Effects of Ebrotidine on Aspirin-Induced Gastric Mucosal Damage and Blood Flow in Humans

Nonsteroidal anti-inflammatory agents (NSAIDs) such as aspirin (ASA) damage the gastric mucosa both in normal subjects and in arthritic patients. The aim of this study was to investigate the protective action of a new H₂-receptor antagonist, ebrotidine, in the prevention of ASA-induced acute mucosal injury in the stomach of healthy volunteers. In a double-blind randomized crossover study 10 male volunteers received treatment with either placebo plus ASA (500 mg) or ebrotidine (800 mg) plus ASA twice daily for 3 days with 10 days' washout period between treatments. The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 ± 0.3) was significantly lower than that after placebo plus ASA (3.7 ± 0.2). This reduction in lesion core by ebrotidine was accompanied by a significant increase in gastric blood flow (by 15% in corpus and 26% in antrum), by a rise in transmucosal potential difference (by 12%), and by a decrease of mucosal microbleeding. Ebrotidine afforded substantial protection from ASA-induced injury to the gastric mucosa, and this was accompanied by increase of the mucosal blood flow. We conclude that ebrotidine provides mucosal protection for patients taking NSAIDs     

Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.     

Burn-Induced Gastric Mucosal Hemodynamic Disturbance in the Rat: Role of Platelet-Activating Factor

The role of platelet-activating factor (PAF) as a mediator of gastric damage associated with burn injury was examined in the rat. Gastric mucosal hemodynamics was recorded continuously by means of laser-Doppler flowmetry and reflectance spectrophotometry. Burn injury induced prolonged hypotension and rapid-onset and long-lasting gastric mucosal hemodynamic derangement—that is, ischemia with congestion. This hemodynamic disturbance was significantly inhibited by CV-6209, a specific PAF antagonist. Elevated tissue levels of thiobarbituric acid reactants and pathologic changes in the gastric mucosa subsequent to burn injury were also significantly alleviated by the preadministration of CV-6209. These results strongly suggest a role of PAF as an important mediator of gastric damage after burn injury through its potent vasoactive effect on gastric microcirculation.     

Paradoxical Role of Helicobacter pylori Infection: Protective Effect Against Ethanol-Induced Gastric Mucosal Injury in Mongolian Gerbils

We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E₂ concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE₂. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE₂ and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents.     

The Role of Zinc Sulfate and Metallothionein in Protection Against Ethanol-Induced Gastric Damage in Rats

In this study, the effects of zinc sulfate against ethanol-induced acute gastric damage in rats were investigated, morphologically and biochemically. In addition, the present investigation has demonstrated the distribution of metallothionein stimulated by zinc in gastric mucosal tissues, immunohistochemically. The gastric damage was induced by intragastric administration of 1 ml absolute ethanol per rat. Rats received zinc sulfate (100 mg/kg/day) for 3 consecutive days 2 hr prior to the administration of absolute ethanol. Acute ethanol exposure caused degenerative morphological changes, a decrease in metallothionein immunreactivity; an increase in lipid peroxidation (LPO) levels, and a decrease in reduced glutathione (GSH) levels in gastric mucosa. On the other hand, zinc sulfate administration to ethanol-treated rats caused a significant reduction in the histological damage, an increase in metallothionein immunreactivity, a decrease in LPO levels, and an increase in GSH levels in gastric mucosa. As a result, the present study indicates that zinc sulfate has a protective effect against ethanol-induced acute gastric damage. In addition, we might say that the zinc given as exogenous protection against acute gastric damage has a protective effect both by stimulation of metallothionein synthesis and through GSH as well as having antioxidative potential.     

Gastric Mucosa Epithelial Cell Kinetics Are Differentiated by Anatomic Site and Helicobacter Pylori Infection

Changes in epithelial cell turnover related to Helicobacter pylori infection may contribute to gastric cancer development. The response of different anatomic sites of the gastric mucosa to H. pylori is not known. We studied apoptosis and cell proliferation at the grater and lesser curvature of the antrum and corpus, the fundus, and the cardia from 9 H. pylori gastritis patients and 11 H. pylori-negative controls with normal histology. Proliferation was highest at the major curve of the antrum and lowest at the fundus, and apoptosis was highest at the cardia and lowest at the major curve of the antrum in both H. pylori gastritis and normal mucosa. Proliferation was significantly higher at all anatomic sites, while apoptosis was significantly lower only at the major and lesser curve of the corpus in H. pylori gastritis compared with normal controls. Our data suggest that gastric mucosa epithelial cell kinetics is differentiated by the anatomic site and H. pylori infection.     

