Sample records for ethyl glucuronide etg

  1. SENSITIVITY OF COMMERCIAL ETHYL GLUCURONIDE (ETG) TESTING IN SCREENING FOR ALCOHOL ABSTINENCE

    Microsoft Academic Search

    MARK H. WOJCIK; JEFFREY S. HAWTHORNE

    2007-01-01

    The '80 h Ethyl Glucuronide (EtG) test' has become an idiom of the alcohol testing community, a review of the literature shows this window of detection applies only to extreme cases. EtG testing is becoming more common as a method to test for alcohol consumption in individuals who have been ordered to abstain from alcohol consumption. We tested 19 subjects

  2. Ethyl glucuronide

    Microsoft Academic Search

    Friedrich Martin Wurst; Christoph Kempter; Joerg Metzger; Stephan Seidl; Andreas Alt

    2000-01-01

    A marker with a specific time spectrum of detection and both high sensitivity and specificity is required to diminish the clinically as well as forensically important gap on the time axis between short- and long-term markers of alcohol consumption like ethanol and CDT, GGT or MCV, respectively. Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable upon storage, direct metabolite of

  3. High levels of agreement between clinic-based ethyl glucuronide (EtG) immunoassays and laboratory-based mass spectrometry

    PubMed Central

    Leickly, Emily; McDonell, Michael G.; Vilardaga, Roger; Angelo, Frank A.; Lowe, Jessica M.; McPherson, Sterling; Srebnik, Debra; Roll, John M.; Ries, Richard K.

    2015-01-01

    Background Immunoassay urine drug screening cups that detect use for two or more days are commonly used in addiction treatment settings. Until recently, there has been no comparable immunoassay test for alcohol use in these settings. Objectives The aim of this study was to assess the agreement of a commercially available ethyl glucuronide immunoassay (EtG-I) test conducted at an outpatient addiction clinic and lab-based EtG mass spectrometry (EtG-MS) conducted at a drug testing laboratory at three cut-off levels. High agreement between these two measures would support the usefulness of EtG-I as a clinical tool for monitoring alcohol use. Methods Forty adults with co-occurring alcohol dependence and serious mental illnesses submitted 1068 urine samples over a 16-week alcohol treatment study. All samples were tested using EtG-I on a benchtop analyzer and 149 were randomly selected for EtG-MS analysis at a local laboratory. Agreement was defined as the number of samples where EtG-I and EtG-MS were both above or below a specific cut-off level. Agreement was calculated at low cut-off levels (100 and 250 ng/ml), as well as at a higher cut-off level (500 ng/ml) recommended by most by commercial drug testing laboratories. Results Agreement between EtG-I and EtG-MS was high across all cut-off levels (90.6% at 100 ng/ml, and 96.6% at 250 and 500 ng/ml). Conclusions EtG immunoassays conducted at low cut-off levels in point-of-care testing settings have high agreement with lab-based EtG-MS. EtG-I can be considered a useful clinical monitoring tool for alcohol use in community-based addiction treatment settings. PMID:25695340

  4. Ethyl glucuronide and ethyl sulfate.

    PubMed

    Walsham, Natalie E; Sherwood, Roy A

    2014-01-01

    Alcohol misuse is associated with significant morbidity and mortality. Although clinical history, examination, and the use of self-report questionnaires may identify subjects with harmful patterns of alcohol use, denial or under-reporting of alcohol intake is common. Existing biomarkers for detecting alcohol misuse include measurement of blood or urine ethanol for acute alcohol consumption, and carbohydrate-deficient transferrin and gamma-glutamyl transferase for chronic alcohol misuse. There is a need for a biomarker that can detect excessive alcohol consumption in the timeframe between 1 day and several weeks. Ethyl glucuronide (EtG) is a direct metabolite of ethanol detectable in urine for up to 90h and longer in hair. Because EtG has high specificity for excess alcohol intake, it has great potential for use in detecting "binge" drinking. Using urine or hair, this noninvasive marker has a role in a variety of clinical and forensic settings. PMID:25735859

  5. Ethyl glucuronide.

    PubMed

    Walsham, Natalie E; Sherwood, Roy A

    2012-03-01

    Alcohol is associated with significant morbidity and mortality. Subjects abusing alcohol can be identified through clinical history, examination or self-report questionnaires. A range of biomarkers is available for detecting alcohol misuse, but there is still a need for a marker that can detect alcohol consumption in the time window between one day (ethanol) and one week (gamma-glutamyl transpeptidase and carbohydrate-deficient transferrin). Ethyl glucuronide is a direct metabolite that can be detected in urine for up to 90 h and has the potential to become a useful marker of 'binge' drinking. As a non-invasive marker, it could have a role in a variety of clinical and forensic settings. PMID:22113954

  6. [Ethyl glucuronide: a biomarker of alcohol consumption].

    PubMed

    Kharbouche, H; Sporkert, F; Staub, C; Mangin, P; Augsburger, M

    2009-11-01

    Excessive alcohol consumption represents a major risk factor for morbidity and mortality. It is therefore indispensable to be able to detect at-risk drinking. Ethyl glucuronide (EtG) is a specific marker of alcohol consumption. The determination of ethyl glucuronide in urine or blood can be used to prove recent driving under the influence of alcohol, even if ethanol is no longer detectable. The commercialization of an EtG specific immunological assay now allows to obtain preliminary results rapidly and easily with satisfying sensitivity. Moreover, the detection of ethyl glucuronide in hair offers the opportunity to evaluate an alcohol consumption over a long period. The EtG concentration in hair is in correlation with the amount of ingested alcohol. Thus, the analysis of ethyl glucuronide can be used to monitor abstinence, to detect alcohol relapse and to identify at-risk drinkers. However, a cut off allowing to detect chronic alcohol abuser reliably still does not exist. Therefore, it is recommended to perform the analysis of ethyl glucuronide in complement to the existing blood markers. A study financed by the Swiss Foundation for Alcohol Research is actually conducted by the West Switzerland University Center of Legal Medicine in order to establish an objective cut-off. PMID:20029783

  7. [Detection and application of ethyl glucuronide in forensic toxicology].

    PubMed

    Zhao, Hui; Zhuo, Xian-yi; Shen, Bao-hua

    2009-02-01

    Ethyl glucuronide is a specific metabolite of ethanol. There have been plenty of articles referring its pharmacokinetics, detection and application as a specific bio-marker of alcohol intake. This article reviews various analytical methods of EtG, relationship between EtG quantification and ethanol intake, and criteria for determining chronic alcohol abuse, and origin of ethanol found in the cadavers by EtG analysis. EtG has its potential application in forensic toxicology. PMID:19397218

  8. Influence of preservatives on the stability of ethyl glucuronide and ethyl sulphate in urine

    Microsoft Academic Search

    Annette Thierauf; Annerose Serr; Claudia C. Halter; Ali Al-Ahmad; Sumandeep Rana; Wolfgang Weinmann

    2008-01-01

    BackgroundEthyl glucuronide (EtG) and ethyl sulphate (EtS) are specific and sensitive markers of ethanol consumption well established in monitoring withdrawal treatment in patients with chronic alcoholism. Recently, bacterial decomposition as well as in vitro and post-mortem formation of EtG was reported. The aim of this study was to investigate the influence of different preservatives on the stability of EtG and

  9. Detection Times for Urinary Ethyl Glucuronide and Ethyl Sulfate in Heavy Drinkers during Alcohol Detoxification

    Microsoft Academic Search

    Anders Helander; Christoph Fehr; Norbert Dahmen; Olof Beck

    2008-01-01

    Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive alcohol biomarkers. This study determined the detection times for EtG and EtS in alcoholic patients undergoing alcohol detoxification. Methods: Alcohol-dependent patients (n

  10. Quantitative determination of ethyl glucuronide in sweat.

    PubMed

    Schummer, Claude; Appenzeller, Brice M R; Wennig, Robert

    2008-08-01

    In this study, ethyl glucuronide (EtG), a specific metabolite of ethanol, was for the first time detected in sweat after alcohol consumption by human volunteers. Sweat was collected using a sweat patch (PharmChek). After collection, chemicals accumulated on the patch were extracted with water and extracts were purified by solid phase extraction. EtG was determined by gas chromatography with mass spectrometric detection in negative chemical ionization mode. In parallel, the amount of sodium deposited on the patch was determined by capillary electrophoresis and used as a correction factor to calculate the volume of sweat accumulated on the patch and, hence, the concentration of EtG in sweat. The EtG sweat concentration observed ranged from 1.7 to 103.0 microg/L for alcohol consumption from 38.0 to 154.6 g equivalent pure ethanol. No EtG was detected in subjects who did not consume alcohol. Our results demonstrate that after ethanol consumption, EtG is detectable in sweat collected using a sweat patch. The simultaneous determination of sodium allows the estimation of the volume of sweat accumulated on the patch and to calculate the concentration of EtG in sweat. This represents the first quantitative determination of a xenobiotic in sweat collected using a sweat patch. This study suggests that EtG determination in sweat could represent an interesting alternative to urine or serum analysis for the control of abstinence of patients included in treatment programs. PMID:18641544

  11. EVALUATION OF A NEW IMMUNOASSAY FOR URINARY ETHYL GLUCURONIDE TESTING

    Microsoft Academic Search

    OLOF BECK; ANDERS HELANDER

    2007-01-01

    Aims: The minor ethanol metabolite ethyl glucuronide (EtG) is used as a sensitive and specific test for recent alcohol consumption with clinical and forensic applications. This study evaluated a new enzyme immunoassay (DRI-EtG EIA, Microgenics Corp.) for determination of the EtG concentration in urine samples. Methods: Evaluation was done using the kit calibrators (range 0-5.0 mg\\/L) and controls, an external

  12. A pharmacokinetic study of ethyl glucuronide in blood and urine: Applications to forensic toxicology

    Microsoft Academic Search

    Gudrun Høiseth; Jean Paul Bernard; Ritva Karinen; Lene Johnsen; Anders Helander; Asbjørg S. Christophersen; Jørg Mørland

    2007-01-01

    This pharmacokinetic study investigated the kinetics of ethanol and its metabolite ethyl glucuronide (EtG) in blood and urine during the whole time course of absorption and elimination. There are few previous studies on the kinetics of EtG in blood, and we wanted to evaluate whether such knowledge could yield valuable information regarding the time of ethanol ingestion in forensic cases,

  13. Ethyl glucuronide: on the time course of excretion in urine during detoxification

    Microsoft Academic Search

    Friedrich Martin Wurst; Stephan Seidl; Dieter Ladewig; Franz Müller-Spahn; Andreas Alt

    2002-01-01

    Ethyl glucuronide (EtG) is a promising new biological state marker of recent alcohol consumption that detects alcohol use reliably over a definite time period. Other currently available markers lack acceptable sensitivity and specificity. Our aim is to elucidate under naturalistic conditions the time course of EtG excretion in urine following alcohol consumption and to show how this can be utilized

  14. Practical use of ethyl glucuronide and ethyl sulfate in postmortem cases as markers of antemortem alcohol ingestion

    Microsoft Academic Search

    Gudrun Høiseth; Ritva Karinen; Asbjørg Christophersen; Jørg Mørland

    2010-01-01

    In postmortem toxicology, it could be difficult to determine whether a positive blood ethanol concentration reflects antemortem\\u000a ingestion or postmortem synthesis of alcohol. Measurement of the nonoxidative ethanol metabolite ethyl glucuronide (EtG) has\\u000a been suggested as a marker of antemortem ingestion of alcohol, but EtG might degrade postmortem which could make interpretation\\u000a difficult. So far, the published articles concern EtG

  15. Biotransformation of Ethanol to Ethyl Glucuronide in a Rat Model after a Single High Oral Dosage

    Microsoft Academic Search

    Trista H. Wright; Kenneth E. Ferslew

    Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest maximum blood EtG (BEtG) concentrations are reached between 3.5 - 5.5 hours post ethanol administration (Hoiseth et al, 2007). This study was undertaken to determine if the Sprague Dawley (SD) rat biotransforms ethanol to EtG after

  16. Solid-phase extraction procedure for ethyl glucuronide in urine.

    PubMed

    Zheng, Yufang; Helander, Anders

    2008-01-01

    Measurement of the conjugated ethanol metabolite ethyl glucuronide (EtG) in urine is increasingly being used as a biomarker for recent alcohol consumption. Prior to quantification of EtG by mass spectrometric (MS) methods [liquid chromatography (LC)-MS or gas chromatography-MS], there is sometimes need for sample cleanup to remove interfering matrix constituents. A solid-phase extraction (SPE) procedure using a HyperSep SAX strong anion exchanger was developed for sample cleanup of urinary EtG prior to LC-MS analysis. The EtG content in a 50-100-microL urine sample was finally reconstituted in the same volume as the original aliquot. The cleaner SPE extracts, without sample dilution, allowed for improved quantification of urinary EtG in the low concentration range. The detection limit of the SPE procedure when combined with LC-MS analysis was < 0.1 mg/L EtG, and the assay imprecision < 5.5% (total CV) in the 0.5-5.0 mg/L concentration range. The absolute recovery of urinary EtG was ~80%, which was compensated for by using a deuterated analogue (EtG-d(5)) as internal standard. The urinary EtG results with SPE followed by LC-MS were highly correlated (r(2) = 0.959) with those obtained using a sensitive and selective ultra-performance LC-tandem MS method. PMID:19021935

  17. A novel and an effective analytical approach for the LCMS determination of ethyl glucuronide and ethyl sulfate in urine

    Microsoft Academic Search

    Donata Favretto; Alessandro Nalesso; Giampietro Frison; Guido Viel; Pietro Traldi; Santo Davide Ferrara

    2010-01-01

    An alternative liquid chromatography-mass spectrometry (LC-MS) method based on no discharge (ND) atmospheric pressure chemical ionization (APCI) was developed for the simultaneous determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine in negative ion conditions. Abundant [M-H] - species of EtG and EtS were obtained, allowing to reach limits of quantification (0.1 ?g\\/ml for both analytes), accuracy, and

  18. Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake

    Microsoft Academic Search

    Claudia C. Halter; Sebastian Dresen; Volker Auwaerter; Friedrich M. Wurst; Wolfgang Weinmann

    2008-01-01

    The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical\\u000a and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study,\\u000a 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51?±?0.17 g\\/kg,

  19. In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulphate

    Microsoft Academic Search

    Stefanie Baranowski; Annerose Serr; Annette Thierauf; Wolfgang Weinmann; Markus Gro?e Perdekamp; Friedrich M. Wurst; Claudia C. Halter

    2008-01-01

    Recent studies show that ethyl glucuronide (EtG) can be decomposed by bacteria; whilst so far no degradation of ethyl sulphate\\u000a (EtS) has been observed. In the present study, in vitro experiments with bacterial colonies were performed. Bacteria (Escherichia coli, Klebsiella pneumoniae, Clostridium sordellii) were isolated from autopsy material (liver, heart blood, urine, ascites, pericardial fluid, pleural fluid) tested for ?-glucuronidase

  20. Measurement of ethyl glucuronide in vitreous humor with liquid chromatography–mass spectrometry

    Microsoft Academic Search

    Alper Keten; Ali Riza Tumer; Aysun Balseven-Odabasi

    2009-01-01

    BackgroundIt is important to detect alcohol intake in postmortem investigations. However it can be difficult to interpret the results of alcohol analysis in putrefied corpses. To avoid this difficulty, there have been studies on detection of ethyl glucuronide (EtG), a non-oxidative metabolite of ethyl alcohol. The aim of this study was investigate EtG levels in vitreous humor (VH), a valuable

  1. IMPROVED ALCOHOL DETECTION TESTING - ETG

    Microsoft Academic Search

    ETHYL GLUCURONIDE

    Ethyl glucuronide (EtG) is a minor metabolite of ethanol (ethyl alcohol). It is formed in vivo as a consequence of alcohol consumption. A small fraction (0.02%) of a dose of ethanol is conjugated in the liver with glucuronic acid to form ethyl glucuronide. This compound is excreted in the urine. EtG can be detected in the blood for up to

  2. Determination of ethyl glucuronide in urine using reversed-phase HPLC and pulsed electrochemical detection (Part II)

    Microsoft Academic Search

    Romina Kaushik; William R. LaCourse; Barry Levine

    2006-01-01

    A direct, versatile method for the determination of ethyl glucuronide (EtG), a biomarker of ethanol consumption, in urine has been developed using reversed-phase liquid chromatography with pulsed electrochemical detection (PED). EtG and methyl glucuronide (MetG), which serves as an internal standard, are readily separated using a mobile phase consisting of 1% acetic acid\\/acetonitrile (98\\/2, v\\/v). Post-column addition of NaOH allows

  3. Urine tested positive for ethyl glucuronide and ethyl sulphate after the consumption of “non-alcoholic” beer

    Microsoft Academic Search

    Annette Thierauf; Heike Gnann; Ariane Wohlfarth; Volker Auwärter; Markus Große Perdekamp; Klaus-Juergen Buttler; Friedrich M. Wurst; Wolfgang Weinmann

    2010-01-01

    In abstinence maintenance programs, for reissuing the driving licence and in workplace monitoring programs abstinence from ethanol and its proof are demanded. Various monitoring programs that mainly use ethyl glucuronide (EtG) as alcohol consumption marker have been established. To abstain from ethanol, but not from the taste of alcoholic beverages, in particular non-alcoholic beer has become more and more popular.

  4. Improvement of ethyl glucuronide determination in human urine and serum samples by solid-phase extraction

    Microsoft Academic Search

    Ines Janda; Andreas Alt

    2001-01-01

    An improved method for the determination of ethyl glucuronide (EtG) in human serum and urine was developed using solid-phase extraction (SPE) and gas chromatography (GC) with mass spectrometric detection (MS). EtG was isolated from serum and urine using aminopropyl SPE columns after deproteination with perchloric acid and hydrochloric acid, respectively. The chromatographic separation was performed on a DB 1701 fused-silica

  5. A study of distribution of ethyl glucuronide in different keratin matrices

    Microsoft Academic Search

    V. Pirro; D. Di Corcia; S. Pellegrino; M. Vincenti; B. Sciutteri; A. Salomone

    2011-01-01

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol, frequently used as a biomarker of alcohol abuse. To this purpose, EtG is preferentially determined in hair samples, using a cut-off value of 30pg\\/mg to discriminate between social and heavy drinkers, as recently fixed by an international consensus conference. Although this cut-off value is assumed for head hair, alternative matrices, such

  6. Ethyl glucuronide in hair – A highly effective test for the monitoring of alcohol consumption

    Microsoft Academic Search

    Ronald Agius; Thomas Nadulski; Hans-Gerhard Kahl; Bertin Dufaux

    In Germany drink driving offenders lose their license and must prove abstinence for one year in order to regain it. In this paper we assess the newly introduced ethyl glucuronide (EtG) tests in urine and hair in this alcohol abstinence monitoring. 20% (80 out of 386) of the 3cm long hair samples were tested positive for EtG in hair, compared

  7. Distribution of ethyl glucuronide in rib bone marrow, other tissues and body liquids as proof of alcohol consumption before death

    Microsoft Academic Search

    Haiko Schloegl; Thomas Rost; Wolfgang Schmidt; Friedrich Martin Wurst; Wolfgang Weinmann

    2006-01-01

    Postmortem ethyl glucuronide (EtG) concentrations in rib bone marrow, liver, muscle, fat tissue, urine, blood and bile have been determined by LC–MS\\/MS. Samples have been taken from twelve corpses during autopsies. In nine corpses EtG could be detected, corresponding blood ethanol concentrations (BAC) were 0.04–0.37g%. In three cases, no EtG was found; two of these cases showed postmortem BACs –

  8. Ethyl glucuronide and ethyl sulfate in urine after consumption of various beverages and foods—misleading results?

    Microsoft Academic Search

    Frank Musshoff; Elena Albermann; Burkhard Madea

    2010-01-01

    Urine testing for ethyl glucuronide (EtG) is used to spot recent alcohol intake and is utilized to document alcohol abstinence.\\u000a However, other possible sources of ethanol existed when special beverages or foods were ingested. EtG concentration curves\\u000a in urine were measured after the consumption of non-alcoholic beers, fruit juices, sauerkraut, and matured bananas. Using\\u000a a cutoff of 0.1 mg\\/l, positive EtG

  9. Voucher-Based Reinforcement for Alcohol Abstinence Using the Ethyl-Glucuronide Alcohol Biomarker

    ERIC Educational Resources Information Center

    McDonell, Michael G.; Howell, Donelle N,; McPherson, Sterling; Cameron, Jennifer M.; Srebnik, Debra; Roll, John M.; Ries, Richard K.

    2012-01-01

    This study assessed the effects of a contingency management (CM) intervention for alcohol consumption in 10 alcohol-dependent participants. An ABCA design was used. Vouchers were provided contingent on results of ethyl glucuronide (EtG) urine tests (an alcohol biomarker with a 2-day detection period) and alcohol breath tests during the C phase.…

  10. Ethyl sulphate and ethyl glucuronide in vitreous humor as postmortem evidence marker for ethanol consumption prior to death

    Microsoft Academic Search

    Annette Thierauf; Jürgen Kempf; Markus Große Perdekamp; Volker Auwärter; Heike Gnann; Ariane Wohlfarth; Wolfgang Weinmann

    2011-01-01

    To clarify the circumstances of death, the degree of inebriation is of importance in many cases, but for several reasons the determination of the ethanol concentration in post-mortem samples can be challenging and the synopsis of ethanol and the direct consumption markers ethyl glucuronide (EtG) and ethyl sulphate (EtS) has proved to be useful. The use of a rather stable

  11. Stability of ethyl glucuronide in urine, post-mortem tissue and blood samples

    Microsoft Academic Search

    Haiko Schloegl; Sebastian Dresen; Karin Spaczynski; Mylène Stoertzel; Friedrich Martin Wurst; Wolfgang Weinmann

    2006-01-01

    The stability of ethyl glucuronide (EtG) under conditions of degradation was examined in urine samples of nine volunteers\\u000a and in post-mortem tissue (liver, skeletal muscle) and blood taken from seven corpses at autopsies. Analysis was performed\\u000a via LC-MS\\/MS. EtG concentrations in urine samples ranged from 2.5 to 296.5 mg\\/l. When stored at 4°C in airtight test tubes,\\u000a EtG concentrations remained relatively

  12. Ethyl glucuronide for detecting alcohol lapses in patients with an alcohol use disorder.

    PubMed

    Lahmek, Pierre; Michel, Laurent; Diviné, Catherine; Meunier, Nadine; Pham, Béatrice; Cassereau, Catherine; Aussel, Christian; Aubin, Henri-Jean

    2012-03-01

    Urine ethyl glucuronide (EtG) was screened in 75 patients during a hospital-based treatment for an alcohol use disorder. During follow-up, EtG was detected in 35 (14.6%) of the 239 urine samples. Positive screens were found in 22 patients (29%), of whom nine were outpatients (39.1% of all outpatients) and 13 inpatients (25.0% of all inpatients). Of the 22 patients with positive EtG, five (22%) also gave a positive breath alcohol test and 10 (45.5%) reported recent alcohol consumption; 12 (54.5%) gave a negative breath alcohol test and declared no alcohol lapse. Ethyl glucuronide has been found useful in detecting covered lapses. PMID:21817916

  13. Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases

    Microsoft Academic Search

    S. Suesse; F. Pragst; T. Mieczkowski; C. M. Selavka; A. Elian; H. Sachs; M. Hastedt; M. Rothe; J. Campbell

    This article presents results from 1872 hair samples, which were analyzed for fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG). The results were evaluated in the context of self-reported drinking behavior, the use of hair cosmetics, the gender of the sample donors and hair sample length. For comparison, CDT and GGT in serum were available in 477 and 454

  14. In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulphate.

    PubMed

    Baranowski, Stefanie; Serr, Annerose; Thierauf, Annette; Weinmann, Wolfgang; Grosse Perdekamp, Markus; Wurst, Friedrich M; Halter, Claudia C

    2008-09-01

    Recent studies show that ethyl glucuronide (EtG) can be decomposed by bacteria; whilst so far no degradation of ethyl sulphate (EtS) has been observed. In the present study, in vitro experiments with bacterial colonies were performed. Bacteria (Escherichia coli, Klebsiella pneumoniae, Clostridium sordellii) were isolated from autopsy material (liver, heart blood, urine, ascites, pericardial fluid, pleural fluid) tested for beta-glucuronidase activity, and three bacterial strains were added to nutrient-deficient medium containing EtG and/or EtS and incubated at 36 +/- 1 degrees C. Samples were taken after various intervals up to 11 days, and EtG and EtS were determined by electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS). EtG was degraded by E. coli and C. sordellii--complete degradation occurred in the range of 3-4 days--and these bacteria exhibited beta-glucuronidase activity. EtS was not affected within 11 days of incubation. PMID:18574590

  15. Practical use of ethyl glucuronide and ethyl sulfate in postmortem cases as markers of antemortem alcohol ingestion.

    PubMed

    Høiseth, Gudrun; Karinen, Ritva; Christophersen, Asbjørg; Mørland, Jørg

    2010-03-01

    In postmortem toxicology, it could be difficult to determine whether a positive blood ethanol concentration reflects antemortem ingestion or postmortem synthesis of alcohol. Measurement of the nonoxidative ethanol metabolite ethyl glucuronide (EtG) has been suggested as a marker of antemortem ingestion of alcohol, but EtG might degrade postmortem which could make interpretation difficult. So far, the published articles concern EtG only. Another nonoxidative metabolite, ethyl sulfate (EtS), which is more stable, has therefore been included in this study. We present a material of 36 deaths where postmortem formation of ethanol was suspected and where both EtG and EtS were measured in blood and urine to assist the interpretation. In 19 cases, EtG and EtS were positive in the body fluids analyzed. The median concentration of EtG and EtS in blood was 0.4 (range 0.1-23.2) and 0.9 mg/L (range 0.04-7.9), respectively. The median concentration of EtG and EtS in urine was 35.9 (range 1.0-182) and 8.5 mg/L (range 0.3-99), respectively. In another 16 cases, there was no trace of EtG or EtS in the specimens analyzed. In one case, there was inconsistency between the results of EtG and EtS; they were both positive in urine, while only EtS was positive in blood. This study showed that, out of 36 cases, antemortem ingestion of alcohol was very likely in 19 and unlikely in 16, according to EtG and EtS results. In the last case, the interpretation was more difficult. One possible explanation would be postmortem degradation of EtG in blood. PMID:19937334

  16. Ethyl glucuronide, ethyl sulfate, and ethanol in urine after intensive exposure to high ethanol content mouthwash.

    PubMed

    Reisfield, Gary M; Goldberger, Bruce A; Pesce, Amadeo J; Crews, Bridgit O; Wilson, George R; Teitelbaum, Scott A; Bertholf, Roger L

    2011-06-01

    To determine the degree of ethanol absorption and the resultant formation and urinary excretion of its conjugated metabolites following intensive use of high ethanol content mouthwash, 10 subjects gargled with Listerine(®) antiseptic 4 times daily for 3¼ days. First morning void urine specimens were collected on each of the four study days and post-gargle specimens were collected at 2, 4, and 6 h after the final gargle of the study. Urine ethanol, ethyl glucuronide (EtG), ethyl sulfate (EtS), and creatinine were measured. Ethanol was below the positive threshold of 20 mg/dL in all of the urine specimens. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (6 and 82 ng/mL; 16 and 83 ?g/g creatinine). Only one specimen contained detectable EtG (173 ng/mL; 117 ?g/g creatinine). EtS was detected in the urine of seven study subjects, but was not detected in the single specimen that had detectable EtG. The maximum EtS concentrations were 104 ng/mL and 112 ?g/g creatinine (in different subjects). Three subjects produced a total of eight (non-baseline) urinary EtS concentrations above 50 ng/mL or 50 ?g/g creatinine and three EtS concentrations exceeding 100 ng/mL or 100 ?g/g creatinine. In patients being monitored for ethanol use by urinary EtG and EtS concentrations, currently accepted EtG and EtS cutoffs of 500 ng/mL are adequate to distinguish between ethanol consumption and four times daily use of high ethanol content mouthwash. PMID:21619720

  17. Ethyl glucuronide excretion in humans following oral administration of and dermal exposure to ethanol.

    PubMed

    Rosano, Thomas G; Lin, Jing

    2008-10-01

    Ethyl glucuronide (EtG) is a direct ethanol biomarker and U.S. Department of Health and Human Services has advised that specificity studies at low EtG levels are needed for distinction of ethanol consumption and incidental exposure. The authors report urinary EtG excretion with ethanol abstinence, dermal exposure and oral consumption. EtG concentration by sensitive liquid chromatography-tandem mass spectrometry measurement in 39 urine specimens from adult alcohol abstainers (< 10-62 microg/L) and in urine from 13 children (< 10-80 microg/L) indicates either unrecognized ethanol exposure or endogenous ethanol metabolism. With repetitive daily dermal exposure to hand sanitizer (60% ethanol) by 9 adults, EtG concentration ranged from < 10 to 114 microg/L in 88 first-morning void specimens. EtG excretion following a 24 g ethanol drink by 4 adults revealed maximum urine EtG concentration (12,200-83,200 microg/L) at 3 to 8 h postdose and an EtG detection window up to 25-39 h, compared to an ethanol window of only 2 to 4 h. Oral ethanol use also showed an increase in the percent (molar equivalent) ethanol excreted as EtG with increasing oral ethanol doses. Human excretion studies show 1. EtG detectable at low concentration (< 100 microg/L) when ethanol use or exposures is not evident, 2. EtG concentration less than 120 microg/L in first morning specimens from adults with repeated dermal exposure to ethanol, 3. EtG levels maximally elevated within 3-8 h and above baseline for up to 39 h after a 24 g ethanol drink, and 4. a dose-dependent increase in the percentage of ethanol excreted as EtG with increasing oral ethanol use. PMID:19007508

  18. Validation of a headspace solid-phase microextraction–GC–MS\\/MS for the determination of ethyl glucuronide in hair according to forensic guidelines

    Microsoft Academic Search

    Ronald Agius; Thomas Nadulski; Hans-Gerhard Kahl; Johannes Schräder; Bertin Dufaux; Michel Yegles; Fritz Pragst

    2010-01-01

    The analysis of ethyl glucuronide (EtG) in hair is a powerful tool for chronic alcohol abuse control because of the typical wide detection window of the hair matrix and due to the possibility of segmentation, allowing evaluation of alcohol consumption in different periods. Additionally, EtG in hair is often the only diagnostic parameter of choice for alcohol abuse when other

  19. Levels of ethyl glucuronide and ethyl sulfate in oral fluid, blood, and urine after use of mouthwash and ingestion of nonalcoholic wine.

    PubMed

    Høiseth, Gudrun; Yttredal, Borghild; Karinen, Ritva; Gjerde, Hallvard; Christophersen, Asbjørg

    2010-03-01

    The aim of this study is to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid and both EtG and ethyl sulfate (EtS) in blood and urine following intense use of mouthwash and ingestion of nonalcoholic wine, which are proven to contain 3 mg/L EtG, 1.5 mg/L EtS, and 0.2 g/L ethanol. Twelve subjects participated in a controlled experiment. All subjects ingesting nonalcoholic wine showed urine samples negative for EtG but positive for EtS (Cmax 2.15 mg/L). All four subjects using mouthwash were negative for EtG and EtS in urine. All samples of oral fluid were negative for EtG and all samples of blood were negative for EtG and EtS. This study showed that ingestion of EtG and EtS as components of nonalcoholic wine lead to detection of urine EtS only, suggesting superior bioavailability of orally ingested EtS compared to EtG. This possibility of false-positive EtS results in urine after ingestion of nonalcoholic wine is important to remember when using EtG and EtS as relapse markers for alcohol. Finally, the study showed that a positive EtG or EtS result after accidental alcohol exposure is unlikely in blood and oral fluid. PMID:20223100

  20. Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse

    Microsoft Academic Search

    Peter Bendroth; Robert Kronstrand; Anders Helander; Jesper Greby; Nikolai Stephanson; Peter Krantz

    2008-01-01

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by

  1. SENSITIVITY AND SPECIFICITY OF URINARY ETHYL GLUCURONIDE AND ETHYL SULFATE IN LIVER DISEASE PATIENTS

    PubMed Central

    Stewart, Scott H.; Koch, David G.; Burgess, Douglas M.; Willner, Ira R.; Reuben, Adrian

    2012-01-01

    Background It is important to monitor alcohol use in the care of liver disease patients, but patient self-report can be unreliable. We therefore evaluated the performance of urine ethyl glucuronide (EtG) and ethyl sulfate (EtS) in detecting alcohol use in the days preceding a clinical encounter. Methods Subjects (n=120) were recruited at a university-based Hepatology clinic or during hospitalization. Alcohol consumption was ascertained by validated self-report measures. Urine EtG (cutoff 100 ng/mL) and EtS (cutoff 25 ng/mL) concentrations were assayed by a contracted laboratory using tandem mass spectrometry. The sensitivity and specificity of each biomarker in the detection of drinking during the 3 and 7 days preceding the clinic visit were determined, as well as the influence of liver disease severity on these results. Results Urine EtG (sensitivity 76%, specificity 93%) and urine EtS (sensitivity 82%, specificity 86%) performed well in identifying recent drinking, and liver disease severity does not affect biomarker performance. After elimination of one false negative self-report, urine EtG > 100 ng/mL was 100% specific for drinking within the past week, whereas 9% of the subjects without evidence of alcohol drinking for at least one week had EtS > 25 ng/mL. Conclusions Urine EtG and EtS can objectively supplement the detection of recent alcohol use in patients with liver disease. Additional research may determine optimal methods for integrating these tests into clinical care. PMID:22725265

  2. Voucher-based reinforcement for alcohol abstinence using the ethyl-glucuronide alcohol biomarker.

    PubMed

    McDonell, Michael G; Howell, Donelle N; McPherson, Sterling; Cameron, Jennifer M; Srebnik, Debra; Roll, John M; Ries, Richard K

    2012-01-01

    This study assessed the effects of a contingency management (CM) intervention for alcohol consumption in 10 alcohol-dependent participants. An ABCA design was used. Vouchers were provided contingent on results of ethyl glucuronide (EtG) urine tests (an alcohol biomarker with a 2-day detection period) and alcohol breath tests during the C phase. The percentage of negative urines was 35% during the first baseline phase, 69% during the C phase, and 20% during the return-to-baseline phase. Results suggest that EtG urine tests may be a feasible method to deliver CM to promote alcohol abstinence. PMID:22403460

  3. VOUCHER-BASED REINFORCEMENT FOR ALCOHOL ABSTINENCE USING THE ETHYL-GLUCURONIDE ALCOHOL BIOMARKER

    PubMed Central

    McDonell, Michael G; Howell, Donelle N; McPherson, Sterling; Cameron, Jennifer M; Srebnik, Debra; Roll, John M; Ries, Richard K

    2012-01-01

    This study assessed the effects of a contingency management (CM) intervention for alcohol consumption in 10 alcohol-dependent participants. An ABCA design was used. Vouchers were provided contingent on results of ethyl glucuronide (EtG) urine tests (an alcohol biomarker with a 2-day detection period) and alcohol breath tests during the C phase. The percentage of negative urines was 35% during the first baseline phase, 69% during the C phase, and 20% during the return-to-baseline phase. Results suggest that EtG urine tests may be a feasible method to deliver CM to promote alcohol abstinence. PMID:22403460

  4. ETHYL GLUCURONIDE — A MARKER OF ALCOHOL CONSUMPTION AND A RELAPSE MARKER WITH CLINICAL AND FORENSIC IMPLICATIONS

    Microsoft Academic Search

    FRIEDRICH MARTIN WURST; CHRISTOPH KEMPTER; STEPHAN SEIDL; ANDREAS ALT

    Ethyl glucuronide (EtG) is a non-volatile, water-soluble, direct metabolite of ethanol that can be detected in body fluids and hair. We investigated urine and serum samples from three patient groups: (1) 33 in-patients in acute alcohol withdrawal; (2) 30 detoxified in-patients (treated for at least 4 weeks) from a 'motivation station'; and (3) 43 neuro-rehabilitation patients (non-alcoholics; most of them

  5. An improved method to detect ethyl glucuronide in urine using reversed-phase liquid chromatography and pulsed electrochemical detection

    Microsoft Academic Search

    Romina Shah; William R. LaCourse

    2006-01-01

    Pulsed electrochemical detection (PED) following reversed-phase liquid chromatography (LC) has been applied recently to the detection of ethyl glucuronide (EtG) in the urine of live and deceased individuals. In this paper, several key improvements to the method are made to enhance sensitivity, reproducibility, and accuracy. These improvements include (i) further optimization of the sample preparation procedure that has increased the

  6. Influence of thermal hair straightening on ethyl glucuronide content in hair.

    PubMed

    Ettlinger, Jana; Kirchen, Luc; Yegles, Michel

    2014-06-01

    Hair analysis of ethyl glucuronide (EtG) has become a valuable marker for the detection of moderate and chronic alcohol consumption. It has been shown that bleaching and perming may decrease EtG content in hair. So far, no studies exist about the influence of thermal hair straightening on EtG content in hair. Forty-one positive EtG hair samples were treated in vitro with a hair straightener at 200°C. Duration of treatment of 1 min was chosen for this study. After washing, pulverization, incubation in ultrasonic bath, solid-phase extraction, and derivatization with heptafluorobutyric anhydride, EtG was determined by gas chromatography-mass spectrometry - negative ion chemical ionization (GC-MS-NICI). The EtG contents in straightened hair strands were then compared with those in the corresponding untreated strands. In 20 of 41 hair samples, a decrease of EtG content was found ranging from 0.7% to 79.3% (average 20%) whereas in 21 cases an increase was shown ranging from 2.0% to 50.9% (average 15%). The variation of the results seems to depend on hair colour. The decrease may be explained by thermic in vitro destruction of EtG. The increase may be explained by denaturation of the hair matrix by thermal treatment possibly causing a better extraction of EtG during incubation in ultrasonic bath. This in vitro study indicates that thermal hair straightening has an impact on the EtG content in hair. This has to be considered for a correct interpretation of EtG results in hair. However, these results should be confirmed by in vivo studies. PMID:24817051

  7. Development and validation of a gas chromatography–negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology

    Microsoft Academic Search

    Hicham Kharbouche; Frank Sporkert; Stéphanie Troxler; Marc Augsburger; Patrice Mangin; Christian Staub

    2009-01-01

    Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography–negative chemical ionization tandem mass spectrometry (GC–NCI-MS\\/MS) for the quantification of EtG in hair. EtG was extracted from about 30mg

  8. [Carbohydrate deficient transferrin and ethyl glucuronide: markers for alcohol use].

    PubMed

    Paling, Erik P; Mostert, Leendert J

    2013-01-01

    In this article, we report on the usefulness of physicians testing for carbohydrate deficient transferrin (CDT) and ethyl glucuronide (EtG) when there are doubts about alcohol use by their patients. A 44-year-old male consulted his general practitioner with depressive symptoms and denied using alcohol. Laboratory examination revealed an elevated CDT value. The latter was caused by chronic alcohol use. The second patient, a 32-year-old female with known alcohol dependence and receiving inpatient treatment at an addiction clinic, came back from leave. She denied having consumed alcohol and her blood alcohol concentration was zero. Examination of her urine showed an elevated EtG/creatinine ratio. This was caused by having had a few drinks during her leave and could not have been caused by using mouthwash or disinfection soap. We describe how to use the results of CDT and EtG testing in the therapeutic process and give recommendations for patient communication before performing these two tests. PMID:23739598

  9. Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake.

