Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.
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PMID:Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. 920 47

Gastric mucosa is exposed to various aggressive factors such as stress, ulcerogenic drugs including acetyl-salicylic acid(ASA)-like agents, ethanol, bacteria, particularly Helicobacter pylori (Hp), and various endogenous irritants such as acid-pepsin secretion and bile salts. The maintenance of the mucosal barrier depends upon the activation of the pre-epithelial (mucus-alkali secretion), epithelial (surface-active phospholipids and rapid mucosal restitution) and post-epithelial (mucosal microcirculation, sensory nerves and mast cells) components of mucosal defense. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is the first of a new generation of H2-receptor antagonists with both antisecretory and cytoprotective activities. Its inhibitory action is similar to that of ranitidine and approximately tenfold greater than cimetidine, and is accompanied by a small and transient increase in plasma gastrin levels. In contrast to ranitidine and other H2-receptor antagonists, ebrotidine exerts a unique cytoprotection against injury by various ulcerogens such as ethanol, ammonia, lipopolysaccharides (LPS), stress and ASA or acidified taurocholate. The mechanism of this protection by ebrotidine is not clear, but it has been shown to stimulate mucus secretion, to increase the quality of adherent mucus gel and to increase gastric mucosal blood flow (GBF), possibly due to enhanced mucosal formation of prostaglandin E2 (PGE2) and nitric oxide (NO). The cytoprotective effects of ebrotidine were observed in rats and confirmed also in humans with gastric lesions induced by ethanol or ASA. Ebrotidine also exerts anti-Helicobacter pylori (Hp) effects by interfering with surface receptors of epithelial cells and inhibiting urease, protease and lipase activity, and by counteracting the noxious effects of Hp-related substances such as ammonia and lipopoly-saccharides (LPS).
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PMID:Studies on the cytoprotective and antisecretory activity of ebrotidine. A review. 920 69

In almost all eradication regimens, which contain antibiotics and bismuth derivatives, the administration of acid suppressing drugs for 4-6 weeks is recommended for healing of duodenal ulcer. The aim of this multicenter double blind study is to elucidate the effect of two classic antibiotics tetracycline (CAS 60-54-8) and metronidazole (CAS 443-48-1) alone or combined with ranitidine (CAS 66357-35-5) on the healing of duodenal ulcer and eradication of Helicobacter Pylori. Patients with duodenal ulcer were randomized to two treatment groups: group A received either ranitidine 4 x 150 mg or tetracycline 4 x 500 mg or metronidazole 3 x 250 mg for 2 weeks. Group B received 4 x placebo + tetracycline and metronidazole as in group A for 2 weeks. A final endoscopy was performed after 8 weeks. Four biopsy specimens were obtained from the antrum (two) and corpus (two) for both urease test and hematoxylin stain for detection of H. pylori. Out of 201 patients entering the study 156 completed the study (78 in A and 78 in B). The healing rate of duodenal ulcer was 98.7% in group A and 97.5 in group B. The eradication rate was only 33.3% in group B but 64% in group A (p < 0.001), when additionally ranitidine was given. The present study shows that treatment with the two antibiotics tetracycline and metronidazole alone results in a very low H. pylori eradication, but almost complete healing of duodenal ulcer after 8 weeks. Prolonged administration of antisecretory drugs in eradication regimens containing two antibiotics is not necessary for duodenal ulcer healing. However, the addition of H2-receptor antagonists or proton pump inhibitors to antibiotics increases the eradication rate.
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PMID:Efficacy of tetracycline and metronidazole alone or with ranitidine on the healing of duodenal ulcer and eradication of Helicobacter pylori. A randomized controlled multicenter study. Tetra-Metro-Ran Study Group. 968 28

A field experiment was carried out at the Shenyang Experimental Station of Ecology (CAS) in order to study the effects of slow-release urea fertilizers high polymer-coated urea (SRU1), SRU1 mixed with dicyandiamide DCD (SRU2), and SRU1 mixed with calcium carbide CaC2 (SRU3) on urease activity, microbial biomass C and N, and nematode communities in an aquic brown soil during the maize growth period. The results demonstrated that the application of slow-release urea fertilizers inhibits soil urease activity and increases the soil NH4+-N content. Soil available N increment could promote its immobilization by microorganisms. Determination of soil microbial biomass N indicated that a combined application of coated urea and nitrification inhibitors increased the soil active N pool. The population of predators/omnivores indicated that treatment with SRU2 could provide enough soil NH4+-N to promote maize growth and increased the food resource for the soil fauna compared with the other treatments.
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PMID:Effects of slow-release urea fertilizers on urease activity, microbial biomass, and nematode communities in an aquic brown soil. 1608 26