In-vitro anti-inflammatory and mosquito larvicidal efficacy of nickel nanoparticles phytofabricated from aqueous leaf extracts of Aegle marmelos Correa

In recent years there is a tremendous growth in the interdisciplinary world of nanotechnology across the globe and emergence of its potential applications remains as a big revolution to the industry. Fusion of green nanotechnology and medicine represents one of the major breakthroughs of modern science with the aim of developing nanomaterials for diagnosis, treatment, prevention of various diseases and overall improving health for the beneficial of mankind. In the present study phytofabrication of nickel nanoparticles (nickel NPs) was carried out by using indigenous Aegle marmelos Correa aqueous leaf extracts as a reducing, stabilizing and capping agents. Nickel NPs were characterized by UV-spectroscopy, FTIR, XRD, SEM, AFM and TGA studies. Phytosynthesis of nickel NPs was monitored both at room temperature (25 °C) and at 60 °C for 5 h. The green synthesis of triangular shape nickel NPs phytofabricated from A. marmelos Correa aqueous leaf extracts having face centered cubic structure showing an average particle size of 80–100 nm which is in consistent with the particle size calculated by XRD Scherer equation. We further explored and compared nickel NPs of A. marmelos Correa with crude leaf extracts of A. marmelos Correa for its in-vitro anti-inflammatory and mosquito larvicidal efficacy against three blood feeding parasites. The results obtained clearly gives an idea that nickel NPs of A. marmelos Correa (NiNPs of AmC) possess an enhanced anti-inflammatory and larvicidal activity when compared to crude leaf extracts of A. marmelos Correa.     

Ascorbic acid secretion in the human stomach and the effect of gastrin

AIM:To investigate the changes of gastric mucosal ascorbic acid secretion in patients with nonulcer dyspepsia and the effect of gastrin on it, and to relate any observed changes to H.pylori infection and mucosal histology.METHODS:Ascorbic acid secretions in patients were examined by collecting continuously gastric juice for one hour after having aspirated and discarded fasting gastric juice. Using the clearance rate (mL/min) of ascorbic acid from blood to gastric juice represented ascorbic acid secretion in the gastric mucosa.Ascorbic acid concentrations in plasma and juice were measured by ferric reduced method.RESULTS:Gastric ascorbic acid secretions in H.pylori-positive patients (1.46mL/min,range 0.27-3.78) did not significantly differ from those in H.pylori-negative patients(1.25mL/min, 0.47-3.14)(P>0.05). There were no significant differences in ascorbic acid secretions between patients with mild (1.56mL/min, 0.50-3.30), moderate (1.34mL/min, 0.27-2.93) and severe (1.36mL/min, 0.47-3.78) inflammation (P >0.05). There were no significant differences in ascorbic acid secretions between patients without activity (1.45mL/min, 0.27-3.14) and with mild (1.32mL/min, 0.61-2.93), moderate (1.49mL/min, 0.50-3.78) and severe (1.43mL/min, 0.51-3.26) activity of chronic gastritis either (P>0.05). Ascorbic acid secretions in patients with severe atrophy (0.56mL/min, 0.27-1.20) were markedly lower than those in patients without atrophy (1.51mL/min, 0.59-3.30) and with mild (1.43mL/min, 0.53-3.78) and moderate (1.31mL/min,0.47-3.16)atrophy(P<0.005). There was a significant negative correlation between ascorbic acid secretion and severity of atrophy (correlation coefficient =-0.43, P<0.005). After administration of pentagastrin, ascorbic acid secretions were markedly elevated (from 1.39mL/min, 0.36-2.96 to 3.53mL/min, 0.84-5.91) (P <0.001).CONCLUSION:Ascorbic acid secretion in gastric mucosa is not affected by H.pylori infection. Gastric ascorbic acid secretion is markedly related to the severity of atrophy, whereas not related to the severity of inflammation and activity. Gastrin may stimulate gastric ascorbic acid secretion. A decreased ascorbic acid secretion may be an important factor in the link between atrophic gastritis and gastric carcinogenesis.     

