Effects of gefarnate on acute gastric lesions in rats

The effects of gefarnate on several acute gastric lesions were studied in rats. Gefarnate, given at either 100 approximately 1000 mg/kg orally or intraduodenally, dose-dependently inhibited the formation of gastric lesions induced by HCl-ethanol, HCl-taurocholate and aspirin. Cimetidine, given at 30 approximately 100 mg/kg as a reference drug, also significantly inhibited both HCl-ethanol and aspirin-induced lesions. The present study suggests that gefarnate, as well as cimetidine, is useful for the treatment of acute gastric lesions in man.     

Effects of troxipide on acute gastric lesions in rats

Effects of troxipide on several acute gastric lesions in rats were investigated in comparison with those of cetraxate. Troxipide (100, 200, 300 mg/kg) and cetraxate (100, 300, 1,000 mg/kg), given orally, dose-dependently protected the gastric mucosa from damage due to ethanol. Aspirin- and 0.6 N HCl-induced gastric lesions were dose-dependently inhibited by troxipide (200, 300 mg/kg), but only significantly inhibited by cetraxate at high dose (1,000 mg/kg). Troxipide (100, 200, 300 mg/kg) dose-dependently prevented the formation of gastric lesions induced by water-immersion stress, whereas cetraxate (600, 1,000 mg/kg) also significantly prevented gastric lesions. That is, protective effects of troxipide were much more potent than those of cetraxate against aspirin-, 0.6 N HCl- and water-immersion stress-induced gastric lesions, whereas both were almost equal against ethanol-induced gastric lesions. In addition, cytoprotective effects of troxipide against ethanol-induced lesions were most remarkable at 10, 30, 60 min after administration (100, 300 mg/kg) and lasted for up to 240 min. These results suggested that troxipide might be useful for the treatment of acute gastric lesions in humans.     

Characterization of dopamine receptor subtypes involved in experimentally induced gastric and duodenal ulcers in rats

There are conflicting reports about the role of dopamine in gastric and duodenal ulcers. This investigation was undertaken to characterize the specific subtypes of dopamine receptor involved in gastric and duodenal ulceration. Administration of dopamine D1 agonist fenoldopam and dopamine D2 antagonist sulpiride elicited a significant decrease in acid secretion, total acid output, pepsin output and histamine content in the gastric juice, and reduced ulcer-index values, in pylorus-ligated rats. However, dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo (d) naptho -(2,1-b) azepine) and the D2 receptor agonist quinpirole led to significant augmentation of these parameters compared with respective controls. In the restraint plus water-immersion stress model the score for intraluminal bleeding and the cumulative gastric lesion length was significantly lower for rats treated with fenoldopam and sulpiride. The opposite effects were observed after pretreatment of rats with SCH 39166 and quinpirole. In the cysteamine-induced duodenal ulcer model the mean ulcer area and the score for intensity were significantly lower for fenoldopam and sulpiride and higher for SCH 39166 and quinpirole. Our data suggest that the dopamine D1 and D2 receptors have opposite effects on gastric and duodenal ulcers. Whereas stimulation of dopamine D1 receptors inhibits the formation of gastric and duodenal ulcers, stimulation of dopamine D2 receptors has a pro-ulcerogenic effect.     

Healing promoting effect of azuletil sodium (KT1-32) on experimental chronic gastric ulcers and acceleration of healing in SPF environment

We examined the healing promoting effects of azuletil sodium on acetic acid and clamping cortisone-induced gastric ulcer in rats. For the experiments on clamping-cortisone gastric ulcer, we used not only conventional rats in conventional conditions but also specific pathogen free (SPF) rats on SPF environment in order to prevent infection. The following results were obtained. 1) In acetic acid ulcer, azuletil sodium (AZE) (greater than or equal to 90 mg/kg/day, p.o.) significantly decreased ulcer index. As estimated on the basis of stage analysis (Ulcer, Healing, Scar), AZE (greater than or equal to 30 mg/kg/day, p.o.) significantly promoted the healing of ulcers. 2) In clamping cortisone ulcer (conventional), AZE (100 mg/kg/day, p.o.) significantly promoted the regeneration of blood vessels. 3) In clamping cortisone ulcer (SPF), AZE at greater than or equal to 30 mg/kg/day and 100 mg/kg/day significantly increased the healing index and mucosal regeneration index, respectively. 4) In clamping cortisone ulcer (SPF), the infection that was observed in the conventional test was not seen at all and the acceleration of healing was observed. Furthermore, the extent of adhesion was also reduced, and the standard errors of various healing indices were smaller. From these results, it is concluded that AZE accelerated the healing of experimentally-induced gastric ulcers in rats.     

Effects of cimetidine and atropine sulfate on gastric secretion and healing of gastric and duodenal ulcers in rats.

Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers.     

