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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori infects over half of the world's population and is thought to be a leading cause of gastric ulcer, gastric carcinoma, and gastric malignant lymphoma of mucosa-associated lymphoid tissue type. Previously, we reported that a gland mucin (MUC6) present in the lower portion of the gastric mucosa containing alpha1,4-N-acetylglucosamine (alpha1,4GlcNAc)-capped core 2-branched O-glycans suppresses H. pylori growth by inhibiting the synthesis of alpha-glucosyl cholesterol, a major constituent of the H. pylori cell wall (Kawakubo et al. 2004. Science. 305:1003-1006). Therefore, we cloned the genomic DNA encoding cholesterol alpha-glucosyltransferase (HP0421) and expressed its soluble form in Escherichia coli. Using this soluble HP0421, we show herein that HP0421 sequentially acts on uridine diphosphoglucose and cholesterol in an ordered Bi-Bi manner. We found that competitive inhibition of HP0421 by alpha1,4GlcNAc-capped core 2-branched O-glycan is much more efficient than noncompetitive inhibition by newly synthesized alpha-glucosyl cholesterol. Utilizing synthetic oligosaccharides, alpha-glucosyl cholesterol, and monosaccharides, we found that alpha1,4GlcNAc-capped core 2-branched O-glycan most efficiently inhibits H. pylori growth. These findings together indicate that alpha1,4GlcNAc-capped O-glycans suppress H. pylori growth by inhibiting HP0421, and that alpha1,4GlcNAc-capped core 2 O-glycans may be useful to treat patients infected with H. pylori.
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PMID:Alpha1,4GlcNAc-capped mucin-type O-glycan inhibits cholesterol alpha-glucosyltransferase from Helicobacter pylori and suppresses H. pylori growth. 1845 30

Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1beta) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1beta was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1beta (200 microg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.
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PMID:Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer. 1854 42

This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin+L-arginine- and simvastatin+N(G)-nitro-L-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E(2) levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E(2) levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with L-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E(2) levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
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PMID:Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. 1921 1

1. Gastric ulcers are common in Type 2 diabetic patients. Of all drugs used in the treatment of Type 2 diabetes, the insulin sensitizers thiazolidinediones (e.g. rosiglitazone) and metformin exhibit additional effects in ameliorating oxidative stress and inflammation, rendering them attractive candidates for the prevention of gastric ulcer in Type 2 diabetes. Thus, the aim of the present study was to evaluate the gastroprotective effects of rosiglitazone and metformin against indomethacin-induced gastric ulcer in Type 2 diabetic and non-diabetic rats. 2. Diabetes was induced by a single injection of streptozotocin (60 mg/kg, i.p., dissolved in 0.1 mol/L cold citrate buffer, pH 4.5), 15 min after administration of 120 mg/kg, i.p., nicotinamide. Three weeks after the successful induction of diabetes, rats were subjected to pyloric ligation and then injected immediately with 30 mg/kg, i.p., indomethacin. Three hours after indomethacin administration, rats were killed and gastric injury was evaluated. Ranitidine (50 mg/kg) was used as a reference drug and was administered in a single oral dose 1 h before indomethacin injection, as were rosiglitazone (3 mg/kg) and metformin (500 mg/kg). 3. Both rosiglitazone and metformin exhibited gastroprotective effects, as evidenced by significant decreases in the ulcer index, free and total acid output in gastric juice and gastric mucosal malondialdehyde concentrations, with concomitant increases in gastric juice pH (only with rosiglitazone), mucin concentrations, gastric mucosal concentrations of nitric oxide and catalase activity compared with untreated diabetic rats. Conversely, rosiglitazone and metformin had no effect on peptic activity and gastric mucosal prostaglandin E(2) content, particularly in the diabetic group, compared with the untreated groups. 4. In conclusion, rosiglitazone and metformin protect Type 2 diabetic rats against indomethacin-induced gastric ulceration, most possibly via antisecretory actions, enhanced mucosal protection and anti-oxidant activity. Rosiglitazone seems to be provide superior gastroprotection to metformin.
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PMID:Gastroprotective effects of the insulin sensitizers rosiglitazone and metformin against indomethacin-induced gastric ulcers in Type 2 diabetic rats. 1956 21

