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Background: Oral omeprazole is the accepted treatment for equine squamous gastric disease (ESGD); however, it is not universally effective. Esomeprazole results in more consistent and pronounced acid suppression in men and is more effective than omeprazole in the treatment of oesophageal and gastric disease. Pharmacodynamic and pilot clinical studies have indicated esomeprazole might also be more effective than omeprazole in horses., Objectives: To compare the efficacy and safety of oral esomeprazole and omeprazole pastes in the treatment of ESGD and, where present, concurrent equine glandular gastric disease (EGGD)., Study Design: Randomised, single-blinded controlled trial., Methods: Horses presenting with grade ≥2 ESGD lesions were randomly allocated to receive 4 mg/kg of either a buffered esomeprazole or omeprazole paste orally once daily for 28 days before gastroscopy being repeated within a further 3 days. Videos and images were anonymised and subsequently graded blind by one researcher. The severity of ESGD (and EGGD) lesions before and after treatment, and thereby treatment responses, were compared using univariable logistic regression., Results: A higher proportion of horses had ESGD healing in response to esomeprazole treatment (63/74, 85%) than with omeprazole treatment (43/73, 59%) (odds ratio [OR]: 4.00, 95% confidence interval [CI]: 1.81, 8.82, p = 0.001). In a subset of horses that had concurrent EGGD, a greater proportion of the horses treated with esomeprazole had lesions ≤grade 1 (esomeprazole 28/51, 55%; omeprazole 6/24, 25%; OR: 3.65, 95% CI: 1.25, 10.71, p = 0.02) Using grade 0 as the benchmark for EGGD healing, the difference remained significant (OR: 4.44, 95% CI: 1.33, 14.85, p = 0.02)., Main Limitations: It may not be possible to extrapolate these results to other populations with different signalment or management., Conclusions: Oral-buffered esomeprazole was a more effective treatment for ESGD (and concurrent EGGD) than oral-buffered omeprazole., (© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

The Zingiberis Rhizoma - Jujubae Fructus herb pair (ZJHP) is a classic herb pair in traditional Chinese medicine. The herb pair shows the effect of dispelling cold, harmonizing the middle and improving gastrointestinal function, and is widely used for patients with stomach cold syndrome (SCS), stomachache and anemofrigid cold. The gingerols, shogaols, flavonoids and triterpenic acids are the important bioactive ingredients of ZJHP. However, few pharmacokinetic studies have been investigated in vivo for the above compounds. To comprehend the kinetics of active components and promote their curative application, a fast and sensitive ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of 12 analytes in normal and SCS rats in this study. The results showed that the pharmacokinetic parameters (C max , T max , t 1/2z , MRT 0-t , AUC 0-t and AUC 0-∞ ) in SCS model were significantly different from those in normal rats. In addition, the pharmacokinetics of rats given ZJHP were also varied from single herb oral administration, especially in model condition. These results indicated that the in vivo processes of the above analytes changed under pathological conditions and the compatibility of the herb pair could significantly influence the absorption of active components, which might provide an insight and further supports for the clinical application of ZJHP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 μIU/ml] in these patients., Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22+/-0.27 μg/kg/die, in the L-LT4 group 1.36+/-0.22 μg/kg/die (p>0.05)., Results: At the basal evaluation the prevalence of patients with a TSH>3.5 μIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 μIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 μIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 μIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 μIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit., Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EB declared a shared affiliation with the author AA to the handling editor at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fallahi, Ragusa, Patrizio, Mazzi, Botrini, Elia, Balestri, Barozzi, Rugani, Palmisano, Cosenza, Varricchi, Ulisse, Benvenga, Ferrari and Antonelli.)

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders., Competing Interests: The authors have declared no conflicts of interest.

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age., (© 2024. The Author(s).)

Ethnopharmacological Relevance: The traditional Chinese medicine formula Lizhong Pill (LZP) and its herbal constituents are frequently utilized in Asian (China, Saudi Arabia, India, Japan, etc.) and some European (Russia, Sweden, UK, etc.) nations to treat various gastrointestinal ailments., Aim of the Study: This study aimed to investigate the protective impact and potential mechanism of LZP against indomethacin (IND)-induced gastric mucosal injury in rats., Material and Methods: Using a biochemical kit, we investigated the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in rat serum, as well as pepsin in rat stomach tissue, using an IND-induced rat model of gastric mucosal injury. Various imaging tools, including HE staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to examine the gastric mucosa's surface morphology and ultrastructure. Furthermore, molecular docking was employed to predict the binding capacity of the primary bioactive components of LZP to the critical molecular protein targets in the IL-17 and TNF signaling pathways. At the same time, immunofluorescence was used to determine the protein expressions of CASP3, VCAM1, MAPK15, MMP3, IL-17RA, and TNFR1., Results: The present study demonstrates that LZP (3.75 and 7.50 g/kg) significantly reduces the gastric mucosal injury index induced by IND. This effect is evidenced by the improved morphology, surface, and structure of the gastric mucosa, as determined by HE, SEM, and TEM findings. Additionally, 3.75 and 7.50 g/kg LZP intervention significantly increased SOD and CAT contents and inhibited pepsin and GST activities. Molecular docking analysis revealed that the small molecular components of LZP can bind spontaneously to crucial proteins involved in the IL-17 and TNF signaling pathways, including MAPK15, MMP3, VCAM1, and CASP3. The immunofluorescence findings proved that LZP (3.75 and 7.50 g/kg) can inhibit the protein expressions of MAPK15, MMP3, VCAM1, CASP3, IL-17RA, and TNFR1., Conclusions: Our investigation findings demonstrate that LZP can potentially ameliorate IND-induced damage to the gastric mucosa by inhibiting IL-17 and TNF signaling pathways. These results offer encouraging support for using alternative medicine to manage drug-induced gastric mucosal injury., Competing Interests: Declaration of competing interest The authors state that no commercial or financial relationships that might be considered a potential conflict of interest existed during the research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: An extended-release injectable omeprazole formulation (ERIO) has become a popular treatment for equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) where it is available; however, published data are limited and optimal treatment regimens have not been determined., Objectives: To compare effects of treatment on ESGD and EGGD when an ERIO formulation is administered at either 5- or 7-day intervals., Study Design: Retrospective clinical study., Methods: Case records and gastroscopy images of horses with ESGD or EGGD treated with ERIO were reviewed. Images were anonymised and graded by one researcher masked to treatment group. Treatment responses were compared between the two treatment schedules using univariable ordered logistic regression., Results: Forty-three horses were treated with ERIO at 5-day intervals and 39 horses at 7-day intervals. Signalment and presenting signs did not differ between groups. The proportions of horses with EGGD healing (to grade 0 or 1) in association with ERIO used at 5-day intervals (93%) were higher than associated with treatment at 7-day intervals (69%; odds ratio [OR]: 2.41, 95% CI: 1.23-4.74, p = 0.01). For ESGD, there was no significant difference in the proportion of horses healing in association with treatment at 5-day intervals (97%) compared with 7-day intervals (82%; OR: 2.75, 95% CI: 0.91-8.31, p = 0.07). Four of 328 injections were associated with an injection-site reaction (1%)., Main Limitations: Retrospective study design, lack of randomisation and limited case numbers., Conclusions: The use of ERIO at 5-day intervals might be more appropriate than the 7-day interval that is used currently., (© 2023 EVJ Ltd.)

