Acute Gastric Mucosal Lesions Research Articles

C-met and c-Jun expression during acute gastric mucosal lesions in rats

c-met and c-Jun expression during acute gastric mucosal lesions in rats

Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury.

Stress reduces gastric blood flow and produces acute gastric mucosal lesions. We studied the role of angiotensin II in gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 receptors were localized in the endothelium of arteries in the gastric mucosa and in all gastric layers. AT1 blockade increased gastric blood flow by 40-50%, prevented gastric ulcer formation by 70-80% after cold-restraint stress, reduced the increase in adrenomedullary epinephrine and tyrosine hydroxylase mRNA without preventing the stress-induced increase in adrenal corticosterone, decreased the stress-induced expression of TNF-alpha and that of the adhesion protein ICAM-1 in arterial endothelium, decreased the neutrophil infiltration in the gastric mucosa, and decreased the gastric content of PGE2. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, and anti-inflammatory effects (with reduction in TNF-alpha and ICAM-1 expression leading to reduced neutrophil infiltration) while maintaining the protective glucocorticoid effects and PGE2 release. Angiotensin II has a crucial role, through stimulation of AT1 receptors, in the production and progression of stress-induced gastric injury, and AT1 receptor antagonists could be of therapeutic benefit.

Giant gastric folds: differential diagnosis at US.

To evaluate ultrasonographic (US) features in the differential diagnosis of giant gastric folds. One hundred sixty-five patients with giant gastric folds at transabdominal US examination (five with Ménétrier disease, 24 with anisakiasis, 61 with acute gastric mucosal lesion [AGML], 13 with gastric lymphoma, and 62 with scirrhous carcinoma) were examined. With 3-6-MHz curved and 5-11-MHz linear-array transducers, the authors evaluated gastric wall thickness, wall stratification, main thickened layer, echogenicity, and compressibility of the lesion in each case. The Fisher protected least-significant-difference method was used to compare statistically the thickness of the gastric wall among diseases. Wall thickness of AGML was significantly (P <.001) less than that of anisakiasis, gastric lymphoma, and scirrhous carcinoma. US findings revealed regular gastric wall thickening of the second or third layer, with preservation of wall stratification in all patients with benign conditions. The fourth layer was thickened only in patients with malignancy. The echogenicity of gastric lymphoma was markedly lower than that of any other condition. Compressibility of scirrhous carcinoma was absent, whereas it was well preserved in all benign conditions. Transabdominal US can depict gastric wall stratification and is a useful noninvasive modality for differential diagnosis of giant gastric folds.

A Case of Ascaris lumbricoides found out by Endoscopic Examination for Hematoemesis

Case was a 63-year-old female. She was admitted to hospital because of hematoemesis. Laboratory data showed slight anemia, increasing data of eosinophil and IgG. No pathological findings were recognized by chest plain X-ray films and abdominal CT scan, At first, we suspected rupture of esophago-gastric varices, portal hypertensive gastropathy and so on, because she attended our hospital for Primary biliary cirrhosis. Upper GI endoscopy performed in an emergency showed oozing from multiple erosions in the stomach. She was hospitalized by the diagnosis of acute gastric mucosal lesion. We performed 2nd upper GI endoscopy on 3 hospitalized days for checking the state of affairs. Endoscopic pictures showed a white roundworm in 2nd portion of the duodenum. This worm could be removed by grasping forceps led to the diagnosis of Ascaris lumbricoides. And then, She was cured of this disease by taking Pyrantel pamoate. In recent years, the Incidence of Ascaris lumbricoides has been decreasing because of improved public hygiene and living standards in Japan. However, there is a slight increasing in number of cases due to the natural foods boom and increasing contact with foreign countries. In this case, the origin was natural foods. It is necessary for clinicians to be able to take parasitosis into consideration.