Capsaicin-sensitive mechanisms and experimentally induced duodenal ulcers in rats

The incidence and degree of cysteamine- or dulcerozine-induced duodenal ulcers are increased by systemic capsaicin desensitization (50 mg kg-1 s.c. 4 days before) in adult rats. Acute administration of capsaicin, but not neurokinins or CGRP, produced a small but distinct plasma extravasation (Evans blue leakage) in the rat proximal duodenum which was absent in capsaicin-pretreated rats. These findings indicate the existence of a capsaicin-sensitive 'duodenal defence mechanism' in rats.     

脑室注射催产素对大鼠胃和十二指肠溃疡的作用

INTRODUCTION Central neurons that synthesize oxytocin are locatedin the supraoptic(SON) and paraventricular nuclei(PVN) of the hypothalamus. Magnocellular neurons inboth nuclei project to the posterior pituitary gland,     

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.     

Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats.

The effect of hyperprolactinaemia, induced by two or four pituitary homografts under the kidney capsule, on gastric and duodenal ulcers has been studied. The acute gastric ulcer models used were pylorus ligation, indometacin-induced and ethanol-induced gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by mercaptamine hydrochloride. After pylorus ligation, there was an approximate 30-40% increase in gastric secretion, a significant increase in total acidity (P < 0.01) and in the ulcer index (P < 0.01) in rats bearing pituitary homografts under the kidney capsule when compared with the sham-operated control. Hyperprolactinaemia did not affect the formation of ethanol-induced gastric ulcers but showed a 40% reduction in the development of indometacin-induced gastric ulcers. It also produced a 20% increase in the ulcer index in acetic acid-induced chronic gastric ulcers and a 30% increase in ulcer area in mercaptamine-induced duodenal ulcers. Our results showed that hyperprolactinaemia induced gastric acid secretion and thereby aggravated gastric and duodenal ulcers in rats. Hyperprolactinaemia did not affect gastric cytoprotection.     

Effects of elcatonin, a synthetic analogue of eel calcitonin, on acute gastric and duodenal lesions and gastroduodenal function in rats

We studied the effects of elcatonin (eel calcitonin), on various gastric and duodenal lesions, gastric acid and duodenal alkaline secretion, and gastric motility in rats. Elcatonin at 1-30 unit/kg, given subcutaneously, dose-dependently inhibited the development of HCl-aspirin-, HCl-ethanol-, water-immersion stress- and indomethacin-induced gastric lesions. This agent also significantly prevented the formation of duodenal lesions induced by indomethacin plus histamine at 30 unit/kg, although it showed only a tendency of inhibition against mepirizole-induced duodenal lesions. 16, 16-Dimethyl prostaglandin E2 (3-30 micrograms/kg), given orally as a reference drug, showed a potent inhibition against all types of lesions tested herein at the dose of 3 micrograms/kg or greater. Elcatonin dose-dependently inhibited gastric secretion (volume, acid and pepsin output) in pylorus-ligated rats and gastric motility in conscious rats, but had no effect on duodenal alkaline secretion in anesthetized rats. On the other hand, 16, 16-dimethyl prostaglandin E2 at 10 micrograms/kg, given intraduodenally, significantly inhibited gastric secretion and motility, but stimulated duodenal alkaline secretion. We conclude that elcatonin markedly protects the gastrointestinal mucosa from injury induced by stress or various irritants. These effects might be in part accounted for by the antisecretory and antimotility activities of this peptide, although some other unknown mechanisms may be involved in the mucosal protection afforded by elcatonin.     

醋氨己酸锌对半胱胺大鼠溃疡模型的影响

用半胱胺在大鼠上引起非弥散性和弥散性十二指肠溃疡，并以雷尼替丁作为对照，研究了醋氨己酸锌对溃疡的预防作用和治疗作用。弥散性十二指肠溃疡有一个较长的愈合过程，在用醋氨己酸锌治疗５０ｄ后，溃疡受到极明显的抑制。对非弥散性十二指肠溃疡也表现了极好的预防作用。另外，对醋氨己酸锌各个剂量溃疡愈合的形态学也进行了比较，发现在不同的剂量时显示不同的损伤修复及愈合情况，明显地加速了受损处的上皮细胞、十二指肠腺及平滑肌细胞的增殖。     

Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by necrotizing agents and experimental gastric or duodenal ulcer in rats

Effects of FRG-8701, a new histamine H2-receptor antagonist, on gastric acid secretion, necrotizing agents-induced gastric lesions and acute gastric or duodenal ulcer in rats were studied. In lumen-perfused rats, intravenous injection of FRG-8701 reduced gastric acid secretion, and its antisecretory effect was almost equipotent to that of famotidine but the duration of action was substantially longer. In pylorus-ligated rats, the antisecretory effect of intraduodenal FRG-8701 administration was about 7 times more potent than that of cimetidine. FRG-8701 effectively inhibited macroscopic gastric hemorrhagic lesions induced by various kinds of necrotizing agents. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ED50 values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand, famotidine failed to reduce these lesions, and the cytoprotective effect of cimetidine was observed only in high doses compared with the doses for antisecretory activity. In addition, the cytoprotective effect of FRG-8701 was not affected by the treatment of indomethacin or N-ethylmaleimide. FRG-8701 showed antiulcer activity against stress and indomethacin gastric ulcer and mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than that of cimetidine. These results indicate that FRG-8701 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.     

