Hiroshi Higashihara

Different effects of constitutive nitric oxide synthase and heme oxygenase on pulmonary or liver metastasis of colon cancer in mice

It has recently been reported that not only endogenous nitric oxide (NO) but also carbon monoxide (CO) produced by heme oxygenase (HO) have many physiological functions. The objective of the present study was to determine whether endogenous NO or CO is involved in the experimental pulmonary or liver metastasis of colon cancer in mice. Intravenous or intrasplenic injection of colon 26 cells from a mouse colon adenocarcinoma cell line resulted in multiple pulmonary or liver metastases. NG-nitro-l-arginine methyl ester (l-NAME), a competitive inhibitor of NO synthase (NOS), or zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG), a competitive inhibitor of HO, was administered to the mice only on the day of tumor inoculation. We assessed the number of tumor cells 24 h later and the outcome of metastases of the target organ. In the pulmonary metastasis model, l-NAME increased both the number of tumor cells 24 h later and outcome of metastases 18 days later, but did not have a significant effect on liver metastasis. On the other hand, metastasis to the liver, but not that to the lung, increased following administration of ZnDPBG. These results suggest that the activities of NOS and HO could influence experimental metastasis in an organ-specific manner.

Rotenone, a mitochondrial electron transport inhibitor, ameliorates ischemia-reperfusion-induced intestinal mucosal damage in rats.

Abstract In ischemia–reperfusion (I/R)-induced tissue injury, oxygen radicals can be generated by several mechanisms. One of the important sources of oxygen radicals is thought to be mitochondrial respiration. The aim of this study was to investigate the antioxidative defense effect of the mitochondrial electron transport inhibitor, rotenone using the I/R-induced rat intestinal mucosal injury model in vivo. Intestinal ischemia was induced for 30 min by applying a small clamp to the superior mesenteric artery in rats. Rotenone at a dose of 100 mg/kg was given to rats orally 2 h before the ischemia. Intraluminal hemoglobin and protein levels, the mucosal content of thiobarbituric acid-reactive substances (TBARS), the mucosal myeloperoxidase activity, and the content of inflammatory cytokines (CINC-1, TNF-α) were all significantly increased from mean basal levels after 60 min of reperfusion. These increases after I/R were inhibited by treatment with rotenone at a dose of 100 mg/kg. Co-administration with succinate (100 mg/kg), a substrate of the mitochondrial electron transport system, cancelled significant reduction of intraluminal hemoglobin and mucosal TBARS treated with rotenone alone. The results of the present study indicate that rotenone inhibited lipid peroxidation and reduced development of the intestinal mucosal inflammation induced by I/R in rats. This investigation suggests that rotenone has potential as a new therapeutic agent for reperfusion injury.

Effects of bile acids and acidic exposure on IL-8 expression in human esophageal epithelial cells

exposed on the surface of remaining tissue Primary squamous oesophageal epithelial cells (Sq cells) were isolated by explant tissue culture of normal oesophageal nmcosa. These cells were subsequently propagated in a low Ca + + serum-free tissue culture maintenance medium Sq cells were allowed to adhere to the luminal basement membrane of either Sq BM orCLO BM. Sq cells cultured in this orientation are at an airdiqind interface, which allow prolderation, stratification and dift?rentiation in response to the high Ca + + medium and interaction with the ECM and basement membrane. Results: The model was cultured for three weeks and histology confirmed sqnamous epithelium colonises sqnamous BM Laminin, an abundant ECM component was characterised by immunohistochemical staining. Conclusions: Tile role of the basement membrane in CLO on Sq cell proliferation and diflerentiation can be examined using this model