Mechanisms Involved in Protection Afforded by l-Arginine in Ibuprofen-Induced Gastric Damage: Role of Nitric Oxide and Prostaglandins

l-Arginine (l-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with l-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral l-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N^G-nitro-l-arginine (l-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). l-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the l-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE₂ content confirmed that biosynthesis of the eicosanoid is maintained by l-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the l-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response.     

Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer

Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world''s population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.     

Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene

Background/Aims

We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population.

Methods

The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA.

Results

CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection.

Conclusions

In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.     

Clinical Significance and Outcome of Gastric Mucosal Erosions: A Long-Term Follow-Up Study

Our purpose was to evaluate the long-term clinical significance of gastric erosions. A series of 117 patients with gastric erosions without peptic ulcer disease, and matched controls were studied in 1974–1979. All available subjects were reinvestigated 17 years later, including detailed clinical history and laboratory analysis. At follow-up, erosions were still more prevalent (39%; 20/50) in the erosion group than in the controls (11; 7/66). In Helicobacter pylori–positive participants, peptic ulcer or a scar was more common in the erosion group (17%; 9/52) than in controls (5%; 3/66). Overall malignancy rate was higher in controls (15%; 17/117) than in erosion group (5%; 6/117; P = .025), but no other differences were seen between the groups or related with current erosion. We conclude that a significant proportion of gastric erosions are chronic or recurrent but mostly without serious complications. However, H. pylori–positive patients with erosions have significant risk to develop a peptic ulcer.     

Mechanisms of Helicobacter pylori-Induced Rat Gastric Mucosal Microcirculatory Disturbances In Vivo

The exact mechanisms by which Helicobacter pylori infection results in gastric mucosal injury are unclear. However, it has been demonstrated that surface protein extracts of the bacterium can induce a number of disturbances within the rat gastric mucosal microcirculation, including platelet aggregation and macromolecular leakage (MML) of labeled albumin. This study aimed to determine the mechanisms involved in inducing these events using the technique of fluorescent in vivo microscopy. Male Wistar rats were pretreated with either ketotifen, a mast cell stabilizer (1 mg/kg), pyrilamine, an H₁-receptor antagonist (30 mg/kg), hexanolamine-PAF, a PAF-receptor antagonist (10 g/kg), l-arginine, the nitric oxide precursor (300 mg/kg) or vehicle, saline. Then 0.5 ml of H. pylori extract was administered to the exteriorized gastric mucosa of the anesthetized rat. Alterations in fluorescein-labeled albumin leak, vessel diameters, and acridine red-labeled leukocyte and platelet activity were determined over a 2-hr period. Saline pretreated animals demonstrated significant MML with a peak at 5 min (11%, P < 0.02). This was prevented with ketotifen and pyrilamine, but not with hexanolamine-PAF (17.5%, P < 0.05) and l-arginine (13%, P < 0.05). Significant numbers of platelet emboli and thrombi were observed within mucosal capillaries and postcapillary venules with vehicle pretreatment; this was prevented with hexanolamine-PAF and l-arginine, but not with ketotifen and pyrilamine. In conclusion, these studies demonstrate that more than one mediator is involved in inducing the rat gastric mucosal microcirculatory disturbances associated with H. pylori administration. Mast cells and histamine are linked to MML, with PAF, probably not derived from mast cells, involved in platelet activation.     

Gastric cancer arising from the remnant stomach after distal gastrectomy: A review

Gastric stump carcinoma was initially reported by Balfore in 1922, and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology, carcinogenesis, Helicobacter pylori (H. pylori) infection, Epstein-Barr virus infection, clinicopathologic characteristics and endoscopic treatment. In particular, it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition, endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast, many issues concerning gastric stump carcinoma remain to be clarified, including molecular biological characteristics and the carcinogenesis of H. pylori infection. We herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date.     

