epidermal-growth-factor and Gastritis--Atrophic

Weikangling capsules (WKLCs) have been widely used in the treatment of chronic gastritis. Whether used alone or combined with omeprazole (OME), it shows a significant effect. However, the mechanisms haven't been established. The study aimed to explore the mechanisms of WKLCs and its combination with OME on chronic gastritis.. The components of WKLCs and EA (the ethyl acetate extraction extracted from WKLCs) fraction were analyzed. Then chronic gastritis model rats were induced by 56 % ethanol and treated with OME, low dose of WKLCs (WKL), high dose of WKLCs (WKH), WKLCs combined with OME (WO), and EA fraction (EA) to evaluate the mechanisms of WKLCs, drug combination and EA fraction.. A total of 22 components of WKLCs were quantified, among them 18 were enriched in EA fraction. WKLCs alleviated the morphology and inflammation of gastric mucosa and downregulated the levels of inflammatory factors (IL-1β, TNF-α, IL-6) and epidermal growth factor (EGF) in serum by inhibiting the EGF-EGFR-ERK pathway, regulating gut microbiota composition and SCFAs contents in feces. WKLCs plus OME was better than OME. EA fraction improved digestive function by increasing pepsin activity and decreasing gastrointestinal hormones (GAS and VIP) compared with WKLCs.. This study elucidated that the effect of WKLCs and its combination with OME in the treatment of chronic gastritis was attributed to regulating the composition of the gut microbiota and inhibiting the EGF-EGFR-ERK pathway. The EA fraction is an inseparable effective substance of WKLCs. This study provides scientific evidence for clinical application.

Topics: Animals; Capsules; Epidermal Growth Factor; ErbB Receptors; Ethanol; Gastritis, Atrophic; Gastrointestinal Microbiome; MAP Kinase Signaling System; Omeprazole; Rats

The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organized inside glands and crypts. Regeneration depends on Wnt/β-catenin pathway activation, but to understand homeostasis and its dysregulation in disease, we need to identify the signaling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen-, and gastric acid-producing cells.. We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief, and parietal cells. We localized the source of the growth factors in the tissue of origin.. We show that epidermal growth factor is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with bone morphogenetic factor/Noggin signals, epidermal growth factor controls the differentiation of foveolar cells vs parietal or chief cells. We also show that epidermal growth factor is likely to underlie alteration of the gastric mucosa in the precancerous condition atrophic gastritis.. Use of our recently established mucosoid cultures in combination with analysis of the tissue of origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signaling microenvironment in the human gastric glands.

Topics: Body Patterning; Bone Morphogenetic Protein 4; Carrier Proteins; Cell Differentiation; Cell Lineage; Cells, Cultured; Cellular Microenvironment; Chief Cells, Gastric; Epidermal Growth Factor; Epithelial Cells; Gastric Mucosa; Gastritis, Atrophic; Gene Expression Regulation, Developmental; Humans; Organoids; Parietal Cells, Gastric; Wnt Signaling Pathway

To evaluate the effects of moxibustion and acupuncture of Zusanli (ST 36) and Zhongwan (CV 12) acupoints on chronic atrophic gastritis (CAG) in rats, and to study the mechanisms behind their actions.. Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40% ethanol combined with free drinking of N-methyl-N'nitro-N-nitrosoguanidine and irregular feeding for 12 weeks, followed by daily treatment with moxibustion or acupuncture for 2 weeks. Histopathologic examination, Western blotting of cytokines [epidermal growth factor (EGF), EGF receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK)], and 1H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment.. Moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK. Only moxibustion treatment regulated the expression of EGF and EGFR. Metabolites that were increased in gastric tissue by CAG induction (alanine, nicotinamide adenine dinucleotide phosphate, uracil DNA glycosylase, lactate, glycerol and adenosine) were restored to normal levels after moxibustion treatment; acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol.. Our findings suggest that moxibustion or acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) can significantly improve the condition of CAG in rats. These treatments exert their effects on CAG through different mechanisms.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Epidermal Growth Factor; ErbB Receptors; Gastritis, Atrophic; Humans; Male; Moxibustion; Rats; Rats, Sprague-Dawley; Treatment Outcome