    PubMed

    Halter, Claudia C; Dresen, Sebastian; Auwaerter, Volker; Wurst, Friedrich M; Weinmann, Wolfgang

    2008-03-01

    The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51 +/- 0.17 g/kg, and blood and urine samples were analyzed for EtG and EtS simultaneously by chromatography-tandem mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9 +/- 1.3 and 2.8 +/- 1.6 micromol/l, respectively, and were reached between 4.0 +/- 0.9 h after the start of drinking (3.0 +/- 0.5 h for EtS). The mean time differences between reaching maximum blood ethanol levels and serum metabolite levels were 2.3 +/- 0.9 h for EtG and 1.2 +/- 0.5 h for EtS. In the last blood samples collected (10-11 h after the start of drinking), 11 (of 13) volunteers were still positive for EtG in serum, whereas only 2 were positive for EtS. In the serum of one female person, no EtS was detectable at any time; however, it was excreted in the urine in (low) concentrations. Ethanol was detectable in the serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak urinary concentrations were 401 +/- 232 micromol/l for EtG and 266 +/- 153 micromol/l for EtS, and mean peak levels were reached 6.2 +/- 0.9 h (EtG) and 5.3 +/- 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and EtS in serum showed a wide interindividual variation and could not be correlated to the maximum blood ethanol concentrations. Correlations (p < 0.001, Kendall's Tau b) were found when comparing pairs of parameters, but mostly involved areas under the curve (AUC) of metabolites or of ethanol; one correlation linked the peak concentrations of EtG and EtS in urine. PMID:17558515

  10. Ethyl glucuronide in hair - A highly effective test for the monitoring of alcohol consumption.

    PubMed

    Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Dufaux, Bertin

    2012-05-10

    In Germany drink driving offenders lose their license and must prove abstinence for one year in order to regain it. In this paper we assess the newly introduced ethyl glucuronide (EtG) tests in urine and hair in this alcohol abstinence monitoring. 20% (80 out of 386) of the 3cm long hair samples were tested positive for EtG in hair, compared to only 2% (92 out of 4248 samples) in urine in the same time period. Additionally 50% of the samples positive for EtG in hair had EtG values greater than 30pg/mg hair, indicating chronic alcohol consumption in the last three months. This study shows that four EtG tests in 3cm hair lengths reveal a significantly higher percentage of drink driving offenders who fail to be sober in the rehabilitation period, than do six random EtG tests in urine. Presumably, the hair test is more adequate to monitor long term alcohol abstinence than the urine test as defined by the new driving license re-granting medical and psychological assessment (MPA) in Germany. PMID:22019393

  11. A study of distribution of ethyl glucuronide in different keratin matrices.

    PubMed

    Pirro, V; Di Corcia, D; Pellegrino, S; Vincenti, M; Sciutteri, B; Salomone, A

    2011-07-15

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol, frequently used as a biomarker of alcohol abuse. To this purpose, EtG is preferentially determined in hair samples, using a cut-off value of 30pg/mg to discriminate between social and heavy drinkers, as recently fixed by an international consensus conference. Although this cut-off value is assumed for head hair, alternative matrices, such as pubic, axillary and chest hair, are often analyzed when head hair is not available. Previous studies suggested that determination of EtG in various keratin matrices may lead to different results; growth cycle and rate, urine contamination, distribution of sebum glands and other environmental factors are likely to contribute to these differences. We analyzed more than 2700 samples (head, pubic, chest and axillary hair) to evaluate the inter- and intra-individual distribution of the EtG concentration in the different keratin matrices. The data were interpreted on a statistical basis, on the assumption that large population data-sets will level off the average alcohol consumption of each group. From both inter- and intra-individual distribution data, significant differences were observed in EtG concentrations recorded in head, axillary and pubic hair samples. It is concluded that pubic hair cannot be utilized alternatively to head hair to prove chronic alcohol abuse, nor is axillary hair, since positive and negative biases respectively affect these determinations. In contrast, for chest hair, EtG distributions similar to head hair were found, although the large discrepancy between the examined population dimensions presently prevents any definitive conclusion. Thus, chest hair represents a promising alternative to head hair for EtG determinations, deserving further investigation on samples collected from the same individuals, in order to establish a clear correlation between their respective EtG concentrations. PMID:21511419

  12. Urine tested positive for ethyl glucuronide and ethyl sulphate after the consumption of "non-alcoholic" beer.

    PubMed

    Thierauf, Annette; Gnann, Heike; Wohlfarth, Ariane; Auwärter, Volker; Perdekamp, Markus Grosse; Buttler, Klaus-Juergen; Wurst, Friedrich M; Weinmann, Wolfgang

    2010-10-10

    In abstinence maintenance programs, for reissuing the driving licence and in workplace monitoring programs abstinence from ethanol and its proof are demanded. Various monitoring programs that mainly use ethyl glucuronide (EtG) as alcohol consumption marker have been established. To abstain from ethanol, but not from the taste of alcoholic beverages, in particular non-alcoholic beer has become more and more popular. In Germany, these "alcohol-free" beverages may still have an ethanol content of up to 0.5vol.% without the duty of declaration. Due to severe negative consequences resulting from positive EtG tests, a drinking experiment with 2.5L of non-alcoholic beer per person was performed to address the question of measurable concentrations of the direct metabolites EtG and EtS (ethyl sulphate) in urine and blood. Both alcohol consumption markers - determined by LC-MS/MS - were found in high concentrations: maximum concentrations in urine found in three volunteers were EtG 0.30-0.87mg/L and EtS 0.04-0.07mg/L, i.e., above the often applied cut-off value for the proof of abstinence of 0.1mg EtG/L. In the urine samples of one further volunteer, EtG and EtS concentrations cumulated over-night and reached up to 14.1mg/L EtG and 16.1mg/L EtS in the next morning's urine. Ethanol concentrations in blood and urine samples were negative (determined by HS-GC-FID and by an ADH-based method). PMID:20457499

  13. Hair Ethyl Glucuronide is Highly Sensitive and Specific for Detecting Moderate-to-Heavy Drinking in Patients with Liver Disease

    PubMed Central

    Stewart, Scott H.; Koch, David G.; Willner, Ira R.; Randall, Patrick K.; Reuben, Adrian

    2013-01-01

    Aims: Hair ethyl glucuronide (EtG) is a promising biomarker of moderate-to-heavy alcohol consumption and may have utility in detecting and monitoring alcohol use in clinical populations where alcohol use is of particular importance. This study evaluated the relationship between hair EtG and drinking in patients with liver disease. Methods: The subjects (n = 200) were patients with liver disease who presented for care at a university medical center. Alcohol use during the 3 months preceding participation in the study was assessed, and a sample of hair was obtained for EtG testing. Classification of drinking status (any drinking or averaging at least 28 g per day) by hair EtG was evaluated, as well as the effects of liver disease severity and demographic and hair care factors. Results: The area under the receiver operating characteristic curve for detecting an average of 28 g or more per day during the prior 90 days was 0.93. The corresponding sensitivity and specificity of hair EtG ?8 pg/mg for averaging at least 28 g of ethanol per day were 92 and 87%, respectively. Cirrhosis and gender may have a modest influence on the relationship between drinking and hair EtG. Conclusion: Hair EtG was highly accurate in differentiating subjects with liver disease averaging at least 28 g of ethanol per day from abstainers and lighter drinkers. PMID:23015609

  14. Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse.

    PubMed

    Bendroth, Peter; Kronstrand, Robert; Helander, Anders; Greby, Jesper; Stephanson, Nikolai; Krantz, Peter

    2008-03-21

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD; LOQ, 0.22 micromol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (> or = 30 pg/mg) compared with 29 for PEth (> or = 0.7 micromol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse. PMID:18023314

  15. Quantitation of ethyl glucuronide in serum & urine by gas chromatography - mass spectrometry

    PubMed Central

    Sharma, Priyamvada; Bharat, Venkatesh; Murthy, Pratima

    2015-01-01

    Background & objectives: Alcohol misuse has now become a serious public health problem and early intervention is important in minimizing the harm. Biochemical markers of recent and high levels of alcohol consumption can play an important role in providing feedback regarding the health consequences of alcohol misuse. Existing markers are not sensitive to recent consumption and in detecting early relapse. Ethyl glucuronide (EtG), a phase-II metabolite of ethanol is a promising marker of recent alcohol use and can be detected in body fluids. In this study an analytical technique for quantitation of EtG in body fluids using solid-phase extraction (SPE) and gas chromatography (GC) with mass spectrometric detection (MS) was developed and validated. Methods: De-proteinization of serum and urine samples was done with perchloric acid and hydrochloric acid, respectively. Serum samples were passed through phospholipids removal cartridges for further clean up. EtG was isolated using amino propyl solid phase extraction columns. Chromatographic separation was achieved by gas chromatography with mass spectrometry. Results: Limit of detection and limit of quantitation were 50 and 150 ng/ml for urine and 80 and 210 ng/ml for serum, respectively. Signal to noise ratio was 3:1, mean absolute recovery was 80-85 per cent. Significant correlation was obtained between breath alcohol and serum EtG levels (r=0.853) and urine EtG and time since last abuse (r = -0.903) in clinical samples. Interpretation & conclusions: In the absence of other standardized techniques to quantitate EtG in biological samples, this GC-MS method was found to have high throughput and was sensitive and specific. PMID:25857498

  16. A high-performance liquid chromatographic-tandem mass spectrometric method for the determination of ethyl glucuronide and ethyl sulfate in urine validated according to forensic guidelines.

    PubMed

    Albermann, M E; Musshoff, F; Madea, B

    2012-01-01

    Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are powerful markers for alcohol intake and abuse. Several analytical procedures for the quantification of EtG and EtG in serum and urine have been developed so far. Many of the published methods show limits of detections (LODs) or limits of quantifications (LOQs) for EtG in urine within the range of 0.1 mg/L or higher. Since this is the actual cutoff value for proving abstinence in Germany, problems may occur if urine samples are highly diluted. In this paper, the validation of a highly sensitive, fast and simple LC-MS-MS for the determination of EtG and EtS in urine is described. The calibration curves for EtG and EtS is linear over the whole range (0.025-2.0 mg/L). Very low detection limits can be achieved (LOD: EtG 0.005 mg/L, EtS 0.005 mg/L; and LOQ: EtG 0.019 mg/L, EtS 0.015 mg/L). All data for selectivity, precision and accuracy, recovery, as well as for the processed sample and the freeze/thaw stability, comply with the guidelines of the German Society of Toxicological and Forensic Chemistry. Strong matrix-related effects can be compensated for by using an internal standard. Finally, the applicability of the procedure is proven by analysis of 87 human urine samples and by successful participation in interlaboratory comparison tests. PMID:22291056

  17. A High-Performance Liquid Chromatographic–Tandem Mass Spectrometric Method for the Determination of Ethyl Glucuronide and Ethyl Sulfate in Urine Validated According to Forensic Guidelines

    PubMed Central

    Albermann, M.E.; Musshoff, F.; Madea, B.

    2012-01-01

    Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are powerful markers for alcohol intake and abuse. Several analytical procedures for the quantification of EtG and EtG in serum and urine have been developed so far. Many of the published methods show limits of detections (LODs) or limits of quantifications (LOQs) for EtG in urine within the range of 0.1 mg/L or higher. Since this is the actual cutoff value for proving abstinence in Germany, problems may occur if urine samples are highly diluted. In this paper, the validation of a highly sensitive, fast and simple LC–MS–MS for the determination of EtG and EtS in urine is described. The calibration curves for EtG and EtS is linear over the whole range (0.025–2.0 mg/L). Very low detection limits can be achieved (LOD: EtG 0.005 mg/L, EtS 0.005 mg/L; and LOQ: EtG 0.019 mg/L, EtS 0.015 mg/L). All data for selectivity, precision and accuracy, recovery, as well as for the processed sample and the freeze/thaw stability, comply with the guidelines of the German Society of Toxicological and Forensic Chemistry. Strong matrix-related effects can be compensated for by using an internal standard. Finally, the applicability of the procedure is proven by analysis of 87 human urine samples and by successful participation in interlaboratory comparison tests. PMID:22291056

  18. Ethyl glucuronide and ethyl sulfate in urine after consumption of various beverages and foods--misleading results?

    PubMed

    Musshoff, Frank; Albermann, Elena; Madea, Burkhard

    2010-11-01

    Urine testing for ethyl glucuronide (EtG) is used to spot recent alcohol intake and is utilized to document alcohol abstinence. However, other possible sources of ethanol existed when special beverages or foods were ingested. EtG concentration curves in urine were measured after the consumption of non-alcoholic beers, fruit juices, sauerkraut, and matured bananas. Using a cutoff of 0.1 mg/l, positive EtG findings were revealed after the ingestion of a lot of non-alcoholic beer up to 13 h later, sauerkraut up to 5 h later, and matured bananas up to 3.5 h later. In German abstinence programs, subjects have to deliver a urine sample within 24 h after advice, and all participants are informed about possible misleading results caused by the consumption of certain beverages or foods. With respect to the present results, a 0.1 mg/l cutoff can be considered useful, and misleading results should not be expected from informed subjects within a 24-h waiting period. PMID:20838803

  19. Urinary concentrations of ethyl glucuronide and ethyl sulfate as thresholds to determine potential ethanol-induced alteration of steroid profiles.

    PubMed

    Thieme, D; Grosse, J; Keller, L; Graw, M

    2011-01-01

    The suppression of steroid biotransformation resulting in a decrease of the major urinary metabolites--androsterone and etiocholanolone--and the elevation of testosterone/epitestosterone (T/E) ratios following ethanol administration is well described. At least the latter parameter T/E represents an important indicator for endogenous steroid abuse in doping control. The quantitative correlation between ethanol consumption markers and steroid profile alteration was evaluated, aiming to differentiate between permitted ethanol administration and potential steroid abuse. Steroid profiles, ethanol, ethyl glucuronide (EtG), and sulfate (EtS) were quantified after administration of ethanol (intended maximum ethanol concentration in blood was 1 mg/g) to 21 male and 15 female volunteers. EtG concentrations in urine (corrected by either specific gravity or creatinine concentration) were found to be most suitable for quantitative evaluations. Gender specific urinary EtG concentrations of 48 ug/ml (men) and 15.5 ug/ml (women) may be considered as useful thresholds for a potential ethanol-induced suppression of steroids biotransformation. PMID:22213685

  20. A novel and an effective analytical approach for the LC-MS determination of ethyl glucuronide and ethyl sulfate in urine.

    PubMed

    Favretto, Donata; Nalesso, Alessandro; Frison, Giampietro; Viel, Guido; Traldi, Pietro; Ferrara, Santo Davide

    2010-03-01

    An alternative liquid chromatography-mass spectrometry (LC-MS) method based on no discharge (ND) atmospheric pressure chemical ionization (APCI) was developed for the simultaneous determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine in negative ion conditions. Abundant [M-H](-) species of EtG and EtS were obtained, allowing to reach limits of quantification (0.1 microg/ml for both analytes), accuracy, and precision comparable to those proposed in the literature. Additionally, the LC-ND-APCI-MS method proved to be reliable, requiring little maintenance even when high throughput analyses (i.e., 6,000 samples per year) were required. PMID:19859726

  1. Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage.

    PubMed

    Wright, Trista H; Ferslew, Kenneth E

    2012-03-01

    Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration. This study was undertaken to determine if the Sprague-Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol. SD rats (male, n=6) were gavaged with a single ethanol dose (4 g/kg), and urine was collected for 3 h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay. Blood and urine ethanol concentrations were 195±23 and 218±19 mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98 ng equivalents/mL and 210±0.29 mg equivalents/dL (X ± standard error of the mean [S.E.M.]). Sixty-six male SD rats were gavaged ethanol (4 g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24 h after administration for ethanol and EtG analysis. Maximum blood ethanol, urine ethanol, and UEtG were reached within 4 h, whereas maximum BEtG was reached 6 h after administration. Maximum concentrations were blood ethanol, 213±20 mg/dL; urine ethanol, 308±34 mg/dL; BEtG, 2,683±145 ng equivalents/mL; UEtG, 1.2±0.06 mg equivalents/mL (X±S.E.M.). Areas under the concentration-time curve were blood ethanol, 1,578 h*mg/dL; urine ethanol, 3,096 h*mg/dL; BEtG, 18,284 h*ng equivalents/mL; and UEtG, 850 h*mg equivalents/dL. Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18 h after ethanol administration. Urine ethanols were below LOD at 18 h, but UEtG was still detectable at 24h after administration. Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it is similar to that of the human. PMID:22019193

  2. A pharmacokinetic study of ethyl glucuronide in blood and urine: applications to forensic toxicology.

    PubMed

    Høiseth, Gudrun; Bernard, Jean Paul; Karinen, Ritva; Johnsen, Lene; Helander, Anders; Christophersen, Asbjørg S; Mørland, Jørg

    2007-10-25

    This pharmacokinetic study investigated the kinetics of ethanol and its metabolite ethyl glucuronide (EtG) in blood and urine during the whole time course of absorption and elimination. There are few previous studies on the kinetics of EtG in blood, and we wanted to evaluate whether such knowledge could yield valuable information regarding the time of ethanol ingestion in forensic cases, such as, for instance, drunk driving. Ten male volunteers consumed ethanol at a fixed dose of 0.5 g/kg body weight in a fasted state. Blood samples were collected for 14 h and urine samples were collected for 45-50 h after the start of drinking. EtG reached its maximum concentration (C(max)) in blood after a median of 4 h (range 3.5-5), a median of 3 h (range 2-4.5) after C(max) for ethanol. The ethanol-to-EtG ratios in blood (ethanol in g/L, EtG in mg/L) were >1 only for the first median 3.5 h (range 2.5-3.5) after drinking. EtG elimination occurred with a median half-life of 2.2 h (range 1.7-3.1 h), and the renal clearance was 8.32 L/h (median, range 5.25-20.86). The concentrations of EtG were always much higher in urine than in blood. The total amount of EtG excreted in the urine was median 30 mg (range 21.5-39.7), representing 0.017% (median, range 0.013-0.022) of the ethanol given, on a molar basis. The information from the present study may be a valuable supplement to determine the time of ethanol ingestion. For this purpose, two subsequent increasing EtG values and a high ethanol-to-EtG ratio in blood would support information of recent drinking. PMID:17306943

  3. An evaluation of washing and extraction techniques in the analysis of ethyl glucuronide and fatty acid ethyl esters from hair samples.

    PubMed

    Bossers, L C A M; Paul, R; Berry, A J; Kingston, R; Middendorp, C; Guwy, A J

    2014-03-15

    Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are alcohol metabolites measured in hair and are after a decade of research thought to be the best markers in hair to indicate alcoholism and abstinence Forensic Sci. Int. 218 (2012) 2. A great body of work concerning EtG and FAEEs detection in hair has been performed. However, no recent extensive comparison has been made concerning washing and extraction procedures. This work shows that the washing procedure of dichloromethane followed by a methanol rinse of the hair sample removes more than 16% of the FAEEs and 50% of the total EtG that is present in and on the hair. A review of ten washing protocols (where the removal is categorised: high, medium or low) showed that a relatively high percentage of FAEEs was removed and "medium" amount of EtG compared to the other washing protocols. This work shows promising results for the extraction of the FAEEs and the combined extraction of FAEEs and EtG by using 30min of sonication with methanol. More FAEEs were recovered from hair with methanol than with any other extraction solvent including the commonly used dimethyl sulfoxide/heptane mixture. When the sonication time was increased a higher percentage of transesterification of the FAEEs was observed, the extraction was "dirtier" as solids and a colour change was observed whereas the extraction efficiency did not increase. Therefore, washing the hair sample with dichloromethane and methanol followed by an addition of 1ml of methanol and sonication for 30min to extract the FAEEs and EtG from hair is recommended for FAEEs as well as for the combined analysis of EtG and FAEEs. A linear calibration curve (r(2)>0.99) was obtained for all analytes. PMID:24590191

  4. Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment.

    PubMed

    Albermann, Maria Elena; Musshoff, Frank; Doberentz, Elke; Heese, Peter; Banger, Markus; Madea, Burkhard

    2012-09-01

    Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are commonly used alcohol markers for previous alcohol consumption. Nevertheless, the optimum EtG cutoff for urinary abstinence tests is still being discussed, and no cutoff has been recommended for EtS yet. The aim of this study was to verify cutoffs by investigating EtG and EtS concentrations (c(EtG) and c(EtS)) in the urine of healthy persons after drinking small, but realistic amounts of alcohol (one or two glasses of beer or white wine), and to look for the window of detection in strongly alcohol-intoxicated patients who were beginning withdrawal treatment. Very high EtG and EtS concentrations were measured in the first urine samples of patients under withdrawal treatment. However, 24 h later, concentrations decreased considerably, and c (EtG)?EtG) and 0.05 mg/l (EtS) were measured for 23.5 and 20.5 h after consuming 0.1 l of white wine or 0.33 l of beer, and 24 h after the experiment, 75 % (9/12) of the urine samples were tested negative for EtG and EtS using the following cutoffs: EtG 0.5 mg/l and EtS 0.1 mg/l. In half of the samples, concentrations below 0.1 mg/l (EtG) and 0.05 mg/l (EtS) were detected. Urinary cutoffs for EtG of 0.5 mg/l or higher are not suitable for testing abstinence. Even 0.1 mg/l is not effective to detect the intake of small amounts of alcohol in the context of abstinence tests. For EtS, 0.05 mg/l were found to be a potential cutoff to exclude the repeated intake of alcohol. Yet, further research is required to verify this cutoff. For a limited time period, EtG and EtS concentrations within the range of these cutoffs are also detectable after unintentional consumption of alcohol. Participants of abstinence programs have to be informed about the alcohol content of certain foods and beverages whose consumption is in conflict with strict abstinence. PMID:22752748

  5. Utility of urinary ethyl glucuronide analysis in post-mortem toxicology when investigating alcohol-related deaths.

    PubMed

    Sundström, M; Jones, A W; Ojanperä, I

    2014-08-01

    Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181 cases, ethanol was negative in urine (<0.2 g/kg), whereas EtG was positive (>0.5 mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2 mg/L and 23.7 mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated. PMID:24954799

  6. Ethyl sulphate and ethyl glucuronide in vitreous humor as postmortem evidence marker for ethanol consumption prior to death.

    PubMed

    Thierauf, Annette; Kempf, Jürgen; Perdekamp, Markus Grosse; Auwärter, Volker; Gnann, Heike; Wohlfarth, Ariane; Weinmann, Wolfgang

    2011-07-15

    To clarify the circumstances of death, the degree of inebriation is of importance in many cases, but for several reasons the determination of the ethanol concentration in post-mortem samples can be challenging and the synopsis of ethanol and the direct consumption markers ethyl glucuronide (EtG) and ethyl sulphate (EtS) has proved to be useful. The use of a rather stable matrix like vitreous humor offers further advantages. The aim of this study was to determine the concentrations of ethanol and the biomarkers in the robust matrix of vitreous humor and to compare them with the respective levels in peripheral venous blood and urine. Samples of urine, blood from the femoral vein and vitreous humor were taken from 26 deceased with suspected ethanol consumption prior to death and analyzed for ethanol, EtS and EtG. In the urine samples creatinine was also determined. The personal data, the circumstances of death, the post-mortem interval and the information about ethanol consumption prior to death were recorded. EtG and EtS analysis in urine was performed by LC-ESI-MS/MS, creatinine concentration was determined using the Jaffé reaction and ethanol was detected by HS-GC-FID and by an ADH-based method. In general, the highest concentrations of the analytes were found in urine and showed statistical significance. The mean concentrations of EtG were 62.8mg/L (EtG100 206.5mg/L) in urine, 4.3mg/L in blood and 2.1mg/L in vitreous humor. EtS was found in the following mean concentrations: 54.6mg/L in urine (EtS100 123.1mg/L), 1.8mg/L in blood and 0.9mg/L in vitreous humor. Ethanol was detected in more vitreous humor samples (mean concentration 2.0g/kg) than in blood and urine (mean concentration 1.6g/kg and 2.1g/kg respectively). There was no correlation between the ethanol and the marker concentrations and no statistical conclusions could be drawn between the markers and matrices. PMID:21367549

  7. Ethyl glucuronide concentrations in two successive urinary voids from drinking drivers: relationship to creatinine content and blood and urine ethanol concentrations

    Microsoft Academic Search

    J Bergström; A Helander; A. W Jones

    2003-01-01

    The concentrations of alcohol in blood (BAC) and two successive urine voids (UAC) from 100 drunk drivers were compared with the concentration of ethyl glucuronide (EtG), a minor metabolite of ethanol in urine, and the urinary creatinine content as an indicator of dilution. The subjects consisted of 87 men with mean age 42.2±14.2 years (±standard deviation, S.D.) and 13 women

  8. Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases.

    PubMed

    Suesse, S; Pragst, F; Mieczkowski, T; Selavka, C M; Elian, A; Sachs, H; Hastedt, M; Rothe, M; Campbell, J

    2012-05-10

    This article presents results from 1872 hair samples, which were analyzed for fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG). The results were evaluated in the context of self-reported drinking behavior, the use of hair cosmetics, the gender of the sample donors and hair sample length. For comparison, CDT and GGT in serum were available in 477 and 454 cases, respectively. A number of alcohol abstainers or low moderate drinkers and excessive drinkers were selected for assessment of cut-offs for FAEEs in the proximal 6cm hair segments and for EtG in the proximal 3cm hair segments. Cut-off values were assessed by ROC analysis. It was found that the cut-offs of 1.0ng/mg FAEE and 30pg/mg EtG presently used for excessive drinking lead to a low portion of false positives (4% and 3% respectively) but to a higher portion of false negatives (23% and 25% respectively). Comparison of the mean and medium concentrations in samples without any reported hair cosmetics (N=1079) and in samples with reported use of hair spray (N=79) showed an increase by the factor of about two for FAEE but no significant difference for EtG. Mean values of EtG were decreased by 80% in bleached samples (N=164) and by 63% in dyed samples (N=96). There was no significant effect of bleaching and dyeing on FAEE. Hair gel and hair wax, oil or grease showed no significant effect on both FAEE and EtG. With respect to gender and investigated hair length ambiguous results were obtained because of major differences in the compared subpopulations of male with higher alcohol consumption and mainly shorter hair, and less drinking female with longer hair. For excessive drinkers FAEEs in the 0-6cm hair segment and EtG in the 0-3cm segment decreased with increasing time of reported abstinence before sample collection. These drinkers attain the level of teetotalers only after more than 10 months of abstinence. In comparison to scalp hair, FAEEs recovered from armpit hair and leg hair were lower and from chest hair were higher. EtG in armpit hair was lower and in leg hair higher than in scalp hair. It is concluded that the combined use of FAEE and EtG essentially increases the accuracy of interpretation since both markers complement each other by a different sensitivity to sources of error. PMID:22036309

  9. Comparison of analytical approaches for liquid chromatography/mass spectrometry determination of the alcohol biomarker ethyl glucuronide in urine.

    PubMed

    Helander, Anders; Kenan, Naama; Beck, Olof

    2010-06-30

    Official guidelines originating from a European Union directive regulate requirements for analytical methods used to identify chemical compounds in biological matrices. This study compared different liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) and tandem mass spectrometry (LC/ESI-MS/MS) procedures for accurate determination of the conjugated ethanol metabolite and alcohol biomarker ethyl glucuronide (EtG) in urine, and the value of combined EtG and ethyl sulfate (EtS) measurement. Analysis was carried out on 482 urines following solid-phase extraction (SPE) sample cleanup or using direct injection of a diluted sample. SPE combined with LC/MS/MS was demonstrated to be the most selective and sensitive method and was chosen as reference method. The EtG results by different methods showed good correlation (r = 0.96-0.98). When comparing five reporting limits for EtG in the range 0.10-1.00 mg/L, the overall agreement with the reference method (frequency of true positives plus true negatives) was 82-97% for direct-injection LC/MS/MS, 90-97% for SPE-LC/MS, 86-98% for direct-injection LC/MS, and 86-98% for direct-injection LC/MS analysis of EtG and EtS. Most deviations were attributable to uncertainty in quantitation, when the value was close to a cutoff but the respective results were slightly above and below, or vice versa, the critical limit. However, for direct-injection LC/MS/MS, despite earning 4 identification points, equally many negative results were due to a product ion ratio outside the +/-20% deviation accepted by the guidelines. These results indicate that the likelihood of different analytical methods to provide reliable analytical results depends on the reporting limit applied. PMID:20499317

  10. COMPARISON BETWEEN THE URINARY ALCOHOL MARKERS EtG, EtS, AND GTOL\\/5HIAA IN A CONTROLLED DRINKING EXPERIMENT

    Microsoft Academic Search

    GUDRUN HØISETH; JEAN PAUL BERNARD; NICOLAI STEPHANSON; PER T. NORMANN; ASBJØRG S. CHRISTOPHERSEN; ANDERS HELANDER

    Aim: Urinary ethyl glucuronide (EtG), ethyl sulfate (EtS), and the ratio between 5-hydroxytryptophol-glucuronide and 5-hydroxyindole-3-acetic acid (GTOL\\/5-HIAA) are all suggested as biomarkers for recent alcohol ingestion with longer detection times than measurement of ethanol itself. The aim of this controlled study was to compare the sensitivities and detection times of EtG, EtS, and GTOL\\/5-HIAA, after a single ingestion of ethanol.

  11. Microwave assisted extraction for the determination of ethyl glucuronide in urine by gas chromatography-mass spectrometry.

    PubMed

    Freire, Iván Alvarez; Barrera, Ana María Bermejo; Silva, Purificación Cid; Duque, María Jesús Tabernero; Gómez, Purificación Fernández; Eijo, Patricia López

    2008-08-01

    Alcohol is the most frequently abused 'addictive substance' that causes serious social problems throughout the world; thus alcoholism is of particular interest in clinical and forensic medicine. Ethyl glucuronide (EtG) is a marker of recent alcohol consumption that detects alcohol use reliably over a definite time period. The present paper describes a new method for the determination of EtG in urine. It was based both on microwave assisted extraction (MAE) to extract the analyte from urine samples, and gas chromatography-mass spectrometry (GC-MS) to identify and quantify the EtG in selected ion monitoring (SIM) mode. The method was applied to 33 urine samples from alcohol users, obtaining positive results in all cases. It was fully validated including a linear range (0.1-100 microg ml(-1)) and the main precision parameters. In summary, the use of microwave assisted extraction turned out to be a substantially simpler, faster and more sensitive procedure than any other conventional sample preparations. PMID:18344200

  12. [Determination of ethyl glucuronide in human urine by solid phase extraction-gas chromatography-mass spectrometry].

    PubMed

    Yu, Tianxiao; Li, Qing; Wan, Tao; Li, Jianbo; Ding, Shijia

    2011-02-01

    A solid phase extraction (SPE) and gas chromatography (GC) with mass spectrometry (MS) method for determination of ethyl glucuronide (EtG) in human urine was established. One mL urine sample was deproteinated by 100 microL 3 mol/L hydrochloric acid and cleaned up through a solid phase extraction column. The target analytes were eluted from an NH2-column with 4% ammonia solution and then treated with bis (trimethylsilyl) trifluoroacetamide (BSTFA) + trimethylchlorosilane (TMCS) (99:1) for derivatization. The derivatized samples were analyzed by GC-MS. Data were acquired in the selected ion monitoring (SIM) mode and the quantitation of EtG was done through internal standard method. Good linearity was obtained at the mass concentration range of 0.1 - 3.2 mg/L with a correlation coefficient (r) of 0.9921. The limit of detection (LOD) was 28.4 microg/L. The range of recoveries was 92.5% - 108.7%, and the relative standard deviations (RSDs) of intra-day and inter-day were all less than 5%. This method is sensitive, specific, accurate and can be applied to the determination of EtG for medicolegal identification and clinical laboratory. PMID:21598520

  13. Degradation of the ethyl glucuronide content in hair by hydrogen peroxide and a non-destructive assay for oxidative hair treatment using infra-red spectroscopy.

    PubMed

    Ammann, Dominic; Becker, Roland; Kohl, Anka; Hänisch, Jessica; Nehls, Irene

    2014-11-01

    The assessment of quantification results of the alcohol abuse marker ethyl glucuronide (EtG) in hair in comparison to the cut-off values for the drinking behavior may be complicated by cosmetic hair bleaching. Thus, the impact of increasing exposure to hydrogen peroxide on the EtG content of hair was investigated. Simultaneously, the change of absorbance in the range of 1000-1100 cm(-1) indicative for the oxidation of cystine was investigated non-destructively by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) using pulverized portions of the respective hair samples. Hair samples treated with hydrogen peroxide consistently displayed a significantly increased absorbance at 1040 cm(-1) associated with the formation of cysteic acid. The EtG content decreased significantly if the hair was treated with alkaline hydrogen peroxide as during cosmetic bleaching. It could be shown that ATR-FTIR is capable of detecting an exposure to hydrogen peroxide when still no brightening was visible and already before the EtG content deteriorated significantly. Thus, hair samples suspected of having been exposed to oxidative treatment may be checked non-destructively by a readily available technique. This assay is also possible retrospectively after EtG extraction and using archived samples. PMID:25180828

  14. Ethyl glucuronide concentrations in oral fluid, blood, and urine after volunteers drank 0.5 and 1.0 g/kg doses of ethanol.

    PubMed

    Høiseth, Gudrun; Yttredal, Borghild; Karinen, Ritva; Gjerde, Hallvard; Mørland, Jørg; Christophersen, Asbjørg

    2010-01-01

    The aim of this study was to investigate the concentrations of ethyl glucuronide (EtG) in oral fluid, blood, and urine after healthy volunteers drank two doses of ethanol, 0.5 (n = 11) and 1.0 g/kg (n = 10), after an overnight fast. Samples of oral fluid, blood, and urine were collected before drinking started and at 1.5, 3.5, 5.5, 8.5, 11.5, and 24 h post-dosing. Following ingestion of low dose of ethanol, the Cmax for EtG was 0.36 mg/L (range 0.28-0.41 mg/L) in blood and 69.8 mg/L (range 47.1-96.5 mg/L) in urine. In oral fluid, the concentrations were < 1% of those in blood, and only three subjects exceeded the limit of quantification for EtG in oral fluid. After ingestion of the high dose of ethanol, the Cmax for EtG was 1.06 mg/L (range 0.8-1.22 mg/L) in blood, 159.9 mg/L (range 97.2-225.5 mg/L) in urine, and 0.032 mg/L (range 0.013-0.059 mg/L) in oral fluid. The median oral fluid/blood ratio was 0.029 (range 0.012-0.054) for EtG. The detection time for EtG was median 11.5 h (range 3.5-11.5 h) in oral fluid. According to this, the detection time for EtG in oral fluid is therefore only a few hours longer than for ethanol itself and represents limited additional value. PMID:20663284

  15. Direct determination of ethyl glucuronide and ethyl sulfate in postmortem urine specimens using hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Al-Asmari, Ahmed I; Anderson, Robert A; Appelblad, Patrik

    2010-06-01

    This work was aimed at developing and validating a hydrophilic interaction chromatography (HILIC)-electrospray ionization (ESI)-ion trap-tandem mass spectrometric method for identification and quantification of ethyl glucuronide (ETG) and ethyl sulfate (ETS) as ethanol biomarkers and at employing this method for analysis of postmortem urine samples. Analytes of interest were separated on a ZIC-HILIC column (150 x 2.1 mm, 3.5 microm) connected to a Thermo Finnigan LCQ Deca Plus liquid chromatographic- tandem mass spectrometric instrument operated in the ESI-selected reaction monitoring mode. Seventy-nine urine case samples were divided into three groups depending on the ethanol concentration found in blood and analyzed by the developed method: group A with postmortem blood ethanol concentrations higher than 200 mg/100 mL; group B with ethanol concentrations in the range 80-200 mg/100 mL; and group C with ethanol concentrations in the range 10-80 mg/100 mL. ETG and ETS had high recoveries of 98-99%, and the HILIC column produced fine, sharp peak shapes and achieved baseline separation in less than 7 min. Both ethanol markers were detected in all groups with overall median concentrations of 100 and 23 mg/L for ETG and ETS, respectively. It can be concluded that the potential for postmortem production of alcohol increased in the low ethanol concentration group as several cases tested negative for both biomarkers in group C. ETG was detected at low concentrations in some cases for which ETS tested negative. Although ETS is stable after being subjected to many stability conditions, the use of ETS as sole evidence of alcohol ingestion may lead to a false-negative result, as we noticed in groups A and C in the present study. The use of ETG is a more reliable ethanol biomarker. Both ethanol biomarkers should be determined in heavily putrefied cases and when the ethanol concentration in postmortem blood is low. PMID:20529460

  16. Detection of ethyl glucuronide in dried human blood using LCMS\\/MS

    Microsoft Academic Search

    Eckhard Kaufmann; Andreas Alt

    2008-01-01

    Ethyl glucuronide, as a direct metabolite of ethanol degradation, has proven useful as a long-term marker in many forensic\\u000a applications. The inability to determine ethyl glucuronide in dried blood left a missing link in many investigations. Here,\\u000a we describe a new method based on mass spectrometry in a Pauli-type ion trap in order to determine this substance in dried\\u000a blood

  17. Clinical Application of Ethyl Glucuronide Testing in the U.S. Army

    Microsoft Academic Search

    R. Gregory Lande; Barbara Marin; Audrey S. Chang

    2010-01-01

    This study examined the clinical characteristics of ethyl glucuronide testing among service members referred to a military substance abuse program. The authors analyzed 1,852 urine specimens from 328 service members collected over a two year period. Among all participants, approximately one-fifth (n = 45\\/262, 17.2%) produced a positive ethyl glucuronide result at the initial assessment. Nearly two-thirds (n = 29\\/45,

  18. Validation of a headspace solid-phase microextraction-GC-MS/MS for the determination of ethyl glucuronide in hair according to forensic guidelines.

    PubMed

    Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Schräder, Johannes; Dufaux, Bertin; Yegles, Michel; Pragst, Fritz

    2010-03-20

    The analysis of ethyl glucuronide (EtG) in hair is a powerful tool for chronic alcohol abuse control because of the typical wide detection window of the hair matrix and due to the possibility of segmentation, allowing evaluation of alcohol consumption in different periods. Additionally, EtG in hair is often the only diagnostic parameter of choice for alcohol abuse when other clinical parameters such as ALT, AST, gammaGT and CDT (asialotransferrin and disialotransferrin) are in the normal range and EtG in urine negative. In this paper, we describe the development, optimization and validation of a new method based on hair extraction with water, clean-up by solid phase extraction (SPE), derivatization with heptafluorobutyric anhydride and headspace solid-phase microextraction (HS-SPME) in combination with GC-MS/MS according to forensic guidelines. The assay linearity of EtG was confirmed over the range from 2.8 to 1000 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The LLOQ was 2.8 pg/mg and the LLOD was 0.6 pg/mg. An error profile calculated according to the "Guide to the Expression of Uncertainty in Measurement" (GUM) at 99% confidence intervals for the range 5-750 pg/mg hair did not exceed 10%. This range corresponds to more than 98% of the positive samples analysed. PMID:20061100

  19. Positive EtG findings in hair as a result of a cosmetic treatment

    Microsoft Academic Search

    Frank Sporkert; Hicham Kharbouche; Marc P. Augsburger; Clementine Klemm; Markus R. Baumgartner

    In a case of a driving ability assessment, hair analysis for ethyl glucuronide (EtG) was requested by the authorities. The person concerned denied alcohol consumption and did not present any clinical sign of alcoholism. However, EtG was found in concentrations of up to 910pg\\/mg in hair from different sampling dates suggesting an excessive drinking behavior. The person declared to use

  20. Effect of succinic acid and tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine.

    PubMed

    Baranov, P A; Kravtsova, O U; Sariev, A K; Sherdev, V P

    2008-07-01

    We studied the effect of succinic acid on the process of glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine after peroral and intraperitoneal administration in the form of succinate or a base. Since the basic form of 2-ethyl-6-methyl-3-hydroxypyridine is insoluble in water, it was administered in 5% Tween-80. It was necessary to evaluate also the effect of Tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine in different administration routes. Quantitative assay of glucuronidated fractions was performed by the method of reversed-phase HPLC with fluorometrical detection. The detection limit for this method was 10 ng/ml. We confirmed that the major excretion pathway for 2-ethyl-6-methyl-3-hydroxypyridine is conjugation with glucuronic acid. It was found that succinic acid increased excretion of glucuronidated metabolite after both peroral and intraperitoneal administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and base in 5% Tween-80. The effect of Tween-80 was detected only after peroral administration, which was probably related to its effect on absorption of this compound. Tween-80 increased excretion of glucuronate after peroral administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and in 5% Tween solution. PMID:19145350

  1. Effect of bleaching on ethyl glucuronide in hair: An in vitro experiment

    Microsoft Academic Search

    Luca Morini; Alessandra Zucchella; Aldo Polettini; Lucia Politi; Angelo Groppi

    2010-01-01

    IntroductionEthyl glucuronide in hair (HEtG) has recently gained great attention, because of its high sensitivity and specificity in the diagnosis of chronic alcohol abuse. Due to its high polarity hydrophilicity, a strong hair treatment followed by a shampooing may lead to removal\\/degradation of this molecule from hair matrix.

  2. A fully validated method for the quantification of ethyl glucuronide and ethyl sulphate in urine by UPLC-ESI-MS/MS applied in a prospective alcohol self-monitoring study.

