Ariyoshi Iwasaki

Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis

Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.

Central effect of melatonin against stress-induced gastric ulcers in rats

WE investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1–1 ng) injected intracisternally (i.c.) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 μg/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.

Protective role of melatonin and the pineal gland in modulating water immersion restraint stress ulcer in rats.

We investigated the protective effect of melatonin on stress-induced gastric lesions in rats. Fasted rats were subjected to water immersion restraint stress for 4 h and the percentage of corpus mucosa containing hemorrhagic lesions was determined. Thirty minutes before restraint stress, melatonin or vehicle was administered i.p. In another experiment, pinealectomy was performed 1 week before water immersion restraint stress. Administration of melatonin at 1 and 5 mg/kg significantly decreased gastric lesions by 46 and 74%, respectively. In contrast, pinealectomy significantly enlarged the lesion area, although this effect was counteracted by melatonin at a dose of 1 mg/kg i.p. However, this protective effect of melatonin was abolished by i.p. pretreatment with indomethacin at 5 mg/kg. These results suggest that melatonin has gastroprotective properties against stress-induced gastric injury in rats and that the pineal gland contributes to gastric protection via prostaglandin-dependent mechanisms.

Helicobacter pylori, neutrophils, interleukins, and gastric epithelial proliferation.

Infection of Helicobacter pylori causes chronic gastritis and plays an important role in the pathogenesis of gastroduodenal ulceration. H. pylori has also been suggested to be involved in the genesis of adenocarcincoma and MALT lymphoma of the stomach. H. pylori infection is associated with increased gastric epithelial proliferation, which can be reversed by a successful eradication of the organism. Although the mechanisms of increased gastric epithelial proliferation is not known, the enhanced epithelial proliferation is important in developing gastric carcinoma. Whether or not H. pylori de nove stimulates gastric epithelial proliferation is controversial, but gastric infection with H. pylori activates a mucosal inflammatory response by consisting of large numbers of polymorphonuclear and mononuclear cells, that also includes expression of various cytokines including interleukin-8. We review the mechanisms of H. pylori in enhanced gastric epithelial cell proliferation and cytokines in patients with H. pylori infection.

Oral peppermint oil is a useful antispasmodic for double-contrast barium meal examination

Background and Aim:  Intraluminally administered peppermint oil (PO) is reportedly a safe and useful antispasmodic for gastroscopy, colonoscopy and double‐contrast barium enema. The aim of this study was to examine the efficacy of oral PO for double‐contrast barium meal examination (DCBM) without other antispasmodics.

Roles of nocturnal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats.

The roles of melatonin and the pineal gland in the circadian variation of water‐immersion restraint stress‐induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water‐immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham‐operated rats were also subjected to water‐immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light‐phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water‐immersion restraint stress. In contrast, melatonin concentrations 4 hr after water‐immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham‐operated rats. These results suggest that circadian rhythm has an important role in the formation of stress‐induced gastric mucosal lesions in rats and that melatonin responses to water‐immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system.

Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H+, K(+)-ATPase.

We purified a compound with strong inhibitory effect on H+, K(+)-ATPase from Paeoniae radix, which has been used in Japan for the treatment of gastritis and peptic ulcers. The compound was identified as 1,2,3,4,6,-penta-o-galloyl-beta-D-glucose by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and fast atomic bombardment mass spectrometry. The IC50 of the compound for H+, K(+)-ATPase was 166 nmol/l. Kinetic analyses indicated that the inhibition of the enzyme by pentagalloylglucose was noncompetitive with respect to K+. Pentagalloylglucose had relatively weak inhibitory effects for Mg(+)-ATPase (IC50: > 10 mumol/l) and Na+, K(+)-ATPase (IC50: 2.7 mumol/l). Pentagalloylglucose also inhibited the accumulation of [14C]aminopyrine in parietal cells that had been isolated from guinea pig stomach and stimulated by 10 mumol/l histamine (IC50: 7.8 mumol/l) and 1 mmol/l dbc-AMP (IC50: 10 mumol/l). These results suggest that pentagalloylglucose is a potent inhibitor of H+, K(+)-ATPase and may be responsible for inhibition of acid secretion by Paeoniae radix.

Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats.

We previously demonstrated the circadian variation of water‐immersion restraint stress (WRS)‐induced gastric mucosal lesions in rats.

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Role of acetylcholine and gastrin-releasing peptide (GRP) in gastrin secretion

Using an isolated rat stomach infusion model, we investigated the role of gastrin-releasing peptide (GRP) and acetylcholine in the secretion of gastrin (which plays a major role in gastric acid secretion), and the relationship between gastrin secretion and stomach pH. Bombesin, which has a structure analogous to that of GRP, was used in the experiment. We also investigated whether acetylcholine has muscarine-like or nicotine-like action. Our findings pointed to the presence of an alternative, GRP-mediated, route for stimulating gastric secretion from G cells, other than the acetylcholine-mediated route. We injected bombesin to confirm the presence of such a GRP-mediated route; significantly increased gastrin secretion was observed, even under acidic conditions, in the gastric lumen, which has been considered to show almost no gastric secretion. This secretion was not inhibited by atropine. The results suggested that there are two routes for inducing gastrin secretion from G cells: an acetylcholine-mediated route and a GRP-mediated route (intramural peptide neurons). As GRP induced gastrin secretion, regardless of stomach pH, GRP was considered to be more closely related to gastrin secretion. The results also suggested that a muscarine-like action, particularly in the M3 receptor-mediated route, plays a significant role in acetylcholine-mediated gastrin secretion and that nicotine-like action is not involved in gastrin secretion.