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Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function. Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value. Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05). Conclusion: The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are commonly prescribed medications used to treat stomach acid-related disorders. While they are generally considered safe and effective, recent research has raised concerns about potential risks associated with their use. Studies published in The British Journal of Clinical Pharmacology have highlighted adverse effects such as mortality, type 2 diabetes, hearing loss, and adverse outcomes in patients with chronic kidney disease. However, evidence of these associations remains weak and further evaluation is needed. PPIs should be prescribed at the lowest effective dose and for the shortest duration possible. It is important to use PPIs judiciously and consider the challenges of dose selection and treatment duration. [Extracted from the article]

BackgroundIn previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function.MethodsPhysiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value.ResultsInjecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05).ConclusionThe results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.

Purpose: To develop a whole physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model to describe the pharmacokinetics and anti-gastric acid secretion of omeprazole in CYP2C19 extensive metabolizers (EMs), intermediate metabolizers (IMs), poor metabolizers (PMs) and ultrarapid metabolizers (UMs) following oral or intravenous administration. Methods: A PBPK/PD model was built using Phoenix WinNolin software. Omeprazole was mainly metabolized by CYP2C19 and CYP3A4 and the CYP2C19 polymorphism was incorporated using in vitro data. We described the PD by using a turn-over model with parameter estimates from dogs and the effect of a meal on the acid secretion was also implemented. The model predictions were compared to 53 sets of clinical data. Results: Predictions of omeprazole plasma concentration (72.2%) and 24 h stomach pH after administration (85%) were within 0.5–2.0-fold of the observed values, indicating that the PBPK-PD model was successfully developed. Sensitivity analysis demonstrated that the contributions of the tested factors to the plasma concentration of omeprazole were Vmax,2C19 ≈ Papp > Vmax,3A4 > Kti, and contributions to its pharmacodynamic were Vmax,2C19 > kome > kms > Papp > Vmax,3A4. The simulations showed that while the initial omeprazole dose in UMs, EMs, and IMs increased 7.5-, 3- and 1.25-fold compared to those of PMs, the therapeutic effect was similar. Conclusions: The successful establishment of this PBPK-PD model highlights that pharmacokinetic and pharmacodynamic profiles of drugs can be predicted using preclinical data. The PBPK-PD model also provided a feasible alternative to empirical guidance for the recommended doses of omeprazole. [ABSTRACT FROM AUTHOR]

About half of the world's population is infected with the bacterium Helicobacter pylori. For colonization, the bacterium neutralizes the low gastric pH and recruits immune cells to the stomach. The immune cells secrete cytokines, i.e. , the pro-inflammatory IL-17A, which directly or indirectly damage surface epithelial cells. Since (I) dietary proteins are known to be digested into bitter tasting peptides in the gastric lumen, and (II) bitter tasting compounds have been demonstrated to reduce the release of pro-inflammatory cytokines through functional involvement of bitter taste receptors (TAS2Rs), we hypothesized that the sweet-tasting plant protein thaumatin would be cleaved into anti-inflammatory bitter peptides during gastric digestion. Using immortalized human parietal cells (HGT-1 cells), we demonstrated a bitter taste receptor TAS2R16-dependent reduction of a H. pylori -evoked IL-17A release by up to 89.7 ± 21.9% (p ≤ 0.01). Functional involvement of TAS2R16 was demonstrated by the study of specific antagonists and siRNA knock-down experiments. [Display omitted] • Sweet-tasting thaumatin is cleaved into bitter peptides during gastric digestion. • Bitter peptides stimulate the proton secretion of immortalized human partial cells. • Native proteins of H. pylori induce increased IL-17A release in HGT-1 cells. • Bitter peptides reduce the release of IL-17A induced by H. pylori. • Stimulation of H+ secretion and reduction of IL-17A release are TAS2R16-mediated. [ABSTRACT FROM AUTHOR]

