scholarly journals Gastrin: From physiology to gastrointestinal malignancies

Function ◽  
2021 ◽  
Author(s):  
Suzann Duan ◽  
Karen Rico ◽  
Juanita L Merchant
Keyword(s):  
Gene Regulation ◽  
Gastric Mucosa ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Peptide Hormone ◽  
Cell Types ◽  
Neuroendocrine Neoplasms ◽  
Gastrointestinal Malignancies ◽  
Distinct Cell ◽  
H Pylori

Abstract Abetted by widespread usage of acid-suppressing proton pump inhibitors, the mitogenic actions of the peptide hormone gastrin are being revisited as a recurring theme in various gastrointestinal malignancies. While pathological gastrin levels are intricately linked to hyperplasia of enterochromaffin-like cells leading to carcinoid development, the signaling effects exerted by gastrin on distinct cell types of the gastric mucosa are more nuanced. Indeed, mounting evidence suggests dichotomous roles for gastrin in both promoting and suppressing tumorigenesis. Here we review the major upstream mediators of gastrin gene regulation, including inflammation secondary to H. pylori infection and the use of proton pump inhibitors. We further explore the molecular biology of gastrin in gastrointestinal malignancies, with particular emphasis on the regulation of gastrin in neuroendocrine neoplasms. Finally, we highlight tissue-specific transcriptional targets as an avenue for targetable therapeutics.

scholarly journals CHARACTERISTICS OF GASTRIC MUCOSA INJURY IN PATIENTS WITH NSAID-INDUCED GASTROPATHY AND CONCOMITANT ISCHEMIC HEART DISEASE, AND WAYS TO CORRECT THIS CONDITION

2020 ◽  
Vol 20 (2) ◽  
pp. 70-75
Author(s):  
V.V. Parkhomenko ◽  
І.М. Skrypnyk ◽  
І.І. Starchenko ◽  
O.F. Gopko
Keyword(s):  
Heart Disease ◽  
Gastric Mucosa ◽  
Ischemic Heart Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Morphological Changes ◽  
Ischemic Heart ◽  
Mucosal Barrier ◽  
Nsaid Gastropathy ◽  
H Pylori

The non-steroidal anti-inflammatory drugs (NSAIDs) in general clinical practice can provoke the development of NSAID-induced gastropathy, which can be complicated by bleeding. The aim of this article was to evaluate the effect of eupatilin on histological changes of the gastric mucosa in patients with NSAID-induced gastropathy and concomitant ischemic heart disease depending on the association with Helicobacter pylori. The study included 125 patients with NSAID-gastropathy and concomitant stable ischemic heart disease I-II functional class. Patients were divided into two groups: I (n=82) included individuals with NSAID-gastropathy, which was not associated with H. pylori, while II (n=43) included individuals with H. pylori-induced gastropathy. Depending on the prescribed treatment complexes, patients were subdivided as follows: I-A (n=44) included patients, who took proton pump inhibitors in standard doses and II-A group (n=23) included patients, who received antihelicobacter therapy according to Maastricht V (2016) guidelines. Patients of groups I-B (n=38) and II-B (n=20) were additionally prescribed 60 mg of eupatilin (1 tablet) 3 times a day for 28 days. The upper endoscopy with the gastric mucosa biopsy, followed by histological examination was done at the beginning of treatment and in 45±2 days. The severity of gastric mucosa erosive and ulcerative injury was assessed endoscopically using a modified Lanzascore scale; morphological changes were evaluated by a semi-quantitative method on a visual-analogue scale. H. pylori is an independent and significant factor determining the severity of endoscopic and morphological changes in NSAID-gastropathy patients with concomitant ischemic heart disease. Acid-suppressive and antihelicobacter therapy can reduce the intensity of the structural injury of the gastric mucosa, but the identified changes substantiate the feasibility of long-term proton pump inhibitors prescribed to the patients with NSAID-gastropathy. Prescribing eupatilin against the background of basic therapy can significantly reduce the severity of erosive-ulcerative gastric mucosa injury assessed by Lanzascore scale while histomorphological parameters by reducing the activity of neutrophilic inflammation, protective effect on mucosal barrier resistance and microcirculatory condition.

