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

Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20-45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9-14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19-48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.
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PMID:Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi. 392 87

Ureolysis was investigated in salivary bacteria from persons with widely-differing oral ureolytic activities. Rate curves and product stoichiometry were established for urea disappearance, ammonia appearance and conversion of [14C]-urea to 14CO2. Ammonia, released stoichiometrically from urea, was best measured by a direct phenate-hypochlorite reaction. About 80 per cent of the urea-C was liberated as free CO2. Slight deviations from ammonia stoichiometry and most of the CO2 loss occurred in the first 5-10 min of reaction, when the rate of urea disappearance was constant and up to 2-fold higher than subsequently. This rate-change suggests that flux in the ureolysis pathway may be under feedback control. Ureolysis by salivary-sediment bacteria followed Michaelis-Menten kinetics with a Km of 2.5 mM; rates of end-product formation were independent of urea concentration between 25 and 500 mM. Ureolysis was inhibited 98 per cent by 5 mM acetohydroxamic acid, a urease inhibitor, and could be partly solubilized by sonication to give an enzyme preparation which, without cofactor supplementation, quantitatively hydrolysed urea. Thus urea metabolism by oral bacteria may principally involve urease-catalysed hydrolysis, rather than non-urease pathways.
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PMID:Kinetics and product stoichiometry of ureolysis by human salivary bacteria and artificial mouth plaques. 393 57

The fastidious growth requirements of mycoplasmas and ureaplasmas necessitated development of special growth media for them. The 1st mycoplasma was isolated from humans in 1937, and in 1954 a previously unknown mycoplasma was isolated from men with nonspecific urethritis. This organism, Ureaplasma urealyticum, is found most frequently in the genitourinary tract, followed by Mycoplasma hominus. M. fermentans and other mycoplasmas are isolated only rarely. Mycoplasmas and ureaplasmas have been implicated in pelvic inflammatory disease, puerperal infection, septic abortion, low birth weight, nongonococcal urethritis, and prostatisis, as well as spontaneous abortion and infertility, but there are no clinical symptoms pathognomonic of these infections. In spite of clinical suggestions of Mycoplasma or Ureaplasma infection, only a properly obtained specimen evaluatd with the use of selective cultures can lead to unequivocal diagnosis. The cultural characteristics and hence diagnostic procedures for Mycoplasma and Ureaplasma are quite different. Sterile calcium alginate swabs are used for obtaining urethral specimens, while sterile cotton swabs can be used for prostatic or vaginal secretions or semen. The swab should not touch antiseptic solutions, creams, or jellies, and the specimen must not dry out. Urine, if cultured, is best examined after centrifugattion at 600 g. Several different transport media are available. Optimally the specimen should be taken directly to the laboratory and subcultured on arrival. The metabolic activity of Mycoplasmas and Ureaplasmas is used in their detection. A phenol red indicator is added to the medium and the color change to or from yellow to pink indicates metabolic change. The growth medium is supplemented with glucose and phenol red for M. fermentans and arginine and phenol red for M. hominis. After color change is observed, the growth medium is subcultured on solid medium, which is obtained by adding .6-.8% Noble agar to the growth medium. Colonies develop best in an atmosphere of 95% N2 and 5% CO2 and reach approximately 200-300 mcm in diameter. They have a fried-egg appearance. Staining with Dienes stain, use of specific antisera, or incident light fluorescence microscopy are used for identification of the classic mycoplasmas. To isolate ureaplasmas, the specimen is transferred on arrival in the laboratory to urease color test broth U9C. During incubation the presence of Ureaplasma induces a rapid color change usually observable in 24-48 hours. A subculture should be done on fresh U9C broth media and on agar media once a color change is observed. Serologic tests for detection of antibodies to mycoplasmas and ureaplasmas are still in the developmental stage.
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PMID:Diagnosis of genital Mycoplasma and Ureaplasma infections. 402 Jul 82

The characteristics of an unclassified Mycobacterium sp. isolated from three patients with Crohn's disease are presented. The organism is extremely fastidious and mycobactin dependent and may require up to 18 months of incubation for primary isolation. Colony morphology is rough. Characteristics are unlike those of any presently defined species. The isolates produced postive niacin, catalase, and 2-week arylsulfatase reactions and were susceptible to neotetrazolium chloride (1:40,000), streptomycin (2 micrograms/ml), and rifampin (0.25 micrograms/ml). Chromogenicity, nitrate reduction, quantitative catalase, Tween hydrolysis, urease, tellurite reduction, pyrazinamidase, and 3-day arylsulfatase tests were negative, and the isolates were resistant to thiophene-2-carboxylic acid hydrazide (10 micrograms/ml) and isoniazid (10 micrograms/ml). Optimum growth in broth was determined to be in 7H9 medium with Dubos oleic albumin complex, Tween 80, and mycobactin J at 37 degrees C without CO2 or agitation and in low medium depth. This Mycobacterium sp. may be a subspecies or biovariant of Mycobacterium paratuberculosis, or it may represent a new species of Mycobacterium. It is suggested that this Mycobacterium sp. may play an etiological role in some cases of Crohn's disease.
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PMID:Characteristics of an unclassified Mycobacterium species isolated from patients with Crohn's disease. 651 78

Lenses produce both ammonia and urea, and a previous report suggested that bovine lenses contain a complete urea cycle capable of synthesizing urea from bicarbonate and ammonia. To determine whether lenses produce urea by a complete urea cycle or by arginase alone, intact lenses were cultured with [guanido-14C]-arginine or [14C]-bicarbonate. The [14C]-urea was volatilized to [14C]-CO2 by urease and collected in KOH. The cultured rat, bovine and human lenses produced [14C]-urea from [14C]-arginine; therefore lens arginase activity was also examined in homogenates of rat and human lenses. Rat lens homogenates had constant arginase activity for at least 2 hr at 37 degrees C, and activity increased linearly with the concentration of lens homogenate. Rat lens arginase had an apparent Vmax of approximately 13 nmol/hr/mg lens wet weight in lens homogenates and produced 4-6 nmol urea/hr/mg at 25 mM arginine. Human lens homogenates produced 1-5 nmol/hr/mg. In contrast, neither bovine nor rat lenses cultured with [14C]-bicarbonate produced detectable [14C]-urea, although label was incorporated into unidentified nonvolatile products. These products were shown by ion exchange chromatography and enzymatic assay to contain no detectable arginine or urea. It was concluded that although arginase activity is present, neither rat nor bovine lenses contain significant urea cycle activity. However, it is possible that arginase serves as a source of lens ornithine.
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PMID:Urea formation in rat, bovine, and human lens. 666 5

Seventeen strains of Haemophilus ducreyi were isolated from genital lesions which were negative for syphilis by dark-field examination. Media used for primary isolation at various times during the study were enriched chocolate agar, chocolate agar plus vancomycin (3 microgram/ml), rabbit blood agar plus vancomycin (3 micrograms/ml), fetal bovine serum agar, and fetal bovine serum agar plus vancomycin (3 micrograms/ml). H. ducreyi was isolated on chocolate agar plus vancomycin from 10 of 14 patients found to be positive on one or more media, on rabbit blood agar plus vancomycin from 16 of 17 patients, and on fetal bovine serum agar plus vancomycin from 9 of 11 patients. Sera from six animal species were tested to determine if any would support the growth of H. ducreyi. Horse and rabbit sera supported light growth of some strains. Fetal bovine serum supported good growth of all strains included in the study. Biochemical and physiological tests were done on the 17 isolates, a reference strain of H. ducreyi, and two reference strains of Haemophilus haemoglobinophilus. The results agreed with those reported by Kilian, except that H. ducreyi produced alpha-hemolysis in stabs on rabbit blood agar and was oxidase positive, three strains were urease positive, and CO2 improved the growth of seven strains. All 17 isolates were beta-lactamase positive. The reference strains were beta-lactamase negative.
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PMID:Isolation and identification of Haemophilus ducreyi in a clinical study. 697 72

Color change of pH indicators in broth medium is commonly used to quantify growth of ureaplasmas. These organisms differ from other members of the Mollicutes by their ability to hydrolyze urea to CO2 and NH3. This study describes a method which continuously monitors color change in ureaplasmal broth cultures. Using this technique we found: (i) there was a pH-dependent absorbance at 554 nm in ureaplasmal broth medium containing phenol red, (ii) a sigmoidal-shaped color changing curve (absorbance at 554 nm versus time) was produced by metabolizing organisms whereas a linear curve was generated by antibiotic-inhibited ureaplasmas, and (iii) the minimum cell density which elicited a growth-inhibited color change was 1.25 x 10(4) colony-forming units per ml. Other have shown that apparently dead ureaplasmas can cause a color change in broth media. This color change is probably due to the presence of an active urease. This study graphically and quantitatively assesses growth-inhibited color change.
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PMID:Effect of antibiotics on the dynamics of color change in Ureaplasma urealyticum cultures. 701 6

The nitrogen excretory metabolism of the myxomycete Physarum polycephalum was studied. When cultured in partially defined broth medium or on agar, the principal excretory product was ammonia nitrogen. A small, variable quantity of urea was excreted in liquid culture. No uric acid or other purines were detected in the cultures. When microplasmodia were incubated with sodium [14C]bicarbonate, radioisotope was incorporated into citrulline, arginine, and urea. Incubation with L-[carbamoyl-14C]citrulline yielded labelled arginine, urea, and CO2. Substantial urease activity was found in extracts of the microplasmodia. These results, in conjunction with the lack of an absolute nutritional requirement for arginine, provide evidence that Physarum has a functional arginine biosynthetic pathway, an arginase, and a urease.
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PMID:Arginine synthesis and nitrogen excretion in the myxomycete Physarum polycephalum. 737 43

Noninvasive detection of Helicobacter pylori (HP) requires serum or salivary antibody testing or the CO2 breath test. Since gastric HP produces a potent urease, a meal rich in 13C-labeled urea should lead to a measurable quantity of isotopic CO2 in the serum. This study investigates the feasibility, sensitivity, specificity, and potential of the measurement of serum 13C-bicarbonate (13CHCO3) in determining the presence of gastric HP. Nineteen patients with upper gastrointestinal symptoms assessed by intensity-duration questionnaire underwent endoscopy and biopsies for histology, Giemsa stain, and urease activity testing by CLOtest. Patients also consumed a 13C-urea-rich meal (5 mg/kg body weight, 99% 13C, MSD Isotopes, Montreal Canada). Serum was collected every 30 min for 3 h for quantitative determination of 13C by mass spectrometry. Fractional elevation of 13C after the enriched meal was then correlated with endoscopy, histology, and CLOtest. Fourteen of the 19 patients studied had histologic evidence of gastritis; 11 of 19 had positive CLOtest and had HP by histology and Giemsa stain. All HP-positive patients had significant elevation of 13CHCO3, compared with HP-negative patients. The mean maximum absolute change from baseline was 15.3 delta 13CHCO3 (range, 6.7-29.9) and occurred from 15 to 90 min; 13CHCO3 in HP-negative patients was significantly less (p < 0.05) than HP-positive patients with a mean value of 2.3 delta 13CHCO3 (range, 0-5.3). We conclude that serum 13CHCO3 analysis accurately reflects HP gastritis. This novel method is noninvasive, less labor intensive, less time consuming, and may have a value as a diagnostic screening tool for humans or in the assessment of the results of therapy in patients with HP infection.
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PMID:Serum 13C-bicarbonate in the assessment of gastric Helicobacter pylori urease activity. 767 76

Recently many reports have shown a strong association between Helicobacter pylori infection in the stomach and recurrent peptic ulcer. Moreover, prospective cohort serological studies showed that H. pylori infected individuals have significantly increased rate of gastric cancer in the USA. H. pylori is a gram-negative spiral organism which has urease activity and produces ammonia and CO2 from urea, and nestles in the gastric pits and overlaying mucus gel layer. Many diagnostic methods of H. pylori infection are available; ie bacterial culture, 13C-urea breath test, histology, serum IgG antibody against H. pylori. We developed a new method, ie tissue IgA antibody against H. pylori and detection of H. pylori DNA in the gastric juice by PCR method. Triple therapies with metronidazole, bismuth compounds, and amoxicillin or tetracyclin are difficult to use in Japan because of their sever side effects. Thus, new methods with proton pump inhibitor (PPI) and amoxicillin have been introduced. We treated 14 patients of whom were H. pylori positive-active peptic ulcer with 30 mg/day of lansoprazole, a new PPI, plus 1,500 mg/day of amoxicillin for 2 weeks and 8 (57%) patients were eradicated. Gastric carcinogenesis are multi-steps and multifactorials process. Hypothetical sequence of intestinal type of gastric cancer is that superficial gastritis-->atrophic gastritis-->intestinal metaplasia-->dysplasia-->gastric cancer and H. pylori infection may play a role in the early stage of the sequence. We examined mucosal IgA antibody against H. pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in 25 resected specimens after gastrectomy for gastric cancer. Positivity rates of tissue H. pylori IgA antibody were lower in the mucosa of intestinal metaplasia than in non-metaplastic gastric mucosa and were negative in carcinoma. Causal relationship between H. pylori infection and gastric cancer is not proven and factors other than H. pylori infection are also important in the gastric carcinogenesis. Finally we introduce 2 reports: (1) NIH Consensus Conference: Helicobacter pylori in peptic ulcer disease (JAMA. 1994; 272: 65-69). The consensus panel concluded that 1. ulcer patients with H. pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; 2. the value of treating nonulcerative dyspepsia patients with H. pylori infection remains to be determined; and 3. the interesting relationship between H. pylori infection and gastric cancer requires further exploration. (2) World Health Organization: Working Group Meeting (Reported in World Congress of Gastroenterology, Los Angeles, 1994). H. pylori plays a causal role in the chain of events leading to cancer of the stomach. Group I: definite carcinogen.
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PMID:[Helicobacter pylori in peptic ulcer and gastric cancer]. 785 88


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