Background: Guidelines for acute upper gastrointestinal bleeding (UGIB) recommend use of proton pump inhibitors (PPI) administered by continuous IV infusion (CI). Although data suggest comparable outcomes with CI and IV push (IVP) dosing post-endoscopy, there are limited data to support IVP PPI as the pre-endoscopy regimen. Objective: To evaluate the impact of a pharmacist-managed protocol for reducing PPI CIs and substitution of PPI IVP dosing in hemodynamically stable patients with suspected acute upper gastrointestinal bleeding (UGIB) prior to endoscopic intervention. Design, Setting, and Participants: Retrospective study; Tertiary-care community teaching hospital; Hemodynamically stable adults with confirmed or suspected UGIB. Hemodynamic stability was defined as a systolic blood pressure >90 mmHg, heart rate <100 beats, mean arterial pressure >65 mmHg, and no requirement for vasopressors. Intervention : All iterations of treatment recommendations encouraged an initial pantoprazole 80 mg IVP dose. In the pre-intervention group, patients were then treated at the at the provider's discretion with the majority receiving CI pantoprazole. After implementation of the original protocol (Phase I), all hemodynamically stable patients were allowed 1 bag of CI pantoprazole (80 mg infused over 10 hours) before being transitioned by the pharmacist to pantoprazole 40 mg IVP every 12 hours. After internal analysis, the protocol was revised to allow patients to be immediately transitioned to IVP dosing without an initial CI (Phase II). Main Outcome: Incidence of continued bleeding or re-bleeding within 7 days of initial PPI dose. Results: A total of 325 patients were included across all 3 study phases. The median number of CI bags per patient was reduced from 4 pre-intervention, to 1.5 in phase I, and to 0 in phase II (P <.001). The primary endpoint of continued bleeding or re-bleeding within 7 days was similar across all 3 groups (5.0% vs 6.5% vs 5.2%, P =.92). Mean intravenous pantoprazole costs were reduced by $21.73/patient. Conclusions: Movement toward preferential use of IVP PPI prior to endoscopy for hemodynamically stable patients with confirmed or suspected UGIBs resulted in similar rates of continued bleeding or re-bleeding and generated modest cost savings. These findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract The association of Helicobacter pylori with chronic duodenal ulceration was a seminal observation in the short history of gastroenterology. However, H. pylori is now known to be an ancient bacterium, whereas there is persuasive evidence that the epidemic of duodenal ulceration began in the second half of the 19th century and continued into the second half of the 20th century. Possible explanations for the epidemic include genomic changes in the organism and environmental or other influences on the human host. While genomic changes resulted in the appearance of virulence factors, these seem likely to have appeared thousands of years ago with minimal effects on gastritis because of coexisting suppression of gastric immunity. In contrast, the emergence of duodenal ulceration is best explained by a change in the pattern of gastritis from inflammation involving the antrum and body in most individuals to a significant minority (10–20%) with antral gastritis but with relative sparing of the body of the stomach. In the latter group, the increase in serum gastrin (particularly G17) associated with antral gastritis had trophic effects on gastric parietal cells with an increase in the parietal cell mass and hypersecretion of gastric acid. Hypersecretion of acid is seen as the major risk factor for duodenal ulceration with significant contributions from environmental factors including smoking and use of nonsteroidal, anti‐inflammatory drugs. Host factors favoring changes in the pattern of gastritis include delayed acquisition of infection and improved nutrition; both with enhancing effects on mucosal immunity.

Inflammatory bowel disease (IBD) constitutes an important clinically significant condition that results in morbidity and mortality. IBD can be generally classified into either ulcerative colitis (UC) or Crohn's disease (CD) that differs in the clinical and histopathology. The role of neuropeptides in the pathogenesis of these conditions is becoming increasingly recognized for their importance in modulating the inflammatory state. Animal models provide the greatest insight to better understand the pathophysiology of both disorders which will hopefully allow for improved treatment strategies. This review will provide a better understanding of the role of murine models for studying colitis.

OPINION STATEMENT:Hypersecretory conditions affecting the stomach account for significant morbidity and mortality manifested in some cases with peptic ulcer, gastrointestinal hemorrhage, and/or gastroesophageal reflux disease (GERD). The diagnosis of gastric acid hypersecretory states can be challenging and relies on the use of quantitative assays to measure gastric acid secretion and serum gastrin. The most common etiology for hypergastrinemia is the use of potent gastric acid inhibitors such as the proton pump inhibitors. The differential diagnosis of this condition is of critical importance, and will dictate management decisions. Conditions such as atrophic gastritis are relatively benign and can lead to hypergastrinemia without the presence of gastric acid hypersecretion. Zollinger-Ellison syndrome, on the other hand, causes hypergastrinemia with profound gastric acid hypersecretion [1]. More common causes of hypergastrinemia include gastric outlet obstruction, ileus, and chronic renal failure [2]. In most cases, proton pump inhibitors will be used to manage these conditions. In some instances, surgical therapy may be required. This chapter will review the important clinical causes of gastric acid hypersecretion and provide insights to the best medical management options to better care for patients with these disorders.