Context: Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear., Objective: To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms., Materials and Methods: C57BL/6 mice were randomized into six groups ( n  = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed., Results: The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa., Discussion and Conclusions: XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

Background: Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research, we focused on the first demonstration of the severe occlusion/ occlusion-like syndrome induced by stomach perforation. The revealed stomach-induced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure. This general point was particularly reviewed. As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely affect endothelium function, the stable gastric pentadecapeptide BPC 157 was resolving therapy., Aim: To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect., Methods: The procedure included deeply anesthetized rats, complete calvariectomy, laparotomy at 15 min thereafter, and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome. At 5 min post-perforation time, rats received therapy [BPC 157 (10 µg or 10 ng/kg) or saline (5 mL/kg, 1 mL/rat) (controls)] into the perforated defect in the stomach). Sacrifice was at 15 min or 60 min post-perforation time. Assessment (gross and microscopy; volume) included: Brain swelling, peripheral vessels (azygos vein, superior mesenteric vein, portal vein, inferior caval vein) and heart, other organs lesions ( i.e., stomach, defect closing or widening); superior sagittal sinus, and peripherally the portal vein, inferior caval vein, and abdominal aorta blood pressures and clots; electrocardiograms; and bleeding time from the perforation(s)., Results: BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect (raised vessel presentation; less bleeding, defect contraction) and occlusion/occlusion-like syndromes counteraction. BPC 157 therapy (into the perforated defect), induced immediate shrinking and contraction of the whole stomach (unlike considerable enlargement by saline application). Accordingly, BPC 157 therapy induced direct blood delivery via the azygos vein, and attenuated/eliminated the intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension. Thrombosis, peripherally (inferior caval vein, portal vein, abdominal aorta) and centrally (superior sagittal sinus) BPC 157 therapy markedly reduced/annihilated. Severe lesions in the brain (swelling, hemorrhage), heart (congestion and arrhythmias), lung (hemorrhage and congestion), and marked congestion in the liver, kidney, and gastrointestinal tract were markedly reduced., Conclusion: We revealed stomach perforation as a severe occlusion/occlusion-like syndrome, peripherally and centrally, and rapid counteraction by BPC 157 therapy. Thereby, further BPC 157 therapy may be warranted., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Artemisia capillaris is among the most abundantly used traditional medicines, utilized in East Asia to treat diverse illnesses, including gastrointestinal tract diseases. We previously reported that an aqueous extract of A. capillaris (AEAC) inhibited gastric inflammation induced by HCl/ethanol via reactive oxygen species scavenging and NF-κB downregulation. To date, the pharmacological potential of AEAC for promoting mucosal integrity has not been studied., Results: Here, we report that a single treatment with AEAC increased mucus production, and repeated administration of AEAC abolished HCl/ethanol-induced mucosal injury in vivo. Single- and multiple-dose AEAC treatments measurably increased the expression of mucosal stabilizing factors in vivo, including mucin (MUC) 5 AC, MUC6, and trefoil factor (TFF) 1 and TFF2 (but not TFF3). AEAC also induced mucosal stabilizing factors in both SNU-601 cells and RGM cells through phosphorylation of extracellular signal-regulated kinases., Conclusion: Taken together, our results suggest that AEAC protects against HCl/ethanol-induced gastritis by upregulating MUCs and TFFs and stabilizing the mucosal epithelium. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

This study aimed to assess the clinical efficacy of pentoxifylline (PTX) and L-glutamine (L-Gln) treatment on ischemia and reperfusion (I/R) injury in the abomasal tissue, acute phase response (APR), oxidative stress (OS), cytokine response, hemostatic, and coagulation disorders in the 96-h period before and after surgery in displaced abomasum (DA) cases. The study sample consisted of 48 dairy cows with DA that were categorized into four groups as group S (Sham group) (9 Left displaced abomasum (LDA)+3 Right displaced abomasum (RDA), group P (PTX) (10 LDA+2 RDA), group G (L-Gln) (10 LDA+2 RDA), and group P+G (PTX+L-Gln) (10 LDA+2 RDA). Acute-phase protein (Haptoglobin), oxidative stress indicators (malondialdehyde, nitric oxide, and glutathione), cytokines (tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β), coagulation factors (D-Dimer, Antithrombin (ATIII), Thrombin-antithrombin complex, Plasminogen activator inhibitor-1), and enzyme activities (lactate dehydrogenase, gamma- -glutamyl transferase, sorbitol dehydrogenase, glutamate dehydrogenase, adenosine deaminase, myeloperoxidase, and creatine phosphokinase) in blood serum samples and coagulometric analyses of blood plasma were performed in samples taken before the operation and at 30 and 60 min and 2, 5, 10, 24, 48, 72, and 96 h after the operation. In DA cases, while post-operative treatment procedures with PTX and L-Gln were effective in decreasing APR and OS, these were ineffective in prohibiting the inflammatory response coordinated by cytokines. For the treatment and prevention of I/R injury in the DA cases, PTX and L-Gln procedures hold promise with their effects on APR, OS, and hemostatic dysfunction. Additional treatment procedures are required for the suppression of inflammatory response, and the effectiveness of preconditioning treatment may be evaluated., (Copyright© by the Polish Academy of Sciences.)

Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets., (Copyright © 2021. Published by Elsevier Masson SAS.)

Multiple theories have been proposed describing the pathogenic mechanisms of Helicobacter pylori ( H. pylori )-associated gastric motility disorders. We assessed ex vivo pyloric activity in H. pylori -infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: 1 ) control group, 2 ) sterile broth (vehicle group), 3 ) amoxicillin control, 4 ) omeperazole control, 5 ) clarithromycin control, 6 ) triple therapy control, 7 ) H. pylori - group, 8 ) H. pylori -clarithromycin group, and 9 ) H. pylori -triple therapy group. Urease enzyme activity was applied as an indicator of H. pylori infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor β (TGFβ), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By H. pylori infection, a significant ( P < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased ( P < 0.001) in the H. pylori- infected group, associated with reduced serum ghrelin, elevated TGFβ, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, H. pylori infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in H. pylori -associated pyloric dysfunction, which might help in the management of human H. pylori manifestations and complications. NEW & NOTEWORTHY This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.

Introduction: Eating and rumination variables were recorded using a pressure sensor integrated into the noseband of a halter in 60 cows with left displaced abomasum (LDA) before and after postoperative administration of flunixin meglumine (FM). Group 1 comprised 9 healthy control cows that were used to establish reference intervals. Group 2 included 60 cows with LDA that received one of the following three treatments: intravenous saline solution (2A, n=20), 1.1 mg/kg FM (2B, n=20) or 2.2 mg/kg FM (2C, n=20) once daily for 3 days after right-flank omentopexy. Median eating times on the day before surgery were 93 (2A), 80 (2B) and 114 (2C) min, which were below the reference interval (246 to 381 min). On the day after surgery, eating times had increased significantly to 201 (2A), 172 (2B) and 216 (2C) min, after which time they continued to increase. Eating and rumination times, numbers of regurgitated feed boluses per day and chewing cycles per bolus did not differ among treated groups. Postoperative administration of FM did not affect eating and rumination variables in this study, and normalisation of these variables was attributable to surgical correction of LDA.

Aims: Saxagliptin, a selective/potent dipeptidyl peptidase-4 inhibitor, has revealed remarkable anti-inflammatory features in murine models of nephrotoxicity, hepatic injury, and neuroinflammation. However, its potential effect on ethanol-induced gastric mucosal injury has not been examined. Hence, the present work investigated the prospect of saxagliptin to attenuate ethanol-evoked gastric injury, with emphasis on the AMPK/mTOR-driven autophagy and NLRP3/ASC/caspase-1 pathway., Materials and Methods: In ethanol-induced gastropathy, the gastric tissues were examined by immunohistochemistry, immunoblotting, histopathology, and ELISA., Key Findings: The results demonstrated that saxagliptin (10 mg/kg; by gavage) suppressed the gastric pathological signs (area of gastric ulcer and ulcer index scores), histopathologic aberrations/damage scores, without provoking hypoglycemia in rats. These protective features were attributed to the enhancement of gastric mucosal autophagy flux, as proven with increased expression of LC3-II and Beclin 1, decreased accumulation of p62 SQSTM1, and activation of the autophagy-linked AMPK/mTOR pathway by increasing the expression of p-AMPK/AMPK and decreasing the expression of the autophagy suppressor p-mTOR/mTOR signal. In tandem, saxagliptin counteracted the ethanol-induced pro-apoptotic events by downregulating Bax, upregulating Bcl2 protein, and lowering the Bax/Bcl2 ratio. Equally important, saxagliptin suppressed the NLRP3 inflammasome in the gastric tissue by lowering the expression of NLRP3, ASC, and nuclear NF-κBp65, decreasing the activity of caspase-1, and diminishing the IL-1β levels. In the same regard, saxagliptin suppressed the mucosal oxidative stress by lowering lipid peroxide levels, increasing GSH and GPx antioxidants, and activating Nrf2/HO-1 pathway., Significance: Saxagliptin may be a promising intervention against ethanol-evoked gastropathy by activating AMPK/mTOR-driven autophagy and inhibiting NLRP3 inflammasome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Zuojin Pill (ZJP) has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. But its effect on non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric injury (GI) is still uncharted., Aim of the Study: This study aims to investigate the therapeutic effect and molecular mechanism of ZJP on indomethacin (IDO) induced gastric injury., Materials and Methods: GI was induced in rat by oral administration of 5 mg/kg IDO. Then the rats were treated with ZJP (1.26, 2.52, 5.04 g/kg, ig). The changes of food intake, body weight, gastric pH and general state observation were carried out to determine the improvement of ZJP in IDO-induced GI: HE staining and AB-PAS staining was analyzed to characterize the thickness of gastric mucosa and micro mucosal injury; in order to elucidate the effect of ZJP on IDO-induced inflammatory injury, the inflammatory infiltration of gastric tissue was observed by MPO immunohistochemical method, and the contents of TNF-α, IL-6 and IL-10 were measured. Furthermore, the regulatory mechanism of ZJP in treating IDO-induced GI was predicted with the help of network pharmacology, and the expression levels of key proteins ERK, p-ERK, P38, p-P38, JNK, p-JNK were determined to elucidate the molecular mechanism of ZJP., Results: Current data strongly demonstrated that ZJP alleviated food intake reduction, weight loss and gastric injury caused by IDO and made gastric pH and mucosal thickness return to normal. In addition, ZJP could reduce the level of MPO to alleviate the inflammatory infiltration of gastric tissue. Simultaneously, ZJP could down regulate the expression of TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage caused by inflammatory, and create a healing environment. Furthermore, ZJP could significantly inhibit the phosphorylation of ERK, p38 and JNK, which leaded to the increase of inflammatory factors and the damage of gastric mucosa., Conclusion: ZJP improved local inflammation by inhibiting MAPK signaling pathway, and had a good therapeutic effect on IDO-induced GI. This study has reference significance for the study of ZJP in the prevention and treatment of NSAID induced gastric injury. In addition, ZJP may be a new treatment option for the prevention and treatment of NSAID induced gastric disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy., Methods: Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk., Results: 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71)., Conclusions: Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy., (© 2021. The Author(s).)

