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

We developed a new gastric ulcer model in which the ulcers are induced by the local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the gastric wall. These ulcers resemble human gastric ulcers that penetrate the muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid alone, gastric ulcers did not form, whereas penetrating ulcers were produced by the simultaneous injection of the Fe/ASA solution in a dose-dependent manner. Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h after the injection of the Fe/ASA solution. This increase in lipid peroxides preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD, recombinant human CuZnSOD) significantly reduced the size of the ulcers and inhibited the accumulation in lipid peroxides in the gastric mucosa, while treatment with apo-SOD or heat-inactivated SOD did not. These results suggest that lipid peroxidation mediated by oxygen radicals plays a crucial role in the pathogenesis of the gastric ulceration induced by the Fe/ASA solution.
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PMID:A new gastric ulcer model in rats produced by ferrous iron and ascorbic acid injection. 853 16

Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) almost invariably cause acute gastroduodenal injury and probably account for approximately 12,000 ulcer bleeding episodes and 1200 deaths per annum in the United Kingdom. Clinically significant intestinal toxicity is also recognized but less clearly defined. The main risk factors for NSAID-related peptic ulcer complications are age, past history, use of higher risk individual NSAIDs, drug dose, concurrent use of warfarin or corticosteroids. The underlying reason for NSAID use and Helicobacter pylori status is not clearly associated with increased risk. Whether NSAIDs cause drug-induced non-ulcer dyspepsia is also controversial. Acute injury occurs more readily with aspirin than with non-aspirin NSAIDs, and the spectrum of acute injury is of little value in predicting clinically significant end points in comparison with different NSAIDs. However, acute studies of co-prescribed protective agents are highly predictive of performance in clinical practice. Gastric mucosal integrity is maintained by the interplay of three protective networks: prostaglandin synthesis, nitric oxide synthesis and the activity of the enteric nervous system. Aspirin and NSAIDs act by inhibiting prostaglandin synthesis catalysed by two cyclooxygenase enzymes. Most existing NSAIDs are unselective and inhibit the activity of the constitutive cyclooxygenase (COX) 1 enzyme in the stomach as much as the cyclooxygenase (COX) 2 enzyme which is induced at sites of inflammation such as joint disease. There are, however, prospects for selective cyclooxygenase 2 inhibitors. Some NSAIDs, particularly aspirin, have additional topical toxicity, which may in part reflect mucosal trapping. Some data favor an effect of NSAIDs in inhibiting mitochondrial oxidative phosphorylation. The principal physiological mechanisms which are compromised by NSAID use are mucosal blood flow, secretion of mucus and bicarbonate and maintenance of a hydrophobic mucosal surface. Animal data suggest that polymorphonuclear leukocytes (PMNs) are important for acute damage though the relevance to humans has yet to be established. As well as damaging the mucosa, NSAIDs impair ulcer healing and are associated with reduced epithelial proliferation and evidence of diminished angiogenesis. An interaction between prostaglandins and growth factors, as well as the synthesis of antiproliferative products of arachidonic acid metabolism may be involved. Healing of NSAID ulcers by conventional doses of H2 antagonists is slow and H2 antagonists are poor at preventing gastric ulcer development or recurrence. These problems can be overcome by the use of more potent acid suppression. Misoprostol heals NSAID-associated ulcers, though whether healing is as fast as with non-NSAID ulcers has not been formally established. Misoprostol is effective prophylactic treatment but has a significant incidence of adverse events, particularly diarrhoea. Misoprostol has been reported to prevent ulcer complications, and in endoscopic studies has been superior as prophylaxis to standard dose ranitidine. Results of its efficacy compared to proton-pump inhibitors are awaited. For many patients appropriate management is avoidance of NSAIDs or use of less potent/toxic alternatives such as ibuprofen. Reductions in prescribing arising from a prior authorization scheme show that this can be achieved. For high-risk patients requiring continuing NSAID use co-prescription of omeprazole or misoprostol should be considered.
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PMID:Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. 889 49