Background: Hydrogen sulfide (H2S) is a new type of gas neurotransmitter discovered in recent years. It plays an important role in various physiological activities. The hypothalamus paraventricular nucleus (PVN) is an important nucleus that regulates gastric function. This study aimed to clarify the role of H2S in the paraventricular nucleus of the hypothalamus on the gastric function of rats. Methods: An immunofluorescence histochemistry double-labelling technique was used to determine whether cystathionine-beta-synthase (CBS) and c-Fos neurons are involved in PVN stress. Through microinjection of different concentrations of NaHS, physiological saline (PS), D-2-Amino-5-phosphonovaleric acid (D-AP5), and pyrrolidine dithiocarbamate (PDTC), we observed gastric motility and gastric acid secretion. Results: c-Fos and CBS co-expressed the most positive neurons after 1 h of restraint and immersion, followed by 3 h, and the least was at 0 h. After injection of different concentrations of NaHS into the PVN, gastric motility and gastric acid secretion in rats were significantly inhibited and promoted, respectively (p < 0.01); however, injection of normal saline, D-AP5, and PDTC did not cause any significant change (p > 0.05). The suppressive effect of NaHS on gastrointestinal motility and the promotional effect of NaHS on gastric acid secretion could be prevented by D-AP5, a specific N-methyl-D-aspartic acid (NMDA) receptor antagonist, and PDTC, an NF- κ B inhibitor. Conclusion: There are neurons co-expressing CBS and c-Fos in the PVN, and the injection of NaHS into the PVN can inhibit gastric motility and promote gastric acid secretion in rats. This effect may be mediated by NMDA receptors and the NF- κ B signalling pathway. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide. Methods: Dyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale. Results: Of the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046). Conclusion: Although acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hypersecretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable. [ABSTRACT FROM AUTHOR]

Ya-hom, a Thai traditional medicine, is used as a treatment for gastric discomfort. We previously found that Ya-hom inhibits both histamine and carbachol-stimulated acid secretion in gastric fistula rats. Herein, we used isolated gastric glands and highly enriched parietal cells from rabbit to determine whether or not Ya-hom acts directly on the acid-secreting parietal cell. Ya-hom inhibited carbachol-stimulated [14C] aminopyrine (AP) accumulation in rabbit gastric glands and prevented carbachol-induced elevation of [Ca2+]i in parietal cells. In contrast, Ya-hom potentiated histamine-stimulated AP accumulation and increased the stimulatory effect of the specific adenylyl cyclase activator, forskolin, in the presence of the histamine H2 receptor antagonist, cimetidine. Ya-hom had no effect on downstream cAMP-dependent signaling events including phosphorylation of LASP1 (LIM and SH3 domain protein 1), and F-actin redistribution. Because the cholinergic signaling pathway is mediated via calcium-dependent mechanisms, we compared effects of Ya-hom on carbachol-induced elevation of [Ca2+]i with those of thapsigargin, a specific endoplasmic reticulum Ca2+ pump inhibitor that also potentiates histamine-stimulated AP accumulation. Both agents similarly potentiated histamine-stimulated AP accumulation and their actions were not additive. Furthermore, Ya-hom inhibited thapsigargin-induced elevation of [Ca2+]i. Based on these findings, we postulate that Ya-hom induces a slow release of calcium from intracellular stores thereby suppressing the cholinergic response and potentiating the cAMP signaling pathway linked to the histamine response. Since Ya-hom directly inhibits the stimulatory effect of carbachol on acid secretion, the gastric action of this herbal remedy may target vagally-dependent HCl secretion. [ABSTRACT FROM AUTHOR]