Background and Aim: Portal hypertensive gastropathy (PHG) is characterized by noninflammatory edema and vasodilatation of the lamina propria of the mucosal epithelium. In addition, the alterations of intercellular junction proteins and dilatation of the endothelial gaps have been reported. In this study, we examined whether irsogladine maleate (IM), a gastric mucosal protective agent, has the potential to improve PHG by restoration of tight junctions (TJs)., Methods: Twenty-four patients with PHG were registered and randomly assigned into two groups: 12 patients in the IM-administration group and 12 patients in the non-administration group. In the administration group, IM (4 mg/day) was administered orally for 12 weeks. Gastric mucosa with a red color in patients with PHG were obtained endoscopically on the registration day and 12 weeks later. The endoscopic findings were evaluated, an immunohistochemical analysis of claudin-3 (a TJ protein) expression in gastric mucosal tissues by a laser microscope was performed, and claudin-3 expression was quantified by western blot analysis., Results: Irsogladine maleate improved the degree of PHG in 2/12 patients endoscopically, in contrast to none of the 12 patients in the non-administration group. Immunohistochemical analysis showed that expression of claudin-3 increased in 8/12 patients in the IM-administration group and 2/12 patients in the non-administration group (P = 0.036). Western blot analysis revealed that the increase in claudin-3 after 12 weeks was significantly higher in the IM-administration group than in the non-administration group (P = 0.010)., Conclusions: The present pilot study suggested that IM might improve the gastric mucosa in PHG through restoration of TJ-protein claudin-3., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: Rapid gastric epithelial progenitor cell (EPC) proliferation and inflammatory response inhibition play key roles in promoting the repair of gastric mucosal damage. However, specific targets inducing these effects are unknown. In this study, we explored the effects of a potential target, Ankyrin repeat domain 22 (ANKRD22)., Methods: An acute gastric mucosal injury model was established with Ankrd22 -/- and Ankrd22 +/+ mice by intragastric administration of acidified ethanol. Organoid culture and flow cytometry were performed to evaluate the effects of ANKRD22 on leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5 + ) gastric EPC proliferation. The mechanisms by which ANKRD22 affects gastric EPC proliferation and inflammatory responses were explored by mitochondrial Ca 2+ influx and immunoblotting. Candidate ANKRD22 inhibitors then were screened virtually and validated in vitro and in vivo., Results: After acute gastric mucosal injury, the number of Lgr5 + gastric EPCs was increased significantly in Ankrd22 -/- mice compared with that in Ankrd22 +/+ mice. Moreover, Ankrd22 knockout attenuated inflammatory cell infiltration into damaged gastric tissues. ANKRD22 deletion also reduced mitochondrial Ca 2+ influx and cytoplasmic nuclear factor of activated T cells in gastric epithelial cells and macrophages, which further induced Lgr5 + gastric EPC proliferation and decreased macrophage release of tumor necrosis factor-α and interleukin 1α. In addition, a small molecule, AV023, was found to show similar effects to those produced by ANKRD22 deletion in vitro. Intraperitoneal injection of AV023 into the mouse model promoted the repair of gastric mucosal damage, with increased proliferation of Lgr5 + gastric EPCs and visible relief of inflammation., Conclusions: ANKRD22 inhibition is a potential target-based therapeutic approach for promoting the repair of gastric mucosal damage., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Infection with the stomach worm Physaloptera spp. in dogs can cause chronic vomiting, although the diagnosis is often difficult owing to a low worm burden, single-sex infections, a failure to produce ova, or ova that are of greater density than solutions routinely used for qualitative fecal flotation. A retrospective evaluation was performed of 27 dogs that had gastric Physaloptera spp. infection confirmed endoscopically. In 23 of 27 dogs (85.2%), chronic vomiting was the chief complaint, and Physaloptera was an incidental finding in 3 dogs with esophageal or gastric foreign bodies. The worm burden was low (1-3 worms) in 21 dogs (77.8%), but 2 dogs were infected with large numbers (>50 worms). Prior therapy with routine doses of anthelmintics was ineffective in eight dogs prior to endoscopy. A higher dose and longer duration of fenbendazole in combination with pyrantel pamoate is recommended for treatment of suspected or confirmed infections. Reinfection is common in some dogs and should not be viewed as treatment failure., (© 2021 by American Animal Hospital Association.)

