Effects of Exogenous Hydrogen Sulfide in the Hypothalamic Paraventricular Nucleus on Gastric Function in Rats

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.

Outcomes of endoscopic submucosal dissection for gastroesophageal reflux disease (ESD-G) for medication-refractory gastroesophageal reflux disease: 35 cases underwent ESD-G including 15 cases followed more than 5 years

Background Although some kinds of endoluminal surgery for patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have been reported, there are few reports on their long-term outcomes. In 2014, we reported the effectiveness of endoscopic surgery for PPI-refractory GERD, which we invented and named endoscopic submucosal dissection for GERD (ESD-G) in 2008. Thereafter, we accumulated more cases and monitored the patients’ condition postoperatively and describe the outcomes herein. Patients and methods This single-center, single-arm trial was conducted at the Osaka Medical and Pharmaceutical University Hospital. We compared outcomes between before and 3–6 months after ESD-G. Additionally, we investigated the outcomes of patients 5 or more years after ESD-G. Results We performed 42 ESD-G procedures in 35 patients between 2008 and 2020. In seven patients, ESD-G was performed twice for various reasons. The frequency scale for the symptoms of GERD score was significantly improved 3–6 months after ESD-G (22 → 10, p < 0.0001); the Los Angeles classification for reflux esophagitis was clearly improved after ESD-G (p = 0.0423). The number of reflux episodes was not decreased by ESD-G. There was a significant difference in the potency unit of gastric acid secretion suppressants for controlling GERD-related symptoms between baseline and 3–6 months after ESD-G (p = 0.0009). In patients without a history of distal gastrectomy who underwent ESD-G, the potency unit of gastric acid secretion suppressants significantly decreased 5 or more years after ESD-G (p = 0.0121). Conclusion ESD-G may be effective in patients with refractory GERD-related symptoms without a history of distal gastrectomy.

The potential of pharmacological activities of the multi-compound treatment for GERD: literature review and a network pharmacology-based analysis

The prevalence of gastroesophageal reflux disease (GERD) is rapidly increasing due to the adoption of a Westernized lifestyle; at the same time, safe and efficient treatment is required due to the side effects and refractoriness of proton pump inhibitors (PPIs). The frequently used multi-compound treatment for GERD in the current traditional Korean medicine (TKM) clinical field comprises Crassostrea gigas Thunberg shell (CGTS), Bambusae Caulis in Taeniam (BCT), Ponciri Fructus Immaturus (PFI), Scutellaria baicalensis Georgi (SBG), medicated leaven (ML) and Glycyrrhizae Radix et Rhizoma (GRR). The current review was based on “Kun-Shin-Choa-Sa” theory and network analysis was conducted to explore the potential pharmacological activities, including efficacy and mechanisms of action of multi-compound treatment against GERD. Hypergeometric test results showed that the targets of multi-compound treatment are significantly associated with GERD gene sets, consistent with the literature review findings. In particular, the enrichment analysis indicated that the SBG targets are related to the IL-17 signaling pathway, bile secretion, small-cell lung cancer, and non-small cell lung cancer, corroborating the literature review, particularly concerning anti-inflammatory effect. In the literature review, CGTS and BCT, classified as “Kun,” play a role in anti-acid, anti-inflammatory, and anti-oxidative effects. The complementary “Shin” herbs, PFI and SBG, showed functions related to improving the prolonged gastric emptying rate, peristalsis, and a gastric cytoprotective effect. With the role of “Choa,” ML was suggested to inhibit H. pylori growth and diminish gastric acid secretion, consistent with the gastric acid secretion pathway in the enrichment analysis. However, the enrichment analysis did not show any significantly related pathways for CGTS and PFI, which may reflect the lack of information in the KEGG database in terms of the link between GERD, its mechanisms, and the abundance of minerals in CGTS. Despite the pharmacological potential of multi-compound treatment, this study should be corroborated by well-designed future experimental studies.

Gastric Serotonin Biosynthesis and Its Functional Role in L-Arginine-Induced Gastric Proton Secretion

Among mammals, serotonin is predominantly found in the gastrointestinal tract, where it has been shown to participate in pathway-regulating satiation. For the stomach, vascular serotonin release induced by gastric distension is thought to chiefly contribute to satiation after food intake. However, little information is available on the capability of gastric cells to synthesize, release and respond to serotonin by functional changes of mechanisms regulating gastric acid secretion. We investigated whether human gastric cells are capable of serotonin synthesis and release. First, HGT-1 cells, derived from a human adenocarcinoma of the stomach, and human stomach specimens were immunostained positive for serotonin. In HGT-1 cells, incubation with the tryptophan hydroxylase inhibitor p-chlorophenylalanine reduced the mean serotonin-induced fluorescence signal intensity by 27%. Serotonin release of 147 ± 18%, compared to control HGT-1 cells (set to 100%) was demonstrated after treatment with 30 mM of the satiating amino acid L-Arg. Granisetron, a 5-HT3 receptor antagonist, reduced this L-Arg-induced serotonin release, as well as L-Arg-induced proton secretion. Similarly to the in vitro experiment, human antrum samples released serotonin upon incubation with 10 mM L-Arg. Overall, our data suggest that human parietal cells in culture, as well as from the gastric antrum, synthesize serotonin and release it after treatment with L-Arg via an HTR3-related mechanism. Moreover, we suggest not only gastric distension but also gastric acid secretion to result in peripheral serotonin release.

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.