Although our present knowledge of the etiology of peptic ulcer is incomplete, the presence or absence of peptic ulcer is determined by the delicate interplay between aggressive factors (secreted gastric acid and pepsin) and defensive factors (mucosal resistance). Peptic ulcer is produced when the aggressive effects of acid-pepsin dominate the protective effects of gastric or duodenal mucosal resistance by predominance of aggressive factors or interruption of defensive factors. KU-54 enhances mucosal resistance to tissue injury by the increase of gastric mucosal blood flow, the stimulation of gastric mucosal metabolism, the increase of glycoprotein of gastric mucus, and the increase of ATP of gastric mucosa. We have treated 38 cases of gastric ulcers with KU-54 300 mg daily for 4-12 weeks for the evaluation of the therapeutic efficacy. Endoscopic, clinical, and laboratory assessments were undergone before and after 4 ~ 12 weeks of the treatment. Major symptoms of gastric ulcer have been improved in 83.3% after the medication with KU-54. The healing rate of gastric ulcer evaluated by endoscopy was observed in 33.3% after 4 weeks, 73.3% after 8 weeks, 76.6% after 12 weeks of the medication with KU-54. The utility rate of KU-54 was 86.7%. We could conclude that KU-54 is the utilizable drug for gastric ulcer.
Adenosine Triphosphate ; Endoscopy ; Gastric Acid ; Gastric Mucosa ; Glycoproteins ; Metabolism ; Mucus ; Peptic Ulcer ; Stomach Ulcer*

AIMTo demonstrate the protective effect of nitric oxide (NO) on gastric mucosa and its relationship to the acid secretion of parietal cells under stress in rats.

METHODSWater immersion-restraint stress (WRS) model in SD rats was performed. The gastric mucosal ulcer index (UI), NO contents in gastric mucosa and H+, K(+) -ATPase activity of parietal cells were measured. The effects of N(G)-nitro-L-arginine methyl ester(L-NAME) and L-arginine (L-Arg) on the H+, K(+)-ATPase activity of parietal cells and stress-induced gastric mucosal lesion were observed.

RESULTSL-NAME pretreatment decreased NO contents in gastric mucosa, activated H+, K(+) -ATPase activity of parietal cells and aggravated gastric mucosal lesion, whereas L-Arg pretreatment increased NO contents, inhibited H+, K(+) -ATPase activity and significantly ameliorated stress-induced gastric mucosal lesion.

CONCLUSIONEndogenous nitric oxide plays an important role in protecting gastric mucosa from stress-induced lesion by inhibiting H+, K(+) -ATPase activity of parietal cells.

Animals ; Arginine ; metabolism ; Gastric Acid ; secretion ; Gastric Mucosa ; metabolism ; H(+)-K(+)-Exchanging ATPase ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress ; Parietal Cells, Gastric ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; metabolism ; pathology ; Stress, Physiological

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

AIM AND METHODSBy hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent fibers, the roles of capsaicin-sensitive afferent fibers and endogenous NO in the gastric acid secretion and hyperemic response to intragastric distention were studied in rats.

RESULTS(1) There was an increase in acid secretion associated with the increase in GMBF to intragastric distention. (2) Pretreatment with a high dose of capsaicin to ablate afferent fibers completely abolished the GMBF and partially inhibited the acid secretion during the intragastric distention. (3) The increase in GMBF to intragastric distention was completely blocked by pretreatment with L-NAME, whereas the acid secretion was significantly attenuated.

CONCLUSIONCapsaicin-sensitive afferent fibers and endogenous NO are involved in the increases of gastric acid secretion and GMBF.

Animals ; Capsaicin ; pharmacology ; Gastric Acid ; secretion ; Gastric Dilatation ; metabolism ; Gastric Juice ; secretion ; Gastric Mucosa ; blood supply ; Male ; NG-Nitroarginine Methyl Ester ; Neurons, Afferent ; drug effects ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley

omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer.
Adult ; Aged ; Arachidonic Acid/metabolism ; Fatty Acids/metabolism* ; Female ; Gastric Mucosa/metabolism* ; Human ; Male ; Middle Age ; Phospholipids/metabolism ; Stomach Neoplasms/metabolism*

BACKGROUND/AIMS: This study was designed to investigate the role of gastric acid in the extent of H. pylori-induced gastritis. METHODS: Twenty eight mice were innoculated with live H. pylori. They were allocated into four groups. Mice in group I received no treatment, group II mice were treated with sham injection, group III received 125microgram/kg body weight of pentagastrin, while group IV received 250microgram/kg body weight of pentagastrin subcutaneously three times a week. After 7 months, the mucosal pH, H. pylori density, neutrophils and monocytes infiltration, and the degree of atrophy were assessed in the stomach. RESULTS: In the gastric body, the densities of H. pylori were not different among groups. The degree of neutrophil infiltration was significantly lower in group IV compared to other groups (p<0.05). The degree of monocyte infiltration was also significantly lower in group IV than group III (p<0.05). In the gastric antrum, there was no significant difference of the H. pylori density, neutrophil and monocyte infiltration, and degree of atrophy among the groups. The mice with the gastric mucosal pH lower than mean of 3.2 had significant lower level of H. pylori density (1.4 vs. 2.4, p=0.04), and infiltration of neutrophils (0.9 vs. 2.3, p=0.018), and monocytes (1.2 vs. 1.8; p=0.011) than the those with mucosal pH above 3.2 in the body of stomach. CONCLUSIONS: Gastric acid plays a role in suppressing the proximal propagation of H. pylori-induced gastritis to the body of stomach.
Animals ; Female ; Gastric Acid/*metabolism ; Gastric Mucosa/pathology ; Gastritis/immunology/*microbiology ; Helicobacter Infections/*immunology/microbiology ; *Helicobacter pylori/isolation & purification ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred C57BL ; Models, Animal

OBJECTIVETo study the mechanism of Tongjiang granule on treating GERD.