Objective: The adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing., Design: Data were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death)., Results: In the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19., Conclusion: Patients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit-risk assessments in the management of acid-related diseases amid the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Helicobacter pylori is a common gastric bacterial pathogen implicated in the pathogenesis of many digestive tract disorders. H. pylori infection prevalence has been reported alarmingly in Iran. A plethora of studies have been conducted to evaluate the efficiency of first-line and second-line eradication attempts in patients diagnosed with H. pylori infections in Iran. The present study, was evaluated the efficacy of first-line and second-line therapy in H. pylori infections in Iran. We aimed to consider the literature review of the various library and electronic databases (Science Direct, PubMed, and Google Scholar) until 2020. The frequency of bacterial resistance to tetracycline, ampicillin, trimethoprim, erythromycin, ofloxacin, and metronidazolewas found to be high in Iran, while the most effective antibiotics were clarithromycin, rifampin, rifampicin, tetracycline, amoxicillin, ciprofloxacin, levofloxacin, moxifloxacin, and azithromycin. The therapeutic choice for H. pylori eradication in Iran could be quadruple therapy using two antibiotics amoxicillin and metronidazole/clarithromycin for the first-line regimen, and a combination of furazolidone plus tetracycline/amoxicillin and bismuth plus proton pump inhibitor for the second-line regimen. Due to increased antibiotic resistance in our region, empirical therapy must be replaced by more targeted treatment based on antimicrobial drug resistance profiles obtained from patients. Although we limited our investigation on the H. pylori eradication regimens in Iran, the results can be generalized to any region as long as the patterns of resistance are the same.

Objective: To compare the therapeutic effect and safety in treatment of functional constipation between electroacupuncture (EA) and gastro-kinetic drugs., Methods: Using "functional constipation"， "prucalopride"， "mosapridecitrate"， "electro-acupuncture" and "randomized controlled trial"， both in Chinese and English, as search terms, the articles of randomized controlled trial (RCT) regarding to the comparison of therapeutic effect on functional constipation in the patients between EA and gastro-kinetic drugs were retrieved from CMB, Wanfang, VIP, CNKI, OpenGrey, CINAHL, Cochrane Library, JBI, PubMed, WOS and Ovid databases. The retrieval time was from the establishment date to June 2018. The two researchers screened articles, extracted data and assessed literature quality in reference to Cochrane Handbook. Using RevMan 5.3 software, the meta-analysis was conducted., Results: A total of 11 articles were included finally, with 744 patients involved. It was found after meta-analysis that in EA group, the weekly spontaneous defecation frequency, constipation related quality of life in patients, depression relief and incidence of adverse reaction were all better than those in gastro-kinetic medication group. The therapeutic effect of the improvements in stool character and defecation difficulty in EA group were better or similar to that in gastro-kinetic medication group., Conclusion: Regarding the therapeutic effect and safety in treatment of functional constipation, the results of electroacupuncture are superior or similar to gastro-kinetic medication, presenting a satisfactory therapeutic prospect.

