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1.
Am J Clin Nutr ; 109(2): 470-477, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30721917

ABSTRACT

Background: Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. Objectives: The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. Methods: We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. Results: There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Conclusions: Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345.


Subject(s)
Galactitol/metabolism , Lactase/metabolism , Lactose Intolerance , Lactose/metabolism , Milk/adverse effects , Nutrition Assessment , Sugar Acids/metabolism , Adult , Animals , Biomarkers/metabolism , Dairy Products/adverse effects , Digestion/genetics , Galactitol/blood , Galactitol/urine , Galactose/blood , Galactose/metabolism , Galactose/urine , Genotype , Humans , Lactase/deficiency , Lactase/genetics , Lactose/blood , Lactose/urine , Lactose Intolerance/genetics , Lactose Intolerance/metabolism , Liver , Male , Milk/chemistry , Polymorphism, Single Nucleotide , Postprandial Period , Sugar Acids/blood , Sugar Acids/urine , Young Adult
2.
Br J Nutr ; 111(2): 332-41, 2014 Jan 28.
Article in English | MEDLINE | ID: mdl-23915700

ABSTRACT

Red meat and dairy products contain high sialic acid (Sia) levels, but the metabolic fate and health impact in children remain unknown. The aims of the present study were to quantify the levels of urinary Sia N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and ketodeoxynonulosonic acid (KDN) and to determine their relationship with dietary Sia intake. Spot urine samples were collected from 386 healthy children aged 3 (n 108), 4 (n 144) and 5 (n 134) years at 06.30-07.00, 11.30-12.00 and 16.30-17.00 hours. Food intake levels were recorded on the day of urine sample collection. Sia levels were quantified using LC-MS/MS with [13C3]Sia as an internal standard. We found that (1) total urinary Sia levels in healthy pre-school children ranged from 40 to 79 mmol Sia/mol creatinine; (2) urinary Sia levels were independent of age and consisted of conjugated Neu5Ac (approximately 70·8 %), free Neu5Ac (approximately 21·3 %), conjugated KDN (approximately 4·2 %) and free KDN (approximately 3·7 %); Neu5Gc was detected in the urine of only one 4-year-old girl; (3) total urinary Sia levels were highest in the morning and declined over time in 4- and 5-year-old children (P< 0·05), but not in 3-year-old children; (4) Sia intake levels at breakfast and lunch were approximately 2·5 and 0·16 mg Sia/kg body weight; and (5) there was no significant correlation between dietary Sia intake levels and urinary Sia levels. Urinary Sia levels varied with age and time of day, but did not correlate with Sia intake in 3- to 5-year-old children. The difference in urinary Sia levels in children of different age groups suggests that the metabolism and utilisation rates of dietary Sia are age dependent.


Subject(s)
Chromatography, Liquid , Food Analysis , N-Acetylneuraminic Acid/metabolism , N-Acetylneuraminic Acid/urine , Neuraminic Acids/urine , Sugar Acids/urine , Tandem Mass Spectrometry , Animals , Child , Child, Preschool , China , Diet , Eggs , Female , Humans , Male , Meat , Milk
3.
Clin Chem ; 56(7): 1177-82, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20489133