To explore the molecular mechanism of moxibustion at stomach meridian acupoints for precancerous lesions of chronic atrophic gastritis (CAG).. Fifty male SD rats were randomly divided into a normal group, a model group, a stomach meridian group, a control point group and a vitacoenzyme group, 10 rats in each group. The CAG precancerous lesion model was made in all the groups except the normal group. The rats in the normal group and model group were bundled for 30 min per day; the rats in the stomach meridian group and control point group were bundled and treated with moxibustion at stomach meridian acupoints or control points for 30 min per day; the rats in the vitacoenzyme group were treated with intragastric administration of vitacoenzyme, once per day. All the treatment was given for 20 weeks. The pathological morphological change of gastric mucosa was observed under optical microscope; the expression of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF), gastric mucosal proliferatig cell nuclear antigen (PCNA), argyrophilic protein of nucleolar organizer regions (Ag-NORs) in gastric mucosal cells were detected by enzyme linked immuno sorbent assay (ELISA).. Compared with the normal group, in the model group the gastric mucosal cells showed dysplasia and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosa cells in the model group was increased significantly (all P < 0.05). Compared with the model group, the gastric mucosa lesion gradually recovered and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosal cells was gradually decreased in the stomach meridian group, control point group and vitacoenzyme group, in which the stomach meridian group had the most significant effects (all P < 0.05).. Moxibustion at stomach meridian acupoints can obviously decrease the expression of cell proliferative factors in gastric mucosa in rats with CAG precancerous lesions, inhibit the gastric mucosal cell dysplasia, and promote the recovery of gastric mucosa.

Topics: Acupuncture Points; Animals; Cell Proliferation; Epidermal Growth Factor; Gastric Mucosa; Gastritis, Atrophic; Humans; Hyperplasia; Male; Moxibustion; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A

Gastric secretion can provide valuable information especially when Helicobacter pylori (Hp) infection results in chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) preceding adenocarcinoma (AdCa).. Looking for a potential biomarker of malignant transformation in the setting of chronic inflammation we studied the levels of prostaglandin E2 (PGE(2)), as well as peptide growth factors [epidermal growth factor (EGF) and transforming growth factor α (TGFα)], harbingers of injury and repair, in gastric juice aspirated at endoscopy from patients with CAG, CAG/IM, AdCa, and controls.. The PGE(2), EGF and TGFα concentrations in the gastric juice were measured using radioimmunoassays (RIAs).. In patients with AdCa gastric juice PGE(2) increased fivefold versus controls (P < 0.01) and almost threefold versus patients with CAG (P < 0.05). The EGF levels in patients with AdCa were fourfold higher versus controls (P < 0.001) and almost threefold higher versus CAG (P < 0.05). In patients with CAG/IM the EGF levels were also almost 3 times higher versus controls. The TGFα levels in patients with AdCa were half the value of controls and CAG (P < 0.05). In patients with CAG/IM the levels were as low as 1/5 of controls or CAG (P < 0.05).. Testing the gastric juice for PGE(2), EGF, and TGFα in patients with endoscopy and biopsy proven CAG, may be helpful in follow up of patients who may potentially progress to IM and ultimately AdCa. This could be considered as an adjunct to histologic assessment especially that even the best surveillance biopsy specimen regimens are inherited with sampling errors.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Digestive System Neoplasms; Dinoprostone; Epidermal Growth Factor; Female; Gastric Juice; Gastritis, Atrophic; Helicobacter Infections; Humans; Intestines; Male; Metaplasia; Middle Aged; Pilot Projects; Transforming Growth Factor alpha

To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms.. Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E) and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (microm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE(2), EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue.. Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+/-0.28) microg/L, EGF in CAG (2.24+/-0.83) microg/L was significantly higher (P<0.05). The levels of PGE(2) and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in the nucleus of epithelial cells. The former was higher positively expressed in atrophic gland, while the later was higher positively stained in normal gastric tissue. bcl-2 protein was positively stained in the cytoplasma in atrophic gastric gland, while very weakly stained in normal gastric tissue.. The pathological findings in gastric gland accorded with the Houston diagnostic criteria of antrum-predominant CAG. CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. There was high protein expression of oncogene, while inhibitor of suppressor gene in CAG rats indicated high trend of carcinogenesis.

Topics: Animals; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Immunohistochemistry; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Tumor Suppressor Protein p53

This study, carried out on 51 patients with multifocal atrophic gastritis (MAG) and 92 age and sex-matched dyspeptic controls, was designed to examine both exocrine (gastric acid) and endocrine (gastrin) gastric secretion before and after therapeutic intervention including Helicobacter pylori eradication and vitamin C treatment.. Fasting and gastrin-releasing peptide-induced gastric acid secretion, serum levels of gastrin and proinflammatory (IL-1beta, IL-8, TNF-alpha) as well as gastric mucosal gene expression of ornithine decarboxylase (ODC), cyclooxygenase 2 (COX-2) and growth factors (epidermal growth factor and transforming growth factor alpha) were determined before and after the eradication of Helicobacter pylori and therapy with large doses (1 g/d) of vitamin C for 3 months.. The H. pylori eradication, assessed by C-urea breath test, and vitamin C therapy failed to reverse the histological atrophy of the gastric mucosa but improved significantly the functional status of the atrophied mucosa, especially its exocrine and endocrine secretory activities, attenuated the expression of premalignant markers such as ODC and COX-2, raised the production of growth factors and diminished the release of proinflammatory cytokines.. These results indicate that MAG may be considered as an environmental disease of the gastric mucosa, whose functional status can be improved by the eradication of H. pylori combined with antioxidant therapy with large doses of vitamin C.

Topics: Adult; Aged; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Case-Control Studies; Cyclooxygenase 2; Cytokines; Epidermal Growth Factor; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Ornithine Decarboxylase; RNA, Messenger; Transforming Growth Factor alpha

To investigate the mechanism of isinglass in the prevention and treatment of chronic atrophic gastritis (CAG) in rats.. Animal models of SD rats with CAG were made in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while CAG rat model was being made. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed. Then the length of the proliferation zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth hormones (GH)level were studied.. In isinglass prevention groups and high dose isinglass reverse group, the length of the proliferation zone of the gastric mucosa was very close to that in normal control group (P > 0.05), much better than model control group (P < 0.01). In low dose isinglass reverse group, it was lower than that in normal control group (P < 0.01), but much better than model control group (P < 0.01). In both prevention and reverse groups, serum EGF level was higher than that in normal (P < 0.01) and model control group (P < 0.05). Serum GH level was the same in every group (P > 0.05).. The mechanism of isinglass in the prevention and treatment of CAG rats lies in revitalizing and proliferating gastric mucosal cells by stimulating endogenous EGF secretion.

Topics: Animals; Chronic Disease; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Gastritis, Atrophic; Gelatin; Growth Hormone; Materia Medica; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley

To investigate the epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) expression in atrophic gastritis in rats to explore the relationship between EGF and chronic atrophic gastritis(CAG).. The serum EGF and gastric mucosal, EGFR level were measured in 20 rats with CAG and 20 normal controls.. The average EGF level (0.149+/-0.020) microg/L and 80% positive rate of EGFR expression observed in CAG group were significantly higher than those in control group[(0.043+/-0.003) microg/L and 0%,P<0.01].. The study demonstrates an association of high levels of EGF and positive EGFR expression in CAG rats. Further studies are necessary to clarify whether EGF/EGFR play a significant role in the pathogenesis of CAG.

Topics: Animals; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastritis, Atrophic; Male; Rats; Rats, Sprague-Dawley

Epidermal growth factor (EGF) receptor ligands (EGFRL) including transforming growth factor alpha (TGF-alpha), amphiregulin, and heparin binding-EGF (HB-EGF) are involved in gastric mucosal repair in chronic gastritis. Their mRNA expression has been shown to be upregulated after Helicobacter pylori (H.p.)-eradication but little is known about this gene expression in atrophic gastritis. The purpose of our study was to investigate EGFRL mRNA expression in gastric mucosa of patients with atrophic gastritis before and after H.p.-eradication.. Antral mucosal biopsies were obtained during endoscopy in 10 H.p. positive patients with atrophic gastritis and in 10 H.p. negative controls with intact mucosa. Total RNA of antral biopsies was extracted and RT-PCR was performed, the PCR-products being measured densitometrically. Values were compared with mRNA expressions in H.p. negative antral mucosa (n=10).. Gastric biopsies revealed mRNA expression for TGF-alpha, amphiregulin and HB-EGF, both in H.p. positive atrophic antritis and in H.p. negative healthy mucosa. The mRNA expression of TGF-alpha in atrophic gastritis was significantly upregulated after H.p.-eradication, whereas that of amphiregulin did not change after this eradication. Expression of HB-EGF mRNA was higher in H.p.-infection than after H.p.-eradication or in H.p. negative healthy subjects.. H.p. positive atrophic gastritis is associated with differential mRNA expression of EGF receptor ligands. H.p.-eradication in this entity leads to unequal changes of these growth factor expressions compared to chronic active gastritis without atrophy.

Topics: Amphiregulin; Base Sequence; DNA Primers; EGF Family of Proteins; Epidermal Growth Factor; ErbB Receptors; Gastritis, Atrophic; Glycoproteins; Growth Substances; Helicobacter Infections; Helicobacter pylori; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Ligands; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor alpha

To investigate the effect of various combinations of Spleen invigorating and Dampness removing recipes and western medicine on level of serum epidermal growth factor (sEGF) in patients of chronic atrophic gastritis (CAG).. By means of Syndrome Differentiation three groups were divided as (1) Spleen invigorating I group (SI-I); (2) Spleen invigorating II group (SI-II); (3) Dampness removing group (DR); (4) western medicine group (WM); (5) healthy volunteers served as normal control group. The changes of symptoms and sEGF level were determined and compared between groups as well as before and after treatment.. The sEGF in various groups of CAG were higher than that in the normal control (P < 0.01). In patients of SI-I and II groups, symptoms and pathological manifestations were improved significantly (P < 0.01), and sEGF dropped markedly after treatment (P < 0.01 and P < 0.05). The level of sEGF in DR raised after treatment (P < 0.05), but the level of sEGF in WM group lowered insignificantly.. Inflammation of gastric mucosa could cause responsive elevation of sEGF in CAG patients. After treated with Spleen invigorating and Dampness removing Chinese drugs, the symptoms of CAG improved, simultaneously with the restoration of sEGF. sEGF could be taken as a sensitive index of the prognosis of CAG.

Topics: Adult; Biomarkers; Drugs, Chinese Herbal; Epidermal Growth Factor; Female; Gastritis, Atrophic; Humans; Male; Middle Aged; Phytotherapy; Prognosis

We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy.. We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment.. TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission.. In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Megaloblastic; Animals; Bone Marrow; Epidermal Growth Factor; Female; Folic Acid; Follow-Up Studies; Gastritis, Atrophic; Homocysteine; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Peripheral Nervous System Diseases; Rats; Species Specificity; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 12 Deficiency

To study the effect of epidermal growth factor (EGF) on the pathologic changes of gastric mucosa in rats with chronic atrophic gastritis(CAG).. The established rat models of CAG were divided into therapy group and control group. The rats in the therapy group received EGF 10 microg/kg subcutaneously (SC), whereas these in the control group the same volume of normal saline SC. 12 weeks later, all rats were killed by cervical dislocation and their gastric mucosa were examined with microscope.. The grade of inflammatory cell infiltration in the therapy group was lower than that in the control group (P < 0.01). The thickness of gastric mucosal gland layer was (215.0 +/- 20.7) microm in the therapy group and (139.2 +/- 13.8) microm in the control group (P < 0.01). The ratio of the thickness of gastric mucosal glands and muscularis mucosa(L(1)/L(2)) was 2.70 +/- 0.34 in the therapy group and 1.27 +/- 0.27 in the control group (P < 0.01). The number of gastric glands in 1 mm length of mucosal layer was 26.20 +/- 1.27 in the therapy group and 19.90 +/- 1.78 in the control group (P < 0.01). In the therapy group, the gastric glands were rearranged in order, without signs of malignant proliferation. The width of the expression of proliferating cell nuclear antigen (PCNA ) of gastric mucosa was higher in the therapy group than in the control group [(77.70 +/- 4.16) microm vs (54.40 +/- 4.54) microm, P < 0.01].. EGF played a therapeutic role in reversing the gastric mucosal atrophy of the rats with CAG. It promoted the expression of PCNA, which induced a protective proliferation of the gastric mucosal lesions in the rats with CAG.

Topics: Animals; Epidermal Growth Factor; Gastric Mucosa; Gastritis, Atrophic; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley

Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined.. The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice.. INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor alpha. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (< or = 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P < or = 0.05).. These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer.

Topics: Animals; Cell Count; Epidermal Growth Factor; Epithelial Cells; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Heparin; Heparin-binding EGF-like Growth Factor; Hyperplasia; Hypertrophy; Intercellular Signaling Peptides and Proteins; Metaplasia; Mice; Mice, Transgenic; Stomach Neoplasms; Transforming Growth Factor alpha

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Transforming Growth Factor alpha

In 10 patients with Helicobacter pylori (HP) positive chronic gastritis, gastric mucosal content of interleukin (IL)-1 beta, IL-8, Transforming Growth Factor (TGF)-beta 1, Epidermal Growth Factor (EGF) and Polyamines (putrescine, spermine and spermidine) was evaluated before and after eradicating treatment. Histologically, in all patients eradication of HP was accompanied by a marked reduction of the inflammatory infiltrate. At the same time, at the end of the therapeutical regimen, elevated levels of IL-1 beta, IL-8, TGF-beta 1, putrescine and spermidine/spermine ratio significantly dropped, while EGF mucosal content, significantly increased. Results are discussed in terms of the reciprocal role of inflammatory cytokines, growth factors and polyamines in the evolution of the HP-associated chronic gastritis.

Topics: Cytokines; Epidermal Growth Factor; Gastric Mucosa; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Polyamines

Pancreatic acinar metaplasia of the gastric mucosa is a newly recognized entity. Its physiological relevance and association with other pathological conditions in the stomach remain to be elucidated. We studied by immunohistochemistry the expression of growth markers in the gastric mucosa in biopsies from 15 patients with recognized pancreatic metaplasia. Pancreatic metaplasia (both acinar and dispersed forms) was found in routine paraffin sections and confirmed by strong lipase immunoreactivity. In parallel paraffin sections we performed immunostaining for epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) and epidermal growth factor receptor (EGFr) using a biotin streptavidin method. Strong expression of TGF alpha but only weak expression of EGF was noted within metaplastic mucosa. EGFr was strongly expressed, not only in areas of pancreatic metaplasia but also in the surrounding gastric mucosa.

Topics: Antibodies; Epidermal Growth Factor; Female; Gastric Mucosa; Gastritis, Atrophic; Humans; Lipase; Male; Metaplasia; Pancreas; Stomach; Transforming Growth Factor alpha