In the present work, hybrid microgels based on chitosan and SiO 2 nanoparticles (NPs) were synthesized. Both chitosan and the SiO 2 NPs were submitted to chemical modification reactions to having vinyl groups incorporated into their structures. The microgels were synthesized by emulsion polymerization. SEM analysis indicated a high dispersity of diameter for the microgels, ranging between (18.7 ± 12.3) μm for the samples without SiO 2 -VTS and (11.3 ± 8.07) μm for the microgels with SiO 2 -VTS. The material showed pH-responsiveness, especially in acidic pHs. The longest release lasted 45 min and large amounts of drugs were released as soon as the material was added to the release medium. It is interesting for oral drug delivery systems, especially for gastric wound treatment. The fast release of high amounts of drugs promotes an immediate relief of the pain and the following controlled release allows the gradual recovery of the damaged area., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Equine squamous gastric disease (ESGD) is a highly prevalent disease in horses, particularly in elite athletes. Some horses respond slowly, or fail to respond, to the licensed treatment, oral omeprazole (ORLO)., Objectives: To compare rates of ESGD healing and improvement between ORLO and a long-acting injectable omeprazole preparation (LAIO)., Study Design: Retrospective clinical study., Methods: The case records and gastroscopy images of horses presenting to Rainbow Equine Hospital over a 12-month period were reviewed, with images being reviewed blind by one of the authors (David Rendle). Treatment responses were compared between horses that received 2 or 4 injections of 4 mg/kg LAIO at weekly intervals, and horses that received ORLO at 4 mg/kg PO SID for 4 weeks. Data were compared using a Mann-Whitney test with post hoc Dunn's test, chi-squared test or Fisher's exact test., Results: Fifty-six horses met the inclusion criteria: 29 received LAIO and 27 received ORLO. Treatment groups were comparable in terms of signalment and ESGD lesions. There was a difference in rate of healing when LAIO and ORLO treatment groups were compared at 28 days (LAIO-97%; ORLO-67%; p = .005; OR = 14(1.8-158)), but no difference between LAIO at 14 days and ORLO at 28 days (LAIO-86%; ORLO-67%; p = .12; OR = 3.1 (0.9-10)). Five localised and self-limiting injection site reactions were identified in 3 horses out of 98 injections (5.1%)., Main Limitations: The study was limited by its retrospective nature, absence of randomisation and limited numbers., Conclusions: Four weeks of treatment with LAIO resulted in better rates of ESGD healing than 4 weeks of ORLO. Larger more robust studies of LAIO are warranted., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Tuberculosis of the stomach is quite rare, both as a primary or secondary infection. It has varied presentation ranging from non-specific abdominal pain and constitutional symptoms to hematemesis, gastric outlet obstruction and pyrexia of unknown origin. Here, we report a rare, interesting case of locally advanced gastric tuberculosis, which morphologically mimicked liver abscess initially in a young, immunocompetent patient presenting with fever and abdominal pain. The disease was diagnosed by GeneXpert MTB/RIF assay, and responded well to antituberculosis medication without surgery. Clinicians must bear in mind that, even in the absence of immunodeficiency, as in this case, tuberculosis can involve any site in the gastrointestinal tract and may present with a variety of presentation and infiltrating adjacent organ that might be mistaken as malignancy. This is first case report of gastric tuberculosis, which is locally advanced with adjacent liver infiltration initially thought to be left lobe liver abscess., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Zanthoxylum nitidum (Roxb.) DC. is a traditional Chinese medicine characterised by anti-inflammatory and anti-Helicobacter pylori, which is widely used to treat H. pylori-induced gastric disease in China. However, the underlying mechanism related to its anti-H. pylori activity remains unclear. Urease plays a crucial role in the colonisation and survival of H. pylori., Aim of the Study: The root aqueous extract of Z. nitidum against H. pylori urease (HPU) and jack bean urease (JBU) was investigated to illuminate the inhibitory potency, kinetics and potential mechanism., Materials and Methods: Z. nitidum components were determined by UPLC. The enzyme inhibitory effects of Z. nitidum were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. Urease inhibition kinetics were determined by Lineweaver-Burk plots. Sulfhydryl group reagents and Ni 2+ -binding inhibitors were used in the mechanism study. Moreover, the molecular docking technique was used to investigate the binding conformations of the main compounds of Z. nitidum on Urease., Results: According to UPLC results, the major components of Z. nitidum were magnoflorine, sanguinarine, nitidine chloride, chelerythrine, skimmianine and L-Sesamin. Z. nitidum has higher enzyme inhibitory activity on HPU (IC 50  = 1.29 ± 0.10 mg/mL) than on JBU (IC 50  = 2.04 ± 0.27 mg/mL). Enzyme inhibitory kinetic analysis revealed that the type of Z. nitidum inhibition against HPU was a slow-binding and mixed-type, whereas a slow-binding and non-competitive type inhibited JBU. Further mechanism study indicated that the active site of sulfhydryl group might be the target of inhibition by Z. nitidum. The molecular docking study indicated that the above six main components of Z. nitidum exhibited stronger affinity to HPU than to JBU through interacting with the key amino acid residues located on the mobile flap or interacting with the active site Ni 2+ . Results indicated that these components are potential active ingredients directed against urease., Conclusions: Z. nitidum inactivated urease in a concentration-dependent manner through slow-binding inhibition and binding to the urease active site sulfhydryl group. Our investigation might provide experimental evidence for the traditional application of Z. nitidum in the treatment of H. pylori-associated gastric disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg -1 ), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg -1 , respectively) plus indomethacin, and sucralfate (1.71 mL·kg -1 ) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E 2 (PGE 2 ) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg -1 ) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin)., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory and fibrotic condition. The disease is characterized by tissue infiltration with dense lymphoplasmacytes and IgG4-positive plasma cells., Summary: The aim of this study was to provide gastroenterologists with novel insights into evaluating the gastroesophageal involvement with IgG4-RD or mimickers of this condition and to give special attention to clinicopathological features. A literature review was performed using the PubMed database. A total of 39 studies presenting cases in the form of isolated, typical, and nontypical gastroesophageal involvement with IgG4-RD published between 2010 and 2018 were included. These studies were thoroughly reviewed for symptoms, lesion location, lesion type, lesion size, immune-histopathology, associated diseases, treatment, and follow-up. Of the 39 studies reviewed, 9 were esophageal IgG4-RD lesions, isolated esophageal IgG4-RD 66.66% (6/9), a typical form of esophageal IgG4-RD 11.11% (1/9), and nontypical form esophageal IgG4-RD 22.22% (2/9). The 30 gastric IgG4-RD that include isolated gastric IgG4-RD 46.66% (14/30), typical gastric IgG4-RD 40% (12/30), and nontypical gastric IgG4-RD 13.33% (4/30). The majority of lesions were inflammatory tumors, ulceration, nodular lesions, chronic gastritis, and malignant lesions. Key Messages: IgG4-RD may be manifested by isolated, typical and nontypical forms of gastroesophageal lesions and should be taken into consideration in the differential diagnosis. Corticosteroids may be the sole diagnostic treatment for this condition., (© 2019 S. Karger AG, Basel.)

As we approach the end of the antibiotic era, newer therapeutic options, such as antimicrobial peptides (AMPs), are in urgent demand. AMP surface grafting onto biomaterials has been described as a good strategy to overcome problems associated with their in vivo stability. Helicobacter pylori is among the bacteria that pose greatest threat to human health, being MSI-78A one of the few bactericidal AMPs against this bacterium. Here, we report that MSI-78A grafted onto model surfaces (Self-Assembled Monolayers -SAMs), in a concentration of 30.3 ± 1.2 ng/cm 2 determined by quartz crystal microbalance with dissipation (QCM-D), was able to kill, by contact, 98% of planktonic H. pylori in only 2 h. This fact was not verified against the control bacteria (Staphylococcus epidermidis), although the minimal inhibitory concentration (MIC) of MSI-78A in solution is much lower for S. epidermidis (2 μg/mL) than for H. pylori (64 μg/mL). Our results also demonstrated that, in opposite to other bacteria, H. pylori cells were attracted to ethylene glycol terminated (antiadhesive) surfaces, which can explain the high bactericidal potential of grafted MSI-78A. This proof of concept study establishes the foundations for development of MSI-78A grafted nanoparticles for gastric infection management within a targeted nanomedicine concept.

Gut health is the starting place for maintaining the overall health of an animal. Strategies to maintain gut health are, thus, an important part in achieving the goal of improving animal health. A new strategy to do this involves two molecules: the iron transport protein ovotransferrin (IT) and α-tocopheryl polyethylene glycol succinate (TPGS), which result in the novel formulation of ITPGS. These molecules help reduce gut pathogens, while enhancing the absorption and bioavailability of therapeutic drugs, phytomedicines, and nanomedicines. This, in turn, helps to maintain normal health in animals. Maintaining the gastrointestinal tract (GIT) in its normal condition is key for successful absorption and efficacy of any nutrient. A compromised GIT, due to an imbalance (dysbiosis) in the GIT microbiome, can lead to an impaired GI barrier system with impaired absorption and overall health of the animal. The molecules in ITPGS may address the issue of poor absorption by keeping the GI system healthy by maintaining the normal microbiome and improving the absorption of nutrients through multiple mechanisms involving antioxidative, anti-inflammatory, immunomodulatory, and antimicrobial activities. The ITPGS technology can allow the dose of active pharmaceutical or herbal medicine to be significantly reduced in order to attain equal or better efficacy. With complimentary actions between IT and TPGS, ITPGS presents a novel approach to increase the bioavailability of drugs, phytoconstituents, nutrients, and nanomedicines by enhanced transport to the tissues at the site of action, while reducing gut pathogen load. The ITPGS approach appears to be a novel strategy for maintaining the health of animals by manipulation of microbiota.

