• Archives of Pharmacal Research
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• v.9 no.3
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• pp.163-167
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• 1986

Twenty six urea analogues, most of which have already been approved for human use, were tested for their antiurease activity in vitro. Cell-free extracts obtained from a clinical isolate of Proteus mirabilis was used as the source of enzyme. Acetohydroxamic acid which is a proven potent urease inhibitor but not approved for human use was again shown to be the most active compound among the tested. Phenacemide, cycloserine, and deferoxamine were demonstrated to be moderate inhibitors. Oxtetracycline, trimethoprim, and cefamandole revealed a demonstrable antiruease activity, but only at very high concentrations. The antiurease activity of cycloserine, trimethoprim, and cefamandole was pH dependent-only active at acidic pH. The inhibitory activity of acetohydroxamic acid however was independent of change in pH. The inhibitory activity of acetohydroxamic acid however was independent of change in pH. Hydrogen ion concentration plays an important role in urease activity and acidification (pH 5. 5) alone eliminates approximately 65% of the enzymic activity. Adjustment of pH therefore appears to be an important adjunct in reducing unrease activity and should always be studied to maximize the effcacy of antiurease compounds under investigation.

• Journal of Microbiology and Biotechnology
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• v.13 no.5
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• pp.673-679
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• 2003

Glutamine and urea, abundant in body fluids or plasma, yield net ammonium ions upon hydrolysis by ${\gamma}-glutamyl$ transpeptidase (${\gamma}-GTP$) and urease, respectively, and these two enzymes are largely produced from Helicobacter pylori. To investigate bacterial potential of ammonium production, we first quantified those in whole-cell systems and found that the relative ratio of their amounts varied greatly, especially with pH values and the cell's aging. During the H. pylori cultivation, the ratio appeared to be inversely proportional to each other, showing a progressive increase of the ${\gamma}-GTP$ with decreasing of the urease. Under the urease-defective conditions due to low pH or coccoids, the bacterial cells still possessed a considerable amount of ${\gamma}-GTP$, which was found exclusively in the external compartment, therefore, the cell's ammonium production was found to be solely dependent upon glutamine, and the external ammonium concentration was constant without any contribution of urea concentration. Such ammonium constancy would definitely have an adverse effect on the host, because of its absolute requirement for vacuolar degeneration by H. pylori VacA, maximized at approximately 10 mM $NH_4Cl$. It was also found that, by using the metal-saturated membrane vesicles, ammonium ions were likely to be involved in the pH-dependent cation-flux across the H. pylori membrane, where the role of ${\gamma}-GTP$ in ammonium homeostasis around cells was suggested, especially under the hostile conditions against H. pylori.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.56-59
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• 2005

Urease plays an important role in the urea metabolism and the effect of urease activity on human and environment is enormous. For instance, urease acts as a virulence factor of the urinary and gastrointestinal tracts infections in human and animal, being involved in kidney stone formation, catheter encrusatation, pyelonephritis, ammonia encephalopathy, hepatic coma, and urinary tract infections. Widespread urease activity in soil induces a plant damage due to ammonia toxicity and pH increase. Therefore, urease activity regulation through urease inhibitors would lead to an enhanced efficiency of urea nitrogen uptake in plants and to the improved therapeutic strategies for ureolytic bacterial infections. To search for new inhibitory compounds on urease activity from herbs, MeOH extracts of herbs were screened. Among of them, the MeOH extracts of Areca catechu exhibited an excellent inhibitory effect on urease activity. Two compounds were isolated from the ethyl acetate fraction by the activity guided fractionation. Their chemical structures were identified as (+)-catechin(compound I) and allantoin(compound II) by spectroscopic evidence, respectively. Compound I showed a stronger inhibitory effect on urease activity than compound II.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.1
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• pp.18-27
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• 2001

Purpose: The aims of this study are to investigate the effect of the eradication of H. pylori on histological change of gastric mucosa in children with H. pylori gastritis and to determine whether the histological grading by the Sydney system is valuable in predicting the effect of treatment. Methods: 1) Histological scores by the Sydney system and the endoscopic characteristics were assessed before and at least four weeks after anti-H. pylori therapy in 42 children with H. pylori gastritis. 2) In 32 children treated with omeprazole, amoxicillin and clarithromycin (OAC), pretreatment histological scores and endoscopic findings were compared between the eradicated and the noneradicated to evaluate their predictive value for the successful eradication. Results: 1) In the eradicated (27 cases), nodular gastritis significantly decreased from 89% to 63% (p<0.05). There was an significant improvement in the mean activity score from 2.06 before treatment to 0.24 after treatment (p<0.01). The mean inflammatory score also improved from 2.61 before treatment to 1.89 after treatment (p<0.05). Lymphoid follicles significantly decreased from 48% to 15% (p<0.05). Epithelial damage improved in all 4 cases. But in the noneradicated (15 cases), there was no significant change in the frequency of nodular gastritis, the mean activity score, the mean inflammatory score and the frequency of the lymphoid follicles. 2) In 32 children treated with OAC, there was a tendency that the higher was the pretreatment score of the bacterial density, the lower was the eradication rate of H. pylori (p=0.072). Conclusion: The loss of the polymorphonuclear cell infiltration is the most prominent histological change after successful eradication. There may be negative correlation of the grade of the bacterial density with the success rate of the anti-H. pylori therapy.