25) as the control group. TLR4 Asp299Gly, Thr399Ile were determined by Polymerase chain reaction-length of polymorphisms (PCR-RFLP) in all the patients. Asp299Gly, Thr399Ile were not detected in all 243 patients enrolled in this study. In conclusion, our data suggest that TLR4 Asp299Gly, Thr399Ile are very rare in Japanese population and thus they may not be a important factor in determining the outcome of H. pylori infected individuals in Japan.
Radiofrequency ablation has been applied to treat hepatocellular carcinoma, with favorable therapeutic outcomes. Nevertheless, practitioners have approached radiofrequency ablation with some reluctance due to the difficulty of identifying isoechoic tumors and recurrent tumors. The aim of the present study is to investigate the efficacy of Real-time Virtual Sonography to treat hepatocellular carcinoma difficult to detect by conventional ultrasonography. Real-time Virtual Sonography is a system generating multiplanar reconstruction images in real-time using the Hitachi medico EUB-8500 equipped with a probe. The system included following components: 1) digital imaging and communications in medicine (DICOM) data from dynamic CT, 2) a magnetic field generator to match the multiplanar reconstruction image on the monitor and the actual ultrasonography image, 3) the cross section with the tumor displayed as a multiplanar reconstruction image. Total twenty-five nodules of twenty-one patients underwent radiofrequency ablation monitored by Real-time Virtual Sonography. All nodules difficult to detect via conventional ultrasonography were clearly visualized in real-time. The average nodule diameter was 2.4 ± 1.6 cm, and punctures and coagulation were performed an average of 2.2 and 3 times per session. Dynamic CT after session confirmed effective coagulation of each nodule. In conclusion, this study demonstrates that the present system is capable of effectively and accurately treating tumors difficult to detect by conventional ultrasonography.