ABSTRACT

BACKGROUND: Duarte galactosemia (DG) is frequently detected in newborn-screening programs. DG patients do not manifest the symptoms of classic galactosemia, but whether they require dietary galactose restriction is controversial. We sought to assess the relationships of selected galactose metabolites (plasma galactose, plasma galactitol, erythrocyte (RBC) galactitol, RBC galactonate, and urine galactitol and galactonate) to RBC galactose 1-phosphate (Gal-1-P), dietary galactose intake, and neurodevelopmental/clinical outcomes in DG children. METHODS: We studied 30 children 1-6 years of age who had DG galactosemia and were on a regular diet. All participants underwent a physical and ophthalmologic examination and a neurodevelopmental assessment. RBC galactitol, RBC galactonate, RBC Gal-1-P, plasma galactose, plasma galactonate, and urine galactitol and galactonate concentrations were measured. RESULTS: RBC galactitol and galactonate concentrations were about 2 and 6 times higher, respectively, than control values. Plasma galactose and galactitol concentrations were also about twice the control values. The mean values for RBC Gal-1-P and urine galactitol were within the reference interval. We found a relationship between plasma and urine galactitol concentrations but no relationship between RBC galactose metabolites and urine galactitol. There was a significant relationship between galactose intake and RBC galactose metabolites, especially RBC galactitol (P < 0.0005) and RBC galactonate (P < 0.0005). Galactose intake was not related to the urine galactitol, plasma galactose, or plasma galactitol concentration. RBC galactitol, RBC galactonate, plasma galactose, plasma galactitol, and urine galactonate concentrations showed no relationship with clinical or developmental outcomes. CONCLUSIONS: DG children on a regular diet have RBC Gal-1-P concentrations within the reference interval but increased concentrations of other galactose metabolites, including RBC galactitol and RBC galactonate. These increased concentrations correlate with galactose intake and neither cause any developmental or clinical pathology during early childhood nor oblige a lactose-restricted diet.


Subject(s)
Galactitol/analysis , Galactose/analysis , Galactosemias/blood , Galactosemias/urine , Galactosephosphates/analysis , Sugar Acids/analysis , Child , Child, Preschool , Dietary Carbohydrates/administration & dosage , Erythrocytes/metabolism , Female , Galactitol/blood , Galactitol/urine , Galactose/administration & dosage , Galactose/blood , Galactose/urine , Galactosemias/physiopathology , Galactosephosphates/blood , Galactosephosphates/urine , Humans , Infant , Male , Monitoring, Physiologic , Reference Values , Sugar Acids/blood , Sugar Acids/urine
4.
Magn Reson Chem ; 47 Suppl 1: S12-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19768707

ABSTRACT

In the present study, NMR-based urinary metabonomic profiles resulting from dosing with widely recognized microsomal enzyme inducers were evaluated in male rats. Wistar or Sprague-Dawley rats were dosed daily by oral gavage with phenobarbital (PB; 100 mg/kg), diallyl sulfide (DAS; 500 mg/kg), the investigational compound DMP-904 (150 mg/kg), or beta-naphthoflavone (BNF; 100 mg/kg) for 4 days, and urine was collected daily for analysis. Compounds known to increase cytochrome P450 2B enzymes, including PB, DAS and DMP-904, increased the urinary excretion of gulonic and ascorbic acid in a time-dependent manner, reaching a maximum following 3-4 days of dosing. In contrast, BNF, an agent that induces primarily Cyp1A enzymes, did not increase gulonic or ascorbic acid excretion, despite inducing Cyp1A1 more than 200-fold. Given the metabonomic results, hepatic transcriptional changes in the regulation of ascorbic acid biosynthesis were determined by RT-PCR. All Cyp2B inducers increased hepatic mRNA levels of aldo-keto reductase 1A1, an enzyme that catalyzes the formation of gulonic acid from glucuronate with concurrent decreased expression of both regucalcin (Rgn), the enzyme responsible for conversion of gulonic acid to gulono-1, 4-lactone and gulonolactone oxidase (Gulo), the rate-limiting enzyme in ascorbate biosynthesis. These effects would be expected to increase levels of gulonic acid. In addition, Cyp2B inducers also increased hepatic expression of enzymes regulating ascorbic acid reutilization including glutaredoxin reductase (Glrx2) and thioredoxin reductase (Txnrd1). In contrast, BNF did not effect hepatic expression of any enzyme regulating gulonic or ascorbic acid biosynthesis. Thus, some microsomal enzyme inducers alter transcriptional regulation of ascorbic acid biosynthesis, and these changes are detected by noninvasive metabonomic profiling. However, not all microsomal enzyme inducers appear to alter ascorbic acid metabolism. Finally, the work illustrates how metabonomic results can direct additional studies to determine the biochemical mechanisms underlying changes in urinary metabolite excretion.


