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 restoration of gastric tissue after ulceration involves cellular and matrix components. Our aim was to investigate the kinetics of collagen expression and cellular proliferation in an animal model of gastric ulcer. To demonstrate the expression of type I and IV collagen mRNAs by proliferating cells, a method combining in-situ hybridization and immunohistochemistry was devised. In order to avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were utilized and combined with single-step immunohistochemistry. This method proved sensitive enough to detect type I and IV procollagen mRNA transcripts in the submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In addition, a subset of cells transcribing either procollagen type I or IV RNA was concomitantly positive for proliferating cell nuclear antigen by immunohistochemistry. Focal proliferation of cells simultaneously expressing extracellular matrix components may therefore occur in the gastric submucosa after ulceration, starting as soon as 3 days after the insult and continuing for several weeks. The devised method of combined in-situ hybridization and immunohistochemistry can be used with standard paraffin-embedded tissues, yields results within 2 days, and avoids radioisotopes.
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PMID:Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined in-situ hybridization and immunohistochemistry technique applicable to paraffin-embedded tissue. 902 1

This study was done to investigate the gene expression and localization of tenascin in ulcerated gastric tissues during the healing process with Northern blot analysis and immunohistochemical technique. Gastric ulcers in rats were produced by acetic acid. Tenascin mRNA levels in the ulcerated tissue were significantly increased in a biphasic manner (12 h and day 5), preceding the increase in collagen type IV and laminin mRNA levels, and returned to control levels on day 11. In intact tissues, tenascin was mainly localized in the basement membrane above the proliferative zone, in contrast to the predominant localization of collagen type IV and laminin below the proliferative zone. On the ulcer margin from 12 h to day 5, tenascin was abundantly observed in the lamina propria around nonproliferating new epithelial cells, but collagen type IV and laminin were not seen in this lamina propria. On day 7, tenascin, expressed in the lamina propria, was replaced by collagen type IV and laminin. Thus, the rapid expression and unique localization of tenascin suggest the important role of tenascin in gastric ulcer healing.
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PMID:Rapid expression and specific localization of tenascin in gastric ulcer healing in rats. 914 1

An association between eosinophils and tissue damage has been observed in numerous disorders. However, few reports have addressed the role of infiltrating eosinophils in gastric ulcer healing. The aim of this study was to investigate the kinetics and role of eosinophils infiltrating experimental chronic gastric ulcers in the rat. We developed a monoclonal antibody against human matrix metalloproteinase 1 (MMP1) purified from conditioned culture medium of human skin fibroblasts. Acetic acid-induced gastric ulcers were resected from rats on days 1, 3, 5, 10, 20, 40, and 180 after the days of induction (day 0). Tissue specimens were immunostained with this antibody and examined with an electron microscope. Few eosinophils were observed in the granulation tissue until day 20. By days 40 and 180, MMP1-positive eosinophils had increased in the granulation tissue of open ulcers. Azan staining revealed dispersed collagen fibers around infiltrating eosinophils. In contrast, scars demonstrated few eosinophils in fibrous tissue on days 40 and 180. Eosinophils which express MMP1 infiltrate granulation tissue at the chronic stage of gastric ulceration. The results suggest that eosinophils may play a role in tissue remodeling and deterioration of ulceration.
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PMID:Kinetics and collagenolytic role of eosinophils in chronic gastric ulcer in the rat. 937 22

Gene expression of matrix degrading enzymes was investigated in surgical specimens of perforated gastric ulcers. In these ulcers, the inflammatory cells infiltrating into the granulation tissue were granulocytes, particularly eosinophils. The extracellular matrix of the stomach wall consists mainly of collagen types I and III, which are selectively degraded by matrix metalloproteinase-1 (MMP-1). MMP-1 mRNA was detected in the cytoplasm of infiltrating cells, suggesting that eosinophils play an important role in ulcer recurrence and in perforation of the stomach wall. The degree of eosinophil infiltration into an ulcer base may be a useful marker for the risk of perforation. Patients showing this marker may benefit from a prophylactic therapy for preventing severe complications. The control of MMP gene expression represents a potential strategy for the treatment of recurrent gastric ulcer.
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PMID:Matrix metalloproteinase gene expression in chronic gastric ulcer: a potential role of eosinophils in perforation. 947 34

A case of collagenous colitis is reported. A 48 year old female who had been complaining of mild diarrhea had been under medication for a gastric ulcer. Colonoscopy revealed almost normal appearance of the colonic mucosa except for one hyperplastic polyp of the cecum. Specimens of the ascending, transverse and descending colon showed a distinctively thickened collagen band beneath the surface epithelium, 10-20 microns thick, which was irregularly distributed, even within the same specimen. In some areas, the thickened collagen band was found around the upper part of the pits. Periodic acid-Schiff (PAS), Azan staining and silver impregnation were positive for this thickened collagen band. Immunohistochemically, the thickened collagen band was weakly positive for collagen type III, but negative for collagen types I and IV. Plasma cells, lymphocytes and eosinophils were observed in the lamina propria in addition to intraepithelial lymphocytic infiltration. Capillaries were increased in the thickened collagen band. The arrangement of surface epithelial cells was irregular. Crypts were not distorted. Edema, diffuse or extensive fibrosis and congestion were not found. Through these findings the patient was diagnosed as having collagenous colitis. Many cases of this had been reported in western countries, but very few in Japan. The Japanese literature was reviewed for cases of collagenous colitis and it was found that only two cases had been presented.
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PMID:Collagenous colitis in a Japanese patient. 1084 72

