Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

Lysophosphatidic acid type 2 receptor agonists in targeted drug development offer broad therapeutic potential.

The growth factor-like lipid mediator, lysophosphatidic acid (LPA), is a potent signaling molecule that influences numerous physiologic and pathologic processes. Manipulation of LPA signaling is of growing pharmacotherapeutic interest, especially because LPA resembles compounds with drug-like features. The action of LPA is mediated through activation of multiple types of molecular targets, including six G protein-coupled receptors that are clear targets for drug development. However, the LPA signaling has been linked to pathological responses that include promotion of fibrosis, atherogenesis, tumorigenesis, and metastasis. Thus, a question arises: Can we harness, in an LPA-like drug, the many beneficial activities of this lipid without eliciting its dreadful actions? We developed octadecyl thiophosphate (OTP; subsequently licensed as Rx100), an LPA mimic with higher stability in vivo than LPA. This article highlights progress made toward developing analogs like OTP and exploring prosurvival and regenerative LPA signaling. We determined that LPA prevents cell death triggered by various cellular stresses, including genotoxic stressors, and rescues cells condemned to apoptosis. LPA2 agonists provide a new treatment option for secretory diarrhea and reduce gastric erosion caused by nonsteroidal anti-inflammatory drugs. The potential uses of LPA2 agonists like OTP and sulfamoyl benzoic acid-based radioprotectins must be further explored for therapeutic uses.

Do glucocorticoids affect the development of ulcers and erosions of the upper gastrointestinal tract in patients taking NSAIDs.

AIM: To assess the frequency of ulceration and erosion in patients with rheumatic diseases (RD) receiving NSAIDs, depending on the concomitant use of GC. MATERIALS AND METHODS: A retrospective comparison was made of the incidence of gastrointestinal lesions detected in patients with RD during endoscopic examination in one medical center for 2007-2016. Three groups were formed: in group 1 patients took only NSAIDs (n=4823, women 80.7%, age 51.1 + 15.4 years), in group 2 patients took NSAIDs and GC (n = 1608, women 89, 8%, age 50.4 + 14.6 years), in group 3 - only patients took GC (n=1135, women 92.7%, age 44.1 + 15.3 years). The detection of multiple erosions (>10, ME) and gastric and / or duodenal ulcers was as-sessed. RESULTS: The frequency of ME and ulcers in patients of groups 1 and 2 did not differ significantly: 10.5% and 8.5%, odds ratio 0.799 (95% confidence interval 0.546-1.169, p=0.072). Risk factors, such as age > 65 years, ulcer history and low-dose aspirin, did not affect this pattern. The incidence of ME and ulcers was significantly lower in Group 3 patients than in Groups 1 and 2: 6.3% (p<0.001, p=0.032). CONCLUSION: The use of GC does not increase the risk of erosion and ulcers of the upper GI tract when taking NSAIDs.

Stress-induced corticosterone rise maintain gastric mucosal integrity in rats.

BACKGROUND AND PURPOSE: To investigate contribution of glucocorticoids to the maintenance of gastric mucosal integrity during stress we predominantly used ulcerogenic stress models. Using these models we demonstrated that glucocorticoids released in response to the ulcerogenic stimuli attenuated their harmful action on the gastric mucosa. In the present study we hypothesized that mild stressors does not damage the gastric mucosa due to gastroprotective action of glucocorticoids released in response to these stressors. METHODS: To verify the hypothesis the effects of normally non-ulcerogenic mild stimuli (15-30 min cold-restraint) on the gastric mucosal integrity have been studied under the circumstances of inhibition of the hypothalamic-pituitaryadrenocortical axis in rats. The hypothalamic-pituitary-adrenocortical axis was inhibited by: 1) fast inhibitory action of metyrapone, inhibitor glucocorticoid synthesis; 2) fast inhibitory action of NBI 27914, the selective antagonist of cortricotropin- releasing factor receptor type 1; 3) delayed inhibitory action of a single pharmacological dose of cortisol injected one week before the onset of stress stimulus. RESULTS: Each of these pretreatments significantly decreased 15-30 min cold-restraint-produced corticosterone levels: 37.2±1 vs 22.5±1.2 (p<0.05) after metyrapone; 52.1±0.9 vs 41.4±1 (p<0.05) after NBI, and 64.2±4.2 vs 16.7±1.5 (p<0.05) after cortisol pretreatment. The inhibition of stress-induced corticosterone rise resulted in an ap - pearance of gastric lesions after the onset of these mild stressors in rats. CONCLUSION: The results suggest that in rats with inhibited stress-induced corticosterone rise normally non-ulcerogenic stimuli are transformed into ulcerogenic ones and confirm the hypothesis. The findings further support for the point of view that glucocorticoids released during acute stress are gastroprotective factors.

