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International Journal of Molecular... Sep 2020is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which interacts with... (Review)
Review
is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of bacteria, virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by infection, CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing infection. The effectiveness of such cytoprotection is related to strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.
Topics: Animals; Antioxidants; Ascorbic Acid; Carcinogenesis; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Phytochemicals; Stomach Neoplasms
PubMed: 32899442
DOI: 10.3390/ijms21176451 -
International Journal of Molecular... Oct 2019The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both... (Review)
Review
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
Topics: Animals; Carcinoma, Neuroendocrine; Chronic Disease; Gastrinoma; Gastrins; Humans; Proton Pump Inhibitors; Risk Factors; Stomach Diseases; Time Factors; Treatment Outcome; Zollinger-Ellison Syndrome
PubMed: 31623145
DOI: 10.3390/ijms20205128 -
Microorganisms Nov 2020Autoimmune atrophic gastritis is an organ-specific immune-mediated condition characterized by atrophy of the oxyntic mucosa. Autoimmune atrophic gastritis (AIG) is... (Review)
Review
Autoimmune atrophic gastritis is an organ-specific immune-mediated condition characterized by atrophy of the oxyntic mucosa. Autoimmune atrophic gastritis (AIG) is characterized by a progressive loss of acid-secreting parietal cells leading to hypo-achlorhydria. Due to this peculiar intra-gastric environment, gastric microbiota composition in individuals with autoimmune atrophic gastritis was first supposed and then recently reported to be different from subjects with a normal acidic healthy stomach. Recent data confirm the prominent role of as the main bacterium responsible for gastric disease and long-term complications. However, other bacteria than , for example, Streptococci, were found in subjects who developed gastric cancer and in subjects at risk of this fearful complication, as well as those with autoimmune gastritis. Gastric microbiota composition is challenging to study due to the acidic gastric environment, the difficulty of obtaining representative samples of the entire gastric microbiota, and the possible contamination by oral or throat microorganisms, which can potentially lead to the distortion of the original gastric microbial composition, but innovative molecular approaches based on the analysis of the hyper-variable region of the 16S rRNA gene have been developed, permitting us to obtain an overall microbial composition view of the RNA gene that is present only in prokaryotic cells.
PubMed: 33228138
DOI: 10.3390/microorganisms8111827 -
Advances in Nutrition (Bethesda, Md.) Jun 2021There is growing awareness that intestinal dysfunction determines the clinical outcomes of situations as diverse as undernourished children in urban tropical slums and...
There is growing awareness that intestinal dysfunction determines the clinical outcomes of situations as diverse as undernourished children in urban tropical slums and undernourished surgical patients in intensive care units. As experimental starvation in humans has only rarely been studied, and largely not using current biomedical research tools, we must draw inference from disparate clinical and experimental observations as to the derangements present in the starved gut. There is good evidence of intestinal atrophy and achlorhydria in starvation and severe undernutrition. Historical reports from concentration camps and conflict settings consistently reported a noncontagious phenomenon called "hunger diarrhea," but in settings where starved individuals are isolated from others (prisoners on hunger strike, anorexia nervosa) diarrhea is not a feature. Changes in intestinal permeability and absorption have been infrequently studied in experimental starvation; available data suggest that short-term starvation reduces sugar absorption but not permeability. Severe acute malnutrition in children is associated with severe changes in the intestinal mucosa. Experimental animal models may help explain some observations in humans. Starved rats develop a hypersecretory state and intestinal barrier defects. Starved pigs demonstrate prolongation of rotavirus diarrhea and reproduce some of the absorptive and barrier defects observed in malnourished children. However, there remains much to be learned about the effects of starvation on the gut. Given the high prevalence of undernutrition in hospitals and disadvantaged communities, the lack of attention to the interaction between undernutrition and gastrointestinal damage is surprising and needs to be corrected. Current sophisticated cellular and molecular techniques now provide the opportunity to create fresh understanding of gastrointestinal changes in pure undernutrition, using volunteer studies and samples from anorexia nervosa.
Topics: Animals; Child Nutrition Disorders; Diarrhea; Humans; Intestinal Mucosa; Malnutrition; Rats; Starvation; Swine
PubMed: 33271592
DOI: 10.1093/advances/nmaa135 -
Current Opinion in Gastroenterology Nov 2022Autoimmune gastritis is characterized by atrophy of acid secreting parietal cells resulting in achlorhydria. Upper gastrointestinal symptoms are common in autoimmune... (Review)
Review
PURPOSE OF REVIEW
Autoimmune gastritis is characterized by atrophy of acid secreting parietal cells resulting in achlorhydria. Upper gastrointestinal symptoms are common in autoimmune gastritis and frequently result in prescriptions for acid suppressant medications despite the inability of the stomach to secrete acid. Evidence-based recommendations for management of gastrointestinal symptoms in autoimmune gastritis are lacking.
RECENT FINDINGS
The most common symptoms in patients with autoimmune gastritis are dyspepsia, heartburn, and regurgitation. Gastroesophageal reflux should be confirmed by pH-impedance testing and is typically weakly acid or alkaline. Therapy for reflux focuses on mechanical prevention of reflux (i.e., elevation of the head of the bed and alginates) or when severe, antireflux surgery. The etiology of dyspepsia in autoimmune gastritis is unclear and largely unstudied. In the first half of the 20th century, oral administration of acid to "aid digestion" was widely used with reported success. However, randomized, placebo-controlled trials are lacking. Here, we provide suggestions for attempting gastric acidification therapy.
SUMMARY
Upper GI symptoms are common in autoimmune gastritis. Their pathogenesis and therapy remain incompletely understood. Acid suppressant medications are useless and should be discontinued. A trial of acid replacement therapy is recommended especially in the form of placebo-controlled trials.
Topics: Alginates; Dyspepsia; Gastritis; Gastroesophageal Reflux; Heartburn; Humans
PubMed: 36165039
DOI: 10.1097/MOG.0000000000000878