Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The calculolytic effect of a diet designed to reduce the urine concentration of urea, P, and Mg was evaluated in female Beagles with induced urease-positive urinary tract infections and struvite urolithiasis and in female Beagles with induced sterile struvite urolithiasis. The reduced-protein calculolytic diet induced urolith dissolution in 5 of 6 infected dogs with struvite urolithiasis in 2 to 5 months (means = 14.4 weeks). At the end of 6 months, uroliths in comparable control dogs fed a maintenance diet were 5 times larger and 14 times heavier than at the beginning of the study. The calculolytic diet induced urolith dissolution in 6 of 6 noninfected dogs with struvite uroliths in 2 to 4 weeks (means = 3.3 weeks). Four uroliths in noninfected dogs fed the maintenance diet dissolved over a period of 2 to 5 months (means = 14 weeks). Urolith dissolution in dogs fed the calculolytic diet was associated with diet-induced diuresis, reduction in urine pH, reduction in urine concentration of urea ammonia, P, and Mg, and increase in urine titratable acidity. Consumption of the calculolytic diet was also associated with significant (P = less than 0.01) reduction in the serum concentration of urea and albumin and a significant (P = less than 0.01) increase in serum hepatic alkaline phosphatase activity. Concomitant occurrence of hydropic degeneration of hepatocytes indicated that these biochemical and morphologic changes were associated with dietary protein restriction.
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PMID:Evaluation of a calculolytic diet in female dogs with induced struvite urolithiasis. 647 63

Hydroxamic acid, a potent urease inhibitor, having a high urinary excretion rate is expected to be a therapeutic agent for urolithiasis caused by urea-splitting bacterial infection of the urinary tract. Twenty-one new derivatives of N-aliphatic-acylglycinohydroxamic acids (GHAs) were synthesized, and their inhibitory potencies against the urease activity of sword bean in a phosphate buffer and against the ureolytic activity of Proteus mirabilis in human urine, and their urinary excretion rates in rats were also measured for this purpose I50 values of most of GHAs against the urease activity of sword bean were about 1 to 10 microM and 2-ethyl-n-butyroyl GHA was the most potent inhibitor with the value of 0.79 microM. I50 values of most of the GHAs against the ureolytic activity of Proteus mirabilis were about 5 to 50 microM and n-nonaroyl GHA was the most potent inhibitor with the value of 3.6 microM. 2,2-Dimethylpropionyl GHA had the highest urinary excretion rate with the recovery of 11%. Routes of administration of 2,2-dimethylpropionyl GHA and sex of rats used did not affect the amount of urinary excretion at all. The results in this report suggest that DL 2-methyl-n-butyroyl, 2-ethyl-n-butyroyl and 2,2-dimethylpropionyl GHA are the most hopeful therapeutic agents for urolithiasis among them.
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PMID:Therapy for urolithiasis by hydroxamic acids. III. Urease inhibitory potency and urinary excretion rate of N-acylglycinohydroxamic acids. 700 14

With the aim of finding a prospective therapeutic compound with a promising potential for the treatment of urolithiasis, we evaluated the effectiveness of a new potent inhibitor of urease, N-(pivaloyl)glycinohydroxamic acid. The present study revealed that N-(pivaloyl)glycinohydroxamic acid effectively inhibited the alkalinization of urine and the stone formation in vitro and in vivo, due to its strong inhibitory potency against the ureolytic activity of intact Proteus mirabilis. The possibility of the clinical application of this compound in the prevention of struvite stone formation caused by infection of urea-splitting bacteria awaits evaluation of the safety of this compound.
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PMID:Therapy for urolithiasis with hydroxamic acids. IV. Prevention of infected urinary stone formation with N-(pivaloyl)glycinohydroxamic acid. 702 44

The analysed material includes 100 children with urolithiasis treated in the Pediatric Clinic of the National Research Institute of Mother and Child in Warsaw between 1976 and 1978. Patients' age was from 3 months to 18 years. The analysed group included 51 boys and 49 girls. Urinary tract infection was found in 54 cases, i.e. 57,4% of the analysed material. The most common bacterial strains were those producing urease. They were detected in 48 children i.e. 88,9% of cases with urinary tract infection. Mostly these were bacteria of Proteus group--sporadically Pseudomonas aeruginosa and Staphylococcus albus. In the analysed patients urinary tract obstruction was observed in 36 children, i.e. 36% of cases. In 77% of the analysed material, localization of concrements was in upper urinary tract in 19% in the ureters and in 4% in the lover urinary tract. While in adult patients the most common compound of urinary stones was calcium oxalate, in children the most common stone compounds were phosphates (found in 38 cases i.e. 58,4% of the analysed material). The second frequent compound was oxalate found in 20 cases (30,7%). Less frequent compounds were uric acid and cystine. Performed study allowed to establish the cause of urolithiasis in 93 out of 100 examined children. Metabolic reasons of urolithiasis were found in 26 cases, i.e. 26% of the analysed material. They were as follows: idiopathic hypercalciuria--12 cases, uric acid urolithiasis--8 cases, primary hyperoxaluria--3 cases, cystinuria--2 cases, and incomplete acidosis of distal renal tubuli--1 case. Urolithiasis of probably metabolic origin was detected in 13 children (13%). Other reasons of urolithiasis in children were: infection (31%), idiopathic urolithiasis (17%) and others (6%). In 7 cases the reason of urolithiasis was not established.
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PMID:[Metabolic etiology of urinary calculi in children]. 717 91

Struvite (magnesium ammonium phosphate) uroliths are found more frequently in the urinary tracts, of dogs than are other types of uroliths. Infection of the urinary tract with urease-producing bacteria, especially staphylococci, plays an important role in urolith formation. An inherited predisposition to urinary tract infection may be associated with the high rat of occurrence of struvite uroliths in some dogs. Diagnosis of struvite urolithiasis should encompass analysis of the mineral composition of calculi and identification of concomitant urinary tract infection. Since urinary tract infections occur as sequelae to abnormalities in local or systemic host-defense mechanisms, appropriate effort should be directed toward detection of these abnormalities. Therapy of struvite urolithiasis should encompass relief of obstruction to outflow when necessary, elimination of existing calculi, eradication or control of urinary tract infection, and prevention of recurrence. Although surgical removal remains as the preferred method to eliminate struvite uroliths from dogs, nonsurgical methods of urolith dissolution should be considered. Recurrence of struvite uroliths may be prevented by various combinations of antimicrobial therapy, administration of urease inhibitors, acidification of urine, and induction of diuresis.
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PMID:Canine struvite urolithiasis: problems and their dissolution. 728 47

Magnesium ammonium phosphate calculi developed in the urinary bladders and urethras of four of five offspring of Miniature Schnauzer parents with recurrent struvite urolithiasis. Calculi were detected by radiograhy when the dogs were 12 to 15 months old. Males and females were affected. A significant number of urease-producing staphylococci were identified in the urine of three of four dogs before urolith formation, and in one dog after urolith formation. The dogs were evaluated until they were 26 months old. Serum concentrations of calcium, phosphorus, and magnesium were inside usual limits throughout the study. Abnormalities that might predispose to urinary tract infection were not identified by radiography or necropsy studies. In one dog, bladder calculi recurred after surgical removal of multiple cystoliths. In another, urethral obstruction and acute generalized pyelonephritis induced a lethal uremic crisis. Gross and microscopic lesions, detected after necropsy of all dogs with uroliths, were typical of bacterial infection.
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PMID:Struvite urolithiasis in a litter of miniature Schnauzer dogs. 740 90

Urease (urea amidohydrolase; EC 3.5.1.5) catalyzes the hydrolysis of urea to yield ammonia and carbamate. The latter compound spontaneously decomposes to yield another molecule of ammonia and carbonic acid. The urease phenotype is widely distributed across the bacterial kingdom, and the gene clusters encoding this enzyme have been cloned from numerous bacterial species. The complete nucleotide sequence, ranging from 5.15 to 6.45 kb, has been determined for five species including Bacillus sp. strain TB-90, Klebsiella aerogenes, Proteus mirabilis, Helicobacter pylori, and Yersinia enterocolitica. Sequences for selected genes have been determined for at least 10 other bacterial species and the jack bean enzyme. Urease synthesis can be nitrogen regulated, urea inducible, or constitutive. The crystal structure of the K. aerogenes enzyme has been determined. When combined with chemical modification studies, biophysical and spectroscopic analyses, site-directed mutagenesis results, and kinetic inhibition experiments, the structure provides important insight into the mechanism of catalysis. Synthesis of active enzyme requires incorporation of both carbon dioxide and nickel ions into the protein. Accessory genes have been shown to be required for activation of urease apoprotein, and roles for the accessory proteins in metallocenter assembly have been proposed. Urease is central to the virulence of P. mirabilis and H. pylori. Urea hydrolysis by P. mirabilis in the urinary tract leads directly to urolithiasis (stone formation) and contributes to the development of acute pyelonephritis. The urease of H. pylori is necessary for colonization of the gastric mucosa in experimental animal models of gastritis and serves as the major antigen and diagnostic marker for gastritis and peptic ulcer disease in humans. In addition, the urease of Y. enterocolitica has been implicated as an arthritogenic factor in the development of infection-induced reactive arthritis. The significant progress in our understanding of the molecular biology of microbial ureases is reviewed.
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PMID:Molecular biology of microbial ureases. 756 14

Culture of stones and electrical microscopic observation were performed with stones collected from forty-eight patients who underwent surgery for urolithiasis. Thirty-six strains of bacteria in the stones obtained form stone culture were classified as nineteen strains of bacteria deriving from primary infection stones (Group A-I) and seventeen strains of bacteria deriving from metabolic stones (Group A-M). As for their ability to produce urease and glycocalyx, they were studied in comparison with forty-nine strains of stone surface-adhering bacteria (Group B). Glycocalyx producing ability was examined by the provisional quantitative toluidine blue assay and safranine straining method. As for the electrical microscopic observation, formation of biofilm bacterium was observed in all twenty cases of primary infection stones and in thirteen cases (46.4%) of twenty-eight cases of metabolic stones. Urease producing ability per stone was 6/14 (43.9%) in Group A-I, 4/13 (30.8%) in Group A-M and, 4/32 (12.5%) in Group B. There was a significant difference (p < 0.05) between Group A-I and Group B. Similarly for the glycocalyx producing ratio (toluidine blue assay), the values were 9/14 (64.3%) in Group A-I, 11/3 (84.6%) in Group A-M and 10/32 (31.3%) in Group B. As for the glycocalyx producing ration (safranine method), the values were 10/14 (71.4%) in Group A-I, 9/13 (69.2%) in Group A-M and 9/32 (28.1%) in Group B. As for the glycocalyx producing ability, Group A-I and Group A-M both showed significantly higher production ratios compared to Group B for both toluidine blue method and safranine method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on characteristics of bacteria which cause infectious stone]. 761 19

Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis.
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PMID:Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection. 851 76

Proteus mirabilis, associated with complicated urinary tract infection, expresses mannose-resistant/Proteus-like (MR/P) fimbriae. Expression of these surface structures, which mediate haemagglutination and have a demonstrated role in virulence, undergoes phase variation. By DNA sequence analysis, a 252 bp invertible element was found in the intergenic region between mrpl, the putative site-specific recombinase gene, and mrpA, the primary structural subunit gene. The invertible segment is flanked by identical 21 bp inverted repeats and the presumptive half-sites for recombinase binding show homology to those recognized by FimB and FimE encoded by the Escherichia coli fim (Type 1 fimbriae) gene cluster. When amplified by the polymerase chain reaction (PCR) from static broth cultures expressing MR/P fimbriae, the switch region was found in both ON and OFF positions. When PCR was used to amplify agar cultures which do not express the fimbriae, the switch region was OFF only. A canonical sigma 70 promoter inside the invertible element drives the transcription of mrpA when in the ON position; in the OFF position it is directed away from mrpA but does not appear to drive expression of mrpI. The mrpI gene was able to confer inversion of the mrp switch region in trans from both ON to OFF and OFF to ON. To examine the position of the switch in vivo, urine, bladder, and kidneys from mice transurethrally infected with P. mirabilis were used to prepare template DNA for PCR amplification. In the absence of urolithiasis (urease-mediated stone formation), the switch was found 100% in the ON position, a condition never observed following in vitro culture. We conclude that MR/P phase variation is regulated at the transcriptional level by the action of MrpI on an invertible element and that there is strong selective pressure for the expression of MR/P fimbriae in vivo.
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PMID:In vivo phase variation of MR/P fimbrial gene expression in Proteus mirabilis infecting the urinary tract. 907 37


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