Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to clarify the effect of basic fibroblast growth factor (bFGF) on nitric oxide (NO) synthesis during healing of rat gastric ulcers. After experimental gastric ulcers were induced by acetic acid, rats were treated with vehicle, recombinant human bFGF (CS23, 10 micrograms/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg), an NO synthase (NOS) inhibitor, through an orogastric tube twice daily for 3 days or 1 week. CS23 significantly reduced ulcer size, and L-NAME significantly delayed healing compared with the vehicle group and significantly inhibited the efficacy of CS23. Although constitutive NOS (cNOS) activity significantly decreased and inducible NOS (iNOS) activity significantly increased in the vehicle group, CS23 significantly inhibited these changes. cNOS immunoreactivity on the vessels and neurons disappeared in the vehicle group, and newly formed vessels as well as neurons were observed with positive endothelial and neuronal NOS immunoreactivity in the CS23-treated group. External administration of bFGF accelerated ulcer healing, with recovery of NO synthesis in both endothelial cells and neurons. These observations suggested that increased NO synthesis with angiogenesis and reinnervation has a beneficial effect on gastric ulcer healing.
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PMID:Basic fibroblast growth factor increases constitutive nitric oxide synthase during healing of rat gastric ulcers. 947 38

1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.
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PMID:Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats. 959 85

We investigated the relationship between microcirculatory disturbance and the host response to Helicobacter pylori infections in gastric ulcer scars to determine the role of endothelin-1 (ET) in ulcer recurrence. The subjects were divided into three groups. The GuS group consisted of patients who had red scarring (S1 stage) at the gastric angle with H. pylori, the gast+ group who had gastritis with H. pylori, and the gast- group who had gastritis without H. pylori. During endoscopic examination, biopsies were taken from the gastric angle. Mucosal ET, nitric oxide (NO), interleukin-8 (IL-8), and RANTES were measured. ET, inducible NO synthase (iNOS), and endothelial constitutive NOS (ecNOS) were immunostained. Mucosal ET and oxides of nitrogen (NOx) were significantly higher in the GuS group than in the other groups. IL-8 was elevated in the GuS and gast+ groups, and RANTES was elevated in the gast+ group (p < 0.01). There was prominent inflammatory cell infiltration in the GuS group. ET-positive cells were found in vascular smooth muscle, gastric epithelium, and gastric smooth muscle. iNOS-positive cells were found in vascular smooth muscle, gastric epithelium, gastric smooth muscle, and inflammatory cells. In conclusion, local inflammation and microcirculatory disturbance persist at the center of the ulcer scar (S1). Decreased cytokine levels and increased ET and NO (mainly synthesized by iNOS) levels suggested that microcirculatory disturbance is a more important factor than immune response in ulcer recurrence.
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PMID:Relationship between recurrence of gastric ulcer and the microcirculation. 959 26

We have recently reported that steady-state gastric mucosal blood flow (GMBF) is decreased in streptozotocin (STZ) diabetic rats, and that their GMBF response to burn-stress is impaired, probably via a nitric oxide (NO)-mediated mechanism. Accordingly, this study was designed to investigate the relation of aldose reductase (AR) and NO synthase to the regulation of GMBF during chronic hyperglycemia. STZ rats were treated with or without chronic oral administration of an AR inhibitor, epalrestat (EPA) and/or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). GMBF was measured by laser-Doppler velocimetry (LDV). In the STZ rats, GMBF after a 24-h fasting period was decreased significantly 4 weeks after the onset of diabetes and this was accompanied by an increase in the gastric ulcer index (UI) (a measure of the length of gastric erosions and ulcers). Chronic oral administration of EPA to the STZ rats dose-dependently inhibited the increased UI and the decreased GMBF after the fasting stress, whereas chronic oral administration of L-NAME further increased the UI and further decreased the GMBF. EPA administered in combination with L-NAME to the STZ rats reduced the effects of L-NAME, but the effects did not reach significance. These results suggest that EPA protects the gastric mucosa of diabetic rats, by preventing the decrease in GMBF that is, at least in part, caused by NO-related mechanisms.
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PMID:Epalrestat prevents the decrease in gastric mucosal blood flow and protects the gastric mucosa in streptozotocin diabetic rats. 1021 35

