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.

Adaptive Mechanisms Make Lupin a Choice Crop for Acidic Soils Affected by Aluminum Toxicity

Almost half of the world’s agricultural soils are acidic, and most of them present significant levels of aluminum (Al) contamination, with Al3+ as the prevailing phytotoxic species. Lupin is a protein crop that is considered as an optimal alternative to soybean cultivation in cold climates. Lupins establish symbiosis with certain soil bacteria, collectively known as rhizobia, which are capable of fixing atmospheric nitrogen. Moreover, some lupin species, especially white lupin, form cluster roots, bottlebrush-like structures specialized in the mobilization and uptake of nutrients in poor soils. Cluster roots are also induced by Al toxicity. They exude phenolic compounds and organic acids that chelate Al to form non-phytotoxic complexes in the rhizosphere and inside the root cells, where Al complexes are accumulated in the vacuole. Lupins flourish in highly acidic soils where most crops, including other legumes, are unable to grow. Some lupin response mechanisms to Al toxicity are common to other plants, but lupin presents specific tolerance mechanisms, partly as a result of the formation of cluster roots. Al-induced lupin organic acid secretion differs from P-induced secretion, and organic acid transporters functions differ from those in other legumes. Additionally, symbiotic rhizobia can contribute to Al detoxification. After revising the existing knowledge on lupin distinct Al tolerance mechanisms, we conclude that further research is required to elucidate the specific organic acid secretion and Al accumulation mechanisms in this unique legume, but definitely, white lupin arises as a choice crop for cultivation in Al-rich acidic soils in temperate climate regions.

Regulation of Gastric Acid Secretion of Liriope platyphylla Extract in Gastroesophageal Reflux Disease

Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion.Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2’-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulationResults: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE.Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.

Formulation, Development and Evaluation of Gastroretentive Sustained Release Tablets of Lansoprazole Using Natural Polymer

The goal of this study is to develop a long-acting Lansoprazole delivery system. Lansoprazole belongs to a class of antisecretory drugs known as substituted benzimidazoles, which decrease gastric acid secretion by inhibiting the (H+,K+)-ATPase enzyme system at the secretory membrane of the stomach parietal cell. Due to its mechanism of action, despite its short half-life of 1-5 hours, it can effectively block acid secretion for 24 hours. However, as his plasma concentration falls, the effect will diminish. Lansoprazole will be given as a sustained release tablet to avoid multiple dosing or to reduce the frequency of dose. Lansoprazole was produced and analysed utilizing natural and synthetic polymers such as Xanthan gum, Gellan gum, Carbopol 940 P, and Chitosan. Based on the findings of this experiment, it was determined that formulation F7 demonstrated sustained drug release for up to 12 hours in all developed formulations. Formulation (F1, F2, F3, F4, F5, and F6) were tested in vitro for drug release. For the improved formulation F7, the formulation and release kinetics were estimated. When the regression coefficient values of were evaluated, it was found that Peppas had the highest ‘r2' value, 0.952, indicating that drug release from formulations followed Peppas release kinetics. Key words: Lansoprazole, Sustain release tablets, Synthetic and Natural Polymers, formulation, evaluation

Parameters of blood short-chain peptides and digestive hydrolases in patients with chronic hepatitis B virus infection

The aim of the study was to examine specifics of changes in the level of stomach- and pancreas-released blood hydrolases in chronic viral hepatitis B and analyze the mechanisms underlying such changes. We assessed serum markers of HBV infection, liver enzymes tests as well as gastric and pancreatic hydrolase level. The patients examined were divided into three groups: control (healthy) and two study groups — HBV post-infection and chronic HBV infection. Patients with HBV post-infection had no significant deviations from normal range for blood level of gastric and pancreatic hydrolases. Patients with chronic HBV infection were found to contain increased blood level of amylase and lipase, which may evidence about increasing pancreatic functional activity and development of covert pancreatitis. At the same time, decline in the concentration of serum pepsinogen-1 below 40 μg/l could indicate about prominently decreased secretion of hydrochloric acid and development of atrophic gastritis, and it was found that the major factor contributing to development of such disorders was the short-chain peptide CCK-8, which utilization declines in patients with chronic HBV infection. CCK-8 can play a pivotal role in inhibiting stimulation of gastric acid secretion and controls gastric acid, plasma gastrin and somatostatin secretion. Cholecystokinin has been found to inhibit acid secretion by activating CCK type A receptors as well as via somatostatin-involving mechanism. The secretion of gastric somatostatin-14 increased by fivefold due to CCK-8 alone, but was blocked by the CCK-A receptor blocker loxiglumide. These data show that CCK-8 directly inhibits acid reactions by stimulating the release of gastric somatostatin indirectly through the CCK-A receptor. Thus, it can be assumed that normally CCK-8 is mainly utilized by the liver, which is altered during chronic hepatitis B resulting in elevated blood CCK-8 concentration. As a consequence, it enhances pancreatic secretion resulting in developing pancreatitis that is paralleled with inhibited gastric secretion and emerged atrophic gastritis.

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.