    PubMed

    Kummer, Natalie; Wille, Sarah; Di Fazio, Vincent; Lambert, Willy; Samyn, Nele

    2013-06-15

    A method for the quantification of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in human urine is developed and fully validated according to international guidelines. Protein precipitation is used as sample preparation. During the development of the method on an UPLC-ESI-MS/MS system using a CSH C18 column, special attention was paid to reduce matrix effects to improve assay sensitivity and to improve detection of the second transition for EtS for specificity purposes. The method was linear from 0.1 to 10?g/mL for both analytes. Ion suppression less than 24% (RSD<15%) was observed for EtG and no significant matrix effect was measured for EtS. The recovery was around 80% (RSD<14%) for both compounds. This method provides good precision (RSDr and RSDt<10%) and bias (<15%) for internal and external quality control samples. The reproducibility of the method was demonstrated by the successful participation to proficiency tests (z-score<0.86). This method was finally used to analyze urine samples obtained from twenty-seven volunteers whose alcohol consumption during the 5 days before sampling was monitored. Concentrations between 0.5 and 101.9?g/mL (mean 10.9, median 1.4) for EtG and between 0.1 and 37.9?g/mL (mean 3.6, median 0.3) for EtS were detected in urine samples of volunteers who declared having consumed alcohol the day before the sampling. EtG and EtS concentrations in urine were highly correlated (r=0.996, p<0.001). A moderate correlation between the number of drinks the day before sampling and the concentration of EtG (r=0.448, p<0.02) or EtS (r=0.406, p<0.04) was observed. Using a cut-off value at 0.1?g/mL for EtG and EtS, this method is able to detect social alcohol consumption approximately 24h after the intake, without showing any false positive result. PMID:23685426

  3. Urine tested positive for ethyl glucuronide and ethyl sulfate after the consumption of yeast and sugar

    Microsoft Academic Search

    Annette Thierauf; Ariane Wohlfarth; Volker Auwärter; Markus Große Perdekamp; Friedrich Martin Wurst; Wolfgang Weinmann

    2010-01-01

    BackgroundTo an increasing degree, EtG and EtS are routinely used for the proof of abstinence for purposes of traffic, occupational, addiction and social medicine. This routine use demands further investigations on the sensitivity and specificity of these analytes and the examination of possible genesis of positive EtG and EtS concentrations even without the consumption of ethanol. In vivo fermentation with

  4. Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol consumption

    Microsoft Academic Search

    Friedrich Martin Wurst; Sebastian Dresen; John P. Allen; Gerhard Wiesbeck; Marc Graf; Wolfgang Weinmann

    2006-01-01

    Background Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are dif- ferences between the two markers in their pathways for formation and degradation. Aims (a) To assess the excre- tion of EtS compared to EtG and

  5. Positive EtG findings in hair as a result of a cosmetic treatment.

    PubMed

    Sporkert, Frank; Kharbouche, Hicham; Augsburger, Marc P; Klemm, Clementine; Baumgartner, Markus R

    2012-05-10

    In a case of a driving ability assessment, hair analysis for ethyl glucuronide (EtG) was requested by the authorities. The person concerned denied alcohol consumption and did not present any clinical sign of alcoholism. However, EtG was found in concentrations of up to 910pg/mg in hair from different sampling dates suggesting an excessive drinking behavior. The person declared to use a hair lotion on a regularly base. To evaluate a possible effect of the hair lotion, prospective blood and urine controls as well as hair sampling of scalp and pubic hair were performed. The traditional clinical biomarkers of ethanol consumption, CDT and GGT, were inconspicuous in three blood samples taken. EtG was not detected in all collected urine samples. The hair lotion was transmitted to our laboratory. The ethanol concentration in this lotion was determined with 35g/L. The EtG immunoassay gave a positive result indicating EtG, which could be confirmed by GC-MS/MS-NCI. In a follow-up experiment the lotion was applied to the hair of a volunteer over a period of six weeks. After this treatment, EtG could be measured in the hair at a concentration of 72pg/mg suggesting chronic and excessive alcohol consumption. Overnight incubation of EtG free hair in the lotion yielded an EtG concentration of 140pg/mg. In the present case, the positive EtG hair findings could be interpreted as the result of an EtG containing hair care product. To our knowledge, the existence of such a product has not yet been reported, and it is exceptionally unusual to find EtG in cosmetics. Therefore, external sources for hair contamination should always be taken into account when unusual cosmetic treatment is mentioned. In those cases, it is recommended to analyze the hair product for a possible contamination with EtG. The analysis of body hair can help to reveal problems occurring from cosmetic treatment of head hair. As a consequence, the assessment of drinking behavior should be based on more than one diagnostic parameter. PMID:22018742

  6. Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS).

    PubMed

    Redondo, Ana Hernández; Körber, Christiane; König, Stefan; Längin, Andreas; Al-Ahmad, Ali; Weinmann, Wolfgang

    2012-03-01

    Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct alcohol consumption markers widely used nowadays for clinical and forensic applications. They are detectable in blood and urine even after consumption of trace amounts of ethanol and for a longer time frame, being detectable even when no more ethanol is present. The instability of EtG against bacterial degradation in contaminated urine samples and/or the possible postcollection synthesis of this metabolite in samples containing, e.g., Escherichia coli and ethanol, may cause false identification of alcohol uptake. Therefore, it is of paramount importance to constrict these error sources by inhibition of any bacterial growth causing hydrolization or synthesis of EtG. This study evaluates a new method of collecting urine samples on filter paper, dried urine spots (DUS), for simultaneous detection of EtG, EtS and creatinine, having the great advantage of inhibiting bacterial activity. In addition, a method validation for the determination of EtG and EtS in DUS was performed according to the FDA guidelines. Sterile-filtered urine was spiked with EtG and EtS, inoculated with E. coli and incubated. Liquid and dried urine samples were collected after various time intervals up to 96 h. Liquid samples were frozen immediately after collection, whereas aliquots for DUS were pipetted onto filter paper, allowed to dry and stored at RT until analysis 1 week after. The specimens were analyzed by LC-ESI-MS/MS. As expected, degradation of EtG, but not of EtS, was observed in contaminated liquid urine samples. However, the specimens collected on filter paper and stored at RT showed no degradation during storage. Therefore, collecting urine samples on filter paper for EtG and EtS analysis turns out to be a reliable method to avoid bacterial degradation of EtG and EtS, and consequently, stabilization of these ethanol metabolites is achieved. In addition, simultaneous measurement of creatinine content as an indicator of urine dilution helps to interpret the results. Method validation for EtG and EtS in DUS was satisfactory, showing the linearity of the calibration curves in the studied concentration range, good precision, accuracy and selectivity. PMID:22249418

  7. Forensic confirmatory analysis of ethyl sulfate—A new marker for alcohol consumption—by liquid-chromatography\\/electrospray ionization\\/tandem mass spectrometry

    Microsoft Academic Search

    Sebastian Dresen; Wolfgang Weinmann; Friedrich Martin Wurst

    2004-01-01

    Ethyl sulfate (EtS)—a new direct marker for ethanol intake besides ethyl glucuronide (EtG) and others—was detected in urine\\u000a samples by electrospray ionization tandem mass-spectrometry (LC-ESI-MS\\/MS). Ethyl sulfate sodium salt was used for method\\u000a development, yielding a precursor [M?H]?\\u000a m\\/z 125 and product ions m\\/z 97 [HSO4]? and m\\/z 80 [SO3]?. Pentadeuterated EtS (D5-EtS) was synthesized by esterification of sulfuric acid

  8. Direct quantification of steroid glucuronides in human urine by liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Pozo, Oscar J; Van Eenoo, Peter; Van Thuyne, Wim; Deventer, Koen; Delbeke, Frans T

    2008-03-01

    A method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the direct quantification of glucuronides of testosterone (TG), epitestosterone (EPG), androsterone (AG) and etiocholanolone (ETG) has been developed. The method allowed for the direct determination of these analytes avoiding hydrolysis and derivatization, which are usual steps in commonly used methods based on gas chromatography-mass spectrometry (GC-MS). The electrospray ionization and the product ion spectra of the glucuronides have been studied in order to obtain the most specific transitions. The use of the selected transitions is necessary for the determination of the analytes at low ng/ml concentration levels. Two different approaches have been tested for sample preparation: direct injection after filtration and acidic liquid-liquid extraction (LLE) with ethyl acetate. Both approaches have been validated obtaining satisfactory values for accuracy and precision with limits of detection lower than 1 ng/ml for TG and EPG. Ion suppression was more pronounced after LLE probably due to the concentration of interferences from acidic urine. The applicability of the method has been checked by the analysis of 40 urine samples. The results were compared with those obtained with the common GC-MS method. Results have shown a good correlation between both methods with correlation coefficients higher than 0.97. A slope close to 1 was obtained for all analytes except for AG possibly due to losses during the extraction process prior to GC-MS. PMID:18258241

  9. Direct quantification of steroid glucuronides in human urine by liquid chromatography–electrospray tandem mass spectrometry

    Microsoft Academic Search

    Oscar J. Pozo; Peter Van Eenoo; Wim Van Thuyne; Koen Deventer; Frans T. Delbeke

    2008-01-01

    A method based on liquid chromatography–tandem mass spectrometry (LC–MS\\/MS) for the direct quantification of glucuronides of testosterone (TG), epitestosterone (EPG), androsterone (AG) and etiocholanolone (ETG) has been developed. The method allowed for the direct determination of these analytes avoiding hydrolysis and derivatization, which are usual steps in commonly used methods based on gas chromatography–mass spectrometry (GC–MS). The electrospray ionization and

  10. Autism and Phthalate Metabolite Glucuronidation

    PubMed Central

    Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

    2013-01-01

    Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were collected and analyzed for the fraction of each metabolite conjugated by isotope dilution-liquid chromatography mass spectrometry-mass spectrometry. The degree of glucuronidation was lower with the ASD group. The glucuronidation pathway may differ in some children with ASD. PMID:23575644

  11. Advanced Fluctuation Diagnostics for ITG and ETG modes on NSTX*

    NASA Astrophysics Data System (ADS)

    Park, H.; Hahm, T. S.; Mazzucato, E.; Munsat, T.; Synakowski, E.; Domier Luhmann, C. W., Jr.; Idehara, T.

    2002-11-01

    Recent progress in Microwave Imaging Reflectometry clearly demonstrated that the conventional reflectometry operating in the diffraction limit, which has been widely used for ITG modes (k_bot ?i ˜ 0.2) in toroidal devices, has severe constraints in real applications. Imaging Reflectometry for long wavelength ITG modes can remedy these shortcoming on NSTX although the high magnetic shear and low magnetic field of NSTX may add more complexity to the system compared to that of the conventional tokamak (e.g. TEXTOR). The electron thermal transport has been cited in recent years as one of the major scientific transport challenges in fusion research. Recent numerical simulations have shown that extremely small amplitude ( ˜0.1 %) and short-scale (k_bot ?e ˜ 0.2) turbulent fluctuations driven by the ETG mode could significantly affect the transport of electrons in NSTX. The high magnetic shear in the ST provides an excellent spatial resolution for coherent scattering which is ideal for the search for ETG modes. On NSTX, advance diagnostic systems such as MIR system and high-resolution scattering system with the excellent spatial and k resolution for both ITG and ETG turbulence studies, are essential for understanding the transport physics of the Spherical Torus.

  12. Icosapent Ethyl

    MedlinePLUS

    ... are allergic to icosapent ethyl; fish, including shellfish (clams, scallops, shrimp, lobster, crayfish, crab, oyster, mussels, others); ... water pills'); estrogen-containing contraceptives (birth control pills, patches, rings, and injections); or estrogen replacement therapy. Your ...

  13. The UV window on counter rotating ETGs: insight from SPH simulations with chemo-photometric implementation

    NASA Astrophysics Data System (ADS)

    Bettoni, D.; Mazzei, P.; Rampazzo, R.; Marino, A.; Galletta, G.; Buson, L. M.

    2014-11-01

    The Galaxy Evolution Explorer ( GALEX) detected ultraviolet emission in about 50 % of multi-spin early-type galaxies (ETGs), suggesting the occurrence of a recent rejuvenation episode connected to the formation of these kinematical features. With the aim at investigating the complex evolutionary scenario leading to the formation of counter rotating ETGs (CR-ETGs) we use our Smooth Particle Hydrodynamic (SPH) code with chemo-photometric implementation. We discuss here the UV evolutionary path of two CR-ETGs, NGC 3593 and NGC 5173, concurrently best fitting their global observed properties, i.e., morphology, dynamics, as well as their total B-band absolute magnitude and spectral energy distribution (SED) extended over three orders of magnitude in wavelength. These simulations correspond to our predictions about the target evolution which we follow in the color-magnitude diagram (CMD), near-UV (NUV) versus r-band absolute magnitude, as a powerful diagnostic tool to emphasize rejuvenation episodes.

  14. Determination of testosterone and epitestosterone glucuronides in urine by ultra performance liquid chromatography-ion mobility-mass spectrometry.

    PubMed

    Kaur-Atwal, Gushinder; Reynolds, James C; Mussell, Christopher; Champarnaud, Elodie; Knapman, Tom W; Ashcroft, Alison E; O'Connor, Gavin; Christie, Steven D R; Creaser, Colin S

    2011-10-01

    UPLC-ion mobility spectrometry separations combined with mass spectrometry (UPLC-IM-MS) and tandem mass spectrometry (UPLC-IM-MS/MS) have been investigated for the simultaneous determination of testosterone and epitestosterone glucuronides in urine. The glucuronide epimers of testosterone and epitestosterone were separated by ion mobility spectrometry prior to mass analysis on the basis of differences in their collision cross sections, which have been measured in nitrogen. Combining ion mobility separation with UPLC/MS enhances the analysis of these low-abundance steroids in urine by selective interrogation of specific retention time, mass-to-charge and mobility regions. Detection limits for the UPLC-IM-MS/MS analysis of TG and ETG were 9.9 ng mL(-1) and 98 ng mL(-1) respectively, equivalent to 0.7 ng mL(-1) and 7.4 ng mL(-1) in urine, with linear dynamic ranges corresponding to 0.7-108 ng mL(-1) and 7.4-147 ng mL(-1) in urine. Repeatability (%RSD) for urine extracts was 0.64% and 2.31% for TG and ETG respectively. PMID:21842047

  15. DNA adducts, mutant frequencies, and mutation spectra in various organs of lambda lacZ mice exposed to ethylating agents.

    PubMed

    Mientjes, E J; Luiten-Schuite, A; van der Wolf, E; Borsboom, Y; Bergmans, A; Berends, F; Lohman, P H; Baan, R A; van Delft, J H

    1998-01-01

    To investigate tissue-specific relations between DNA adducts and mutagenesis in vivo, lambda lacZ transgenic mice were treated i.p. with N-ethyl-N-nitrosourea (ENU), diethylnitrosamine (DEN), and ethyl methanesulphonate (EMS). In liver, bone marrow, and brain DNA from mice sacrificed at several time points after treatment O6-ethylguanine (O6-EtG) and N7-ethylguanine (N7-EtG) levels were determined as well as the mutant frequency (MF) in lacZ. In liver DNA of ENU- and DEN-treated mice, the bulk of O6-EtG was removed at 3 days after treatment, while the MF continued to increase thereafter. This suggests that O6-EtG is not the major premutagenic lesion in the liver. Indeed, sequence analysis of mutants showed only 24% GC-->AT transitions, consistent with the O6-EtG lesion, and 28% TA-->AT transversions, expected from O2-ethylthymine. In bone marrow after ENU treatment, a maximum mutation induction occurred at 3 days post-treatment, of which 43% were GC-->AT mutations and 22% were TA-->AT mutations. This suggests that in bone marrow O6-EtG may be a major premutagenic lesion at the 3-day time point. In liver and bone marrow, EMS treatment gave rise to a high level of N7-EtG and a low level of O6-EtG but no increase in MF. No adducts or mutation induction were observed in bone marrow of DEN-treated mice. No MF increase was observed in the brain of either ENU- or EMS-treated mice, although O6- and N7-adducts were present. PMID:9464312

  16. Ethyl glucuronide and ethyl sulfate in autopsy samples 27 years after death

    Microsoft Academic Search

    Lucia Politi; Luca Morini; Francesco Mari; Angelo Groppi; Elisabetta Bertol

    2008-01-01

    The unique case of a 50-year-old known alcoholic whose corpse was exhumed 27 years after death is reported. The man apparently\\u000a committed suicide by hanging, but many years later the case was questioned and homicide—linked to a long-lasting serial killer\\u000a case—was suspected. Thus, the corpse was exhumed, and at the autopsy it was found to be naturally mummified. This fact permitted

  17. Numerical Study of Electromagnetic ETG Turbulence: -dependence of Electron Heat Transport

    E-print Network

    , which describes the evolution of three macroscopic fields: the electrostatic potential, the vectorNumerical Study of Electromagnetic ETG Turbulence: -dependence of Electron Heat Transport B. Labit potential and the electron pressure. There is some evidence from experiments on Tore Supra tokamak

  18. Measurement of direct ethanol metabolites in a case of a former driving under the influence (DUI) of alcohol offender, now claiming abstinence

    Microsoft Academic Search

    Friedrich M. Wurst; Michel Yegles; Christer Alling; Steina Aradottir; Jutta Dierkes; Gerhard A. Wiesbeck; Claudia C. Halter; Fritz Pragst; Volker Auwaerter

    2008-01-01

    A 37-year-old female subject had been convicted of driving under the influence of alcohol, and 19 months later, claimed abstinence\\u000a after supervised disulfiram treatment. Our aim was to elucidate the value of direct ethanol metabolites as measures of abstinence.\\u000a Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) in hair, phosphatidylethanol in whole blood and EtG and ethyl sulphate\\u000a in urine

  19. Fate of glucuronide conjugated estradiol in soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reproductive hormone, 17ß-estradiol (E2), is made more water soluble (polar) in the body by attachment of glucuronide acid to E2, facilitating urinary elimination. The fate of this potentially more mobile polar form of E2 is not well understood. Soil sorption studies were conducted using [14C] 1...

  20. Disposition of Naringenin via Glucuronidation Pathway Is Affected by Compensating Efflux Transporters of Hydrophilic Glucuronides

    PubMed Central

    Xu, Haiyan; Kulkarni, Kaustubh H.; Singh, Rashim; Yang, Zhen; Wang, Stephen W.J.; Tam, Vincent H.; Hu, Ming

    2010-01-01

    The purposes of this study were to investigate how efflux transporters and UDP-glucuronosyltransferases (UGT) affect the disposition of naringenin. A rat intestinal perfusion model with bile duct cannulation was used along with rat intestinal and liver microsomes. In the intestinal perfusion model, both absorption and subsequent excretion of naringenin metabolites were rapid and site-dependent (p < 0.05). Naringenin was absorbed the most in colon and its glucuronides were excreted the most in duodenum. In metabolism studies, the intrinsic clearance value of naringenin glucuronidation was the highest in jejunum microsomes, followed by liver, ileal and colonic microsomes. The rapid metabolism in microsomes did not always translate into more efficient excretion in the rat perfusion model, however, because of presence of rate-limiting efflux transporters. When used separately, MK-571 (an inhibitor of multidrug resistance-related protein 2 or Mrp2) or dipyridamole (an inhibitor of breast cancer resistance protein or Bcrp1) did not affect excretion of naringenin glucuronides, but when used together, they significantly (p < 0.05) decreased intestinal and biliary excretion of naringenin glucuronides. In conclusion, efflux transporters Mrp2 and Bcrp1 are shown to compensate for each other and enable the intestinal excretion of flavonoid (i.e., naringenin) glucuronides. PMID:19736994

  1. Inhibition of SN38 glucuronidation by ketoconazole

    Microsoft Academic Search

    W. Yong; J. Ramirez; F. Innocenti; M. J. Ratain

    2005-01-01

    Background\\/Aims: Ketoconazole has been shown to inhibit the glucuronidation of the UGT2B7 substrates AZT and lorazepam. Its effect on UGT1A substrates is unknown. A recent study (Kehrer et al, JClin Oncol, 2002) found that co-administration of irinotecan and ketoconazole led to a significant increase in the formation of SN-38. This study investigates whether ketoconazole contributes to the increase in SN-38

  2. Star-forming blue ETGs in two newly discovered galaxy overdensities in the HUDF at z=1.84 and 1.9: unveiling the progenitors of passive ETGs in cluster cores

    E-print Network

    Mei, Simona; Pentericci, Laura; Newman, Jeffrey A; Weiner, Benjamin J; Ashby, Matthew L N; Castellano, Marco; Conselice, Chistopher J; Filkelstein, Steven L; Galametz, Audrey; Grogin, Norman A; Koekemoer, Anton M; Huertas-Company, Marc; Lani, Caterina; Lucas, Ray A; Papovich, Casey; Rafelski, Marc; Tepliz, Harry I

    2014-01-01

    We present the discovery of two galaxy overdensities in the HST UDF: a proto-cluster, HUDFJ0332.4-2746.6 at $z = 1.84 \\pm 0.01$, and a group, HUDFJ0332.5-2747.3 at $z =1.90 \\pm 0.01$. The velocity dispersion of HUDFJ0332.4-2746.6 implies a mass of $M_{200}= (2.2 \\pm 1.8) \\times 10^{14} M_{\\odot}$, consistent with the lack of extended X-ray emission. Neither overdensity shows evidence of a red sequence. About $50\\%$ of their members show interactions and/or disturbed morphologies, which are a signature of merger remnants. Most of their morphologically classified ETGs have blue colors and show recent star-formation. These observations reveal for the first time large fractions of spectroscopically confirmed star-forming blue ETGs in proto-clusters at $z\\approx 2$. These star-forming ETGs are most likely among the progenitors of the quiescent population in clusters at more recent epochs. Their mass-size relation is consistent with that of passive ETGs in clusters at $z\\sim0.7-1.5$. If these galaxies are the proge...

  3. UDP-Glucuronosyltransferases 1A6 and 1A9 are the Major Isozymes Responsible for the 7-O-Glucuronidation of Esculetin and 4-Methylesculetin in Human Liver Microsomes.

    PubMed

    Zhu, Lijun; Lu, Linlin; Zeng, Shan; Luo, Feifei; Dai, Peimin; Wu, Peng; Wang, Ying; Liu, Liang; Hu, Ming; Liu, Zhongqiu

    2015-07-01

    Esculetin (6,7-dihydroxycoumarin, ET) and 4-methylesculetin (6,7-dihydroxy-4-methylcoumarin, 4-ME) are typical coumarin derivatives that are attracting considerable attention because of their wide spectrum of biologic activities, but their metabolism remains unknown. This study aimed to elucidate the in vitro UDP-glucuronosyltransferase (UGT) metabolism characteristics of ET and 4-ME. 7-O-monoglucuronide esculetin (ET-G) and 7-O-monoglucuronide 4-methylesculetin (4-ME-G) were identified by liquid chromatography-mass spectrometry (LC-MS) and (1)H-nuclear magnetic resonance ((1)HNMR) when ET or 4-ME was incubated with human liver (HLM) in the presence of UDP-glucuronic acid. Screening assays with 12 human expressed UGTs demonstrated that the formations of ET-G and 4-ME-G were almost exclusively catalyzed by UGT1A6 and UGT1A9. Phenylbutazone and carvacrol (UGT1A6 and UGT1A9 chemical inhibitors, respectively) at different concentrations (50, 100, and 200 ?M) significantly inhibited the formation of glucuronidates of ET and 4-ME in HLM, UGT1A6, and UGT1A9 when the concentrations of ET and 4-ME ranged from 10 to 300 ?M (P < 0.05). Clearance rates of ET in HLM, HIM, UGT1A6, and UGT1A9 were 0.54, 0.16, 0.69, and 0.14 ml/min/mg, respectively. Corresponding clearance rates values of 4-ME were 0.59, 0.03, 0.14, and 0.04 ml/min/mg, respectively. In conclusion, 7-O-monoglucuronidation by UGT1A6 and UGT1A9 was the predominant UGT metabolic pathway for both ET and 4-ME in vitro. The liver is probably the major contributor to the glucuronidation metabolism of ET and 4-ME. ET showed more rapid metabolism than 4-ME in glucuronidation. PMID:25854527

  4. Detection of pentachlorophenol and its glucuronide and sulfate conjugates in fish bile and exposure water

    SciTech Connect

    Stehly, G.R.; Hayton, W.L.

    1988-08-01

    The glucuronide and sulfate conjugates of pentachlorophenol (PCP) that were present in the bile and exposure water of goldfish (Carassius auratus) were used to develop methodology to quantify PCP and its metabolites. Reverse phase HPLC with radioactivity detection separated PCP and its metabolites, and was used to verify a method of quantification that used differential extraction and scintillation counting. Extractions of aqueous phase at pH 2 or 8, with butanol, ethyl acetate, or ether indicated that ether at pH 8 best separated PCP from its metabolites. The sulfate conjugate of PCP was the major metabolite produced when goldfish were exposed to 125 micrograms UC-PCP/l. It was present primarily in the exposure water, but also appeared in the bile.

  5. Deconjugation of soy isoflavone glucuronides needed for estrogenic activity.

    PubMed

    Islam, M A; Bekele, R; Vanden Berg, J H J; Kuswanti, Y; Thapa, O; Soltani, S; van Leeuwen, F X R; Rietjens, I M C M; Murk, A J

    2015-06-01

    Soy isoflavones (SIF) are present in the systemic circulation as conjugated forms of which the estrogenic potency is not yet clear. The present study provides evidence that the major SIF glucuronide metabolites in blood, genistein-7-O-glucuronide (GG) and daidzein-7-O-glucuronide (DG), only become estrogenic after deconjugation. The estrogenic potencies of genistein (Ge), daidzein (Da), GG and DG were determined using stably transfected U2OS-ER?, U2OS-ER? reporter gene cells and proliferation was tested in T47D-ER? cells mimicking the ER?/ER? ratio of healthy breast cells and inT47D breast cancer cells. In all assays applied, the estrogenic potency of the aglycones was significantly higher than that of their corresponding glucuronides. UPLC analysis revealed that in U2OS and T47D cells, 0.2-1.6% of the glucuronides were deconjugated to their corresponding aglycones. The resulting aglycone concentrations can account for the estrogenicity observed upon glucuronide exposure. Interestingly, under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating these glucuronides than human breast tissue S9 fraction. Our study confirms that SIF glucuronides are not estrogenic as such, and that the small % of deconjugation in the cell is enough to explain the slight bioactivity observed for the SIF-glucuronides. Species differences in deconjugation capacity should be taken into account when basing risk-benefit assessment of these SIF for the human population on animal data. PMID:25661160

  6. Resveratrol is absorbed in the small intestine as resveratrol glucuronide.

    PubMed

    Kuhnle, G; Spencer, J P; Chowrimootoo, G; Schroeter, H; Debnam, E S; Srai, S K; Rice-Evans, C; Hahn, U

    2000-05-27

    We have studied the absorption and metabolism of resveratrol in the jejunum in an isolated rat small intestine model. Only small amounts of resveratrol were absorbed across the enterocytes of the jejunum and ileum unmetabolised. The major compound detected on the serosal side was the glucuronide conjugate of resveratrol (96.5% +/- 4.6 of the amount absorbed) indicating the susceptibility of resveratrol to glucuronidation during transfer across the rat jejunum. The presence of the glucuronide was confirmed using HPLC-PDA and nanoES-MS/MS techniques. These findings suggest that resveratrol is most likely to be in the form of a glucuronide conjugate after crossing the small intestine and entering the blood circulation. This will have important implications for the biological functions of resveratrol in vivo. PMID:10872829

  7. The small intestine can both absorb and glucuronidate luminal flavonoids.

    PubMed

    Spencer, J P; Chowrimootoo, G; Choudhury, R; Debnam, E S; Srai, S K; Rice-Evans, C

    1999-09-17

    We have studied the perfusion of the jejunum and ileum in an isolated rat intestine model with flavonoids and hydroxycinnamates and the influence of glycosylation on the subsequent metabolism. Flavone and flavonol glucosides and their corresponding aglycones are glucuronidated during transfer across the rat jejunum and ileum and this glucuronidation occurs without the need for gut microflora. Furthermore, this suggests the presence of glycosidases as well as UDP-glucuronyl transferase in the jejunum. In contrast, quercetin-3-glucoside and rutin are mainly absorbed unmetabolised. The results suggest that the more highly reducing phenolics are absorbed predominantly as glucuronides (96.5%+/-4.6) of the amount absorbed, whereas monophenolic hydroxycinnamates and monophenolic B-ring flavonoids are less predisposed to glucuronidation and higher levels of aglycone (88.1%+/-10.1) are detected on absorption through both the jejunum and ileum. PMID:10481070

  8. Hepatic UDP-glucuronosyltransferase is responsible for eslicarbazepine glucuronidation.

    PubMed

    Loureiro, Ana I; Fernandes-Lopes, Carlos; Bonifácio, Maria J; Wright, Lyndon C; Soares-da-Silva, Patricio

    2011-09-01

    Eslicarbazepine acetate (ESL) is a once-daily novel antiepileptic drug approved in Europe for use as adjunctive therapy for refractory partial-onset seizures with or without secondary generalization. Metabolism of ESL consists primarily of hydrolysis to eslicarbazepine, which is then subject to glucuronidation followed by renal excretion. In this study, we have identified that human liver microsomes (HLM) enriched with uridine 5'-diphosphoglucuronic acid give origin to a single Escherichia coli ?-glucuronidase-sensitive eslicarbazepine glucuronide (most likely the O-glucuronide). The kinetics of eslicarbazepine glucuronidation in HLM was investigated in the presence and absence of bovine serum albumin (BSA). The apparent K(m) were 412.2 ± 63.8 and 349.7 ± 74.3 ?M in the presence and absence of BSA, respectively. Incubations with recombinant human UDP glucuronosyltransferases (UGTs) indicated that UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17 appear to be involved in eslicarbazepine conjugation. The UGT with the highest affinity for conjugation was UGT2B4 (K(m) = 157.0 ± 31.2 and 28.7 ± 10.1 ?M, in the absence and presence of BSA, respectively). There was a significant correlation between eslicarbazepine glucuronidation and trifluoperazine glucuronidation, a typical UGT1A4 substrate; however, no correlation was found with typical substrates for UGT1A1 and UGT1A9. Diclofenac inhibited eslicarbazepine glucuronidation in HLM with an IC(50) value of 17 ?M. In conclusion, glucuronidation of eslicarbazepine results from the contribution of UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17, but the high-affinity component of the UGT2B4 isozyme may play a major role at therapeutic plasma concentrations of unbound eslicarbazepine. PMID:21673130

  9. Stereoselective glucuronidation of formoterol by human liver microsomes

    PubMed Central

    Zhang, Mei; Fawcett, J Paul; Kennedy, Julia M; Shaw, John P

    2000-01-01

    Aims Formoterol is a ?2-adrenoceptor agonist marketed as a racemic mixture of the active (R; R)- and inactive (S; S)-enantiomers (rac-formoterol). The drug produces prolonged bronchodilation by inhalation but there is significant interpatient variability in duration of effect. Previous work has shown that in humans formoterol is metabolized by conjugation with glucuronic acid but little is known about the stereoselectivity of this reaction. The aim of the present study was to investigate the glucuronidation of formoterol enantiomers in vitro by human liver microsomes. Methods The kinetics of formation of formoterol glucuronides during incubation of racemate and of single formoterol enantiomers with human liver microsomes (n = 9) was characterized by chiral h.p.l.c. assay. Results The kinetics of glucuronidation of the two formoterol enantiomers obeyed the Michaelis-Menten equation. Glucuronidation of formoterol was stereoselective and occurred more than two times faster for (S; S)-formoterol than for (R; R)-formoterol. In incubations with single formoterol enantiomers, the median (n = 9) Km values for (R; R)-glucuronide and (S; S)-glucuronide were 827.6 and 840.4 ?m, respectively, and the median Vmax values were 2625 and 4304 pmol min?1 mg?1, respectively. Corresponding values determined in incubations with rac-formoterol were 357.2 and 312.1 ?m and 1435 and 2086 pmol min?1 mg?1 for (R; R)- and (S; S)-glucuronide, respectively. Interindividual variation was large with the ratio of Vmax/Km (S; S/R; R) ranging from 0.57 to 6.90 for incubations with rac-formoterol. Conclusions Our study demonstrates that glucuronidation of formoterol by human liver microsomes is stereoselective and subject to high interindividual variability. These findings suggest that clearance of formoterol in humans is subject to variable stereoselectivity which could explain the variation in duration of bronchodilation produced by inhaled formoterol in patients with asthma. PMID:10671910

  10. Conjugation position of quercetin glucuronides and effect on biological activity

    Microsoft Academic Search

    Andrea J Day; Yongping Bao; Michael R. A Morgan; Gary Williamson

    2000-01-01

    Quercetin glycosides are common dietary antioxidants. In general, however, potential biological effects of the circulating plasma metabolites (e.g., glucuronide conjugates) have not been measured. We have determined the rate of glucuronidation of quercetin at each position on the polyphenol ring by human liver cell-free extracts containing UDP-glucuronosyltransferases. The apparent affinity of UDP-glucuronosyltransferase followed the order 4?- > 3?- > 7-

  11. ETHYL GLUCURONIDE: A BIOMARKER TO IDENTIFY ALCOHOL USE BY HEALTH PROFESSIONALS RECOVERING FROM SUBSTANCE USE DISORDERS

    Microsoft Academic Search

    GREGORY E. SKIPPER; WOLFGANG WEINMANN; ANNETTE THIERAUF; PATRICK SCHAEFER; GERHARD WIESBECK; JOHN P ALLEN; MICHAEL MILLER; FRIEDRICH MARTIN WURST

    Aims: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half- life

  12. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation.

    PubMed

    Zhu, Liangliang; Xiao, Ling; Xia, Yangliu; Zhou, Kun; Wang, Huili; Huang, Minyi; Ge, Guangbo; Wu, Yan; Wu, Ganlin; Yang, Ling

    2015-03-01

    This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1±0.3?M, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In the presence of DES (0-6.25?M), Km values for E2-17-O-glucuronidation are located in the range of 7.2-7.4?M, while Vmax values range from 0.38 to 1.54nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2?M) can elevate Vmax from 0.016 to 0.81nmol/min/mg, while lifting Km in a much lesser extent from 4.4 to 11?M. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with KA, ?, and ? values of 0.077±0.18?M, 3.3±1.1 and 104±56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. PMID:25596428

  13. Glucuronidation of 7-hydroxy-4-methylcoumarin by human liver microsomes. Inhibition by certain drugs

    Microsoft Academic Search

    Y. M. Irshaid; K. I. Gharaybeh; F. F. Ammari; N. M. Rawashdeh

    1990-01-01

    Summary  Glucuronidation of 7-hydroxy-4-methylcoumarin (7-OH-4-MC) was comparable in three of the four human liver samples studied.\\u000a In liver sample IV the glucuronidation rate of 7-OH-4-MC was almost 40% of that in the other samples. That might be due to\\u000a interindividual variation in the capacity to glucuronidate. Glucuronidation rates were not reduced in the one human liver\\u000a sample which displayed mild centrilobular

  14. Ethyl alcohol production

    SciTech Connect

    Hofman, V.; Hauck, D.

    1980-11-01

    Recent price increases and temporary shortages of petroleum products have caused farmers to search for alternate sources of fuel. The production of ethyl alcohol from grain is described and the processes involved include saccharification, fermentation and distillation. The resulting stillage has potential as a livestock feed.

  15. Studies on the renal excretion of the acyl glucuronide, phenolic glucuronide and sulphate conjugates of diflunisal.

    PubMed Central

    Dickinson, R G; King, A R; McKinnon, G E; Hooper, W D; Eadie, M J; Herkes, G K

    1993-01-01

    1. In five healthy male volunteers given multiple doses of diflunisal (DF), renal clearances (CLR) of the acyl glucuronide (DAG), phenolic glucuronide (DPG) and sulphate (DS) conjugates were about 42, 25 and 13 ml min-1, respectively. 2. These relatively low CLR values are probably due largely to the very high plasma protein binding of the conjugates, found in vitro to be 99.0%, 97.8% and 99.45%, respectively. 3. Thus glomerular filtration plays the minor and active tubular secretion the major role in renal excretion of the three conjugates. 4. This conclusion was supported by the effect of probenecid co-administration, which decreased CLR of DAG and DPG by about 70%. CLR for DS could not be calculated when probenecid was co-administered (because of interference by probenecid metabolites in the analysis of DS in urine). 5. Water-induced diuresis had no effect on CLR of the DF conjugates, consistent with tubular reabsorption being negligible. PMID:8329288

  16. Induction of cytokine release by the acyl glucuronide of mycophenolic acid: a link to side effects?

    Microsoft Academic Search

    Eberhard Wieland; Maria Shipkova; Ulrike Schellhaas; Ekkehard Schütz; Paul Dieter Niedmann; Victor William Armstrong; Michael Oellerich

    2000-01-01

    Objectives: We have identified an acyl glucuronide (M-2) of the immunosuppressant mycophenolic acid (MPA). Acyl glucuronides have toxic potential and may contribute to drug toxicity. Whether acyl glucuronides are able to induce release of proinflammatory cytokines is unknown. Gastrointestinal disturbances have been observed during MPA therapy and may involve an inflammatory reaction. This study investigated whether M-2 can induce IL-6

  17. Morphine-6-glucuronide: actions and mechanisms.

    PubMed

    Kilpatrick, Gavin J; Smith, Terry W

    2005-09-01

    Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the micro-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the micro-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the micro-opioid receptor, (3) M6G has a lower affinity for the kappa-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether micro-opioid receptors in these brain areas differ in either their regulation or pharmacology. PMID:15952175

  18. Use of alcohol and drugs by Norwegian employees: a pilot study using questionnaires and analysis of oral fluid

    Microsoft Academic Search

    Hallvard Gjerde; Asbjørg S Christophersen; Inger S Moan; Borghild Yttredal; J Michael Walsh; Per T Normann; Jørg Mørland

    2010-01-01

    BACKGROUND: The use of alcohol and drugs may affect workplace safety and productivity. Little is known about the magnitude of this problem in Norway. METHODS: Employee recruitment methods with or without individual follow-up were compared. The employees filled in a questionnaire and provided a sample of oral fluid. Samples were analysed for alcohol, ethyl glucuronide (EtG; a biological marker of

  19. Analysis of glucuronide and sulfate steroids in urine by ultra-high-performance supercritical-fluid chromatography hyphenated tandem mass spectrometry.

    PubMed

    Doué, Mickael; Dervilly-Pinel, Gaud; Pouponneau, Karinne; Monteau, Fabrice; Le Bizec, Bruno

    2015-06-01

    Profiling conjugated urinary steroids to detect anabolic-steroid misuse is recognized as an efficient analytical strategy in both chemical-food-safety and anti-doping fields. The relevance and robustness of such profiling rely on the analysis of glucuronide and sulfate steroids, which is expected to have properties including accuracy, specificity, sensitivity, and, if possible, rapidity. In this context, the ability of ultra-high-performance supercritical-fluid chromatography (UHPSFC) hyphenated tandem mass spectrometry (MS-MS) to provide reliable and accurate phase II analysis of steroids was assessed. Four stationary phases with sub-2 ?m particles (BEH, BEH 2-ethyl-pyridine, HSS C18 SB, and CSH fluorophenyl) were screened for their capacity to separate several conjugated steroid isomers. Analytical conditions including stationary phase, modifier composition and percentage, back pressure, column temperature, and composition and flow rate of make-up solvent were investigated to improve the separation and/or the sensitivity. Thus, an analytical procedure enabling the analysis of eight glucuronide and 12 sulfate steroids by two different methods in 12 and 15 min, respectively, was optimized. The two procedures were evaluated, and UHPSFC-MS-MS analysis revealed its ability to provide sensitive (limits of quantification: 0.1 ng mL(-1) and 0.5 ng mL(-1) for sulfate and glucuronide steroids, respectively) and reliable quantitative performance (R (2)?>?0.995, RSD?Glucuronide and sulfate steroids analysis in urine by ultra-high performance supercritical fluid chromatography hyphenated tandem mass spectrometry. PMID:25736246

  20. EPA dashes ethyl`s hopes for MMT

    Microsoft Academic Search

    Heller

    1992-01-01

    Up until the Environmental Protection Agency (EPA; Washington) decided to deny Ethyl`s (Richmond, VA) petition to sell manganese-based gasoline additive MMT, many on Wall Street were bullish. Bets were that MMT sales could create an up to $200 million\\/year sales windfall for Ethyl with $60 million\\/year income, and push its near $26\\/share price up by at least 50 cts. But

  1. Glucuronidation patterns of common urinary and serum monoester phthalate metabolites

    Microsoft Academic Search

    Manori J. Silva; Dana B. Barr; John A. Reidy; Kayoko Kato; Nicole A. Malek; Carolyn C. Hodge; Donald Hurtz; Antonia M. Calafat; Larry L. Needham; John W. Brock

    2003-01-01

    Metabolism of most diesters of phthalic acid in humans occurs by an initial phase I biotransformation in which phthalate monoesters are formed, followed by a phase II biotransformation in which phthalate monoesters react with glucuronic acid to form their respective glucuronide conjugates. The phase II conjugation increases water solubility and facilitates urinary excretion of phthalate, and reduces the potential biological

  2. Glucuronidation in humans. Pharmacogenetic and developmental aspects.

    PubMed

    de Wildt, S N; Kearns, G L; Leeder, J S; van den Anker, J N

    1999-06-01

    During human development impressive changes in drug disposition occur. An important determinant of drug clearance is metabolism, something that is not only determined by ontogenic regulation but also by genetic processes which add to the variability of drug metabolism during different stages of childhood. Therefore, an understanding of the developmental regulation of different metabolic pathways, together with information on the genetic determinants of drug metabolism, will increase the knowledge of inter- and intraindividual variability in drug disposition during childhood. Conjugation has historically received less attention than cytochrome P450 metabolism. An important group of conjugation reactions are catalysed by the uridine 5'-diphosphate (UDP)-glucuronosyltransferases (UGTs); to date at least 10 different UGT isoforms have been identified. The UGTs are not only involved in the metabolism of many drugs [e.g. morphine, paracetamol (acetaminophen)] but also capable of the biotransformation of important endogenous substrates (e.g. bilirubin, ethinylestradiol) and several xenobiotics. Isoform specificity for these substrates has, however, not been fully characterised. Serious adverse events associated with chloramphenicol toxicity in the neonate have highlighted the importance of developmental changes in UGT activity. However, isoform-specific differences preclude the generalisation of a simple developmental pattern for UGT activity. UGT2B7 is the only UGT isoform for which ontogeny has been characterised both in vitro and in vivo, using morphine as the probe drug. However, no general developmental pattern for the individual UGT isoforms which might be of value for the clinician is currently available. Genetic polymorphisms have been identified for the UGT family. Not only for the UGT1A gene, which reduces bilirubin glucuronidation, leading to genetic hyperbilirubinaemia (the Crigler-Najjar and Gilbert's syndromes), but also for 3 other UGT isoforms. However, the impact of these genetic differences on drug metabolism remains to be established because of overlapping isoform specificity of the drugs studied, as well as a lack of specific probe substrates to test the activity of individual UGT isoforms in relation to these gene mutations. Clearly, an information gap exists regarding the developmental and genetic aspects of UGT regulation and its potential impact on therapy. More research is needed on the pharmacogenetics and ontogeny of the UGTs for effective translation of scientific information into clinically applicable knowledge. PMID:10427468

  3. Ethyl Alcohol Production. 

    E-print Network

    O'Neal, Henry

    1981-01-01

    mixture is known as beer. 6. The next step is to separate the ethyl alcohol from the beer using two 12-inch diameter plate distillation columns, each 20 feet in height. All of the fermented mash is put into the first column (beer column) with steam... of the second column (rectifying column) where alcohol vapor is driven off at the top and condensed to yield liquid alcohol. The normal production proof of the Texas A&M University plant is 182 to 184. 7. The solid grain residues are separated from...