Subject(s)
Ascorbic Acid/metabolism , Cytochrome P-450 Enzyme System/metabolism , Metabolomics , Sugar Acids/metabolism , Allyl Compounds/pharmacology , Animals , Ascorbic Acid/urine , Cytochrome P-450 Enzyme System/drug effects , Cytochrome P-450 Enzyme System/genetics , Gene Expression Profiling , Liver/enzymology , Liver/metabolism , Magnetic Resonance Spectroscopy , Male , Phenobarbital/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Sugar Acids/urine , Sulfides/pharmacology , Time Factors , Transcriptional Activation
5.
J Pharm Biomed Anal ; 50(5): 878-85, 2009 Dec 05.
Article in English | MEDLINE | ID: mdl-19615840

ABSTRACT

The 1H NMR spectrum of urine exhibits a large number of detectable and quantifiable metabolites and hence urine metabolite profiling is potentially useful for the study of systems biology and the discovery of biomarkers for drug development or clinical applications. While a number of metabolites (50-100) are readily detectable in urine by NMR, a much larger number is potentially available if lower concentration species can be detected unambiguously. Lower concentration metabolites are thought to be more specific to certain disease states and thus it is important to detect these metabolites with certainty. We report the identification of 4-deoxythreonic acid, a relatively low concentration endogenous metabolite that has not been previously identified in the 1H NMR spectrum of human urine. The use of HPLC and NMR spectroscopy facilitated the unequivocal and non-invasive identification of the molecule in urine which is complicated by extensive peak overlap and multiple, similar resonances from other metabolites such as 3-hydroxybutanoic acid. High-resolution detection and good sensitivity were achieved by the combination of multiple chromatographic fraction collection, sample pre-concentration, and the use of a cryogenically cooled NMR probe.


Subject(s)
Chromatography, High Pressure Liquid/methods , Magnetic Resonance Spectroscopy/methods , Sugar Acids/urine , Butyrates/analysis , Chemistry Techniques, Analytical , Chemistry, Pharmaceutical/methods , Drug Stability , Humans , Metabolomics/methods , Models, Chemical , Pharmaceutical Preparations , Sugar Acids/chemistry , Time Factors , Urinalysis/methods
6.
Clin Chim Acta ; 366(1-2): 216-24, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16336956

ABSTRACT

BACKGROUND: Measurements of urine galactitol have been used to monitor the adequacy of diet therapy in the treatment of galactosemia. We have devised a gas chromatographic mass spectrometry (GC/MS) isotope-dilution method for the simultaneous quantification of urine galactitol and another alternate pathway product, galactonate. METHODS: We prepared trimethylsilyl (TMS) derivatives and used D-[UL-13C]galactitol and D-[UL-13C]galactonate as the internal standard for GC/MS. Results obtained with this method were compared with those determined by the established GC method for galactitol and the NMR method for galactonate. Thirty-three normal urine specimens were analyzed by the isotope dilution technique for galactitol and galactonate. Results of galactitol in 6 of these urine specimens along with 18 from classic galactosemics and 19 variant galactosemics were compared with the established GC method. Results for galactonate in 15 urine specimens from galactosemics were compared to the established NMR technique. RESULTS: The method was linear up to 200 nmol with lower limits of detection of 1.1 nmol (1.75 mmol/mol creatinine) (Cr) and 0.8 nmol (1.28 mmol/mol Cr) for galactitol and galactonate, respectively. Intra- and Interassay imprecision ranged from 2.1-6.7% for galactitol and 3.5-8.0% for galactonate. The excretion of both metabolites was age dependent in both normal and galactosemics. In 12 normal urines from subjects under 1 year, values for galactitol ranged from 8-107 mmol/mol Cr, and in 7 over age 6, ranged from 2-5 mmol/mol Cr. Under 1 year, the range for galactonate was non-detectable to 231 and in the over 6 years group non-detectable to 25 mmol/mol Cr. In galactosemics under 1 year, the value for galactitol ranged from 397-743 and for galactonate 92-132 mmol/mol Cr while in nine patients over age 6 the range was 125-274 mmol/mol Cr for galactitol and 17-46 mmol/mol Cr for galactonate. CONCLUSIONS: The GC/MS method enables the simultaneous determination of urine galactitol and galactonate and is precise and useful over the wide range of concentrations needed to assess the galactose burden in patients with galactosemia.


