Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

BACKGROUND/AIMS: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice. METHODS: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, lorglumide (CCK1 receptor antagonist), ondansetron, and haloperidol alone and in combination. RESULTS: IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8. CONCLUSIONS: These results suggest that CCK-CCK1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT3 and Dopamine D2 Receptors in Mice.

BACKGROUND/AIMS: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice. METHODS: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.5 h after re-feeding. The effects of atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, ondansetron, haloperidol, and dietary taurocholate and cholestyramine were also examined. RESULTS: IND (10 mg/kg, s.c.) induced severe lesions only in the gastric antrum in the re-fed model. The antral lesion index and the amount of food intake during the 2-h refeeding period were positively correlated. Atropine and dopamine delayed gastric emptying, increased bile reflux, and worsened IND-induced antral lesions. SR57227 and apomorphine worsened antral lesions with increased bile reflux. These effects were prevented by the anti-emetic drugs ondansetron and haloperidol, respectively. The anti-emetic drugs markedly decreased the severity of antral lesions and the increase of bile reflux induced by atropine or dopamine without affecting delayed gastric emptying. Antral lesions induced by IND were increased by dietary taurocholate but decreased by the addition of the bile acid sequestrant cholestyramine. CONCLUSIONS: These results suggest that gastroparesis induced by atropine or dopamine worsens NSAID-induced gastric antral ulcers by increasing duodenogastric bile reflux via activation of 5-HT3 and dopamine D2 receptors.

Proton Pump Inhibitors Prevent Gastric Antral Ulcers Induced by NSAIDs via Activation of Capsaicin-Sensitive Afferent Nerves in Mice.

BACKGROUND/AIMS: We examined the effects of proton pump inhibitors (PPIs) on gastric antral ulcers induced by non-steroidal anti-inflammatory drugs in re-fed mice and the role of capsaicin-sensitive afferent nerves (CSANs) in the protective effects of PPIs on the antral mucosa. METHODS: Male mice were administered indomethacin after 2 h of re-feeding of diet after a 24-h fast, and gastric lesions were examined 24 h after indomethacin dosing. The effects of PPIs (lansoprazole and omeprazole), histamine H2-receptor antagonists (H2-RAs, famotidine, ranitidine), capsaicin and misoprostol on the formation of antral ulcers induced by indomethacin were examined. Functional ablation of CSANs was caused by pretreatment of mice with a high dose of capsaicin. RESULTS: Indomethacin produced lesions selectively in the gastric antrum in re-fed conditions. Formation of antral ulcers was not affected by H2-RAs, but inhibited by PPIs, capsaicin and misoprostol. The anti-ulcer effect of lansoprazole was 30 times stronger than that of omeprazole. Antral ulcers induced by indomethacin were markedly aggravated in mice with ablated CSANs. The effects of PPIs and capsaicin on ulcer formation were inhibited by ablation of CSANs, pretreatment with a capsaicin receptor antagonist (capsazepine/ruthenium red) and an inhibitor of nitric oxide synthesis (L-NAME). However, the inhibitory effect of misoprostol was not prevented by the ablation of CSANs or drugs. CONCLUSIONS: The results suggested that CSANs play an important role in protection of the antral mucosa and that both lansoprazole and omeprazole are capable of preventing NSAID-induced antral ulcers by activating CSANs.

A case report of Strongyloides stercoralis infection in Leshan City / 中国血吸虫病防治杂志

This paper reports one case of gastric antral ulcer due to Strongyloides stercoralis infection in Leshan Traditional Chinese Medicine Hospital.

Refractory gastric antral ulcers without Helicobacter pylori infection and non-steroidal anti-inflammatory drugs.

Herein, we describe a rare case of refractory gastric antral ulcers. A woman in her 50 s was admitted to Nagoya City University Hospital with epigastric pain after being diagnosed with gastric antral submucosal tumor at another hospital. Findings from esophagogastroduodenoscopy and endoscopic ultrasound examination revealed that the lesion was a gastric ulcer. The patient had no Helicobacter pylori infection and no recent history of using non-steroidal anti-inflammatory drugs. On the basis of these findings, we diagnosed this as a case of refractory gastric antral ulcer (RGAU). RGAU is considered a new disease concept and detailed analyses are expected in the future.

[A case report of Strongyloides stercoralis infection in Leshan City].

This paper reports one case of gastric antral ulcer due to Strongyloides stercoralis infection in Leshan Traditional Chinese Medicine Hospital.

A case report of Strongyloides stercoralis infection in Leshan City / 中国血吸虫病防治杂志

This paper reports one case of gastric antral ulcer due to Strongyloides stercoralis infection in Leshan Traditional Chinese Medicine Hospital.