  4. Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity.

    PubMed

    Frizzell, Caroline; Uhlig, Silvio; Miles, Christopher O; Verhaegen, Steven; Elliott, Christopher T; Eriksen, Gunnar S; Sørlie, Morten; Ropstad, Erik; Connolly, Lisa

    2015-04-01

    Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. Once ingested, ZEN may be absorbed and metabolised to ?- and ?-zearalenol (?-ZOL, ?-ZOL), and to a lesser extent ?- and ?-zearalanol (?-ZAL, ?-ZAL). Further biotransformation to glucuronide conjugates also occurs to facilitate the elimination of these toxins from the body. Unlike ZEN and its metabolites, information regarding the estrogenic activity of these glucuronide conjugates in various tissues is lacking. ZEN-14-O-glucuronide, ?-ZOL-14-O-glucuronide, ?-ZOL-7-O-glucuronide, ?-ZOL-14-O-glucuronide and ?-ZOL-16-O-glucuronide, previously obtained as the major products from preparative enzymatic synthesis, were investigated for their potential to cause endocrine disruption through interference with estrogen receptor transcriptional activity. All five glucuronide conjugates showed a very weak agonist response in an estrogen responsive reporter gene assay (RGA), with activity ranging from 0.0001% to 0.01% of that of 17?-estradiol, and also less than that of ZEN, ?-ZOL and ?-ZOL which have previously shown estrogenic potencies of the order 17?-estradiol>?-ZOL>ZEN>?-ZOL. Confirmatory mass spectrometry revealed that any activity observed was likely a result of minor deconjugation of the glucuronide moiety. This study confirms that formation of ZEN and ZOL glucuronides is a detoxification reaction with regard to estrogenicity, serving as a potential host defence mechanism against ZEN-induced estrogenic activity. PMID:25645597

  5. Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases.

    PubMed

    Manevski, Nenad; Kurkela, Mika; Höglund, Camilla; Mauriala, Timo; Court, Michael H; Yli-Kauhaluoma, Jari; Finel, Moshe

    2010-03-01

    We have examined the glucuronidation of psilocin, a hallucinogenic indole alkaloid, by the 19 recombinant human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B. The glucuronidation of 4-hydroxyindole, a related indole that lacks the N,N-dimethylaminoethyl side chain, was studied as well. UGT1A10 exhibited the highest psilocin glucuronidation activity, whereas the activities of UGTs 1A9, 1A8, 1A7, and 1A6 were significantly lower. On the other hand, UGT1A6 was by far the most active enzyme mediating 4-hydroxyindole glucuronidation, whereas the activities of UGTs 1A7-1A10 toward 4-hydroxyindole resembled their respective psilocin glucuronidation rates. Psilocin glucuronidation by UGT1A10 followed Michaelis-Menten kinetics in which psilocin is a low-affinity high-turnover substrate (K(m) = 3.8 mM; V(max) = 2.5 nmol/min/mg). The kinetics of psilocin glucuronidation by UGT1A9 was more complex and may be best described by biphasic kinetics with both intermediate (K(m1) = 1.0 mM) and very low affinity components. The glucuronidation of 4-hydroxyindole by UGT1A6 exhibited higher affinity (K(m) = 178 microM) and strong substrate inhibition. Experiments with human liver and intestinal microsomes (HLM and HIM, respectively) revealed similar psilocin glucuronidation activity in both samples, but a much higher 4-hydroxyindole glucuronidation rate was found in HLM versus HIM. The expression levels of UGTs 1A6-1A10 in different tissues were studied by quantitative real-time-PCR, and the results, together with the activity assays findings, suggest that whereas psilocin may be subjected to extensive glucuronidation by UGT1A10 in the small intestine, UGT1A9 is likely the main contributor to its glucuronidation once it has been absorbed into the circulation. PMID:20007669

  6. Carboxyl-glucuronidation of mitiglinide by human UDP-glucuronosyltransferases

    Microsoft Academic Search

    Lushan Yu; Sijie Lu; Yongjun Lin; Su Zeng

    2007-01-01

    Mitiglinide (MGN) is a new potassium channel antagonist for the treatment of type 2 diabetes mellitus. In the present study, a potential metabolic pathway of MGN, via carboxyl-linked glucuronic acid conjugation, was found. MGN carboxyl-glucuronide was isolated from a reaction mixture consisting of MGN and human liver microsomes fortified with UDP-glucuronic acid (UDPGA) and identified by a hydrolysis reaction with

  7. Unreliable alcohol testing in a shipping safety programme

    Microsoft Academic Search

    Anders Helander; Charlotte Asker Hagelberg; Olof Beck; Björn Petrini

    2009-01-01

    BackgroundWithin a maritime alcohol and drug testing programme, a case showing an unphysiological urine ethanol concentration (235mmol\\/L, 10.8g\\/L) was found. The sample contained low levels of the ethanol metabolites ethyl glucuronide (EtG) and ethyl sulphate (EtS) which confirmed prior drinking, but also tested positive for the fermenting yeast Candida albicans which suggested post-sampling ethanol formation. This and other questionable cases

  8. Ethyl`s MMT ready to hit the road

    SciTech Connect

    Stringer, J.

    1996-01-03

    After spending two decades and about $30 million on the fight to sell the fuel octane booster methylcyclopentadienyl manganese tricarbonyl (MMT), Ethyl has started marketing the product. Ethyl president and chief operating officer Thomas Gottwald says he expects a profit from MMT from the outset. {open_quotes}MMT is a gangbuster new product,{close_quotes} says Paul Raman, an analyst with S.G. Warburg (New York), {open_quotes}and it will be very profitable for Ethyl.{close_quotes} Ethyl`s effort to bring MMT to market faced pressure from EPA and automakers. EPA says MMT should not be marketed until more research is done on health effects of the manganese-based additive. US automakers oppose MMT, fearing it will damage catalytic converters. Last October Ethyl won a federal appeals court decision compelling EPA to approve MMT use. Gottwald says the MMT fight has been well worth it: {open_quotes}We fought with our eye on the bottom line.{close_quotes}

  9. Organochlorines inhibit acetaminophen glucuronidation by redirecting UDP-glucuronic acid towards the D-glucuronate pathway

    SciTech Connect

    Chan, Tom S. [Centre Hospitalier de l'Universite de Montreal, 264 Rene Levesque E, Montreal, Quebec, H2X 1P1 (Canada)], E-mail: chatsy@gmail.com; Wilson, John X. [Department of Exercise and Nutritional Sciences, University at Buffalo, Buffalo, New York, 14214 (United States); Selliah, Subajini; Bilodeau, Marc; Zwingmann, Claudia [Centre Hospitalier de l'Universite de Montreal, 264 Rene Levesque E, Montreal, Quebec, H2X 1P1 (Canada); Poon, Raymond [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); O'Brien, Peter J. [Faculty of Pharmacy, University of Toronto, Toronto, Ontario, M5S 3M2 (Canada)

    2008-11-01

    Industry-derived organochlorines are persistent environmental pollutants that are a continuing health concern. The effects of these compounds on drug metabolism are not well understood. In the current study we present evidence that the inhibition of acetaminophen (APAP) glucuronidation by minute concentrations of organochlorines correlates well with their ability to stimulate the D-glucuronate pathway leading to ascorbate synthesis. A set of 6 arylated organochlorines, including 5 PCB (polychlorinated biphenyl) congeners, were assessed for their effects on APAP glucuronidation in isolated hepatocytes from male Sprague-Dawley rats. The capacity of each organochlorine to inhibit APAP glucuronidation was found to be directly proportional to its capacity to stimulate ascorbate synthesis. PCB153, PCB28 and bis-(4-chlorophenyl sulfone) (BCPS) in increasing order were the most effective organochlorines for inhibiting APAP glucuronidation and stimulating the D-glucuronate pathway. None of the 3 inhibitors of APAP glucuronidation were able to alter the expression of UGT1A6, UGT1A7 and UGT1A8 (the major isoforms responsible for APAP glucuronidation in the rat), however, their efficacy at inhibiting APAP glucuronidation was proportional to their capacity to deplete UDP-glucuronic acid (UDPGA). BCPS-mediated inhibition of APAP glucuronidation in isolated hepatocytes had non-competitive characteristics and was insensitive to the inactivation of cytochrome P450. The effective organochlorines were also able to selectively stimulate the hydrolysis of UDPGA to UDP and glucuronate in isolated microsomes, but could not inhibit APAP glucuronidation in microsomes when UDPGA was in excess. We conclude that organochlorines are able to inhibit APAP glucuronidation in hepatocytes by depleting UDPGA via redirecting UDPGA towards the D-glucuronate pathway. Because the inhibition is non-competitive, low concentrations of these compounds could have long term inhibitory effects on the glucuronidating capacity of hepatocytes.

  10. Enzyme-assisted synthesis and structural characterization of pure benzodiazepine glucuronide epimers

    Microsoft Academic Search

    T. Pallmann; U. Jonas; M. Wagner; M. Thevis; H. Kaeferstein; M. A. Rothschild; K. Bender

    2010-01-01

    The three hydroxybenzodiazepines oxazepam, temazepam, and lorazepam used for their anxiolytic, sedative, and anticonvulsant properties are metabolized by glucuronidation, which is the predominant pathway in the clearance mechanism of exogenous and endogenous substances during phase II metabolism. The aim of this study was the synthesis of benzodiazepine-O-glucuronides as analytical reference substances. All benzodiazepines are prescribed clinically as racemic formulations. The

  11. Multiplexed Targeted Quantitative Proteomics Predicts Hepatic Glucuronidation Potential.

    PubMed

    Margaillan, Guillaume; Rouleau, Michèle; Klein, Kathrin; Fallon, John K; Caron, Patrick; Villeneuve, Lyne; Smith, Philip C; Zanger, Ulrich M; Guillemette, Chantal

    2015-09-01

    Phase II metabolism is prominently governed by UDP-glucuronosyltransferases (UGTs) in humans. These enzymes regulate the bioactivity of many drugs and endogenous small molecules in many organs, including the liver, a major site of regulation by the glucuronidation pathway. This study determined the expression of hepatic UGTs by targeted proteomics in 48 liver samples and by measuring the glucuronidation activity using probe substrates. It demonstrates the sensitivity and accuracy of nano-ultra-performance liquid chromatography with tandem mass spectrometry to establish the complex expression profiles of 14 hepatic UGTs in a single analysis. UGT2B7 is the most abundant UGT in our collection of livers, expressed at 69 pmol/mg microsomal proteins, whereas UGT1A1, UGT1A4, UGT2B4, and UGT2B15 are similarly abundant, averaging 30-34 pmol/mg proteins. The average relative abundance of these five UGTs represents 81% of the measured hepatic UGTs. Our data further highlight the strong relationships in the expression of several UGTs. Most notably, UGT1A4 correlates with most measured UGTs, and the expression levels of UGT2B4/UGT2B7 displayed the strongest correlation. However, significant interindividual variability is observed for all UGTs, both at the level of enzyme concentrations and activity (coefficient of variation: 45%-184%). The reliability of targeted proteomics quantification is supported by the high correlation between UGT concentration and activity. Collectively, these findings expand our understanding of hepatic UGT profiles by establishing absolute hepatic concentrations of 14 UGTs and further suggest coregulated expression between most abundant hepatic UGTs. Data support the value of multiplexed targeted quantitative proteomics to accurately assess specific UGT concentrations in liver samples and hepatic glucuronidation potential. PMID:26076694

  12. Species differences in the formation of vabicaserin carbamoyl glucuronide.

    PubMed

    Tong, Zeen; Chandrasekaran, Appavu; DeMaio, William; Jordan, Ronald; Li, Hongshan; Moore, Robin; Poola, Nagaraju; Burghart, Peter; Hultin, Theresa; Scatina, JoAnn

    2010-04-01

    Vabicaserin is a potent 5-hydroxtryptamine 2C full agonist with therapeutic potential for a wide array of psychiatric disorders. Metabolite profiles indicated that vabicaserin was extensively metabolized via carbamoyl glucuronidation after oral administration in humans. In the present study, the differences in the extent of vabicaserin carbamoyl glucuronide (CG) formation in humans and in animals used for safety assessment were investigated. After oral dosing, the systemic exposure ratios of CG to vabicaserin were approximately 12 and up to 29 in monkeys and humans, respectively, and the ratios of CG to vabicaserin were approximately 1.5 and 1.7 in mice and dogs, respectively. These differences in systemic levels of CG are likely related to species differences in the rate and extent of CG formation and elimination. Whereas CG was the predominant circulating metabolite in humans and a major metabolite in mice, dogs, and monkeys, it was a relatively minor metabolite in rats, in which oxidative metabolism was the major metabolic pathway. Although the CG was not detected in plasma or urine of rats, approximately 5% of the dose was excreted in bile as CG in the 24-h collection postdose, indicating the rat had the metabolic capability of producing the CG. In vitro, in a CO(2)-enriched environment, the CG was the predominant metabolite in dog and human liver microsomes, a major metabolite in monkey and mice, and only a very minor metabolite in rats. Carbamoyl glucuronidation and hydroxylation had similar contributions to vabicaserin metabolism in mouse and monkey liver microsomes. However, only trace amounts of CG were formed in rat liver microsomes, and other metabolites were more prominent than the CG. In conclusion, significant differences in the extent of formation of the CG were observed among the various species examined. The exposure ratios of CG to vabicaserin were highest in humans, followed by monkeys, then mice and dogs, and lowest in rats, and the in vitro metabolite profiles generally correlated well with the in vivo metabolites. PMID:20032194

  13. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...added the equivalent of 4.25 gallons of 100 percent ethyl acetate. It is used in accordance with good feeding practices in ruminant feed supplements as a source of added energy. [46 FR 52333, Oct. 27, 1981, as amended at 72 FR 41620, July 31,...

  14. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...added the equivalent of 4.25 gallons of 100 percent ethyl acetate. It is used in accordance with good feeding practices in ruminant feed supplements as a source of added energy. [46 FR 52333, Oct. 27, 1981, as amended at 72 FR 41620, July 31,...

  15. Detection and identification of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide in nitrite adulterated urine specimens containing morphine and its glucuronides.

    PubMed

    Luong, Susan; Fu, Shanlin

    2014-03-01

    In vitro urine adulteration is a well-documented practice adopted by individuals aiming to evade detection of drug use, when required to undergo mandatory sports and workplace drug testing. Potassium nitrite is an effective urine adulterant due to its oxidizing potential, and has been shown to mask the presence of many drugs of abuse. However, limited research has been conducted to understand its mechanism of action, and to explore the possibility of the drugs undergoing direct oxidation to form stable reaction products. In this study, opiates including morphine, codeine, morphine-3-glucuronide and morphine-6-glucuronide were exposed to potassium nitrite in water and urine to mimic the process of nitrite adulteration. It was found that two stable reaction products were detected by liquid chromatography-mass spectrometry (LC-MS) when morphine and morphine-6-glucuronide were exposed to nitrite. Isolation and elucidation using spectrometric and spectroscopic techniques revealed that they were 2-nitro-morphine and 2-nitro-morphine-6-glucuronide, respectively. These reaction products were also formed when an authentic morphine-positive urine specimen was fortified with nitrite. 2-Nitro-morphine was found to be stable enough to undergo the enzymatic hydrolysis procedure and also detectable by gas chromatography-mass spectrometry (GC-MS) after forming a trimethylsilyl derivative. On the contrary, morphine-3-glucuronide did not appear to be chemically manipulated when exposed to potassium nitrite in urine. These reaction products are not endogenously produced, are relatively stable and can be monitored with both LC-MS and GC-MS confirmatory techniques. As a result, these findings have revealed the possibility for the use of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide as markers for the indirect monitoring of morphine and morphine-6-glucuronide in urine specimens adulterated with nitrite. PMID:23592389

  16. Hesperetin glucuronide, a photoprotective agent arising from flavonoid metabolism in human skin fibroblasts.

    PubMed

    Proteggente, Anna R; Basu-Modak, Sharmila; Kuhnle, Gunter; Gordon, Matthew J; Youdim, Kuresh; Tyrrell, Rex; Rice-Evans, Catherine A

    2003-09-01

    There is considerable interest in the biological properties of flavonoids in terms of their antioxidant and cytoprotective actions. The interaction of the flavanone hesperetin with human skin fibroblasts (FEK4) has revealed the potential for metabolism to hesperetin glucuronide and its subsequent extrusion. As a consequence of this observation, the effectiveness of hesperetin glucuronides, in comparison with that of the aglycone form, in protecting against UV-A radiation has been investigated. The results indicate that hesperetin glucuronides, but not hesperetin, protect against UV-A-induced necrotic cell death. PMID:14556312

  17. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Firearms 1 2012-04-01 2012-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products...AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific...

  18. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...Firearms 1 2013-04-01 2013-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products...AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific...

  19. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Firearms 1 2014-04-01 2014-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products...AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific...

  20. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Firearms 1 2010-04-01 2010-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products...AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific...

  1. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  2. A rapid and sensitive UPLC-MS/MS method for the simultaneous quantification of serum androsterone glucuronide, etiocholanolone glucuronide, and androstan-3?, 17? diol 17-glucuronide in postmenopausal women.

    PubMed

    Ke, Yuyong; Gonthier, Renaud; Isabelle, Maxim; Bertin, Jonathan; Simard, Jean-Nicolas; Dury, Alain Y; Labrie, Fernand

    2015-05-01

    Quantification of steroidal glucuronide conjugates by the indirect methods of immunoassay and GC-MS/MS may underestimate some conjugates since hydrolysis is needed in sample processing. In the present work, a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous direct quantification of androsterone glucuronide, etiocholanolone glucuronide, and androstan-3?, 17? diol 17-glucuronide in postmenopausal women's serum. The quantification limits are 0.1ng/mL for 3?-diol-17G and 4ng/mL for both ADT-G and Etio-G, respectively, with an extraction from 200?L serum while the total run time is less than 6min for all three glucuronides. In this method, solid phase extraction is used for sample preparation. The assay has been validated in compliance with EndoCeutics SOPs and FDA guidelines for bioanalytical method development and validation. The recovery of glucuronides in stripped serum is consistent with that in unstripped serum, where the average difference in stripped and unstripped is less than 10%. A linear regression model fits well the standard curves of all three compounds with R?0.99 where the weighting factor is 1/X. Interday accuracy and CV for all levels of QCs are within the range of 15% in both stripped and unstripped serum while all calibration curves are within the range of 6% except for LLOQs, which are within the range of 9%. Other parameters have also been assessed such as selectivity, matrix, lipemic and hemolysis effects as well as stabilities in solution and matrix. Incurred sample reanalysis has been performed with a result of over 93% within 20% of the original values. This reliable, sensitive and fast method is ready for large-scale clinical sample assays. PMID:25701608

  3. DEVELOPMENT OF A CLASS-SELECTIVE ENZYME IMMUNOASSAY FOR URINARY PHENOLIC GLUCURONIDES. (R825433)

    EPA Science Inventory

    Class-selective immunoassays for the measurement of glucuronides in human urine can aid evaluation of human exposure to complex mixtures of xenobiotics. Therefore, an enzyme immunoassay (EIA) for the group-selective detection of phenolic ...

  4. Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes

    Microsoft Academic Search

    Christian Mignat; Uta Wille; Albrecht Ziegler

    1995-01-01

    The affinity of morphine, codeine, dihydrocodeine and their glucuronides for ?-, ?,- and ?-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [3H]DAMGO, [3H]DPDPE, and [3H]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the ??-ratio nor that of ??. Glucuronidation of the 6-hydroxyl group of

  5. Movement of Fluorescein and Its Glucuronide Across Retinal Pigment Epithelium-Choroid

    Microsoft Academic Search

    Satoshi Koyano; Makoto Araie; Shuichiro Eguchi

    Purpose. To characterize movement of fluorescein and its glucuronide across the blood-retinal barrier. Methods. Retinal pigment epithelium (RPE)-choroid preparations from New Zealand albino rabbit were sealed in an Ussing-type chamber in a stabilized condition for 3 hr, where move- ment of fluorescein and fluorescein glucuronide across the RPE-choroid was studied under a short circuit condition. Results. The outward (vitreous-choroid) permeability

  6. In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative MetabolitesS?

    PubMed Central

    Schebb, N. H.; Franze, B.; Maul, R.; Ranganathan, A.

    2012-01-01

    Triclocarban (3,4,4?-trichlorocarbanilide; TCC) is widely used as an antibacterial in bar soaps. During use of these soaps, a significant portion of TCC is absorbed by humans. For the elimination from the body, glucuronidation plays a key role in both biliary and renal clearance. To investigate this metabolic pathway, we performed microsomal incubations of TCC and its hydroxylated metabolites 2?-OH-TCC, 3?-OH-TCC, and 6-OH-TCC. Using a new liquid chromatography-UV-mass spectrometry method, we could show a rapid glucuronidation for all OH-TCCs by the uridine-5?-diphosphate-glucuronosyltransferases (UGT) present in liver microsomes of humans (HLM), cynomolgus monkeys (CLM), rats (RLM), and mice (MLM). Among the tested human UGT isoforms, UGT1A7, UGT1A8, and UGT1A9 showed the highest activity for the conjugation of hydroxylated TCC metabolites followed by UGT1A1, UGT1A3, and UGT1A10. Due to this broad pattern of active UGTs, OH-TCCs can be efficiently glucuronidated in various tissues, as shown for microsomes from human kidney (HKM) and intestine (HIM). The major renal metabolites in humans, TCC-N-glucuronide and TCC-N?-glucuronide, were formed at very low conversion rates (<1%) by microsomal incubations. Low amounts of N-glucuronides were generated by HLM, HIM, and HKM, as well as by MLM and CLM, but not by RLM, according to the observed species specificity of this metabolic pathway. Among the human UGT isoforms, only UGT1A9 had activity for the N-glucuronidation of TCC. These results present an anomaly where in vivo the predominant urinary metabolites of TCC are N and N?-glucuronides, but these compounds are slowly produced in vitro. PMID:21953915

  7. A concise synthesis of glucuronide metabolites of urolithin-B, resveratrol, and hydroxytyrosol

    Microsoft Academic Search

    Ricardo Lucas; David Alcantara; Juan Carlos Morales

    2009-01-01

    A simple and direct strategy to chemically synthesize O-?-d-glucuronides of urolithin-B 4, resveratrol 5, and the corresponding hydroxytyrosol derivatives 6, 7 (as a regioisomeric mixture), and 8 is described. The critical glycosylation step has been optimized using a structurally simple phenol, urolithin-B, by modification of several reaction parameters (solvent, promoter, and glucuronide donor). Very high yields have been obtained in

  8. Identification of UDP-glucuronosyltransferase isoforms responsible for leonurine glucuronidation in human liver and intestinal microsomes.

    PubMed

    Tan, Bo; Cai, Weimin; Zhang, Jinlian; Zhou, Ning; Ma, Guo; Yang, Ping; Zhu, Qing; Zhu, Yizhun

    2014-09-01

    Leonurine is a potent component of herbal medicine Herba leonuri. The detail information on leonurine metabolism in human has not been revealed so far. Two primary metabolites, leonurine O-glucuronide and demethylated leonurine, were observed and identified in pooled human liver microsomes (HLMs) and O-glucuronide is the predominant one. Among 12 recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A8, UGT1A9, and UGT1A10 showed catalyzing activity toward leonurine glucuronidation. The intrinsic clearance (CLint) of UGT1A1 was approximately 15-to 20-fold higher than that of UGT1A8, UGT1A9, and UGT1A10, respectively. Both chemical inhibition study and correlation study demonstrated that leonurine glucuronidation activities in HLMs had significant relationship with UGT1A1 activities. Leonurine glucuronide was the major metabolite in human liver microsomes. UGT1A1 was principal enzyme that responsible for leonurine glucuronidation in human liver and intestine microsomes. PMID:24635759

  9. Species-Associated Differences in the Inhibition of Propofol Glucuronidation by Magnolol

    PubMed Central

    Yang, Lu; Zhu, Liangliang; Ge, Guangbo; Xiao, Ling; Wu, Yan; Liang, Sicheng; Cao, Yunfeng; Yang, Ling; Wang, Dong

    2014-01-01

    Magnolol, a major active constituent in herbal medicine, potently inhibits propofol glucuronidation in human liver microsomes, with inhibition constants in the nanomolar range. This study was conducted to investigate magnolol-induced inhibition of propofol glucuronidation in liver microsomes from Swiss–Hauschka mice, Sprague–Dawley rats, Chinese Bama pigs, and cynomolgus macaques. Results indicated that magnolol (10 ?M) inhibited propofol glucuronidation in liver microsomes from Bama pigs and cynomolgus macaques but not in those from mice or rats. Data from liver microsomes from Bama pigs indicated a competitive inhibition mechanism, with a Ki of 1.7 ?M. In contrast to that of pig liver microsomes, the inhibition of microsomes from cynomolgus macaques followed a noncompetitive mechanism, with a Ki of 3.4 ?M. In summary, this study indicates that magnolol-induced inhibition of propofol glucuronidation varies substantially among species, and the Ki values determined by using liver microsomes from various experimental animal species far exceed that for human liver microsomes. The inhibition of propofol glucuronidation by magnolol in liver microsomes from all animal species tested was significantly lower than the inhibition previously demonstrated in human liver microsomes. Hepatic microsomes from Swiss–Hauschka mice, Sprague–Dawley rats, Chinese Bama pigs, and cynomolgus macaques are not effective models of the inhibition of glucuronidation induced by magnolol in humans. PMID:25199099

  10. Species-associated differences in the inhibition of propofol glucuronidation by magnolol.

    PubMed

    Yang, Lu; Zhu, Liangliang; Ge, Guangbo; Xiao, Ling; Wu, Yan; Liang, Sicheng; Cao, Yunfeng; Yang, Ling; Wang, Dong

    2014-07-01

    Magnolol, a major active constituent in herbal medicine, potently inhibits propofol glucuronidation in human liver microsomes, with inhibition constants in the nanomolar range. This study was conducted to investigate magnolol-induced inhibition of propofol glucuronidation in liver microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques. Results indicated that magnolol (10 ?M) inhibited propofol glucuronidation in liver microsomes from Bama pigs and cynomolgus macaques but not in those from mice or rats. Data from liver microsomes from Bama pigs indicated a competitive inhibition mechanism, with a Ki of 1.7 ?M. In contrast to that of pig liver microsomes, the inhibition of microsomes from cynomolgus macaques followed a noncompetitive mechanism, with a Ki of 3.4 ?M. In summary, this study indicates that magnolol-induced inhibition of propofol glucuronidation varies substantially among species, and the Ki values determined by using liver microsomes from various experimental animal species far exceed that for human liver microsomes. The inhibition of propofol glucuronidation by magnolol in liver microsomes from all animal species tested was significantly lower than the inhibition previously demonstrated in human liver microsomes. Hepatic microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques are not effective models of the inhibition of glucuronidation induced by magnolol in humans. PMID:25199099

  11. Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

    PubMed

    Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

    2012-04-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates. PMID:22275465

  12. Structure of ethyl phenyl selenone.

    PubMed

    Hoier, H; Carrell, H L; Glusker, J P; Spears, C P

    1993-03-15

    C8H10O2Se, M(r) = 217.13, monoclinic, P2(1)/n, a = 9.511 (2), b = 15.741 (3) c = 11.467 (2) A, beta = 91.31 (2) degrees, V = 1716.3 (6) A3, Z = 8 (two molecules per asymmetric unit), Dx = 1.68 Mg m-3, lambda (Mo K alpha) = 0.71069 A, mu = 4.19 mm-1, F(000) = 864, T congruent to 295 K, R(obs) = 0.060 for 1944 unique reflections with I > 2 sigma (I). The two molecules in the asymmetric unit are very similar; they differ only in the conformation of the ethyl side chain. There is considerable disorder in one molecule, that possibly can be represented by torsion about the Se-C(ethyl) bond. In each case the O atoms of the SeO2 group lie near the plane of the phenyl group. Se-O ... H-C interactions appear to be the only significant intermolecular interactions. These involve an H atom of the alpha-C atom of the ethyl group in addition to the H atoms of the phenyl group. PMID:8484923

  13. Correlation between plasma estradiol and estrone-3-glucuronide in urine during the monitoring of ovarian induction therapy.

    PubMed

    Catalan, R; Castellanos, J M; Palomino, T; Senti, M; Antolin, M; Galard, R M

    1989-01-01

    An improved radioimmunoassay was developed to determine estrone-3-glucuronide in daily urine. Resulting levels were compared with those of estradiol in plasma of 10 healthy women and 14 undergoing ovulation induction therapy with human menopausal gonadotropin and human chorionic gonadotropin. A highly significant correlation between plasma estradiol and urinary estrone-3-glucuronide in normal (r = .9209; P less than .01) and stimulated (r = .9229; P less than .01) women was demonstrated. These results proved that the pattern of excretion of estrone-3-glucuronide perfectly reflected the changes in plasmatic estradiol levels when monitoring ovarian induction and that estrone-3-glucuronide determinations can provide clinically useful information in human induction therapy. PMID:2570765

  14. In vitro glucuronidation kinetics of deoxynivalenol by human and animal microsomes and recombinant human UGT enzymes.

    PubMed

    Maul, Ronald; Warth, Benedikt; Schebb, Nils Helge; Krska, Rudolf; Koch, Matthias; Sulyok, Michael

    2015-06-01

    The mycotoxin deoxynivalenol (DON), formed by Fusarium species, is one of the most abundant mycotoxins contaminating food and feed worldwide. Upon ingestion, the majority of the toxin is excreted by humans and animal species as glucuronide conjugate. First in vitro data indicated that DON phase II metabolism is strongly species dependent. However, kinetic data on the in vitro metabolism as well as investigations on the specific enzymes responsible for DON glucuronidation in human are lacking. In the present study, the DON metabolism was investigated using human microsomal fractions and uridine-diphosphoglucuronyltransferases (UGTs) as well as liver microsomes from five animal species. Only two of the twelve tested human recombinant UGTs led to the formation of DON glucuronides with a different regiospecificity. UGT2B4 predominantly catalyzed the formation of DON-15-O-glucuronide (DON-15GlcA), while for UGT2B7 the DON-3-O-glucuronide (DON-3GlcA) metabolite prevailed. For human UGTs, liver, and intestinal microsomes, the glucuronidation activities were low. The estimated apparent intrinsic clearance (Clapp,int) for all human UGT as well as tissue homogenates was <1 mL/min mg protein. For the animal liver microsomes, moderate Clapp,int between 1.5 and 10 mL/min mg protein were calculated for carp, trout, and porcine liver. An elevated glucuronidation activity was detected for rat and bovine liver microsomes leading to Clapp,int between 20 and 80 mL/min mg protein. The obtained in vitro data points out that none of the animal models is suitable for estimating the human DON metabolism with respect to the metabolite pattern and formation rate. PMID:24927789

  15. Human hydroxylated metabolites of BDE-47 and BDE-99 are glucuronidated and sulfated in vitro.

    PubMed

    Erratico, Claudio; Zheng, Xiaobo; Ryden, Andreas; Marsh, Goran; Maho, Walid; Covaci, Adrian

    2015-07-16

    Polybrominated diphenyl ethers (PBDEs) were used worldwide as additive flame retardants and are classified as persistent, bioaccumulable and toxic environmental pollutants. In humans, the hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) formed in vitro have also been detected in vivo. To further characterize the metabolism of BDE-47 and BDE-99 and to identify candidate markers for monitoring the human exposure to PBDEs using non-invasive approaches, glucuronidation and sulfation of hydroxylated metabolites of BDE-47 and BDE-99 were investigated using human liver microsomes and cytoplasm, respectively. The formed Phase II metabolites were analyzed by liquid chromatography-tandem mass spectrometry using a novel approach to develop analytical methods in absence of authentic standards. All available standards for hydroxylated metabolites of BDE-47 and BDE-99 were glucuronidated and sulfated, showing that glucuronidation and sulfation are part of the metabolism pathway of BDE-47 and BDE-99 in vitro. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-47 were (a) 2,4-DBP-Gluc and 5-Gluc-BDE-47, and (b) 2'-Sulf-BDE-28, 4-Sulf-BDE-42 and 3-Sulf-BDE-47, respectively. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-99 were (a) 2,4,5-TBP-Gluc and 6'-Gluc-BDE-99, and (b) 3'-Sulf-BDE-99 and 5'-Sulf-BDE-99, respectively. Apparent Km values associated with the formation of sulfated metabolites of BDE-47 and BDE-99 were ten times lower than those of the corresponding glucuronidated metabolites, suggesting that sulfated rather than glucuronidated metabolites of OH-PBDEs might be used as markers of human exposure to PBDEs using a non-invasive approach based on urine sample collection. PMID:25956475

  16. Interpretation problems in a forensic case of abstinence determination using alcohol markers in hair

    Microsoft Academic Search

    Fritz Pragst

    In a child custody case a mother with a longstanding history of alcohol misuse had to show absolute abstinence for one year. She entered a residential rehabilitation for six months and was tested two months later by way of a hair test for ethyl glucuronide (EtG) with the result of 22pg\\/mg in the proximal 0–1cm segment and the segments 1–2cm

  17. A general synthesis of ethyl 4-aminophenyl and ethyl 4-[amino(hydroxyimino)methyl]phenyl phosphonates

    Microsoft Academic Search

    Stanislav Gobec; Katja Štrancar; Uroš Urleb

    2002-01-01

    Diethyl phosphonates were conveniently converted into ethyl 4-aminophenyl and ethyl 4-[amino(hydroxyimino)methyl]phenyl phosphonates as potentially useful intermediates for the preparation of functionalized phenyl phosphonates.

  18. Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation.

    PubMed Central

    Burchell, B; Coughtrie, M W

    1997-01-01

    Glucuronidation and sulfation are phase 2 metabolic reactions catalyzed by large families of different isoenzymes in man. The textbook view that glucuronidation and sulfation lead to the production of harmless conjugates for simple excretion is not valid. Biologically active and toxic sulfates and glucuronides are produced and leed to adverse drug reactions, including immune hypersensitivity. Considerable variation in xenobiotic conjugation is observed as a result of altered expression of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (STs). Recent cloning and expression of human cDNA encoding UGTs and STs has facilitated characterization of isoform substrate specificity, which has been further validated using specific antibodies and human tissue fractions. The availability of cloned/expressed human enzymes and specific antibodies has enabled the investigation of xenobiotic induction and metabolic disruption leeding to adverse responses. Genetic polymorphisms of glucuronidation and sulfation are known to exist although the characterization and assessment of the importance of these variations are hampered by appropriate ethical studies in men with suitable safe model compounds. Genetic analysis has allowed molecular identification of defects in well-known hyperbilirubinemias. However, full characterization of the specific functional roles of human UGTs and STs requires rigorous kinetic and molecular analyses of the role of each enzyme in vivo through the use of specific antibodies and inhibitors. This will leed to the better prediction of variation of xenobiotic glucuronidation and sulfation in man. PMID:9255555

  19. Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis.

    PubMed

    Ferslew, B C; Johnston, C K; Tsakalozou, E; Bridges, A S; Paine, M F; Jia, W; Stewart, P W; Barritt, A S; Brouwer, K L R

    2015-04-01

    The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (Cmax ) and area under the concentration-time curve (AUC0-last ) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225 nM and 58.8 vs. 37.2 µM*min, respectively; P???0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide Cmax and AUC0-last (P < 0.001). Fasting serum glycocholate, taurocholate, and total bile acid concentrations were associated with NASH severity (P < 0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population. PMID:25669174

  20. Carboxyl nonsteroidal anti-inflammatory drugs are efficiently glucuronidated by microsomes of the human gastrointestinal tract.

    PubMed

    Sabolovic, Nicole; Heydel, Jean-Marie; Li, Xin; Little, Joanna M; Humbert, Anne-Claude; Radominska-Pandya, Anna; Magdalou, Jacques

    2004-11-18

    Limited studies have been carried out on the biotransformation of carboxyl nonsteroidal anti-inflammatory drugs (NSAIDs) in the liver. However, the role of the intestine in NSAID metabolism has not been investigated. In this report, the contribution of UDP-glucuronosyltransferases (UGTs) in the human gastrointestinal (GI) tract from five donors to the glucuronidation of the NSAIDs, RS-ketoprofen, S-naproxen, RS- and S-etodolac, was investigated. UGT activity and, for some donors, mRNA levels were evaluated. All NSAIDs were glucuronidated throughout the GI tract; however, glucuronidation was low in stomach and duodenum as compared to the remainder of the intestine. RT-PCR analysis demonstrated that the UGT1A isoforms, UGT1A3, 1A8, and 1A10, and UGT2B7 were expressed in the GI tract. Human recombinant UGT1A3, 1A9, 1A10 and 2B7 were actively involved in the glucuronidation of all NSAIDs while UGT1A7 and the intestine-specific UGT1A8 had no glucuronidating activity towards those compounds. Despite interindividual variations in both the levels of mRNA and the distribution of activity through the intestine, UGTs in the GI tract may contribute significantly to the first pass metabolism of orally administered NSAIDs. PMID:15535975

  1. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...Tolerances are established for residues of the herbicide quizalofop ethyl, including its...Tolerances are established for residues of the herbicide quizalofop ethyl, including...registration are established for residues of the herbicide quizalofop ethyl,...

  2. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...Tolerances are established for residues of the herbicide quizalofop ethyl, including its...Tolerances are established for residues of the herbicide quizalofop ethyl, including...registration are established for residues of the herbicide quizalofop ethyl,...

  3. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...Tolerances are established for residues of the herbicide quizalofop ethyl, including its...Tolerances are established for residues of the herbicide quizalofop ethyl, including...registration are established for residues of the herbicide quizalofop ethyl,...

  4. Simplified analysis of acetaminophen glucuronide for quantifying gluconeogenesis and glycogenolysis using deuterated water.

    PubMed

    Jones, J; Kahl, S; Carvalho, F; Barosa, C; Roden, M

    2015-06-15

    Measurement of acetaminophen glucuronide (AG) (2)H enrichment from deuterated water ((2)H2O) by (2)H nuclear magnetic resonance (NMR) analysis of its monoacetone glucose (MAG) derivative provides estimation of gluconeogenic and glycogenolytic contributions to endogenous glucose production (EGP). However, AG derivatization to MAG is laborious and unsuitable for high-throughput studies. An alternative derivative, 5-O-acetyl monoacetone glucuronolactone (MAGLA), was tested. Eleven healthy subjects ingested (2)H2O to 0.5% body water enrichment and 500mg of acetaminophen. Plasma glucose and urinary glucuronide positional (2)H enrichments were measured by (2)H NMR spectroscopy of MAG and MAGLA, respectively. A Bland-Altman analysis indicated agreement at the 95% confidence level between glucose and glucuronide estimates. PMID:25800563

  5. Stereoselective urinary excretion of formoterol and its glucuronide conjugate in human

    PubMed Central

    Zhang, Mei; Fawcett, J Paul; Shaw, John P

    2002-01-01

    Aims Formoterol is an inhaled ?2-adrenoceptor agonist used as a racemic mixture of the active (R; R)- and inactive (S; S)-enantiomers (rac-formoterol). Glucuronidation is an important route of metabolism in humans which occurs faster for (S; S)-formoterol in human liver microsomes. The aim of this study was to investigate the stereoselectivity of urinary excretion of formoterol and its glucuronide conjugate after oral dosing with rac-formoterol. Methods Seven nonsmoking volunteers (six males, one female) were included in the study. After an overnight fast, a single 60 µg oral dose of rac-formoterol fumarate dihydrate was ingested. Urine samples were collected at 1 h intervals for the first 4 h, and at 6, 8, 12 and 24 h after dosing. Formoterol enantiomers were analysed by chiral h.p.l.c. assay and formoterol glucuronides were determined as formoterol enantiomers after enzymatic cleavage with ?-glucuronidase. Results The female subject displayed a different pattern of metabolism and statistical analysis was therefore limited to data for the six males. The median (range) of the total urinary excretion of formoterol was 37.8% (20.9–51.2%) of the dose. The medians (ranges) of the amounts of (R; R)- and (S; S)-formoterol and of (R; R)- and (S; S)-formoterol glucuronide excreted were 2.1 (1.0–2.9), 3.5 (2.6–3.8), 21.0 (13.1–31.0) and 10.3 (4.2–14.6)%, respectively, of the dose. Unchanged (S; S)-formoterol excretion was significantly greater than that of unchanged (R; R)-formoterol and (R; R)-formoterol glucuronide excretion was significantly greater than that of (S; S)-formoterol glucuronide. The total RR-formoterol (unchanged drug plus glucuronide) excreted was significantly greater than the total (S; S)-formoterol. Conclusions Our study demonstrates that the urinary excretion of formoterol in male humans after oral administration of rac-formoterol is stereoselective with preferential excretion of the active (R; R)-formoterol as unchanged drug and glucuronide. The different pattern of metabolism in the female subject provides impetus for further studies of the effect of gender on the stereoselective metabolism and pharmacokinetics of formoterol. PMID:12236843

  6. Transport of estradiol-17?-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems.

    PubMed

    Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

    2014-03-01

    Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17?-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. Based on their physicochemical properties such compounds are not favored for passive diffusion and therefore likely necessitate transport system(s) to cross the ER membrane in either direction. The current study aims to investigate the transport of taurocholate, estradiol-17?-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR(-) rat liver. Time-dependent and bidirectional transport was demonstrated for taurocholate, showing higher uptake rates in SER than RER vesicles. For estradiol-17?-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. Estrone-3-sulfate uptake was time-dependent and higher in SER than in RER vesicles. Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17?-glucuronide transport. Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17?-glucuronide across the ER membrane. PMID:24406246

  7. Glucuronidation and Covalent Protein Binding of Benoxaprofen and Flunoxaprofen in Sandwich-Cultured Rat and Human Hepatocytes

    PubMed Central

    Dong, Jennifer Q.