scholarly journals REGULARITY OF CHANGES IN THE LEVEL OF ACIDITY, HELICOBACTER INFECTION AND CLINICAL MANIFESTATIONS IN THE FORM OF HEARTBURN IN PATIENTS WITH CHRONIC NON-ATROPHIC GASTRITIS BEFORE AND AFTER TREATMENT WITHOUT USE OF PROTON PUMP INHIBITORS

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
A.A. Avramenko
Keyword(s):  
Gastric Mucosa ◽  
Atrophic Gastritis ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Clinical Manifestations ◽  
Average Level ◽  
Comparative Characteristic ◽  
Urease Test ◽  
Before And After ◽  
H Pylori

The aim of the work – to study the regularity of changes in the level of acidity, H.pylori infection and the clinical manifestation of heartburn in patients with chronic nonatrophic gastritis before and after treatment that did not include proton pump inhibitors.Material and methods. We have analyzed the results of a comprehensive examinationof 38 patients with chronic non-atrophic gastritis, suffering from heartburn, before andafter treatment that did not include proton pump inhibitors. Comprehensive examinationbefore treatment included a step-by-step pH-metry, esophagogastroduodenoscopy,double testing for Helicobacter pylori infection (urease test and microscopy of the stainedsmears-prints) using mucosal biopsy specimens from 4 topographic zones of the stomach;histological examination of the gastric mucosa, material for which was taken from thesame areas, and HELIC test. After the treatment, pH-meter control and HELIС test wereperformed.Results. When carrying out a comparative characteristic of the obtained data, ithasbeen found that the average level of acidity after the treatment increased from moderateminimal hypoacidity to pronounced absolute hyperacidity, while the average level ofcontamination of the gastric mucosa by H. pylori infection, tracked by the level of theHELIC test, decreased from 16.4 ± 0.12 mm to 2.3 ± 0.12 mm, and the "heartburn"symptom disappeared in 100% of cases.Conclusions. In the formation of the “heartburn”symptom in patients with chronicnon-atrophic gastritis, the leading factor is the level of ammonia produced by H. pyloriinfection.

scholarly journals Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis

2021 ◽  
Vol 35 ◽  
pp. 205873842110303
Author(s):  
Wenwen Gao ◽  
Xiang Zhang ◽  
Yanhui Yin ◽  
Shuwen Yu ◽  
Lu Wang
Keyword(s):  
Helicobacter Pylori ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Eradication Rate ◽  
Standard Dose ◽  
Statistical Significance ◽  
High Dose ◽  
Clarithromycin Resistance ◽  
H Pylori ◽  
New Generation

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.

scholarly journals Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence

2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Randomized Clinical Trials ◽  
Bacterial Overgrowth ◽  
Current Evidence ◽  
Neoplastic Progression ◽  
Increased Risk ◽  
H Pylori

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.

scholarly journals In vitro antibacterial activity of omeprazole and its selectivity for Helicobacter spp. are dependent on incubation conditions.

1996 ◽  
Vol 40 (3) ◽  
pp. 621-626 ◽  
Author(s):  
J E Sjöström ◽  
J Fryklund ◽  
T Kühler ◽  
H Larsson
Keyword(s):  
Antibacterial Activity ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bactericidal Activity ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Antibacterial Activities ◽  
In Vitro Antibacterial Activity ◽  
H Pylori

Factors affecting the in vitro antibacterial activity of omeprazole were studied. Our data show that 3H-labeled omeprazole covalently bound to Helicobacter pylori and to other gram-negative and gram-positive bacteria. The compound was found to bind to a broad range of proteins in H. pylori, and at pH 5, binding was enhanced 15-fold compared with binding at pH 7. The bactericidal activity correlated to the degree of binding, and at pH 5, a pH at which omeprazole readily converts to the active sulfenamide form, beta-mercaptoethanol, a known scavenger of sulfenamide, and fetal calf serum, to which noncovalent protein binding of omeprazole is known to occur, reduced the level of binding and almost entirely abolished the bactericidal activity. At pH 7 the killing activities of omeprazole and structural analogs (e.g., proton pump inhibitors) were dependent on the time-dependent conversion (half-life) to the corresponding sulfenamide. The bactericidal activity exerted by the sulfenamide form at pH 5 was not specific for the genus Helicobacter. However, in brucella broth at pH 7 with 10% fetal calf serum, only Helicobacter spp. were susceptible to omeprazole, with MBCs in the range of 32 to 64 micrograms/ml, and MBCs for more stable proton pump inhibitors were higher. Wild-type H. pylori and its isogenic urease-deficient mutant were equally susceptible to omeprazole. Thus, the urease is not a lethal target for omeprazole action in H. pylori. In conclusion, the antibacterial activities of omeprazole and analogs are dependent on pH and the composition of the medium used. Thus, at a low pH in buffer, these compounds have a nonselective action, whereas in broth at neutral pH, the mechanism of action is selective for Helicobacter spp.

