epidermal-growth-factor and Gastrointestinal-Hemorrhage

Ten healthy young male subjects took part in a double-blind, placebo-controlled crossover study to assess the effects of nocloprost on gastric microbleeding and endoscopic mucosal injury induced by the administration of aspirin (2.5 g). In addition, basal and pentagastrin-induced gastric acid and pepsin secretion and salivary and plasma contents of epidermal growth factor (EGF) were measured after placebo plus aspirin or nocloprost plus aspirin treatment in these subjects. Nocloprost (100 micrograms/dose) significantly reduced spontaneous gastric microbleeding and almost completely prevented gastric mucosal injury induced by aspirin. Nocloprost failed to affect basal and pentagastrin-stimulated gastric acid and pepsin secretion but increased significantly the salivary outputs and plasma concentrations of EGF. In conclusion, nocloprost is effective in preventing gastric injury by aspirin even at a non-antisecretory dose, and this protection may involve an excessive release of EGF.

Topics: Adult; Aspirin; Double-Blind Method; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Pepsin A; Prostaglandins F, Synthetic; Saliva; Vasodilator Agents

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

 To explore the predictive value of serum gastrin (GAS), epidermal growth factor (EGF) levels in gastric ulcer complicated with acute upper gastrointestinal bleeding.. A descriptive study.. Department of Emergency, Beijing Jiangong Hospital, China, from January 2019 to June 2020.. One hundred and twenty-five patients with gastric ulcer and acute upper gastrointestinal bleeding were selected as Group A. One hundred and twenty-five patients with gastric ulcer and no upper gastrointestinal bleeding were selected as Group B. Logistic regression analysis was used to analyse the risk factors of gastric ulcer complicated with acute upper gastrointestinal bleeding. The value of serum GAS, EGF in early diagnosis of gastric ulcer with upper gastrointestinal bleeding was evaluated by receiver operating characteristic (ROC) curve.. Univariate analysis showed statistically significant differences between Group A and Group B in taking non-steroidal anti-inflammatory drugs (NSAIDs), helicobacter pylori (Hp) infection, serum GAS and EGF (all p <0.001). Logistic regression analysis showed that raised serum GAS and serum EGF were independent risk factors for gastric ulcer and upper gastrointestinal bleeding (both p <0.001). The ROC area of serum EGF to predict gastric ulcer and acute upper gastrointestinal bleeding was 0.810 (95% CI: 0.753-0.867, p <0.001), greater than ROC area of serum GAS. At serum EGF of ≤109.95 pg/mL, had the 84.8%, sensitivity to predict gastric ulcer and acute upper gastrointestinal bleeding with specificity of 68.8%.. The predictive value of serum GAS and EGF is high for gastric ulcer complicated with acute upper gastrointestinal bleeding; the predictive value of serum EGF is greater than that of serum GAS. Key Words: Gastric ulcer, Acute upper gastrointestinal bleeding, Serum, Gastrin (GAS), Epidermal growth factor (EGF), Logistic regression, Receiver operating characteristic (ROC) curve.

Topics: Anti-Inflammatory Agents, Non-Steroidal; China; Epidermal Growth Factor; Gastrins; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Risk Factors; Stomach Ulcer

Most intractable tissue-degenerative disorders share a common pathogenic condition, so-called proteinopathy. Amyloid-related disorders are the most common proteinopathies and are characterized by amyloid fibril deposits in the brain or other organs. Aging is generally associated with the development of these amyloid-related disorders, but we still do not fully understand how functional proteins become pathogenic amyloid deposits during the human aging process. We identified a novel amyloidogenic protein, named epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), in massive venous amyloid deposits in specimens that we obtained from an autopsied patient who died of gastrointestinal bleeding. Our postmortem analyses of additional patients indicate that EFEMP1 amyloid deposits frequently developed in systemic venous walls of elderly people. EFEMP1 was highly expressed in veins, and aging enhanced venous EFEMP1 expression. In addition, biochemical analyses indicated that these venous amyloid deposits consisted of C-terminal regions of EFEMP1. In vitro studies showed that C-terminal regions formed amyloid fibrils, which inhibited venous tube formation and cell viability. EFEMP1 thus caused a novel age-related venous amyloid-related disorder frequently found in the elderly population. Understanding EFEMP1 amyloid formation provides new insights into amyloid-related disorders occurring during the aging process. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Topics: Aged, 80 and over; Amyloidosis; Biomarkers; Calcium-Binding Proteins; Dose-Response Relationship, Drug; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Gastrointestinal Hemorrhage; Human Umbilical Vein Endothelial Cells; Humans; Intestine, Large; Vascular Diseases; Veins