    2009-01-01

    Benoxaprofen (BNX), a nonsteroidal anti-inflammatory drug (NSAID) that was withdrawn because of hepatotoxicity, is more toxic than its structural analog flunoxaprofen (FLX) in humans and rats. Acyl glucuronides have been hypothesized to be reactive metabolites and may be associated with toxicity. Both time- and concentration-dependent glucuronidation and covalent binding of BNX, FLX, and ibuprofen (IBP) were determined by exposing sandwich-cultured rat hepatocytes to each NSAID. The levels of glucuronide and covalent protein adduct measured in cells followed the order BNX > FLX > IBP. These results indicate that 1) BNX-glucuronide (G) is more reactive than FLX-G, and 2) IBP-G is the least reactive metabolite, which support previous in vivo studies in rats. The proportional increases of protein adduct formation for BNX, FLX, and IBP as acyl glucuronidation increased also support the hypothesis that part of the covalent binding of all three NSAIDs to hepatic proteins is acyl glucuronide-dependent. Moreover, theses studies confirmed the feasibility of using sandwich-cultured rat hepatocytes for studying glucuronidation and covalent binding to hepatocellular proteins. These studies also showed that these in vitro methods can be applied using human tissues for the study of acyl glucuronide reactivity. More BNX-protein adduct was formed in sandwich-cultured human hepatocytes than FLX-protein adduct, which not only agreed with its relative toxicity in humans but also was consistent with the in vitro findings using rat hepatocyte cultures. These data support the use of sandwich-cultured human hepatocytes as an in vitro screening model of acyl glucuronide exposure and reactivity. PMID:19773537

  8. Profiling serum bile acid glucuronides in humans: gender divergences, genetic determinants, and response to fenofibrate.

    PubMed

    Trottier, J; Perreault, M; Rudkowska, I; Levy, C; Dallaire-Theroux, A; Verreault, M; Caron, P; Staels, B; Vohl, M-C; Straka, R J; Barbier, O

    2013-10-01

    Glucuronidation, catalyzed by uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic bile acids (BAs). We aimed to (i) characterize the circulating BA-glucuronide (BA-G) pool composition in humans, (ii) determine how sex and UGT polymorphisms influence this composition, and (iii) analyze the effects of the lipid-lowering drug fenofibrate on the circulating BA-G profile in 300 volunteers and 5 cholestatic patients. Eleven BA-Gs were determined in pre- and postfenofibrate samples. Men exhibited higher BA-G concentrations, and various genotype/BA-G associations were discovered in relevant UGT genes. The chenodeoxycholic acid-3G (CDCA-3G) concentration was associated with the UGT2B7 802C>T polymorphism. Glucuronidation assays confirmed the predominant role of UGT2B7 and UGT1A4 in CDCA-3G formation. Fenofibrate exposure increased the serum levels of five BA-G species, including CDCA-3G, and upregulated expression of UGT1A4, but not UGT2B7, in hepatic cells. This study demonstrated that fenofibrate stimulates BA glucuronidation in humans and thus reduces BA toxicity in the liver. PMID:23756370

  9. The formation of bilirubin and p-nitrophenyl glucuronides by rabbit liver

    PubMed Central

    Tomlinson, Geraldine A.; Yaffe, Sumner J.

    1966-01-01

    1. Glucuronide formation of bilirubin and p-nitrophenol in vitro with excess of UDP-glucuronic acid by UDP-glucuronyltransferase from livers of young and adult rabbits was studied. 2. The development of UDP-glucuronyltransferase for the two substrates followed a markedly different pattern during maturation of young rabbits, p-nitrophenol-conjugation ability being much higher at birth than that for bilirubin. 3. Mg2+ increased bilirubin conjugation, but inhibited p-nitrophenyl glucuronide formation. 4. p-Nitrophenol acted as a potent non-competitive inhibitor for bilirubin conjugation but bilirubin did not affect p-nitrophenyl glucuronidation. 5. The enzyme for bilirubin conjugation was inactivated at pH9 during treatment with snake venom, whereas in the same preparation the activity of the corresponding enzyme for p-nitrophenol was enhanced. In addition, some solubilization of the latter enzyme could be achieved by this method. 6. The possibility of the existence of more than one enzyme system for the formation of O-glucuronides is discussed. PMID:5944248

  10. Differences in the Glucuronidation of Resveratrol and Pterostilbene: Altered Enzyme Specificity and Potential Gender Differences

    PubMed Central

    Dellinger, Ryan W.; Gomez Garcia, Angela M.; Meyskens, Frank L.

    2015-01-01

    Summary Resveratrol, a natural polyphenol found in grapes, berries and other plants, has been proposed as an ideal chemopreventative agent due to its plethora of health promoting activities. However, despite its lofty promise as a cancer prevention agent its success in human clinical trials has been limited due to its poor bioavailability. Thus, interest in other natural polyphenols is intensifying including the naturally occurring dimethylated analog of resveratrol, pterostilbene. The UDP-glucuronosyltransferase (UGT) family of enzymes plays a vital role in the metabolism of both resveratrol and pterostilbene. The current study sought to elucidate the UGT family members responsible for the metabolism of pterostilbene and to examine gender differences in the glucuronidation of resveratrol and pterostilbene. We demonstrate that UGT1A1 and UGT1A3 are mainly responsible for pterostilbene glucuronidation although UGT1A8, UGT1A9 and UGT1A10 also had detectable activity. Intriguingly, UGT1A1 exhibits the highest activity against both resveratrol and pterostilbene despite altered hydroxyl group specificity. Using pooled human liver microsomes, enzyme kinetics were determined for pterostilbene and resveratrol glucuronides. In all cases females were more efficient than males, indicating potential gender differences in stilbene metabolism. Importantly, the glucuronidation of pterostilbene is much less efficient than that of resveratrol, indicating that pterostilbene will have dramatically decreased metabolism in humans. PMID:23965644

  11. In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative MetabolitesS

    E-print Network

    Hammock, Bruce D.

    In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative MetabolitesS N. H: Triclocarban (3,4,4 -trichlorocarbanilide; TCC) is widely used as an antibacterial in bar soaps. During use,4,4 -trichlorocarbanilide; TCC) (Fig. 1) is widely used as an antibacterial agent in bar soaps in the United States. It can

  12. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

  13. The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients

    Microsoft Academic Search

    Anthony G. Johnson; Russell J. Rigby; Paul J. Taylor; Christopher E. Jones; Joan Allen; Kirsten Franzen; Michael C. Falk; David Nicol

    1999-01-01

    Background: Mycophenolic acid kinetics have been reported to vary after renal transplantation, and mycophenolic acid area under the concentration–time curve (AUC) is the best predictor of suppression of graft rejection.Methods: To determine whether mycophenolic acid kinetics vary after renal transplantation and to examine the potential role of enterohepatic recirculation, we investigated the kinetics of mycophenolic acid and mycophenolic acid glucuronide

  14. Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Pharmacokinetic Parameters of Rosiglitazone in Healthy Subjects

    PubMed Central

    Braeckman, Rene A; Stirtan, William G; Soni, Paresh N

    2015-01-01

    Background Icosapent ethyl is a high-purity form of eicosapentaenoic acid ethyl ester approved to reduce triglyceride levels in adults with triglycerides ?500?mg/dL. Candidates for triglyceride-lowering therapy include patients with diabetes mellitus who may be receiving rosiglitazone. We assessed the effects of icosapent ethyl on the pharmacokinetic parameters of rosiglitazone. Methods Subjects received a single 8-mg oral dose of rosiglitazone alone and with oral icosapent ethyl 4?g/day in this open-label drug–drug interaction study. Pharmacokinetic end points included area under the concentration versus time curve from time zero to infinity (AUC0–inf) and maximum observed concentration (Cmax) for rosiglitazone with and without icosapent ethyl. Results Of 30 subjects enrolled, 28 completed the study. Icosapent ethyl 4?g/day at steady-state did not significantly change the single-dose AUC0–inf or Cmax of rosiglitazone 8?mg. Least squares geometric mean ratios (90% confidence interval) for AUC0–inf and Cmax of rosiglitazone given with icosapent ethyl versus rosiglitazone alone were 0.90 (87.00–93.40) and 1.01 (92.02–109.9), respectively. No serious adverse events were reported and no subject discontinued due to an adverse event. Conclusions At steady-state concentrations, icosapent ethyl did not inhibit the pharmacokinetics of rosiglitazone. Co-administration of icosapent ethyl and rosiglitazone was safe and well tolerated.

  15. Role of Glucuronidation for Hepatic Detoxification and Urinary Elimination of Toxic Bile Acids during Biliary Obstruction

    PubMed Central

    Perreault, Martin; Bia?ek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Milkiewicz, Piotr; Barbier, Olivier

    2013-01-01

    Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives. PMID:24244729

  16. Mitochondrial Dysfunction Leads to Deconjugation of Quercetin Glucuronides in Inflammatory Macrophages

    PubMed Central

    Miki, Satomi; Shiba, Yuko; Minekawa, Shoko; Nishikawa, Tomomi; Mukai, Rie; Terao, Junji; Kawai, Yoshichika

    2013-01-01

    Dietary flavonoids, such as quercetin, have long been recognized to protect blood vessels from atherogenic inflammation by yet unknown mechanisms. We have previously discovered the specific localization of quercetin-3-O-glucuronide (Q3GA), a phase II metabolite of quercetin, in macrophage cells in the human atherosclerotic lesions, but the biological significance is poorly understood. We have now demonstrated the molecular basis of the interaction between quercetin glucuronides and macrophages, leading to deconjugation of the glucuronides into the active aglycone. In vitro experiments showed that Q3GA was bound to the cell surface proteins of macrophages through anion binding and was readily deconjugated into the aglycone. It is of interest that the macrophage-mediated deconjugation of Q3GA was significantly enhanced upon inflammatory activation by lipopolysaccharide (LPS). Zymography and immunoblotting analysis revealed that ?-glucuronidase is the major enzyme responsible for the deglucuronidation, whereas the secretion rate was not affected after LPS treatment. We found that extracellular acidification, which is required for the activity of ?-glucuronidase, was significantly induced upon LPS treatment and was due to the increased lactate secretion associated with mitochondrial dysfunction. In addition, the ?-glucuronidase secretion, which is triggered by intracellular calcium ions, was also induced by mitochondria dysfunction characterized using antimycin-A (a mitochondrial inhibitor) and siRNA-knockdown of Atg7 (an essential gene for autophagy). The deconjugated aglycone, quercetin, acts as an anti-inflammatory agent in the stimulated macrophages by inhibiting the c-Jun N-terminal kinase activation, whereas Q3GA acts only in the presence of extracellular ?-glucuronidase activity. Finally, we demonstrated the deconjugation of quercetin glucuronides including the sulfoglucuronides in vivo in the spleen of mice challenged with LPS. These results showed that mitochondrial dysfunction plays a crucial role in the deconjugation of quercetin glucuronides in macrophages. Collectively, this study contributes to clarifying the mechanism responsible for the anti-inflammatory activity of dietary flavonoids within the inflammation sites. PMID:24260490

  17. Tissue and species differences in the glucuronidation of glabridin with UDP-glucuronosyltransferases.

    PubMed

    Guo, Bin; Fang, Zhongze; Yang, Lu; Xiao, Ling; Xia, Yangliu; Gonzalez, Frank J; Zhu, Liangliang; Cao, Yunfeng; Ge, Guangbo; Yang, Ling; Sun, Hongzhi

    2015-04-25

    Glabridin (GA) has gained wide application in the cosmetics and food industry. This study was performed to investigate its metabolic inactivation and elimination by glucuronidation by use of liver and intestine microsomes from humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4 positions of the B ring are conjugated to generate two mono-glucuronides (M1 and M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation with intrinsic clearance values (Clint) above 2000 ?L/min/mg, with little measurable M1 formation activity. DLM displayed considerable activity both in M1 and M2 formation, with Clint values of 71 and 214 ?L/min/mg, respectively, while HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with Clint values all below 20 ?L/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7, 2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the highest activity with a Clint value more than 5-fold higher than the other isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9, 2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal GA glucuronidation in humans. In summary, this in vitro study demonstrated large species differences in GA glucuronidation by liver and intestinal microsomes, and that intestinal UGTs are important for the pathway in humans. PMID:25765239

  18. Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide.

    PubMed

    Rühl, R; Thiel, R; Lacker, T S; Strohschein, S; Albert, K; Nau, H

    2001-06-01

    Retinoic acid-glucuronides are known as retinoids with activity in acne therapy, limited placental transfer and reduced retinoid adverse effects. We synthesized the glucuronide of a novel retinoid, CD271 (adapalene), used for the treatment of moderate acne. The synthesis product ("CD271 glucuronide", CD271G) was purified by preparative HPLC. It undergoes in aqueous solution, like other glucuronides, rapid acyl-migration of the bound aglycone leading to position isomers. Thus characterization of purified CD271G could be only achieved by HPLC-NMR coupling. A subfraction ("CD271GB") consisting essentially of 2'- and 3'-CD271G was used for pharmacokinetic studies. After a single subcutaneous injection at a dosage of 30 mg/kg the substance showed considerable uptake and metabolism to CD271 indicating that CD271GB could serve as a prodrug for CD271. PMID:11419733

  19. Predominant Contribution of UDP-Glucuronosyltransferase 2B7 in the Glucuronidation of Racemic Flurbiprofen in the Human Liver

    Microsoft Academic Search

    Yuji Mano; Takashi Usui; Hidetaka Kamimura

    2007-01-01

    Flurbiprofen is a nonsteroidal anti-inflammatory drug used as a racemic mixture. Although glucuronidation is one of its elimination pathways, the role of UDP-glucuronosyltransferase (UGT) in this process remains to be investigated. Thus, the kinetics of the ste- reoselective glucuronidation of racemic (R,S)-flurbiprofen by re- combinant UGT isozymes and human liver microsomes (HLMs) were investigated, and the major human UGT isozymes

  20. Overestimation of Flavonoid Aglycones as a Result of the ex vivo Deconjugation of Glucuronides by the Tissue ?-Glucuronidase

    PubMed Central

    Lu, Qing-Yi; Zhang, Lifeng; Eibl, Guido; Go, Vay-Liang W.

    2013-01-01

    Flavonoid glucuronides are the main circulating metabolites of flavonoids in humans and animals. There has been a growing interest in the biological function of glucuronides. In order to differentiate biological activity and to assess efficacy it is essential to accurately determine the levels of flavonoid aglycone and metabolic conjugate in vivo. Many organs and body fluids of humans and animals exhibit ?-glucuronidase against flavonoid glucuronides. Studies have shown that ?-glucuronidase within the tissues hydrolyzes glucuronides to their aglycones during the tissue extraction, leading to artificially higher reported tissue levels of aglycone than actual in vivo concentrations. The aims of this study were to estimate the extent by which the aglycones were overestimated and to investigate the use of saccharo-1,4-lactone, a ?-glucuronidase inhibitor, to block the ex vivo hydrolysis of flavonoid glucuronides. Our data demonstrate that in mouse liver tissues and human tumor xenografts levels of quercetin and methylated quercetin aglycones could be over-estimated by 7 fold. The inhibition of deconjugation of quercetin and baicalein glucuronides by saccharo-1,4-lactone is dose-dependent. The amount of saccharo-1,4-lactone used to produce optimal inhibition of the enzyme activity is in the range of 15 – 24 ?mol per gram of liver tissue. The use of ?-glucuronidase inhibitor blocks the ex vivo deconjugation resulting in an accurate estimation of tissue levels of aglycone and conjugate. Our study described here can be extended to other animal models and human studies with different types of substrates of ?-glucuronidase. PMID:24176739

  1. The Contribution of Common UGT2B10 and CYP2A6 Alleles to Variation in Nicotine Glucuronidation among European Americans

    PubMed Central

    Bloom, A. Joseph; von Weymarn, Linda B.; Martinez, Maribel; Bierut, Laura J.; Goate, Alison; Murphy, Sharon E.

    2014-01-01

    UDP-glucuronosytransferase-2B10 (UGT2B10) is the primary catalyst of nicotine glucuronidation. To develop a predictive genetic model of nicotine metabolism, the conversion of deuterated (D2)-nicotine to D2-nicotine-glucuronide, D2-cotinine, D2-cotinine-glucuronide, and D2-trans-3'-hydroxycotinine were quantified in 188 European Americans, and the contribution of UGT2B10 genotype to variability in first-pass nicotine glucuronidation assessed, following a procedure previously applied to nicotine C-oxidation. The proportion of total nicotine converted to nicotine-glucuronide (D2-nicotine-glucuronide/ (D2-nicotine +D2-nicotine-glucuronide +D2-cotinine +D2-cotinine-glucuronide +D2-trans-3'-hydroxycotinine)) was the primary phenotype. The variant, rs61750900T (D67Y) (minor allele frequency (MAF) = 10%), is confirmed to abolish nicotine glucuronidation activity. Another variant, rs112561475G (N397D) (MAF = 2%), is significantly associated with enhanced glucuronidation. rs112561475G is the ancestral allele of a well-conserved amino acid, indicating that the majority of human UGT2B10 alleles are derived hypomorphic alleles. CYP2A6 and UGT2B10 genotype explain 53% of the variance in oral nicotine glucuronidation in this sample. CYP2A6 and UGT2B10 genetic variants are also significantly associated with un-deuterated (D0) nicotine glucuronidation in subjects smoking ad libitum. We find no evidence for further common variation markedly influencing hepatic UGT2B10 expression in European Americans. PMID:24192532

  2. Epicatechin and catechin are O-methylated and glucuronidated in the small intestine.

    PubMed

    Kuhnle, G; Spencer, J P; Schroeter, H; Shenoy, B; Debnam, E S; Srai, S K; Rice-Evans, C; Hahn, U

    2000-10-22

    There is considerable interest in the bioavailability of polyphenols and their bioactivity in vivo. We have studied the absorption and metabolism of catechin and epicatechin in the small intestine and the comparative transfer across the jejunum and ileum. Perfusion of isolated jejunum with the flavanols resulted in glucuronidation ( approximately 45%), O-methylation: 3'-O-Methyl- and 4'-O-methyl- ( approximately 30%), and O-methyl-glucuronidation ( approximately 20% of total flavanols identified) during transfer across the enterocytes to the serosal side. This demonstrates the activity of catechol-O-methyl transferases in the metabolism of flavanols and suggests that these metabolites and conjugates are likely to enter the portal vein. In contrast, in the case of the ileum, the majority of the flavanols appeared on the serosal side unmetabolised and the total percentage of flavanols transferred was higher than that in the jejunum ( approximately fivefold). PMID:11032751

  3. Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

    SciTech Connect

    Mendizabal, A.F.; Quiroga, S.; Farinati, Z.; Lahoz, M.; Nagle, C.

    1984-11-01

    The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E/sub 3/G) and pregnanediol-3-glucuronide (P/sub 2/G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E/sub 3/G and P/sub 2/G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E/sub 3/G and P/sub 2/G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit.

  4. A new cyclopamine glucuronide prodrug with improved kinetics of drug release.

    PubMed

    Renoux, Brigitte; Legigan, Thibaut; Bensalma, Souheyla; Chadéneau, Corinne; Muller, Jean-Marc; Papot, Sébastien

    2011-12-21

    We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of ?-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity. PMID:22042246

  5. Valproate Reduces the Glucuronidation of Asenapine Without Affecting Asenapine Plasma Concentrations

    Microsoft Academic Search

    Mireille G. F. Gerrits; Rik de Greef; Peter Dogterom; Pierre A. M. Peeters

    2012-01-01

    Asenapine is indicated for treatment of schizophrenia in the United States and acute treatment of manic or mixed episodes, as monotherapy (United States and European Union) or adjunct therapy (United States only), associated with bipolar I disorder. It is extensively metabolized; the 2 main metabolites are asenapine N-glucuronide and N-desmethyl-asenapine. The authors investigated the pharmacokinetic interactions between asenapine and valproate

  6. A new oleanene glucuronide having a branched-chain sugar from Melilotus officinalis.

    PubMed

    Udayama, M; Kinjo, J; Yoshida, N; Nohara, T

    1998-03-01

    A new oleanene glucuronide called melilotus-saponin O1 (1) was isolated together with three known ones from the roots of Melilotus officinalis (L.) PALLAS (Leguminosae). The structure of 1 was determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1--> 3)]- beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl soyasapogenol B by spectroscopic and chemical methods. PMID:9549893

  7. Chemical reactivity of the naproxen acyl glucuronide and the naproxen coenzyme A thioester towards bionucleophiles

    Microsoft Academic Search

    Jørgen Olsen; Inga Bjørnsdottir; Jette Tjørnelund; Steen Honoré Hansen

    2002-01-01

    Drugs may be metabolised to reactive electrophilic species that spontaneously react with proteins. The presence of such drug–protein adducts has been associated with drug toxicity. In this study, the reactivity of the major metabolite of naproxen—the 1-?-O-glucuronide (Nap-GlcU)—was compared to the corresponding naproxen coenzyme A (Nap-CoA) thioester. The reactivity of the two metabolites was assessed in vitro in a phosphate

  8. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation.

    PubMed

    Abernethy, D R; Greenblatt, D J; Ameer, B; Shader, R I

    1985-08-01

    Eleven subjects received acetaminophen (650 mg i.v.) on two occasions in random sequence, with and without concurrent administration of probenecid (500 mg) every 6 hr. Nine subjects similarly received lorazepam (2 mg. i.v.) with and without concurrent probenecid. Acetaminophen half-life was prolonged during probenecid treatment (mean +/- S.E., 4.30 +/- 0.23 vs. 2.51 +/- 0.16 hr; P less than .001) due to markedly decreased clearance (178 +/- 13 vs. 329 +/- 24 ml/min; P less than .001) with no change in volume of distribution (65 +/- 4 vs. 69 +/- 3 l; NS). Urinary excretion of acetaminophen glucuronide during 24 hr was decreased (84 +/- 9 vs. 260 +/- 21 mg of acetaminophen as glucuronide; P less than .001) and acetaminophen sulfate excretion was increased (323 +/- 25 vs. 217 +/- 17 mg of acetaminophen as sulfate; P less than .005) during concurrent probenecid treatment. However, the sum of the two conjugated metabolites was not significantly different (407 +/- 28 vs. 476 +/- 20 mg of acetaminophen as glucuronide plus sulfate excreted per 24 hr; NS). Lorazepam half-life was also prolonged during probenecid treatment (33.0 +/- 3.9 vs. 14.3 +/- 1.08 hr; P less than .001) due to decreased clearance (44.7 +/- 5.4 vs. 80.3 +/- 13.2 ml/min; P less than .001) with no change in volume of distribution (111 +/- 5 vs. 111 +/- 7 l; NS). Formation of the ether glucuronides of acetaminophen and lorazepam is impaired markedly by therapeutic doses of probenecid. Sulfate conjugation is not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4020675

  9. High-performance liquid chromatography determination of mycophenolic acid and its glucuronide metabolite in human plasma

    Microsoft Academic Search

    Christopher E Jones; Paul J Taylor; Anthony G Johnson

    1998-01-01

    Two HPLC–UV assays are reported here: one is a rapid assay for mycophenolic acid (MPA) and the other is a simultaneous assay for MPA and its metabolite mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500 ?l) with added internal standard were acidified and extracted using C18 solid-phase extraction cartridges. Chromatographic separation was achieved on a C18 Novapak column

  10. Rapid and sensitive determination of propofol glucuronide in hair by liquid chromatography and tandem mass spectrometry.

    PubMed

    Kim, Hee Seung; Cheong, Jae Chul; Lee, Jae Il; In, Moon Kyo

    2013-11-01

    A fast, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantitation of propofol glucuronide in human hair has been developed and validated. Propofol glucuronide was extracted from 10mg of hair using a simple methanol extraction method, with recovery greater than 91% at 3 quality control samples (15, 100, 4000 pg/mg). A reversed phase column (C8) was used to analyze and the mobile phase was composed of ammonium formate and acetonitrile gradient at a flow rate of 0.2 mL/min. The lower limit of quantitation (LLOQ) was 5 pg/mg and the assay was linear to 5000 pg/mg. The intra- and inter-day precision (% CV, coefficient of variation) ranged from 1.26 to 4.50% while the accuracy (% RE, relative error) were -4.24 to 4.4%. The matrix effects were monitored at 3 different concentrations and the %CV of the results for these concentrations was less than 10.6%. Propofol glucuronide was stable during processing and analysis in human hair. The procedure was validated and applied to the analysis of hair samples in human subjects previously administered in propofol. PMID:23872469

  11. The effect of various drugs on the glucuronidation of zidovudine (azidothymidine; AZT) by human liver microsomes.

    PubMed Central

    Sim, S M; Back, D J; Breckenridge, A M

    1991-01-01

    1. Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the drug of proven efficacy available for the treatment of patients with AIDS or ARC. It is eliminated mainly by hepatic glucuronidation. Therefore, interference with this metabolic pathway may lead to enhancement of AZT effect or to increased toxicity of the drug. We have examined the effect of a number of drugs which themselves undergo glucuronidation on AZT conjugation by human liver microsomes in vitro. 2. AZT glucuronidation followed Michaelis-Menten kinetics. The apparent Km and Vmax values (mean +/- s.d., n = 5), were 2.60 +/- 0.52 mM and 68.0 +/- 23.4 nmol h-1 mg-1, respectively, as determined from Eadie-Hofstee plots. 3. Dideoxyinosine, sulphanilamide and paracetamol were essentially non-inhibitory at concentrations up to 10 mM (4 times the concentration of AZT in the incubation). The most marked inhibitory effects were seen with indomethacin, naproxen, chloramphenicol, probenecid and ethinyloestradiol, with enzyme activity decreased by 97.7, 94.9, 88.7, 83.4% and 79.0%, respectively, at a concentration of 10 mM. Other compounds producing some inhibition of AZT conjugation were oxazepam, salicylic acid and acetylsalicylic acid. 4. Further studies are necessary to characterise the inhibition observed but the method described enables a screen of potentially important drug interactions to be carried out. PMID:1909542

  12. Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3'-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities.

    PubMed

    Yamamoto, Masaki; Jokura, Hiroko; Hashizume, Koujiro; Ominami, Hideo; Shibuya, Yusuke; Suzuki, Atsushi; Hase, Tadashi; Shimotoyodome, Akira

    2013-09-01

    Orally ingested hesperidin (HES) is hydrolyzed into hesperetin in the gastrointestinal tract and conjugated during absorption. Hesperetin conjugates are the main circulating metabolites in human and rat plasma. We previously reported that glucosyl hesperidin (GHES), a water-soluble HES derivative, prevents hypertension via improvement of endothelial dysfunction in spontaneously hypertensive rats (SHRs). Although these hesperetin conjugates seem to be responsible for hypotensive and endothelium-dependent vasodilatory activities of dietary GHES, little is known about the mechanisms of action of these conjugated metabolites. Therefore, the aim of the present study was to investigate the effects of hesperetin-7-O-?-d-glucuronide (HPT7G) and hesperetin-3'-O-?-d-glucuronide (HPT3'G), which are the predominant HES metabolites in rat plasma, on blood pressure and endothelial function. Intravenous administration of HPT7G (5 mg kg(-1)) decreased blood pressure in anesthetized SHRs. HPT7G enhanced endothelium-dependent vasodilation in response to acetylcholine, but had no effect on endothelium-independent vasodilation in response to sodium nitroprusside (SNP) in aortas isolated from SHRs. HPT7G decreased hydrogen peroxide-induced intracellular adhesion molecule-1 and monocyte chemoattractant protein-1 mRNA expression in rat aortic endothelial cells. In contrast, HPT3'G had little effect on these parameters. In conclusion, HPT7G exerted hypotensive, vasodilatory and anti-inflammatory activities, similar to hesperetin and these effects are associated, in part, with the activity of GHES and HES to improve hypertension and endothelial dysfunction. PMID:23831969

  13. Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry

    PubMed Central

    Niemeyer, Emily D.; Brodbelt, Jennifer S.

    2013-01-01

    The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide. PMID:23713759

  14. 40 CFR 180.429 - Chlorimuron ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...180.429 Chlorimuron ethyl; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide chlorimuron ethyl, including its metabolites and degradates, in or on the commodities in the table below....

  15. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...false Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441 ...AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.441 Quizalofop ethyl; tolerances for residues. (a) General. (1)...

  16. Elastic electron scattering by ethyl vinyl ether

    SciTech Connect

    Khakoo, M. A.; Hong, L.; Kim, B.; Winstead, C.; McKoy, V. [Department of Physics, California State University, Fullerton, California 92834 (United States); Troy High School, 2200 Dorothy Lane, Fullerton, California 92831 (United States); A. A. Noyes Laboratory of Chemical Physics, California Institute of Technology, Pasadena, California 91125 (United States)

    2010-02-15

    We report measured and calculated results for elastic scattering of low-energy electrons by ethyl vinyl ether (ethoxyethene), a prototype system for studying indirect dissociative attachment processes that may play a role in DNA damage. The integral cross section displays the expected {pi}{sup *} shape resonance. The agreement between the calculated and measured cross sections is generally good.

  17. Striations in an ethyl alcohol glow discharge

    NASA Astrophysics Data System (ADS)

    Reyes, P. G.; Gómez, A.; Torres, C.; Martínez, H.; Castillo, F.; Vergara, J.

    2015-03-01

    This research shows the behavior of striations in glow discharge generated with high purity ethyl alcohol at a pressure of 0.6 Torr. This paper present the number of striations as a function of the of current and voltage discharge.

  18. 27 CFR 21.107 - Ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...107 Ethyl acetate. (a) 85 percent ester: (1) Acidity (as acetic acid). Not more than 0.015 percent by weight...and none above 80 °C. (b) 100 percent ester: (1) Acidity (as acetic acid). Not more than 0.010 percent by...

  19. 27 CFR 21.107 - Ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...107 Ethyl acetate. (a) 85 percent ester: (1) Acidity (as acetic acid). Not more than 0.015 percent by weight...and none above 80 °C. (b) 100 percent ester: (1) Acidity (as acetic acid). Not more than 0.010 percent by...

  20. 27 CFR 21.107 - Ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...107 Ethyl acetate. (a) 85 percent ester: (1) Acidity (as acetic acid). Not more than 0.015 percent by weight...and none above 80 °C. (b) 100 percent ester: (1) Acidity (as acetic acid). Not more than 0.010 percent by...

  1. Manufacturing Ethyl Acetate From Fermentation Ethanol

    NASA Technical Reports Server (NTRS)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  2. Glass Ratio Glass Ratio pentane (tech) ethyl ether

    E-print Network

    Turro, Claudia

    Glass Ratio Glass Ratio pentane (tech) ethyl ether Petroleum Ether (30-60) 2-methyl-THF 2-methylpentane ethyl ether/isopentane 1:1, 1:2 3-methylpentane ethyl ether/methylcyclohexane 2:3 3-ethylpentane propyl ether/pentane 2:1 2,3-dimethylpentane EtOH 3-methylhexane glycerol 4-methylheptane 1-propanol 3

  3. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...2010-10-01 2010-10-01 false Ethyl ether. 151.50-42 Section 151.50-42...Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks shall...taken to prevent the contamination of ethyl ether by strong oxidizing agents. (h)...

  4. Experimental study of the density and viscosity of 1-ethyl-3 -methylimidazolium ethyl sulfate

    Microsoft Academic Search

    H. Schmidt; M. Stephan; J. Safarov; I. Kul; J. Nocke; I. M. Abdulagatov; E. Hassel

    Density and viscosity of 1-ethyl-3-methylimidazolium ethyl sulfate [EMIM][EtSO4] have been measured over the temperature range from 283.15 K to 413.15 K and at pressures up to 140 MPa and in the temperature range from 283.15 K to 373.15 K at 0.1 MPa, respectively. The expanded uncertainty of the density, pressure, temperature, and viscosity measurements at the 95 % confidence level

  5. Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts.

    PubMed

    Spencer, J P; Schroeter, H; Crossthwaithe, A J; Kuhnle, G; Williams, R J; Rice-Evans, C

    2001-11-01

    The purpose of this study was to examine the comparative mechanisms by which the dietary form of the flavonoid epicatechin and its predominant in vivo metabolite, epicatechin glucuronide, influence oxidative stress-induced cell death in fibroblasts and neurons. The results demonstrate the contrasting influences of in vivo glucuronidation and methylation on the bioactivity of epicatechin. PMID:11677047

  6. Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis

    PubMed Central

    Davé, Shaival H.; Tilstra, Jeremy S.; Matsuoka, Katsuyoshi; Li, Fengling; DeMarco, Richard A.; Beer-Stolz, Donna; Sepulveda, Antonia R.; Fink, Mitchell P.; Lotze, Michael T.; Plevy, Scott E.

    2009-01-01

    Signals from stressed cells and the enteric microbiota activate macrophages and dendritic cells and mediate intestinal inflammation. HMGB1 serves as an immunogenic stimuli causing release of inflammatory cytokines by myeloid cells. Ethyl pyruvate inhibits secretion of HMGB1 and improves survival in models of endotoxemia and hemorrhagic shock. We reasoned that ethyl pyruvate may be protective in colitis, which involves similar inflammatory pathways. In IL-10?/? mice with established chronic colitis, ethyl pyruvate administration ameliorated colitis and reduced intestinal cytokine production. IL-10?/? mice demonstrated increased intestinal HMGB1 expression and decreased expression of RAGE compared with wild-type mice. Fecal HMGB1 levels were decreased in ethyl pyruvate-treated mice. Furthermore, ethyl pyruvate induced HO-1 expression in intestinal tissue. In TNBS-induced colitis, intrarectal administration of ethyl pyruvate resulted in amelioration of colitis and reduced intestinal cytokine production. In LPS-activated murine macrophages, ethyl pyruvate decreased expression of IL-12 p40 and NO production but did not affect IL-10 levels. Ethyl pyruvate did not inhibit nuclear translocation of NF-?B family members but attenuated NF-?B DNA binding. Additionally, ethyl pyruvate induced HO-1 mRNA and protein expression and HO-1 promoter activation. Moreover, ethyl pyruvate prevented nuclear-to-cytoplasmic translocation of HMGB1. In conclusion, the HMGB1/RAGE pathway has pathophysiologic and diagnostic significance in experimental colitis. Ethyl pyruvate and other strategies to inhibit HMGB1 release and function represent promising interventions in chronic inflammatory diseases. PMID:19454652

  7. Antimicrobial and demelanizing activity of Ganoderma lucidum extract, p-hydroxybenzoic and cinnamic acids and their synthetic acetylated glucuronide methyl esters.

    PubMed

    Heleno, Sandrina A; Ferreira, Isabel C F R; Esteves, Ana P; ?iri?, Ana; Glamo?lija, Jasmina; Martins, Anabela; Sokovi?, Marina; Queiroz, Maria João R P

    2013-08-01

    Mushroom extracts or isolated compounds may be useful in the search of new potent antimicrobial agents. Herein, it is described the synthesis of protected (acetylated) glucuronide derivatives of p-hydroxybenzoic and cinnamic acids, two compounds identified in the medicinal mushroom Ganoderma lucidum. Their antimicrobial and demelanizing activities were evaluated and compared to the parent acids and G. lucidum extract. p-Hydroxybenzoic and cinnamic acids, as also their protected glucuronide derivatives revealed high antimicrobial (antibacterial and antifungal) activity, even better than the one showed by commercial standards. Despite the variation in the order of parent acids and the protected glucuronide derivatives, their antimicrobial activity was always higher than the one revealed by the extract. Nevertheless, the extract was the only one with demelanizing activity against Aspergillus niger. The acetylated glucuronide derivatives could be deprotected to obtain glucuronide metabolites, which circulate in the human organism as products of the metabolism of the parent compounds. PMID:23607932

  8. Glucuronidation of macelignan by human liver microsomes and expressed UGT enzymes: identification of UGT1A1 and 2B7 as the main contributing enzymes.

    PubMed

    Liu, Hongming; Wu, Zhufeng; Ma, Zhiguo; Wu, Baojian

    2014-12-01

    Macelignan is a natural phenolic compound that possesses many types of health benefits such as antiinflammation. This study aimed to characterize the metabolism of macelignan via the glucuronidation pathway and to identify the main UGT enzymes involved in macelignan glucuronidation. The rates of glucuronidation were determined by incubating macelignan with UDPGA-supplemented microsomes. Kinetic parameters were derived by fitting an appropriate model to the data. Reaction phenotyping, the relative activity factor (RAF) approach and activity correlation analysis were employed to identify the main UGT enzymes contributing to the hepatic metabolism of macelignan. Glucuronidation of macelignan in pooled human liver microsomes (pHLM) was rather efficient with a high CLint (the intrinsic clearance) value of 13.90 ml/min/mg. All UGT enzymes, except UGT1A4, 1A6 and 2B10, showed metabolic activities toward macelignan. UGT1A1 and 2B7 were the enzymes with the highest activities; the CLint values were 4.92 and 2.13 ml/min/mg, respectively. Further, macelignan glucuronidation was significantly correlated with 3-O-glucuronidation of ?-estradiol (r = 0.69; p < 0.01) and glucuronidation of zidovudine (r = 0.60; p < 0.05) in a bank of individual HLMs (n = 14). Based on the RAF approach, UGT1A1 and 2B7, respectively, contributed 55.40% and 32.20% of macelignan glucuronidation in pHLM. In conclusion, macelignan was efficiently metabolized via the glucuronidation pathway. It was also shown that UGT1A1 and 2B7 were probably the main contributors to the hepatic glucuronidation of macelignan. PMID:25099990

  9. 2D QSAR Study for Gemfibrozil Glucuronide as the Mechanism-based Inhibitor of CYP2C8

    PubMed Central

    Taxak, N.; Bharatam, P. V.

    2013-01-01

    Mechanism-based inhibition of cytochrome P450 involves the bioactivation of the drug to a reactive metabolite, which leads to cytochrome inhibition via various mechanisms. This is generally seen in the Phase I of drug metabolism. However, gemfibrozil (hypolipidemic drug) leads to mechanism-based inhibition after generating glucuronide conjugate (gemfibrozil acyl-?-glucuronide) in the Phase II metabolism reaction. The mechanism involves the covalent binding of the benzyl radical (generated from the oxidation of aromatic methyl group in conjugate) to the heme of CYP2C8. This article deals with the development of a 2D QSAR model based on the inhibitory potential of gemfibrozil, its analogues and corresponding glucuronide conjugates in inhibiting the CYP2C8-catalysed amodiaquine N-deethylation. The 2D QSAR model was developed using multiple linear regression analysis in Accelrys Discovery Studio 2.5 and helps in identifying the descriptors, which are actually contributing to the inhibitory potency of the molecules studied. The built model was further validated using leave one out method. The best quantitative structure activity relationship model was selected having a correlation coefficient (r) of 0.814 and cross-validated correlation coefficient (q2) of 0.799. 2D QSAR revealed the importance of volume descriptor (Mor15v), shape descriptor (SP09) and 3D matrix-based descriptor (SpMax_RG) in defining the activity for this series of molecules. It was observed that volume and 3D matrix-based descriptors were crucial in imparting higher potency to gemfibrozil glucuronide conjugate, as compared with other molecules. The results obtained from the present study may be useful in predicting the inhibitory potential (IC50 for CYP2C8 inhibition) of the glucuronide conjugates of new molecules and compare with the standard gemfibrozil acyl-?-glucuronide (in terms of pIC50 values) in early stages of drug discovery and development. PMID:24591743

  10. Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue ?-glucuronidase.

    PubMed

    Lu, Qing-Yi; Zhang, Lifeng; Eibl, Guido; Go, Vay Liang W

    2014-01-01

    Flavonoid glucuronides are the main circulating metabolites of flavonoids in humans and animals. There has been a growing interest in the biological function of glucuronides. In order to differentiate biological activity and to assess efficacy it is essential to accurately determine the levels of flavonoid aglycone and metabolic conjugate in vivo. Many organs and body fluids of humans and animals exhibit ?-glucuronidase against flavonoid glucuronides. Studies have shown that ?-glucuronidase within the tissues hydrolyzes glucuronides to their aglycones during the tissue extraction, leading to artificially higher reported tissue levels of aglycone than actual in vivo concentrations. The aims of this study were to estimate the extent by which the aglycones were overestimated and to investigate the use of saccharo-1,4-lactone, a ?-glucuronidase inhibitor, to block the ex vivo hydrolysis of flavonoid glucuronides. Our data demonstrate that in mouse liver tissues and human tumor xenografts levels of quercetin and methylated quercetin aglycones could be over-estimated by 7-fold. The inhibition of deconjugation of quercetin and baicalein glucuronides by saccharo-1,4-lactone is dose-dependent. The amount of saccharo-1,4-lactone used to produce optimal inhibition of the enzyme activity is in the range of 15-24?mol per gram of liver tissue. The use of ?-glucuronidase inhibitor blocks the ex vivo deconjugation resulting in an accurate estimation of tissue levels of aglycone and conjugate. Our study described here can be extended to other animal models and human studies with different types of substrates of ?-glucuronidase. PMID:24176739

  11. 2D QSAR Study for Gemfibrozil Glucuronide as the Mechanism-based Inhibitor of CYP2C8.