Subject(s)
Galactitol/urine , Gas Chromatography-Mass Spectrometry/methods , Sugar Acids/urine , Adolescent , Adult , Calibration , Child , Child, Preschool , Galactosemias/urine , Humans , Infant , Infant, Newborn , Radioisotope Dilution Technique , Reference Values , Reproducibility of Results
7.
Article in English | MEDLINE | ID: mdl-14751793

ABSTRACT

A stable isotope dilution assay was developed for the sensitive determination of D-galactonic acid. D-[U-13C(6)]galactono-1,4-lactone was prepared as internal standard. Unlabelled and U-13C-labelled D-galactonic acid species were converted to the N-(1-butyl)galactonamide pentaacetate derivatives and assessed by gas chromatography-mass spectrometry (GC-MS). Positive chemical ionisation and monitoring of the [MH-60](+)-ions in the galactonate chromatographic peak at m/z 402 and m/z 408 were used for quantification. The procedure was applied to study the variability of D-galactonate excretion in healthy subjects and galactosemic patients and to monitor the D-galactonate-D-galactitol ratio in human urine.


Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Sugar Acids/urine , Adolescent , Adult , Carbon Isotopes , Child , Child, Preschool , Female , Galactitol/urine , Galactose/urine , Galactosemias/urine , Humans , Indicator Dilution Techniques , Lactones/urine , Male , Quality Control , Sensitivity and Specificity
8.
Mol Genet Metab ; 81(1): 31-44, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14728989

ABSTRACT

The age dependence of endogenous galactose formation was investigated in Q188R homozygous galactosemic patients (n=18; 4-38 years) using the primed continuous infusion approach with D-[1-13C]galactose as a substrate. Studies were conducted under postabsorptive conditions (fasting >10h) and good metabolic control. In the patients, the release of galactose from endogenous sources into plasma (R(a)) decreased with age and ranged from 4.6 to 2.0 micromol/kg body weight per h. Galactitol and galactonate release rates paralleled the galactose R(a) but at a lower level. The mean relation of galactose, galactitol, and galactonate release was 10:5:1. Statistically, there was a highly significant (p<0.0001) inverse correlation between total galactose release (i.e., sum of R(a) plus galactitol and galactonate release) and age. The data (total galactose=y, age=t) were best fitted to the simple exponential model y=y(0)+axexp(-bt) by non-linear regression analysis. The parameter estimates were y(0)=3.0+/-0.2, a=6.5+/-0.4, and b=0.11+/-0.02. The value of y(0) provides an estimate of total galactose release in adult patients (i.e., approximately 13 mg/kg body weight per day), summation operator (y(0)+a) provides an estimate for galactosemic newborns (i.e., approximately 41 mg/kg body weight per day). The data show that significant amounts of endogenous galactose are formed in galactosemic patients with release rates being several fold higher in infants than in adults. The present findings can explain the persistently elevated galactose-1-phosphate levels in erythrocytes-and its age dependence-in galactosemic patients even when under strict dietary treatment.