Effect of ketotifen on acute gastric lesions and gastric secretion in rats.

Ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, significantly protected the rat gastric mucosa against lesions induced by necrotizing agents, histamine or compound 48/80. The agent significantly inhibited the basal gastric acid secretion, but had little or no effect on the histamine-stimulated secretion. The mucosal protective effect was observed even at a dose that had little or no effect on gastric acid secretion, suggesting that ketotifen exhibits so-called cytoprotective activity.     

Anti-ulcer mechanism of mezolidon on water-immersion stress induced gastric ulcers in rats

To elucidate the anti-ulcer mechanism of mezolidon (KM-1146, 2-(3,4-dimethoxyphenyl)-5-methylthiazolidine-4-one), we investigated gastric mucosal blood flow (laser-Doppler method), transmucosal potential difference, gastroduodenal mucosal surface pH and blood viscosity in rats under a water-immersion stress condition. In the control group, gastric mucosal ulcers occurred three hours after the onset of water-immersion. At that time, gastric mucosal blood flow decreased to 40% and the potential difference decreased to 48%. In the mezolidon-pretreated group, gastric mucosal ulcers were significantly reduced, and the potential difference was significantly higher than in the control group. Gastric mucosal blood flow increased significantly to 120% twenty minutes after the onset of water-immersion and then decreased, but was significantly higher than in the control group. Gastroduodenal mucosal surface pH was not affected by the pretreatment with mezolidon under this condition. Pretreatment with mezolidon did not affect blood viscosity. In conclusion, the anti-ulcer effect of mezolidon may involve the increase and/or maintenance of gastric mucosal blood flow, but more investigations are necessary to understand the mechanism involved.     

胃乐散对溃疡大鼠免疫球蛋白、IL-2及IL-4的影响

目的观察胃乐散对实验性溃疡大鼠的免疫球蛋白及白细胞介素2(IL-2)、白细胞介素4(IL-4)的影响,并探讨其作用机制。方法取SD大鼠48只,随机均分为正常组、模型组、胃乐散低、中、高剂量组和雷尼替丁组,采用冰醋酸烧灼法制备大鼠的胃溃疡模型。连续用药14 d后,处死大鼠,取血清,用ELISA法检测血清中IL-2、IL-4,用免疫比浊法测量血清中免疫球蛋白IgG、IgA、IgM水平的变化。结果模型组大鼠的IL-2、IL-4明显低于正常组。与模型组比较,胃乐散能提高大鼠的IL-2、IL-4的水平(P<0.05),也能增加血清中IgG、IgA、IgM的含量(P<0.05)。结论胃乐散治疗胃溃疡的机制之一可能与提高机体的细胞免疫和体液免疫有关。     

The coexistence of gastric cancer and duodenal ulcers

The records of 356 gastric carcinoma patients who were treated surgically were reviewed. Among them, six patients (1.7%) had duodenal ulcers. Five cancers of the six patients were "early" gastric cancers classified as type "IIc" or "IIc + III" according to "The general rules for the gastric cancer study in surgery and pathology". The cancers of the six patients were located in the lower half of the stomach. Gastric secretion activity was normal in four and above normal in two cases. Three had signet ring cell carcinomas, two had poorly differentiated adenocarcinomas and one had a well differentiated adinocarcinoma. Our results were similar to other results reported in many papers. In Japan gastric carcinomas coexisting with duodenal ulcers were more often confirmed in the "early" gastric cancer stage. This is probably because endoscopic examinations of the stomach were more often performed in Japan than in other countries because of te large number of gastric disease patients. In addition, it is assumed that the growth of gastric cancer in the stomach is slow because of the very active gastric secretion.     

Effects of nicotine on activity and stress-induced gastric ulcers in rats.

Nicotine is known to influence locomotor activity. The alkaloid also intensifies gastric ulcer formation in stressed rats. The effects of nicotine on locomotor activity in relation to gastric lesions induced by restraint at 4 degrees C for 2 h (stress) were, therefore, studied. Ten-day treatment with nicotine 25 or 50 micrograms/ml drinking water potentiated stress-evoked ulceration and mast cell degranulation. These same doses of nicotine increased vertical motor activity; only the higher dose of the alkaloid enhanced horizontal movements. Phenobarbitone (12.5, 25, or 50 mg/kg, SC) dose dependently reduced vertical activity, as well as stress-induced gastric ulceration and mucosal mast cell degranulation. The drug also lessened the potentiating effects of nicotine on motor activity and stress-evoked gastric lesion formation. It is concluded that the ability of chronic nicotine treatment to intensify stress-induced gastric ulceration most likely owes part of its action to a mechanism evoking increased activity, which possibly reflects an influence on the CNS, as well as to enhancement of mast cell degranulation in the stomach glandular mucosa.