    PubMed

    Taxak, N; Bharatam, P V

    2013-11-01

    Mechanism-based inhibition of cytochrome P450 involves the bioactivation of the drug to a reactive metabolite, which leads to cytochrome inhibition via various mechanisms. This is generally seen in the Phase I of drug metabolism. However, gemfibrozil (hypolipidemic drug) leads to mechanism-based inhibition after generating glucuronide conjugate (gemfibrozil acyl-?-glucuronide) in the Phase II metabolism reaction. The mechanism involves the covalent binding of the benzyl radical (generated from the oxidation of aromatic methyl group in conjugate) to the heme of CYP2C8. This article deals with the development of a 2D QSAR model based on the inhibitory potential of gemfibrozil, its analogues and corresponding glucuronide conjugates in inhibiting the CYP2C8-catalysed amodiaquine N-deethylation. The 2D QSAR model was developed using multiple linear regression analysis in Accelrys Discovery Studio 2.5 and helps in identifying the descriptors, which are actually contributing to the inhibitory potency of the molecules studied. The built model was further validated using leave one out method. The best quantitative structure activity relationship model was selected having a correlation coefficient (r) of 0.814 and cross-validated correlation coefficient (q(2)) of 0.799. 2D QSAR revealed the importance of volume descriptor (Mor15v), shape descriptor (SP09) and 3D matrix-based descriptor (SpMax_RG) in defining the activity for this series of molecules. It was observed that volume and 3D matrix-based descriptors were crucial in imparting higher potency to gemfibrozil glucuronide conjugate, as compared with other molecules. The results obtained from the present study may be useful in predicting the inhibitory potential (IC50 for CYP2C8 inhibition) of the glucuronide conjugates of new molecules and compare with the standard gemfibrozil acyl-?-glucuronide (in terms of pIC50 values) in early stages of drug discovery and development. PMID:24591743

  12. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

    PubMed Central

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2012-01-01

    Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3?-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of ?-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

  13. Inhibition of Genistein Glucuronidation by Bisphenol A in Human and Rat Liver Microsomes

    PubMed Central

    Coughlin, Janis L.; Thomas, Paul E.

    2012-01-01

    Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a synthetic chemical used in the production of polycarbonate plastics. Both genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing concerns of altered xenobiotic metabolism due to concomitant exposures from soy milk in BPA-laden baby bottles has warranted the investigation of the glucuronidation rate of genistein in the absence and presence (25 ?M) of BPA by human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield Vmax values of 0.93 ± 0.10 nmol · min?1 · mg?1 and 0.62 ± 0.05 nmol · min?1 · mg?1 in the absence and presence of BPA, respectively. Km values for genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 ± 7.9 ?M and 21.5 ± 7.7 ?M, respectively, resulting in a Ki value of 58.7 ?M for BPA. Significantly reduced Vmax and unchanged Km in the presence of BPA in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA resulted in a Ki of 35.7 ?M, an insignificant change in Vmax (2.91 ± 0.26 nmol · min?1 · mg?1 and 3.05 ± 0.41 nmol · min?1 · mg?1 in the absence and presence of BPA, respectively), and an increase in apparent Km (49.4 ± 14 ?M with no BPA and 84.0 ± 28 ?M with BPA), indicative of competitive inhibition. These findings are significant because they suggest that BPA is capable of inhibiting the glucuronidation of genistein in vitro, and that the type of inhibition is different between HLM and RLM. PMID:22146138

  14. Chemical and thermochemical aspects of the ozonolysis of ethyl oleate: decomposition enthalpy of ethyl oleate ozonide.

    PubMed

    Cataldo, Franco

    2013-01-01

    Neat ethyl oleate was ozonized in a bubble reactor and the progress of the ozonolysis was followed by infrared (FT-IR) spectroscopy and by the differential scanning calorimetry (DSC). The ozonolysis was conducted till a molar ratio O3/C=C?1 when the exothermal reaction spontaneously went to completion. A specific thermochemical calculation on ethyl oleate ozonation has been made to determine the theoretical heat of the ozonization reaction using the group increment approach. A linear relationship was found both in the integrated absorptivity of the ozonide infrared band at 1110 cm(-1) and the ozonolysis time as well as the thermal decomposition enthalpy of the ozonides and peroxides formed as a result of the ozonation. The DSC decomposition temperature of ozonated ethyl oleate occurs with an exothermal peak at about 150-155 °C with a decomposition enthalpy of 243.0 kJ/mol at molar ratio O3/C=C?1. It is shown that the decomposition enthalpy of ozonized ethyl oleate is a constant value (?243 kJ/mol) at any stage of the O3/C=C once an adequate normalization of the decomposition enthalpy for the amount of the adsorbed ozone is taken into consideration. The decomposition enthalpy of ozonized ethyl oleate was also calculated using a simplified thermochemical model, obtaining a result in reasonable agreement with the experimental value. PMID:23969233

  15. Glucuronidation of acetaminophen catalyzed by multiple rat phenol UDP-glucuronosyltransferases.

    PubMed

    Kessler, Fay K; Kessler, Marissa R; Auyeung, Diana J; Ritter, Joseph K

    2002-03-01

    Gunn rats glucuronidate acetaminophen (APAP) at reduced rates and show increased susceptibility to APAP-induced hepatotoxicity. This defect is presumed to involve UDP-glucuronosyltransferase (UGT) 1A6, which is nonfunctional in Gunn rats, but it is currently unclear whether other 1A family members are also involved. In humans, two 1A isoforms are known to be active (1A6 and 1A9) but 1A6 form has a 25-fold lower apparent K(m) (2 mM). Rat liver microsomal APAP UGT activity is induced by in vivo treatment with beta-naphthoflavone or oltipraz, an effect correlating with induction of 1A6 and 1A7. To address a possible role of 1A7 in APAP glucuronidation relative to other 1A forms, cDNAs encoding UGTs 1A1, 1A5, 1A6, 1A7, and 1A8 were expressed in human embryonic kidney cells and the contents of expressed enzyme in prepared membrane fractions determined by quantitative immunoblotting. At 2.5 mM APAP, 1A7 showed the highest specific activity (2.8 nmol/min/nmol 1A7 protein), followed by 1A6 (1.1 nmol/min/nmol), and 1A8 (0.27 nmol/min/nmol). 1A1 and 1A5 were essentially inactive. Kinetic comparisons indicated 1A7 had a similar apparent K(m) as 1A6 (4.7 versus 3.9 mM, respectively) but a 2.4-fold higher catalytic activity. These data suggest that in rats, 1A7 plays a major role in APAP glucuronidation and contributes to protection against APAP-induced hepatotoxicity. The involvement of other UGTs besides 1A6 is further underscored by the presence of significant residual APAP-glucuronidating activity by Gunn rat hepatocytes, indicating the activity of an unknown UGT2 family member. PMID:11854153

  16. Enzyme-assisted synthesis of the glucuronide conjugate of psilocin, an hallucinogenic component of magic mushrooms.

    PubMed

    Shoda, Takuji; Fukuhara, Kiyoshi; Goda, Yukihiro; Okuda, Haruhiro

    2011-09-01

    An enzyme-assisted synthesis of psilocin glucuronide (PCG), a metabolite excreted in the urine of magic mushroom (MM) users, is described. In the presence of Aroclor 1254 pretreated rat liver microsomes, psilocin and the cofactor UDPGA were incubated for 20 h. Purification by HPLC gave PCG in 19% yield (3.6 mg). The compound structure was characterized by MS and NMR. The milligram amounts of PCG produced by this method will allow the direct identification and quantification of PCG in the urine of MM users. PMID:21960543

  17. Synthesis and characterization of deoxynivalenol glucuronide: its comparative immunotoxicity with deoxynivalenol.

    PubMed

    Wu, Xianai; Murphy, Patricia; Cunnick, Joan; Hendrich, Suzanne

    2007-10-01

    Deoxynivalenol (DON) is a mycotoxin commonly contaminating wheat, barley and corn. DON glucuronide (DONGLU) is a major DON metabolite. We synthesized and purified DONGLU and tested its immunotoxicity, hypothesizing that DONGLU would be much less toxic to K562 cells compared with DON. DONGLU was synthesized using rat liver microsomes, uridine-5'-diphosphoglucuronic acid and DON, and purified with a Sephadex LH-20 column and reverse phase HPLC. beta-Glucuronidase hydrolysis formed a product with retention time and UV spectrum identical with DON. Using atmospheric pressure chemical ionization in negative mode, the molecular mass (M-1) of purified DONGLU was 471 g/mol; in agreement with an expected molecular weight of 472 g/mol. MS and NMR indicated that the glucuronide moiety was conjugated with the carbon-3-hydroxyl group of DON. The cytotoxicity of DON and DONGLU were compared in cell culture using human erythroleukemia cell line K562. Fifty percent inhibition of cell number was observed with a DON concentration of 1.31 microM using a methylthaizol tetrazolium (MTS) cell viability assay whereas no significant cytotoxicity was observed for DONGLU at up to 270 microM. DONGLU did not influence DON toxicity at 0.5 microM, 1.3 microM and 8.4 microM concentration combinations of each compound. These data verified that DONGLU is a detoxification product of DON. PMID:17507135

  18. Determination of ajulemic acid and its glucuronide in human plasma by gas chromatography-mass spectrometry.

    PubMed

    Batista, Catarina; Berisha, Myftar; Karst, Matthias; Salim, Kahlid; Schneider, Udo; Brenneisen, Rudolf

    2005-06-01

    A method using gas chromatography-mass spectrometry (GC-MS) and solid-phase extraction (SPE) was developed for the determination of ajulemic acid (AJA), a non-psychoactive synthetic cannabinoid with interesting therapeutic potential, in human plasma. When using two calibration graphs, the assay linearity ranged from 10 to 750 ng/ml, and 750 to 3000 ng/ml AJA. The intra- and inter-day precision (R.S.D., %), assessed across the linear ranges of the assay, was between 1.5 and 7.0, and 3.6 and 7.9, respectively. The limit of quantitation (LOQ) was 10 ng/ml. The amount of AJA glucuronide was determined by calculating the difference in the AJA concentration before ("free AJA") and after enzymatic hydrolysis ("total AJA"). The present method was used within a clinical study on 21 patients suffering from neuropathic pain with hyperalgesia and allodynia. For example, plasma levels of 599.4+/-37.2 ng/ml (mean+/-R.S.D., n=9) AJA were obtained for samples taken 2 h after the administration of an oral dose of 20 mg AJA. The mean AJA glucuronide concentration at 2h was 63.8+/-127.9 ng/ml. PMID:15866495

  19. Synthesis and antibacterial activity of novel C12 ethyl ketolides.

    PubMed

    Burger, Matthew T; Hiebert, Christy; Seid, Mehran; Chu, Daniel T; Barker, Lynn; Langhorne, Mike; Shawar, Ribhi; Kidney, Jolene; Desai, Manoj C; Plattner, Jacob J

    2006-08-15

    A novel series of C(12) ethyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens, including those resistant to erythromycin. The C(12) modification involves replacing the natural C(12) methyl group in the erythromycin core with an ethyl group via chemical synthesis. From the C(12) ethyl macrolide core, a series of C(12) ethyl ketolides were prepared and tested for antibacterial activity against a panel of relevant clinical isolates. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria, whether resistance was due to ribosome methylation (erm) or efflux (mef). In particular, the C(12) ethyl ketolides 4k,4s,4q,4m, and 4t showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. The in vivo efficacy of several C(12) ethyl ketolides was demonstrated in a mouse infection model with Streptococcus pneumoniae as pathogen. PMID:16697203

  20. Direct gradient reversed-phase high-performance liquid chromatographic determination of salicylic acid, with the corresponding glycine and glucuronide conjugates in human plasma and urine.

    PubMed

    Vree, T B; van Ewijk-Beneken Kolmer, E W; Verwey-van Wissen, C P; Hekster, Y A

    1994-02-11

    A gradient reversed-phase HPLC analysis for the direct measurement of salicylic acid (SA) with the corresponding glycine and glucuronide conjugates in plasma and urine of humans was developed. The glucuronides were isolated by preparative HPLC from human urine samples. The concentration of the glucuronides in the isolated fraction were determined after enzymatic hydrolysis. Salicylic acid acyl glucuronide (SAAG) was not present in plasma. No isoglucuronides were present in acidic and alkaline urine of the volunteer. The limits of quantitation in plasma are: SA 0.2 microgram/ml, salicyluric acid (SU) 0.1 microgram/ml, salicylic acid phenolic glucuronide (SAPG) 0.4 microgram/ml and salicyluric acid phenolic glucuronide (SUPG) 0.2 microgram/ml. The limit of quantitation in urine is for all compounds 5 micrograms/ml. Salicylic acid acyl glucuronide is stable in phosphate buffer pH 4.9 during 8 h at 37 degrees C; thereafter it declines to 80% after 24 h. The subject's urine was therefore acidified by the oral intake of 4 x 1.2 g of ammonium chloride/day. With acidic urine, hardly any salicylic acid is excreted unchanged (0.6%). It is predominantly excreted as salicyluric acid (68.7%). PMID:8006100

  1. Glucuronidation genotypes and nicotine metabolic phenotypes: Importance of UGT2B10 and UGT2B17 knock-out polymorphisms

    PubMed Central

    Chen, Gang; Giambrone, Nino E.; Dluzen, Douglas F.; Muscat, Joshua E.; Berg, Arthur; Gallagher, Carla J.; Lazarus, Philip

    2010-01-01

    Glucuronidation is an important pathway in the metabolism of nicotine, with previous studies suggesting that ~22% of urinary nicotine metabolites are in the form of glucuronidated compounds. Recent in vitro studies have suggested that the UGTs 2B10 and 2B17 play major roles in nicotine glucuronidation with polymorphisms in both enzymes shown to significantly alter the levels of nicotine-, cotinine-, and trans-3?-hydroxy-cotinine (3HC)-glucuronides in human liver microsomes in vitro. In the present study, the relationship between the levels of urinary nicotine metabolites and functional polymorphisms in UGTs 2B10 and 2B17 were analyzed in urine specimens from 104 Caucasian smokers. Based on their percentage of total urinary nicotine metabolites, the levels of nicotine-glucuronide and cotinine-glucuronide were 42% (p<0.0005) and 48% (p<0.0001), respectively, lower in the urine from smokers exhibiting the UGT2B10 (*1/*2) genotype and 95% (p<0.05) and 98% (p<0.05), respectively, lower in the urine from smokers with the UGT2B10 (*2/*2) genotype as compared to the urinary levels in smokers having the wild-type UGT2B10 (*1/*1) genotype. The levels of 3HC-glucuronide was 42% (p<0.001) lower in the urine from smokers exhibiting the homozygous UGT2B17 (*2/*2) deletion genotype as compared to the levels in urine from wild-type UGT2B17 subjects. These data are consistent with previous in vitro studies and demonstrate that UGTs 2B10 and 2B17 play important roles in the glucuronidation of nicotine, cotinine and 3HC and suggest that the UGT2B10 codon 67 SNP and the UGT2B17 deletion significantly reduce overall glucuronidation rates of nicotine and its major metabolites in smokers. PMID:20876810

  2. Pallidol hexa­acetate ethyl acetate monosolvate

    PubMed Central

    Mao, Qinyong; Taylor, Dennis K.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    The entire mol­ecule of pallidol hexa­acetate {systematic name: (±)-(4bR,5R,9bR,10R)-5,10-bis­[4-(acet­yloxy)phen­yl]-4b,5,9b,10-tetra­hydro­indeno­[2,1-a]indene-1,3,6,8-tetrayl tetra­acetate} is completed by the application of twofold rotational symmetry in the title ethyl acetate solvate, C40H34O12·C4H8O2. The ethyl acetate mol­ecule was highly disordered and was treated with the SQUEEZE routine [Spek (2009 ?). Acta Cryst. D65, 148–155]; the crystallographic data take into account the presence of the solvent. In pallidol hexa­acetate, the dihedral angle between the fused five-membered rings (r.m.s. deviation = 0.100?Å) is 54.73?(6)°, indicating a significant fold in the mol­ecule. Significant twists between residues are also evident as seen in the dihedral angle of 80.70?(5)° between the five-membered ring and the pendent benzene ring to which it is attached. Similarly, the acetate residues are twisted with respect to the benzene ring to which they are attached [C—O(carb­oxy)—C—C torsion angles = ?70.24?(14), ?114.43?(10) and ?72.54?(13)°]. In the crystal, a three-dimensional architecture is sustained by C—H?O inter­actions which encompass channels in which the disordered ethyl acetate mol­ecules reside. PMID:24046702

  3. RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDS, PCDFS AND PCBS

    EPA Science Inventory

    RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDs, PCDFs AND PCBs. D G Ross, K M Crofton, M J DeVito, NHEERL, ORD, USEPA, RTP, NC. Many PHAHs decrease thyroxine (T4), possibly due to inducti...

  4. Human and Rat ABC Transporter Efflux of Bisphenol A and Bisphenol A Glucuronide: Interspecies Comparison and Implications for Pharmacokinetic Assessment

    EPA Science Inventory

    Significant interspecies differences exist between human and rodent with respect to absorption, distribution, and excretion of bisphenol A (BPA) and its primary metabolite, BPA-glucuronide (BPA-G). ATP-Binding Cassette (ABC) transporter enzymes play important roles in these physi...

  5. In vitro glucuronidation of xanthohumol, a flavonoid in hop and beer, by rat and human liver microsomes

    Microsoft Academic Search

    M. Yilmazer; J. F. Stevens; D. R. Buhler

    2001-01-01

    Xanthohumol (XN) is the major prenylated flavonoid of hop plants and has been detected in beer. Previous studies suggest a variety of potential cancer chemopreventive effects for XN, but there is no information on its metabolism. The aim of this study was to investigate in vitro glucuronidation of XN by rat and human liver microsomes. Using high-performance liquid chromatography, two

  6. HPLC with laser-induced native fluorescence detection for morphine and morphine glucuronides from blood after immunoaffinity extraction.

    PubMed

    Hupka, Y; Beike, J; Roegener, J; Brinkmann, B; Blaschke, G; Köhler, H

    2005-05-01

    A new immunoaffinity solid phase extraction of morphine and its phase II metabolites, morphine-3-beta-D-glucuronide and morphine-6-beta-D-glucuronide is described. An immunoadsorber was applied which was created for the first time by the immobilisation of specific antibodies (polyclonal, host: rabbit) by the sol-gel method. The extraction method in combination with high performance liquid chromatography-fluorescence determination has been validated and shown to be applicable to blood samples of heroin victims in a low concentration range. Blood extracts were essentially free of interfering matrix components when compared to C8-extracts. Additionally, a novel, sensitive and selective detection system for wavelength-resolved analysis of laser-induced fluorescence coupled to HPLC was developed. The analytes were excited with a frequency tripled Ti:Sa laser (lambda=244 nm quasi cw). The total emission spectrum was recorded with a detection system consisting of an imaging spectrograph and a back-illuminated CCD camera. This technique of detection, combined with an extended optical path (at least 6 mm could be illuminated by the laser), resulted in an optimal fluorescence intensity of the analytes. The method permitted the analysis of morphine, morphine-3-beta-D-glucuronide and morphine-6-beta-D-glucuronide in a low concentration range and could be applied to a complex matrix such as postmortem blood samples because analyte peaks could be discriminated from matrix peaks by their characteristic emission spectra. PMID:15657745

  7. Convenient Synthesis of Benzoylecgonine Ethyl Ester, a Homolog of Cocaine

    Microsoft Academic Search

    Monica R. Brzezinski; Charles D. Christian; Meng-Feng Lin; Robert A. Dean; William F. Bosron; Edwin T. Harper

    1992-01-01

    Benzoylecgonine reacted with tetramethylethylenediamine to form a lipophilic ion pair, which was alkylated in the absence of water. The ethyl ester was readily recrystallized for pharmacological studies.

  8. Use of Isoform-Specific UGT Metabolism to Determine and Describe Rates and Profiles of Glucuronidation of Wogonin and Oroxylin A by Human Liver and Intestinal Microsomes

    Microsoft Academic Search

    Qiong Zhou; Zhijie Zheng; Bijun Xia; Lan Tang; Chang Lv; Wei Liu; Zhongqiu Liu; Ming Hu

    2010-01-01

    Purposes  Glucuronidation via UDP-glucuronosyltransferases (or UGTs) is a major metabolic pathway. The purposes of this study are to\\u000a determine the UGT-isoform-specific metabolic fingerprint (or GSMF) of wogonin and oroxylin A, and to use isoform-specific\\u000a metabolism rates and kinetics to determine and describe their glucuronidation behaviors in tissue microsomes.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  \\u000a In vitro glucuronidation rates and profiles were measured using expressed UGTs and

  9. The in vivo glucuronidation of buprenorphine and norbuprenorphine determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Huang, Wei; Moody, David E; McCance-Katz, Elinore F

    2006-04-01

    The opioid partial agonist medication, buprenorphine (BUP), and its primary metabolite, norbuprenorphine (NBUP), are extensively glucuronidated. Sensitive analytical methods that include determination of buprenorphine-3-glucuronide (BUPG) and norbuprenorphine-3-glucuronide (NBUPG) are needed to more fully understand the metabolism and pharmacokinetics of buprenorphine. A method has now been developed that uses solid-phase extraction followed by liquid chromatography-electrospray ionization-tandem mass spectrometry. BUP-d4, NBUP-d3, and morphine-3-glucuronide-d3 were used as internal standards. The lower limit of quantitation was 0.1 and 0.5 ng/mL for each of the analytes in 1-mL of human plasma and urine, respectively, except for NBUP in urine in which it was 2.5 ng/mL. The analytes were stable under the following conditions: plasma and urine at room temperature, up to 20 hours; plasma and urine at -20 degrees C for 119 and 85 days, respectively; plasma freeze-thaw, up to 3 cycles; processed sample, up to 96 hours at -20 degrees C and up to 48 hours on the autosampler; stock solutions at room temperature and at -20 degrees C, up to 6 hours and 128 days, respectively. In plasma collected from 5 subjects on maintenance daily sublingual doses of 16 mg BUP and 4 mg naloxone, respective 0- to 24-hour areas under the curve were 32, 88, 26, and 316 ng/mL x h for BUP, NBUP, BUPG, and NBUPG. In urine samples respective percent of daily dose excreted in the 24-hour urine were 0.014%, 1.89%, 1.01%, and 7.76%. This method allowed us to determine that NBUPG is a major metabolite present in plasma and urine of BUP. Because urinary elimination is limited ( approximately 11% of daily dose), the role of NBUPG in total clearance of buprenorphine is not yet known. PMID:16628138

  10. Focused ultrasound-assisted acceleration of enzymatic hydrolysis of alkylphenols and 17?-oestradiol glucuronide in fish bile.

    PubMed

    Vallejo, Asier; Usobiaga, Aresatz; Ortiz-Zarragoitia, Maren; Cajaraville, Miren P; Fernández, Luis A; Zuloaga, Olatz

    2010-11-01

    According to the European Water Framework Directive (WFD), alkylphenols, such as octylphenols and nonylphenols, and 17?-oestradiol are considered as priority or emerging pollutants, respectively, mainly due to their possible properties as endocrine-disrupting compounds (EDCs). EDCs are accumulated in liver, fat, kidney and bile in the glucuronide form. In order to determine the concentration of these compounds in bile, an enzymatic hydrolysis step is necessary. This step is usually long (~16 h), and in this sense, ultrasound probes were studied as a possible alternative energy source to accelerate this process. Enzymatic hydrolysis was reduced to 20 min using an ultrasound probe at one cycle and 10% of amplitude. For validation of analytical procedure, nonylphenol glucuronide (4NP-G), 4-tert-octylphenol glucuronide (4tOP-G) and 4-n-octylphenol glucuronide (4nOP-G) were synthesised while 17?-oestradiol glucuronide (E2-G) was commercially available. Bile from thick-lip grey mullets (Chelon labrosus) was spiked with known amounts of 4NP-G, 4tOP-G, 4nOP-G and E2-G and submitted to the optimised procedure. Good recoveries (77-122%), precision in the 5% to 12% range and limits of detection, ranging from the low nanogramme per gramme level for 4tOP, 4nOP and E2 to the low microgramme per gramme level for nonylphenols, were obtained. The optimised method was applied for the determination of alkylphenol in the bile of thick-lip grey mullets fish bile from the Urdaibai estuary (UNESCO reserve of the Biosphere, Bay of Biscay), and high concentrations (2.3-14.2 ?g/g), such as those obtained in polluted areas, were measured. E2 was determined in the bile of thick-lip grey mullets, intraperitoneally injected with E2. PMID:20835815

  11. NMR characterization of an S-linked glucuronide metabolite of the potent, novel, nonsteroidal progesterone agonist tanaproget.

    PubMed

    Keating, Kelly A; McConnell, Oliver; Zhang, Yingru; Shen, Li; Demaio, William; Mallis, Larry; Elmarakby, Sayed; Chandrasekaran, Appavu

    2006-08-01

    Tanaproget is a first-in-class nonsteroidal progesterone receptor agonist that is being investigated for use in contraception. A major in vitro and in vivo metabolite of tanaproget formed in humans was initially characterized as a glucuronide of tanaproget. However, whether the glucuronide was linked to the nitrogen or sulfur of the benzoxazine-2-thione group in tanaproget could not be determined by liquid chromatography/mass spectrometry (LC/MS) and LC-tandem mass spectrometry analysis. To obtain additional structural details for this metabolite, additional quantities were generated from rat liver microsomal incubations and purified by high-performance liquid chromatography (HPLC) for NMR analysis. The NMR data for the metabolite confirmed that the glucuronide was covalently bound to either the sulfur or the nitrogen of the benzoxazine-2-thione moiety. The lack of key through-bond (scalar) and through-space (dipolar) one-dimensional (1D) and two-dimensional (2D) NMR couplings and correlations in the metabolite spectra (due primarily to low sample concentration) precluded an unambiguous structure elucidation. Subsequent synthesis of the S- and N-glucuronides of tanaproget from tanaproget facilitated the unambiguous regio- and stereochemical assignment of the metabolite by comparison of 1D NMR chemical shifts and scalar coupling constants, 2D NMR correlations, and HPLC and LC/MS characteristics between the synthetic compounds and the metabolite. From extensive comparison of the spectral and chromatographic data of the microsomally derived metabolite and the synthetic compounds, the metabolite has been determined to be the S-(beta)-D-glucuronide of tanaproget. PMID:16698893

  12. IRIS TOXICOLOGICAL REVIEW OF METHYL ETHYL KETONE (2003 Final)

    EPA Science Inventory

    EPA is announcing the release of the final report, "Toxicological Review of Methyl Ethyl Ketone: in support of the Integrated Risk Information System (IRIS)". The updated Summary for Methyl Ethyl Ketone and accompanying Quickview have also been added to the IRIS Database. ...

  13. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...Tolerances are established for residues of the herbicide fenoxaprop-ethyl, including...tolerances are established for residues of the herbicide fenoxaprop-ethyl...are established for residues of the herbicide fenoxaprop-ethyl,...

  14. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. (a) Chemical substance...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  15. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. (a) Chemical substance...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  16. 40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. (a) Chemical substance...acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester (PMN...

  17. 19 CFR 10.99 - Importation of ethyl alcohol for nonbeverage purposes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 false Importation of ethyl alcohol for nonbeverage purposes. 10.99 Section...REDUCED RATE, ETC. General Provisions Ethyl Alcohol § 10.99 Importation of ethyl alcohol for nonbeverage purposes. (a)...

  18. 19 CFR 10.99 - Importation of ethyl alcohol for nonbeverage purposes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 false Importation of ethyl alcohol for nonbeverage purposes. 10.99 Section...REDUCED RATE, ETC. General Provisions Ethyl Alcohol § 10.99 Importation of ethyl alcohol for nonbeverage purposes. (a)...

  19. Bilirubin kinetics in intact rats and isolated perfused liver. Evidence for hepatic deconjugation of bilirubin glucuronides.

    PubMed Central

    Gollan, J; Hammaker, L; Licko, V; Schmid, R

    1981-01-01

    Most previous compartmental models describing bilirubin transport and metabolism in the liver have been validated solely by analysis of the plasma disappearance of radiolabeled bilirubin in human subjects. We now have determined the transport kinetics of a bilirubin tracer pulse by analysis of plasma, liver, and bile radioactivity data from 30 intact rats. Plasma [3H]bilirubin disappearance was best described by the sum of three exponentials, and a six-compartment model, derived by simulation analysis, was necessary and adequate to describe all experimental data. Examination of the injected radiolabeled bilirubin by extraction with hexadecyltrimethylammonium bromide and thin-layer chromatography revealed that 6.6% (mean) of the original pigment had been degraded to labeled nonbilirubin derivatives during preparation of the tracer dose. This material exhibited a significantly longer half-life (mean 50.6 min) of the plasma terminal exponential than that of authentic radiobilirubin (20.6 min). In isolated perfused rat liver, the kinetics of [3H]bilirubin in perfusate and bile readily fitted the proposed model. Compatibility of the model with the data obtained, both in the isolated liver and in vivo, required that a fraction of bilirubin conjugated in the liver be deconjugated and returned to the plasma. Deconjugation of bilirubin glucuronides was evaluated directly by infusion of bilirubin monoglucuronides, containing 14C in the glucuronosyl group, into rats with an external bile fistula. Since metabolic degradation of hydrolyzed 14C-labeled glucuronic acid yields 14CO2, this was measured in expired air. Whereas 86% of the administered labeled pigment was recovered in bile, 7% of the label appeared in 14CO2. These findings directly validate a portion of the proposed kinetic model and suggest that hepatic deconjugation of a small fraction of bilirubin glucuronides is a physiological event. Deconjugation may also account, at least in part, for the presence of increased concentrations of unconjugated bilirubin in the plasma of patients with cholestasis. PMID:7204563

  20. Specific localization of quercetin-3-O-glucuronide in human brain.

    PubMed

    Ishisaka, Akari; Mukai, Rie; Terao, Junji; Shibata, Noriyuki; Kawai, Yoshichika

    2014-09-01

    In recent years, many papers have suggested that dietary flavonoids may exert beneficial effects in the brain tissue for the protection of neurons against oxidative stress and inflammation. However, the bioavailability of flavonoids across the blood-brain barrier and the localization in the brain remain controversial. Thus, we examined the localization of quercetin-3-O-glucuronide (Q3GA), a major phase-II metabolite of quercetin, in the human brain tissues with or without cerebral infarction by immunohistochemical staining using anti-Q3GA antibody. A significant immunoreactivity was observed in the epithelial cells of the choroid plexus, which constitute the structural basis of the blood-cerebrospinal fluid (CSF) barrier, and in the foamy macrophages of recent infarcts. The cellular accumulation of Q3GA was also reproduced in vitro in macrophage-like RAW264, microglial MG6, and brain capillary endothelial RBEC1. It is of interest that a common feature of these cell lines is the deconjugation of Q3GA, resulting in the cellular accumulation of non-conjugated quercetin and the methylated forms. We then examined the anti-inflammatory activity of Q3GA and the deconjugated forms in the lipopolysaccharide-stimulated macrophage cells and revealed that the deconjugated forms (quercetin and a methylated form isorhamnetin), but not Q3GA itself, exhibited inhibitory effects on the inflammatory responses through attenuation of the c-Jun N-terminal kinase pathway. These results suggested that a quercetin glucuronide can pass through the blood-brain barrier, perhaps the CSF barrier, accumulate in specific types of cells, such as macrophages, and act as anti-inflammatory agents in the brain through deconjugation into the bioactive non-conjugated forms. PMID:24893148

  1. Uremic toxins inhibit renal metabolic capacity through interference with glucuronidation and mitochondrial respiration.

    PubMed

    Mutsaers, H A M; Wilmer, M J G; Reijnders, D; Jansen, J; van den Broek, P H H; Forkink, M; Schepers, E; Glorieux, G; Vanholder, R; van den Heuvel, L P; Hoenderop, J G; Masereeuw, R

    2013-01-01

    During chronic kidney disease (CKD), drug metabolism is affected leading to changes in drug disposition. Furthermore, there is a progressive accumulation of uremic retention solutes due to impaired renal clearance. Here, we investigated whether uremic toxins can influence the metabolic functionality of human conditionally immortalized renal proximal tubule epithelial cells (ciPTEC) with the focus on UDP-glucuronosyltransferases (UGTs) and mitochondrial activity. Our results showed that ciPTEC express a wide variety of metabolic enzymes, including UGTs. These enzymes were functionally active as demonstrated by the glucuronidation of 7-hydroxycoumarin (7-OHC; K(m) of 12±2?M and a V(max) of 76±3pmol/min/mg) and p-cresol (K(m) of 33±13?M and a V(max) of 266±25pmol/min/mg). Furthermore, a wide variety of uremic toxins, including indole-3-acetic acid, indoxyl sulfate, phenylacetic acid and kynurenic acid, reduced 7-OHC glucuronidation with more than 30% as compared with controls (p<0.05), whereas UGT1A and UGT2B protein expressions remained unaltered. In addition, our results showed that several uremic toxins inhibited mitochondrial succinate dehydrogenase (i.e. complex II) activity with more than 20% as compared with controls (p<0.05). Moreover, indole-3-acetic acid decreased the reserve capacity of the electron transport system with 18% (p<0.03). In conclusion, this study shows that multiple uremic toxins inhibit UGT activity and mitochondrial activity in ciPTEC, thereby affecting the metabolic capacity of the kidney during CKD. This may have a significant impact on drug and uremic retention solute disposition in CKD patients. PMID:23017367

  2. Structural evaluation of the glucuronides of morphine and formoterol using chemical derivatization with 1,2-dimethylimidazole-4-sulfonyl chloride and liquid chromatography/ion trap mass spectrometry.

    PubMed

    Salomonsson, Matilda Lampinen; Bondesson, Ulf; Hedeland, Mikael

    2008-09-01

    For the first time chemical derivatization of isomeric drug glucuronides with 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) has been successfully applied as a tool for determining the site of conjugation. This provides a way to differentiate between glucuronide isomers containing aliphatic and phenolic hydroxyl groups. The analyses were performed with liquid chromatography/electrospray ion trap mass spectrometry (LC/ESI-MSn). DMISC has previously been shown to react selectively with phenols in estrogens, thus improving sensitivity in ESI-MS. The model compounds selected for this study were commercially available standards of formoterol, morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G). Formoterol glucuronides were produced with an enzymatic method in house. Both formoterol and morphine possess one phenolic and one aliphatic hydroxyl group where glucuronidation could take place. The product ion mass spectra of the native morphine glucuronides were indistinguishable due to the initial neutral loss of monodehydrated glucuronic acid (176 u). However, a significant difference between the isomers was observed with DMISC derivatization, as only the form with a free phenol, M6G, gave a detectable reaction product. Formoterol formed two detectable glucuronide isomers in the enzymatic reaction. Their respective sites of conjugation could not be directly determined from the product ion spectra. Reaction with DMISC, however, gave a detectable product with only one of the isomers. Based on previous experience of the preferred DMISC reactions with phenols, and interpretation of the fragmentation pattern of the derivative, it was concluded that the reactive isomer had a free phenol, and was thus conjugated on the aliphatic chain. PMID:18677706

  3. Identification of Flavone Glucuronide Isomers by Metal Complexation and Tandem Mass Spectrometry: Regioselectivity of UDP-Glucuronosyltransferase Isozymes in the Biotransformation of Flavones

    PubMed Central

    Robotham, Scott A.; Brodbelt, Jennifer S.

    2013-01-01

    Flavone Glucuronide isomers of five flavones (chrysin, apigenin, luteolin, baicalein, and scutellarein) were differentiated by collision induced dissociation (CID) of [Co(II) (flavone-H) (4,7-diphenyl-1,10-phenanthroline)2]+ complexes. The complexes were generated via post-column addition of a metal/ligand solution after separation of the glucuronide products generated upon incubation of each flavone with an array of UDP-glucuronosyl-transferase (UGT) isozymes. Elucidation of the glucuronide isomers allowed a systematic investigation of the regioselectivity of twelve human UDP-glucuronosyl-transferase (UGT) isozymes, including eight UGT1A and four UGT2B isozymes. Glucuronidation of the 7-OH position was the preferred site for all the flavones except for luteolin, which possessed adjacent hydroxyl groups on the B ring. For all flavones and UGT isozymes, glucuronidation of the 5-OH position was never observed. As confirmed by the metal complexation/MS/MS strategy, glucuronidation of the 6-OH position only occurred for baicalein and scutellarein when incubated with three of the UGT isozymes. PMID:23362992

  4. Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b.

    PubMed

    Vasilyeva, Aksana; Durmus, Selvi; Li, Lie; Wagenaar, Els; Hu, Shuiying; Gibson, Alice A; Panetta, John C; Mani, Sridhar; Sparreboom, Alex; Baker, Sharyn D; Schinkel, Alfred H

    2015-07-01

    Recently, an efficient liver detoxification process dubbed "hepatocyte hopping" was proposed on the basis of findings with the endogenous compound, bilirubin glucuronide. According to this model, hepatocytic bilirubin glucuronide can follow a liver-to-blood shuttling loop via Abcc3 transporter-mediated efflux and subsequent Oatp1a/1b-mediated liver uptake. We hypothesized that glucuronide conjugates of xenobiotics, such as the anticancer drug sorafenib, can also undergo hepatocyte hopping. Using transporter-deficient mouse models, we show here that sorafenib-glucuronide can be extruded from hepatocytes into the bile by Abcc2 or back into the systemic circulation by Abcc3, and that it can be taken up efficiently again into neighboring hepatocytes by Oatp1a/1b. We further demonstrate that sorafenib-glucuronide excreted into the gut lumen can be cleaved by microbial enzymes to sorafenib, which is then reabsorbed, supporting its persistence in the systemic circulation. Our results suggest broad relevance of a hepatocyte shuttling process known as "hepatocyte hopping"-a novel concept in clinical pharmacology-for detoxification of targeted cancer drugs that undergo hepatic glucuronidation, such as sorafenib. Cancer Res; 75(13); 2729-36. ©2015 AACR. PMID:25952649

  5. Perspectives for the biotechnological production of ethyl acetate by yeasts.

    PubMed

    Löser, Christian; Urit, Thanet; Bley, Thomas

    2014-06-01

    Ethyl acetate is an environmentally friendly solvent with many industrial applications. The production of ethyl acetate currently proceeds by energy-intensive petrochemical processes which are based on natural gas and crude oil without exception. Microbial synthesis of ethyl acetate could become an interesting alternative. The formation of esters as aroma compounds in food has been repeatedly reviewed, but a survey which deals with microbial synthesis of ethyl acetate as a bulk product is missing. The ability of yeasts for producing larger amounts of this ester is known for a long time. In the past, this potential was mainly of scientific interest, but in the future, it could be applied to large-scale ester production from renewable raw materials. Pichia anomala, Candida utilis, and Kluyveromyces marxianus are yeasts which convert sugar into ethyl acetate with a high yield where the latter is the most promising one. Special attention was paid to the mechanism of ester synthesis including regulatory aspects and to the maximum and expectable yield. Synthesis of much ethyl acetate requires oxygen which is usually supplied by aeration. Ethyl acetate is highly volatile so that aeration results in its phase transfer and stripping. This stripping process cannot be avoided but requires adequate handling during experimentation and offers a chance for a cost-efficient process-integrated recovery of the synthesized ester. PMID:24788328

  6. Ethanol-related death of a child: an unusual case report.

    PubMed

    K?ys, Ma?gorzata; Wo?niak, Krzysztof; Rojek, Sebastian; Rzepecka-Wo?niak, Ewa; Kowalski, Piotr

    2008-07-18

    The report describes a fatal outcome in a 5-year-old male who died after drinking a fatal dose of ethanol at the party held by his parents. Urine and blood alcohol level of the deceased was 0.4 and 0.5 g/dL, what might explain the sudden death of the child. In addition, the analysis of the boy's hair demonstrated the presence of ethyl glucuronide (EtG), a marker of alcohol consumption; hair EtG concentration levels indicated that the boy might have occasionally imbibed alcohol prior to death. Pathological lesions of the liver observed in histopathology did not contradict such a hypothesis. PMID:18455894

  7. [Direct metabolites of ethanol as biological markers of alcohol use: basic aspects and applications].

    PubMed

    Thon, N; Weinmann, W; Yegles, M; Preuss, U; Wurst, F M

    2013-09-01

    In addition to self reports and questionnaires, biomarkers are of relevance in the diagnosis of and therapy for alcohol use disorders. Traditional biomarkers such as gamma-glutamyl transpeptidase or mean corpuscular volume are indirect biomarkers and are subject to the influence of age, gender and non-alcohol related diseases, among others. Direct metabolites of ethanol such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake - EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programmes, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and foetal alcohol syndrome. Due to their properties, they open up new perspectives for prevention, interdisciplinary cooperation, diagnosis of and therapy for alcohol-related problems. PMID:23856980

  8. Measurement of direct ethanol metabolites in a case of a former driving under the influence (DUI) of alcohol offender, now claiming abstinence.

