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

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.
 ...
PMID:Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines. 1464 93

In acute inflammatory condition, little is known about the expression of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in the gastric fibroblasts. To clarify the role of human gastric fibroblasts in acute inflammatory conditions such as gastric ulcer, the effects of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on the expression of uPA and uPAR, which were suggested to be associated with tissue remodeling, in gastric fibroblasts were investigated. The expression level of uPA mRNA and the amount of uPA antigen increased significantly on treatment with each concentration of IL-1beta (1 and 10 ng/ml) and 10 ng/ml TNF-alpha. On the other hand, the amounts of uPA antigen on cell surfaces were not affected significantly by IL-1beta and TNF-alpha stimulation. The expression level of uPAR mRNA increased in a dose-dependent manner on IL-1beta stimulation. The effect of indomethacin on uPA and uPAR expression in these cells was also examined. When gastric fibroblasts were treated with 50 microM indomethacin, the expression level of uPA mRNA decreased significantly, and the amount of uPA antigen in the culture medium and on cell surfaces decreased significantly with indomethacin in a dose-dependent manner. The increased uPAR mRNA expression caused by IL-1beta was reduced to the basal level by treatment with 50 microM indomethacin. Furthermore, we investigated the role of prostaglandin E2 (PGE2), which is suggested to play major roles in acute inflammation of the stomatch, on uPA and uPAR expression in gastric fibroblasts. The expression level of uPAR mRNA and the amount of uPA antigen on cell surfaces increased in a dose-dependent manner on treatment with PGE2 (10 and 50 ng/ml). These results suggest that uPA and uPAR expression in gastric fibroblasts is involved in the regulating system of PGE2 and that NSAIDs may delay healing of gastric mucosal injury in part through suppressing uPA production via inhibition of endogenous PG production.
 ...
PMID:Expression of urokinase-type plasminogen activator and its receptor in gastric fibroblasts and effects of nonsteroidal antiinflammatory drugs and prostaglandin. 1471 9

This case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent upper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori-positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1 beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.
 ...
PMID:Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori. 1516 24

The objective of this research was to analyse the gastroprotective effect of Cissus quadrangularis extract (CQE) along with its mechanism underlying the therapeutic action against the gastric mucosal damage induced by aspirin. In this study, we investigated the effect of CQE on the course of experimentally induced gastric ulcer by analyzing the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), microvascular permeability, activity of nitric oxide synthase-2 (NOS-2), mitochondrial antioxidants, lipid peroxidation and DNA damage. A significant increase in vascular permeability, NOS-2 activity, TNF-alpha, IL-1beta levels and oxidative damage were noted in aspirin administered rats. Pretreatment with CQE (500 mg/kg bw/day) by oral gavage for 7 days significantly attenuated these biochemical changes caused by aspirin in rats. Tissue damage was showed by decreased levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and an associated rise in lipid peroxidation (LPO) in mitochondria, which were reversed by CQE. In addition, CQE prevents oxidative damage of DNA by reducing DNA fragmentation indicating its block on cell death. Ulcer protection in CQE treated rats was confirmed by histoarchitecture, which was comprised of reduced size of ulcer crater and restoration of mucosal epithelium. Thus, reduced neutrophil infiltration, antiapoptotic and antioxidant action have a pivotal role in the gastroprotective effect of CQE.
 ...
PMID:Gastroprotective action of Cissus quadrangularis extract against NSAID induced gastric ulcer: role of proinflammatory cytokines and oxidative damage. 1679 7

Wound healing in the gastrointestinal tract is an orderly process involving orchestrated responses of various cell types. Lipopolysaccharides (LPS) are major components of the outer membrane of Gram-negative bacteria, which are known to impair gastric ulcer healing in animals. The influence of LPS on intercellular communication in wound healing, however, is unknown. We examined the effects of LPS-induced macrophage activation on the proliferative response in cultured rat gastric epithelial cells (RGM-1) and fibroblasts JHU-25. Rat peritoneal resident macrophages were activated with increasing doses of LPS. The supernatant from the activated macrophage preparation, designated as macrophage-conditioned medium, was then used to treat RGM-1 or JHU-25 cells. Cell proliferation and migration were determined by [(3)H]-thymidine incorporation and a monolayer wound-healing assay, respectively. Macrophage-conditioned medium significantly suppressed RGM-1 cell proliferation but had no effect on cell migration. The same medium, however, increased JHU-25 cell proliferation. LPS treatment alone suppressed JHU-25 cell proliferation while it had no effect on RGM-1 cell proliferation, indicating that the differential effects of the macrophage-conditioned medium on cell proliferation were elicited by the factors derived from macrophages. In this regard, tumor necrosis factor (TNF)-alpha stimulated while interleukin (IL)-1beta suppressed RGM-1 cell proliferation, suggesting that IL-1beta but not TNF-alpha may play a part in the mediation of the antiproliferative effect of macrophage-conditioned medium on gastric epithelial cells. In contrast, IL-1beta suppressed while TNF-alpha had no effect on JHU-25 cell proliferation. Collectively, LPS-activated macrophages delay gastric mucosal regeneration but promote fibroblast proliferation in vitro. Such changes may partly elucidate the detrimental effect of bacterial infection on tissue repair in the stomach.
 ...
PMID:Shift of homeostasis from parenchymal regeneration to fibroblast proliferation induced by lipopolysaccharide-activated macrophages in gastric mucosal healing in vitro. 1735 54