Subject(s)
Galactose/metabolism , Galactosemias/genetics , Mutation , Adolescent , Adult , Age Factors , Body Height , Body Weight , Carbon Isotopes , Child , Child, Preschool , Galactitol/blood , Galactitol/metabolism , Galactitol/urine , Galactose/blood , Galactose/urine , Galactosemias/metabolism , Humans , Infusion Pumps , Models, Biological , Sugar Acids/blood , Sugar Acids/metabolism , Sugar Acids/urine , UTP-Hexose-1-Phosphate Uridylyltransferase/metabolism
9.
Clin Chem ; 50(2): 403-9, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14684624

ABSTRACT

BACKGROUND: Sialic acid storage diseases (SSDs) are severe autosomal recessive neurodegenerative disorders caused by a transport defect across the lysosomal membrane, which leads to accumulation of sialic acid in tissues, fibroblasts, and urine. Defective free sialic acid transport can be established by quantification of free sialic acid in urine. METHODS: Urine sample size was adjusted to the equivalent of 100 nmol of creatinine. After addition of 2-keto-3-deoxy-d-glycero-d-galactonononic acid as internal standard, samples were diluted with water to an end volume of 250 microL. We used 10 microL for HPLC-tandem mass spectrometric analysis in the negative electrospray ionization mode, monitoring transitions m/z 308.3-->m/z 86.9 (sialic acid) and m/z 267.2-->m/z 86.9 (internal standard). The overall method was validated and studied for ion suppression, interfering compounds, and pH effects. Samples from controls (n = 72) and SSD patients (n = 3) were analyzed. RESULTS: The limit of detection was 3 micromol/L. Intraassay imprecision (CV; n = 10) was 6%, 3%, and 2% at 30, 130, and 1000 mmol/mol creatinine, respectively; corresponding interassay CV (n = 10) were 5%, 5%, and 2%. Recovery was 109% (100-1000 mmol/mol creatinine). The mean (SD) [range] excretion rates (mmol/mol creatinine) were 31.3 (16.6) [0.7-56.9] at 0-1 year (n = 20), 21.2 (9.8) [6.3-38.3] at 1-3 years (n = 15), 14.4 (8.2) [1.7-32.9] at 3-10 years (n = 25), and 4.6 (2.6) [0-9.8] above age 10 years (n = 12). SSD patients 1.2, 3.9, and 12 years of age had concentrations of 111.5, 54.2, and 36.1 mmol/mol creatinine, respectively. CONCLUSIONS: The HPLC-tandem MS method for free sialic acid in urine is more rapid, accurate, sensitive, selective, and robust than earlier methods and may serve as a candidate reference method for free sialic acid in diagnosis of SSD.


Subject(s)
N-Acetylneuraminic Acid/urine , Sialic Acid Storage Disease/diagnosis , Child , Child, Preschool , Chromatography, High Pressure Liquid , Humans , Infant , Infant, Newborn , Reproducibility of Results , Spectrometry, Mass, Electrospray Ionization , Sugar Acids/urine
10.
Pediatr Res ; 42(6): 855-61, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9396569

ABSTRACT

Although numerous reports have appeared showing high levels of galactitol in the urine of patients with galactose-1-phosphate uridylyltransferase deficiency, little attention has been paid to measurement of urinary galactonate. Herein we explored the use of 1H and 13C nuclear magnetic resonance, which required only the concentration of urine without derivatization, to detect and quantitate urinary galactonate. We report that transferase deficient infants, as well as adults on galactose restricted diets excrete significant amounts of galactonate, whereas none is detected in the urine of normal subjects. Galactose-toxic infants were found to excrete large amounts of galactonate, which decreased when the lactose-free diet was instituted. We also found that normal individuals subjected to an oral galactose load also excrete high levels of galactonate for at least 4 h after galactose ingestion. Our data provide evidence that the first reaction in the oxidative pathway of galactose metabolism described in rat liver in 1966 is activated in patients with a variety of galactose-1-phosphate uridylyltransferase gene mutations even while on a lactose-restricted diet. In both patients and normal individuals, flux through the alternate galactonate pathway appears to be related to the body galactose burden.