Based on our previous studies that aspirin (ASA) -induced gastric ulceration in rats can be significantly reduced if the drug is chemically associated with phosphatidylcholine (PC), we undertook the present study to compare gastric ulcer healing rates in rats administered either unmodified or PC-complexed ASA. Gastric ulcers were induced in anesthetized rats by briefly exposing the mucosal surface to 0.2 ml 60% acetic acid followed by randomization of the rats to study groups; daily intragastrically administered saline (control), ASA (36, 54 mg/kg), or ASA-PC complex. In contrast to the 65-70% reduction in ulcer size recorded in controls, ulcer healing was significantly retarded in rats administered unmodified ASA. Conversely, the size of the experimentally induced ulcers was less than control values in rats daily administered the PC-associated ASA, suggesting an acceleration in the rate of ulcer healing. Daily intragastric administration of ASA to rats over the study period also resulted in a significant decrease in surface hydrophobicity from control values as measured by contact angle analysis. However, surface hydrophobicity was partially restored in rats administered the PC-complexed ASA. Consistent with these findings, it was determined that ASA-treated rats had a lower hematocrit than control values, as an index of gastrointestinal bleeding, whereas this parameter remained at control levels in rats administered the PC-complexed ASA. We conclude that PC-associated ASA promotes ulcer healing above the values measured in rats treated with ASA or saline. This property may be attributable to the fact that in contrast to unmodified ASA, which aggravates ulcer healing by transforming the stomach to an acid-permeable state, the protective hydrophobic lining of the stomach is maintained in rats administered PC-associated ASA, thereby allowing ulcer healing of the tissue to proceed.
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PMID:Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats. 955 35

The quality of ulcer repair remains crucial for the stability of the injured tissue and for preventing recurrence. Therefore, we studied the temporo-spatial expression of the fibrillar and basement membrane collagens (types I, III, and IV), the collagenase MMP-2 as well as its inhibitor TIMP-1 before and after oral administration of basic fibroblast growth factor (b-FGF) over 30 days in acetic acid-induced rat gastric ulcers. The alterations and the exact location of the mRNA transcripts and their precipitated proteins were visualized by means of radioactive in situ hybridization and immunohistochemistry. Our data show that hybridization signals of procollagen I could first be identified 2 hours after ulcer induction. After 12 hours the ulcer was established and the mRNA was enhanced at the ulcer margin. After 24-48 hours the other procollagen transcripts were detected and all were further upregulated over the mesenchymal cells of all gastric layers up to 21 days, then declined at 30 days. In contrast, MMP-2 became prominent after 48 hours and up to 21 days. TIMP-1 was enhanced at 72 hours. After oral administration of b-FGF the transcriptional activity of the procollagens and MMP-2 was not significantly altered, while ulcer diameter was significantly reduced. We conclude that the early onset and long duration of collagens' expression points to their central structural and functional role in gastric ulcer healing. MMP-2 seems to be involved in both active ulceration and ECM remodeling. The timing of TIMP/MMP expression may be critical for proper restoration of gastric wall integrity.
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PMID:Remodeling of extracellular matrix in gastric ulceration. 1152 57

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.
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PMID:Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines. 1464 93

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 +/- 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 +/- 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.
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PMID:Endoscopy in asymptomatic minidose aspirin consumers. 1571 41

Allophylus serratus is known to possess various therapeutic properties. We evaluated the anti-ulcerogenic property of crude ethanolic extract of Allophylus serratus (AS) in different ulcer models in Sprague-Dawley rats. The extract at 400 mg/kg body weight, once daily, orally has a significant effect in cold restraint (CRU, 2 h cold restraint stress), aspirin (ASA, 150 mg/kg body weight, orally), alcohol (AL, 1 ml/200 gm of absolute alcohol) and pyloric ligation (PL, 4h ligation) induced gastric ulcer models as it showed protection index of 71.28, 62.50, 90.84 and 64.29% protection, respectively whereas, standard drug omeprazole (OMZ, 10mg/kg body weight) has shown protection index of 85.70, 74.99 and 74.99 in CRU, ASA and PL model respectively. Sucralfate (SUC, 500 mg/kg body weight) as a standard drug in AL model has 93.20% protection. Furthermore, AS has significantly decreased the free acidity (72.41%), total acidity (47.97%) and peptic activity (24.59%), respectively as well as has significantly increased the mucus secretion (29.41%). Conclusively the ulcer protective effect of AS may be due to its anti-secretory along with cytoprotective mechanism.
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PMID:Allophylus serratus: a plant with potential anti-ulcerogenic activity. 1587 49