    PubMed

    Wurst, Friedrich M; Yegles, Michel; Alling, Christer; Aradottir, Steina; Dierkes, Jutta; Wiesbeck, Gerhard A; Halter, Claudia C; Pragst, Fritz; Auwaerter, Volker

    2008-05-01

    A 37-year-old female subject had been convicted of driving under the influence of alcohol, and 19 months later, claimed abstinence after supervised disulfiram treatment. Our aim was to elucidate the value of direct ethanol metabolites as measures of abstinence. Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) in hair, phosphatidylethanol in whole blood and EtG and ethyl sulphate in urine were measured. The results were compared with self-report of alcohol consumption and traditional blood biomarkers for chronically elevated alcohol consumption as carbohydrate deficient transferrin (CDT), gamma glutamyl transpeptidase, mean corpuscular erythrocyte volume, aspartate aminotransferase and alanine aminotransferase. EtG was found in distal parts of hair only, whereas the proximal parts were negative. Furthermore, FAEE concentrations were found in the typical distribution over the hair length and showed values typical for either moderate social drinking or abstinence. CDT was above cut-off in 9 out of 16 analyses with a decreasing tendency and the lowest values in the last 2 months before the end of sampling. The data suggest that in addition to traditional markers, a combination of direct ethanol metabolites can be useful in the expert assessment of judging driving ability. A careful individual interpretation of the results for the different markers, however, is an absolute necessity. PMID:18253745

  9. Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography

    Microsoft Academic Search

    H. W. Peng; F. C. Cheng; Y. T. Huang; C. F. Chen; T. H. Tsai

    1998-01-01

    An isocratic high-performance liquid chromatographic method with ultraviolet detection was utilized for the investigation of the pharmacokinetics of naringenin and its glucuronide conjugate in rat plasma and brain tissue. Plasma and brain tissue were deproteinized by acetonitrile, then centrifuged for sample clean-up. The drugs were separated by a reversed-phase C18 column with a mobile phase consisting of acetonitrile–orthophosphoric acid solution

  10. Antitumor activity of vincristine encapsulated in glucuronide-modified long-circulating liposomes in mice bearing Meth A sarcoma

    Microsoft Academic Search

    Yoshihiro Tokudome; Naoto Oku; Kanako Doi; Yukihiro Namba; Shoji Okada

    1996-01-01

    Liposomes modified with the uronic acid derivative palmityl-d-glucuronide (PGlcUA) have a long-circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine\\/cholesterol\\/PGlcUA= 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method,

  11. Identification of a novel intestinal first pass metabolic pathway: NQO1 mediated quinone reduction and subsequent glucuronidation.

    PubMed

    Hao, Haiping; Wang, Guangji; Cui, Nan; Li, Jing; Xie, Lin; Ding, Zuoqi

    2007-02-01

    Quinones represent a very important class of compounds found in nature and for the chemically synthesized drugs. The present study was designed to elucidate the intestinal first pass metabolic pathways in vivo and in vitro, of tanshinone IIA (TS), a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza. Five metabolites, proposed to be TS catechol glucuronides (two position isomers), dehydrotanshinone IIA and its two catechol glucuronides, were identified from the rat intestinal homogenates after oral administration of TS. TS metabolism was further conducted in the subcellular system including cytosol, microsomes, mitochondrial and S9 under both phase I and phase II metabolic conditions. TS underwent negligible metabolism in all of the subcellular systems under phase I metabolic condition using NADPH as the cofactor. However, significant and substantial metabolic elimination of TS was observed in the cytosol and S9 fractions, while not in the microsomes fractions, when both NADPH and UDPGA were added. Two TS catechol glucuronides were identified from such an in vitro metabolic medium. Dicoumarol, a specific inhibitor of the NAD(P)H dependent quinone oxidoreductase (NQO1), significantly inhibited the metabolic elimination of TS in a noncompetitive way, suggesting that NQO1 was responsible for the quinone reduction of TS to form the catechol intermediate. The catechol intermediate failed to be detected directly was proved to be highly unstable and autoxidized back to TS accompanied with hydrogen peroxide generation. Dicoumarol exhibited a significant inhibitory effect on the hydrogen peroxide generation, further supporting that the reduction of TS was catalyzed by NQO1. The absolute bioavailability of TS was significantly enhanced by oral dicoumarol pretreatment. In conclusion, a novel intestinal metabolic pathway for quinones, NQO1 mediated reduction and subsequent glucuronidation, was determined using TS as a model compound. This study should be helpful for the general understanding of quinones absorption and intestinal first pass metabolism. PMID:17305492

  12. Ethyl chloride decomposition on oxide-supported platinum catalysts

    SciTech Connect

    McGee, K.C.; Driessen, M.D.; Grassian, V.H. [Univ. of Iowa, Iowa City, IA (United States)] [Univ. of Iowa, Iowa City, IA (United States)

    1995-12-01

    Ethyl chloride decomposition on Pt/SiO{sub 2} and Pt/Al{sub 2}O{sub 3} catalysts has been investigated by infrared spectroscopy and mass spectrometry. Ethyl chloride reacts on Pt particles at low temperatures near 200 K to form adsorbed C{sub 2} hydrocarbon fragments. By comparison to literature infrared spectra, three species are identified to be adsorbed on the Pt catalysts-ethyl (C{sub 2}H{sub 5}), ethylene (C{sub 2}H{sub 4}), and ethylidyne (C{sub 2}H{sub 3}). The C{sub 2}H{sub x} species coexist to a greater extent on the surface of the Pt particles than on single crystal Pt surfaces. The infrared data suggest there are two different reaction pathways that ethyl chloride may undergo on the Pt particles. The first reaction pathway involves {alpha}{beta}-elimination of HC{sub 1} to give adsorbed ethylene. The second reaction pathway results from C-Cl bond dissociation to give adsorbed ethyl groups and chlorine atoms. Adsorbed ethyl groups dehydrogenate to ethylidyne upon warming. In the presence of hydrogen, C{sub 2} fragments can be hydrogenated to give ethane. The data show that adsorbed ethyl and ethylene hydrogenate much more readily than ethylidyne. At higher temperatures near 473 K, ethyl chloride reacts on Pt/SiO{sub 2} and Pt/Al{sub 2}O{sub 3} to yield gas-phase ethylene, ethane, methane, and hydrogen chloride. The reaction rate is enhanced in the presence of hydrogen and there is a greater amount of ethane produced relative to ethylene. Ethyl chloride can react with the oxide support as well at high temperatures. Surface hydroxyl groups on the alumina support react with ethyl chloride to give ethoxy, AlOCH{sub 2}CH{sub 3}, near 473 K, whereas silica hydroxyl groups show no reaction with ethyl chloride up to 573 K. Possible mechanisms for the high-temperature reaction of ethyl chloride on oxide-supported Pt catalysts are discussed. 33 refs., 12 figs., 2 tabs.

  13. 77 FR 41346 - Trinexapac-ethyl; Proposed Pesticide Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ...the existing trinexapac-ethyl tolerance levels for wheat, forage and wheat, middlings as well as change the commodity definition...in or on barley, bran; sugarcane, molasses; and wheat, bran under the Federal Food, Drug, and...

  14. Pregnane × Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    PubMed Central

    2010-01-01

    Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11) is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR), we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies. Conclusion Our results demonstrate that tumoral metabolism of SN38 is affected by PXR and point to potential therapeutic significance of PXR quantification in the prediction of irinotecan response. Furthermore, our observations are pharmacologically relevant since many patients suffering from cancer diseases are often exposed to co-medications, food additives or herbal supplements able to activate PXR. A substantial part of the variability observed among patients might be caused by such interactions PMID:20196838

  15. Ethyl Carbamate in Foods and Beverages – A Review

    Microsoft Academic Search

    J. V. Weber; V. I. Sharypov

    \\u000a Foods and beverages contain many toxic chemicals that raise health concerns. Ethyl carbamate (EC) or urethane is the ethyl\\u000a ester of carbamic acid. It occurs at low levels, from ng\\/L to mg\\/L, in many fermented foods and beverages. EC is genotoxic\\u000a and carcinogenic for a number of species such as mice, rats, hamsters and monkeys. It has been classified as

  16. Electron diffraction investigation of the molecular structures of ethyl isocyanate and ethyl isothiocyanate

    NASA Astrophysics Data System (ADS)

    Cradock, Stephen; Durig, J. R.; Sullivan, J. F.

    1985-10-01

    Electron diffraction (ED) measurements and published microwave spectra are used to define the molecular structures of ethyl isocyanate and ethyl isothiocyanate in the gas phase. A cis-conformation is compatible with the data in both cases, while ED data for EtNCO are also consistent with a deviation of 45° from the cis conformation. An interpretation (in general terms) of the very complex microwave spectra in terms of an anharmonic two-dimensional motion combining the bend at nitrogen and the C?N torsion is proposed. An average cis structure ( r* av basis) consistent with ED and microwave data with removal of the effects of the torsional motion is proposed in each case, with skeletal parameters (NCO, NCS) rC?N 144.8 pm, 143.8; rC?C 152.4, 152.0 pm; rN?C 121.8 pm, 118.7; rC?O 117.4 pm, rC?S 158.0 pm; ?CCN 114.7°, 111.0°; ?CNC 132.2°, 147,4°; ?NCO 192.2°, ?NCS 184.5°.

  17. Vapor–liquid equilibria of ternary systems with 1-ethyl-3-methylimidazolium ethyl sulfate using headspace gas chromatography

    Microsoft Academic Search

    Hiroyuki Matsuda; Katsumi Tochigi; Vincent Liebert; Jürgen Gmehling

    2011-01-01

    Vapor–liquid equilibria (VLE) for two binary systems 1-propanol+water and methyl acetate+methanol, and the ternary mixtures with the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulfate [EMIM]+[EtSO4]? as entrainer were measured by headspace gas chromatography. From the experimental VLE data, the influence of the ionic liquid on the separation factors was investigated. The experimental results for the ternary systems show that [EMIM]+[EtSO4]? has a

  18. Quercetin-3-O-glucuronide induces ABCA1 expression by LXR? activation in murine macrophages

    SciTech Connect

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)] [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan)] [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)] [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan)] [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)] [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)] [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXR?. •Q3GA induced ABCA1 via LXR? activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXR?), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXR? in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  19. Molecular Pathways: GLI1-Induced Drug Glucuronidation in Resistant Cancer Cells.

    PubMed

    Zahreddine, Hiba Ahmad; Borden, Katherine L B

    2015-05-15

    Drug resistance remains a major impediment in the development of durable cancer therapies. Studies in acute myelogenous leukemia (AML) patients revealed a new form of multidrug resistance. Here, increased glioma-associated protein GLI1 leads to elevation of the UDP-glucuronosyl transferase (UGT) enzymes. UGTs add glucuronic acid to xenobiotics and metabolites. Traditionally, the loss of these enzymes is thought to contribute to cancer as a result of impaired clearance of environmental carcinogens. However, we demonstrate that overexpression of UGTs can contribute to oncogenesis by promoting drug resistance. Indeed, UGT levels in AML patients treated with ribavirin and/or cytarabine were elevated at relapse relative to diagnosis. This was reversed by GLI1 inhibition, suggesting a clinically relevant strategy to overcome drug resistance. Further, overexpression of UGTs can also lead to drug resistance in other cancers, such as certain Hsp90 inhibitors and vorinostat in colorectal and chronic lymphoblastic leukemia, respectively. Not all drugs are targets of glucuronidation, suggesting that UGT status could be relevant to treatment choice. Here, we describe several facets of UGT biology and how these could be exploited clinically. These studies demonstrate how drugs in cancer cells can be metabolized differentially than their normal counterparts. In summary, we describe a new form of drug resistance relevant to a variety of cancer contexts. Clin Cancer Res; 21(10); 2207-10. ©2015 AACR. PMID:25810373

  20. Quantitative Determination of Common Urinary Odorants and Their Glucuronide Conjugates in Human Urine

    PubMed Central

    Wagenstaller, Maria; Buettner, Andrea

    2013-01-01

    Our previous study on the identification of common odorants and their conjugates in human urine demonstrated that this substance fraction is a little-understood but nonetheless a promising medium for analysis and diagnostics in this easily accessible physiological medium. Smell as an indicator for diseases, or volatile excretion in the course of dietary processes bares high potential for a series of physiological insights. Still, little is known today about the quantitative composition of odorous or volatile targets, as well as their non-volatile conjugates, both with regard to their common occurrence in urine of healthy subjects, as well as in that of individuals suffering from diseases or other physiological misbalancing. Accordingly, the aim of our study was to develop a highly sensitive and selective approach to determine the common quantitative composition of selected odorant markers in healthy human subjects, as well as their corresponding glucuronide conjugates. We used one- and two-dimensional high resolution gas chromatography-mass spectrometry in combination with stable isotope dilution assays to quantify commonly occurring and potent odorants in human urine. The studies were carried out on both native urine and on urine that had been treated by glucuronidase assays, with analysis of the liberated odor-active compounds using the same techniques. Analytical data are discussed with regard to their potential translation as future diagnostic tool. PMID:24958143

  1. Fabrication of polymerized crystalline colloidal array thin film modified ?-cyclodextrin polymer for paraoxon-ethyl and parathion-ethyl detection.

    PubMed

    Bui, Minh-Phuong N; Seo, Seong S

    2014-01-01

    We have developed an optical chemical sensor for the detection of organophosphate (OP) compounds using a polymerized crystalline colloidal array (PCCA) thin film composed of a close-packed colloidal array of polystyrene particles. The PCCA thin film was modified with ?-cyclodextrin (?-CD) polymer as a capping cavity for the selective detection of paraoxon-ethyl and parathion-ethyl chemical agents. The fabrication of the modified PCCA thin film was optimized and the structure was characterized using scanning electron microscopy (SEM). The arrangement of polystyrene particles in the PCCA follows a pattern of the fcc (111) planes with strong diffraction peak in the visible spectral region and pH dependence. The diffraction peak of the ?-CD modified PCCA thin film showed a red shift according to the change of paraoxon-ethyl and parathion-ethyl concentrations at a fast response time (10 s) and high sensitivity with detection limits of 2.0 and 3.4 ppb, respectively. Furthermore, the proposed interaction mechanism of ?-CD with paraoxon-ethyl and parathion-ethyl in the ?-CD modified PCCA thin film were discussed. PMID:24813957

  2. [Iminium compounds against bacteria and fungi. 29. 3-Alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chloride].

    PubMed

    Pernak, J; Skrzypczak, A; Michalak, L; Jedraszczyk, J; Krysi?ski, J; Kazmierczak, M; Mrówczy?ski, B

    1993-04-01

    Syntheses and antimicrobial activity of 3-alkoxymethyl-1-ethyl-, 3-alkylthiomethyl-1-ethyl-, 3-alkoxymethyl-1-butyl-, and 3-alkylthiomethyl-1-butylbenzimidazolium chlorides are described. The compounds were obtained by reaction of 1-ethyl- or 1-butylbenzimidazole with chloromethylalkyl ethers or chloromethylalkyl sulfide. Antibacterial properties were tested on 13 strains of bacteria and fungi. 3-Dodecylthio-methyl-1-ethyl-benzimidazolium chloride exhibited the highest antibacterial activity. PMID:8494485

  3. Decreased Expression of Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) Leads to Reduced Glucuronidation of Flavonoids in UGT1A1-Overexpressing HeLa Cells: The Role of Futile Recycling.

    PubMed

    Sun, Hua; Zhou, Xiaotong; Zhang, Xingwang; Wu, Baojian

    2015-07-01

    In this study, the role of futile recycling (or deglucuronidation) in the disposition of two flavonoids (i.e., genistein and apigenin) was explored using UGT1A1-overexpressing HeLa cells (or HeLa1A1 cells). Glucuronidation of the flavonoids by HeLa1A1 cell lysate followed the substrate inhibition kinetics (Vmax = 0.10 nmol/min/mg, Km = 0.54 ?M, and Ksi = 2.0 ?M for genistein; Vmax = 0.19 nmol/min/mg, Km = 0.56 ?M, and Ksi = 3.7 ?M for apigenin). Glucuronide was efficiently generated and excreted after incubation of the cells with the aglycone (at doses of 1.25-20 nmol). The excretion rates were 0.40-0.69 and 0.84-1.1 nmol/min/mg protein for genistein glucuronide (GG) and apigenin glucuronide (AG), respectively. Furthermore, glucuronide excretion and total glucuronidation were significantly reduced in MRP4 knocked-down as compared to control cells. The alterations were well characterized by a two-compartment pharmacokinetic model incorporating the process of futile recycling (defined by a first-order rate constant, Kde). The derived Kde values were 15 and 25 h(-1) for GG and AG, respectively. This was well consistent with the in vitro observation that AG was subjected to more efficient futile recycling compared to GG. In conclusion, futile recycling was involved in cellular glucuronidation, accounting for transporter-dependent glucuronidation of flavonoids. PMID:26066637

  4. Is urine an alternative to cosmetically treated hair for the detection of drugs and alcohol?

    PubMed

    Agius, Ronald; Dufaux, Bertin; Kahl, Hans-Gerhard; Nadulski, Thomas

    2014-06-01

    This study attempts to assess the utility of the urine matrix as an alternative to cosmetically treated hair for the detection of drugs and alcohol for driving licence re-granting in 1026 cosmetically treated hair samples and 33 262 urine routine samples. No significant difference was observed between the percentage positive samples in cosmetically treated hair to those in urine at both the 95% and 99% significance level for amphetamines, cocaine, opiates, benzodiazepines, and methadone. Significant difference was found between the positivity rates of cannabinoids in cosmetically treated hair and that in urine indicating urine to be a better alternative to the use of the hair matrix even when cosmetically treated. The opposite was observed for the alcohol consumption marker ethyl glucuronide (EtG) for which the positivity rate in cosmetically treated hair was twice that in urine samples. Particularly for alcohol abstinence monitoring, as for the rehabilitative driving licence re-granting medical and psychological assessment (MPA) programme in Germany, it seems that ethyl glucuronide (EtG) in hair presents a much better alternative than urine testing, even when cosmetically treated hair is analyzed. Moreover, segmentation is an additional advantage of hair testing which can provide additional useful information. PMID:24817057

  5. A review of the genetic effects of ethyl methanesulfonate.

    PubMed

    Sega, G A

    1984-01-01

    Ethyl methanesulfonate (EMS) is a monofunctional ethylating agent that has been found to be mutagenic in a wide variety of genetic test systems from viruses to mammals. It has also been shown to be carcinogenic in mammals. Alkylation of cellular, nucleophilic sites by EMS occurs via a mixed SN1/SN2 reaction mechanism. While ethylation of DNA occurs principally at nitrogen positions in the bases, because of the partial SN1 character of the reaction, EMS is also able to produce significant levels of alkylation at oxygens such as the O6 of guanine and in the DNA phosphate groups. Genetic data obtained using microorganisms suggest that EMS may produce both GC to AT and AT to GC transition mutations. There is also some evidence that EMS can cause base-pair insertions or deletions as well as more extensive intragenic deletions. In higher organisms, there is clear-cut evidence that EMS is able to break chromosomes, although the mechanisms involved are not well understood. An often cited hypothesis is that DNA bases ethylated by EMS (mostly the N-7 position of guanine) gradually hydrolyze from the deoxyribose on the DNA backbone leaving behind an apurinic (or possibly an apyrimidinic) site that is unstable and can lead to single-strand breakage of the DNA. Data also exist that suggest that ethylation of some chromosomal proteins in mouse spermatids by EMS may be an important factor in causing chromosome breakage. PMID:6390190

  6. Effect of urinary pH on the pharmacokinetics of salicylic acid, with its glycine and glucuronide conjugates in human.

    PubMed

    Vree, T B; Van Ewijk-Beneken Kolmer, E W; Verwey-Van Wissen, C P; Hekster, Y A

    1994-10-01

    We studied the effects of urinary pH on the kinetics of salicylic acid (SA) with its metabolites and assessed the contribution of alkaline hydrolysis of salicylic acid acyl glucuronide to the renal clearance of salicylic acid. Hydrolysis of SAAG in alkaline urine contributes marginally to the high renal clearance and excretion of salicylic acid, validating alkalinization of a patient with SA overdose. Under acidic urine conditions, salicylic acid (SA) had a terminal plasma t1/2 value of 3.29 +/- 0.52 hours while under alkaline urine conditions this t1/2 was significantly reduced to 2.50 +/- 0.41 hours (p = 0.0156). The total oral body clearance of salicylic acid under acidic conditions (1.38 +/- 0.43 l/h) is significantly lower than under alkaline urine conditions (2.27 +/- 0.83 l/h; p = 0.0410). The Km and Vmax values of SA, and its conjugates salicylic acid phenolic glucuronide (SAPG), salicyluric acid (SU) and salicyluric acid phenolic glucuronide (SUPG) did not differ statistically under acidic and alkaline urine conditions. The protein binding of SA was 93.8 +/- 1.0% and that of SU was 89.7 +/- 2.2% in vivo and in vitro. SUPG had a protein binding of 84.8 +/- 1.8%, while SAPG showed no protein binding at all. The renal excretion of salicylic acid depends strongly on the urinary pH. The percentage of the dose excreted unchanged increased from 2.3 +/- 1.5% under acidic conditions to 30.5 +/- 9.1% under alkaline conditions (p = 0.0006). Alkaline urine lowered by 50% the percentage of the dose excreted as SU (p = 0.0028), SAAG (p = 0.0013), and SUPG (p = 0.0296), while SAPG is only marginally lowered (p = 0.0589).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834163

  7. Determination of sulfates and glucuronides of endogenic steroids in biofluids by high-performance liquid chromatography/orbitrap mass spectrometry

    NASA Astrophysics Data System (ADS)

    Semenistaya, E. N.; Virus, E. D.; Rodchenkov, G. M.

    2009-04-01

    the possibility of selective determination of testosterone and epitestosterone glucuronides in urine by high-performance liquid chromatography/high-resolution mass spectrometry using solid phase microextraction on a meps cartridge was studied. the effect of the biological matrix on the spectra of conjugated steroids can be taken into account by using the spectra of conjugates recorded for urine samples after hydrolysis as reference spectra. the conditions of fragmentation in the ion source were optimized for separate analytes. this method was used for analyzing real samples with different testosterone/epitestosterone ratios. variations in conjugate contents and qualitative changes in the steroid profile of endogenic compounds were observed.

  8. Effect of pH and human serum albumin on the cytotoxicity of a glucuronide prodrug of 9-aminocamptothecin

    Microsoft Academic Search

    Zeljko M. Prijovich; Yu-Lin Leu; Steve R. Roffler

    2007-01-01

    Purpose\\u000a   9-aminocamptothecin glucuronide (9ACG) is a prodrug of 9-aminocamptothecin (9AC) that displays potent antitumor activity against\\u000a human tumor xenografts in nude mice. Camptothecins exist in a pH dependent equilibrium between active lactone and inactive\\u000a carboxy forms that can be altered by binding to human serum albumin (HSA). Here we investigated the influence of pH and HSA\\u000a on the lactone-carboxy equilibrium,

  9. Accelerated Koenigs-Knorr glucuronidation of a deactivated nitrophenol: unveiling the role of polyamine additive 1,1,4,7,10,10-hexamethyltriethylenetetramine through design of experiments.

    PubMed

    Stazi, Federica; Palmisano, Giovanni; Turconi, Marco; Clini, Simona; Santagostino, Marco

    2004-02-20

    1,1,4,7,10,10-Hexamethyltriethylenetetramine (HMTTA) emerged from a limited parallel screening of selected polyamines as the most appropriate additive for an especially problematic Koenigs-Knorr glucuronidation. This initial finding rapidly evolved into a reliable and high-yielding procedure through the use of two sets of experimental designs. The detailed effect of the stoichiometry of reagents and the amount of amine additive on reaction yield was elucidated. The complexity of the response surface for product yield, described by a third-order polynomial equation, together with ancillary kinetic experiments evidenced the multiple role of HMTTA in the present glucuronidation process. PMID:14961657

  10. Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats

    SciTech Connect

    Abbott, F.V.; Palmour, R.M.

    1988-01-01

    The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced and increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catelepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of (/sup 3/H)-etorphine, (/sup 3/H)-dihydromorphine and (/sup 3/H)-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with K/sub i/ values of about 30 nM, as compared to morphine K/sub i/ values of about 3 nM.

  11. Meconium Indicators of Maternal Alcohol Abuse during Pregnancy and Association with Patient Characteristics

    PubMed Central

    Goecke, Tamme W.; Burger, Pascal; Fasching, Peter A.; Bakdash, Abdulsallam; Engel, Anne; Häberle, Lothar; Voigt, Franziska; Faschingbauer, Florian; Raabe, Eva; Maass, Nicolai; Rothe, Michael; Beckmann, Matthias W.; Pragst, Fritz

    2014-01-01

    Aim. Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium. Methods. A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics. Results. We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P < 0.01). This association was inverse in cases with EtG value above 120?ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found. Conclusion. Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established. PMID:24800249

  12. Tris(ethyl­enediamine)zinc(II) hexa­fluorido­silicate

    PubMed Central

    Li, Yang; Shi, Qi; Slawin, Alexandra M. Z.; Woollins, J. Derek; Dong, Jinxiang

    2009-01-01

    The title compound, [Zn(C2H8N2)3](SiF6), was synthesized ionothermally using choline chloride–imidazolidone as solvent and template provider. In the crystal structure, the anions and cations are located on special positions of site symmetry 3.2 and show a typical octa­hedral geometry. The ZnII ion is coordinated by six N atoms from three ethyl­enediamine mol­ecules. The crystal structure displays weak hydrogen bonding between [SiF6]2? anions and the ethyl­enediamine NH hydrogen atoms. PMID:21578568

  13. Intermediate syndrome with delayed distal polyneuropathy from ethyl parathion poisoning.

    PubMed

    Nisse, P; Forceville, X; Cezard, C; Ameri, A; Mathieu-Nolf, M

    1998-12-01

    An acute poisoning in a 44-y-old female who ingested 50 ml of ethyl parathion concentrate (25 g) is described. She was treated by gastric lavage, administration of pralidoxime and atropine, and mechanical ventilation. As signs of intoxication disappeared at day 3, treatment was discontinued. The patient had a relapse of acute cholinergic crisis at day 4, and the same treatment was applied again. The acute poisoning phase was followed by an intermediate syndrome and delayed distal polyneuropathy. The clinical course of this severe ethyl parathion poisoning was favorable after 40 d. PMID:9830697

  14. Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases.

    PubMed

    Olson, Kristine C; Sun, Dongxiao; Chen, Gang; Sharma, Arun K; Amin, Shantu; Ropson, Ira J; Spratt, Thomas E; Lazarus, Philip

    2011-09-19

    Dibenzo[a,l]pyrene (DB[a,l]P) (dibenzo[def,p]chrysene) is a highly carcinogenic polycyclic aromatic hydrocarbon (PAH) that has been identified in tobacco smoke and is found in our environment due to incomplete combustion of organic matter. Its metabolites are known to form stable DNA adducts in bacteria and mammalian cells, and can lead to tumors in animal models. Glucuronidation of major metabolites of DB[a,l]P by the uridine-5'-diphosphate glucuronosyltransferase (UGT) family of enzymes is an important route of detoxification of this pro-carcinogen. The focus of the current study was to characterize the glucuronidation of the pro-carcinogenic enantiomers DB[a,l]P-(+)-trans-11S,12S-diol and DB[a,l]P-(-)-trans-11R,12R-diol. Glucuronidation assays with HEK293 cell lines overexpressing individual human UGT enzymes demonstrated that UGTs 1A1, 1A4, 1A7, 1A8, 1A9, 1A10, and 2B7 glucuronidated one or both DB[a,l]P-trans-11,12-diol enantiomers. Three glucuronide conjugates were observed in activity assays with UGTs 1A1 and 1A10, while two glucuronides were formed by UGTs 1A7, 1A8, and 1A9, and one glucuronide was made by UGT1A4 and UGT2B7. Enzyme kinetic analysis indicated that UGT1A9 was the most efficient UGT at forming both the (+)-DB[a,l]P-11-Gluc and (-)-DB[a,l]P-11-Gluc products, while UGTs 1A1 and 1A10 were the most efficient at forming the (+)-DB[a,l]P-12-Gluc product (as determined by k(cat)/K(M)). Incubations with human liver microsomes showed the formation of three diastereomeric glucuronide products: (+)-DB[a,l]P-11-Gluc, (+)-DB[a,l]P-12-Gluc, and (-)-DB[a,l]P-11-Gluc, with an average overall ratio of 31:32:37 in four liver specimens. Human bronchus and trachea tissue homogenates demonstrated glucuronidation activity against both DB[a,l]P-trans-11,12-diol enantiomers, with both tissues producing the (+)-DB[a,l]P-11-Gluc and (+)-DB[a,l]P-12-Gluc with little or no formation of (-)-DB[a,l]P-11-Gluc. These results indicate that multiple UGTs are involved in the stereospecific glucuronidation of DB[a,l]P-trans-11,12-diol in a pattern consistent with their expression in respiratory tract tissues and that glucuronidation may be an important first-line detoxification mechanism of DB[a,l]P metabolites. PMID:21780761

  15. 40 CFR 721.10075 - Carbon black, 4-[[2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic...2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic...2-(Sulfooxy) ethyl]substituted] phenyl-modified, sodium salts (PMN...

  16. 40 CFR 721.10075 - Carbon black, 4-[[2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic...2-(Sulfooxy) ethyl]substituted] phenyl- modified, sodium salts (generic...2-(Sulfooxy) ethyl]substituted] phenyl-modified, sodium salts (PMN...

  17. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 false Deletion of methyl ethyl ketone from the list of hazardous...List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK,...

  18. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain.

    PubMed

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup; Drewes, Asbjørn Mohr; Christrup, Lona Louring; Kreilgaard, Mads

    2015-07-10

    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can be used to quantify dose-response relationships for the population as well as interindividual and interoccasion variability. Additionally, relevant covariates for population subgroups that deviate from the typical population can be identified and help clinicians in dose optimisation. This review provides a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates. Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course of response. Lastly, the impact of study design on the likelihood of determining accurate pharmacodynamic parameters for morphine response was evaluated. PMID:25861720

  19. Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity.

    PubMed

    Coldham, Nick G; Zhang, Ai-Qin; Key, Pauline; Sauer, Maurice J

    2002-01-01

    The systemic plasma pharmacokinetics of genistein were determined in rats to evaluate the absolute oral bioavailability and make comparison with similar data in the literature derived from humans subjects. The plasma concentrations of genistein, genistein glucuronide and carbon-14 were determined by LC-MS/MS and liquid scintillation counting following oral and intravenous dosing with [14C]genistein (4 mg kg(-1) body weight). The absorption of total radioactivity from the gut, (parent compound and metabolites), was 56 and 111% in male and female rats, respectively. In contrast, the absolute oral bioavailability of genistein in male and female rats was 7 and 15%. There was a significant (P<0.001) difference between Cmax of genistein after intravenous (6921 and 4392 ng/ml) and oral (21 and 22 ng/ml) dosing in male and female rats, respectively. After oral administration, the concentration profile of genistein glucuronide in plasma greatly exceeded that of parent compound during the absorption/distribution phase suggesting extensive first pass metabolism, and provided evidence of entero-hepatic circulation. Selective plasma analysis by LC-MS/MS, without prior enzymatic hydrolysis, enabled ready discrimination between parent and conjugated metabolites and prevented gross overestimation of genistein bioavailability. Pharmacokinetic parameters Cmax, Tmax and AUC were similar to those reported in humans, which supports the use of the rat model for genistein toxicity studies. PMID:12587954

  20. Metabolic engineering of Escherichia coli for the biosynthesis of flavonoid-O-glucuronides and flavonoid-O-galactoside.

    PubMed

    Kim, So Yeon; Lee, Hye Rin; Park, Kwang-Su; Kim, Bong-Gyu; Ahn, Joong-Hoon

    2015-03-01

    Most flavonoids are glycosylated and the nature of the attached sugar can strongly affect their physiological properties. Although many flavonoid glycosides have been synthesized in Escherichia coli, most of them are glucosylated. In order to synthesize flavonoids attached to alternate sugars such as glucuronic acid and galactoside, E. coli was genetically modified to express a uridine diphosphate (UDP)-dependent glycosyltransferase (UGT) specific for UDP-glucuronic acid (AmUGT10 from Antirrhinum majus or VvUGT from Vitis vinifera) and UDP-galactoside (PhUGT from Petunia hybrid) along with the appropriate nucleotide biosynthetic genes to enable simultaneous production of their substrates, UDP-glucuronic acid and UDP-galactose. To engineer UDP-glucuronic acid biosynthesis, the araA gene encoding UDP-4-deoxy-4-formamido-L-arabinose formyltransferase/UDP-glucuronic acid C-4? decarboxylase, which also used UDP-glucuronic acid as a substrate, was deleted in E. coli, and UDP-glucose dehydrogenase (ugd) gene was overexpressed to increase biosynthesis of UDP-glucuronic acid. Using these strategies, luteolin-7-O-glucuronide and quercetin-3-O-glucuronide were biosynthesized to levels of 300 and 687 mg/L, respectively. For the synthesis of quercetin 3-O-galactoside, UGE (encoding UDP-glucose epimerase from Oryza sativa) was overexpressed along with a glycosyltransferase specific for quercetin and UDP-galactose. Using this approach, quercetin 3-O-galactoside was successfully synthesized to a level of 280 mg/L. PMID:25515812

  1. Screening of 4-androstenedione misuse in cattle by LC-MS/MS profiling of glucuronide and sulfate steroids in urine.

    PubMed

    Anizan, Sebastien; Bichon, Emmanuelle; Di Nardo, Domenica; Monteau, Fabrice; Cesbron, Nora; Antignac, Jean-Philippe; Le Bizec, Bruno

    2011-10-30

    The use of anabolic agents in food producing animals is prohibited within the European Union since 1988. The illegal use of natural steroid hormones control is however still a current challenge, especially regarding the limitations of existing screening methods. In this context, the present study aimed to develop a new screening approach based on the emerging 'untargeted profiling' concept, but with a special emphasis on steroids phase II conjugated metabolites, in the scope of revealing potential biomarkers signing a fraudulent administration of 4-androstenedione. After extraction and separation of the urinary glucuronide and sulfate steroid fractions, each one was analyzed separately by UPLC-MS/MS using the precursor ion scan acquisition mode. This approach was carried out in order to monitor product ion characteristic of sulfate (m/z 97) and glucuronide (m/z 113) functional groups, and then to fish for any potential conjugated steroid leading to these ionic species after fragmentation. After statistical analysis, 86 metabolites (33 from steroid compounds and 53 from other unknown substances) were highlighted as potential biomarkers of 4-androstenedione abuse. After application of several robustness criteria, 26 metabolites (whom 5 were unambiguously structurally identified), were finally selected to build a statistical model which could be used as new diagnostic tool for screening purposes. PMID:22063529

  2. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...General. (1) Tolerances are established for residues of the herbicide, flufenpyr-ethyl; acetic acid, [2-chloro-4-fluoro-5...01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid,...

  3. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...General. Tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its metabolites and...Time-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its...

  4. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...General. (1) Tolerances are established for residues of the herbicide, flufenpyr-ethyl; acetic acid, [2-chloro-4-fluoro-5...01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid,...

  5. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...General. (1) Tolerances are established for residues of the herbicide, flufenpyr-ethyl; acetic acid, [2-chloro-4-fluoro-5...01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid,...

  6. 40 CFR 180.515 - Carfentrazone-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...515 Carfentrazone-ethyl; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide carfentrazone-ethyl, including its metabolites and degradates, in or on the commodities listed in the following...

  7. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...General. (1) Tolerances are established for residues of the herbicide, flufenpyr-ethyl; acetic acid, [2-chloro-4-fluoro-5...01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid,...

  8. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...General. Tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its metabolites and...Time-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its...

  9. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...General. Tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its metabolites and...Time-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its...

  10. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 false Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether. 151.50-40 Section...Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl...

  11. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 false Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether. 151.50-40 Section...Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl...

  12. 40 CFR 721.10109 - Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane. 721.10109 Section...Chemical Substances § 721.10109 Hexanoic acid, 2-ethyl-, mixed triesters with...

  13. 40 CFR 721.10109 - Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane. 721.10109 Section...Chemical Substances § 721.10109 Hexanoic acid, 2-ethyl-, mixed triesters with...

  14. 40 CFR 721.10109 - Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane. 721.10109 Section...Chemical Substances § 721.10109 Hexanoic acid, 2-ethyl-, mixed triesters with...

  15. 40 CFR 721.10109 - Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane. 721.10109 Section...Chemical Substances § 721.10109 Hexanoic acid, 2-ethyl-, mixed triesters with...

  16. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with modified...generic). (a) Chemical substance and significant...reporting. (1) The chemical substance identified...as Ethyl silicate, reaction products with...

  17. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with modified...generic). (a) Chemical substance and significant...reporting. (1) The chemical substance identified...as Ethyl silicate, reaction products with...

  18. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with modified...generic). (a) Chemical substance and significant...reporting. (1) The chemical substance identified...as Ethyl silicate, reaction products with...

  19. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with modified...generic). (a) Chemical substance and significant...reporting. (1) The chemical substance identified...as Ethyl silicate, reaction products with...

  20. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...established for the combined residues of the herbicide quizalofop (2-[4-(6-chloroquinoxalin-2-yl...established for the combined residues of the herbicide quizalofop (2-[4-(6-chloroquinoxalin-2-yl...established for the combined residues of the herbicide quizalofop-p ethyl ester...

  1. A green and regioselective acetylation of thioglycoside with ethyl acetate

    Microsoft Academic Search

    Pi-Hui Liang; Yin-Jen Lu; Ting-Hsuan Tang

    2010-01-01

    Treatment of saccharidic polyols in ethyl acetate with catalytic sulfuric acid leads to the corresponding primary monoacetate derivatives in good yields. The transesterification was realized by simple stirring without rigorous exclusion of moisture or oxygen. Our protocol is applicable to the regioselective monoacetylation of amino sugars having different substituents at the 2-positions.

  2. 77 FR 60917 - Trinexapac-ethyl; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ...ppm; sugarcane, molasses at 2.5 ppm; and wheat, bran at 6.0 ppm. The rule also proposed...the existing trinexapac-ethyl tolerances for wheat, forage from 1.5 to 1.0 ppm and wheat, middlings from 6.5 to 10.5 ppm, as...

  3. Synthesis of Ethyl Nalidixate: A Medicinal Chemistry Experiment

    ERIC Educational Resources Information Center

    Leslie, Ray; Leeb, Elaine; Smith, Robert B.

    2012-01-01

    A series of laboratory experiments that complement a medicinal chemistry lecture course in drug design and development have been developed. The synthesis of ethyl nalidixate covers three separate experimental procedures, all of which can be completed in three, standard three-hour lab classes and incorporate aspects of green chemistry such as…

  4. Kinetics of Ethyl Acetate Synthesis Catalyzed by Acidic Resins

    ERIC Educational Resources Information Center

    Antunes, Bruno M.; Cardoso, Simao P.; Silva, Carlos M.; Portugal, Ines

    2011-01-01

    A low-cost experiment to carry out the second-order reversible reaction of acetic acid esterification with ethanol to produce ethyl acetate is presented to illustrate concepts of kinetics and reactor modeling. The reaction is performed in a batch reactor, and the acetic acid concentration is measured by acid-base titration versus time. The…

  5. Asymmetric hydrogenation of ethyl pyruvate: Diffusion effects on enantioselectivity

    SciTech Connect

    Sun, Yongkui; Wang, Jian; LeBlond, C. [Merck & Co., Inc., Rahway, NJ (United States)] [and others] [Merck & Co., Inc., Rahway, NJ (United States); and others

    1996-07-01

    Enantioselectivity in the hydrogenation of ethyl pyruvate over cinchona-alkaloid-modified Pt has been studied. Kinetic studies indicated different mechanisms in different reaction regimes. Solution hydrogen concentration strongly corrrelated with reaction rates and enantioselectivity. 28 refs., 5 figs., 2 tabs.

  6. Surface tension of aqueous lithium bromide + 2-ethyl-1-hexanol

    SciTech Connect

    Kim, K.J.; Berman, N.S. (Arizona State Univ., Tempe, AZ (United States)); Wood, B.D. (Arizona State Univ., Tempe, AZ (United States))

    1994-01-01

    The surface tension of an aqueous lithium bromide solution containing an active surfactant (2-ethyl-1-hexanol) was measured over the lithium bromide concentration range 40 [<=] C[sub LiBr] [<=] 60 wt % and surfactant concentration range 0 [<=] C[sub sur] [<=] 200 ppm. The Du Nouy ring method was employed to determine the surface tension.

  7. Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?

    PubMed

    Kalogera, Eleni; Pistos, Constantinos; Provatopoulou, Xeni; Athanaselis, Sotirios; Spiliopoulou, Chara; Gounaris, Antonia

    2013-12-01

    Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies. PMID:24140653

  8. Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene

    Microsoft Academic Search

    Margaret O. James; Leah D. Stuchal; Beatrice A. Nyagode

    2008-01-01

    The organochlorine pesticide, methoxychlor (MXC), is metabolized in animals to phenolic mono- and bis-demethylated metabolites (OH-MXC and HPTE, respectively) that interact with estrogen receptors and may be endocrine disruptors. The phase II detoxication of these compounds will influence the duration of action of the estrogenic metabolites, but has not been investigated extensively. In this study, the glucuronidation and sulfonation of

  9. The Apparent Inhibition of Inosine Monophosphate Dehydrogenase by Mycophenolic Acid Glucuronide Is Attributable to the Presence of Trace Quantities of Mycophenolic Acid

    Microsoft Academic Search

    Magdalena Korecka; Dejan Nikolic; Richard B. van Breemen; Leslie M. Shaw

    Background: Mycophenolic acid glucuronide, the pri- mary metabolite of the immunosuppressive agent my- cophenolic acid, affords weak inhibition of proliferat- ing and resting lymphocytes and recombinant human inosine monophosphate dehydrogenase in comparison to the active drug. We evaluated the hypothesis that mycophenolic acid is a trace contaminant of the gluc- uronide metabolite preparation and that this accounts for the observed

  10. UGT1A4*3 encodes significantly increased glucuronidation of olanzapine in patients on maintenance treatment and in recombinant systems.