Subject(s)
Galactosemias/urine , Magnetic Resonance Spectroscopy/methods , Sugar Acids/urine , Adolescent , Adult , Carbon Isotopes , Case-Control Studies , Child , Child, Preschool , Female , Humans , Hydrogen-Ion Concentration , Infant , Infant, Newborn , Male , Middle Aged , Protons , Reference Values
11.
J Chromatogr ; 570(2): 277-84, 1991 Oct 04.
Article in English | MEDLINE | ID: mdl-1797843

ABSTRACT

A reversed-phase liquid chromatographic assay was developed for the specific evaluation of metabolic by-products in the urine of galactosemic patients and based on the simultaneous determination of gluconolactone, galactonolactone and galactitol. The procedure involved a lyophilization step and the formation of phenylisocyanate derivatives, followed by injection directly into the chromatograph. Analytical results showed good selectivity, linearity, precision and accuracy. The method enabled the detection of levels as low as 0.05-0.1 ng, and compared favourably with other published techniques for the estimation of aldonic acids in biological fluids.


Subject(s)
Galactitol/urine , Galactosemias/urine , Gluconates/urine , Sugar Acids/urine , Chromatography, High Pressure Liquid , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/urine , Lactones , Male , Spectrophotometry, Ultraviolet
12.
Cancer Res ; 50(11): 3351-66, 1990 Jun 01.
Article in English | MEDLINE | ID: mdl-2334930

ABSTRACT

The aim of the present study was to establish screening biomarkers of exposure to antineoplastic drugs administered to 11 patients undergoing cancer chemotherapy. Among the anticancer drugs administered were cyclophosphamide (all), Adriamycin (5 of 11), methotrexate (3 of 11), 5-fluorouracil (4 of 11), vincristine (3 of 11), megestrol acetate (1 of 11), and procarbazine (1 of 11). The noninvasive urinary parameters investigated were thioethers, D-glucaric acid, elements, and forward and reverse mutagenesis using bacterial bioassays. The data were analyzed in terms of the observed concentrations and those corrected for personal baseline. Personal baseline correction for parameters with significant nonexposure baseline levels was essential. While glucaric acid and thioethers were increased by the drug treatments, the correlations with baseline-uncorrected data showing an inverse relationship proved spurious, because saturation of the detoxification systems occurred at the high doses administered. Glucaric acid was also influenced by methotrexate and vincristine. Thioether content was affected by cyclophosphamide only. The forward mutagenesis assay was directly correlated to cyclophosphamide dose but the reverse assay was not, in the presence or absence of rat S9 fraction. The forward assay was not sensitive to the effects of smoking. Relative to controls, the elements changed by cyclophosphamide were K, S, and P. Those affected by Adriamycin were Ca, Mg, and Na; 5-fluorouracil affected Ca, Mg, Na, and C; methotrexate changed P and S. The forward mutagenesis assay and D-glucaric acid concentrations were the screening biomarkers best suited to monitoring for extent of exposure to these antineoplastic drugs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/metabolism , Creatinine/urine , Electrolytes/urine , Glucaric Acid/urine , Sugar Acids/urine , Sulfides/urine , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cyclophosphamide/metabolism , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/metabolism , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/metabolism , Humans , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Methotrexate/metabolism , Middle Aged , Monitoring, Physiologic , Mutagenicity Tests , Vincristine/administration & dosage , Vincristine/adverse effects , Vincristine/metabolism
13.
Br J Ind Med ; 47(1): 58-61, 1990 Jan.
Article in English | MEDLINE | ID: mdl-2310708