Background: Hydrogen sulfide (H2S) is a new type of gas neurotransmitter discovered in recent years. It plays an important role in various physiological activities. The hypothalamus paraventricular nucleus (PVN) is an important nucleus that regulates gastric function. This study aimed to clarify the role of H2S in the paraventricular nucleus of the hypothalamus on the gastric function of rats.Methods: An immunofluorescence histochemistry double-labelling technique was used to determine whether cystathionine-beta-synthase (CBS) and c-Fos neurons are involved in PVN stress. Through microinjection of different concentrations of NaHS, physiological saline (PS), D-2-Amino-5-phosphonovaleric acid (D-AP5), and pyrrolidine dithiocarbamate (PDTC), we observed gastric motility and gastric acid secretion.Results: c-Fos and CBS co-expressed the most positive neurons after 1 h of restraint and immersion, followed by 3 h, and the least was at 0 h. After injection of different concentrations of NaHS into the PVN, gastric motility and gastric acid secretion in rats were significantly inhibited and promoted, respectively (p < 0.01); however, injection of normal saline, D-AP5, and PDTC did not cause any significant change (p > 0.05). The suppressive effect of NaHS on gastrointestinal motility and the promotional effect of NaHS on gastric acid secretion could be prevented by D-AP5, a specific N-methyl-D-aspartic acid (NMDA) receptor antagonist, and PDTC, an NF-κB inhibitor.Conclusion: There are neurons co-expressing CBS and c-Fos in the PVN, and the injection of NaHS into the PVN can inhibit gastric motility and promote gastric acid secretion in rats. This effect may be mediated by NMDA receptors and the NF-κB signalling pathway.

Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H 2 S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H 2 S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H 2 S, resulting in the regulation of gastric function., Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value., Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats ( p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes ( p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats ( p < 0.01), but is eliminated by injection D-AP5 ( p > 0.05)., Conclusion: The results indicate that both exogenous L-Glu and H 2 S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H 2 S pathway that regulates gastric function., 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., (Copyright © 2024 Sun, Li, Shi, Wang, Li, Fan, Yu, Ji, Gao, Hou and Li.)

The association of Helicobacter pylori with chronic duodenal ulceration was a seminal observation in the short history of gastroenterology. However, H. pylori is now known to be an ancient bacterium, whereas there is persuasive evidence that the epidemic of duodenal ulceration began in the second half of the 19th century and continued into the second half of the 20th century. Possible explanations for the epidemic include genomic changes in the organism and environmental or other influences on the human host. While genomic changes resulted in the appearance of virulence factors, these seem likely to have appeared thousands of years ago with minimal effects on gastritis because of coexisting suppression of gastric immunity. In contrast, the emergence of duodenal ulceration is best explained by a change in the pattern of gastritis from inflammation involving the antrum and body in most individuals to a significant minority (10–20%) with antral gastritis but with relative sparing of the body of the stomach. In the latter group, the increase in serum gastrin (particularly G17) associated with antral gastritis had trophic effects on gastric parietal cells with an increase in the parietal cell mass and hypersecretion of gastric acid. Hypersecretion of acid is seen as the major risk factor for duodenal ulceration with significant contributions from environmental factors including smoking and use of nonsteroidal, anti‐inflammatory drugs. Host factors favoring changes in the pattern of gastritis include delayed acquisition of infection and improved nutrition; both with enhancing effects on mucosal immunity. [ABSTRACT FROM AUTHOR]

Background: Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. Methods: Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. Results: Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3] mEq/10 min vs. 1.4 [2.0] mEq/10 min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40–3.5). Conclusions: This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion.

Hydrogen sulfide (H2S) is a neuromodulator in the central nervous system. The physiological function of H2S in the nucleus tractus solitarii (NTS) has rarely been reported. This research aimed to explore the role of H2S in regulating gastric functions. Wistar rats were randomly assigned to sodium hydrosulfide (NaHS; 4 and 8 nmol) groups, physiological saline (PS) group, capsazepine (10 pmol) + NaHS (4 nmol) group, L703606 (4 nmol) + NaHS (4 nmol) group, and pyrrolidine dithiocarbamate (4 nmol) + NaHS (4 nmol) group. The pH values of gastric acid were measured using a pH meter pre- and post-injection. It was found that the microinjetion of NaHS (4 and 8 nmol), an exogenous H2S donor, into the NTS (n = 6) remarkably decreased the pH values of gastric juice. The inductive effect of NaHS on gastric juice production could be suppressed by capsazepine (a transient receptor potential vanilloid 1 antagonist), L703606 (a NK1 receptor antagonist) and pyrrolidine dithiocarbamate (a nuclear fator-kB inhibitor). However, the same amount of PS did not induce any significant change in the pH value of gastric acid (P > 0.05). The findings of this study revealed that NaHS within the NTS remarkably promoted gastric acid secretion via the activation of TRPV1 channels and nuclear factor-γB-dependent mechanism in rats. [ABSTRACT FROM AUTHOR]

