• Archives of Pharmacal Research
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• 제9권3호
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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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• 제13권5호
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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.

• 생약학회지
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• 제36권1호통권140호
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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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• 제4권1호
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• pp.18-27
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• 2001

목 적: 소아 H. pylori 위염에서 균 박멸 후의 조직학적 변화에 대한 연구는 거의 없는 실정이며 치료전의 조직소견과 균 박멸과의 관련성 또한 잘 밝혀져 있지 않다. 이에 저자들은 H. pylori 위염 소아들을 대상으로 치료 전후의 내시경 및 조직소견을 분석하여 균 박멸로 초래되는 위염의 내시경적, 조직학적 변화 및 균 박멸의 성공에 영향을 주는 치료 전 조직소견들을 알아보고자 하였다. 방 법: 95년 6월부터 99년 5월까지 만성 복통으로 내원하여 치료 전후 내시경 생검을 시행받은 소아들 중 조직 검사상 균이 관찰되면서 urease 검사가 양성인 만성위염 소아 42명을 대상으로 하였다. 박멸요법 후 4주 이후에 추적 내시경 검사를 시행하여 위 두 가지 검사 및 배양 검사가 모두 음성인 경우를 균 박멸로 판정하였고, 조직 소견상 위전정부의 균밀도 및 염증 소견들을 최근의 시드니 위염분류법에 따라 0, 1, 2, 3으로 등급화하여 분석하였다. 또한 OAC로 치료받은 32명의 소아들을 박멸에 성공한 군과 실패한 군으로 나누어 각각의 경우 시드니 위염분류법에 따른 치료 전 조직 소견에 차이가 있는지를 분석하였다. 결 과: 1) 균이 박멸된 소아들(27례)의 경우 결절성 위염은 치료 전 89%에서 치료 후 63%로 유의하게 감소하였다(p<0.05). 조직 소견상 호중구 침윤등급은 평균 2.06에서 0.24로 현저하게 감소하였고(p<0.01), 만성염증세포 침윤등급은 평균 2.61에서 1.89로 유의하게 감소하였으나(p<0.05) 완전히 호전된 예는 없었다. 림프여포는 48%에서 15%로 유의하게 감소하였고(p<0.05), 점막 상피손상은 치료 후 모두 소실되었다. 균박멸에 실패한 소아들(15례)의 경우는 치료 전후 결절성 위염의 빈도, 조직 소견상 호중구 및 만성염증세포 침윤등급, 림프여포의 빈도에 유의한 변화가 없었다. 2) OAC 세 약제 치료 후 성공적으로 균이 박멸된 소아들(18례)과 균 박멸에 실패한 소아들(14례)의 치료전 내시경 소견과 조직소견을 비교하였을 때 결절성 위염의 빈도, 호중구 및 만성 염증세포침윤등급, 림프 여포 및 상피손상의 빈도에 모두 유의한 차이가 없었으나, 균밀도는 균박멸에 실패한 소아들에서 더 높은 경향을 보였다(p=0.072). 결 론: 소아 H. pylori 위염에서 균박멸 치료 4주 이후 호중구 침윤은 현저한 감소를 보이며, 만성염증세포 침윤정도, 림프여포와 내시경상 결절성 위염도 의미 있는 호전을 보인다. 시드니 위염분류법에 따른 치료 전의 조직학적인 등급 중 균밀도는 높을수록 균박멸이 낮은 경향이 있어서 치료의 성공여부를 예측하는 데 이용될 수 있는 가능성이 있다.