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At least 19 recordsLinked to original sources
PubMed1979

[Investigations on 131I-hippurate-clearance in obstructive-uropathy; extraction of para-aminohippuric acid and 131I-hippurate in the acutely obstructed canine kidney (author's transl)].

The results of more recent clinical and experimental investigations have thrown doubt on the usefulness of determining the individual 131I-hippurate clearance for evaluation of the function of acutely obstructed kidneys. There is a significant difference (5% level) between the kidney performance determined with external measurement on the one hand and with PAH and 125I-hippurate clearance in the steady state on the other. With the steady state method, the restriction of function to be expected in consequence of urinary obstruction is demonstrated, whereas with simultaneous measurement with catheterless 131I-hippurate clearance, an increase in function is detected. In the clearance studies carried out in the conventional way with PAH and 125I-hippurate, it was difficult to determine quantitatively the urine produced during urinary obstruction. The renal extraction of p-aminohippuric acid and 131I-hippurate was therefore determined in simultaneous measurement in six dogs before and after acute urinary obstruction with a constant plasma level of the test substances. The results obtained with this very elaborate method which is, however, independent of urine collection show that an acute urinary obstruction leads to a decrease of renal extraction both of PAH and of 131I-hippurate. Since with conventional clearance, the measurement result is proportional to the amount of substance excreted with the urine, a restriction of function must also result with the steady state methods in determining the performance of acutely obstructed kidneys. The results of the extraction investigations hence confirm the results of the clearance studies mentioned. In addition, they show that the "increase" of renal performance immediately after an experimentally induced urinary obstruction repeatedly found with catheterless determination of 131I-hippurate-clearance cannot be explained by a different kinetic behavior of PAH and 131I-hippurate in the acutely obstructed kidney.

Acute Disease↗
PubMed1991

A new derivatization procedure for the analysis of hippuric acid and m-methyl-hippuric acid by gas chromatography.

The industrial solvents, toluene and xylene, have physicochemical properties that can be hazardous to the workers exposed. Since hippuric acid and m-methyl-hippuric acid represent the products of toluene and xylene biotransformation in urine, they are used as biological markers in studies on occupational exposure to these solvents. Several methods have been used to determine hippuric acid and m-methyl-hippuric acid--either based on gas chromatography or on high-performance liquid chromatography. In this study we propose the derivatization of hippuric acid and methyl-hippuric acid using methanol in acid medium (HCl), a low-cost reagent with a low level of toxicity. The method has been routinely used in our laboratory for 1 year and has proven to be a reliable procedure for the biological control of occupational exposure to toluene and/or xylene.

Chromatography, Gas↗
PubMed2003

Hippuric acid and methyl hippuric acid in rat hair: possible monitoring of xylene and toluene exposure.

Thinner is mainly composed of toluene and xylenes, and we studied the incorporation of the main metabolites of toluene and xylenes, hippuric acid (HA) and o-, m-, and p-methyl hippuric acids (o-, m-, p-MHA), in dark agouti rats' hair. Rat black hair was shaved before any exposure with an electric shaver designed for animals. Studies were performed in vivo with exposures of 30 min per day at three different concentrations (100, 300, and 1000 ppm) of toluene and o-, m-, and p-xylene for a total of 10 times over 2 weeks. Newly grown hair was tweezed out from the root with tweezers at seventh of the last exposure. Hair samples were then washed, extracted, derivatized, and analyzed by gas chromatography-mass spectrometry (GC-MS). HA and o-, m-, and p-MHA were not detected (ND) in the unexposed rat hair. After exposure, the metabolite concentration in the hair changed depending on the exposure concentration. Mean concentrations ranged from ND to 7.6 ng/mg, from ND to 13.8 ng/mg, from ND to 10.1 ng/mg, and from ND to 9.2 ng/ml hair for HA, o-, m-, and p-MHA, respectively. These results indicate that the metabolites concentrations in hair are effective indices of thinner exposure.

Animals↗
PubMed1989

Renal clearance of substituted hippurates in the dog. I. Benzoylglycine (hippurate) and methyl-substituted benzoylglycines.

Plasma kinetics and renal excretion of benzoylglycine (hippurate) and methyl-substituted benzoylglycines were studied in three Beagle dogs, after rapid i.v. administration of about 1 g of glycine conjugate. Benzoylglycine and the 3- and 4-methyl analogs showed nonlinear plasma protein binding varying between 20 and 80% over a concentration range of 5 to 450 micrograms/ml. For 2-methylbenzoylglycine an extremely high protein binding, practically approaching 100%, was observed at low plasma levels (less than 50 micrograms/ml). All conjugates were cleared largely via the kidney (greater than 80% of the dose) and, except for the 2-methyl analog, eliminated rapidly from plasma. Plasma concentration and renal excretion rate data were analyzed simultaneously with a previously developed physiologically based kidney model. Tubular secretion appeared to be a function of the total drug concentration in renal plasma, except for 2-methylbenzoylglycine, presumably due to its tight protein binding. The average values of the parameters characterizing the tubular transport maximum (TM in milligrams per minute) and the apparent affinity for the secretory system (KT in micrograms per milliliter) were: benzoylglycine TM = 5.5 +/- 0.8, KT = 40 +/- 5; 3-methylbenzoylglycine TM = 7.1 +/- 3.3, KT = 49 +/- 1; 4-methylbenzoylglycine TM = 8.0 +/- 1.6, KT = 14 +/- 6. Secretion of 2-methylbenzoylglycine was not saturated. Accordingly, only the ratio TM/KT = 163 +/- 54 ml/min could be calculated. An interesting observation was the partial deconjugation of 4-methylbenzoylglycine to its corresponding benzoate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Evaluation of liver function by co-administration methodology using 13C-labelled benzoic acid and hippuric acid coupled with nuclear magnetic resonance spectroscopy.

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.

Animals↗
PubMed2004

Molecular and ultrastructural characterization of porcine hippurate-negative Brachyspira pilosicoli.

Brachyspira pilosicoli, the causative agent of porcine intestinal spirochetosis, usually has hippurate-cleaving capacity. We have regularly isolated hippurate-negative B. pilosicoli from cases of porcine diarrhea. In this study, we show that these biochemically atypical B. pilosicoli isolates can be classified as B. pilosicoli. 16S ribosomal DNA was partially sequenced from eight hippurate-negative and two hippurate-positive B. pilosicoli-like isolates from seven herds. The differences in nucleotide sequence with B. pilosicoli P43/6/78 type strain were not associated with hippurate cleavage. In 877 bp, the hippurate-negative isolates had a similarity of 98.63 to 100% to the type strain, with the corresponding figures for the two hippurate-positive isolates being 98.86 and 100%. The nucleotide sequences of hippurate-positive isolates were identical to the respective sequences of hippurate-negative isolates from one herd. The DNA macrorestriction patterns of a total of 20 hippurate-negative and -positive B. pilosicoli isolates were diverse, and no clustering in conjunction with the hippurate reaction was found. In two herds, hippurate-positive and -negative B. pilosicoli isolates had a common macrorestriction pattern. The ultrastructure of hippurate-negative isolates was similar to the type strain. In conclusion, B. pilosicoli can be either hippurate positive or negative and, thus, the scheme for biochemical differentiation of porcine Brachyspira should be revised to include identification of hippurate-negative B. pilosicoli.

Animals↗
PubMed1990

Analysis of plasma hippurate in humans using gas chromatography-mass spectrometry: concentration and incorporation of infused [15N]glycine.

To allow in vivo determination of synthetic rates for individual proteins, physiological incorporation of infused [15N]glycine into urinary hippuric acid has been used as an indicator of intrahepatic tracer dilution. Although the kidneys might contribute to hippurate production, the relationship between hepatic, plasma, and urinary hippurate has not yet been established in humans. To further investigate these issues we developed a fast, sensitive, and reliable method for measuring simultaneously hippurate concentrations and in vivo tracer incorporation into hippurate in plasma and urine using stable isotopes and gas chromatography-mass spectrometry. We then tested this assay under several experimental conditions. Reference compounds [( 15N]- and [ring-2H5]hippurate) were synthesized and gave linear standard curves. Postabsorptive hippurate plasma levels in healthy subjects ranged from 1.2 to 10.5 microM and protein binding was 79 +/- 6% (mean +/- SD). Following a bolus dose of [15N]glycine tracer appeared in plasma hippurate; enrichment in hippurate was indistinguishable from that in glycine after an equilibration period of 20 min, indicating a close relationship between intracellular glycine and plasma hippurate. A 16-h infusion of [15N]glycine resulted in identical enrichment levels in urinary and plasma hippurate; glycine enrichment in a hepatic export protein (VLDL-ApoB) was approaching plasma hippurate but not plasma free glycine enrichment. The ability to monitor plasma hippurate is of practical advantage compared to the sampling of urine. Furthermore it allows the monitoring of rapid events in the intrahepatic dilution of an infused glycine tracer. This assay may, therefore, become an important tool in the study of hepatic protein metabolism.

Administration, Oral↗
PubMed1978

Binding of hippurate in normal plasma and in uremic plasma pre- and postdialysis.

The protein binding of 14C-hippurate has been measured by conventional ultrafiltration techniques in the plasma of normal subjects and in uremic subjects pre- and postdialysis. In addition, the clearance of 14C-hippurate was determined in vitro in both isotonic saline and plasma to assess binding limitations on hippurate removal during dialysis. Binding levels of hippurate in normal subjects of 68+/-1.8% (n = 5) were significantly higher than either postdialysis (48.3+/-15.4%; n = 7) or predialysis (36.6+/-11.7%; n = 7) levels in the same uremic subjects. Actual levels of plasma hippurate were, however, considerably greater in uremics (24.7+/-11.2 mg/dl' n = 7) than in normal subjects (congruent to 0.5 mg%). The difference in hippurate binding between pre- and postdialysis samples in uremics was significantly different from zero (p less than 0.01, t = 5.36), indicating depletion of competitive site-binding species during dialysis. The saline clearance of hippuric acid (99.1 +/-0.5 ml/min; n = 6) under standard conditions in a capillary dialyzer (CDAK-4) was consistent with the expected clearance of a solute of its molecular weight. Hippurate clearance in citrated plasma, where binding was determined as 50+/-3%, was 65+/-0.7 ml/min (n = 6), in good agreement with a theoretically predicted clearance of 60 ml/min for this level of binding. High serum levels of hippurate and its derivatives, may depress effective function of various organs. In addition to the normal dietary intake of hippurate and its precursors, patients on dialysis receive a further burden of hippurate precursor in the form of benzyl alcohol, the common preservative in heparin solutions. The large body burdens of hippurate in dialysis patients, coupled with its impaired removal on dialysis due to binding, point to the necessity for a through investigation of the potential toxicity of this compound.

Carbon Radioisotopes↗
PubMed1999

Differences in excretion of hippurate, as a metabolite of benzoate and as an administered species, in the single-pass isolated perfused rat kidney explained.

The extents of excretion of [14C]hippurate and [3H]hippurate were compared in the single-pass, constant flow (8 ml/min) isolated rat kidney which was perfused simultaneously with tracer concentrations of [14C]benzoate and [3H]hippurate. The steady-state renal extraction ratio of [14C]benzoate was 0.26 +/- 0.04 and was associated with a renal clearance of 1.13 +/- 0.17 ml/min/g. The urinary clearance of [14C]benzoic acid was low (0.011 +/- 0.01 ml/min/g), yielding a low fractional excretion [unbound urinary clearance/glomerular filtration rate (GFR)] value of 0.27 +/- 0.19 and suggesting that glycination of [14C]benzoate to [14C]hippurate accounted almost completely for the total renal clearance. Fractional excretion for preformed [3H]hippurate was eight times that of GFR, but the steady-state renal extraction ratio of preformed [3H]hippurate, E(pmi) (0.24 +/- 0.05) was much lower than the apparent extraction ratio of the renally formed [14C]hippuric acid [E(mi) = 0.39 +/- 0.09] (p <.05). The theoretical basis for the discrepancy was explored with mathematical formulations developed from a physiologically based model of the kidney. It was found that parent drug kinetic parameters (transport and metabolic intrinsic clearance of benzoate) were unimportant for E(mi) or E(pmi). Rather, the value of EK(mi) exceeded EK(pmi) because of the ratio of efflux clearances at the basolateral and luminal membranes for hippurate [corrected] was less than 26.089, a value determined by the GFR, plasma renal flow, and the unbound fraction of hippurate of the system that would render E(mi) to equal E(pmi) in the system. The influx clearance for hippurate to enter from plasma to cell at the basolateral membrane and the reabsorption clearance of hippurate to enter from tubular urine to cell at the luminal membrane failed to alter the ratio of EK(pmi)/EK(mi).

Animals↗
PubMed1996

Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.

UNLABELLED: We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. METHODS: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins. RESULTS: Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings. CONCLUSION: Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Capillary gas chromatographic assay of residual methenamine hippurate in equipment cleaning validation swabs.