The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions

The role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effects of quercetin were evaluated in an experimental model. In addition, the effects of quercetin on gastric damage were evaluated histopathologically. Rats were divided into three groups as control rats, ethanol treated rats and ethanol+quercetin treated rats. Ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. Quercetin (200 mg/kg body wt.) was given by intragastric gavage 120 min before the administration of ethanol. Gastric tissue thiobarbituric acid reactive substance levels, carbonyl compounds, histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats and quercetin treatment reversed these increases. No statistically significant changes were found between all groups in catalase activity. The superoxide dismutase activity dropped significantly after ethanol treatment and quercetin treatment increased this enzyme activity. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells and gastric erosions in ethanol treated rats. It was also confirmed that quercetin treatment significantly decreased the number of mast cells and reduced the area of gastric erosions. The results suggest that the gastroprotective effect of quercetin in this experimental model could be due to its antiperoxidative, antioxidant and antihistaminic effects.

PROTECTIVE EFFECT OF OMEPRAZOLE AGAINST ACUTE GASTRIC MUCOSAL LESIONS INDUCED BY COMPOUND 48/80, A MAST CELL DEGRANULATOR, IN RATS

Omeprazole, a proton pump inhibitor is known to function not only as a proton pump inhibitor but also as an anti-inflammatory agent, an antioxidant or a stimulator of gastric mucus secretion. We have shown that the pathogenesis of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats involves neutrophil infiltration, lipid peroxidation, and mucin depletion, but not acid secretion, in the gastric mucosal tissue. Therefore, we examined whether omeprazole protects against acute gastric mucosal lesions induced by compound 48/80 in rats. Rats were injected with omeprazole (10 or 50 mg kg −1, i.p.) at 0.5 h before injection of compound 48/80 (0.75 mg kg −1, i.p.). Omeprazole prevented gastric mucosal lesion development at 0.5 and 3 h after compound 48/80 injection. Omeprazole attenuated decreased nonprotein sulfhydryl content and increased myeloperoxidase and xanthine oxidase (XO) activities and lipid peroxide (LPO) content in the gastric mucosa at 0.5 h after compound 48/80 injection and increased myeloperoxidase and XO activities and LPO content, but not decreased hexosamine and adherent mucus contents, in the gastric mucosa at 3 h. These results indicate that omeprazole protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its anti-inflammatory and antioxidant actions.

Acute Gastric Mucosal Injury Caused by Ingestion of Chlorinated Fungicide

We encountered a patient with acute gastric mucosal injury caused by ingestion of a chlorinated fungicide. Approximately 15 h after the episode of ingestion, endoscopic views were compatible with the acute gastric mucosal lesion of severe degree throughout the stomach. At that time, endoscopic biopsy showed congestion in the epithelial layer of the mucosa, along with lymphocytic infiltration that had likely existed from the onset of the condition. On the third day, the mucosal lesion looked more serious with peculiar hemorrhagic folds, and biopsy revealed exfoliation of the epithelial surface and neutrophilic infiltration in the stroma of the epithelial layer. On the seventh day, endoscopic images showed persistence of the lesion, but biopsy demonstrated the development of regenerating epithelium along with a marked reduction in infiltration of neutrophils and edema in the stroma.

Protective Effect of Ebselen, a Seleno-Organic Compound, Against the Progression of Acute Gastric Mucosal Lesions Induced by Compound 48/80, a Mast Cell Degranulator, in Rats

The protective effect of ebselen, which possesses glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, against the progression of acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Ebselen (50, 100 or 200 mg/kg) was orally administered 0.5 h after compound 48/80 treatment, at which time gastric mucosal lesions appeared. Post-administered ebselen suppressed gastric mucosal lesion progression at 3 h after compound 48/80 treatment dose-dependently, although no dose of ebselen affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. A decrease in Se-glutathione peroxidase activity and increases in myeloperoxidase and xanthine oxidase activities and the concentration of thiobarbituric acid reactive substances were found in gastric mucosal tissues at 0.5 h after compound 48/80 treatment, and these changes were further enhanced at 3 h. Post-administered ebselen attenuated all these changes found at 3 h after compound 48/80 treatment dose-dependently. The present results indicate that ebselen exerts a protective effect against the progression of compound 48/80-induced acute gastric mucosal lesions in rats, and they suggest that this protective effect of ebselen could be due to its glutathione peroxidase-like activity and its antioxidative and anti-inflammatory properties.