The healing effect of heparin on gastric ulcer and its underlying mechanisms were studied. The influences of protamine on these effects were also investigated. Gastric ulcer was induced by acetic acid in rats. Heparin (100-1000 U/kg i.v.) was given once daily for 4 or 7 days. Ulcer area was measured; gastric mucosal regeneration, proliferation, and angiogenesis were determined by histological or immunohistochemical methods. Gastric mucosal basic fibroblast growth factor (bFGF) level was assessed by an enzyme-linked immunosorbent assay, and the mucosal epidermal growth factor (EGF) level and nitric oxide synthase (NOS) activity were measured by radioimmunoassay. The anticoagulant action of heparin was determined by the duration of bleeding time. The results showed that heparin given for 4 or 7 days significantly accelerated gastric ulcer healing in a dose-dependent manner. The three doses of heparin significantly stimulated mucosal regeneration and proliferation as well as angiogenesis but not the contraction of ulcer base. Similar effects were observed in gastric mucosal bFGF and EGF levels and constitutive NOS activity. Protamine not only abolished the anticoagulant action of heparin but also significantly potentiated its effects on ulcer healing, gastric mucosal proliferation, angiogenesis, and constitutive NOS activity. These findings indicate that heparin can accelerate gastric ulcer healing, which is associated with mucosal regeneration, proliferation, and angiogenesis. These actions are likely to be stimulated by bFGF, EGF, and constitutive NOS activity in the gastric mucosa. Protamine potentiates the ulcer-healing effect of heparin, which is probably acting through constitutive NOS activation.
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PMID:Association of heparin with basic fibroblast growth factor, epidermal growth factor, and constitutive nitric oxide synthase on healing of gastric ulcer in rats. 1041 93

Cigarette smoking is associated with peptic ulcer diseases. Smokers have lower levels of salivary epidermal growth factor (EGF) than nonsmokers. We investigated whether reduction of EGF is involved in the delay of gastric ulcer healing by cigarette smoking. Rats with acetic acid-induced ulcers were exposed to cigarette smoke (0, 2, or 4% vol/vol) 1 day after ulcer induction. EGF level was elevated 1 day after ulcer induction in salivary glands and serum, and 4 days after ulcer induction in the gastric mucosa. However, cigarette smoke depressed these beneficial effects and EGF mRNA expression in salivary glands and gastric mucosa. Cigarette smoke delayed gastric ulcer healing and reduced cell proliferation, angiogenesis, and mucus synthesis. Exogenous EGF (10 and 20 microg/kg i.v.) before smoke exposure reversed the adverse effects of cigarette smoke, whereas vascular endothelial growth factor level and nitric oxide synthase activity were unaffected. It is concluded that the detrimental effect of cigarette smoke on ulcer healing is a consequence of reduction of angiogenesis, cell proliferation, and mucus secretion through the depressive action on EGF biosynthesis and its mRNA expression in salivary glands and gastric mucosa.
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PMID:Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking. 1064 56

Nitric oxide has been shown to be beneficial for gastric ulcer healing. We determined the relative effects of endothelial and inducible nitric oxide synthases on gastric ulcer healing in rats. Ulcers were induced by serosal application of acetic acid. Ulcer severity, angiogenesis, and nitric oxide synthase expression were assessed 3-10 days later. The effects of inhibitors of nitric oxide synthase were also examined. Inducible nitric oxide synthase mRNA was only detected in ulcerated tissue (maximal at day 3), whereas the endothelial isoform mRNA was detected in normal tissue and increased during ulcer healing. Inducible nitric oxide synthase was expressed in inflammatory cells in the ulcer bed, whereas endothelial nitric oxide synthase was found in the vascular endothelium and in some mucosal cells in both normal and ulcerated tissues. Angiogenesis changed in parallel with endothelial nitric oxide synthase expression. N(6)-(iminoethyl)-L-lysine did not affect angiogenesis or ulcer healing, while N(G)-nitro-L-arginine methyl ester significantly reduced both. In conclusion, endothelial nitric oxide synthase, but not the inducible isoform, plays a significant role in gastric ulcer healing.
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PMID:Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. 1091 43