Pongamia pinnata has been advocated in Ayurveda for the treatment of various inflammatory conditions and dyspepsia. The present work includes initial phytochemical screening and study of ulcer protective and healing effects of methanolic extract of seeds of P. pinnata (PPSM) in rats. Phytochemical tests indicated the presence of flavonoids in PPSM. PPSM when administered orally (po) showed dose-dependent (12.5-50 mg/kg for 5 days) ulcer protective effects against gastric ulcer induced by 2 h cold restraint stress. Optimal effective dose of PPSM (25 mg/kg) showed antiulcerogenic activity against acute gastric ulcers (GU) induced by pylorus ligation and aspirin and duodenal ulcer induced by cysteamine but not against ethanol-induced GU. It healed chronic gastric ulcer induced by acetic acid when given for 5 and 10 days. Further, its effects were studied on various parameters of gastric offensive acid-pepsin secretion, lipid peroxidation (LPO) and nitric oxide (NO) and defensive mucosal factors like mucin secretion and mucosal cell shedding, glycoproteins, proliferation and antioxidants; catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels. PPSM tended to decrease acid output and increased mucin secretion and mucosal glycoproteins, while it decreased gastric mucosal cell shedding without any effect on cell proliferation. PPSM significantly reversed the increase in gastric mucosal LPO, NO and SOD levels caused by CRS near to the normal level while it tended to increase CAT and GSH level decreased by CRS and ethanol respectively. Thus, the ulcer protective effects of PPSM may be attributed to the presence of flavonoids and the actions may be due to its effects both on mucosal offensive and defensive factors.
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PMID:Effect of methanolic extract of Pongamia pinnata Linn seed on gastro-duodenal ulceration and mucosal offensive and defensive factors in rats. 1977 71

Nonsteroidal anti-inflammatory drugs (NSAIDs) are combined with paracetamol (PCM) with a view to enhance analgesic efficacy and reduce gastric toxicity. However, there are reports of enhanced nephrotoxicity with nonselective NSAID with PCM combinations. The present study investigated the analgesic efficacy, gastrotoxicity and nephrotoxicity of nonselective, preferential and selective cyclooxygenase inhibitors and their combination with PCM in rats. Graded doses of ibuprofen, meloxicam and celecoxib alone and their combination with fixed dose of PCM were administered to the rats by gavage for 14 days. The results showed that PCM potentiated the analgesic effect of all three classes of NSAIDs significantly as evidenced by increase in tail-flick latency in radiant heat method. Dose-dependent gastromucosal damage was produced by all the drugs, which was augmented significantly with PCM in the form of decreased total carbohydrate/protein ratio of mucin and increased gastric ulcer index. It was further confirmed by histopathology of rat's stomach. The renal histopathology was conducted to evaluate inflammation, tubular damage, papillary necrosis, and interstitial changes. Increased nephrotoxicity was observed with all NSAIDs in dose-dependent manner and in combination with PCM. Our study revealed the augmented analgesia as well as enhanced gastrotoxicity and nephrotoxicity with all three major NSAIDs classes when combined with PCM. These findings highlighted the need for large pharmacoepidemiological studies to evaluate the magnitude of gastrotoxicity and nephrotoxicity in population who are on long-term treatment with NSAID combinations.
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PMID:Evaluation of analgesic efficacy, gastrotoxicity and nephrotoxicity of fixed-dose combinations of nonselective, preferential and selective cyclooxygenase inhibitors with paracetamol in rats. 1980 Feb 6

Diabetes has been reported to cause an increase in offensive and decrease in defensive gastric mucosal factors, the imbalance of which can cause ulceration and delay the ulcer healing. Eugenia jambolana has been documented to have both antidiabetic and antiulcer activities. The present study evaluates the effects of ethanolic extract of E. jambolana on gastric ulcer healing and on rat gastric mucosal defensive factors in gastric ulcer with co-occurring diabetes. E. jambolana extract was administered orally in the dose of 200 mg/kg once daily for 10 days. E. jambolana extract increased mucin secretion, mucosal glycoprotein and glutathione levels and decreased the lipid peroxidation in gastric mucosa of diabetic rats. Its treatment also reversed the decrease in life span of gastric mucosal cells as indicated by decreased cell shedding in the gastric juice but found to have no effect on cell proliferation, indicating enhanced defensive status. E. jambolana extract was effective in reversing the delayed healing of gastric ulcer in diabetic rats near to the normal level. E. jambolana showed better ulcer healing effect than glibenclamide, because of its both antihyperglycemic and mucosal defensive actions. It could thus, be a better choice for treating gastric ulcers co-occurring with diabetes.
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PMID:Ulcer healing properties of ethanolic extract of Eugenia jambolana seed in diabetic rats: study on gastric mucosal defensive factors. 1981 May 72

