Atrophy Of Gastric Glands Research Articles

Lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 Helicobacter pylori isolate that provided by low iron diet

Background: Helicobacter pylori (H. pylori) infection is associated with various gastrointestinal diseases including gastritis, peptic ulcers, gastric carcinoma, and gastric mucosa-associated lymphoid-tissue lymphoma (MALT) lymphoma. Several studies have shown that H. pylori plays a role in iron deficiency that is refractory to iron administration. This study aims to analyze whether the lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 H. pylori isolate that is provided by a low iron diet. Methods: This research was an experimental study by inoculating the bacterial isolate H. pylori Bali 03 in two groups of BALB/c mice. The treatment group was given a low iron diet at a dose of <3 mg/kgBW of mice, while the control group was given a normal dose of iron diet at a dose of 40 mg/kgBW of mice. The cellular immune response of the two groups of BALB/c mice was measured by comparing the expression of IFN-γ, granzyme B, IFN-γ/IL-10 ratio to the degree of gastric inflammation. Results: The results of the research were that the H. pylori Bali 03 isolate caused inflammation in 36 (100%) gastric of the mice. The degree of gastric inflammation of mice was more severe in the treatment group than in the control group, within 6 weeks precancerous lesions occurred, namely gastric gland atrophy and metaplasia in the treatment group, 1 (2.7%). There is a significant difference between the control group and the treatment group (p=0.019). There was a significant difference in IFN-γ expression between the treatment group and the control group (p=0.034). Conclusion: Iron deficiency affects the degree of gastric inflammation through IFN-γ expression in BALB/c infected with H. pylori isolate Bali 03. Iron deficiency worsens the degree of gastric inflammation in BALB/c mice infected with H. pylori isolate Bali 03.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Toxicological impact of rabeprazole and evaluation of toxic effects on the plant-based eukaryotic test models

Background: Rabeprazole (RPZ), a widely used proton pump inhibitor, is known to have toxic effects on human beings. Objective: To evaluate the current understanding of its toxicological effects on humans and animals, a literature and laboratory-based study was conducted. Methods: A comprehensive search of published literature was conducted in various databases up until April 2020, using specific keywords. Additionally, toxic effects of RPZ-Na (0.025-0.4 mM) were evaluated on Allium cepa, Allium sativum and Cicer arietinum at different exposure times using CuSO4 as a reference standard. Results: The literature review revealed that RPZ has a wide range of side effects including nausea, vomiting, diarrhea, headache, rhinitis, myalgia, pharyngitis, abdominal pain, dyspepsia, and eye disorders. Chronic exposure to RPZ has also been associated with significant biochemical and hematological alterations, as well as various toxicological effects such as hypergastrinemia, hyperplasia, atrophy of gastric glands, gastric anti-secretory effect, and hypochlorhydria. The laboratory analysis showed that RPZ-Na concentration-dependently inhibited root length of A. cepa and A. sativum, as well as shoot and root lengths of C. arietinum. Conclusions: This study highlights the toxicological impacts of RPZ and its formulations on human and animals. Results suggest that RPZ-Na has a concentration-dependent toxic effect on A. cepa, A. sativum, and C. arietinum. Therefore, it is important to take adequate precautions during its long-term use.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND Dendrobium officinale is an herb of Traditional Chinese Medicine (TCM) commonly used for treating stomach diseases. One formula of Granule Dendrobii (GD) consists of Dendrobium officinale and American Ginseng (Radix Panacis quinquefolii), and is a potent TCM product in China. Whether treatment with GD can promote gastric acid secretion and alleviate gastric gland atrophy in chronic atrophic gastritis (CAG) requires verification.AIMTo determine the effect of GD treatment on CAG and its potential cellular mechanism.METHODSA CAG model was induced by feeding rats N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 wk. After oral administration of low, moderate, and high doses of GD in CAG rats for 8 wk, its effects on body weight, gastric mucosa histology, mucosal atrophy, intestinal metaplasia, immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2, and hemoglobin and red blood cells were examined.RESULTSThe body weights of MNNG-induced CAG model rats before treatment (143.5 ± 14.26 g) were significantly lower than that of healthy rats (220.2 ± 31.20 g, P < 0.01). At the 8th week of treatment, the body weights of rats in the low-, moderate-, and high-dose groups of GD (220.1 ± 36.62 g) were significantly higher than those in the untreated group (173.3 ± 28.09 g, all P < 0.01). The level of inflammation in gastric tissue of the high-dose group (1.68 ± 0.54) was significantly reduced (P < 0.01) compared with that of the untreated group (3.00 ± 0.00, P < 0.05). The number and thickness of gastric glands in the high-dose group (31.50 ± 6.07/mm, 306.4 ± 49.32 µm) were significantly higher than those in the untreated group (26.86 ± 6.41/mm, 244.3 ± 51.82 µm, respectively, P < 0.01 and P < 0.05), indicating improved atrophy of gastric mucosa. The areas of intestinal metaplasia were significantly lower in the high-dose group (1.74% ± 1.13%), medium-dose group (1.81% ± 0.66%) and low-dose group (2.36% ± 1.08%) than in the untreated group (3.91% ± 0.96%, all P < 0.01). The expression of PCNA in high-dose group was significantly reduced compared with that in untreated group (P < 0.01). Hemoglobin level in the high-dose group (145.3 ± 5.90 g/L), medium-dose group (139.3 ± 5.71 g/L) and low-dose group (137.5 ± 7.56 g/L) was markedly increased compared with the untreated group (132.1 ± 7.76 g/L; P < 0.01 or P < 0.05).CONCLUSIONTreatment with GD for 8 wk demonstrate that GD is effective in the treatment of CAG in the MNNG model by improving the histopathology of gastric mucosa, reversing gastric atrophy and intestinal metaplasia, and alleviating gastric inflammation.

Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.

Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5‐year follow‐up in the LOTUS trial

Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals. To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266). Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy. Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin. Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Histopathological changes of gastric mucosa following oral administration of fumonisin B1 in mice

Fumonisin B1 is a common secondary metabolite produced by Fusarium moniliforme that occurs in corn and corn-based foods. This mycotoxin is toxic to many species of laboratory and domestic animals and is known to induce a variety of diseases such as hepatic cancer and renal and hepatic dysfunction. The structure of fumonisin B1 (FB1) resembles sphingolipids so it can inhibit synthesis of ceramide, an enzyme in the sphingolipid biosynthetic pathway. This inhibition leads to the disruption of sphingolipid metabolism and increased levels of sphinganine and sphingosine (sphingoid bases) in the serum of treated animals. It is believed that the toxicity effect of fumonisin B1 is the result of these sphingoid bases. In the present research, mice were treated with FB1 to determine its pathological effects on gastric gland and gastric mucosa in the treated mice. For this purpose, the mice were randomly assigned into two groups, namely, control (n = 14) and treatment (n = 15). The treatment group was fed with prepared food containing FB1 (150 mg/kg) for a period of 4 months. One day after the last treatment, all animals in both groups were euthanized and their stomach were sampled and prepared for microscopic analysis. Histopathological analysis revealed a significant decrease in parietal cell number and a significant increase in the number of inflammatory cells in gastric mucosa. Also, atrophy of gastric glands was observed. The study confirmed that FB1 poisoning can have toxicopathological effects such as gastric gland atrophy and gastritis on mice gastric tissue.

Histopathological analysis of chronic gastritis and correlation of pathological features with each other and with endoscopic findings

Chronic gastritis is a very common disorder which is commonly caused by Helicobacter pylori. Histopathological examination is the mainstay of the diagnosis. We evaluated 300 gastric antral biopsies using revised Sydney system and concluded that it helps to analyse gastric biopsies in a very comprehensive manner. It was seen that H. pylori, chronic inflammatory infiltrate, neutrophilic infiltration, presence of lymphoid follicles and aggregates and surface epithelial damage are strongly associated with each other. The presence of one of these histological feature is a strong indicator for presence of other features. On the other hand intestinal metaplasia and atrophy of gastric glands was not associated with the above mentioned histological features. In the presence of dense chronic inflammation and infiltration by neutrophils one should carefully search for H. pylori organism. We also correlated histological features with endoscopy and found that cases of duodenal ulcer had more severe antral gastritis on histology as compared to those with hyperemia or antral erosions.

Muscovite Reverses Gastric Gland Atrophy and Intestinal Metaplasia by Promoting Cell Proliferation in Rats with Atrophic Gastritis

Objective: To detect whether muscovite exerts its protective role in the progression of atrophic gastritis (AG) and evaluate the possible mechanism. Methods: AG rats were established and then randomly divided into groups administrated with different doses of muscovite for 8 weeks. Histological changes in gastric antrum and the number of parietal cells, chief cells, and G/D cells were observed. Serum gastrin and prostaglandin E₂ (PGE₂) were evaluated by enzyme-linked immunosorbent assay (ELISA). The expression of proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), C-erbB-2, p21, p53, p16 and bcl-2 in gastric tissue were detected by immunohistochemistry. The concentrations of TNF-α and IL-1β secreted by THP-1 cells were detected when incubated with different doses of muscovite. Results: The grade of inflammation in muscovite groups was lower (p < 0.05), while the thickness and number of gastric glands were significantly elevated in muscovite groups (p < 0.01). The expression height of PCNA in the muscovite group was higher than in the AG group (p < 0.01). Immunohistochemistry results showed a positive expression rate of EGFR; p16 in muscovite-treated AG rats was increased (p < 0.05), while C-erbB-2 and p21 were decreased (p < 0.05). Serum gastrin and PGE₂ were significantly elevated in the high-dose muscovite-treated rats (p < 0.05). In vitro studies showed that muscovite had a dose-dependent adsorption of TNF-α and IL-1β. Conclusion: Muscovite could reverse gastric gland atrophy and intestinal metaplasia by promoting cell proliferation and revitalization in gastric mucosa in AG rats.

Helicobacter pylori, a causative agent of vitamin B12 deficiency

Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. A total of 60 patients suffering from gastric disease due to H. pylori infection were evaluated. Endoscopy was performed and gastric biopsies were obtained for histopathology and urease test. Blood was simultaneously collected for the determination of the levels of vitamin B12 and the MCV. Vitamin B12 levels were determined by chemiluminescent assay. Our results indicate that the mean vitamin B12 level +/- SEM for the total population, the H.pylori infected and non-infected patients were 264.5+/-22.9, 207.7+/-21.9 and 419.7+/-39.8 respectively. H. pylori was found in 71.7% (43/60) of the patients tested. The level of vitamin B12 was lower than 200pg/ml (deficient) in 67.4% (29/43) of patients tested positive for H. pylori. H. pylori appears to be implicated in causing vitamin B12 deficiency.

Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency?

Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. We performed a prospective cohort study involving 138 patients who had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients.

Gastric effects of the CCK-B/gastrin receptor ligand CI-988 in cynomolgus monkeys

We have previously demonstrated that the CCK-B/gastrin receptor ligand CI-988 induces gastric gland degeneration and atrophy in cynomolgus monkeys, an effect consistent with gastrin receptor antagonism and inhibition of gastrin's trophic effects on oxyntic mucosa. However, gastrin receptor ligands of the dipeptoid chemical series to which CI-988 belongs have been reported to act as agonists or antagonists towards gastrin-related events, depending on the animal model and the functional endpoint examined. To investigate further these apparently conflicting data, basal gastric acid secretion was monitored acutely in conscious monkeys given CI-988 orally at 10 mg/kg or intravenously at 0.01 μmol/kg/hr and histological changes in gastric mucosa were evaluated in monkeys given CI-988 orally at 5, 25 or 75 mg/kg/day for 4 weeks. Degeneration and atrophy of gastric glands occurred at 25 and 75 mg/kg with statistically significant decrements in gastric mucosal height at 75 mg/kg. In addition, CI-988 stimulated gastric acid secretion when given either orally or intravenously. Co-administration of the structurally unrelated CCK-B/gastrin antagonist L-365 260 completely blocked CI-988-stimulated acid secretion, confirming that CI-988's agonist effect on acid secretion is mediated by the gastrin receptor. Assuming that gastric mucosal degeneration is the result of inhibition of gastrin's trophic activity, CI-988 appears to induce paradoxical agonist and antagonist gastrin-receptor mediated effects.

Severe gastric mucosal changes following vagotomy with duodenogastric reflux.

We conducted an experimental study of the morphological changes in gastric mucosa following vagotomy, in particular of the chronic effects of duodenogastric reflux. Male Wistar rats were divided into four groups: sham operation, duodenogastric reflux (DGR), truncal vagotomy with duodenogastric reflux (TV + DGR), and truncal vagotomy with bypass (TV + bypass). The last operation was performed to observe the effects of vagotomy without reflux. The duodenogastric reflux procedure was established by cutting the duodenum just distal to the orifice of bile and pancreatic ducts following gastrojejunostomy. After 12 and 30 weeks, animals were killed for morphological studies of gastric mucosa. The TV + DGR group showed formation of multiple elevated lesions macroscopically, and microscopically showed marked atrophy of gastric glands and proliferation of cystically dilated adenomatous lesions, which were regarded as precancerous or paracancerous lesions. The DGR group showed chronic gastric ulcer and hyperplasia of the gastric glands. However, the TV + bypass group showed no remarkable changes in the gastric mucosa. These results indicate that chronic effects of duodenogastric reflux following vagotomy induce severe inflammatory changes as well as structural alteration of the gastric mucosa. Therefore, a regular follow-up observation is necessary after vagotomy when combined with a drainage procedure because the latter could promote duodenogastric reflux and produces pathological changes to the stomach.