Gastrointestinal endoscopy is a standard diagnostic tool for gastrointestinal ulcers and cancer. In this study, we have developed recombinant human epidermal growth factor-containing ulcer-coating polymeric sol-gel for endoscopic application. Chitosan and pluronic F127 were employed for their thermoresponsive and bioadhesive properties. At temperatures below 21, polymeric sol-gel remains liquid during endoscopic application and transforms to gel at body temperature after application on ulcers. In an in vitro cellular wounding assay, recombinant human epidermal growth factor sol-gel significantly enhanced the cell migration and decreased the wounding area (68%) compared to nontreated, recombinant human epidermal growth factor solution, and sol-gel without recombinant human epidermal growth factor (42, 49, and 32 % decreased at day 1). The in vivo ulcer-healing study was performed in an acetic acid-induced gastric ulcer rat model and proved that our recombinant human epidermal growth factor endoscopic sol-gel facilitated the ulcer-healing process more efficiently than the other treatments. Ulcer sizes in the recombinant human epidermal growth factor sol-gel group were decreased 2.9- and 2.1-fold compared with those in the nontreated group on days 1 and 3 after ulceration, respectively. The mucosal thickness in the recombinant human epidermal growth factor sol-gel group was significantly increased compared to that in the nontreated group (3.2- and 6.9-fold on days 1 and 3 after ulceration, respectively). In a gastric retention study, recombinant human epidermal growth factor sol-gel stayed on the gastric mucosa more than 2 h after application. The present study suggests that recombinant human epidermal growth factor sol-gel is a prospective candidate for treating gastric ulcers via endoscopic application.

Topics: Cell Line; Endoscopy; Epidermal Growth Factor; Gastrointestinal Hemorrhage; Gels; Humans; Recombinant Proteins; Stomach Ulcer

Transforming growth factor-alpha (TGF-alpha), which binds to epidermal growth factor receptors (EGF-R), stimulates esophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. The aim of the present study was to examine epithelial proliferation and dynamics of TGF-alpha and EGF-R gene and protein expression in rat chronic acid reflux esophagitis.. Gastric acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion, and by covering the duodenum near the pyloric ring with a small piece of an 18Fr Nélaton catheter. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake. Expression of TGF-alpha and EGF-R mRNA and protein was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.. Esophageal lesions were observed in the lower and middle esophagus. Histologically, a significant increase in mucosal thickening with elongation of lamina propria papillae and basal cell hyperplasia was observed. The BrdU labeling index was significantly increased from 2.7 +/- 1.0 in normal mucosa and 2.8 +/- 1.2 in background mucosa adjacent to the esophageal lesion, to 60.3 +/- 32.7 in the lesions of chronic esophagitis. Expression of TGF-alpha and EGF-R mRNA in the esophageal lesion significantly increased compared to those in the control and background tissue, whereas treatment with rabeprazole significantly inhibited increases in TGF-alpha and EGF-R mRNA expression. According to immunohistochemical study, TGF-alpha and EGF-R revealed strong expression in esophageal lesions compared with control and background mucosa. The superficial layer of the esophagus was strongly positive for TGF-alpha and most cells in regions of basal hyperplasia had a positive reaction for EGF-R in the esophagitis lesion.. Epithelial proliferation and expression of TGF-alpha and EGF-R were significantly increased in rat chronic reflux esophagitis. Activation of TGF-alpha and EGF-R genes in response to acid reflux may facilitate rapid mucosal healing by stimulating epithelial proliferation. These results suggest that TGF-alpha and EGF-R play crucial roles in rat chronic reflux esophagitis.

Topics: Amino Acid Sequence; Analysis of Variance; Animals; Blotting, Western; Chronic Disease; Disease Models, Animal; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Esophagitis, Peptic; Esophagus; Gastrointestinal Hemorrhage; Gene Expression; Immunoenzyme Techniques; Ligation; Male; Molecular Sequence Data; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor alpha

Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is present and confined to the basal layer.. To examine histological changes in and dynamics of EGF-R expression during healing after acid reflux oesophagitis in a rat model.. Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF-R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF-R mRNA and protein by RT-PCR and Western blotting or immunohistochemistry.. Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 +/- 3.09 microm in controls to 142.73 +/- 11.59 microm (P < 0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU-positive cells among basal cells on day 14 was significantly increased from 7.1 +/- 0.8/field in controls to 30.9 +/- 3.0/field in ligated rats. Expression of EGF-R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF-R staining.. Acid reflux-induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF-R expression. Activation of EGF-R gene and protein in response to acid reflux-induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.