METHODThe rats in the model group received steel wire ring-cardiamyopexy. A steel wire ring was fixed firmly on cardia. The rats in the control group underwent the cardia-plasty plus pylori ligation plus stomach-empty intestine Roux-en-Y anastomosis. The rats were divided into six groups after operations at random, which were fed up respectively with Tongjiang granule of different dosage and perpulsid. No treatment groups were taken as control.

RESULTThe experiment showed that Tongjiang granule could lighten or cure RE in the pathology, decrease the hydrochloric acid in gastric juice, in the meantime, increase the motilin in the animal blood. This study indicated that the effect of Tongjiang granule group from experimental research was better than that of the control group (perpulsid).

CONCLUSIONThe effects of Tongjiang granule on treating GERD can be achieved by decreasing the hydrochloric acid in gastric juice, increasing the motilin in blood and promoting the gastric impetus in the animal experiment.

Animals ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Esophagitis, Peptic ; drug therapy ; physiopathology ; Esophagus ; pathology ; Female ; Gastric Acid ; metabolism ; Gastric Emptying ; drug effects ; Hydrochloric Acid ; metabolism ; Male ; Motilin ; blood ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.
Adhesiveness ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Gastric Mucins ; metabolism ; Lactic Acid ; chemistry ; metabolism ; Nanoparticles ; Plant Lectins ; chemistry ; metabolism ; Polyglycolic Acid ; chemistry ; metabolism ; Protein Binding ; Wheat Germ Agglutinins ; chemistry ; metabolism

To prepare and evaluate in vitro the 20 (S) -Protopanaxadiol (Ppd) pharmacosome. The Ppd pharmacosome was successfully prepared by thin film-dispersion and its stability in vitro was studied. The particle size of pharmacosome was evaluated by dynamic scattering (DLS) and the encapsulation efficiency was determined by using centrifugal ultra-filtration. The encapsulation efficiency of Ppd pharmacosome was (80.84 +/- 0.53)% with the diameter of 100. 1 nm; While the encapsulation efficiency of Ppd pharmacosome that added Brij 78 added was (72.76 +/- 0.63)% with the diameter of 117. 3 nm. In addition, the effect of some factors on the encapsulation efficiency and the particles size, such as temperature, alcohol, pH and artificial gastrointestinal fluids, were investigated respectively. The selected formulation and technology are simple and practical to prepare Ppd pharmacosome and preparation properties are more stable.
Chemistry, Pharmaceutical ; Drug Stability ; Ethanol ; chemistry ; Gastric Acid ; metabolism ; Hydrogen-Ion Concentration ; Light ; Particle Size ; Sapogenins ; chemistry ; metabolism ; Scattering, Radiation ; Temperature

BACKGROUND/AIMS: Data from previous studies on gastric acid secretion and the prevalence of H. pylori in liver cirrhosis patients remain poorly defined. H. pylori is a potential source of NH3, but the possible role of H. pylori in hepatic encephalopathy is not clear. The purpose of this study was to compare gastric acid secretion, the impact of H. pylori infection, and the production of NH3 between cirrhotic patients and healthy, matched controls. METHODS: Twenty-nine patients with liver cirrhosis (HBV, n=12; Alcohol, n=12; HCV, n=5) were matched with 33 healthy persons for age and sex. None of the patients or controls were being treated with antacids, H2-receptor blockers or proton pump inhibitors. The pH and NH3 concentration was measured in gastric juice obtained by endoscopy. H. pylori infection was diagnosed using the rapid urease test. The level of NH3 in venous blood was also measured. RESULTS: The average gastric pH was significantly higher in cirrhosis patients compared to controls (3.91 vs. 2.99, P<0.05). In addition, the prevalence of hypochlorhydria (defined as pH>4) was significantly greater in cirrhosis patients (45 vs. 21%, P<0.05). In contrast, the prevalence of H. pylori infection (62% vs. 58%) and gastric NH3 concentrations (3.4 vs. 3.3 mM/L) were similar between both groups. However, venous NH3 levels were significantly higher in cirrhotics than in controls (63.1 vs. 25.2 micro M/L, P<0.05). The patients with H. pylori infection had significantly higher gastric NH3 concentration (3.8 vs. 1.6 mM/L) and gastric pH (3.87 vs. 2.76, P<0.05) than those without infection, but no significant difference in venous NH3 levels were detected (39.6 vs. 48.1 micro M/L). In patients with cirrhosis, the presence of H. pylori infection was not correlated with either gastric or blood NH3 levels. CONCLUSIONS: The gastric pH of liver cirrhosis patients is higher than that of controls and a larger proportion of cirrhotic patients have hypochlorhydria. The prevalence of H. pylori in liver cirrhosis patients was similar to that in controls and no correlation was found between gastric and blood NH3 levels. Thus, H. pylori infection does not seem to play a major role in generation of elevated NH3 associated with hepatic encephalopathy.
Achlorhydria/complications ; Ammonia/analysis ; English Abstract ; Female ; Gastric Acid/secretion ; *Gastric Acidity Determination ; Helicobacter Infections/*complications/physiopathology ; *Helicobacter pylori ; Humans ; Hydrogen-Ion Concentration ; Liver Cirrhosis/*metabolism/microbiology/physiopathology ; Male ; Middle Aged