Protective Effect of a Novel Rice Extract Against Ethanol-Induced Gastric Mucosal Injury in Rat

The aim of this study was to investigate the protective action of rice extract on ethanol-induced mucosal damage in vivo and wound healing of epithelial cells in vitro. Also, the effect of rice extract on gastric mucosal prostaglandin E₂ level, HSP72 expression, gastric acid secretion, and contribution of vanilloid receptor-mediated action was studied. In addition, using cultured gastric mucosal cells (RGM-1), the effect of rice extract on cytoprotection and wound healing of epithelial cells was evaluated. Rice extract significantly reduced gastric mucosal damage produced by ethanol in vivo, and heat treatment (80°C, 3 min) of this agent did not alter its protective effect. Rice extract also protected RGM-1 from ethanol-induced damage in a dose-dependent manner. Rice extract accelerated wound healing of gastric epithelial cells. Our results demonstrate that rice extract could be an alternative ulcer treatment that provides cytoprotection and enhancement of wound healing not dependent on acid secretion, prostaglandin E₂ level, HSP72 expression, or vanilloid receptors.     

Three other types of duodenal polyps: Mucosal cysts,focal foveolar hyperplasia,and hyperplastic polyp originating from islands of gastric mucosa

Summary Seven cases are reported that initially presented on endoscopic examination as duodenal polyps originating from islands of gastric mucosa within the duodenal bulb. Microscopic examination revealed mucosal cysts (MC), focal foveolar hyperplasia (FFH), and hyperplastic polyp (HPP). These lesions must be added to the list of neoplastic and tumorlike lesions of the duodenum that may endoscopically present as polyps.     

The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer

CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.     

Use of Flow Cytometry to Quantify Mouse Gastric Epithelial Cell Populations

Flow cytometry provides the opportunity to quantify cell populations within a total cell suspension. The quality of flow cytometry is strongly dependent on the isolation of intact viable cells. However, techniques to isolate mouse gastric cells for flow cytometry have not been evaluated. The objective of this study was to develop an effective method for isolating intact viable cells from mouse gastric tissue for flow cytometry. Cells were isolated from mouse stomach and spleen by either enzymatic separation or mechanical dissociation. A Percoll density gradient was used to separate viable cells from cellular debris. Cells were labeled with fluorescently tagged ligand or antibody and analyzed by flow cytometry. According to propidium iodide staining, there was a higher percentage of viable cells after mechanical dissociation (10–20%) compared to enzymatic separation (1%). After Percoll centrifugation there was a further increase in the percent of viable cells (50–80%). Gastrin (G), somatostatin (D), and parietal cells represented 0.6%, 3%, and 8% of the total epithelial cell population, respectively. T and B lymphocytes made up 4% and 2% in the gastric mucosa. Dissociated splenocytes were comprised of 20% T cells and 14% B cells. The ability to reliably resolve a cellular fraction that comprises only 0.6% of the input marks a substantial improvement over morphometric methods. Therefore, mechanical dissociation of the stomach followed by use of a Percoll gradient is the preferred method for isolating viable intact gastric epithelial cells for flow cytometry.     

Quantitative Evaluation of Mucosal Regeneration in Gastric Ulcers by Electronic Endoscopy —Comparison between Tractable and Intractable Ulcers—

Abstract: The electronic endoscope named TGS-50B (TOSHIBA) provides a fine resolvable image (Fig. 6) and flat white balance covering a wide range (Fig. 7). Using this electronic endoscope, the regenerative mucosal patterns in 15 cases with intractable and 30 cases with tractable gastric ulcers (Table 1) were observed at 2-week intervals until the healed stage or until 12 weeks after the start of H₂-blocker administration. To clarify the difference between intractable and tractable gastric ulcers, the electronic endoscopic images were fed into an image analyzer; SPICCA (AVIONICS). The regenerative mucosal pattern was converted into 20 binary digited particles by the image analyzer (Fig. 4, Color) and quantified by the oval specification (OSF) value (Fig. 5). The OSF value of the tractable ulcers significantly increased in the healing stage I (H₁) and healing stage 2 (H₂), in comparison with those of intractable ulcers (Fig. 8). Moreover, the OSF value of the tractable ulcer significantly increased at 4 weeks after the start of an H₂-blocker, comparing with that at 2 weeks. Consequently, the OSF values of the tractable ulcers were significantly high in comparison with those of the intractable ulcers, at 4, 6 and 8 weeks after the start of administration of H₂-blockers (Fig. 9). By histological study of the biopsy specimen, an increase in the OSF value suggested an extension of the regenerative mucosa by a well progressed annular contraction of the gastric wall. In conclusion, it is thought that intractability of gastric ulcers may be objectively predictable in its early healing stages by determination of the OSF value using the electronic endoscope and the image analyzer.