AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized t...AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.展开更多
AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotectiv...AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.展开更多
AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induce...AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.展开更多
文摘AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.
文摘AIM To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH 2Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective activity. METHODS AND RESULTS Oral administration of NH 2Cl (120*!mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs. Both irsogladine ( 1*!mg/*!kg - 10*!mg/*!kg , po ) and rebamipide ( 30*!mg/*!kg - 100*!mg/*!kg , po ) dose dependently prevented the development of these lesions in response to NH 2Cl, the effect of irsogladine was significant at 3*!mg/*!kg or greater, and that of rebamipide only at 100*!mg/*!kg . The protective effect of irsogladine on NH 2Cl induced gastric lesions was significantly reduced by N G nitro L arginine methyl ester (L NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L NAME. Topical application of NH 2Cl (20*!mM) caused a marked reduction of potential difference (PD) in ex vivo stomachs. This PD reduction was not affected by mucosal application of irsogladine, but significantly prevented by rebamipide. The mucosal exposure to NH 4OH (120*!mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH 4OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L NAME sensitive manner. CONCLUSION These results suggest that ① NH 2Cl generated either exogenously or endogenously damages the gastric mucosa, ② both irsogladine and rebamipide protect the stomach against injury caused by NH 2Cl, and ③ the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.
文摘AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.