Mucosal IgA depositon in Henoch–Schönlein purpura with duodenal ulcer

and renal function tests were normal. The erythrocyte sedimentation rate (ESR) was 15 mm/h, and C-reactive protein (CRP) was 0.9 mg/dL. Results of urinalysis were normal. Occult blood was found in the feces, but cultures for bacteria and intestinal parasites were negative.We performed an upper gastrointestinal endoscopy and a colonoscopy because the patient complained of nausea, epigastral pain, and lower abdominal pain after admission. The findings of gastrointestinal endoscopy showed extensive ulceration of the duodenum from the second to the third portion. Results of culture of the biopsy specimens and urea breath test were negative for Helicobacter pylori infection. Histological examination of biopsy specimens obtained from the duodenal ulcer revealed that the stroma were fibrous and infiltrated by acute and chronic inflammatory cells, including moderate neutrophilic, lymphocytic, and eosinophilic infiltration. No specific changes were found at the duodenal ulcer on the abdominal angiography.The purpuric rash and the joint pain had disappeared by the time the endoscopy was performed. Subsequently, we administered famotidine (20 mg/day) intravenously and sucralfate (750 mg/day) orally, without using steroid. Within a few days of administration of medication, the upper and lower abdominal pain had disappeared and no occult blood was observed. Gastrointestinal endoscopy 3 weeks after administration of medication showed scarring on the duodenal ulcer from the second to the third part. The patient was discharged after the epigastral pain disappeared, and during the 6 months To the Editor, Our patient was diagnosed with Henoch–Schönlein purpura (HSP), suffered from duodenal ulcer and was administered famotidine and sucralfate. Because deposition of IgA was detected in the biopsy materials in the ulcer scar after medication, these findings suggest that the deposition of IgA did not play an important role in the duodenal mucosal damage. Henoch–Schönlein purpura is a multisystem vasculitic disorder characterized by purpuric skin lesions, colicky abdominal pain, arthralgia, arthritis, and nephritis.Various Gram-positive bacterial or viral infections have been associated with HSP. The dermal and mesangial deposition of IgA has been established to be characteristic of HSP. Some reports have proposed the possibility of gastrointestinal mucosal damage associated with the deposition of IgA. We describe here the case of a patient with HSP combined with extensive ulcer in the second portion of the duodenum, and examined the deposition of IgA at the ulcer before and after administration of medication. An 18-year-old woman was admitted to our hospital with pyrexia, joint pain, and a purpuric rash over the whole body.The dermatologist diagnosed her as having anaphylactoid purpura based on her symptoms and the histological findings of the purpuric rash. Her hemoglobin level was 11.5 g/dL, her white blood cell count 4500/mL, and her platelet count 689 000/mL. Her serum total protein concentration was 7.6 mg/dL, with an albumin concentration of 3.9 mg/dL. Results of hepatic LETTER TO THE EDITOR

Hypoxia-reoxygenation enhances interleukin-8 production from U937 human monocytic cells.

Abstract Hypoxia–reoxygenation (H/R) occurs in both inflammatory spots and tumor tissues, sites in which damage is amplified either acutely or chronically through the infiltration of inflammatory cells. Interleukin-8 (IL-8) is a cytokine with chemotactic and angiogenic properties. This study was designed to investigate the effects of H/R on IL-8 production in the U937 human monocytic cell line. Two hours of hypoxia followed by 4 h of reoxygenation induced a significant increase in IL-8 protein production and IL-8 mRNA expression in U937 cells. Pretreatment with proteasome inhibitor (PSI), a peptide aldehyde known to inhibit the chymotrypsin-like activity of the 26S proteasome specifically, suppressed IL-8 protein production and IL-8 mRNA expression induced by H/R. The production of IL-8 protein induced by H/R was decreased by pioglitazone and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), which have been identified as peroxisome proliferator-activated receptorγ (PPAR-γ) ligands. Moreover, transfection of U937 cells with a dominant negative IκBαexpression vector (IκBαM) decreased IL-8 protein production induced by H/R. These results suggest that NF-κB and PPAR-γ regulate H/R-stimulated IL-8 production in U937 cells.

Rotenone, mitochondrial electron transport inhibitor, ameliorates ischemia-reperfusion-induced intestinal mucosal damage in rats

In ischemia-reperfusion (I/R)-induced tissue injury, oxygen radicals can be generated by several mechanisms. One of the important sources of oxygen radicals is thought to be mitochondrial respiration. The aim of this study was to investigate the antioxidative defense effect of the mitochondrial electron transport inhibitor, rotenone using the I/R-induced rat intestinal mucosal injury model in vivo. Intestinal ischemia was induced for 30 min by applying a small clamp to the superior mesenteric artery in rats. Rotenone at a dose of 100 mg/kg was given to rats orally 2 h before the ischemia. Intraluminal hemoglobin and protein levels, the mucosal content of thiobarbituric acid-reactive substances (TBARS), the mucosal myeloperoxidase activity, and the content of inflammatory cytokines (CINC-1, TNF-alpha) were all significantly increased from mean basal levels after 60 min of reperfusion. These increases after I/R were inhibited by treatment with rotenone at a dose of 100 mg/kg. Co-administration with succinate (100 mg/kg), a substrate of the mitochondrial electron transport system, cancelled significant reduction of intraluminal hemoglobin and mucosal TBARS treated with rotenone alone. The results of the present study indicate that rotenone inhibited lipid peroxidation and reduced development of the intestinal mucosal inflammation induced by I/R in rats. This investigation suggests that rotenone has potential as a new therapeutic agent for reperfusion injury.