Objective(s): Transforming growth factor alpha (TGF-α) has been shown to modulate the gastric acid secretion. Therefore, the aim of the present study was to investigate the effect of sodium hydrosulfide (NaHS) on TGF-α expression in gastric mucosa in rats. Materials and Methods: Eighteen rats were randomly divided into 3 groups (6 per group). To determine the effect of NaHS on gene and protein expression of TGF-α in gastric mucosa in response to gastric acid, the acid output induced by gastric distension. At the end of experiment, rats were euthanized by anesthetics, and gastric effluents, in addition to mucosa were collected to measure the pH of gastric effluents and to quantify protein and gene expression of TGF-α. Results: The stimulated gastric acid upregulated expression levels of TGF-α in gastric mucosa. These levels were higher in animals pretreated with NaHS. Conclusion: TGF-α upregulatory effect of sodium hydrosulfate implied that TGF-α is involved in the acid inhibitory effect of NaHS.

Several studies have confirmed that thyroid hormones influence acid secretion particularly in mammals, but little attention is given to the influence of thyroid hormone on gastric acid secretion in amphibians. In this study, the basal and stimulated gastric acid secretions in carbimazole and thyroxinetreated common Africa toads were compared with controls. Thirty toads (100- 120g b.w) were divided into three groups of ten toads each; Group “A” the control, Group “B” the hypothyroid group given carbimazole (5mg/250g b.w) and Group “C” the hyperthyroid group treated with thyroxine (5μg/100g b.w) treatments were carried out for 35 days by daily oral administration. Serum T3, T4 and TSH levels confirmed the thyroid status of the toads. The mean Basal Gastric Acid (GAS) secretion in the control toads was significantly (p<0.05) higher than that of the carbimazole treated group, while the basal GAS of the thyroxine treated group was significantly (p<0.05) increased compared to the control. Administration of histamine intramuscularly increased significantly (p<0.05) the basal GAS of hyperthyroid toads, and the increment is higher than the GAS in control animals and in carbimazole treated toads. The parietal cells counts were significantly (p<0.05) higher in thyroxine treatment and lowered in carbimazole treated toads compared with control animals. In conclusion, increased thyroid hormone is associated with a rise in the basal secretion of gastric acid which is associated with increased histaminergic and zymogenic cell activities. [ABSTRACT FROM AUTHOR]

Abstract Objective Abnormal gastric acid secretion and gastric dyskinesia are common gastroenterological ailments. Our study aims to investigate the effect of orexin-A in the paraventricular nucleus (PVN) gastric motility and gastric acid secretion. Methods The source of orexin-A neuronal projections to the PVN were explored by retrograde tracing and fluorescence immunohistochemistry experiments. Neuronal discharge recordings of single cells were taken within the PVN. Gastric motility was recorded using a force transducer implanted into the stomach, and gastric acid secretion measured through a pyloric catheter. Results Orexin-A-positive neuronal projections from LHA to PVN were found. Administration of orexin-A to PVN activated the firing of 63.2% NPY-excited/GD-excitatory (GD-E) neurons but suppressed the firing of 55.9% NPY-inhibited/GD-inhibitory (GD-I) neurons, promoted gastric motility and gastric acid secretion in a dose-dependent manner. Responses produced by orexin-A could be partially blocked by Y 1 receptor antagonist GR-231118; Electrical stimulation to the the hypothalamic lateral area (LHA) altered NPY-sensitive/GD neuronal activity in the PVN, stimulated gastric motility and gastric acid secretion. Additionally, these effects induced by LHA electrical stimulation were blocked by administration of the OX1R antagonist SB-334867 to the PVN. Conclusion Orexin-A from LHA neurons act on the PVN to enhance gastric motility and gastric acid secretion, with Y 1 receptor signaling playing a critical role. Highlights • A portion of the LHA orexin-A- immunopositive neurons in the LHA may project their axons directly to the PVN. • The PVN orexin-A signaling promotes gastric acid secretion and gastric motility mainly through the activation Y 1 receptor. • The LHA may participate in orexin's stimulatory effect on gastric motility and gastric acid secretion. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and aim: It is well established that the rate of gastric lesions increases in diabetic rats. Recently, the protective effect of hydrogen sulfide (H2S) in gastric mucosa has been proven. This study aimed to determine the release of H2S and mRNA expression of cystathionine gamma lyase (CSE) in gastric mucosa in alloxan-diabetic rats in response to distention-induced gastric acid secretion. Twenty-four rats were randomly assigned to 4 groups (6 in each). They were the normal-control, distention-control, diabetic-control, and distention-diabetic groups. Under anesthesia, animals underwent a tracheotomy and midline laparotomy. To washout the gastric contents, a catheter was inserted in the stomach through the duodenum. To determine the effect of distention-induced gastric acid secretion on H2S release and mRNA expression of CSE, the stomachs were distended by normal saline. At the end of experiments, animals were sacrificed and the gastric mucosa was collected to determine H2S concentration and to quantify mRNA expression of CSE by quantitative real-time PCR. Mucosal release of H2S and mRNA expression of CSE significantly increased in response to stimulated gastric acid secretion in normal rats (P