Gastric ulcer is a multifaceted process including acid secretion, reactive oxygen species generation, prostaglandin inhibition, and extracellular matrix (ECM) degradation. Matrix metalloproteinases (MMPs) have the ability to cleave and remodel the ECM. We investigated the activity and expression of MMP-9 and -2 in ethanol-induced acute gastric ulceration in rats. We found that severity of gastric ulcer was strongly correlated with increasing doses of ethanol and increased secretion of proMMP-9. ProMMP-9 was upregulated approximately 25-fold at maximum ulcer index. Increased secretion of proMMP-9 was associated with increased expression of tumor necrosis factor-alpha and interleukin-6. We examined the effect of H(2)-receptor antagonists and antioxidants on proMMP-9 secretion and synthesis during prevention of ethanol-induced gastric ulcer. Our data reveal that famotidine dose dependently blocked increased secretion and synthesis of proMMP-9 during gastroprotection and arrested infiltration of inflammatory cells as well as oxidative stress in rat gastric tissues. Similar to H(2)-receptor antagonists, N-acetylcysteine and dimethyl sulfoxide, well-known antioxidants, inhibited proMMP-9 upregulation to the control level. In conclusion, ethanol-induced gastric ulceration is associated with increased expression of proMMP-9 that can be attenuated by H(2)-receptor antagonists and antioxidants. These findings furnish a novel MMP-9-mediated pathway and its inhibition via proinflammatory cytokines by famotidine in ethanol-induced gastric ulceration.
 ...
PMID:Novel role of famotidine in downregulation of matrix metalloproteinase-9 during protection of ethanol-induced acute gastric ulcer. 1760 38

Melatonin (MT) is an ubiquitous molecule, representing one of the phylogenetically oldest signaling mechanisms. Our previous studies demonstrated that MT and its precursor L-tryptophan (L-Trp) show strong protective effect on gastric mucosa. The aim of the present study was: 1) to assess the effect of MT and L-Trp on healing of chronic gastric ulcer and accompanying changes in gastric mucosal blood flow (GBF); 2) to study the effect of MT and L-Trp on expression of iNOS. cNOS and HSP70 in ulcerated mucosa; 3) to compare the effect of L-Trp free and L-Trp rich diet on ulcer healing and gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD), cyclooxygenase-2 (COX-2) and NFkappaB-p65 protein expression in ulcer area and intact non-ulcerated. Chronic ulcers were induced in Wistar rats by Okabe's modification of acetic acid method. Rats with chronic gastric ulcers were divided in following treatment groups: 1) vehicle (saline); 2) MT (20mg/kg-d i.p.) and 3) L-Trp (100 mg/kg i.p.). The expression of iNOS, cNOS and HSP70 protein was measured by Western blot. In separate experiments, the influence of commercially available (Bio-Serv, USA) L-Trp free diet (TFD) was compared to the L-Trp rich diet (TRD) on the course of ulcer healing was assessed. The ulcer area was measured by planimetry. The expression of TNFalpha, COX-2 and SOD mRNA in ulcerated mucosa was analyzed by RT-PCR method. MT and its precursor L-Trp significantly accelerated ulcer healing. Healing ulcerated mucosa showed increased protein expression of iNOS and HSP70 as compared to intact gastric mucosa. TFD in contrast to normal diet significantly attenuated the ulcer healing, whereas the TRD exerted opposite effects and significantly accelerated ulcer healing. This last effect was accompanied by significant decrease of TNF-alpha mRNA expression and expression of NFkB-p65 in gastric mucosa. We conclude that: 1) MT and its precursor L-Trp significantly accelerate healing of gastric ulcer; 2) L-Trp free diet significantly attenuates experimental ulcer healing and this is due to decreased synthesis of MT from L-Trp by EE cells in gastric mucosa and 3) MT shows strong anti-inflammatory effects due to inhibition of NFkappaB and TNF-alpha expression.
 ...
PMID:Tryptophan free diet delays healing of chronic gastric ulcers in rat. 1881 28