scholarly journals Potential use of methylmethionine sulfonium chloride as a component of combination therapy for peptic ulcer and gastroduodenitis

2018 ◽  
pp. 28-32 ◽  
Author(s):  
I. G. Pakhomova
Keyword(s):  
Peptic Ulcer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Significant Proportion ◽  
Dietary Recommendations ◽  
Therapeutic Concept ◽  
Vitamin U ◽  
Drug Regimens ◽  
H Pylori ◽  
The Individual

It is known that gastritis, gastroduodenitis and peptic ulcer belong to the group of acid-dependent diseases, which occupy a significant proportion among the digestive system diseases. Despite the use of proton pump inhibitors in therapy, the discovery of an important role of H. pylori infection in the genesis of these diseases and the development of eradication schemes, the urgency of the problem persists due to the development of formidable complications (bleeding, perforation). The modern therapeutic concept of treatment of peptic ulcer (including gastroduodenitis) provides active therapeutic tactics and includes multicomponent drug regimens. Along with proton pump inhibitors, the dietary recommendations, appointment of gastro-cytoprotectors, including ones of natural origin, and the individual approach to the patient in each specific case have not outlived their usefulness. Methylmethionine sulfonium chloride (vitamin U) Gastrarex, which improves the secretory and reparative function of the stomach, may be administered as one of the components of the complex therapy of peptic ulcer and gastroduodenitis.

Comparative Effect of Proton-Pump Inhibitors on the Success of Triple and Quadruple Therapy for Helicobacter pylori Infection

2020 ◽  
Vol 38 (5) ◽  
pp. 408-414 ◽  
Author(s):  
Doron Boltin ◽  
Zohar Levi ◽  
Rachel Gingold-Belfer ◽  
Hemda Schmilovitz-Weiss ◽  
Tzippy Shochat ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Treatment Success ◽  
Helicobacter Pylori Infection ◽  
Comparative Effect ◽  
Quadruple Therapy ◽  
13C Urea Breath Test ◽  
H Pylori ◽  
Current Guidelines

Introduction: Suppression of gastric acid secretion with proton-pump inhibitors (PPI) is an integral part of the treatment of Helicobacter pylori infection. Esomeprazole has been shown to be superior to other PPIs when used in the context of triple therapy; however, comparative data for PPI efficacy in quadruple therapy are lacking. Current guidelines recommend H. pylori eradication with quadruple therapy in areas with high clarithromycin resistance. Objective: To determine whether esomeprazole is more effective than other PPIs in the context of quadruple therapy for H. pylori eradication. Methods: We retrospectively identified 25- to 60-year-old subjects with a positive 13C-urea breath test and no prior laboratory or endoscopic test for H. pylori infection. Pharmacy dispensation data were retrieved. Results: A total of 7,896 subjects including 2,856 (36.2%) males, aged 40.4 ± 10.6 years, were identified. Of those, 78.1% received omeprazole, 20.1% received lansoprazole, 1.5% received esomeprazole, and 0.34% received pantoprazole together with antibiotics for H. pylori eradication. Esomeprazole was associated with a greater proportion of successful eradication (85.0 vs. 77.5%, esomeprazole vs. omeprazole, OR 1.64; 95% CI 0.99–2.72; p = 0.05). A nonsignificant trend favored esomeprazole over omeprazole among subjects receiving quadruple therapy (90.0 vs. 82.0%, respectively, OR 1.98; 95% CI 0.68–5.72; p = 0.16). Independent predictors of treatment success included older age and quadruple therapy. Conclusion: Esomeprazole is more beneficial than other PPIs for H. pylori eradication. Studies with larger subgroups are necessary to confirm our findings among subjects receiving quadruple therapy.

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