Modulation of Stem Cell Progeny by Probiotics during Regeneration of Gastric Mucosal Erosions

Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even cancer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gastric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H+,K+-ATPase and pepsinogen involved in the production of the harsh acidic environment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages.

Gastroprotective Mechanism and Ulcer Resolution Effect of Cyrtocarpa procera Methanolic Extract on Ethanol-Induced Gastric Injury

Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. We have previously reported the remarkable gastroprotective and anti-Helicobacter pylori activities of the methanolic extract (CpMet) of Cyrtocarpa procera bark. This work investigates, in a murine model, the CpMet gastroprotective mechanism and establishes its preclinical efficacy in the resolution of ethanol-induced gastric ulcers. The results showed that the gastroprotective activity of CpMet is mainly associated with endogenous NO and prostaglandins, followed by sulfhydryl groups and KATP channels. Furthermore, CpMet (300 mg/kg, twice a day) orally administered during 20 consecutive days promoted an ulcer area reduction of 62.65% at the 20th day of the treatment. The effect was confirmed macroscopically by the alleviation of gastric mucosal erosions and microscopically by an increase in mucin content and a reduction in the inflammatory infiltration at the site of the ulcer. No clinical symptoms or signs of toxicity were observed in the treated animals. The results indicate the safety and efficacy of CpMet in promoting high quality of ulcer healing by different mechanisms, but mostly through cytoprotective and anti-inflammatory effects, making it a promising phytodrug for ulcer treatment.

Transfusion-Dependent Anaemia: An Overlooked Complication of Paraoesophageal Hernias

Introduction. A paraoesophageal hernia (PH) may be one reason for iron-deficiency anaemia (IDA) but is often overlooked as a cause. We aimed to assess the incidence and resolution of transfusion-dependent IDA in patients presenting for hiatal hernia surgery. Methods. We analysed a prospective database of patients undergoing laparoscopic hiatal repair in order to identify patients with severe IDA requiring red cell/iron transfusion. Results. Of 138 patients with PH managed over a 4-year period, 7 patients (5.1%; M : F 2 : 5; median age 62 yrs (range 57–82)) with IDA requiring red cell/iron transfusion were identified. Preoperatively, 3/7 patients underwent repetitive and unnecessary diagnostic endoscopic investigations prior to surgery. Only 2/7 ever demonstrated gastric mucosal erosions (Cameron ulcers). All patients were cured from anaemia postoperatively. Discussion. PH is an important differential diagnosis in patients with IDA, even those with marked anaemia and no endoscopically identifiable mucosal lesions. Early recognition can avoid unnecessary additional diagnostic endoscopies. Laparoscopic repair is associated with low morbidity and results in resolution of anaemia.

Protective effect of Punica granatum peel extract against gastric mucosal erosions induced by ethanol in experimental rabbit models

The present study was designed to detect the gastroprotective effect of ethanolic (96%) extract of Punica granatum peel, besides investigation of its activity as hepatoprotective and nephroprotective agent. 1 ml of 80% ethanol/rabbit was given as a single oral dose for induction of gastric erosions and hepato-renal changes in both induction (ethanol group) and treatment groups at the 16 th day of experiment (i.e. following 15 days of daily treatment with pomegranate peel extract).These effects were assessed by examination of some biochemical tests including; blood glucose, triglycerides, renal function test (urea, creatinine), and liver function test (ALT, GGT), in addition to the evaluation of the histopathological changes of the stomach samples. Animals pretreated with Punica granatum peel ethanolic extract at a dose of 200 mg/kg/day orally for 15 days showed significant reduction in blood glucose, urea, creatinine, ALT, and GGT where as blood TG was not affected in comparison with the ethanol group (P ≤ 0.05).On the other hand, microscopic examination of stomach samples of the treatment group revealed regenerated gastric ulcer and lesions, and the distorted superficial gland in the mucosa are regenerated when compared with those observed on the samples of the ethanol 80% group.In conclusion, the obtained data demonstrate that pomegranate peel ethanolic extract is a potent gastroprotective agent and suppresses ethanol 80%-induced gastric damage in rabbits.

Should patients with pH-documented laryngopharyngeal reflux routinely undergo oesophagogastroduodenoscopy? A retrospective analysis

Objectives:Patients with laryngopharyngeal reflux uncommonly suffer from conditions associated with gastroesophageal reflux disease. However, in some laryngopharyngeal reflux patients, oesophagitis and Barrett's metaplasia can be diagnosed by oesophagogastroduodenoscopy. However, it is unclear which patients with laryngopharyngeal reflux would benefit from routine oesophagogastroduodenoscopy.Study design:Retrospective analysis.Materials and methods:Analysis of the results of oesophagogastroduodenoscopy in 28 patients with pH-documented laryngopharyngeal reflux.Results:Oesophagogastroduodenoscopy showed oesophagitis in five patients (four with grade A, one with grade B), hiatus hernia in 10 patients (36 per cent), Barrett's metaplasia in two patients, Helicobacter pylori-associated chronic gastritis in two patients and gastric mucosal erosions in seven patients (25 per cent). In 13 patients, no abnormalities were detected (46 per cent). Barrett's metaplasia or grade B oesophagitis was diagnosed only in patients with heartburn as their main presenting symptom.Conclusions:Oesophagogastroduodenoscopy is indicated in at least those laryngopharyngeal reflux patients reporting heartburn as their main complaint.

Role of gastric acid secretion and blood flow in the development of vagal stimulation induced gastric mucosal damage

Vagal stimulation has been shown to result in the development of gastric mucosal erosions in the rat, although the mechanisms underlying the development of such erosions are not known. The effects of vagal stimulation on gastric acid secretion and mucosal blood flow were examined in urethane-anesthetized male Sprague–Dawley rats to determine whether changes in these factors correlate with the mucosal damage in response to vagal stimulation. Electrical stimulation (5 Hz, 5 V, 1 ms for 60 min) of afferent or efferent components of the vagi was not found to induce any significant increase in the mean acid secretory rate compared with control animals (p > 0.05). In contrast, stimulation of intact vagus nerves induced a significant increase in the mean acid secretory rate compared with control and efferent- and afferent-stimulated groups (p < 0.01). Measurement of gastric blood flow with laser-Doppler flowmetry demonstrated intact vagal stimulation to have no significant effect on gastric blood flow. These data suggest that such vagal stimulation induced increases in acid secretion in urethane-anesthetized animals may represent a part of the integrated physiological response to such stimulation which leads to the development of gastric mucosal erosions within 60 min. Pretreatment with antisecretory agents such as cimetidine and inter-leukin-1β significantly reduce the gastric mucosal injury compared with untreated animals (p < 0.05), emphasizing the important role of acid secretion in the development of vagal-induced gastric damage.Key words: vagus, acid secretion, blood flow, gastric.

Lateral hypothalamic lesions cause gastric injury by stimulating gastric contractility

Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions.