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PubMed2002

Methenamine hippurate for preventing urinary tract infections.

BACKGROUND: Methenamine salts are often used for the prevention of urinary tract infection (UTI). OBJECTIVES: To assess the effectiveness of methenamine hippurate in preventing UTI. SEARCH STRATEGY: Published and unpublished randomised controlled trials were identified from the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, Current Contents, reference lists of review articles and retrieved trials. The manufacturers' of methenamine salts were contacted for unpublished studies and contact was made with known investigators in the area. SELECTION CRITERIA: Randomised and quasi-randomised trials of methenamine hippurate used for the prevention of UTIs in all population groups were eligible for inclusion. A comparison with a control (no treatment) group was a prerequisite to selection. DATA COLLECTION AND ANALYSIS: Two reviewers (BL and TB) performed independent assessment and data extraction using a standardised format. Discrepancies, methodological and interpretative issues were discussed with JS or JC. An exploration of heterogeneity as well as a detailed description of results grouped by population was conducted. MAIN RESULTS: Eleven studies met the inclusion criteria. All trials were included in a descriptive analysis. Seven trials were included in meta-analyses. Four trials (199 patients) studied symptomatic bacteriuria and six trials (341 patients) studied bacteriuria as an outcome measure. Overall, trial quality was poor. The direction of six of the pooled trials was towards a favourable treatment effect from methenamine hippurate. Interpretation of the pooled estimates was not done in view of underlying heterogeneity. The study by Pettersson 1989 explained some, but not all, of the underlying heterogeneity. This study differed from all others by including patients with known upper renal tract abnormalities. Adverse reactions were mentioned by 10 studies. The rate of adverse events was low. REVIEWER'S CONCLUSIONS: There is not enough evidence to conclusively support the use of methenamine hippurate for urinary prophylaxis. An exploration of heterogeneity raises the (hypothesis generating) possibility that methenamine hippurate may have some efficacy in patients without but not in patients with known upper renal tract abnormality (with asymptomatic bacteriuria as the outcome measure). Due to the small sample size and methodological problems within the studies involved, interpretation of these data should be done cautiously. The rate of adverse events reported by the trials was low, which suggests that current usage is unlikely to be causing significant harm.

Anti-Infective Agents, Urinary↗
PubMed2004

Benzylmercapturic acid is superior to hippuric acid and o-cresol as a urinary marker of occupational exposure to toluene.

The present study was initiated to examine whether urinary benzylmercapturic acid (or N-acetyl-S-benzyl cysteine, BMA), a mercapturate metabolite of toluene, increases in relation to the intensity of toluene exposure, and whether this metabolite is a better marker of occupational exposure to toluene than two traditional markers, hippuric acid and o-cresol. Accordingly, end-of-shift urine samples were collected from 122 printers and 30 office clerks (all men) in the second half of a working week. Solvent (toluene) exposure of the day (8 h) was monitored by means of diffusive sampling. Quantitative relation with toluene showed that BMA had a greater correlation coefficient with toluene (r = 0.7) than hippuric acid (r = 0.6) or o-cresol (r = 0.6). The levels in the urine of the non-exposed control subjects were below the detection limit of 0.2 microg/l for BMA, whereas it was at substantial levels for hippuric acid and o-cresol (239 mg/l and 32 microg/l as a geometric mean, respectively). Thus, BMA, hippuric acid and o-cresol could separate the exposed from the non-exposed when toluene was at < 1, 50 and 3 ppm, respectively. Overall, therefore, it appeared reasonable to conclude that BMA is superior to hippuric acid and o-cresol as a marker of occupational exposure to toluene.

Acetylcysteine↗
PubMed1984

Effects of pretreatment with toluene, phenobarbital and 3-methylcholantrene on the in vivo metabolism of toluene and on the excretion of hippuric acid in the rat.

The limit of the capacity of male adult Sprague-Dawley rats to metabolize toluene and excrete it as hippuric acid was reached at a dose of 10 mmol toluene/kg. At this dose of benzoic acid or hippuric acid, the excretion of hippuric acid was 1.5-fold and 4-fold, respectively, greater than that following this dose of toluene. When toluene was given after phenobarbital pretreatment the excretion rate of hippuric acid increased 3-4-fold, but 3-methylcholanthrene pretreatment had no effect. Consecutive toluene exposures increased hippuric acid excretion on the third day by about 2-fold. It seems that the side-chain oxidation is the rate-limiting step in toluene metabolism of uninduced rats, and toluene accelerates its own metabolism by inducing cytochrome P-450 dependent microsomal monooxygenases.

Animals↗
PubMed2001

Interactions of d(10) metal ions with hippuric acid and cytosine. X-ray structure of the first cadmium (II)-amino acid derivative-nucleobase ternary compound.

The interactions of Zn(II), Cd(II) and Hg(II) with hippuric acid (hipH) were studied and several novel compounds were synthesized and studied by NMR. Some new metal-hippuric-cytosine ternary compounds were formed and the structure of the [Cd(hip)(2)(cyt)(H(2)O)](2) ternary complex resolved. Each cadmium (II) atom has a distorted trigonal bipyramid coordination which is linked to a water molecule, a cytosine via N(3), a carboxylic oxygen atom of a hippurate moiety and two bridging dicoordinated hippurates bound through the carboxylic oxygen atoms. To these five main bonds, two longer ancillary interactions can be observed: the second oxygen of the monocoordinated hippurate group and the carboxylic oxygen of the cytosine ligand. The compound is stabilized by an intramolecular stacking between the benzene and cytosine rings and by the hydrogen bonds between the coordinated water molecules and the ligands. This is, to our knowledge, the first structure of a cadmium-amino acid derivative-natural nucleobase compound described so far.

Cadmium↗
PubMed1995

Drug-induced changes in renal hippurate clearance as a measure of renal blood flow.

We studied the accuracy of the plasma 131I-hippurate clearance technique to monitor drug-induced changes in renal blood flow (RBF) by comparing it to a flow probe technique in six conscious, chronically instrumented dogs. Placebo caused no change in RBF, either established by hippurate clearance (ERPFhip) or by renal blood flow probe (RBFprobe). Enalaprilate induced a rise in ERPFhip and RBFprobe (+26 +/- 5 and 44 +/- 12%), as did dopamine (+16 +/- 4 and +33 +/- 5%). Intravenous infusion of norepinephrine induced a rise in ERPFhip (+2 +/- 6%, NS) and in RBFprobe (+18 +/- 3%), as did nitroprusside (+14 +/- 4% and +13 +/- 6%, NS). Indomethacin induced a fall in ERPFhip (-8 +/- 2%) and in RBFprobe (-7 +/- 3%, NS), as did angiotensin II (-19 +/- 1 and -26 +/- 3%). Renal hippurate extraction (Ehip) was affected by enalaprilate, dopamine, and angiotensin II (-5 +/- 2, -7 +/- 1, and +5 +/- 2%, respectively). Hematocrit (Hct) was affected by dopamine, norepinephrine, and nitroprusside (+2 +/- 1, +6 +/- 1, and -6 +/- 2%, respectively). Drug-induced changes in ERPFhip correlated well with changes in RBFprobe (r = 0.902, P < 0.01). Changes in Ehip did not independently affect this relation, whereas changes in Hct did: delta RBF(% of baseline) = 1.529 x delta ERPFhip(% of baseline) + 1.296 x delta Hct(% of baseline). These data indicate that drug-induced changes in plasma hippurate clearance can, even when changes in renal hippurate extraction are unknown, be used as a reliable indicator of changes in renal blood flow if changes in hematocrit are taken into account.

Animals↗
PubMed2001

Characterization of p-hydroxy-hippuric acid as an inhibitor of Ca2+-ATPase in end-stage renal failure.

Characterization of p-hydroxy-hippuric acid as an inhibitor of Ca2+-ATPase in end-stage renal failure. In patients with end-stage renal failure (ESRF), disturbances of Ca2+ metabolism are common. Besides hormonal changes, inhibition of cellular Ca2+-ATPase was postulated to contribute to uremic toxicity. We purified a potent inhibitor of the Ca2+-ATPase from the ultrafiltrate of patients with ESRF by multiple steps of high-performance liquid chromatography to homogeneity, and identified the isolated inhibitor by mass spectrometric methods as p-hydroxy-hippuric acid. The enzyme used for the Ca2+-ATPase assay system was isolated from red blood cells by cross-flow filtration. The activity of the Ca2+-ATPase was measured spectrophotometrically as the difference in hydrolysis of adenosine 5'-triphosphate (ATP) in the presence and absence of Ca2+ with different concentrations of ATP and p-hydroxyhippuric acid. The Ca2+-ATPase was found to be inhibited by p-hydroxy-hippuric acid at a concentration above 11.7 micromol/L. p-Hydroxyhippuric acid inhibited the erythrocyte Ca2+-ATPase by reducing Vmax and increasing the Km value. The EC50 (log mol/L; mean +/- SEM) for p-hydroxy-hippuric acid was calculated as 4.82 +/- 0.14. In conclusion, p-hydroxy-hippuric acid may play a role in disturbed Ca2+ metabolism in end-stage renal failure.

Calcium-Transporting ATPases↗
PubMedDate not supplied

Determination of urinary hippuric acid and o-cresol levels as biological indicators of toluene exposure in shoe-workers and glue sniffers.

In this study, groups exposed to toluene either intentionally (glue sniffers) or unintentionally (shoe-workers) were compared. The groups were evaluated in terms of urinary levels of the toluene metabolites hippuric acid and o-cresol. Results were also compared with control values. Hippuric acid levels were determined by high performance liquid chromatography and o-cresol levels by gas liquid chromatography. The levels of hippuric acid and o-cresol were found to be statistically significantly higher in glue sniffers than in shoe-workers (p <0.001) or controls (p <0.001). In addition, the differences between the levels of urinary hippuric acid and o-cresol in the shoe-workers and in the controls were statistically significant (p <0.05 and p <0.001, respectively). These results suggest that extremely high levels of urinary hippuric acid and o-cresol indicate massive exposure to toluene.

Adolescent↗
PubMed2005

Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine.

BACKGROUND: A major portion of the catechins in green tea is not absorbed in the small intestine. Bacteria in the colon convert nonabsorbed catechins into simpler phenolic compounds, which may also be absorbed. During the production of black tea, most catechins are polymerized to complex molecules called thearubigins. Little is known about the microbial degradation of these complex polyphenols, but hippuric acid has been identified as a major excretion product associated with black tea consumption. OBJECTIVE: To investigate whether green tea and black tea have the same metabolic fate in humans. DESIGN: Seventeen healthy male volunteers were studied with a randomized, full-crossover design. Each intervention period lasted 4 d, ie, a 2-d run-in period with a low-polyphenol diet followed by a 2-d treatment period. Volunteers consumed a daily dose of 6 g green tea solids, 6 g black tea solids, or 360 mg caffeine. Intervention periods were separated by a 10-d washout period. Twenty-four-hour urine samples were collected during the second day of each treatment period. Hippuric acid was analyzed with HPLC-tandem mass spectrometry. RESULTS: The mean excretion of urinary hippuric acid during black tea and green tea consumption was 3.75 +/- 0.28 mmol/24 h and 4.22 +/- 0.28 mmol/24 h, respectively (95% CI for the difference: -0.37 to +1.30 mmol/24 h). The hippuric acid excretion during the control treatment was much lower (1.89 +/- 0.28 mmol/24 h; P < 0.0001, compared with both black tea and green tea). CONCLUSION: The ingestion of either green tea or black tea results in a major increase in the excretion of hippuric acid into urine.

Adult↗
PubMedDate not supplied

Long-term treatment with methenamine hippurate in recurrent urinary tract infection.

Twenty-four patients with a history of recurrent urinary tract infection and in whom residual urine was considered to be a factor of importance for chronicity, have been treated for an average of 16 months with 1 g methenamine hippurate morning and evening. No patient had urinary calculus at the commencement of treatment and neither did any patient have an indwelling catheter. In patients without urinary tract infection or in whom abacteriuria was achieved with methenamine hippurate, the number of reinfections was reduced by approximately two thirds compared to periods prior to treatment. No patient was completely free from infection throughout the whole treatment period. However, in no case did bacteria with extensive resistance appear. When urinary tract infection was treated with methenamine hippurate, abacteriuria was achieved in only 6 of 14 patients. It would therefore seem that this agent is only of limited value for treatment of established infection. In the event of manifest infection it would appear appropriate to treat the infection primarily with antibiotics and to use methenamine hippurate for prophylaxis when abacteriuria has been achieved. No patient developed urinary calculus during treatment with methenamine hippurate and no deterioration of renal function or haematological change was observed.

Adult↗
PubMed1982

Hippurate hydrolysis by and triphenyltetrazolium tolerance of Campylobacter fetus.

A rapid test of hippurate hydrolysis and a test of tolerance to triphenyltetrazolium chloride (TTC) were studied in 315 strains of Campylobacter fetus subsp. jejuni to determine their usefulness for biotyping this organism and for distinguishing it from C. fetus subsp. intestinalis. Of the 315 strains tested, 84% hydrolyzed hippurate and 97% were resistant to TTC. Ability to hydrolyze hippurate was seen in 99% of 155 human isolates, 75% of 60 avian isolates, 100% of 41 cattle and dog isolates, 84% of 31 zoo mammal isolates, and none of 28 hog isolates. Resistance to 400 micrograms of TTC per ml was seen in 97% of the human isolates, 95% of the avian isolates, and 100% of the mammalian isolates (other than human). In no case did any of the 315 isolates of C. fetus subsp. jejuni show both lack of ability to hydrolyze hippurate and sensitivity to TTC. In contrast, all 18 strains of C. fetus subsp. intestinalis failed to hydrolyze hippurate and were sensitive to TTC. These two tests may be useful to distinguish between C. fetus subsp. jejuni and subsp. intestinalis and also to biotype strains of C. fetus subsp. jejuni.

Animals↗
PubMed1986

Two-dimensional thin-layer chromatography for the specific detection of hippurate hydrolysis by microorganisms.

Glycine, one of the end products of hippurate hydrolysis by microorganisms, was detected by a rapid, specific technique utilizing two-dimensional thin-layer chromatography. A loopful of growth of each organism from its suitable agar medium was washed, suspended, and incubated with 0.1% sodium hippurate for 30 min at 37 degrees C. The supernatant of the incubated suspension from each organism was then dansylated, and the dansyl derivatives were separated by two-dimensional thin-layer chromatography on polyamide sheets. Glycine, a product of hippurate hydrolysis, was detected under UV light. This technique does not require prolonged incubation and was found to be more specific and reliable than the standard ninhydrin reaction. In addition, it is inexpensive and can be easily conducted in a clinical microbiological reference laboratory. By this method, 100% (22/22) of Campylobacter jejuni and 0% (0/9) of Campylobacter coli reference strains were positive. In addition, 100% (13/13) of group B streptococci, 100% (24/24) of group D streptococci, and 90% (18/20) of Gardenerella vaginalis clinical isolates were positive for hippurate hydrolysis. This method is useful for the identification to the species level of Campylobacter organisms and the biotyping of Gardnerella organisms and for the detection of hippurate hydrolysis by unknown microorganisms.

Bacteria↗
PubMed1987

Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.

Acute Disease↗
PubMed2001

Hippuric acid test using 13C-labelling and NMR spectroscopy.

This article describes a 13C-labelling and nuclear magnetic resonance approach for hippuric acid test which is potentially useful for evaluating liver reserve. In this approach, urine samples collected after ingestion of 13C-labelled benzoic acid were directly analysed by 13C nuclear magnetic resonance spectroscopy, and the excreted 13C-labelled hippuric acid formed from the administered benzoic acid was quantitated. The amount of labelled hippuric acid excreted in a specified time can be a useful index of liver reserve. In this study, the feasibility of the nuclear magnetic resonance approach has been investigated in several healthy subjects. This approach is simple and convenient compared with conventional analytical procedures, because no chromatographic separation is required. The approach could give new insights into the liver reserve, because the benzoic acid conversion to hippuric acid intimately relates to the hepatic energy metabolism. This measurement can be conducted at a wide range of dosages without interference from endogenous hippuric acid.

Administration, Oral↗
PubMed1976

Post-mortem survival of hippuric acid formation in rat and human cadaver tissue samples.

1. A rapid and sensitive semi-micro method for the determination of hippuric acid formation by tissue samples in vitro is described and applied to the determination of the post-mortem survival of hippuric acid formation in rat and human cadaver tissue samples. 2. Hippuric acid formation survived in rat and human cadaver liver for at least 72 h when corpses were stored at 4 degrees. 3. Hippuric acid formation was detected in human cadaver liver and kidney samples and was absent from brain, intestine, heart and lung. 4. Post-mortem liver samples from a case of acute pancreatitis failed to form hippuric acid as did kidney samples from a case of systemic lupus erythematosus with renal involvement.

Adult↗
PubMed1991

Effect of hippurate on glucose utilization in rat kidney cortex slices.

Hippurate action on glucose utilization was evaluated in rat kidney cortex slices. Studies have shown the following. (1) Hippurate inhibits markedly basal as well as insulin-stimulated glucose utilization and basal gluconeogenesis. (2) Ca deficiency and specific Ca channel blockers diltiazem and isradipine abolish the hippurate inhibition of glucose utilization. (3) K+ channel blockers, i.e. the increased K+ concentration in incubation medium, procaine and sulfonylurea drugs also abolish the hippurate inhibition of glucose utilization. It is concluded that hippurate and benzoate operate through the ATP-dependent K+ channel.

Animals↗
PubMed1982

Urine and tissue oxalate and hippurate levels in ethylene glycol intoxication in the dog.

Oxalate, hippurate and ethylene glycol were measured in dogs given 5 ml/kg ethylene glycol orally. Eight hours after administration, oxalate levels were 7.2-9.1 ppm in renal tissue and 10-100 ppm in urine. Hippurate was 40-90 ppm in urine. Ethylene glycol was 10-100 ppm in renal tissue and 5,300-27,000 ppm in urine. The above substances were measured in urine and renal tissue from normal dogs, dogs in non-toxic renal failure and clinical cases of ethylene glycol intoxication. Urine was analyzed for ethylene glycol by gas chromatography using direct injection. Ethyl ether extraction provided good recovery of ethylene glycol from tissues and blood. Results were confirmed by gas chromatography/mass spectrometry (GC/MS). Oxalic acid (CA oxalate) was extracted with acidic methanol, methylated and analyzed by GC. Results were confirmed by GC/MS. Hippuric acid (calcium hippurate) was extracted with acidic methanol and chromatographed by thin layer chromatography (TLC). Ultraviolet spectrometry and mass spectroscopy were used to confirm the results. High performance liquid chromatography (HPLC) and TLC with densitometry were used to quantitate hippuric acid.

Animals↗
PubMedDate not supplied

[Occupational exposure and individual factors influencing urinary elimination of hippuric acid].

The influence of not occupational factors (smoking, alcohol, coffee, drugs, sport, sex, age and body weight) on hippuric acid excretion was analyzed in two groups of healthy male subjects. A group was constituted of 710 painters occupied in wood and coach workings and the other one of 109 not occupational. The 5 degrees, 50 degrees, 95 degrees percentiles of the two distribution were 208, 605, 1784 and 153, 538, 1700 mg/g creatinine respectively. The analysis of variance undertaken on exposed subjects showed that there was a significative difference between urinary hippuric acid levels of subjects consuming alcohol and the not ones. Multiple regression analysis on hippuric acid excretion values distribution in not exposed group showed that only the variable "coffee consumption" resulted statistically significative (Ln hippuric acid = 5.0287 + 0.8062; R2 = 01221). Coffee consumption increase excretion rate (mg/hour) of hippuric acid likely an exposure to a toluene air concentration of 50 mg/m3. The authors suggest an action of caffeine on endogenous amount of benzoic acid.

Adolescent↗
PubMed1983

Prognostic value of post-transplant hippurate scintigraphy.

131Iodine hippurate sequential scintigrams obtained after transplantation contain prognostic information about the long-term development of a graft. Results of 131 131iodine hippurate sequential scintigrams made within 48 hours after graft implantation were compared to the graft status 2 years after transplantation. Hippurate uptake and transport were rated on a 4-step scale. Disturbed hippurate uptake and abnormal tracer transit were associated with increased frequency of early graft destruction and with a high frequency of chronic rejection. The chi-square test demonstrated a significant relationship between results of the initial hippurate scintigrams and long-term graft development.

Adolescent↗