Reina Ohba

New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline

Background : In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported.

Large Brunner’s Gland Hyperplasia Treated with Modified Endoscopic Submucosal Dissection

Brunner’s glands are mucosal and submucosal alkalinesecreting glands that are most commonly located in the duodenum, especially in the first part of the duodenum, although they are rarely found in the pylorus and jejunum. Hyperplasia of these glands is normally seen in 2% of upper gastrointestinal (GI) endoscopies [1]. Five percent to 10% of benign duodenal tumors are caused by lesions of Brunner’s gland [2]. They are usually asymptomatic and lesions are discovered incidentally but they can occasionally cause symptoms such as GI hemorrhage and obstruction when they reach sizes >2 cm [3, 4]. In this paper, we report a case of large hyperplasia of Brunner’s gland successfully treated by modified endoscopic submucosal dissection (ESD) technique.

Selective adenosine A2A receptor agonist, ATL‐146e, attenuates stress‐induced gastric lesions in rats

Background:  Activation of adenosine A2A receptors reduces the production of various pro‐inflammatory cytokines and suppresses neutrophil activation. Water‐immersion restraint is well known to cause gastric mucosal lesions due to stress. The pathogenesis of stress‐induced gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A2A receptors are known to be anti‐inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A2A receptor agonist, ATL‐146e, on water‐immersion stress‐induced gastric mucosal lesions was studied.

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice

Backgroundd-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor-α (TNF-α) plays a pivotal role. We examined the effects of a highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.MethodsMice were given an intraperitoneal dose of GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e (0.01 µg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF-α levels in the serum were determined.ResultsThe serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 ± 2800 IU/ml and was reduced by 63% to 7800 ± 1670 IU/ml by treatment with 0.01 µg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF-α and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12 h from 65% to 13%.ConclusionThe present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-α secretion.

Successful Treatment of Refractory Duodenal Crohn’s Disease with Infliximab

Since the introduction of the anti-tumor necrosis factor (TNF) monoclonal antibody infliximab 1997, the treatment of Crohn’s disease has changed dramatically [1]. Duodenal Crohn’s disease is rare and unique in that its clinical response to medical therapy is universally poor and usually requires surgical therapy such as gastrojejunal bypass [2]. We present one case of duodenal Crohn’s disease with severe stricture that was resolved by treatment with infliximab. In March 2004, a 17-year-old man presented with abdominal pain and diarrhea; he was diagnosed as having Crohn’s disease in the colon. He was treated with corticosteroid (predonisolone, 40 mg/day) and mesalazine (Pentasa, 3.0 g/day). His symptoms and colonic lesions resolved and he was discharged in June 2004. He was maintained on mesalazine (Pentasa, 3.0 g/day) and corticosteroid (predonisolone, 10 mg/day) to prevent recurrence. Also, he was on enteral nutrition therapy using an elemental diet. In August 2004, he suddenly developed severe upper abdominal pain, abdominal distension, nausea, and vomiting. Abdominal CT scan showed marked wall thickness of duodenum. An upper GI X-ray showed a stricture of duodenum (Fig. 1). Endoscopic examination revealed a stricture with a large ulceration and mucosal edema in the duodenum bulb. Histologically, the biopsy specimen of the duodenal mucosa revealed marked active chronic inflammation with

Effect of cilostazol, a selective type-III phosphodiesterase inhibitor, on water-immersion stress-induced gastric mucosal injury in rats

BackgroundCilostazol, a specific type-III phosphodiesterase inhibitor, is widely used for the treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to the suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The pathogenesis of stress-induced gastric mucosal lesions is characterized by the activation of inflammatory cells and the production of inflammatory cytokines. The effects of cilostazol on the development of gastric mucosal lesions have not been reported. In the present study, we examined the effect of a cilostazol on water-immersion stress-induced gastric mucosal lesions.MethodsRats were subjected to water-immersion stress with or without pretreatment with a single intraperitoneal injection of the selective type-III phosphodiesterase inhibitor, cilostazol. We measured the gastric mucosal lesion and the concentrations of myeloperoxidase (MPO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), as an index of neutrophil accumulation and pro-inflammatory cytokine production.ResultsCilostazol ameliorated the gastric mucosal injury induced by water-immersion stress (P < 0.001). The gastric contents of MPO, TNF-α, IL-1β, and CRO/CINC-1 were all increased after water-immersion stress and were reduced to almost normal levels by cilostazol.ConclusionsIn this study, we demonstrated that a selective type-III phosphodiesterase inhibitor, cilostazol, inhibited stress-induced gastric inflammation and damage via suppressing the production of pro-inflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions.

Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide-induced liver injury in rats

Background and Aims:  Rolipram  is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro‐inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)‐induced liver injury in rats as a model.

Mechanical strain stress suppresses expression of HSP70 and wound restoration in gastric mucosal cells

The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a “molecular chaperone.” However, the influence of HSP70 on gastric mucosal healing under physical stimulation or stress is not completely understood. Rat gastric mucosal cells (RGM-1) were stably transfected with pBK-CMV containing the human HSP70 gene (7018-RGM-1) or pBK-CMV alone (pBK-CMV-12). Artificial wounds were created. Mechanical stretch was applied to 7018-RGM-1 cells or pBK-CMV-12 cells. The effect of mechanical stretch on HSP70 expression was assessed by Western blot analysis. Expression of HSP70 was decreased by mechanical stretch in pBK-CMV-12 cells. However, expression of HSP70 was not decreased by mechanical stretch in 7018-RGM-1 cells. Furthermore, the wound restoration of pBK-CMV-12 cells was suppressed under mechanical stretch condition. On the other hand, the wound restoration of 7018-RGM-1 cells was not affected by mechanical stretch. These results suggest that HSP70 plays an important role in gastric wound healing under physical stress.

Salvage endoscopic submucosal dissection for the esophagus-localized recurrence of esophageal squamous cell cancer after definitive chemoradiotherapy

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Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates aspirin-induced gastric mucosal injury in rats.

Inhibition of type IV phosphodiesterase (PDE IV) activity reduces the production of various proinflammatory cytokine and suppresses neutrophil activation. Nonsteroidal anti-inflammatory drugs such as aspirin induce gastric mucosal lesions. In the pathogenesis of aspirin-induced gastric mucosal lesion, the contributions, of activated inflammatory cells and proinflammatory cytokine production are critical. The specific PDE IV inhibitor rolipram is known to be a potent inhibitor of inflammation by increasing intracellular cyclic AMP in leukocytes. The aim of the present study was to determine whether rolipram can ameliorate aspirin-induced gastric mucosal lesions in rats and whether the agent can inhibit the inrease in neutrophil accumulation and the production of proinflammatory cytokines. Gastric lesions were produced by administration of aspirin (200 mg/kg) and HCl (0.15 N; 8.0 ml/kg). Rolipram was injected 30 min before aspirin administration. The tissue myeloperoxidase concentration in gastric mucosa was measured as an indicat or of neutrophil infiltration. The gastric mucosal concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by ELISA. The intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. Gastric mucosal lesions induced by aspirin were significantly inhibited by treatment with rolipram. The mucosal myeloperoxidase concentration was also suppressed by rolipram. Increases in the gastric content of TNF-α and IL-1β after aspirin administration were inhibited by pretreatment with rolipram. We demonstrated that the specific type IV PDE inhibitor, rolipram, could have a potent antiulcer effect, presumably mediated by its anti-inflammatory properties.