Objective: The aim of this study was to investigate the effects of nesfatin-1 on gastric motility and gastric acid secretion and the role of nesfatin-1 neural pathway in the arcuate nucleus (ARC) -the lateral hypothalamic area (LHA) in this process. Methods: The retrograde tracing and immunohistochemical staining was used to observe the projection of nesfatin-1 nerve fibers. The effect of nesfatin-1 or electric stimulation of the Arc on the amplitude and frequency of gastric contraction was observed by Gastric motility recording in vivo. Pylorus ligation was used to measure gastric secretion volume and acid output. Results: Administration of nesfatin-1 into LHA could inhibite gastric motility and gastric acid secretion, however pretreatment with PMC-3881-PI could attenuate the inhibitory effect of nesfatin-1 on gastric motility and gastric acid secretion. Electrical stimulation of Arc promoted the gastric motility and gastric secretion Nesfatin-1 antibody or PMC-3881-PI had no significant effect on Arc stimulation-induced gastric motility, but was able to alter Arc stimulation-induced gastric acid secretion. Conclusion: The nesfafin-1 pathway between ARC-LHA regulates gastric motility and gastric acid secretion in rats, and melanin-concentrating hormone is also involved in regulating this process. [ABSTRACT FROM AUTHOR]

The gastric acidity acts as a barrier against microorganisms entering the stomach, facilitates the digestion of proteins, the absorption of non-heme iron, calcium and vitamin B12. The fundic and corporeal glands have parietal cells, which excrete protons in the gastric lumen via a specific pump. Acid secretion is finely regulated by various paracrine, hormonal and neuroendocrine mechanisms. The main stimulants of acid secretion are histamine, gastrin and acetylcholine. The main inhibitor is somatostatin. An imbalance in the regulation of acid secretion and/or protective mechanisms is responsible for ulcerative pathology. Helicobacter pylori is responsible for the occurrence of duodenal ulcers by increasing gastric acid secretion. PPIs, after cimetidine, have revolutionized the management of pathologies related to hyperacidity. They have an excellent safety prof ile, but their clinical use is imperfect, both in terms of indications and prescriptions. [ABSTRACT FROM AUTHOR]

Myricetin (3,3’,4’,5,5’,7-hexahydroxyflavone), a major flavonoid in berries and red wine, has been recently used as a health food supplement based on its antioxidant and antitumor properties. We report here that myricetin preferentially exerts inhibitory effects on gastric H + , K + -ATPase. Myricetin inhibited H + , K + -ATPase with a sub-micromolar IC 50 value in an enzyme assay using freeze-dried tubulovesicles prepared from hog stomach. Na + , K + -ATPase and Ca 2+ -ATPase were also inhibited by myricetin in a dose-dependent manner, but the IC 50 values for these enzymes were approximately an order of magnitude higher compared to the H + , K + -ATPase. In structure-inhibitory functional analysis of sixteen myricetin derivatives, several phenolic hydroxy groups attached to the flavonoid backbone were highlighted as essential modifications for the inhibition of P 2 -type ATPases. Furthermore, oral administration of myricetin significantly attenuated histamine-induced gastric acid secretion in an in vivo mouse assessment. Therefore, myricetin derivatives seem to be useful seed compounds for developing new drugs and supplements to alleviate gastric acid secretion. [ABSTRACT FROM AUTHOR]