Topics: Amino Acid Sequence; Animals; Blotting, Western; Disease Models, Animal; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Esophagitis, Peptic; Esophagus; Gastrointestinal Hemorrhage; Gene Expression; Ligation; Male; Molecular Sequence Data; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

1. The interaction between endogenous nitric oxide (NO) and factors from the rat submandibular salivary gland such as epidermal growth factor (EGF) on gastric mucosal integrity in the rat has been investigated. 2. Bolus administration of the NO synthase inhibitor, NG nitro-L-arginine methyl ester (L-NAME; 6.25-50 mg kg-1, i.v.) to animals treated intraluminally with 0.15 N HCl resulted in a significant increase in the area of mucosal haemorrhagic damage at doses 12.5 and 50 mg kg-1. Concurrent administration of indomethacin (5 mg kg-1, i.v.) resulted in a significant haemorrhagic mucosal damage in response to L-NAME (12.5-50 mg kg-1). Administration of the highest dose of L-NAME resulted in an increase in histological damage to the rat gastric mucosa. 3. When compared to control animals, the extent of damage produced by L-NAME or L-NAME in combination with indomethacin was significantly exacerbated in rats which had been sialoadenectomized (SALX) by removal of the submandibular salivary glands. The mucosal damage in SALX rats was ameliorated by treatment with EGF (5 and 10 micrograms kg-1, i.v.). 4. L-NAME administration resulted in a small reduction of gastric mucosal blood flow as assessed by laser Doppler flowmetry (LDF). The reduction in LDF by 25 and 50 mg kg-1 L-NAME was significantly greater in SALX rats than in rats with intact salivary glands. Pretreatment of SALX rats with indomethacin did not augment this large decrease in LDF suggesting that endogenous prostanoids do not interact with NO and salivary factors in regulating mucosal microcirculation. 5. Mucosal NO biosynthesis as assessed by ['4C]-citrulline formation was reduced in SALX rats when compared to control animals. Pretreatment of SALX animals with parenterally-administered EGF(10 microg kg-1) was associated with an increase in [14C]-citrulline formation in the gastric mucosa to levels observed in control SALX rats.6. These data suggest that factors which originate from the salivary gland such as EGF interact with NO in the maintenance of mucosal integrity. The effects may be mediated at least in part by changes in gastric mucosal blood flow. Salivary glands and EGF may mediate these effects to some extent via changes in mucosal NO biosynthesis.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Blood Pressure; Epidermal Growth Factor; Gastric Mucosa; Gastrointestinal Hemorrhage; Indomethacin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Salivary Glands; Stomach Ulcer; Submandibular Gland

We have observed that removal of the salivary glands is associated with an increase in the susceptibility to gastric mucosal damage in the rat. In the present study, we have examined the effect of sialoadenectomy on ethanol-induced mucosal hemorrhagic damage and myeloperoxidase (MPO) activity. Hemorrhagic damage and MPO activity in response to intragastric 50% w/v ethanol were greater in sialoadenectomized rats when compared with sham-operated animals. Pretreatment with 16,16-dimethylprostaglandin E2 (0.3 micrograms/kg s.c.) reduced damage and MPO activity in both sialoadenectomized and sham control rats receiving 50% ethanol. The reduction in these parameters was greater in control than in sialoadenectomized rats. Pretreatment with epidermal growth factor (5 micrograms/kg s.c.) significantly reduced MPO activity but did not significantly affect the extent of damage. These data suggest that sialoadenectomy is associated with an increase in mucosal inflammation in animals given ethanol. However, in some situations tissue inflammation (as indicated by MPO activity) was reduced, while the proportion of gastric mucosa exhibiting hemorrhagic damage was not changed.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Dinoprostone; Epidermal Growth Factor; Ethanol; Gastrointestinal Hemorrhage; Male; Neutrophils; Peroxidase; Rats; Rats, Inbred Strains; Salivary Glands; Stomach Ulcer