The bark and leaves of Eucommia ulmoides Oliv (Eucommiaceae) and "Siberian ginseng" (Ezoukogi in Japanese) prepared from the root bark or stem bark of Eleutherococcus senticosus Maxim (Acanthopanax senticosus Harms) have been used as tonic and anti-stress drug. The extracts of Eucommia showed anti-hypertensive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promoting collagen synthesis, accelating granuloma formation, and other pharmacological effects. The Siberian ginseng exhibited anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effect. By now, 40, 28, and 10 compounds have been isolated from Eucommia ulmoides bark, Eucommia ulmoides leaves, and Siberian ginseng, respectively, and their structures were elucidated. Their pharmacological activities were mainly due to lignans and iridoid glycosides.
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PMID:Constituents and pharmacological effects of Eucommia and Siberian ginseng. 1174 1

The healing of gastric ulcers requires not only the complete epithelial covering but also the restitution of connective tissue. Transforming growth factor-beta (TGF-beta) and its downstream mediator, connective tissue growth factor (CTGF), are potent stimulators for connective tissue formation during wound healing. The expression of TGF-beta, CTGF and type III collagen mRNA in indomethacin-induced gastric ulcers in rat, was investigated by Northern blot analysis. We also examined the localization of CTGF producing cells by in situ hybridization. Northern blot analysis showed expression of TGF-beta mRNA on days 1 and 3 after indomethacin administration, expression of CTGF mRNA on days 1, 3 and 7 and type III collagen mRNA expression on days 1, 3, 7 and 12, respectively. Control animals showed no expression of TGF-beta, CTGF or type III collagen mRNA. In situ hybridization showed CTGF mRNA positive cells on days 1, 3 and 7 after ulcer induction in fibroblast-like cells and in some of the blood vessels. Thus our findings indicate that growth factor CTGF, together with TGF-beta, participates in gastric ulcer healing by regulating connective tissue formation and angiogenesis. These results are compatible with the role of CTGF as a downstream mediator of TGF-beta effects.
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PMID:Connective tissue growth factor in indomethacin-induced rat gastric ulcer. 1207 10

The natural resin collected from the trunk wood of Protium heptaphyllum is used in folk medicine to treat inflammatory conditions and to hasten wound repair. In the search of new potential anti-inflammatory agents with gastroprotective property, the present study evaluated its effects in experimental models of gastric ulcer and inflammation. In mice, the resin (200 and 400 mg/kg) significantly attenuated the gastric damage induced by ethanol or acidified ethanol (HCl/ethanol), in a manner similar to N-acetyl-L-cysteine (NAC), a replenisher of sulfhydryls. Unlike NAC the resin failed to restore the ethanol-induced depletion of non-protein sulfhydryl content, indicating a different mechanism of gastroprotection. However, in 4-h pylorus-ligated rats, the resin significantly reduced the total acidity without much change in gastric secretory volume. In rats, at similar doses the resin did not modify the hind-paw edema induced by carrageenan, but effectively reduced the formation of cotton pellet-induced granuloma, suggesting its inhibitory effect on collagen formation but not on acute edema. Furthermore, the vascular permeability increase induced by acetic acid was significantly reduced in mice that received 400 mg/kg resin. The resin demonstrated no overt toxicity in mice up to an oral dose of 5 g/kg. Phytochemical analysis revealed the presence of alpha- and beta-amyrins as principal triterpenoid constituents of resin, which were previously described to have anti-ulcer property. These findings indicate the potential gastroprotective and anti-inflammatory property of P. heptaphyllum resin and further support its popular use in gastrointestinal disorders.
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PMID:Gastroprotective and anti-inflammatory effects of resin from Protium heptaphyllum in mice and rats. 1464 90

Endothelin (ET)-1 is a potent inducer of peptic ulcers. The roles of ET-1 in ulcer healing, however, have remained unclear, and these were investigated in mice. Gastric ulcers were induced in mice by serosal application of acetic acid. Three days later, mice were given a neutralizing ET-1 antibody or nonimmunized serum. The ulcer size, amount of fibrosis and myofibroblasts, and localization of ET-1 and ET(A/B) receptors were analyzed. To elucidate the mechanisms underlying the effects of ET-1, we examined the proliferation, migration, and release of growth and angiogenic factors in gastric myofibroblasts with or without ET-1. The expression of prepro-ET-1 (an ET-1 precursor) and ET-converting enzyme-1 was examined in gastric myofibroblasts using RT-PCR. Immunoneutralization of ET-1 delayed gastric ulcer healing. The areas of fibrosis and myofibroblasts were smaller in the anti-ET-1 antibody group than in the control. ET-1 was expressed in the gastric epithelium, myofibroblasts, and other cell types. ET(A) receptors, but not ET(B) receptors, were present in myofibroblasts. ET-1 increased proliferation and migration of gastric myofibroblasts. ET-1 stimulated the release of hepatocyte growth factor, VEGF, PGE(2), and IL-6 from gastric myofibroblasts. mRNA for prepro-ET-1 and ET-converting enzyme-1 was also expressed. ET-1 promotes the accumulation of gastric myofibroblasts and collagen fibrils at gastric ulcers. ET-1 also stimulates migration and proliferation of gastric myofibroblasts and enhances the release of growth factors, angiogenic factors, and PGE(2). Thus ET-1 has important roles not only in ulcer formation but also in ulcer healing via mobilizing myofibroblasts and inducing production of stroma-derived factors.
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PMID:Endothelin-1, an ulcer inducer, promotes gastric ulcer healing via mobilizing gastric myofibroblasts and stimulates production of stroma-derived factors. 1638 72

Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling.
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PMID:The human tri-peptide GHK and tissue remodeling. 1864 25


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