The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

In this study, protein/polysaccharide core-shell-corona (PP-CSC) nano delivery systems (NDS) were prepared by using bovine serum albumin (BSA) and chitosan (CS). The potential of PP-CSC-NDS for increasing the stability and bio-accessibility of ε-poly-l-lysine (ε-PL) as effective therapy for gastric Helicobacter pylori was investigated. The presence of CS-shell increased the size (223 ± 1.7 nm) of BSA-core as compared to BSA-shell on CS-core (191 ± 2.6 nm). Conversely, encapsulation efficiency of ε-PL was reduced for C(B)NDS [CS-shell on BSA-core] to 73 ± 1% than 82 ± 2% for B(C)NDS [BSA-shell on CS-core] due to cationic nature of ε-PL. Scanning electron microscopy of PP-CSC-NDS displayed smooth and non-flocculated morphology. FTIR analyses verified that the electrostatic interactions, H-bonding, and hydrophobic effects were involved in PP-CSC formation. Zeta analyses revealed that the net charge depends on the corona layer and the encapsulated antimicrobials. Moreover, CS corona improved the antimicrobial potential, controlled release, mucoadhesion and stability of ε-PL loaded C(B)NDS in simulated gastric fluid due to inherent antimicrobial and mucoadhesive properties of CS polymer. In contrast, protein corona improved the penetration into bacterial biofilms for better eradiation of H. pylori. Thus, conjugated nano-systems with selected corona can improve the overall efficacy of antimicrobials to develop effective nano-therapeutics against gastric infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications., Objectives: To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease., Study Design: Prospective, clinical study., Methods: Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 μg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg sucralfate per os BID where drugs were given 1 h prior to feeding and sucralfate given 60 min after omeprazole; allocation was dependent upon centre. Gastroscopy was repeated at 28-35 days. Evaluators of the gastroscopy images were blinded to the treatments the horses received and images were reviewed independently., Results: The most common presenting sign in both treatment groups was poor performance (Overall - 65.1%; M - 60.5% and OS - 75%). Overall healing (P<0.001; OR = 11 [2.8-45]) and improvement (P = 0.006; OR = 11 [1.9-59]) of lesions were associated with resolution of clinical signs. Misoprostol was shown to be superior to combined omeprazole-sucralfate both for healing (M - 72% [95% CI 43-67] and OS - 20% [95% CI 7-41]; P<0.001) and improvement (M - 98% [95% CI 90-100] and OS - 65% [95% CI 43-83]; P<0.001)., Main Limitations: Relatively small, clinical study, reliance on client questionnaire data, clients not blinded to the treatments the horse received, diet could have affected drug pharmacodynamics although mimics clinical practice and no validated scoring system available for glandular lesions., Conclusions: These results suggest that gastric glandular disease does indeed result in clinical signs. In this population of horses, misoprostol was superior to omeprazole and sucralfate and warrants further evaluation in a large scale, multi-centre trial., (© 2019 EVJ Ltd.)

Tuberculosis of the stomach is an extremely rare manifestation of Mycobacterium tuberculosis infection and mimics gastric carcinoma in its presentation. Most of our knowledge about this rare disease comes from case reports and there are only a few case series published on this disease and thus the majority of the part remains uncovered. Diagnosis is made commonly only after a major surgery. Endoscopy and guided biopsy are the diagnostic modality of choice. Surgery is indicated in cases which present with complications. Patients respond well to antituberculous therapy. The authors encountered 4 cases of gastric tuberculosis over 5 years. This study summarises the available literature and gives comprehensive update on this rare disease., (Copyright © 2018 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Helicobacter pylori is a major global pathogen, and its infection represents a key factor in the etiology of various gastric diseases, including gastritis, peptic ulcers, and gastric carcinoma. The efficacy of current standard treatment for H. pylori infection including two broad-spectrum antibiotics is compromised by toxicity toward the gut microbiota and the development of drug resistance, which will likely only be resolved through novel and selective antibacterial strategies. Here, we synthesized a small molecule, zinc linolenate (ZnLla), and investigated its therapeutic potential for the treatment of H. pylori infection. ZnLla showed effective antibacterial activity against standard strains and drug-resistant clinical isolates of H. pylori in vitro with no development of resistance during continuous serial passaging. The mechanisms of ZnLla action against H. pylori involved the disruption of bacterial cell membranes and generation of reactive oxygen species. In mouse models of multidrug-resistant H. pylori infection, ZnLla showed in vivo killing efficacy comparable and superior to the triple therapy approach when use as a monotherapy and a combined therapy with omeprazole, respectively. Moreover, ZnLla treatment induces negligible toxicity against normal tissues and causes minimal effects on both the diversity and composition of the murine gut microbiota. Thus, the high degree of selectivity of ZnLla for H. pylori provides an attractive candidate for novel targeted anti- H. pylori treatment., (Copyright © 2019 American Society for Microbiology.)

Background: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX-LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD., Case Presentation: We describe the case of a 70-year-old woman with MTX-LPD of the stomach and duodenum. Disease regression was temporarily achieved after cessation of MTX treatment; however, it subsequently recurred, and complete response was only achieved after six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) chemotherapy., Conclusions: The first-choice therapy for patients taking MTX who develop suspected MTX-LPD should be the withdrawal of MTX treatment. Even after remission is achieved, patients should be kept under careful observation, and if the disease recurs, chemotherapy should be commenced promptly.