Despite the fact that dietary habits and lifestyles are incredibly advancing, gastric ulceration is still a terrible complaint. Extensive use of non-steroidal anti-inflammatory drugs (NSAIDs) and alcohol, in addition to stress, are all predisposing factors for ulcers. Most medical treatments are always time consuming and not efficient or satisfactory to the patients. Cardiovascular patients always need NSAIDs, or mostly cannot quit alcohols, while using many cardiovascular drugs. We aim to study a possible benefit of a common nitrogen oxide donor, anti-anginal drug, nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate ester], in managing acute gastric ulcers through studying its effect on some relevant intermediates to ulcerogenesis as lipid peroxidation, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). In addition, gastric mucosal histology was studied to pursue the drug effects on tissue level. Our study revealed that both indomethacin and alcohol induced gastric ulcer mainly through up-regulation of gastric mucosal lipid peroxidation, local tissue inflammation, leukocytic infiltration, and necrosis. Both ulcerogens significantly elevated TNF-alpha and decreased NO, initiating ulcer formation. Nicorandil pretreatment depicted a higher preventive index in indomethacin- (89.8%) and alcohol-induced (77.7%) acute ulceration. On the tissue level, it also protected the gastric mucosa combating leukocyte infiltration and tissue congestion. Nicorandil protected tissue necrosis through decreasing oxidative stress, elevating NO levels, and down-regulating the ulcerogen-induced TNF-alpha elevation and improved sub-mucosal blood supply. We conclude that nicorandil may be a suitable bimodal treatment for cardiovascular patients who are at high risk of gastric ulcers by using variable analgesics to alleviate possible cardiac pain episodes, and probably frequent doses will offer a more established and long-lasting protection.
 ...
PMID:Gastroprotective effect of nicorandil in indomethacin and alcohol-induced acute ulcers. 1893 48

The antiulcer effect of bisdemethoxycurcumin, a yellow pigment found mainly in rhizomes of Curcuma longa, was compared with curcumin in gastric ulcer model systems to validate its clinical application as a remedy for peptic ulcer. Western blot analysis of mouse macrophage cell line RAW 264.7 activated with lipopolysaccharide showed that bisdemethoxycurcumin inhibited inducible nitric oxide synthase (iNOS) production significantly but had no effect on tumor necrosis factor-alpha (TNF-alpha) production, whereas curcumin showed stronger suppression of iNOS protein production and inhibited TNF-alpha protein production significantly. However, bisdemethoxycurcumin and curcumin possessed similar potency in scavenging nitric oxide generated from mouse macrophage cell line RAW 264.7. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that both curcuminoids inhibited the induction of iNOS dose-dependently at the transcriptional level and curcumin also appeared to inhibit the induction of TNF-alpha at post-transcriptional level. In an animal model, intraduodenal administration of bisdemethoxycurcumin (5-80 mg/kg body wt.) showed a strong inhibitory effect on gastric acid secretion in pylorus-ligated rats whereas curcumin (5-20 mg/kg body wt.) showed a less inhibitory effect, with maximum potency at a dose of 20mg/kg body wt. Moreover, oral administration of bisdemethoxycurcumin at doses of 20-80 mg/kg body wt. twice daily for 10 days showed a significant curative efficacy in accelerating the healing of acetic acid-induced chronic gastric ulcer and promotion of mucosal regeneration in the ulcerated portion in a dose-related manner with potency equal to curcumin. In contrast, the curative potency of curcumin tended to decrease at doses over 160 mg/kg body wt./day. Western blot analysis in ulcerated gastric mucosa showed that bisdemethoxycurcumin dose-dependently reduced the increased protein expression level of iNOS but not TNF-alpha. These results indicated that bisdemethoxycurcumin directly accelerates gastric ulcer healing with potency equal to curcumin. Its antiulcer effect might be due to its properties of decreasing gastric acid secretion and enhancing the mucosal defensive mechanism through suppression of iNOS-mediated inflammation.
 ...
PMID:Comparative antiulcer effect of bisdemethoxycurcumin and curcumin in a gastric ulcer model system. 1918 55

The pathogenesis of gastric ulcer is associated with remodeling of extracellular matrix (ECM) by various matrix metalloproteinases (MMPs). However, how MMPs are regulated during nonsteroidal anti-inflammatory drug (NSAID)-induced acute gastric ulceration is not well studied. In this study, different NSAIDs (80 mg/kg b.w.) were applied to generate acute gastric ulcer in the BALB/c mouse and the regulation of MMPs were investigated. NSAIDs caused dose-dependent induction in MMP-9 and -3 activities and expressions in ulcerated gastric tissues along with significant infiltration of inflammatory cells and disruption of gastric mucosal layer. In addition, an increase in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 expression, excessive generation of hydroxyl radical ((*)OH), and protein oxidation and lipid peroxidation were observed in acute ulcerated gastric tissues. In this study, the efficacy of melatonin on activities of MMP-9 and -3 during prevention of gastric ulcers was tested. Melatonin at a dose of 60 mg/kg b.w. downregulated MMP-9 and -3 both at the enzyme and protein levels in mouse gastric tissues during prevention as well as healing of acute gastric ulcers. It also blocked oxidative stress via inhibition of protein oxidation, lipid peroxidation, (*)OH generation and SOD-2 expression. Moreover, it suppressed myeloperoxidase activity and expressions of TNF-alpha, IL-1beta and IL-8. This study documents for the first time that induction of MMP-9 and -3 activities accompany NSAID-induced inflammation and oxidative stress in gastric tissues and indicates that, melatonin may be a preventive or therapeutic remedy for gastric ulcers.
 ...
PMID:Induction of matrix metalloproteinase-9 and -3 in nonsteroidal anti-inflammatory drug-induced acute gastric ulcers in mice: regulation by melatonin. 1952 38


<< Previous 1 2 3 4 5 6 7 8 9 Next >>