Laparoscopic repair of gastro-duodenal fistula secondary to band erosion.

Laparoscopic gastric banding is one of the most common surgical treatments for morbid obesity performed worldwide. The procedure, however, has many well-documented risks and complications, including band erosion. We present here a gastric banding patient who was referred to our tertiary care centre after secondarily forming an entero-enteric fistula with complaints of pain, nausea, vomiting and severe reflux. She was successfully treated with laparoscopic dissection and due to her existing anatomy, and the patient's desire for continued weight loss, she was converted to Roux-en-Y gastric bypass.

Zinc Acetate Dihydrate Tablet-associated Gastric Lesions.

Objective This study aimed to determine the prevalence and endoscopic features of zinc acetate dihydrate tablet-associated gastric lesions. Methods We retrospectively examined the endoscopic features of 47 patients taking zinc acetate dihydrate tablets who underwent esophagogastroduodenoscopy. Results Gastric mucosal alterations, including redness, erosions, ulcers, and adhesion of the white coat, were observed in 29 of 47 patients (61.7%). Among patients with gastric lesions (group A), there was a significantly higher percentage of symptomatic patients in comparison to patients without lesions (group B) (65.5% vs. 22.2%; p<0.01). The background characteristics of the two groups did not differ to a statistically significant extent. On esophagogastroduodenoscopy, mucosal redness (n=27, 93.1%), erosions (n=26, 90.0%), adhesion of the white coat (n=25, 86.2%), and ulcers (n=9, 31.0%) were observed. None of the 19 patients who previously underwent esophagogastroduodenoscopy had gastric lesions before starting zinc acetate dihydrate. Esophagogastroduodenoscopy was performed after the cessation of zinc acetate dihydrate intake in six patients, and revealed the resolution of gastric lesions. Conclusion Gastric lesions were observed in 29 of 47 patients who were taking zinc acetate dihydrate tablets. The most common endoscopic findings were mucosal redness (93.1%), erosions (90.0%), adhesion of the white coat (86.2%), and ulcers (31.0%). Although the exact pathogenesis is uncertain, we believe that understanding the unique manifestations of this gastric lesion will help physicians manage adverse events in patients taking zinc acetate dihydrate tablets.

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.

Mesh migration into stomach following diaphragmatic hernia repair: a rare complication.

Mesh erosion and migration are considered the gravest of complications of mesh repairs. To the best of our knowledge, mesh erosion and migration into the stomach following a mesh repair of adult diaphragmatic hernia has yet to be reported in the literature. A case of mesh eroding into the stomach, after a prosthetic repair of an adult diaphragmatic hernia, is presented here because of its rarity.

Glucocorticoids are Gastroprotective under Physiologic Conditions.

Stress may contribute to the development and progression of gastrointestinal disorders. Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the main characteristics of stress. For several decades it was generally accepted that glucocorticoids released during stress are ulcerogenic hormones. We designed some experimental studies in rats to clarify the validity of this widely held view. To achieve this goal, we examined the effect of glucocorticoid deficiency followed by corticosterone replacement or the glucocorticoid receptor antagonist, RU-38486, on stress-induced gastric erosion and the parameters of gastric function in rats. The data obtained shows that the reduction in the stress-induced corticosterone release, or its actions, aggravates stress-caused gastric erosion. It is suggested that an acute increase in corticosterone during stress protects the stomach against stress-induced injury. According to our results, various ulcerogenic stimuli, similar to stress, induce an increase in corticosterone that helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids exhibit their gastroprotective effect by both maintaining local defensive factors and inhibiting pathogenic elements. Furthermore, the contribution of glucocorticoids to gastroprotection is tightly related to their contribution to general body homeostasis. Glucocorticoids provide gastroprotective actions in co-operation with prosta-glandins, nitric oxide and capsaicin-sensitive sensory neurons. The results obtained do not support the traditional paradigm and suggest that glucocorticoids released during acute activation of the HPA axis are naturally occurring gastroprotective factors. In this article, we review our recent publications on the role of glucocorticoids in gastroprotection.