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)

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

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

Glycosaminoglycans (GAGs) are suspended in urine and are present on tissue surfaces in the urinary tract. Consequently, they have the potential to influence any pathological disorder in this environment, including urinary tract infections by Proteus mirabilis and struvite (NH4MgPO4.6H2(0)) urolithiasis. Although GAGs, suspended in urine, may inhibit the formation of other types of calculus minerals, no such effect has been reported in struvite calculi. Nevertheless, GAGs are a major component of the organic matrix of all types of urinary calculi. In contrast, there is evidence that the GAG layer on the bladder surface may act as a defence mechanism against infection by inhibiting bacterial adhesion. More studies are needed to elucidate fully the role of GAGs in urinary infections and struvite urolithiasis.
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PMID:Glycosaminoglycans and struvite calculi. 801 16

To study a clinical problem in urolithiasis complicated with bacteriuria treated by extracorporeal shock wave lithotripsy (ESWL), we studied relationships between the frequency of bacteriuria and some clinical factors such as sex, location of, size of and composition of calculi in patients with upper urinary tract calculi. We also evaluated whether bacteriuria caused fever elevation after ESWL monotherapy. Six hundred seventy patients with upper urinary tract calculi, 440 renal calculi and 230 ureteral calculi, were subjected to the present study. The results were summarized as follows: 1) Bacteriuria was found in 40 of 440 patients with renal calculi (9%) and 12 of 230 patients with ureteral calculi (5%). 2) The frequency of bacteriuria was significantly higher in female (11%) than in male (6%) (p < 0.05). 3) Ten strains of Pseudomonas aeruginosa, 7 of Escherichia coli and 6 of Proteus mirabilis were isolated in patients with bacteriuria. 4) On the location of renal calculi in patients with bacteriuria, 37 out of 40 patients (93%) were found in R2. In contrast, bacteriuria was the most frequently found in DS 6 (19%), whereas the positive rates were about 10% in DS 3 (7%), DS 4 (*7%) and DS 5 (9%). The presence of bacteriuria was not related to the location of calculi or the size of calculi in patients with ureteral calculi. 5) Most of the calculi with bacteriuria were composed of magnesium ammonium phosphate or the mixture of calcium phosphate and carbonate with or without oxalate. 6) Patients with bacteriuria had a significantly higher rate of fever elevation after ESWL than those without bacteriuria (p < 0.01).
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PMID:[A clinical study on upper urinary tract calculi treated with extracorporeal shock wave lithotripsy (ESWL) monotherapy, with regard to bacteriuria before ESWL treatment]. 832 Aug 92

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

The virulence of a urease-negative mutant of uropathogenic Proteus mirabilis and its wild-type parent strain was assessed by using a CBA mouse model of catheterized urinary tract infection. Overall, catheterized mice were significantly more susceptible than uncatheterized mice to infection by wild-type P. mirabilis. At a high inoculum, the urease-negative mutant successfully colonized bladders of catheterized mice but did not cause urolithiasis and was still severely attenuated in its ability to ascend to kidneys. Using confocal laser scanning microscopy and scanning electron microscopy, we demonstrated the presence of P. mirabilis within the urease-induced stone matrix. Alizarin red S staining was used to detect calcium-containing deposits in bladder and kidney tissues of P. mirabilis-infected mice.
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PMID:Visualization of Proteus mirabilis within the matrix of urease-induced bladder stones during experimental urinary tract infection. 1174 5

The authors review the effectiveness of a novel fluoroquinolone drug sparfloxacine (Sparflo, Dr. Reddy's Laboratories) in the treatment of patients with complicated forms of pyelonephritis and prostatitis. Both gramnegative and grampositive agents causing complicated urologic infections were highly sensitive to sparfloxacine: Enterobacter spp.--40.8%, Pseudomonas aeruginosa--38.5%, Proteus spp.--42.6%, E. coli--91.4%, Staphylococcus spp.--80.0%, Enterococcus faecalis--21.4%. Sparfloxacine was used in the treatment of 43 patients with complicated pyelonephritis and prostatitis. The complicating factors were the following: urolithiasis, renal anomalies, hydronephrotic transformation, nephroptosis, benign prostatic hyperplasia. Clinical response reached 83.7%; microbiological--78.7%. Thus, sparfloxacin has a wide spectrum of antibacterial activity and can be effectively used in patients with complicated infections of the urinary tract.
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PMID:[Use of sparfloxacin (Sparflo) in treating complicated urologic infections]. 1207 17

Proteus mirabilis is a documented cause of urinary tract infection (UTI) in the complicated urinary tract. Urease-mediated urea hydrolysis is responsible for both virulence of the organism and the ability to cause urolithiasis. A urease-negative mutant of P. mirabilis is unable to initiate stone formation and colonizes the kidney at a significantly lower rate. The considerable pathology caused by P. mirabilis warrants the development of a vaccine. We have initiated the advancement of vaccine studies and have determined that the MR/P fimbria, a surface adhesin of P. mirabilis, is a promising vaccine candidate. Successful vaccination would be expected both to prevent colonization by P. mirabilis and urolithiasis.
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PMID:Vaccines for Proteus mirabilis in urinary tract infection. 1213 33


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