Soluble Dietary Fiber Can Protect the Gastrointestinal Mucosa Against Nonsteroidal Anti-Inflammatory Drugs in Mice.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious problem in patients, but effective therapy is not available at present. AIMS: The effects of feeding conditions and dietary fiber (DF) on NSAID-induced gastrointestinal lesions were examined in mice. METHODS: NSAIDs (indomethacin, diclofenac, loxoprofen, aspirin) were administered to male mice in various feeding conditions. Gastrointestinal lesions were examined 24 h after NSAID dosing. Regular diets, dietary-fiber-free diet (FFD), and diets supplemented with various types of DF were given to mice. RESULTS: NSAIDs produced marked ulcers and perforations selectively in the gastric antrum when they were administered after feeding of regular diet for 2 h after a 22-h fast. When NSAIDs, except for aspirin, were administered in unfasted conditions, they caused marked lesions in the small intestine. When mice were given FFD, antral ulcers and intestinal lesions induced by indomethacin (30 mg/kg, s.c.) markedly decreased, but when cellulose, an insoluble DF, was added to FFD, the lesions appeared again. The addition of pectin, a soluble DF, to regular diet containing 4.1 % crude fiber significantly inhibited the formation of antral ulcers as well as intestinal lesions caused by indomethacin or diclofenac (100 mg/kg, s.c.). CONCLUSIONS: The results indicated that NSAIDs given after feeding of diet produced ulcers selectively in the gastric antrum. The severity of the gastrointestinal lesions depended on the concentration of soluble or insoluble DF in food. Our results suggest that soluble DF such as pectin may be a safe means for protecting the gastrointestinal mucosa against NSAIDs.

Protective Effect of 4-(3,4-Dihydroxyphenyl)-3-Buten-2-One from Phellinus linteus on Naproxen-Induced Gastric Antral Ulcers in Rats.

The present study investigated the protective effect of naturally purified 4-(3,4- dihydroxyphenyl)-3-buten-2-one (DHP) from Phellinus linteus against naproxen-induced gastric antral ulcers in rats. To verify the protective effect of DHP on naproxen-induced gastric antral ulcers, various doses (1, 5, and 10 µg/kg) of DHP were pretreated for 3 days, and then gastric damage was caused by 80 mg/kg naproxen applied for 3 days. DHP prevented naproxen-induced gastric antral ulcers in a dose-dependent manner. In particular, 10 µg/kg DHP showed the best protective effect against naproxen-induced gastric antral ulcers. Moreover, DHP significantly attenuated the naproxen-induced lipid peroxide level in gastric mucosa and increased the activities of radical scavenging enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in a dose-dependent manner. A histological examination clearly demonstrated that the gastric antral ulcer induced by naproxen nearly disappeared after the pretreatment of DHP. These results suggest that DHP can inhibit naproxen-induced gastric antral ulcers through prevention of lipid peroxidation and activation of radical scavenging enzymes.

Evaluation of Six Cases of Idiopathic Gastric Antral Ulcer.

Six cases of gastric antral ulcer with an unknown cause encountered at our hospital and related facilities during the last 5 years were evaluated. The frequency of the disease was 1.3% of all gastric ulcers. The lesions were multiple in 3 and solitary in 3. All these lesions were ellipsoidal and small ulcers 1 cm or less in long diameter with mucosal elevations around them, located primarily in the greater curvature, and accompanied by reddened erosions in other areas of the antrum. The patients were middle-aged or older, 5 of them were females, half of them had a history of bleeding, and 4 showed resistance to treatment with proton pump inhibitors. The 6 patients had common clinical features, suggesting that they had the same disease. From the presence of reddened erosion, mutual friction of the antral mucosa was suspected to be a cause of the disease. Similar ulcers are found in the literature, but they have not been described or evaluated in detail. The further accumulation of cases and clarification of details of the disease are desired.

Recombinant Human Epidermal Growth Factor Alleviates Gastric Antral Ulcer Induced by Naproxen: A Non-steroidal Anti Inflammatory Drug.

BACKGROUND: To study the effect (s) of recombinant human Epidermal Growth Factor (rhEGF) on naproxen induced gastric ulcer in Wistar NIN rats. METHODS: Male Wistar NIN rats were randomly divided into six experimental groups: Group I - Control, Group II - Naproxen treated, Group III - Naproxen with rhEGF/7 days, Group IV - Naproxen without rhEGF/7 days, Group V - Naproxen with rhEGF/14 days, and Group VI - Naproxen without rhEGF/14 days. Gastric ulcer was induced with naproxen at a concentration of 80 mg/kg by oral administration. After 24 hours of induction of ulcer, rhEGF treatment was started at a concentration of 100 µg/kg. Ulcer presence and healing were confirmed by histopathology study and molecular markers. RESULTS: Naproxen per se induced gastric antral ulcers in Wistar NIN rats. Compared with control rats, naproxen induced rats had increased lipid peroxide content in serum. Subsequent decrease in lipid peroxide was observed in rhEGF treated groups. Treatment with rhEGF significantly resulted in healing of the ulcers, which was evident by 7 days of rhEGF treatment with total healing seen by 14 days. Significant increase in immunoreactivity for Cox-2 was observed when compared to control groups, whereas less immunoreactivity of Cox-2 was observed in rhEGF treated group. Compared with control group, naproxen induced group exhibited more gene expression of both Cox-2 and TGF beta while gene expression of Cox-2 and TGF beta in rhEGF group was comparable to control group. CONCLUSIONS: The beneficial effects of rhEGF in the management of ulcer healing can be understood. Oral rhEGF can promote healing of the rats with gastric ulcer by stimulating Cox-2 and TGF-beta expression.