Introduction: The incidence rate of gastric erosions and ulcers in diabetic patients are higher due to failure of mucosal antioxidant defense and maintain enough blood flow. The present study evaluated the gastro-protective effect of sodium hydrosulfide (NaHS) against indomethacin-induced gastric lesions in diabetic rats. Methods: In order to test anti-ulcer activity of NaHS against indomethacin, four diabetic groups of rats including diabetic control and 3 NaHS-treated groups received a single dose of physiologic saline or NaHS at 320, 640 and 1280 μg/kg respectively, 30 min before ulcer induction by indomethacin. Five hours later, the animals were killed and their stomachs were removed for macroscopically and microscopically evaluations. In order to evaluate the antacid effect of NaHS, 4 groups of diabetic rats received physiologic saline or NaHS at 320, 640 and 1280 μg/kg and 30 min later anesthetized, underwent a midline laparotomy and then their pylorus ligated. Five hours later, the animals were killed, their stomachs were removed and pH of gastric effluents were measured. Results: Indomethacin induced gastric lesions in glandular part of the stomach. NaHS at 640 and 1280 μg/kg significantly decreased the indomethacin-induced gastric lesions in diabetic rats. The pH of gastric effluents and mucus content increased by NaHS at doses of 640 and 1280 μg/kg. Macroscopic and microscopic observations showed that mucosal erosions induced by indomethacin were significantly inhibited by NaHS. Conclusion: results suggest NaHS through decreasing the rate of gastric acid output and increasing the mucus production, protected the gastric mucosa against indomethacin-induced gastric lesions in diabetic rats. [ABSTRACT FROM AUTHOR]

Objective(s): Transforming growth factor alpha (TGF-a) has been shown to modulate the gastric acid secretion. Therefore, the aim of the present study was to investigate the effect of sodium hydrosulfide (NaHS) on TGF-a expression in gastric mucosa in rats. Materials and Methods: Eighteen rats were randomly divided into 3 groups (6 per group). To determine the effect of NaHS on gene and protein expression of TGF-α in gastric mucosa in response to gastric acid, the acid output induced by gastric distension. At the end of experiment, rats were euthanized by anesthetics, and gastric effluents, in addition to mucosa were collected to measure the pH of gastric effluents and to quantify protein and gene expression of TGF-α. Results: The stimulated gastric acid upregulated expression levels of TGF-α in gastric mucosa. These levels were higher in animals pretreated with NaHS. Conclusion: TGF-α upregulatory effect of sodium hydrosulfate implied that TGF-α is involved in the acid inhibitory effect of NaHS. [ABSTRACT FROM AUTHOR]

Moringa oleifera Lam is a plant used extensively both in traditional and orthodox medicine to treat myriad ailments, including gastrointestinal disorders. This study was carried out to investigate the effect of leaf extract of M. oleifera some gastrointestinal function parameters in high salt loaded rats. Acute toxicity study was done using 70 male white mice (18-20 g) were used for the study. They were randomly selected and assigned to 7 cages of 10 animals per cage. Percentage mortalities were converted to probits and plotted against the log10 of the dose of the extract from which the LD50 value was calculated. Fresh leaf extract of M. oleifera was Soxhlet extracted. 24 albino Wistar rats were randomly assigned into 4 main groups of 6 rats each. Fed on normal rat chow, high salt (8% NaCl) diet + 1% NaCl drinking water and/or M. oleifera extract (600 mg/kg bw). The feeding regimens lasted for 42 days. Results obtained revealed that the extract had an LD50 value of 1,872.22 mg/kg from which a test dose of 600 mg/kg was derived for the feeding regimen. The salt fed rats had significantly (p

Objective: Gut–brain axis (GBA) is very important in creation and modulation of gastrointestinal problems. Aloe vera gel has gastroprotective properties. The purpose of this study was to evaluate the effect of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid gastric ulcer induction. Materials and Methods: Gastric ulcer was induced by injection of 20% acetic acid into the subserosal layer in male rats. Rats were randomly assigned into three groups: intact group, gastric ulcer group and Aloe vera group (treatment with Aloe vera following gastric ulcer induction). The acid levels and brain and intestinal water content of each sample were measured eight days after the gastric ulcer induction. Results: Gastric acid levels were significantly decreased in Aloe vera group when compared with gastric ulcer group (p