Telmisartan is an angiotensin II T1 receptor blocker (ARB) with partial peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic properties; two actions that are suggested to be efficacious for protecting against gastric ulcers. Hence, the aim of the present study was to evaluate the gastroprotective effect of telmisartan (1, 3, and 10 mg/kg) on indomethacin- and cold restraint stress (CRS)-induced gastric ulcer models in rats. Candesartan, another ARB with the lowest PPARgamma affinity, was used to justify the possible role of PPARgamma agonistic activity of telmisartan in gastroprotection. Ranitidine was used as a reference drug. Pre-treatment with telmisartan dose-dependently attenuated gastric ulcer indices induced by both models. The protective effect of telmisartan was accompanied by a significant rise in gastric mucosal nitric oxide (as nitrite/nitrate) with a concomitant fall in malondialdehyde concentrations as compared to the corresponding non-treated groups. Moreover, telmisartan significantly reduced free and total acid outputs in indomethacin-treated rats. On the other hand, telmisartan at the doses used did not alter gastric juice pH, peptic activity, mucin concentration or gastric mucosal prostaglandin E2 content in both ulcer models. The telmisartan-treated rats exhibited greater protection from gastric ulceration than candesartan-treated animals. In conclusion, telmisartan, in a dose-dependent manner, protected rats' gastric mucosa from ulcerations possibly through its anti-oxidant action against oxidative stress induced by either indomethacin or CRS. Also, the greater gastroprotection afforded by telmisartan compared to candesartan could be partly ascribed to its PPARgamma-inducing property.
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PMID:Gastroprotective effects of telmisartan on experimentally-induced gastric ulcers in rats. 1982 1

Gastric ulcer is a multi-step disease caused due to imbalance between mucosal defense and aggressive factors. Available anti-ulcer drugs although effective at various steps of ulcer pathogenecity, pose adverse effects. Pectic polysaccharide (SRPP) from swallow root (Decalepis hamiltonii) - previously shown to possess ulcer preventive effect against swim stress and ethanol induced gastric ulcers. In the current study, alteration of matrix metalloproteinases, gastric mucin and prostaglandin E(2) levels during polysaccharide mediated ulcer healing was determined in acetic acid induced gastric ulcer model in Wistar albino rats. Results indicated the potential ulcer healing effect of SRPP as evidenced by approximately 90% reduction in ulcer index; improvement in the antioxidant defense such as increase of glutathione levels together with significant reduction in lipid and protein oxidation and protection to damaged gastric mucin. Further, histological studies substantiated the result of the recovery of mucin that was eroded during ulceration, rejuvenation of mucosal epithelium and enhancement of high molecular mass mucin as opposed to the degraded approximately 55 kDa mucin that appeared only during ulcer condition. Matrix metalloproteinases (MMPs) that are involved in tissue injury was found to be modulated by SRPP treatment in addition to increased cytoprotectivity due to enhanced synthesis of PGE(2) that necessitates the active proliferation of gastric mucin cells. Further, reduction in approximately 3 folds of galectin-3, an inflammatory marker suggests gastro protection against acid induced inflammation and gastric wall damages. Overall, studies show the effectiveness of SRPP in inhibiting MMPs and galectin-3 levels which were up-regulated during ulcer conditions. In addition SRPP ensured cytoprotectivity and rejuvenation of mucosal barrier via PGE(2) trigger leading to ulcer healing.
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PMID:Alterations of matrix metalloproteinases, gastric mucin and prostaglandin E(2) levels by pectic polysaccharide of swallow root (Decalepis hamiltonii) during ulcer healing. 1985 4

In the present study, the gastroprotective mechanism of Xylocarpus granatum fruit and its active constituents gedunin and photogedunin was investigated. Chloroform fraction (Fr-CHCl(3)) of X. granatum fruit was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats and histamine (HA) induced duodenal ulcer model in guinea pigs. Potential anti-ulcer activity of Fr-CHCl(3) was observed against CRU (58.28%), AS (67.81%), AL (84.38%), PL (65.66%) and HA (61.93%) induced ulcer models. The standard drug omeprazole (10mg/kg, p.o.) showed 68.25% protection against CRU, 57.08% against AS and 69.42% against PL model and 70.79% against HA induced duodenal ulcer. Sucralfate, another standard drug (500 mg/kg, p.o.) showed 62.72% protection in AL induced ulcer model. Fr-CHCl(3) significantly reduced free acidity (51.42%), total acidity (30.76%) and upregulated mucin secretion by 58.37% respectively. Phytochemical investigations of Fr-CHCl(3) yielded gedunin (36%), photogedunin (2%). Further, Fr-CHCl(3) and its compounds gedunin and photogedunin significantly inhibited H(+) K(+)-ATPase activity in vitro with IC(50) of 89.37, 56.86 and 66.54 microg/ml respectively as compared to the IC(50) value of omeprazole (30.24 microg/ml) confirming their anti-secretory activity. Conclusively, Fr-CHCl(3) of Xylocarpus granatum was found to possess anti-ulcerogenic activity which might be due to its anti-secretory activity and subsequent strengthening of the defensive mechanism. This study is the first of its kind to show significant anti-secretory effect of gedunin and photogedunin. Therefore it could act as a potent therapeutic agent against peptic ulcer disease.
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PMID:Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. 1996 86


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