COX-1 and COX-2 are two cyclooxygenase enzymes responsible for prostanoid production. COX-2 is expressed in inflammatory cells and fibroblasts of the gastric mucosa, and through the production of various growth factors including hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), plays a key role in the tissue repair process. Aspirin induces and acetylates COX-2 to produce 15-(R)-epi-lipoxinA4, an anti-inflammatory mediator thought to protect the gastric mucosa against aspirin-induced injury. Recently, three different PGE synthases have been identified, that convert COX-2 metabolites into PGE2. mPGE synthase (mPGES)-1 has been shown to be inducible, and to colocalize with COX-2 in fibroblasts and macrophages infiltrating the gastric ulcer bed. cPGES and mPGES-2 have been found expressed in normal gastric mucosa, with no change in expression levels seen in gastritis or gastric ulcer tissue. Finally, this review discusses the role of these enzymes in the pathophysiology of the gastric mucosa, as well as the biologcal significance of their inhibition.
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PMID:The role of cyclooxygenase in gastric mucosal protection. 1618 16

Aspirin and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding is recognized as an important health problem. We performed a single-center randomized clinical trial to compare the effect of high-dose intravenous proton pump inhibitor (omeprazole) alone (group 1) with omeprazole in combination with a low-dose prostaglandin analog (misoprostol; group 2) on clinical outcomes in patients with aspirin/NSAID-induced upper gastrointestinal bleeding. Additionally, we evaluated the contribution of Helicobacter pylori eradication therapy on the late consequences. Patients were recruited to the study if they had upper gastrointestinal bleeding with history of taking aspirin or other NSAIDs within the week before the onset of bleeding. All were evaluated in terms of probable risk factors. After the standard treatment protocol, patients with histologically proven H pylori infection were prescribed a triple eradication therapy for 14 days. The primary end points were recurrent bleeding, surgery requirement, and death rates before discharge and at the end of follow-up period. This study lasted for 2 years. A total of 249 patients with upper gastrointestinal bleeding were admitted, and 49.7% of these patients were users of aspirin/NSAIDs. There were 67 patients in group 1 and 56 in group 2. The distributions for gender, age, comorbidity, H pylori infection, and high-risk ulcer rate were similar in both groups. Among aspirin/NSAID users, endoscopy revealed duodenal ulcer in 47 (38.2%), gastric ulcer in 10 (8.1%), and erosive gastropathy in 33 (26.8%). The overall rebleeding occurred in 12.2%, death in 2.4% of the patients. The in-hospital death (P=.414), rebleeding (P=.925), and surgery (P=.547) rates were similar in both treatment groups. After the follow-up period of 3 months, overall rebleeding occurred in 4.1%, and death in 4.8% of the patients. The overall mortality rate was highest in those >65 years old, who were chronic low-dose aspirin users with comorbidity. One died of transfusion-related graft-versus-host disease. In this pilot study, we indicated that adding misoprostol (600 microg/day) to standardized proton pump inhibitor treatment did not improve or change the rebleeding or mortality rates of patients with upper gastrointestinal bleeding related to aspirin/NSAID use. Other prospective studies on higher doses of misoprostol are needed to establish the coeffect. One should bear in mind that all blood products must be irradiated before transfused to the host.
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PMID:Does adding misoprostol to standard intravenous proton pump inhibitor protocol improve the outcome of aspirin/NSAID-induced upper gastrointestinal bleeding?: a randomized prospective study. 1715 2

Irritable bowel syndrome occurs most frequently in young adults in response to emotional and other factors. The 20th century western epidemic of diverticular disease may be linked to low dietary fiber intake. Peptic ulceration is determined by genetic and environmental factors including tobacco and coffee. Aspirin specifically predisposes to gastric ulcer. The incidence of peptic ulcer is declining. Crohn's disease is increasing in frequency although the incidence of ulcerative colitis is fairly steady. Gastrointestinal cancer is closely related to dietary factors including ingested procarcinogens, excessive carbohydrate, fat and animal protein. There is potential for control of some intestinal cancers.
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PMID:Epidemiology of gastrointestinal disorders. 2130 48


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