The aim of this study was to investigate the effect of nitric oxide (NO) on the gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus), D-NAME (10 mg/kg i.v. bolus), or L-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + L-NAME were administered. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO) activity, and gastric protein oxidation (PO) levels were determined. In histological analysis a destructive effect of L-NAME (NO synthase inhibitor) was demonstrated. L-NAME treatment increased gastric MPO activity, L-arginine reversed this effect and D-NAME had no effect. Tissue PO activity was found to be increased in L-NAME-treated rats; L-arginine treatment reversed this activity. It is concluded that gastric barrier function is altered after hemorrhagic shock, and L-arginine (NO precursor) can prevent mucosal injury in the stomach. This effect of NO may be on gastric blood flow and can be mediated by tissue neutrophils.
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PMID:Role of nitric oxide in gastric injury induced by hemorrhagic shock in rats. 1094 Jul 85

Previous studies have been shown that the adrenergic system involves in gastric secretion and pathogenesis of peptic lesion and activation of alpha(2)-adrenoceptors located on the vagus nerve inhibits gastric acid secretion. Bromocriptine, a dopamine receptor agonist, also has alpha(2) agonistic effect and prevents indomethacin-induced gastric ulcer. alpha(2)-Adrenoceptors involve in the release of nitric oxide which has cytoprotective activity in gastric mucosa. Cyclosporin A (CsA) has also been suppressed stress-induced gastric mucosal lesions, dose dependently. The object of this study was to clarify the interaction between the anti-ulcer effect of bromocriptine (2, 4, 8 mg kg(-1)) or cyclosporin A (5, 10, 20 mg kg(-1)) and nitric oxide. Intraperitoneal injections of bromocriptine and cyclosporin A prevented water immersion stress-induced gastric ulcer in rats. L-Nitro-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased stress-induced lesions while L-arginine, a precursor of nitric oxide, decreased these lesions. In conclusion, increasing level of nitric oxide by bromocriptine and cyclosporin A may be one of the contributory factors in their protective effects on gastric mucosa.
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PMID:Evidences for involvement of nitric oxide in the gastroprotective effect of bromocriptine and cyclosporin A on water immersion stress-induced gastric lesions. 1245 25

Usnea longissima, a medicinal lichen of Anatolia (Turkey), is used in the treatment of gastric ulcer in local folk medicine. In this paper, the gastroprotective effect of usnic acid (UA) isolated from Usnea longissima was investigated in the indomethacin-induced gastric ulcers in rats at doses of 25, 50, 100 and 200 mg/kg body weight. The gastric lesions were significantly reduced by all doses of UA as compared with the indomethacin (25 mg/kg body weight) treated group. In the stomach tissues of treated animals, the in vivo antioxidant levels were evaluated. The administration of indomethacin caused a significant decrease in the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH), and an increase in the lipid peroxidation (LPO) level (p < 0.05). The administration of all doses of UA reversed the trend, inducing a significant increase of SOD, GSH and GPx levels and a reduction in LPO level in tissues. However, catalase (CAT), glutathione reductase (GR) and myeloperoxidase (MPx) activities, increased by indomethacin, were found to be lower in the UA- and ranitidine-treated groups. The gastric mucosal constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities were also investigated in tissues of UA- (100 mg/kg), ranitidine- (50 mg/kg) and indomethacin-treated rat groups. The administration of UA and ranitidine increased the cNOS activity and lowered the iNOS activity as compared with indomethacin-treated group. These results suggest that the gastroprotective effect of UA can be attributed to its reducing effect on the oxidative damage and neutrophil infiltration in tissues.
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PMID:Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. 1616 75


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