Free gastroomental flap for head and neck reconstruction: Assessment in an animal model

This study was performed to evaluate the free gastroomental flap for the reconstruction of mucosal and soft tissue defects after ablative surgery for head and neck cancer. Its use in a dog model was assessed in terms of the feasability of the surgical technique, acid secretion by the gastric mucosa, changes in the cell population of the graft, and the possibility that the omentum may augment lymphatic drainage after cervical node dissection. Gastroomental flaps were harvested, based on the gastroepiploic artery, and transplanted to the neck in ten dogs. Neck dissection and creation of a defect in the floor of the mouth were followed by microvascular anastamosis of the gastroepiploic vessels to suitable recipient vessels in the neck. Following this, the flap was sutured into place, reconstructing the defect in the floor of the mouth. The omentum was draped over the carotid artery and into the upper mediastinum. Intraoral pH remained stable during a 6-month follow-up period and there was no stomatitis noted. Radionuclide images suggested that the omental lymphatics contributed to regional lymphatic drainage. Histologic examination following sacrifice at 6 months showed atrophy of gastric glands but no epithelial metaplasia. We conclude that the free gastroomental flap is feasible, provides immediate restoration of soft tissue bulk, supplies a mucosal surface that adapts to the oral environment, and may augment regional lymphatic drainage.

Gastric histology and fasting bile reflux after partial gastrectomy

Forty-four randomized, partially gastrectomized subjects were studied to assess whether gastric histologie findings after partial gastrectomy were related to reflux. Gastric biopsy specimens (12) were taken at different distances from the anastomosis. Histologic findings were as follows: (a) hyperplastic changes of the foveolar epithelium and (b) loss of the chief and parietal gland cells with atrophy of gastric glands (chronic atrophic gastritis). Hyperplastic changes typical of the perianastomotic area gradually decreased with increasing distance from the anastomosis. Hyperplastic changes showed a greater prevalence in Billroth II than in Billroth I subjects (100% vs. 29.4%). No significant association was found between histologic findings and symptoms. Hourly bile acid quantity (fasting bile reflux) and concentration were determined in the gastric aspirates. Bile reflux was greater after Billroth II than after Billroth I (fasting bile reflux median values: 30.5 vs. 0.18 μmol/h, respectively). The same was true for bile acid concentration (mean bile acid concentration median values: 624.9 vs. 17.5 μmol/L, respectively). Moreover, Billroth I subjects with hyperplasia had a greater quantity and concentration of reflux than those without hyperplasia (fasting bile reflux and mean bile acid concentration median values: 2.6 vs. 0.8 μmol/h and 4.7 vs. 2.7 μmol/L, respectively). These findings show that bile reflux is correlated with hyperplastic changes of the foveolar epithelium, but prevalence and severity of atrophic gastritis were not related to reflux. Therefore, although we failed to show any relationship between chronic atrophic gastritis and reflux, foveolar hyperplasia was shown to be reflux related.

Illuminating the Antrum

Atrophic gastritis consists of chronic inflammation and atrophy of the gastric mucosa. As the atrophy of gastric glands progresses, particularly in pernicious anemia, a heavy cellular infiltrate of...

Uremic Gastropathy in the Dog

Stomachs of four dogs with uremia and four normal dogs were examined. Uremic stomachs represented four types of disease: atrophic, amyloidotic, ulcerative and necrotic gastropathy. Pathologic changes common to all uremic stomachs were expansion of the lamina propria, atrophy of gastric glands, and submucosal arteriopathy; lesions were limited to body and fundic zones. Lamina propria was markedly expanded by edema, mastocytosis, deposition of acidic mucosubstances, fibroplasia and mineralization. Capillaries in lamina propria had swollen endothelium and calcium salts were present extracellularly as amorphous granular laminae. Gastric glands were distorted and irregular and had fewer cells per unit of tissue. Parietal cells were swollen and had fragmentation of cytocavitary network and mitochondrial swelling with calcification. Chief cells were shrunken, agranular and atrophic with foci of glycogen and dilation of endoplasmic reticulum. Argentaffin cell content was diminished. Muscular arteries of submucosae had segmental degenerative lesions characterized by myocyte necrosis, calcification, and deposition of acidic mucosubstances and fibrin; thrombosis and obstructive arteriopathy were common. These studies suggest that uremic gastropathy is a disease of mucosal lamina propria and that lesions were due to anoxia caused by diffuse vascular injury and to altered parietal cell function.