A capillary gas chromatographic method is described for the determination of methenamine hippurate residue in swabs collected from manufacturing equipment surfaces. Any residual methenamine hippurate remaining on process equipment after cleaning is removed by swabbing with one wet polyester Absorbond swab (4" x 4") pre-moistened with water followed by a dry Absorbond swab. The residual methenamine hippurate is chromatographed on a 30 x 0.32 mm (i.d.) Supelcowax-10 capillary column of 0.25-micron film thickness. The amount of residual methenamine hippurate is determined by comparing the ratio of methenamine hippurate peak area response to that of p-cresol (internal standard) obtained for the sample to a linear calibration curve obtained for a series of standard solutions. The method is demonstrated to be sufficiently linear, accurate, precise, sensitive and rugged for the determination of low levels of methenamine hippurate on equipment surfaces. Using this method, the mean recovery of methenamine hippurate from spiked Absorbond swab samples contained in high density polyethylene bottles was 105.2%, with a relative standard deviation (RSD) of +/- 7.1% (n = 25). The mean recoveries of methenamine hippurate from spiked test plates for '180 Grit' Stainless Steel, Teflon and WARCO White (neoprene and PVC) gasket material were 77.2, 96.1 and 50.6%, with RSDs of +/- 9.4 (n = 25), +/- 4.3 (n = 25) and +/- 36% (n = 20), respectively. Recovery correction factors have been incorporated into the method. The method was successfully applied to the assay of actual equipment cleaning validation swab samples. Stability studies demonstrate that methenamine hippurate is not very stable on the equipment surfaces or in the swabs. It is recommended that the surfaces be swabbed immediately after cleaning and the swabs analyzed within 24 h after sample collection. The results demonstrate that in order to fully validate the cleaning procedures, it is not only necessary to investigate the recovery of the drug from equipment surfaces and swabs but also that the stability of the drug on the surfaces and swabs be determined.

Anti-Infective Agents, Urinary↗
PubMed1987

Prevalence and characterization of hippurate-negative Campylobacter jejuni in King County, Washington.

A total of 593 strains of thermophilic Campylobacter species were isolated either from humans with diarrhea or from poultry in King County, Washington. Of these strains, 98 (52 hippurate-positive strains and all 46 of the hippurate-negative strains) were selected for further phenotypic characterization and genetic classification. Hippurate hydrolysis, the test typically used to differentiate Campylobacter jejuni and C. coli, did not always correlate with the genetic classification. All hippurate-positive strains were classified as C. jejuni. Of the hippurate-negative strains, 20% were C. jejuni, 78% were C. coli, and 2% were C. laridis. Assuming that the remaining hippurate-positive strains were all C. jejuni, then hippurate-negative C. jejuni represented a small percentage (9 of 556 or 1.6%) of C. jejuni strains but a significant percentage (9 of 46 or 20%) of hippurate-negative strains. This finding suggests that hippurate hydrolysis should not be used as the sole criterion for differentiating thermophilic Campylobacter species, particularly when describing the disease states associated with these organisms.

Animals↗
PubMed1993

An assessment of percutaneous transhepatic biliary drainage in the correction of the metabolic capacity of the jaundiced liver by hippurate-synthesizing test.

Hippurate-synthesizing ability was investigated in patients with jaundice with percutaneous transhepatic biliary drainage (PTBD) in relation to hepatic metabolic capacity. In 16 patients with PTBD because of obstructive jaundice and 11 patients without hepatic disease, 1.77 grams of sodium benzoate was injected and the amount of hippurate synthesized and excreted in the urine collected at 30, 60, 120 and 180 minutes was measured (hippurate test). In patients with jaundice and patients in the control group, an almost linear increase was observed in the level of urinary hippurate after benzoate loading. However, the values of the patients with jaundice at one and two hours after the benzoate loading were significantly lower than those of the patients in the control group. Serum levels of glutamate oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin and direct bilirubin were significantly decreased during PTBD (p < 0.05). Bilirubin levels were closely correlated with hippurate test values (r = 0.567, p < 0.05). Values were also correlated with the period of PTBD before the hippurate test was performed (r = 0.632, p < 0.05). Recovery in hippurate synthesizing ability was observed when the total bilirubin levels decreased to less than 5 milligrams per deciliter or PTBD was maintained for more than three weeks. Because hippurate synthesis is dependent on adenosine triphosphate supply in the hepatic mitochondria, the value of the hippurate test reflects the metabolic viability of the liver in relation to energy metabolism. It is also suggested that the steady maintenance of PTBD for three weeks or more with a decrease in total bilirubin level less than 5 milligrams per deciliter is necessary for full recovery of the metabolic capacity of the jaundiced liver.

Adult↗