ABSTRACT

Workers at a printing plant exposed to low concentrations of toluene (43-401 mg/m3, median 155 mg/m3) had increased urinary D-glucaric acid (3.55-5.12 mmol/mol creatinine) excretion at the end of the shift compared with controls (2.45-3.35 mmol/mol creatinine). No increase was found after the summer holiday (1.92-2.89 mmol/mol creatinine) but excretion had increased two weeks later (4.05-5.55 mmol/mol creatinine). These changes in the excretion of D-glucaric acid were not correlated to levels of exposure, to changes of urinary hippuric acid and o-cresol half lives (three to eight hours), nor to o-cresol/hippuric acid concentration ratios when measured at the end of daily exposure. Since a significant intra and interindividual variability of urinary D-glucaric acid was found in all groups, urinary D-glucaric acid excretion is suitable to monitor group but not individual exposure.


Subject(s)
Glucaric Acid/urine , Sugar Acids/urine , Toluene/adverse effects , Environmental Exposure , Environmental Monitoring , Humans , Printing
14.
Teratog Carcinog Mutagen ; 9(6): 359-68, 1989.
Article in English | MEDLINE | ID: mdl-2576815

ABSTRACT

Mutagenic hazards related to occupational exposure to nitrous oxide and enflurane was studied in the personnel of five operating rooms using a coupled environmental and biological monitoring approach. The environmental monitoring revealed air concentrations of the two anesthetics exceedings the TLVs by 10-15-fold. These values were correlated individually with the concentrations of the two anesthetics in the expired air of the exposed subjects. The biological monitoring was carried out by determining two parameters associated with mutagen exposure (urinary mutagenicity and thioethers) and a parameter associated with the enzymatic induction (D-glucaric acid) in the urine of exposed and unexposed subjects (N = 64 and N = 37, respectively). The results showed no difference in the two groups for urine mutagenicity and D-glucaric acid, but urine thioethers were significantly increased among highly exposed subjects.


Subject(s)
Air Pollutants, Occupational/analysis , Anesthetics/pharmacokinetics , Glucaric Acid/urine , Mutagens/urine , Operating Rooms , Personnel, Hospital , Sugar Acids/urine , Sulfides/urine , Adult , Anesthesiology , Anesthetics/analysis , Enflurane/pharmacokinetics , Environmental Exposure , Environmental Monitoring , Female , General Surgery , Humans , Male , Nitrous Oxide/pharmacokinetics , Operating Room Nursing
15.
Int Arch Occup Environ Health ; 61(5): 335-40, 1989.
Article in English | MEDLINE | ID: mdl-2707871

ABSTRACT

The authors carried out biological monitoring of the mutagenic/carcinogenic hazards associated with exposure to bitumen fumes during paving operations, analysing some biological parameters in the urine of a group of exposed workers. The urine samples were studied for mutagenicity by the Ames test and for thioethers concentration. D-Glucaric acid urine excretion was also determined to investigate the enzymatic induction potential of bitumens. Even though, in a previous environmental monitoring phase, a low content of mutagenic/carcinogenic compounds was found in bitumen and air samples, urinary mutagenicity data of exposed workers were statistically higher than those of a group of unexposed subjects. The urinary mutagenicity increased further if exposure to bitumens was associated with cigarette smoking. Thioethers were higher only in subjects exposed simultaneously to bitumens and cigarettes. D-Glucaric acid excretion did not increase significantly. The authors think that this type of coupled environmental and biological monitoring is a valid tool for a better evaluation of the mutagenic/carcinogenic exposure to bitumens or similar complex mixtures.


Subject(s)
Air Pollutants, Occupational/adverse effects , Glucaric Acid/urine , Hydrocarbons/adverse effects , Mutagens/urine , Sugar Acids/urine , Sulfides/urine , Environmental Exposure , Environmental Monitoring , Humans , Male
16.
Clin Chem ; 34(11): 2283-90, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3180424

ABSTRACT

Urinary excretion of D-glucaric acid (uGA) is an index of type II hepatic microsomal enzyme induction, indirectly revealing possible organic effects of some drugs and environmental pollutants. However, its determination is often cumbersome. We suggest a new, fast microanalytical method for uGA determination in which beta-glucuronidase (BG; EC 3.2.1.31) activity inhibition produced by uGA-derived 1,4-D-glucarolactone is measured. With use of purified BG, the method is suitable for centrifugal analyzers, allowing assay of greater than 100 samples per day. Moreover, the method measures uGA more accurately than other enzymatic methods based on BG inhibition. The within-day CV ranges from 7.9% to 4.6% (uGA 31.55-121.31 mumol/L); the between-day CV ranges from 11.5% to 5.0% (uGA 26.09-124.10 mumol/L). The detection limit is 6.0 mumol/L. The standard curve is linear from 10 to 200 mumol/L. Mean analytical recovery is 100%. Comparison with the method of Simmons et al. (Clin Chim Acta 1974;51:47-51) gave a correlation of r = 0.978, y = 1.40x-2.81. Reference intervals were established in a healthy population sample of 369 people (165 under 14 y), and uGA, expressed in micromoles per gram of creatinine, was higher in women than in girls or in males.


Subject(s)
Glucaric Acid/urine , Sugar Acids/urine , Adolescent , Adult , Autoanalysis/methods , Child , Child, Preschool , Female , Glucaric Acid/analogs & derivatives , Glucaric Acid/metabolism , Glucuronidase/antagonists & inhibitors , Humans , Male , Microchemistry/methods , Microsomes, Liver/enzymology , Reference Values , Software
17.
Clin Biochem ; 21(3): 193-8, 1988 Jun.
Article in English | MEDLINE | ID: mdl-2898981

ABSTRACT

Urinary D-glucaric acid (DGA) and the activities of gamma-glutamyl transferase (GGT) and other hepatic enzymes in serum were determined in 33 noncirrhotic male alcoholics who had continued to consume alcohol until at least 24 h prior to the taking of samples. DGA excretion was significantly greater in them than in a group of 30 healthy controls (p less than 0.001), exceeding the upper reference level in 38% of the alcoholic cases (as compared with 88% for GGT). In the alcoholic patients, there was highly significant correlation between urinary DGA and serum GGT (r = 0.613, p less than 0.001), suggesting that in both cases the increased levels are due to enzyme induction. None of the biochemical variables studied were significantly correlated with estimated daily alcohol consumption. Urinary DGA levels fell off rapidly with abstinence, and in 31 alcoholic patients who had consumed no alcohol for 5 days, there was no statistically significant correlation between DGA excretion and serum GGT (r = 0.158, p congruent to 0.4).


Subject(s)
Alcoholism/metabolism , Glucaric Acid/urine , Liver/enzymology , Sugar Acids/urine , Adult , Aged , Alcoholism/enzymology , Alcoholism/urine , Chronic Disease , Humans , Male , Middle Aged , gamma-Glutamyltransferase/blood
19.
J Clin Chem Clin Biochem ; 25(12): 855-8, 1987 Dec.
Article in English | MEDLINE | ID: mdl-2895161

ABSTRACT

Twenty patients with porphyria cutanea tarda who had ingested no alcohol for at least 10 days before sampling were found to possess urinary D-glucaric acid levels similar to those of 30 clinically healthy controls. Correlation between urinary excretion of D-glucaric acid on the one hand and plasma or urinary porphyrin concentrations on the other was not statistically significant. These results suggest that the high urinary concentrations of D-glucaric acid found in porphyria cutanea tarda patients by Budillon et al. (Acta Hepato-Gastroenterol. 25 (1978) 267) may have been due to recent consumption of alcohol rather than to the porphyrin pathology.


Subject(s)
Glucaric Acid/urine , Porphyrias/urine , Skin Diseases/urine , Sugar Acids/urine , Alcohol Drinking , Humans , Male , Porphyrins/blood , Porphyrins/urine , gamma-Glutamyltransferase/blood
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