Cytoprotection by propolis ethanol extract of acute absolute ethanol-induced gastric mucosal lesions.

Acute p.o. administration of absolute ethanol (1.0 ml/kg) to fasted rats produced extensive necrosis of gastric mucosa. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could effectively and dose-dependently prevent such necrosis. This protective effect is called "cytoprotection. "The maximal cytoprotective effect against absolute ethanol (AE)-induced gastric mucosal lesion was observed 1 hour after PEE administration. A gross examination of the gastric mucosa showed a marked improvement in groups receiving PEE. In order to further investigate the gastric protective mechanism of PEE, lipid peroxidation (LPO) levels in vivo and in vitro were estimated. PEE exhibited dose-dependent superoxide scavenging activity and antioxidant effects on AE-induced LPO in rat gastric mucosal homogenates. It was concluded that the gastric protective mechanism of PEE was due, at least in part, to its ability to inhibit LPO, and hence indirectly protect the gastric mucosa from oxidative stress.

Right Gastric Artery Embolization to Prevent Acute Gastric Mucosal Lesions in Patients Undergoing Repeat Hepatic Arterial Infusion Chemotherapy

The purpose of the study was to investigate the technical outcome and clinical effect of right gastric artery (RGA) embolization to prevent acute gastric mucosal lesions caused by influx of anticancer agents into the RGA in patients undergoing repeat hepatic arterial infusion chemotherapy (HAIC). In 217 patients with malignant hepatic tumors, we attempted RGA embolization with use of metallic coils and/or a mixture of n-butyl cyanoacrylate (n-BCA) and iodized oil, along with the embolization of the gastroduodenal artery. After this procedure, an infusion catheter was placed radiologically and HAIC was performed. We then evaluated the technical outcome and clinical effect of RGA embolization. RGA embolization was technically successful in 201 of 217 patients (93%). Major complications--nausea, epigastric pain, and fever--were noted in 12%, 4%, and 2% of successful cases, respectively, and were treated conservatively. Recanalization occurred in 4% (nine of 201) of the patients. Eventually, sufficient RGA embolization was achieved in 192 patients. The incidence of acute gastric mucosal lesions confirmed endoscopically was only 3% (five of 192) in patients with sufficient RGA embolization, whereas it was 36% (nine of 25) in patients without sufficient RGA embolization, with a significant difference (P <.01). RGA embolization is a highly feasible procedure that can reduce the incidence of acute gastric mucosal lesions associated with HAIC.

Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: relation to capsaicin-sensitive sensory neurons.

We examined the effects of monochloramine (NH2Cl) on the gastric mucosal blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in rats. Rats fasted for 18 h were given the 99% ethanol p.o. for induction of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine, at non-ulcerogenic doses (5 to approximately 20 mmol/L), was given p.o. twice daily for 7 days, starting 2 h after ethanol treatment. Gastric lesions caused by ethanol healed almost completely within 7 days with re-epithelialization. The repeated administration of NH2Cl significantly delayed the healing of ethanol-induced gastric lesions in a dose-dependent manner. The damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid loss, but this process was accompanied by an increase of mucosal blood flow. Monochloramine did not affect the increased mucosal H+ permeability observed in the stomach after damage by ethanol, but significantly inhibited the mucosal hyperemic response associated with luminal acid loss. Prior exposure of the mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a nitric oxide donor), but totally attenuated the increase of GMBF in response to intragastric capsaicin. Impaired healing and GMBF responses were also observed in rats following chemical ablation of capsaicin-sensitive sensory neurons. These results suggest that NH2Cl impaired the healing of acute gastric mucosal lesions at low concentrations, and this action may be attributable, at least partly, to the impairment of gastric hyperemic response caused by the dysfunction of capsaicin-sensitive sensory neurons.

Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80

The preventive effect of ebselen, a seleno-organic compound, which is known to possess glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, on the development of acute gastric mucosal lesions was examined in rats with a single injection of compound 48/80 (0.75 mg/kg, i.p.), a mast cell degranulator. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, prevented gastric mucosal lesion development at 3 h, but not gastric mucosal lesion formation at 0.5 h, after compound 48/80 injection, although any dose of pre-administered ebselen did not affect decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 0.5 and 3 h after compound 48/80 injection. A decrease in Se-glutathione peroxidase activity and increases in the activities of myeloperoxidase, an index of tissue neutrophil infiltration, and xanthine oxidase and the concentration of thiobarbituric acid reactive substances, an index of lipid peroxidation, were found in gastric mucosal tissues at 0.5 h after compound 48/80 injection and these changes were further enhanced at 3 h. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, attenuated all these changes found at 3 h after compound 48/80 injection. These preventive effects of ebselen occurred in a dose-dependent manner. The present results indicate that pre-administered ebselen prevents the development of compound 48/80-induced acute gastric mucosal lesions in rats, and suggest that this preventive effect of ebselen could be due to its glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties.

Melatonin's gastroprotective and antistress roles involve both central and peripheral effects.

Systemic administration of melatonin (5 to 20 mg/kg) has been reported to inhibit the induction of acute gastric mucosal lesions by stress or ischemia-reperfusion in rats. We recently demonstrated that intracisternal (i.c.) melatonin at low doses (1 to 100 ng) dose-dependently decreased acid and pepsin outputs in rats. The aim of the present study was to further investigate the peripheral and central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay, we measured melatonin concentrations in the plasma and cerebrospinal fluid (CSF) of the cisterna magna in rats subjected to water immersion restraint stress and given intraperitoneal (i.p.) or i.c. injection of melatonin. Water immersion restraint stress was followed by a significant duration-related increase in peripheral plasma melatonin levels; the stress similarly produced a time-dependent increase in the extent of gastric mucosal lesions. Administration of melatonin (1 or 10 mg/kg, i.p., or 100 ng/10 microl, i.c.) significantly reduced the extent of stress-induced gastric damage, by 46%, 67%, and 54%, respectively. The effective i.c. dose of melatonin was at least 10,000-fold smaller than the effective i.p. dose. Melatonin levels in plasma and CSF after the i.p. injection of melatonin at 10 mg/kg were dramatically higher than those after the i.c. injection of vehicle or 100 ng of melatonin. Our results suggest that the peripheral gastroprotective action of melatonin should be investigated with due regard to these central effects.

Influence of acute copper deficiency, cold-restraint stress and the H2 blocker ranitidine on the severity of acute gastric mucosal lesions and lipid peroxidation in rats

Acute copper deficiency produces disturbances in the microcirculation and structure of extracellular matrix proteins, causes an increase in mast cell population, which is followed by an increased content of their degranulation products, produces disturbances in histamine metabolism and decreases the activity of some antioxidant enzymes. These pathogenic mechanisms are similar to the processes underlying stress ulcer formation. The histamine H2-receptor antagonist ranitidine, a drug with the highest application for stress ulcer prophylaxis, has the ability to helate the copper ion and to influence its tissue distribution and the processes of generation and neutralization of reactive oxygen species (ROS). In order to determine the interrelation between the disturbances of copper homeostasis, stress ulcers and ranitidine, we investigated the impact of a short-term diet with powdered milk in combination with cold-restraint stress with or without ranitidine on the severity of acute gastric mucosal lesions, copper content, lipid peroxidation and the activity of superoxide dismutase and catalase in the stomachs of rats.

A non-toxic heat shock protein 70 inducer, geranyl-geranyl-acetone, restores the heat shock response in gastric mucosa of protein-malnourished rats