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett's esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.

Aim: This research was conducted to obtain accurate information on the protective effects of Portulaca oleracea L. against hepatogastric diseases., Results: P. oleracea L. (Purslane) has traditionally been used for the treatment of hepatogastric diseases. However, the low number of research studies has shown that P. oleracea L. possesses protective effects against hepatotoxic agents. The safety of P. oleracea L. has been demonstrated in several clinical trials., Conclusion: Modern pharmacological studies have indicated the gastroprotective and hepatoprotective effects of P. oleracea L. by using in vivo and in vitro models. However, due to lack of information of its effects in humans, more studies should be conducted to confirm the efficacy of P. oleracea L. in humans., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

Objectives: This study aimed to evaluate the effects of periodontal therapy on the efficacy of Helicobacter pylori eradication and on the recurrence of infection after eradication., Methods: We conducted a prospective randomized trial on 698 gastric H. pylori-infected patients, of whom 347 received gastric H. pylori treatment alone and 342 received gastric H. pylori treatment plus periodontal therapy. The presence of H. pylori and associated virulence genes were detected by real-time polymerase chain reaction., Results: After eradication of gastric H. pylori infection, the recurrence of gastric H. pylori was significantly lower in the gastric H. pylori treatment plus periodontal therapy group than in the group receiving gastric H. pylori treatment alone (OR 0.67; 95% CI 0.45 to 0.99), whereas the eradication rate was not significantly different (OR 0.87; 95% CI 0.68 to 0.98). There was a close relationship between the presence of H. pylori in saliva and its presence in the stomach., Conclusions: The oral cavity is an important reservoir for gastric H. pylori infection. Adjunctive periodontal therapy could enhance the efficiency of H. pylori treatment and reduce the recurrence of gastric H. pylori infection.

An 81-year-old male presented with loss of appetite, early satiety and iron deficiency anaemia. A computed tomography (CT) scan of the abdomen and pelvis during initial work-up revealed diffuse gastric mural thickening associated with a large ulcer and adjacent gastro-hepatic lymphadenopathy. The CT appearances, together with the clinical features, were highly suspicious for an infiltrative type of gastric malignancy. Endoscopic biopsy however showed erosive inflammation, IgG4 plasmacytosis and fibrosis, raising the possibility of IgG4-related disease. A serologic assay for IgG showed normal IgG4 and elevated IgG2 serum levels. After appropriate steroid treatment, endoscopy and CT scan showed resolution of the ulcer and gastric wall thickening. This case shows yet another possible appearance of gastric involvement in IgG4-related disease on the current evolving spectrum of this disease presentation. Greater awareness and education of this disease would help in patient care, ensuring earlier diagnosis, prevention of severe organ damage and morbidity, as well as unnecessary surgery.

We presented a case with massive hepatic portovenous gas (HPVG) and gastric emphysema, probably due to increased intraluminal pressure in the stomach after bagging and noninvasive ventilation. There are multiple microbubbles in the inferior vena cava, right atrium and right ventricle. There has been only one case report ever published showing the similar features of the "aquarium sign" in the right heart in a patient with intussusception. We believe our case is a good illustration of this extremely rare entity in echocardiography., (© 2018 Wiley Periodicals, Inc.)

To explore the medication regularity of Tibetan medicine in the treatment of spleen and stomach diseases, analyze the potential drug targets and interactions of the prescriptions, and reveal the mechanism of Tibetan medicine in the treatment of spleen and stomach diseases. The prescriptions in Tibetan medicine for treatment of spleen and stomach diseases were collected, and Traditional Chinese Medicine Inheritance Support System (TCMISS) was used to analyze the association rules between the herbs and discover the core herbs and new prescriptions. The integrated pharmacology platform V1.0 software was used to construct "herb-compound-target" network and investigate the interactions between various herbs and related pathways of Tibetan medicine Wuwei Shiliu powder in the treatment of spleen and stomach diseases. Among the 216 prescriptions of Tibetan medicine in the treatment of spleen and stomach diseases, pomegranate seed was used at a highest frequency (118 times), followed by white cardamom (107 times) and comatose (107 times). 12 new prescriptions were evolved by using the association rules (support>=34%, confidence>=0.85). 5 242 related drug targets and 20 related pathways were obtained from classic formula Wuwei Shiliu Powder (FDR<0.01). It was proposed that Tibetan medicine treatment for spleen and stomach diseases was mainly based on proliferation of "stomach fire" and the main drugs were for regulating Qi-flowing for strengthening spleen. The mechanism may be associated with regulation of digestive juice secretion, proton pump, mitochondria, regulation of intestinal digestion and immunity, the body's immunity to microorganisms function and other multiple targets and pathways to achieve the joint intervention., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: The use of medicines to treat common complaints, such as headache, stomachache, difficulty in getting to sleep and nervousness, is widespread among adolescents, and is increasing. The aim of this survey was to estimate the prevalence of recurrent specific complaints among 15-year-old adolescents in Tuscany over three years (2006, 2010 and 2014) and that of medicine use to treat these complaints among boys and girls., Methods: The present study is based on data from the Tuscan HBSC studies at three time points (2006, 2010 and 2014), which involved 2830 adolescents, aged 15 years old (1395 boys and 1435 girls)., Results: Overall, the data confirm that adolescents who suffer from recurrent complaints are more likely to use medicines. The prevalence rates of all complaints were higher in girls than in boys in the three years considered. Over the whole period, headache, stomachache and difficulty in getting to sleep increased in girls, while boys displayed significant decrease in nervousness and stomachache., Conclusion: Our findings underline the fact that the use of medicines in adolescence is a public health concern and constitutes an emerging issue that needs greater attention and investigation on the part of scientific research.

Two cases of a chemical dissolution of gastric phytobezoars are presented. The novel approach of that management is the pharmacological mixture than completely made disappear the bezoars in patients fated to surgery removal.