Remodeling of the gastric environment in Helicobacter pylori-induced atrophic gastritis.

Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori-induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori-infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry. We detected striking differences in the protein content of corpus and antrum tissues. Four hundred ninety-two proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori-infected corpus tissues exhibiting atrophic gastritis compared with infected corpus tissues exhibiting non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. The corresponding alterations were not detected in animals infected with a H. pylori ∆cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions.IMPORTANCEA normal stomach is organized into distinct regions known as the corpus and antrum, which have different functions, cell types, and gland architectures. Previous studies have primarily used histologic methods to differentiate these regions and detect H. pylori-induced alterations leading to stomach cancer. In this study, we investigated H. pylori-induced gastric molecular alterations in a Mongolian gerbil model of carcinogenesis. We report the detection of numerous proteins that are preferentially localized to the gastric corpus but not the antrum in a normal stomach. We show that stomachs with H. pylori-induced atrophic gastritis (a precancerous condition characterized by the loss of specialized cell types) exhibit marked changes in the abundance and localization of proteins normally localized to the gastric corpus. These results provide new insights into H. pylori-induced gastric molecular alterations that are associated with the development of stomach cancer.

Efficacy and Safety of Intravenous Ferric Carboxymaltose Treatment of Iron Deficiency Anaemia in Patients with Corpus Atrophic Gastritis: A Retrospective Study.

Corpus Atrophic Gastritis (CAG) is characterised by iron malabsorption leading to iron deficiency anaemia (IDA), which rarely responds to oral therapy. Ferric carboxymaltose (FCM), shown to be a safe and effective intravenous iron therapy in other diseases, has not been investigated yet in CAG. Thus, we aimed to assess the safety and efficacy of FCM in CAG-related IDA. A retrospective study on 91 patients identified CAG as the only cause of IDA treated with FCM. Twenty-three were excluded for incomplete follow-up. Sixty-eight were evaluated for safety and efficacy, while three were evaluated for safety only due to infusion interruption for side effects. Haemoglobin and iron storage were evaluated pre-infusion (T0), at 4 weeks (T4) and 12 weeks (T12) after infusion. An eventual IDA relapse was analysed. Two cases reported mild side effects. Haemoglobin significantly increased at T4, and T12, reaching +3.1 g/dL. Ferritin increased at T4, decreasing at T12, while transferrin saturation increased progressively until reaching a plateau. IDA relapsed in 55.4% of patients at a mean of 24.6 months. The only factor associated with relapse was female gender [OR (95% CI): 6.6 (1.5-28.6)]. FCM proved to be safe and effective in treating CAG-related IDA, ensuring quick and long-lasting recovery.

Rutaecarpine Ameliorates Murine N-Methyl-N'-Nitro-N-Nitrosoguanidine-Induced Chronic Atrophic Gastritis by Sonic Hedgehog Pathway.

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.

PPIs and gastric cancer: any causal relationship?

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based  focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality.  Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.

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. AIM: To determine the effect of GD treatment on CAG and its potential cellular mechanism. METHODS: A 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. RESULTS: The 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). CONCLUSION: Treatment 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.

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

BACKGROUNDS: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. METHODS: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. RESULTS: The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. CONCLUSIONS: The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.

Zuojin Pill ameliorates chronic atrophic gastritis induced by MNNG through TGF-ß1/PI3K/Akt axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases. AIM OF THIS STUDY: The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG. MATERIALS AND METHODS: The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-ß1/PI3K/Akt signal axis were detected by RT-PCR and Western blot. RESULTS: The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1ß, inhibit the expression of TGF-ß1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. CONCLUSION: ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-ß1/PI3K/Akt signal pathway.

Gastric neuroendocrine tumours from long-term proton pump inhibitor users are indolent tumours with good prognosis.

AIMS: Proton pump inhibitors (PPIs) are among the most widely used medications in the United States. Most PPI users have persistent hypergastrinaemia during treatment. However, gastric neuroendocrine tumours diagnosed in long-term PPI users are rarely reported. Their clinicopathological features and prognosis are not characterised. It remains unclear whether or not they can be classified as Type III sporadic tumours. METHODS AND RESULTS: We retrospectively characterised 66 gastric neuroendocrine tumours from patients without atrophic gastritis and gastrinoma from two tertiary care medical centres, including 38 tumours in patients who had used PPIs for at least 1 year and 28 tumours from patients without long-term PPI use (control group, Type III tumours). Compared to controls, tumours from long-term PPI users tended to be in the pT1-2 category (98% versus 79%, P = 0.09) and less often invaded the serosa (3% versus 18%, P = 0.08) or lymphovascular spaces (11% versus 32%, P = 0.06). Using Kaplan-Meier analysis, long-term PPI users had significantly longer overall survival than controls (P = 0.035). While three control patients developed distant metastasis and seven died, long-term PPI users were without distant metastasis (P = 0.06) or death (P = 0.002) during follow-up. However, five long-term PPI users developed additional gastric neuroendocrine tumour(s), while none of the controls did (P = 0.07). CONCLUSIONS: Our results show that gastric neuroendocrine tumours of long-term PPI users are probably less aggressive compared to Type III sporadic tumours and have an indolent disease course. Our findings support the classification of gastric neuroendocrine tumours in long-term PPI users as a separate subtype.

Proton Pump Inhibitor Induction of Gastric Cobblestone-like Lesions in the Stomach.

Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed. The biopsy specimens from patients with gastric cobblestone-like lesions (GCLLs) were examined histopathologically. Patients This study analyzed 171 patients who underwent upper gastrointestinal endoscopy after more than 6 months of PPI use in Mitsugi Public General Hospital from January 1, 2015, to March 31, 2016. Results Of the 171 patients, 60 (35.1%) had GCLLs and 111 (64.9%) did not. There were no significant between-group differences in age, sex, duration of PPI use, and receipt of Helicobacter pylori eradication therapy. Atrophic gastritis of the corpus was significantly less frequent in the GCLL than in the non-GCLL group (55.0% vs. 47.8%, p=0.0097). Among the GCLL group, histological examinations of 24 patients revealed cystic dilation of the fundic gland in 19 (79.2%), parietal cell hyperplasia in 18 (75.0%), and cytoplasmic vacuolation in 7 (29.2%). Conclusion GCLLs occurred frequently in long-term PPI users, especially in patients without atrophic gastritis. The pathological findings of GCLLs included parietal cell hyperplasia and fundic gland cysts. The clinical importance of these new lesions remains uncertain, but they should be observed carefully.

Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal diseases. Recently, some studies have reported that PPIs can alter the gastric mucosal architecture; however, the relationship remains controversial. This meta-analysis study was designed to quantify the association between long-term PPI administration and gastric atrophy. MATERIALS AND METHODS: A PubMed search was conducted to identify studies using the keywords proton pump inhibitors or PPI and gastric atrophy or atrophic gastritis; the timeframe of publication searched was up to May 2016. Heterogeneity among studies was tested with the Q test; odds ratios (OR) and 95% confidence intervals (CI) were calculated. P values were calculated by I2 tests and regarded as statistically significant when <0.05. RESULTS: We identified 13 studies that included 1465 patients under long-term PPI therapy and 1603 controls, with a total gastric atrophy rate of 14.50%. There was a higher presence of gastric atrophy (15.84%; statistically significant) in PPI group compared to the control group (13.29%) (OR: 1.55, 95% CI: 1.00-2.41). CONCLUSIONS: The pooled data suggest that long-term PPI use is associated with increased rates of gastric atrophy. Large-scale multicenter studies should be conducted to further investigate the relationship between acid suppressants and precancerous diseases.

Endoscopic findings of the gastric mucosa during long-term use of proton pump inhibitor - a multicenter study.

BACKGROUND AND AIM: It is clinically important to diagnose drug-induced gastric lesions correctly. Recently, the use of proton pump inhibitors (PPI) has increased worldwide. The histological features induced by PPI have been reported; however, few reports have described endoscopic findings induced by PPI. Therefore, we aimed to clarify the characteristic endoscopic features in PPI users and associated pathogenic factors. METHODS: We prospectively registered 1007 consecutive participants (70 PPI users and 937 nonusers) who underwent endoscopic examination for cancer screening in three hospitals/clinics. Clinical data and endoscopic findings were recorded in the registration forms. We compared the endoscopic features between the two groups and evaluated contributing factors via univariate and multivariate analyses. RESULTS: Multiple white elevated lesions (MWEL) and cobblestone-like mucosa (CLM) were more commonly observed in PPI users compared with nonusers (p < .01). Foveolar hyperplastic polyps were also frequently observed in PPI users but were not statistically significantly different (p = .06). MWEL and CLM were more frequently observed in older patients than in younger patients. MWEL was more frequently observed in female patients than in male patients; however, CLM was predominantly observed in male patients. CONCLUSION: MWEL and CLM are characteristic endoscopic features in PPI users. A gender-associated difference was noted in terms of the frequency of these lesions.

High Salt Intake Is Associated with Atrophic Gastritis with Intestinal Metaplasia.

Background: Although several studies have investigated excessive salt intake as a risk factor for gastric precancerous lesions, such as atrophic gastritis and intestinal metaplasia, the evidence is insufficient to make a conclusion. We evaluated the association between gastric precancerous lesions and salt intake.Methods: From 2008 to 2015, the medical records of 728 subjects who underwent upper gastrointestinal endoscopy and sodium excretion in 24-hour urine tests were retrospectively reviewed. Sixty-six subjects were excluded due to diuretics use (n = 55), diagnosis with a gastric neoplasm (n = 4), or the cases of intestinal metaplasia in the absence of atrophy (n = 7), so 662 subjects were included. Atrophic gastritis and intestinal metaplasia were diagnosed by endoscopic findings. The subjects were grouped into three levels by tertiles of 24-hour urine sodium excretion.Results: A total of 192 (29.0%) had atrophic gastritis without intestinal metaplasia and 112 (16.9%) had atrophic gastritis with intestinal metaplasia. A total of 276 subjects (61.5%) were infected with Helicobacter pylori (H. pylori). In multivariate analyses, H. pylori infection [OR = 14.17; 95% confidence interval (CI), 7.12-28.22) was associated with atrophic gastritis without intestinal metaplasia. Highest levels of sodium excretion (OR = 2.870; 95% CI, 1.34-6.14), heavy smoking (≥20 pack-years) (OR = 2.75; 95% CI, 1.02-7.39), and H. pylori infection (OR = 3.96; 95% CI, 2.02-7.76) were associated with atrophic gastritis with intestinal metaplasia.Conclusions: Our endoscopy-based study suggested that high salt intake could be associated with an increased risk of atrophic gastritis with intestinal metaplasia.Impact: Low salt diet might be helpful to prevent gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1133-8. ©2017 AACR.

Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.

BACKGROUND: Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription. OBJECTIVES: To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy. SEARCH METHODS: We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both). DATA COLLECTION AND ANALYSIS: Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI). MAIN RESULTS: We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was difficult to assess possible reporting bias. We pooled 1070 participants from four RCTs to evaluate corporal atrophy development revealing an insignificantly increased OR of 1.50 (95% CI 0.59 to 3.80; P value = 0.39; low-quality evidence) for long-term PPI users relative to non-PPI users. In five eligible trials, corporal intestinal metaplasia was assessed among 1408 participants, also with uncertain results (OR 1.46; 95% CI 0.43 to 5.03; P value = 0.55; low-quality evidence). However, by pooling data of 1705 participants from six RCTs, our meta-analysis showed that participants with PPI maintenance treatment were more likely to experience either diffuse (simple) (OR 5.01; 95% CI 1.54 to 16.26; P value = 0.007; very-low-quality evidence) or linear/micronodular (focal) ECL hyperplasia (OR 3.98; 95% CI 1.31 to 12.16; P value = 0.02; low-quality evidence) than controls. No participant showed any dysplastic or neoplastic change in any included studies. AUTHORS' CONCLUSIONS: There is presently no clear evidence that the long-term use of PPIs can cause or accelerate the progression of corpus gastric atrophy or intestinal metaplasia, although results were imprecise. People with PPI maintenance treatment may have a higher possibility of experiencing either diffuse (simple) or linear/micronodular (focal) ECL cell hyperplasia. However, the clinical importance of this outcome is currently uncertain.

Chronic atrophic gastritis in association with hair mercury level.

The objective of this study was to explore hair mercury level in association with chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus provide a brand new angle of view on the timely intervention of precancerous stage of GC. We recruited 149 healthy volunteers as controls and 152 patients suffering from chronic gastritis as cases. The controls denied upper gastrointestinal discomforts, and the cases were diagnosed as chronic superficial gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy controls and cases of chronic gastritis. The statistic of measurement data was expressed as mean ± standard deviation, which was analyzed using Levene variance equality test and t test. Pearson correlation analysis was employed to determine associated factors affecting hair mercury levels, and multiple stepwise regression analysis was performed to deduce regression equations. Statistical significance is considered if p value is less than 0.05. The overall hair mercury level was 0.908949 ± 0.8844490 ng/g [mean ± standard deviation (SD)] in gastritis cases and 0.460198 ± 0.2712187 ng/g (mean±SD) in healthy controls; the former level was significantly higher than the latter one (p=0.000<0.01). The hair mercury level in chronic atrophic gastritis subgroup was 1.155220 ± 0.9470246 ng/g (mean ± SD) and that in chronic superficial gastritis subgroup was 0.604732 ± 0.6942509 ng/g (mean ± SD); the former level was significantly higher than the latter level (p<0.01). The hair mercury level in chronic superficial gastritis cases was significantly higher than that in healthy controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was significantly higher than that in healthy controls (p<0.01). Stratified analysis indicated that the hair mercury level in healthy controls with eating seafood was significantly higher than that in healthy controls without eating seafood (p<0.01) and that the hair mercury level in chronic atrophic gastritis cases was significantly higher than that in chronic superficial gastritis cases (p<0.01). Pearson correlation analysis indicated that eating seafood was most correlated with hair mercury level and positively correlated in the healthy controls and that the severity of gastritis was most correlated with hair mercury level and positively correlated in the gastritis cases. Multiple stepwise regression analysis indicated that the regression equation of hair mercury level in controls could be expressed as 0.262 multiplied the value of eating seafood plus 0.434, the model that was statistically significant (p<0.01). Multiple stepwise regression analysis also indicated that the regression equation of hair mercury level in gastritis cases could be expressed as 0.305 multiplied the severity of gastritis, the model that was also statistically significant (p<0.01). The graphs of regression standardized residual for both controls and cases conformed to normal distribution. The main positively correlated factor affecting the hair mercury level is eating seafood in healthy people whereas the predominant positively correlated factor affecting the hair mercury level is the severity of gastritis in chronic gastritis patients. That is to say, the severity of chronic gastritis is positively correlated with the level of hair mercury. The incessantly increased level of hair mercury possibly reflects the development of gastritis from normal stomach to superficial gastritis and to atrophic gastritis. The detection of hair mercury is potentially a means to predict the severity of chronic gastritis and possibly to insinuate the environmental mercury threat to human health in terms of gastritis or even carcinogenesis.

Effect of Astragalus polysaccharides on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

This study investigated the effect and mechanism of Astragalus polysaccharides (APS) on chronic atrophic gastritis (CAG) induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in rats. Histomorphological, hormone-level, and immunohistochemistry experiments were used to investigate the gastric mucosal injury. Pathological changes were readily found in CAG rats. Compared to the control rats, the CAG rats showed significantly decreased plasma levels of gastrin and somatostatin while their motilin levels increased. Moreover, PGE2 in gastric tissue increased and serum sIgA decreased significantly, while the GSH/GSSG ratio showed no change. Immunohistochemical detection showed that the expression of EGFR, COX-2, and MMP-2 was higher in the gastric tissue of CAG rats. After APS treatment, the gastric morphology of CAG rats improved. APS increased plasma gastrin and somatostatin levels significantly but had no significant effect on the motilin level. APS also decreased tissue PGE2 and increased serum sIgA in CAG rats without affecting the GSH/GSSH ratio. This study suggested that APS had a beneficial effect on CAG rats by deregulating EGFR at its downstream effectors COX-2 and MMP-2.

[Comparative morphology of the gastric mucosa in asthmatic patients using inhaled glucocorticosteroid therapy].

The immunomorphological characteristics of the gastric mucosa were evaluated and analyzed in patients with asthma of varying severity who received or did not receive inhaled or oral glucocorticosteroid therapy and in the control group. Immunohistological examination and morphometric analysis were used to study inflammatory infiltration in fundic mucosal biopsy specimens from patients with and without asthma. There were crucial immunomorphological differences between the examined patient groups and signs of the gastroprotective effect of inhaled glucocorticosteroids used in the basic therapy of asthma on the gastric mucosa. There was evidence that it is urgent to prevent erosive and atrophic gastritis and other inflammatory stomach diseases in asthma.

Studies on the characteristic and activity of low-molecular fragments from zymosan.

Zymosan was hydrolysed with HCl and fractionated by ultrafiltration and dialysis to obtain water-soluble fragments A, B and C. Physical and chemical analyses showed that these fractions are composed primarily of glucose and have molecular weights of 8 kDa, 5 kDa and 2 kDa, respectively. A glycosidic linkage analysis indicated that they are mainly composed of ß-1,3-glucans. Fragment A, which has the highest molecular weight, contains approximately 30% ß-1,6-linked glucans, but fragment C is almost entirely composed of linear ß-1,3-glucan chains. The anti-chronic atrophic gastritis activity experiments showed that fragment A has significant activity, the activity of zymosan is quite low and the activities of fragments B and C are in between those of fragment A and zymosan.

Correlation between Helicobacter pylori infection and low-dose aspirin use on damage of the upper gastrointestinal tract.

BACKGROUND AND AIM: Low-dose aspirin (LDA), and Helicobacter pylori (HP) infection are considered the two primary causes of peptic ulceration. The interaction between HP infection and non-steroidal anti-inflammatory drugs is, however, a matter of considerable discussion and controversy. In this study, we investigated possible synergistic or negative interactions between HP infection and LDA in gastric mucosal lesions, according to lesion site. METHODS: The subjects were 120 patients attending the Cardiology Outpatients Department (average age, 67.1 ± 8.9 years; male : female ratio 2.9:1). Endoscopic findings were graded using the Modified Lanza score. Lesions were scored for the antral, body and fundal regions. Ulcers were defined as mucosal defects ≥ 5 mm in size. RESULTS: There were 55 HP-positive and 65 HP-negative subjects, and 91 subjects on LDA therapy. The gastric antral Lanza scores were HP(-) LDA(-): 0.2 ± 1.6, HP(-) LDA(+): 1.8 ± 1.5, HP(+) LDA(-): 0.3 ± 0.7, and HP(+) LDA(+): 0.5 ± 1.0. The gastric body and fundal Lanza scores were 0.0 ± 0.0, 0.8 ± 0.9, 0.4 ± 1.1, and 1.0 ± 1.5, respectively, and 0.1 ± 0.3, 0.5 ± 0.9, 0.1 ± 0.3, and 0.1 ± 0.3, respectively. Variance analysis of the correlation between HP infection and LDA by regional Lanza scores identified both HP infection and LDA use as factors that significantly influence the antral Lanza score. However, LDA was an aggressive factor, and HP infection a protective factor. In the gastric body, LDA was a non-significant, and HP infection a significant, aggressive factor. In the gastric fundus, neither HP infection nor LDA was a significant factor (LDA was an aggressive factor, and HP infection a protective factor). CONCLUSIONS: LDA had aggressive effects in all gastric lesions; on the other hand, HP infection had protective effects in the antrum and fundus in the stomach, and aggressive effects in the body in the stomach.

[Risk factors of gastropathy development in workers exposed to dust].

Systemic leucocyte-induced oxidative stress in prolonged occupational exposure to dust modifies oxidative metabolism of neutrophils and RBC, causes inflammatory and destructive, autoimmune processes in gastric lining and possible subsequent occupational gastropathies. To verify gastropathies caused by technogenic dust aerosols, search of preclinical biologic markers of gastric lining damage is essential. The article presents main steps in occupational gastropathies formation, trigger mechanisms, leading pathogenetic factors of gastric lining damage and of atrophic fundus gastritis. Using the mentioned complex of biomarkers in gastric lining state monitoring among workers at periodic and thorough medical examination is main item in forecasting individual risk of occupational gastropathies and in possible approach to their prevention and treatment.

Gastric histology in children treated with proton pump inhibitors long term, with emphasis on enterochromaffin cell-like hyperplasia.

BACKGROUND: There are longstanding concerns that carcinoid tumours or atrophic gastritis might develop in children receiving proton pump inhibitors (PPIs) long term. In children, this has not been studied using stains sensitive and specific for enterochromaffin-like (ECL) cells. AIM: To evaluate gastric biopsies for ECL hyperplasia or gastric atrophy, in children treated long-term with PPIs. METHODS: Synaptophysin and chromogranin immunostaining, biopsies read anonymised, blinded. Endocrine cell numbers graded according to Rindi and Solcia. RESULTS: Of 130 children with gastro-oesophageal reflux disease (GERD), 65 had sequential gastric biopsies, starting at median 8.2 years (<1 to 17). Of the 65, 83% had GERD-predisposing conditions, mostly neurological impairment or repaired oesophageal atresia. Four hundred and fifty-eight tissue blocks (208 antrum, 250 body) were available from a mean of 5.8 endoscopies (2-14). Of 82 gastric body biopsies in 40 patients with ECL hyperplasia, 67 had grade 1 hyperplasia, 15 grade 2. Of the 40, nine had ECL hyperplasia before PPI use; all nine had received H2-receptor antagonists. Median duration of PPI use was 3.17 years in patients with ECL hyperplasia, 2.20 years in those without (P=0.16). Helicobacter pylori was present in four patients; two had ECL hyperplasia. PPI duration was >3 years in 24 patients. In nine patients who received H2-receptor antagonists, changes were present before PPI use. No patient had atrophic gastritis. CONCLUSIONS: A high percentage of children (61%) receiving long-term PPI continuously for up to 10.8 years (median 2.84 years) develop minor degrees of ECL hyperplasia. This has no known clinical significance. Children on PPIs for this duration do not appear to develop atrophic gastritis or carcinoid tumours.