Acute gastric mucosal lesions caused by stress or noxious stimuli are important to consider in the management of critically or chronically ill patients. Protein malnutrition has been implicated as a risk factor for stress ulcer and subsequent complications in those patients. When male Wistar rats fed a 5% or 20% casein diet for 3 weeks were exposed to restraint and water-immersion stress, the low-protein diet significantly increased the ulcer index. The low-protein diet did not change the level of heat shock factor 1 (HSF1) in gastric mucosa but it did attenuate the HSF1 activation after exposure to the stress, resulting in the inhibition of HSP70 mRNA expression and HSP70 induction in gastric mucosa. HSP70 is crucial for the maintenance of cell integrity during pathophysiologic conditions; therefore the impaired HSP70 induction appeared to at least in part aggravate stress ulcer. We also tested whether a non-toxic HSP70 inducer, geranyl-geranyl-acetone (GGA), effectively improved the mucosal integrity by stimulating HSP70 induction under protein malnutrition. Intragastric administration of GGA (200 mg/kg twice a day) to the protein-malnourished rats for up to 1 week failed to stimulate the HSP70 induction. However, the administration of GGA (200 mg/kg twice a day) for 3 weeks restored HSP70 induction and induced higher resistance against stress ulcer as compared with results in vehicle-treated, normally nourished rats. Our results suggest that GGA may have a potential benefit for the prevention of stress ulcer in chronically or critically ill patients with protein malnutrition. (J Lab Clin Med 2000;136:138-48)

Gastric Mucosal Cell Proliferation in Ethanol-Induced Chronic Mucosal Injury Is Related to Oxidative Stress and Lipid Peroxidation in Rats

The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H2-receptor (H2R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H2R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H2R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H2R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal.

The nutraceutical benefit, part iii: honey

The nutraceutical benefit, part iii: honey

Endoscopic hemoclip therapy of a bleeding duodenal diverticulum

Acute upper GI bleeding is an emergency. With the advance of endoscopic technique, the necessity for surgical intervention has been reduced to 6% to 10%.1,2 However, upper GI bleeding remains a common cause of morbidity and mortality.3 In the majority of cases, upper GI bleeding is due to peptic ulcer, acute gastric mucosal lesions, varices, and Mallory-Weiss syndrome.1-3 Almost all lesions are located in the esophagus, stomach, and duodenal bulb. Duodenal diverticula are common in adults with a prevalence of 22% in autopsy series and 5% in patients undergoing upper GI contrast radiography.

3441 Autofluorescence and tissue peroxidation in nsaids-induced acute gastric mucosal lesions in human volunteers.

Background and Aims:We have already reported that gastric mucosal autofluorescence intensity increased in accordance with gastric mucosal lesions formation induced by dicrofenac sodium administration in rats. In this study, we have established an endoscopic apparatus composed with an image processor and a highly-sensitive camera for fluorescence observation named SEFAS: a simultaneous endoscopic fluorescence analyzing system. Using this system, we clarified whether NSAID-treatment increased gastric mucosal fluorescence intensity in human volunteers or not. Moreover, we examined relations of distributions between tissue peroxidation and fluorescent substance. Methods: Healthy human volunteers who completely agreed to take part in this study were administrated 50 mg dicrofenac per os. Mucosal fluorescence intensity were measured with SEFAS before and 1, 2 hour(s) after the dicrofenac treatment. Moreover, volunteers were also administrated 50 mg teprenone, a mucosal prostaglandin inducing agent, 30 min before the dicrofenac treatment, and were also measured mucosal intensities. In each study, some pieces of mucosa were taken from each area of the mucosal fluorescence measurement. These biopsies were rapidly made into specimens of cryosections. They were immunohistochemicaly stained with anti-4-hydroxynonenal antibody, a specific monoclonal antibody for peroxidized tissue, and analyzed distributions of tissue peroxidation. Distributions of autofluorescent substance were also observed. Moreover, autofluorescent substance was analyzed with HPLC. Results: The dicrofenac treatment increased mucosal fluorescence intensity. The administrations of teprenone completely restrained this phenomenon. Fluorescence substances were porphyrins. These fluorescence substances were localized at the disrupted surface layer of the gastric mucosa. Peroxidized tissue was located in middle part of the mucosa. Conclusions: It suggested that tissue peroxidation was induced before mucosal injury formation, and fluorescent porphyrins were generated with tissue disruption. Mucosal fluorescence observations with SEFAS can diagnose NSAID-induced gastric lesions.

Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions.

AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P < 0.01 =, and reached the lowest point, 0.63mL/L ± 0.20mL/L, 10.81mmol/L ± 2.58mmol/L and 2.23mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION:Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment.