epidermal-growth-factor and Duodenal-Ulcer

Important role is attributed to the growth factors in the development, growth, and restitution after injury of the gastrointestinal tract. The common feature of growth factors is their ability to stimulate the growth and mitosis of quiescent cells in a nutritionally complete medium which in itself is not sufficient to initiate cell division. Epidermal growth factor prevents efficiently the experimentally induced acute gastric mucosal lesions induced by aspirin, absolute ethanol, HCl, NaCl, immobilization, and immersion and it accelerates the healing of acetic acid-induced chronic gastric and cysteamine-induced chronic duodenal ulcers. It proved to be also useful in the treatment of human gastric ulcers. Fibroblast growth factor possesses similar gastroprotective and chronic ulcer-healing properties. Its effects is much more potent than that of epidermal growth factor and that of H2-receptor blockers. The "trefoil"-peptides constitute the latest family of growth factors which are supposed to be involved in the regeneration of the normal and the ulcerated gastrointestinal mucosa. Polyamines are non-peptide growth promoting compounds present in all eukaryotic cells; their gastroprotective and ulcer-healing properties have also been published. The use of some growth factors as regenerative and angiogenic therapy could open a new, alternative way in the future management of peptic ulcer disease.

Topics: Animals; Aspirin; Chronic Disease; Duodenal Ulcer; Epidermal Growth Factor; Ethanol; Fibroblast Growth Factors; Gastric Mucosa; Humans; Polyamines; Rats; Stomach Ulcer

Topics: Duodenal Ulcer; Epidermal Growth Factor; Fibroblast Growth Factors; Humans

Our aim was to study the efficacy of oral human recombinant epidermal growth factor (EGF) in the treatment of duodenal ulcers, on the basis of its repairing actions in the gastrointestinal tract.. A placebo-controlled, multicenter, randomized, and double-blind study was conducted. Treatment groups were A) placebo solution, B) 10 microg/ml of human recombinant (hr)-EGF, and C) 50 microg/ml of hr-EGF, three times daily during 6 weeks. Patients, 15-65 years old, with a duodenal ulcer >4 mm, who gave their written informed consent to participate were eligible. Exclusion criteria were gastric ulcer and more than one duodenal ulcer, ulcer-related complications, and previous treatment with oral EGF or other specific anti-ulcer drugs in the previous 2 weeks. The main outcome variable was ulcer healing, evaluated by endoscopy after the 2nd, 4th, and 6th week.. One hundred and three patients were included. The groups were comparable with regard to age, sex, toxic habits, antecedents of ulcerous disease, initial size and depth or the ulcer, initial symptoms, and positivity for Helicobacter pylori. The ulcers were healed in a larger proportion of patients treated with hr-EGF at the highest dose (70.6% in group C versus 40.0% and 35.3% in placebo and low-dose groups, respectively (P = 0.007)). The difference was significant from week 4 on. Groups A and B did not differ. Eighty-eight percent of group C patients were cured or improved versus 57% and 56% in groups A and B, respectively. No adverse reactions were reported.. Oral hr-EGF was effective in the treatment of duodenal ulcer at a 50-microg/ml dose every 8 h but not at 10 microg/ml.

Topics: Administration, Oral; Adolescent; Adult; Aged; Double-Blind Method; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

We designed this study to follow exocrine, endocrine and microstructural changes in duodenal ulcer patients with H. pylori infection in the course and after quadruple eradication regimen. Quadruple therapy appeared to be highly effective method of both ulcer healing and H. pylori eradication. We observed enhanced regeneration of gastric mucosa in the course of treatment. Almost immediate decrease of plasma gastrin and increase of plasma somatostatin and EGF concentration in gastric juice were noticed.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Somatostatin

The epidermal growth factor has been shown to be mucoprotective and to accelerate healing of gastroduodenal ulcers in animals. A prospective, positively controlled clinical trial was conducted. Seventy five patients with duodenal ulcer were randomly distributed in three groups to receive oral human recombinant epidermal growth factor in 1% carboxymethyl cellulose at two different doses (450 mg or 600 mg/day), or cimetidine. Treatment was administered up to a maximum of 6 weeks. The most important assessment criteria was the proportion of patients healed after 2, 4 and 6 weeks of treatment determined by endoscopy. Treatment with both doses of epidermal growth factor showed a long-term healing effect in 76.5% at 6 weeks vs 92.5% with cimetidine (p = N.S.). The evolution of the clinical symptoms was similar in the three groups. Adverse reactions were not detected in any of the patients included in this study. To our knowledge, this is the first report on the oral use of epidermal growth factor in humans.

Topics: Administration, Oral; Adolescent; Adult; Aged; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Time Factors

Epidermal growth factor (EGF) was measured in saliva and in gastric juice under basal conditions and after histamine stimulation (0.04 mg kg-1h-1). Sixty subjects studied comprised 20 normal volunteers, 20 patients with duodenal ulcer (DU), and 20 patients with non-ulcer dyspepsia (NUD). There was no difference in basal salivary EGF concentrations between control and DU or control and NUD subjects, but the EGF concentration in DU patients exceeded that in NUD patients (p < 0.05). Basal gastric juice concentrations of EGF were similar in all three groups. There was no difference between basal salivary and gastric EGF concentrations (p > > 0.05). After histamine stimulation, salivary and gastric EGF concentrations increased in all three groups: the increase was greater in gastric juice than saliva (p < 0.0001). There were no significant differences in the salivary EGF concentrations of controls and NUD patients, or controls and DU patients, but values were significantly higher when DU and NUD patients were compared (p = < 0.05). In the gastric juice, EGF increased more in DU patients than in controls or NUD patients (p < 0.05). This effect was not linked to the greater acid secretion in DU than in the other groups. There was no influence of gender or smoking on the EGF concentration. This evidence suggests that the stomach itself may be able to secrete large amounts of EGF and that histamine is a potent stimulus. It is more likely that the gastric EGF is responding to the presence of a duodenal ulcer than that lack of EGF is responsible for persistence of the ulcer.

Topics: Adult; Duodenal Ulcer; Dyspepsia; Epidermal Growth Factor; Female; Gastric Juice; Histamine; Humans; Male; Middle Aged; Saliva; Stimulation, Chemical

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Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastrins; Gastrointestinal Hemorrhage; Humans; Stomach Ulcer

The aim of our study is to investigate EGF content in biological mediums in children with duodenum ulcer depending on phase of the disease and different variants of its course.. The present study was performed in Federal State Establishment "Nizhniy Novgorod Research Institute of Children Gastroenterology", Nizhniy Novgorod, Russia. 92 children, between the ages of 8 to 17, with duodenum ulcer were under observation. Endoscopy was performed by Pentax endoscope (FG-24V). EGF detection was performed in blood serum, gastric juice and saliva by ELISA method with Human EGF Kit, "Invitrogen", USA.. The peculiarities of EGF level changes in human biological mediums, depending on phase of the disease. The highest EGF level was detected with acute peptic ulcer in the presence of ulcerous defects. EGF level increasing was marked out in the remission phaseas ulcerous defects healing, and it didn't reach normal values in gastric juice. EGF content changes in biological mediums were revealed with different variants of duodenum ulcer clinical course in children. The lowest EGF level was marked out in blood, saliva and gastric juice with unfavorable course of the disease (frequent relapses, cicatricial-ulcerous strains formation), which can serve as a prognostic factor.

Topics: Adolescent; Child; Duodenal Ulcer; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Gastric Juice; Humans; Male; Patient Acuity; Saliva; Serum; Wound Healing

The concentrations of epidermal growth factor (EGF) in saliva, gastric juice, and blood and those of macrophages in mucosal biopsy specimens were determined in children with duodenal ulcer disease. The maximum level of EGF was noted in the saliva. There were unidirectional positive changes in the levels of EGF and macrophages during ulcerative defect healing.

Topics: Adolescent; Cell Count; Child; Duodenal Ulcer; Epidermal Growth Factor; Female; Gastric Juice; Humans; Macrophages; Male; Saliva

Erosive esophagitis frequently develops after successful Helicobacter pylori eradication. Since salivary secretion of epidermal growth factor (EGF) plays a crucial role in the pathogenesis of gastroesophageal reflux disease, the current study objective was to find out whether erosive esophagitis development after Helicobacter pylori eradication is associated with the secretion of EGF in saliva.. A total of 115 H. pylori infected patients (positive results of CLO-test, histology and serology) with a duodenal ulcer were recruited for the study. Gastroscopic examinations and saliva collections were performed twice, prior to H. pylori eradication and one year after its cessation. The salivary EGF was determined using a radioimmunological method.. Salivary EGF secretion was lower in H. pylori infected subjects with erosive esophagitis than without (0.82+/-0.66 vs 1.70+/-3.49 ng/min, p=0.021). However, a year after successful H. pylori eradication, salivary EGF did not differ between the groups (2.17+/-2.06 vs 1.79+/-2.06 ng/min); the lack of difference was due to high peptide secretion in patients who developed erosive esophagitis after eradication.. Erosive esophagitis development following H. pylori eradication is not the result of decreased salivary EGF secretion.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Epidermal Growth Factor; Esophagitis; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Saliva; Young Adult

To investigate the effect of epidermal growth factor (EGF) on mucosal healing in rats with duodenal ulcer.. Male Sprague-Dawley rats were randomly divided into sham operation without EGF, sham operation with EGF, duodenal ulcer without EGF, or duodenal ulcer with EGF groups. Additionally, normal rats without operation served as the control group. Duodenal ulcer was induced in rats by 300 mL/L acetic acid. Rats with EGF were orally administered at a dose of 60 microg/kg/day in drinking water on the next day of operation (day 1). Healing of duodenal ulcer was detected by haematoxylin and eosin staining. Cell growth of damaged mucosa was determined by the contents of nucleic acids and proteins. The level of EGF in duodenal mucosa was measured by ELISA.. The pathological results showed that duodenal ulcer rats with EGF improved mucosal healing compared with those without EGF after day 5. Duodenal ulcer rats with EGF significantly increased duodenal DNA content compared with those without EGF on day 15 (6.44+/-0.54 mg/g vs 1.45+/-0.52 mg/g mucosa, P<0.05). Duodenal RNA and protein contents did not differ between duodenal ulcer rats with and without EGF during the experimental period. Sham operation and duodenal ulcer rats with EGF significantly increased duodenal mucosal EGF content compared with those without EGF on day 5 (76.0+/-13.7 ng/g vs 35.7+/-12.9 ng/g mucosa in sham operation rats, and 68.3+/-10.9 ng/g vs 28.3+/-9.2 ng/g mucosa in duodenal ulcer rats, P<0.05).. Oral EGF can promote mucosal healing of the rats with duodenal ulcer by stimulating mucosal proliferation accompanied by an increase in mucosal EGF content.

Topics: Acetic Acid; Administration, Oral; Animals; DNA; Duodenal Ulcer; Eating; Epidermal Growth Factor; Intestinal Mucosa; Male; Proteins; Rats; Rats, Sprague-Dawley; RNA; Weight Gain; Wound Healing

Helicobacter pylori (Hp) infection causes duodenal ulcers, delays the healing of such ulcers, and is associated with ulcer recurrence. The pathogenic mechanisms involved in Hp-induced duodenal mucosal injury and delay in ulcer healing remain unclear. In this study we sought to investigate the possible pathogenic actions of Hp infection and vacuolating cytotoxin (Vac A) on duodenal epithelial wound healing, using an in vitro wound model consisting of excisionally scraped or eroded IEC-6 duodenal monolayers. Two isogenic strains of Hp were used: wild-type strain 60190, producing Vac A; and an isogenic mutant strain, 60190-v1, that lacks the gene to produce the cytotoxin. The addition of Vac A-positive or Vac A-negative Hp (50:1 ratio of bacterial to epithelial cells) to the eroded or "wounded" IEC-6 monolayers resulted in significant inhibition of wound reepithelialization. The Vac A-positive Hp produced significantly greater inhibition than did the Vac A-negative Hp (70% and 35% inhibition, respectively; P <.001). Additionally, the bacterial supernatant containing Vac A (but not the supernatant lacking the cytotoxin) caused significant inhibition of IEC-6 wound reepithelialization in the absence of Hp infection, indicating that Vac A has an independent inhibitory action on wound reepithelialization. The Vac A inhibition of IEC-6 reepithelialization correlated with down-regulation of actin stress fibers in the migrating cells. Epidermal growth factor (EGF) stimulated IEC-6 wound reepithelialization with a corresponding increase in the formation of actin stress fiber. Vac A-positive bacterial supernatant (but not Vac A-negative supernatant) prevented the EGF-stimulated increase in IEC-6 actin stress fiber formation and wound reepithelialization. These findings demonstrate that Hp infection inhibits the process of duodenal epithelial wound healing. Hp inhibition of duodenal wound healing may therefore be an important pathogenic factor contributing to duodenal mucosal injury and delay in ulcer healing in vivo.

Topics: Actins; Animals; Bacterial Proteins; Cell Division; Cell Line; Down-Regulation; Duodenal Ulcer; Epidermal Growth Factor; Helicobacter Infections; Helicobacter pylori; Intestinal Mucosa; Rats; Wound Healing

Nonsteroidal anti-inflammatory drugs (NSAIDs) delay peptic ulcer healing through mechanisms that are still not entirely understood. Growth factors play a significant role in healing.. To evaluate whether exogenous administration of platelet-derived growth factor (PDGF) reverses the effect of indomethacin in experimental duodenal ulcers in rats and to define the potential mechanisms involved in this process.. Duodenal ulcer was induced in male Wistar rats with acetic acid. The rats were then administered indomethacin (2 mg/kg/day), PDGF-BB (30 ng/100 g/day), epidermal growth factor (EGF) (50 /kg/day) or famotidine (positive control) or the possible combinations of these. Macroscopic area, reduction in microscopic diameter, epithelial and granulation tissue proliferation, collagen secretion by granulation tissue, and gastric acid secretion were analyzed.. Indomethacin delayed duodenal ulcer healing by decreasing cellular proliferation and inhibiting collagen secretion. PDGF and EGF accelerated healing and reversed the effects of indomethacin. The mechanisms involved were associated with an increase in collagen proliferation and secretion without affecting gastric acid secretion. Famotidine also accelerated healing and reversed the effect of indomethacin, and these effects were associated with a marked inhibition of gastric acid secretion and increase in collagen secretion by granulation tissue.. Exogenous administration of PDGF and EGF accelerated healing and reversed the harmful effects of indomethacin in an experimental model of duodenal ulcer.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Duodenal Ulcer; Epidermal Growth Factor; Famotidine; Indomethacin; Male; Platelet-Derived Growth Factor; Rats; Rats, Wistar; Wound Healing

Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication.. The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression.. Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication.. Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Chronic Disease; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; ErbB Receptors; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Polymerase Chain Reaction

Epidermal growth (EGF) and transforming growth factor alpha (TGFalpha) are potent gastric secretory inhibitors, mitogens, and mucosal protectors, but the impact of Helicobacter pylori infection on their mucosal expression and luminal release has not been clarified.. In this study, gene and immunoreactive and immunohistochemical expressions of EGF and TGFalpha were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals, in 22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin + omeprazole) and 4 weeks and 2 years later.. Immunohistochemical expression of EGF and TGFalpha in H. pylori-positive DU and NUD was significantly higher than in H. pylori-negative normals, and this increase persisted at 2 and 4 weeks after therapy but normalized 2 years later. EGF mRNA was detected in the gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H. pylori eradication, but it was not found 2 years after the eradication of H. pylori or in gastric mucosa of H. pylori-negative control subjects. TGFalpha mRNA was detected in the gastric mucosa independently of H. pylori status, with the stronger expression observed in the gastric mucosa of H. pylori-positive DU and NUD before eradication than after this procedure. Plasma gastrin, which was significantly increased in H. pylori-positive DU, normalized already after 2 weeks of triple therapy. The eradication rate as determined by histology after triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years after the eradication the H. pylori reinfection rate was 4.5% among DU patients and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in complete ulcer healing.. 1) Chronic H. pylori infection and resulting antral gastritis are associated with increased plasma gastrin and increased mucosal cell proliferation, probably due to enhanced expression of EGF and TGFalpha, and 2) the H. pylori eradication results in a decrease in plasma gastrin, but the increase in gastric TGFalpha and EGF content is sustained, suggesting that they may be involved in ulcer healing.

Topics: Adult; Cell Division; Duodenal Ulcer; Dyspepsia; Epidermal Growth Factor; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Polymerase Chain Reaction; Proliferating Cell Nuclear Antigen; Radioimmunoassay; Transforming Growth Factor alpha

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and protection but their involvement in Helicobacter pylori associated duodenal ulcer has been little examined.. To assess gastric acid secretion, plasma gastrin concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of these peptides and their receptor (EGFr) as well as salivary and gastric luminal release of EGF under basal conditions and after pentagastrin stimulation in 10 healthy subjects and in 25 H pylori positive patients with duodenal ulcer before and after two weeks of triple anti-H pylori therapy and four weeks after the termination of this therapy.. Pentagastrin stimulation caused a significant increase in salivary and gastric release of EGF both in healthy controls and patients with duodenal ulcers but in the patients, the eradication of H pylori resulted in several fold higher gastric luminal (but not salivary) EGF release than before the anti-H pylori therapy. Mucosal contents of immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and EGFr in H pylori positive patients with duodenal ulcer were significantly higher than those in healthy H pylori negative controls and this increase persisted after eradication of H pylori. Basal plasma gastrin was significantly reduced after two weeks of triple therapy and four weeks after the H pylori eradication all ulcers were completely healed.. (1) H pylori infection in patients with duodenal ulcer was accompanied by enhanced plasma gastrin and increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and enhancement of gastric (but not salivary) luminal release of EGF, particularly after pentagastrin stimulation; and (3) enhanced mucosal content and expression of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute to ulcer healing after eradication of H pylori.

Topics: Duodenal Ulcer; Epidermal Growth Factor; ErbB Receptors; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pentagastrin; Saliva; 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

Epidemiological studies have consistently shown an association between infection of Helicobacter pylori (Hp) and duodenal ulcer (DU) and gastric cancer. The mechanism of the ulcerogenic effect of Hp has been related to excessive gastrin release, gastric acid hypersecretion and gastric metaplasia in duodenum. The implication of Hp in gastric carcinogenesis has not been explained. In this study, mucosal expression of EGF and TGF alpha and luminal release of EGF as well as basal and pentagastrin-stimulated acid secretion and plasma gastrin levels have been determined in healthy subjects, gastric carcinoma and DU patients. It was found that Hp positive DU patients show excessive gastrin release and gastric acid secretion combined with increased expression and luminal release of EGF and TGF alpha. These changes returned to normal values two years after the eradication of Hp. Gastric cancer patients also showed increased expression of EGF and TGF alpha and highly increased plasma gastrin but their gastric acid secretion was markedly reduced possibly due to atrophy of oxyntic mucosa. This study indicates that overexpression of growth factors in gastric mucosa may be implicated in the pathogenesis of both duodenal ulcer and gastric cancer and that Hp positive hypochlorhydric and hypergastrinemic patients may be predisposed to development of gastric cancer.

Topics: Adult; Aged; Carcinoma; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Juice; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunochemistry; Middle Aged; Pentagastrin; Stomach Neoplasms; Transforming Growth Factor alpha

Epidermal growth factor (EGF) is secreted by salivary and Brunner's glands and shows a potent inhibitory effect on gastric acid and stimulatory influence on mucosal growth and protection but little is known about the effect of the Helicobacter pylori (Hp) infection on the release of EGF. In this study the salivary and gastric concentrations of EGF have been measured and gastric mucosal expression of EGF has been determined in 25 Hp positive duodenal ulcer (DU) patients before and after the eradication of Hp (using triple therapy with omeprazole, 20 mg bd, amoxycillin, 500 mg qd and metronidazole, 500 mg bd for 2 weeks) and in 10 healthy controls under basal conditions and following pentagastrin (2 micrograms/kg-h) stimulation. Basal salivary and gastric concentrations of EGF were similar and no significant difference was found between DU patients and healthy controls. Pentagastrin infusion (2 micrograms/kg-h) caused a significant increase in EGF release into saliva and gastric juice both in healthy controls and DU patients but in DU patients the Hp eradication resulted in several folds higher basal and pentagastrin-induced gastric EGF content than that before the anti-Hp therapy, whereas such Hp eradication had no significant influence on basal and pentagastrin-induced salivary EGF. Antral mucosal expression of EGF in Hp-positive DU patients was significantly higher than that in healthy Hp-negative controls and this elevation persisted after eradication of Hp. Basal and pentagastrin-induced gastric acid outputs in Hp-positive DU patients were significantly higher than in healthy controls and they were slightly reduced after the triple therapy. In all DU patients, 4 weeks after termination of anti-Hp therapy, a complete ulcer healing occurred. We conclude that (1) the stomach is capable of secreting large amounts of EGF and pentagastrin appears to be a potent stimulus of salivary and gastric EGF release; (2) the Hp infection reduces the release of gastric EGF and the eradication of Hp results in the augmentation of basal and pentagastrin-induced EGF release into the stomach but not into the saliva and (3) since the eradication of Hp infection in DU patients resulted in DU healing and this was accompanied by an increase in EGF release, we conclude that EGF plays a crucial role in the DU healing process.

Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Pentagastrin; Saliva

Helicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastric acid secretion, and is a powerful mitogen.. We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effects of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease.. GL-EGF was reduced in smokers compared to controls (p = .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p = .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p = .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p = .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU associated and non-ulcer-associated gastritis.. Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals and Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Epidermal Growth Factor; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastritis; Gastrointestinal Contents; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Peptic Ulcer; Smoking

The level of epidermal growth factor (EGF) was measured in the basal and maximally stimulated gastric juice of 20 control subjects and 20 patients each with duodenal ulcer and non-ulcer dyspepsia. Basal gastric juice was analysed for ammonia and urea concentrations, and the [ammonia]3/[urea] ratio was used to show Helicobacter pylori status, as was the [13C]urea breath test in nine controls. There was complete concordance in the nine controls between the two methods for determining H. pylori status. Twenty-five subjects were H. pylori positive (seven with duodenal ulcer, nine with non-ulcer dyspepsia, nine controls) and 35 H. pylori negative (13, 11 and 11 respectively). In H. pylori-positive subjects, the median EGF concentrations in the stimulated secretion of patients with duodenal ulcer and without (non-ulcer dyspepsia and controls combined) were 46.7 and 18.0 ng/ml (P < 0.001), and in H. pylori-negative subjects were 40.0 and 26.5 ng/ml respectively (P < 0.01). There was no difference in EGF concentration between controls and subjects with non-ulcer dyspepsia irrespective of H. pylori status. Lack of EGF is unlikely to be a cause of duodenal ulcer. The increased EGF concentration in patients with ulcer bore no relationship to the H. pylori status of the individual. If this bacterium causes duodenal ulcer, it is not via a reduction in EGF concentration.

Topics: Breath Tests; Duodenal Ulcer; Dyspepsia; Epidermal Growth Factor; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans

Smoking is associated with an increased incidence of duodenal ulcer with a high relapse rate, and smokers tend to be slow healers. The etiology responsible for this remains unknown, and there is general disagreement as to whether smoking affects gastric secretion. The aim of the present study was to investigate both aggressive and protective factors in response to vagal stimulation induced by modified sham feeding (MSF) in duodenal ulcer patients when smoking versus not smoking. On smoking days, nicotine concentrations in plasma averaged about 15 ng/ml and were extremely high in saliva and gastric juice (> 1300 and > 800 ng/ml, respectively). MSF induced a significant decrease in intragastric pH during non-smoking (p = 0.01) but not during smoking. Acid output 1 h after MSF was lower on smoking than on non-smoking days (p = 0.02), as was volume secretion (p = 0.02). Plasma gastrin concentrations were significantly increased during MSF on non-smoking days (p = 0.04) but not on smoking days, the concentrations during the whole day being lower on smoking days (p = 0.002). Plasma catecholamine levels were unaffected by MSF, whether smoking or not. However, plasma concentrations of noradrenaline decreased during the smoking of a single cigarette (p = 0.03), whereas those of adrenaline were increased on smoking days (p = 0.02). Epidermal growth factor concentrations were decreased in gastric juice after MSF during non-smoking (p = 0.01) but not during smoking. Although prostaglandin E2 (PGE2) concentrations in gastric juice were unaffected by MSF, PGE2 output increased after MSF whether smoking or not, the increment being non-significantly less during smoking (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bile Acids and Salts; Catecholamines; Dinoprostone; Duodenal Ulcer; Eating; Epidermal Growth Factor; Female; Gastric Acid; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Nicotine; Saliva; Smoking; Vagus Nerve

The effect of epidermal growth factor (EGF) on alkaline secretion and mucus formation which serve as defenses against mucosal injury was investigated using a perfusion system of the proximal duodenum in rats in situ. In control rats, intravenous or intraduodenal administration of EGF (1 or 10 micrograms/kg/hr) had no effect on mucosal alkaline secretion at high (pH 2.5-3.0) or low (pH 3.0-5.5) luminal acidities. In cysteamine-treated rats (250 mg/kg weight, intramuscular injection), mucosal alkaline secretion by intravenous EGF (10 micrograms/kg/hr) increased significantly only at levels of high luminal acidity, whereas that by intraduodenal EGF (10 micrograms/kg/hr) increased greatly at both high and low luminal acidities. Analysis by a color image processor revealed that cysteamine greatly reduced the PAS-stained mucus in the duodenal mucosa and in Brunner's glands. Intraduodenal administration of EGF significantly increased the PAS-stained mucus in the duodenal mucosa, but not in Brunner's glands. These results indicate that EGF exerts the cytoprotective effect by stimulating alkaline secretion and mucus formation in the duodenal mucosa.

Topics: Animals; Brunner Glands; Cysteamine; Duodenal Ulcer; Duodenum; Epidermal Growth Factor; Hydrogen-Ion Concentration; Intestinal Secretions; Male; Mucus; Rats; Rats, Wistar

Topics: Depression, Chemical; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Male; Saliva; Secretory Rate; Smoking; Stomach Ulcer

Recent animal studies suggest salivary epidermal growth factor (EGF) has a cytoprotective effect in the upper GI tract and is one of the important factors to promote the healing of experimental ulcer. The present study was undertaken to clarify the role of salivary EGF in peptic ulcer patients. Saliva samples were collected from 129 endoscopically normal subjects and 232 peptic ulcer patients. Salivary EGF concentration was measured by RIA. Salivary EGF output in normal subjects was 5.26 +/- 0.26 (ng/5 min) (mean +/- SE). Those in patients with gastric ulcer (GU), duodenal ulcer (DU) and gastroduodenal ulcer (GDU) were 10.74 +/- 0.15, 8.13 +/- 0.83 and 9.79 +/- 0.91. EGF output in GU and GDU patients were higher than that in normal subjects respectively. Tractable GU patients (healed within 3 months with regular regimen) had higher EGF output than intractable GU patients. Among tractable GU patients, those who had healing within 8 weeks had higher output. EGF output in patients with recurrent GU was lower than that in non-recurrent GU patients. In 10 GU patients, EGF output became higher in healing stage than in active stage. Salivary EGF may promote the healing and prevent the recurrence of human gastric ulcer.

Topics: Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Saliva

Immunoreactive epidermal growth factor (IR-EGF) was measured by a highly sensitive and specific radioimmunoassay in gastric juice samples obtained during endoscopy from 26 control subjects, 44 patients with duodenal ulcers, and 18 with benign gastric ulcers. In the active stage, the concentrations of the peptide were consistently reduced, compared with those found in control subjects (592.7 +/- 55.8 pg/ml), in both duodenal (262.6 +/- 21.4 pg/ml) and gastric ulcer patients (320.2 +/- 34.1 pg/ml) (p less than 0.001 and 0.01, respectively). Mean IR-EGF values distinctly lower than in the controls were still present in the gastric juice of patients with inactive duodenal ulcers (349.7 +/- 35.9 pg/ml; p less than 0.001), whereas no difference was observed in patients with healed gastric ulcers (502.2 +/- 132.3 pg/ml). Although these findings suggest a possible role for EGF deficiency in the pathogenesis of peptic ulcer disease, the pathophysiological significance of our results (if any) remains to be elucidated.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Female; Gastric Juice; Humans; Male; Radioimmunoassay; Stomach Ulcer

We examined the pathogenesis of cysteamine-induced duodenal ulcers in rats, especially with reference to epidermal growth factor (EGF). Control, cysteamine (400 mg/kg, s.c.), cysteamine + EGF (20 micrograms/kg/day, i.p.) submandibular resection (SMR), SMR + cysteamine, and SMR + cysteamine + EGF groups were examined for duodenal ulceration. With submandibular resectioning, endogenous EGF decreased, and with the administration of EGF (i.p.), endogenous EGF increased. In the SMR + cysteamine group, serum gastrin increased and the intragastric pH decreased remarkably compared to in the normal control group. The administration of exogenous EGF suppressed this change. Mucosal blood flow, the potential difference and hexosamine, as defensive factors, decreased markedly in the SMR + cysteamine group, but the administration of exogenous EGF reversed these changes. These results suggested that a decrease in EGF is involved in the pathogenesis of cysteamine-induced duodenal ulcers in rats.

Topics: Animals; Cysteamine; Duodenal Ulcer; Duodenum; Epidermal Growth Factor; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Stomach; Submandibular Gland

Numerous studies have indicated a role of epidermal growth factor in the maintenance of the gastrointestinal mucosa. In the present study epidermal growth factor concentrations in saliva and gastric juice of patients with gastric or duodenal ulcer or gastritis are compared with those of healthy controls. For this purpose a novel ELISA system has been developed and shown to be sensitive and specific. It is demonstrated that gastric juice and saliva of patients with gastric ulcer contain less epidermal growth factor than the samples of healthy controls (p less than 0.01). Epidermal growth factor concentrations and outputs (product of epidermal growth factor concentration and the volume secreted in 15 min) in the gastric juice of patients with duodenal ulcer do not differ from those of healthy controls.

Topics: Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Gastric Juice; Gastritis; Humans; Saliva; Stomach Ulcer; Thirst

The authors examined the influence of pregnancy on the healing of chronic gastric and duodenal ulcers in connection with pregnancy-induced changes of growth parameters of gastric-duodenal mucosa and changes in the level of endogenic EGF. Besides, the level of EGF was lowered by the resection of submandibular glands (sialadenectomy). Pregnancy caused an increase in the speed of the healing of gastric and duodenal ulcers, this effect being the result of the appearance of hyperplastic changes in the gastric-duodenal mucosa. This hyperplasia was the result of the increase in the level of endogenic EGF. Sialadenectomy decreased the level of EGF in the blood serum preventing total pregnancy hyperplasia of the mucosa in the stomach and partly in the duodenum, which resulted in the total abolition of favourable influence of pregnancy on the healing of gastric ulcers and reduction of the influence of pregnancy on the healing of duodenal ulcers. The results obtained show that the gastric and duodenal mucosa during pregnancy has an increased ability to regenerate, this ability resulting from the hyperplasia of the mucosa taking place in pregnancy, which is the effect of an increase in the level of endogenic EGF.

Topics: Chronic Disease; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Pregnancy; Pregnancy Complications; Stomach Ulcer; Wound Healing

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action.

Topics: Administration, Oral; Animals; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastrins; Infusions, Parenteral; Intestinal Mucosa; Male; Nucleic Acids; Rats; Rats, Inbred Strains; Somatostatin; Stomach Ulcer; Wound Healing

Increased vagal (parasympathetic) stimulation of gastric secretion has been postulated in patients with duodenal ulcer disease. Since salivary secretion is influenced by parasympathetic nerves, we reasoned that duodenal ulcer patients also might have increased salivary secretion. Furthermore, if salivary secretion in duodenal ulcer patients is under nearly maximal parasympathetic stimulation basally, salivary volume might not increase with additional parasympathetic activation induced by sham feeding. To test these hypotheses, we measured basal and sham-feeding-stimulated salivary flow in duodenal ulcer patients and healthy subjects. Contrary to our hypotheses, both basal salivary flow and the salivary response to sham feeding were almost identical in duodenal ulcer patients and healthy subjects. Also, urogastrone concentrations in saliva were approximately the same in duodenal ulcer patients and normal subjects.

Topics: Duodenal Ulcer; Epidermal Growth Factor; Female; Food; Humans; Male; Middle Aged; Saliva

Topics: Animals; Duodenal Ulcer; Duodenum; Epidermal Growth Factor; Gastric Mucosa; Intestinal Mucosa; Rats

The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more effective than cimetidine alone. These results show that a combination of an agent inhibiting gastric acid secretion and the cytoprotective and growth-stimulating peptide EGF/URO seems to be more effective with regard to duodenal ulcer healing than individual administration of the two substances. Synthetic human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral synthetic human EGF/URO has a significant effect on healing of duodenal ulcers in rats. The amount of synthetic human EGF/URO administered is comparable to that found in saliva during stimulation of the salivary glands. Our results, therefore, suggest that EGF/URO is one of the endogenous factors participating in healing of duodenal ulcers.

Topics: Animals; Cysteamine; Duodenal Ulcer; Epidermal Growth Factor; Female; Gastric Acid; Rats; Rats, Inbred Strains

The pathophysiological structure shows aggressors like increased acid and pepsin, an impaired defence system of the mucosa (mucus, mucosal circulation and possibly PG's and epidermal growth hormone). Disturbances in the interdigestive and digestive motility brings about most clearly the pathophysiological differences between GU and DU. Therapeutic corrections of the high secretion lead to pathological reactions in other parts of the system (gastrin). SPV is the only therapeutic procedure which reduces irreversibly the enlarged secretory capacity of the gastric mucosa (parietal cell reduction). This surgical treatment should therefore have priority in the treatment also of uncomplicated duodenal ulcers and with some exceptions of GU.

Topics: Duodenal Ulcer; Epidermal Growth Factor; Epithelium; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrointestinal Motility; Histamine Release; Humans; Membrane Potentials; Postoperative Complications; Prostaglandins; Stomach Ulcer; Vagotomy, Proximal Gastric

The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300 mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal growth factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition of synthesis and secretion of endogenous epidermal growth factor may be a pathogenetic factor in cysteamine-induced duodenal ulcer.

Topics: Animals; Brunner Glands; Cysteamine; Duodenal Ulcer; Epidermal Growth Factor; Female; Rats; Rats, Inbred Strains

A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Juice; Gastrins; Humans; Intrinsic Factor; Male; Middle Aged; Pentagastrin; Pepsin A; Secretory Rate; Time Factors

Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastrointestinal Hormones; Humans; Peptic Ulcer; Peptides