    PubMed

    Haslemo, T; Loryan, I; Ueda, N; Mannheimer, B; Bertilsson, L; Ingelman-Sundberg, M; Molden, E; Eliasson, E

    2012-08-01

    Olanzapine, a world leader in antipsychotic drugs, is used in the treatment of schizophrenia and bipolar disorder. There is considerable interpatient variability in its hepatic clearance. Polymorphic glucuronidation of olanzapine by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4) was investigated retrospectively in patient samples taken for routine therapeutic drug monitoring (TDM) and in recombinant metabolic systems in vitro. Multivariate analyses revealed that patients who were heterozygous as well as those who were homozygous for the UGT1A4*3 allelic variant had significantly higher concentrations of the major metabolite olanzapine 10-N-glucuronide in serum (+38% (P = 0.011) and +246% (P < 0.001), respectively). This finding was in line with the significant increases in glucuronidation activity of olanzapine observed with recombinant UGT1A4.3 (Val-48) as compared with UGT1A4.1 (Leu-48) (1.3-fold difference, P < 0.001). By contrast, serum concentrations of the parent drug were not significantly influenced by UGT1A4 genotype. Our findings therefore indicate that UGT1A4-mediated metabolism is not a major contributor to interpatient variability in olanzapine levels. However, with respect to other drugs for which UGT1A4 has a dominant role in clearance, increased glucuronidation encoded by UGT1A4*3 might impact the risk for subtherapeutic drug exposure. PMID:22713701

  11. Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity.

    PubMed Central

    Burchell, B; Ebner, T; Baird, S; Bin Senafi, S; Clarke, D; Brierley, C; Sutherland, L

    1994-01-01

    Five cloned human hepatic UDP-glucuronosyltransferase (UGT) cDNAs were stably expressed in tissue culture cell lines. More than 100 drugs and xenobiotics were used as substrates for glucuronidation catalyzed by the cloned human transferases to determine the chemical structures accepted as substrates. UGT-HP1 exhibited a limited substrate specificity for planar phenolic compounds, whereas UGT-HP4 was more accepting of nonplanar phenols, anthraquinones, flavones, alphatic alcohols, aromatic carboxylic acids, steroids and many drugs of varied structure. UGT-HP3 (bilirubin UGT) catalyzed the glucuronidation of ethinylestradiol. UGT-H6 and UGT-H25 (steroid/bile acid UGTs) also catalyzed the glucuronidation of some xenobiotics. Levels of UGT-HP4 activity towards some substrates were sufficient to allow determination of kinetic parameters for the enzyme reaction. Further, metabolism of drugs could be studied by addition to the recombinant cell lines in culture and extraction of the media allowed analysis of glucuronide formation. The protection afforded against cytotoxic drugs was observed. The data presented here demonstrate the potential of using these recombinant cell lines for investigation of phase II metabolism by human UGTs and subtle differences in protein structure which affect their specificity. PMID:7698078

  12. Tentative Structural Assignment of a Glucuronide Metabolite of Methyltestosterone in Tilapia Bile by Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.

    PubMed

    Nishshanka, Upul; Chu, Pak-Sin; Evans, Eric; Reimschuessel, Renate; Hasbrouck, Nicholas; Amarasinghe, Kande; Jayasuriya, Hiranthi

    2015-06-24

    Methyltestosterone (MT), a strong androgenic steroid, is not approved for use in fish aquaculture in the United States. It is used in the U.S. under an investigational new animal drug exemption (INAD) only during the early life stages of fish. There is a possibility that farmers feed fish with MT to enhance production for economic gains. Therefore, there is a need to develop methods for the detection of MT and its metabolite residues in fish tissue for monitoring purposes. Previously, our laboratory developed a liquid chromatography-quadrupole time-of-flight (LC-QTOF) method for characterization of 17-O-glucuronide metabolite (MT-glu) in bile of tilapia dosed with MT. The system used was an Agilent 6530 Q-TOF equipped with electrospray jet stream technology, operating in positive ion mode. Retrospective analysis of the data generated in that experiment by a feature-finding algorithm, combined with a search against an in-house library of possible MT-metabolites, resulted in the discovery of a major glucuronide metabolite of MT in the bile extracts. Preliminary data indicate it to be a glucuronide of a hydroxylated MT (OHMT-glu) which persists in tilapia bile for at least 2 weeks after dosing. We present the tentative structural assignment of the OHMT-glu in tilapia bile and time course of development. This glucuronide can serve as a marker to monitor illegal use of MT in tilapia culture. PMID:25980472

  13. 76 FR 82320 - Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ...Investigation No. 332-288] Ethyl Alcohol for Fuel Use: Determination of the Base...U.S. domestic market for fuel ethyl alcohol during the 12-month period ending on...quantity'' of imports of fuel ethyl alcohol with a zero percent local feedstock...

  14. 75 FR 82069 - Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ...Investigation No. 332-288] Ethyl Alcohol for Fuel Use: Determination of the Base...U.S. domestic market for fuel ethyl alcohol during the 12-month period ending on...quantity'' of imports of fuel ethyl alcohol with a zero percent local feedstock...

  15. 78 FR 9938 - Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ...Investigation No. 332-288] Ethyl Alcohol for Fuel Use: Determination of the Base...U.S. domestic market for fuel ethyl alcohol during the 12-month period ending on...quantity'' of imports of fuel ethyl alcohol, and the Commission transmitted it...

  16. Production of ethyl acetate from dilute ethanol solutions by Candida utilis

    Microsoft Academic Search

    David W. Armstrong; Stanley M. Martin; Hiroshi Yamazaki

    1984-01-01

    The conversion of ethanol to ethyl acetate has an advantage as a method of ethanol recovery since ethyl acetate is amenable to simple solvent extraction. The potential of Candida utilis in this conversion was studied. The kinetics of accumulation of ethanol and ethyl acetate in glucose-grown C. utilis showed that ester formation resulted from ethanol utilization under appropriate aeration and

  17. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...disulfide (carbon bisulfide) and ethyl ether. 151.50-40 Section 151.50-40...disulfide (carbon bisulfide) and ethyl ether. (a) The provisions of this section...bisulfide ) and § 151.50-42 for ethyl ether shall also be observed. [CFGR...

  18. The Impact of Glucuronidation on the Bioactivation and DNA Adduction of the Cooked-Food Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in vivo

    SciTech Connect

    Malfatti, M A; Ubick, E A; Felton, J S

    2005-03-31

    UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of many different chemicals. Glucuronidation is especially important for detoxifying reactive intermediates from metabolic reactions, which otherwise can be biotransformed into highly reactive cytotoxic or carcinogenic species. Detoxification of certain food-borne carcinogenic heterocyclic amines (HAs) is highly dependent on UGT1A-mediated glucuronidation. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant carcinogenic HA found in well-done cooked meat, is extensively glucuronidated by UGT1A proteins. In humans, CYP1A2 catalyzed N-hydroxylation and subsequent UGT1A-mediated glucuronidation is a dominant pathway in the metabolism of PhIP. Therefore, changes in glucuronidation rates could significantly alter PhIP metabolism. To determine the importance of UGT1A-mediated glucuronidation in the biotransformation of PhIP, UGT1A proficient Wistar and UGT1A deficient Gunn rats were exposed to a single 100 {micro}g/kg oral dose of [{sup 14}C]-PhIP. Urine was collected over 24 h and the PhIP urinary metabolite profiles were compared between the two strains. After the 24 h exposure, livers and colon were removed and analyzed for DNA adduct formation by accelerator mass spectrometry. Wistar rats produced several PhIP and N-hydroxy-PhIP glucuronides that accounted for {approx}25% of the total amount of recovered urinary metabolites. In the Gunn rats, PhIP and N-hydroxy-PhIP glucuronides were reduced by 68-92%, compared to the Wistar rats, and comprised only 4% of the total amount of recovered urinary metabolites. PhIP-DNA adduct analysis from the Gunn rats revealed a correlation between reduced PhIP and N-hydroxy-PhIP glucuronide levels in the urine and increased hepatic DNA adducts, compared to the Wistar rats. These results indicate that UGT1A-mediated glucuronidation of PhIP and N-hydroxy-PhIP is an important pathway for PhIP detoxification. Failure to form glucuronide conjugates results in increases in PhIP bioactivation and DNA adduct formation, which can potentially lead to increases in tumor formation. Therefore, diminished UGT1A activity could pose a significant risk for the development of certain cancers from exposure to PhIP.

  19. Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.

    PubMed

    Murphy, Sharon E; Park, Sung-Shim L; Thompson, Elizabeth F; Wilkens, Lynne R; Patel, Yesha; Stram, Daniel O; Le Marchand, Loic

    2014-11-01

    Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk. PMID:25233931

  20. Elevated plasma creatinine due to creatine ethyl ester use.

    PubMed

    Velema, M S; de Ronde, W

    2011-02-01

    Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure. PMID:21411845

  1. Icosapent ethyl for the treatment of severe hypertriglyceridemia

    PubMed Central

    Fares, Hassan; Lavie, Carl J; DiNicolantonio, James J; O’Keefe, James H; Milani, Richard V

    2014-01-01

    Hypertriglyceridemia is a highly prevalent lipid abnormality and it is associated with atherosclerosis, with a growing body of evidence linking elevated triglycerides (TGs) with cardiovascular disease. The current major omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) combination, lowers serum TGs while often increasing levels of low-density lipoprotein cholesterol. Icosapent ethyl is an omega-3 polyunsaturated fatty acid with a 96% pure ethyl ester of EPA that has been recently approved for lowering TG levels in patients with very high TGs (?500 mg/dL), and it does so without significantly affecting serum low-density lipoprotein cholesterol. The potential benefits of omega-3 fatty acid therapy for dyslipidemias will be discussed, including the potential pros and cons of EPA alone versus the more common and readily available EPA/DHA combination therapy. PMID:25028554

  2. [Influence of ethyl alcohol on diabetes pathogenesis type].

    PubMed

    Zasimowicz, Elzbieta; Wolszczak, Blanka; Zasimowicz, Barbara

    2014-03-01

    Relations between metabolism of carbohydrates and ethyl alcohol consumption became a subject of many research because they occur very frequently amongst alcoholics. One of the most often and dangerous effects of abusing ethanol is hypoglycemia. It is caused by hepatic gluconeogenesis disturbed by ethyl alcohol. Chronic result of abusing alcohol is chronic pancreas inflammation (PZT), what causes disorders of exo- and endocrine function of pancreas. Endocrine function is secretion of insulin and the glucagon what regulates metabolism of absorbed compounds. Failure of beta cells of Langerhans islets causes diabetes demanding insulin therapy. The ethanol can cause recurring diabetes resulting from damage of cells of Langerhans islets but can be also the risk factor of diabetes type 2. PMID:24779223

  3. Identification of an antioxidant, ethyl protocatechuate, in peanut seed testa.

    PubMed

    Huang, Shiow Chyn; Yen, Gow-Chin; Chang, Lee-Wen; Yen, Wen-Jye; Duh, Pin-Der

    2003-04-01

    The antioxidant activity and identification of the antioxidant component of peanut seed testa were investigated. The antioxidant activity of peanut seed testa was studied in the linoleic acid model system by using the ferric thiocyanate method. Among the five organic solvent extracts, the ethanolic extracts of peanut seed testa (EEPST) produced higher yields and stronger antioxidant activity than other organic solvent extracts. EEPST was separated into 17 fractions on silica gel column chromatography. Fraction 17, which showed the largest yield and significant antioxidant activity, was separated by thin-layer chromatography. Four major antioxidative subfractions were present. Subfraction 17-2 was found to be effective in preventing oxidation of linoleic acid. This subfraction was further fractionated and isolated and characterized by UV, MS, IR, and (1)H NMR techniques. The active compound was identified as ethyl protocatechuate (3,4-dihydroxybenzoic acid ethyl ester). PMID:12670184

  4. Species differences in sinusoidal and canalicular efflux transport of mycophenolic acid 7-O-glucuronide in sandwich-cultured hepatocytes

    PubMed Central

    Tetsuka, Kazuhiro; Gerst, Nicolas; Tamura, Kouichi; Masters, Jeffrey N

    2014-01-01

    Metabolism and sinusoidal/canalicular efflux of mycophenolic acid (MPA) was investigated using sandwich-cultured hepatocytes (SCHs). After applying MPA to SCHs from humans, wild-type rats, and multidrug resistance-associated protein (Mrp) 2-deficient rats, the MPA metabolites 7-O-glucuronide (MPAG) and acyl glucuronide (AcMPAG) were detected in the intracellular compartment of the SCHs. Sinusoidal efflux of MPAG was detected in all SCH preparations including Mrp2-deficient rat SCHs, whereas canalicular efflux of MPAG was observed in wild-type rat and human SCHs but not in Mrp2-deficient rat SCHs. The ratio of canalicular efflux to net (canalicular plus sinusoidal) efflux was 37 ± 8% in wild-type rat SCHs, while the ratio in human SCHs was significantly lower (20 ± 2%, P < 0.05), indicating species differences in the direction of hepatic MPAG transport. This 20% ratio in human SCHs corresponds to a high sinusoidal MPAG efflux (80%) that can in part account for the urine-dominated recovery of MPAG in humans. Both sinusoidal and canalicular MPAG efflux in rat SCHs shows a good correspondence to urinary and biliary recovery of MPAG after MPA dosing. The sinusoidal efflux of AcMPAG in human SCHs was detected from one out of three donors, suggesting donor-to-donor variation. In conclusion, this study demonstrates the predictive value of SCHs for elucidating the interplay of metabolism and efflux transport, in addition to demonstrating a species difference between rat and human in sinusoidal and canalicular efflux of MPAG. PMID:25505584

  5. Structural analysis of 1-ethyl-3-methylimidazolium bifluoride melt

    Microsoft Academic Search

    Kazuhiko Matsumoto; Rika Hagiwara; Yasuhiko Ito; Shinji Kohara; Kentaro Suzuya

    2003-01-01

    The structure of 1-ethyl-3-methylimidazolium bifluoride (EMImF·HF) melt has been analyzed at 333 K by a high-energy synchrotron X-ray diffraction method. The total correlation function of the EMImF·HF melt was similar to that of the solid state, indicating that not only the short range but also the intermediate-range ordering in the solid are partially preserved in the liquid state. The intra-molecular

  6. Carbon dioxide solubility in 1-ethyl-3-methylimidazolium trifluoromethanesulfonate

    Microsoft Academic Search

    Allan N. Soriano; Bonifacio T. Doma Jr.; Meng-Hui Li

    2009-01-01

    In this work, we present new solubility results for carbon dioxide in the ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate for temperatures ranging from (303.2 to 343.2)K and pressures up to 5.9MPa using a thermogravimetric microbalance. Carbon dioxide solubilities were determined from absorption saturation (equilibrium) results at each fixed temperature and pressure. The buoyancy effect was accounted for in the evaluation of the

  7. An analysis of the fluorescence spectrum of europium ethyl sulphate

    Microsoft Academic Search

    B. R. Judd

    1959-01-01

    A theoretical analysis is made of the splittings induced in the levels F1, F2, F3, F4, F5, F6 of the ion Eu by the electric field of the ethyl sulphate lattice. Four parameters are used to fit the data, and it is found that very good agreement can be established between experiment and theory in the great majority of cases.

  8. Separation optimization for the recovery of phenyl ethyl alcohol.

    PubMed

    Priddy, S A; Hanley, T R; Effler, W T

    1999-01-01

    Phenyl ethyl alcohol is a compound that occurs naturally in flower petals and in many common beverages, such as beer. Desire for the floral, rose-like notes imparted by phenyl ethyl alcohol has created a unique niche for this chemical in flavor and fragrance industries. Phenyl ethyl alcohol can be produced by Saccharomyces cerevisiae via bioconversion. Often this method of production results in extremely low yields, thus placing a great deal of importance on recovery and purification of the valuable metabolite. To determine the best method for recovering the chemical, a primary recovery step and a secondary recovery step were developed. The primary recovery step consisted of comparing dead-end filtration with crossflow ultrafiltration. Crossflow ultrafiltration was ultimately selected to filter the fermentation broth because of its high flow rates and low affinity for the product. The secondary recovery step consisted of a comparison of liquid- liquid extraction and hydrophobic resin recovery. The hydrophobic resin was selected because of its higher rate of recovery and a higher purity than the liquid-liquid extraction, the current practice of Brown-Forman. PMID:15304716

  9. Fragrance material review on ethyl phenyl carbinyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of ethyl phenyl carbinyl acetate when used as a fragrance ingredient is presented. Ethyl phenyl carbinyl acetate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for ethyl phenyl carbinyl acetate were evaluated, then summarized, and includes: physical properties; acute toxicity; skin irritation; and skin sensitization data. A safety assessment of the entire AAASAE will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances. PMID:22433983

  10. Sensory reception of the primer pheromone ethyl oleate

    NASA Astrophysics Data System (ADS)

    Muenz, Thomas S.; Maisonnasse, Alban; Plettner, Erika; Le Conte, Yves; Rössler, Wolfgang

    2012-05-01

    Social work force distribution in honeybee colonies critically depends on subtle adjustments of an age-related polyethism. Pheromones play a crucial role in adjusting physiological and behavioral maturation of nurse bees to foragers. In addition to primer effects of brood pheromone and queen mandibular pheromone—both were shown to influence onset of foraging—direct worker-worker interactions influence adult behavioral maturation. These interactions were narrowed down to the primer pheromone ethyl oleate, which is present at high concentrations in foragers, almost absent in young bees and was shown to delay the onset of foraging. Based on chemical analyses, physiological recordings from the antenna (electroantennograms) and the antennal lobe (calcium imaging), and behavioral assays (associative conditioning of the proboscis extension response), we present evidence that ethyl oleate is most abundant on the cuticle, received by olfactory receptors on the antenna, processed in glomeruli of the antennal lobe, and learned in olfactory centers of the brain. The results are highly suggestive that the primer pheromone ethyl oleate is transmitted and perceived between individuals via olfaction at close range.

  11. Modulation of Strawberry/Cranberry Phenolic Compounds Glucuronidation by Co-Supplementation with Onion: Characterization of Phenolic Metabolites in Rat Plasma Using an Optimized ?SPE-UHPLC-MS/MS Method.

    PubMed

    Dudonné, Stéphanie; Dubé, Pascal; Pilon, Geneviève; Marette, André; Jacques, Hélène; Weisnagel, John; Desjardins, Yves

    2014-03-26

    Plant phenolic compounds are suggested to exert pharmacological activities in regards to obesity and type-2 diabetes, but their mode of action is poorly understood due to a lack of information about their bioavailability. This work aimed to study the bioavailability of GlucoPhenol phenolic compounds, a strawberry-cranberry extracts blend, by characterizing plasma phenolic profile in obese rats. A comparison was performed by co-supplementation with an onion extract. Using an optimized ?SPE-UHPLC-MS/MS method, 21 phenolic metabolites were characterized, mostly conjugated metabolites and microbial degradation products of the native phenolic compounds. Their kinetic profiles revealed either an intestinal or hepatic formation. Among identified metabolites, isorhamnetin glucuronide sulfate was found in greater amount in plasma. Three glucuronidated conjugates of strawberry-cranberry phenolic compounds, p-hydroxybenzoic acid glucuronide, catechins glucuronide, and methyl catechins glucuronide were found in higher quantities when GlucoPhenol was ingested together with onion extract (+252%, +279%, and +118% respectively), suggesting a possible induction of glucuronidation processes by quercetin. This work allowed the characterization of actual phenolic metabolites generated in vivo following a phenolic intake, the analysis of their kinetics and suggested a possible synergistic activity of phenolic compounds for improving bioavailability. PMID:24628392

  12. [What ethanol metabolites as biological markers tell us about alcohol use].

    PubMed

    Wurst, Friedrich Martin; Thon, Natasha; Weinmann, Wolfgang; Yegles, Michel; Preuss, Ulrich

    2014-01-01

    Alcohol and tobacco related disorders are the two leading and most expensive causes of illness in central Europe. In addition to self reports and questionnaires, biomarkers are of relevance in diagnosis and therapy of alcohol use disorders. Traditional biomarkers such as gamma glutamyl transpeptidase or mean corpuscular volume are indirect biomarkers and are subject to influence of age, gender and non alcohol related diseases, among others.Direct ethanol metabolites such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake--EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programs, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and fetal alcohol syndrome. PMID:24322386

  13. Utility of coloured hair for the detection of drugs and alcohol.

    PubMed

    Agius, Ronald

    2014-06-01

    The aim of this paper is to assess the utility of coloured hair for the detection of drugs and alcohol in a large statistically significant population. The positivity rate, the 1st, 5th, 50th, 95th, and 99th percentiles of five amphetamines, cannabinoids, cocaine, four opiates, methadone, buprenorphine, seven benzodiazepines, and ethyl glucuronide (EtG) in 9488 non-treated and 1026 cosmetically treated (dyed or bleached) authentic hair samples was compared. Analytical methods used were accredited for forensic purposes at the cut-offs defined by the German driving licence re-granting medical and psychological assessment (MPA) guidelines. Considering only the drug classes for which at least 10 positive samples were detected, the positivity rate in non-treated hair was highest for alcohol (4.50%; measured using EtG at concentrations ? 7 pg/mg hair), followed by THC (2.00%), cocaine (1.75%), and amphetamine (0.59%). While the 1st to 99th percentile range was significantly lower for drugs in treated, compared to non-treated hair, no significant change was observed for EtG. Additionally, no significant difference in the positivity rate was observed between treated hair and non-treated hair for both drugs and EtG. This study is the first attempt to evaluate the influence of cosmetic treatment, mainly dying, on the positivity rate for both drugs and EtG in hair samples submitted routinely for abstinence testing and the first to indicate that dyed and eventually bleached hair is not necessarily useless in detecting drugs and/or alcohol consumption, thus making coloured hair analysis still useful, often being the only possibility to prove such misuse. PMID:24817056

  14. catena-Poly[[aqua­(4-ethyl­benzoic acid-?O)lanthanum(III)]-tri-?-4-ethyl­benzoato

    PubMed Central

    Yang, Juan; Li, Jiantong; Wang, Qiufen

    2010-01-01

    The reaction of lanthanum nitrate and 4-ethyl­benzoic acid (EBAH) in aqueous solution yielded the title polymer, [La(C9H9O2)3(C9H10O2)(H2O)]n. The asymmetric unit contains one LaIII atom, three 4-ethyl­benzoate (EBA) ligands, one neutral EBAH ligand and one coordinated water mol­ecule. Each LaIII ion is eight-coordinated by six O atoms from six bridging-bidentate EBA ligands, one O atom from a monodentate EBAH ligand and one water O atom in a distorted bicapped trigonal-prismatic geometry. The adjacent LaIII ions are linked by the carboxyl­ate groups of EBA ligands in a bridging-bidetate coordination mode, resulting in an infinite chain structure along the c axis. O—H?O hydrogen-bonding inter­actions involving the water mol­ecules, carboxyl­ate groups and carboxyl H atoms are formed within the one-dimensional polymer. One of the ethyl groups is disordered over two positions with occupancies of 0.717?(7) and 0.283?(7). PMID:21579652

  15. Poly(ethylene glycol) modification of ?-glucuronidase-antibody conjugates for solid-tumor therapy by targeted activation of glucuronide prodrugs

    Microsoft Academic Search

    Tian-Lu Cheng; Bing-Mae Chen; Lai-Yee Chan; Pin-Yi Wu; Ji-Wang Chern; Steve R. Roffler

    1997-01-01

    Methoxypoly(ethylene glycol) (PEG) modification of Escherichia coli?-glucuronidase (?G) was examined as a method to improve the stability and pharmacokinetics of antibody-?G conjugates for\\u000a the targeted activation of glucuronide prodrugs at tumor cells. Introduction of 3 PEG molecules did not affect ?G activity\\u000a whereas higher degrees of PEG modification produced progressively greater loss of enzymatic activity. The enzyme was found\\u000a to

  16. Cure of malignant ascites and generation of protective immunity by monoclonal antibody–targeted activation of a glucuronide prodrug in rats

    Microsoft Academic Search

    Bing-Mae Chen; Lai-Yee Chan; Shing-Ming Wang; Ming-Fang Wu; Ji-Wang Chern; Steve R. Roffler

    1997-01-01

    We examined the in vivo efficacy of targeting b-glucuroni- dase (bG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 mg RH1-bG, a conjugate formed between recombinant bG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted

  17. BIOMARKERS TO DISCLOSE RECENT INTAKE OF ALCOHOL: POTENTIAL OF 5-HYDROXYTRYPTOPHOL GLUCURONIDE TESTING USING NEW DIRECT UPLC-TANDEM MS AND ELISA METHODS

    Microsoft Academic Search

    OLOF BECK; NIKOLAI STEPHANSON; NORBERT DAHMEN

    2007-01-01

    Aims: This study compared two new methods for direct determination of 5-hydroxytryptophol glucuronide (GTOL) in urine, a biomarker for detection of recent alcohol consumption. Methods: Urine samples were collected from ten alcoholic patients during recovery from intoxication. A direct injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS\\/MS) method for measurement of the urinary GTOL to 5-hydroxyindoleacetic acid (5-HIAA) ratio, and an

  18. Diabetes Mellitus Reduces Activity of Human UDP-Glucuronosyltransferase 2B7 in Liver and Kidney Leading to Decreased Formation of Mycophenolic Acid Acyl-Glucuronide Metabolite

    PubMed Central

    Dostalek, Miroslav; Court, Michael H.; Hazarika, Suwagmani

    2011-01-01

    Mycophenolic acid (MPA) is an immunosuppressive agent commonly used after organ transplantation. Altered concentrations of MPA metabolites have been reported in diabetic kidney transplant recipients, although the reason for this difference is unknown. We aimed to compare MPA biotransformation and UDP-glucuronosyltransferase (UGT) expression and activity between liver (n = 16) and kidney (n = 8) from diabetic and nondiabetic donors. Glucuronidation of MPA, as well as the expression and probe substrate activity of UGTs primarily responsible for MPA phenol glucuronide (MPAG) formation (UGT1A1 and UGT1A9), and MPA acyl glucuronide (AcMPAG) formation (UGT2B7), was characterized. We have found that both diabetic and nondiabetic human liver microsomes and kidney microsomes formed MPAG with similar efficiency; however, AcMPAG formation was significantly lower in diabetic samples. This finding is supported by markedly lower glucuronidation of the UGT2B7 probe zidovudine, UGT2B7 protein, and UGT2B7 mRNA in diabetic tissues. UGT genetic polymorphism did not explain this difference because UGT2B7*2 or *1c genotype were not associated with altered microsomal UGT2B7 protein levels or AcMPAG formation. Furthermore, mRNA expression and probe activities for UGT1A1 or UGT1A9, both forming MPAG but not AcMPAG, were comparable between diabetic and nondiabetic tissues, suggesting the effect may be specific to UGT2B7-mediated AcMPAG formation. These findings suggest that diabetes mellitus is associated with significantly reduced UGT2B7 mRNA expression, protein level, and enzymatic activity of human liver and kidney, explaining in part the relatively low circulating concentrations of AcMPAG in diabetic patients. PMID:21123165

  19. Glucuronidation of 39Azido39Deoxythymidine (Zidovudine) by Human Liver Microsomes: Relevance to Clinical Pharmacokinetic Interactions with Atovaquone, Fluconazole, Methadone, and Valproic Acid

    Microsoft Academic Search

    CAROL BRAUN TRAPNELL; RAYMOND W. KLECKER; CARLOS JAMIS-DOW; JERRY M. COLLINS

    1998-01-01

    Zidovudine (3*-azido-3*-deoxythymidine (AZT)), an antiviral nucleoside analog effective in the treatment of human immunodeficiency virus infection, is primarily metabolized to an inactive glucuronide form, GAZT, via uridine-5*-diphospho-glucuronosyltransferase (UGT) enzymes. UGT enzymes exist as different isoforms, each exhibiting substrate specificity. Published clinical studies have shown that atovaquone, fluconazole, metha- done, and valproic acid decreased GAZT formation, presumably due to UGT inhibition.

  20. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR155

    Microsoft Academic Search

    Christine Boesch-Saadatmandi; Agnieszka Loboda; Anika E. Wagner; Anna Stachurska; Alicja Jozkowicz; Jozef Dulak; Frank Döring; Siegfried Wolffram; Gerald Rimbach

    2011-01-01

    In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1?, interleukin 6, macrophage inflammatory

  1. Quantification of free mycophenolic acid and its glucuronide metabolite in human plasma by liquid-chromatography using mass spectrometric and ultraviolet absorbance detection

    Microsoft Academic Search

    Bronwyn Atcheson; Paul J. Taylor; David W. Mudge; David W. Johnson; Peter I. Pillans; Susan E. Tett

    2004-01-01

    The immunosuppressant drug mycophenolic acid (MPA) and its major metabolite, mycophenolic acid glucuronide (MPAG), are highly bound to albumin. An HPLC-tandem-MS (HPLC\\/MS\\/MS) and an HPLC-UV assay were developed to measure free (unbound) concentrations of MPA and MPAG, respectively. Ultrafiltrate was prepared from plasma (500?l) by ultrafiltration at 3000×g for 20min (20°C). Both MPA and MPAG were isolated from ultrafiltrate (100?l)

  2. Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches

    PubMed Central

    Wu, Baojian; Wang, Xiaoqiang; Zhang, Shuxing; Hu, Ming

    2012-01-01

    Purpose The catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics were determined experimentally using 145 phenolics, and analyzed by 3D-QSAR methods. Methods The catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using the CoMFA and CoMSIA techniques. Molecular alignment of the substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered as a separate substrate. Results The 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2= 0.949, r2pred = 0.775; CoMSIA: q2 = 0.579, r2= 0.876, r2pred = 0.700). The contour coefficient maps were applied to elucidate structural features among substrates that are responsible for the selectivity differences. Furthermore, the contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9; this enabled us to identify the UGT1A9 catalytic pocket with a high degree of confidence. Conclusion The CoMFA/CoMSIA models can predict the substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and its substrate selectivity. PMID:22302521

  3. Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates

    PubMed Central

    Suominen, Tina; Uutela, Päivi; Ketola, Raimo A.; Bergquist, Jonas; Hillered, Lars; Finel, Moshe; Zhang, Hongbo; Laakso, Aki; Kostiainen, Risto

    2013-01-01

    An UPLC-MS/MS method was developed for the determination of serotonin (5-HT), dopamine (DA), their phase I metabolites 5-HIAA, DOPAC and HVA, and their sulfate and glucuronide conjugates in human brain microdialysis samples obtained from two patients with acute brain injuries, ventricular cerebrospinal fluid (CSF) samples obtained from four patients with obstructive hydrocephalus, and a lumbar CSF sample pooled mainly from patients undergoing spinal anesthesia in preparation for orthopedic surgery. The method was validated by determining the limits of detection and quantification, linearity, repeatability and specificity. The direct method enabled the analysis of the intact phase II metabolites of 5-HT and DA, without hydrolysis of the conjugates. The method also enabled the analysis of the regioisomers of the conjugates, and several intact glucuronide and sulfate conjugates were identified and quantified for the first time in the human brain microdialysis and CSF samples. We were able to show the presence of 5-HIAA sulfate, and that dopamine-3-O-sulfate predominates over dopamine-4-O-sulfate in the human brain. The quantitative results suggest that sulfonation is a more important phase II metabolism pathway than glucuronidation in the human brain. PMID:23826355

  4. Degradation Processes in Corona-Charged Electret Filter-Media with Exposure to Ethyl Benzene

    Microsoft Academic Search

    Warren J. Jasper; Anushree Mohan; Juan Hinestroza; Roger Barker

    2007-01-01

    The degradation of filtration performance for corona- charged electret filter media exposed to ethyl benzene was assessed. Nonwoven corona-charged polypropy- lene fiber mats were exposed to ethyl-benzene using a custom made apparatus. Evaluated scenarios included ethyl-benzene vapor and liquid exposures. The filtra- tion performance was evaluated using DOP as a test aerosol to measure filtration performance. It was ob- served

  5. Fractionation of menhaden oil ethyl esters using supercritical fluid CO 2

    Microsoft Academic Search

    W. B. Nilsson; E. J. Gauglitz; J. K. Hudson; V. F. Stout; J. Spinelli

    1988-01-01

    Supercritical fluid CO2 was used to fractionate menhaden oil fatty acid ethyl esters to obtain concentrates of the esters of allcis-5,8,11,14,17-eicosapentaenoic acid (EPA) and allcis-4,7,10,13,16,19-docosahexaenoic acid (DHA). Separation of the ethyl esters was found to occur primarily by carbon number,\\u000a thus limiting the degree to which the ethyl esters of EPA and DHA could be concentrated. Urea fractionation of whole

  6. Formation of ethyl acetate by Kluyveromyces marxianus on whey: studies of the ester stripping

    Microsoft Academic Search

    Thanet Urit; Christian Löser; Martin Wunderlich; Thomas Bley

    2011-01-01

    Kluyveromyces marxianus is capable of converting lactose into ethyl acetate offering a chance for an economical reuse of whey. The microbial formation\\u000a of ethyl acetate as a bulk product calls for an aerobic process and, thus, the highly volatile ethyl acetate is discharged\\u000a from the aerated bioreactor. This stripping process was modeled and investigated experimentally. The stripping rate was proportional

  7. Fenfluramine hydrochloride, (+-)-N-ethyl-m-(trifluoromethyl)amphetamine hydrochloride

    E-print Network

    Grunewald, Gary L; Creese, Mary W; Extine, Michael W

    1981-01-01

    ) . SHELX. Program for crya structure determination. Univ. of Cambridge, England. STEWART, R . F . , DAVIDSON, E . R . & SIMPSON, W. T. J. Chem.Phys. 4 2 , 3 1 7 5 - 3 1 8 7 . Acta Cryst. (1981). B37, 1790-1793 Fenfluramine Hydrochloride, (±)-A^-Ethyl-/w-(trifluoromethyl)amphetamine... reflections after anisotropic refinement of all non-H atoms. The solid-state conformations of the fenfluramine and amphetamine cations are the same. Introduction. Single crystals of racemic fenfluramine hydrochloride were obtained by recrystallization from...

  8. [Clinical evaluation of hydroxy-ethylated starch (preparation HAES)].

    PubMed

    Mayzner-Zawadzka, E; Kraska, A; Kami?ski, B

    Hydroxy-ethylated starch (HAES-Fresenius) has been evaluated clinically at the Department of Anesthesiology and Intensive Care, Medical Academy in Warsaw. This plasma substitute is used in several countries as plasma substitute similar to dextran but of better properties. Results of our studies have shown, that HAES is worth its opinion. It is quite good plasma substitute of favourable effect on tissue perfusion. The above features together with a wide therapeutical margin and the lack of any effect on blood coagulation place HAES over dextran plasma substitutes. This preparation should have wider use in Poland. PMID:7689729

  9. Mixture effects during the oxidation of toluene, ethyl acetate and ethanol over a cryptomelane catalyst.

    PubMed

    Santos, V P; Pereira, M F R; Órfão, J J M; Figueiredo, J L

    2011-01-30

    The catalytic oxidation of two-component VOC mixtures (ethanol, ethyl acetate and toluene) was studied over cryptomelane. Remarkable mixture effects were observed on the activity and the selectivity. Toluene inhibits both ethyl acetate and ethanol oxidation, this effect being more evident in the case of ethyl acetate. For instance, the temperature for 100% conversion is about 210 °C when ethyl acetate is oxidised alone, and 250 °C or higher, when it is oxidised in mixtures with toluene. On the contrary, toluene oxidation is only slightly inhibited by the presence of ethyl acetate, while the presence of ethanol has a promoting effect. Concerning the mixtures of ethyl acetate and ethanol, both compounds have a mutual inhibitory effect, which is more evident in the case of ethyl acetate (the temperature for 100% conversion of ethyl acetate is about 45 °C higher when ethyl acetate is oxidised in mixtures with ethanol, while in the case of ethanol the corresponding increase is only 10 °C). PMID:21044815

  10. Effect of hair care and hair cosmetics on the concentrations of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption

    Microsoft Academic Search

    Sven Hartwig; Volker Auwärter; Fritz Pragst

    2003-01-01

    Fatty acid ethyl esters (FAEE) can be used as alcohol markers in hair. It was investigated in this study whether this diagnostic method is disturbed by hair care and hair cosmetics. Traces of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate were detected in all of 49 frequently applied hair care products by headspace solid phase microextraction (HS-SPME) and

  11. 40 CFR 721.10130 - Quino[2,3-b]acridine-7,14-dione, 5,12-dihydro-ar-[4-[[2-(sulfooxy)ethyl]substituted]phenyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (PMN...

  12. 40 CFR 721.10130 - Quino[2,3-b]acridine-7,14-dione, 5,12-dihydro-ar-[4-[[2-(sulfooxy)ethyl]substituted]phenyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (PMN...

  13. 40 CFR 721.10130 - Quino[2,3-b]acridine-7,14-dione, 5,12-dihydro-ar-[4-[[2-(sulfooxy)ethyl]substituted]phenyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (PMN...

  14. 40 CFR 721.10130 - Quino[2,3-b]acridine-7,14-dione, 5,12-dihydro-ar-[4-[[2-(sulfooxy)ethyl]substituted]phenyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (PMN...

  15. 40 CFR 721.10130 - Quino[2,3-b]acridine-7,14-dione, 5,12-dihydro-ar-[4-[[2-(sulfooxy)ethyl]substituted]phenyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (generic). ...2-(sulfooxy)ethyl]substituted]phenyl]-, monosodium salt (PMN...

  16. Transesterification process to manufacture ethyl ester of rape oil

    SciTech Connect

    Korus, R.A.; Hoffman, D.S.; Bam, N.; Peterson, C.L.; Drown, D.C. [Univ. of Idaho, Moscow, ID (United States)

    1993-12-31

    A process for the production of the ethyl ester of winter rape [EEWR] for use as a biodiesel fuel has been studied. The essential part of the process is the transesterification of rape oil with ethanol, in the presence of a catalyst, to yield the ethyl ester of rape oil as a product and glycerin as a by-product. Experiments have been performed to determine the optimum conditions for the preparation of EEWR. The process variables were: (1) temperature, (2) catalyst, (3) rate of agitation, (4) water content of the alcohol used, and (5) the amount of excess alcohol used. The optimum conditions were: (1) room temperature, (2) 0.5% sodium methoxide or 1% potassium hydroxide catalyst by weight of rapeseed oil, (3) extremely vigorous agitation with some splashing during the initial phase of the reaction and agitation was not necessary after the reaction mixture became homogeneous, (4) absolute ethanol was necessary for high conversion, and (5) 50% excess ethanol with NaOCH{sub 3} or 100% excess with KOH gave a maximum conversion. Viscosity, cloud point and pour point of the EEWR were measured. A preliminary break-even cost for the commercial production of EEWR was found to be $0.55/liter [$2.08/US gallon].

  17. DISCOVERY OF METHYL ACETATE AND GAUCHE ETHYL FORMATE IN ORION

    SciTech Connect

    Tercero, B.; Cernicharo, J.; Lopez, A.; Caro, G. M. Munoz [Department of Astrophysics, CAB, INTA-CSIC, Crta Torrejon-Ajalvir, km. 4, E-28850 Torrejon de Ardoz, Madrid (Spain); Kleiner, I.; Nguyen, H. V. L., E-mail: terceromb@cab.inta-csic.es, E-mail: jcernicharo@cab.inta-csic.es, E-mail: lopezja@cab.inta-csic.es, E-mail: munozcg@cab.inta-csic.es, E-mail: isabelle.kleiner@lisa.u-pec.fr, E-mail: nguyen@pc.rwth-aachen.de [Laboratoire Interuniversitaire des Systemes Atmospheriques, CNRS/IPSL UMR7583 et Universites Paris Diderot et Paris Est, 61 av. General de Gaulle, F-94010 Creteil (France)

    2013-06-10

    We report on the discovery of methyl acetate, CH{sub 3}COOCH{sub 3}, through the detection of a large number of rotational lines from each one of the spin states of the molecule: AA species (A{sub 1} or A{sub 2}), EA species (E{sub 1}), AE species (E{sub 2}), and EE species (E{sub 3} or E{sub 4}). We also report, for the first time in space, the detection of the gauche conformer of ethyl formate, CH{sub 3}CH{sub 2}OCOH, in the same source. The trans conformer is also detected for the first time outside the Galactic center source SgrB2. From the derived velocity of the emission of methyl acetate, we conclude that it arises mainly from the compact ridge region with a total column density of (4.2 {+-} 0.5) Multiplication-Sign 10{sup 15} cm{sup -2}. The derived rotational temperature is 150 K. The column density for each conformer of ethyl formate, trans and gauche, is (4.5 {+-} 1.0) Multiplication-Sign 10{sup 14} cm{sup -2}. Their abundance ratio indicates a kinetic temperature of 135 K for the emitting gas and suggests that gas-phase reactions could participate efficiently in the formation of both conformers in addition to cold ice mantle reactions on the surface of dust grains.

  18. A Liquid Chromatography–Tandem Mass Spectrometric Method for Quantification of Curcumin-O-Glucuronide and Curcumin in Human Plasma

    PubMed Central

    Chen, Wei; Fan-Havard, Patty; Yee, Lisa D.; Cao, Yu; Stoner, Gary D.; Chan, Kenneth K.; Liu, Zhongfa

    2012-01-01

    Curcumin is a widely-used herbal medicine for various human diseases including inflammation and cancer. The demonstration and optimization of curcumin’s activities in the clinical setting, however, has been compromised by its poor bioavailability and the lack of analytic methods to monitor its absorption. In this paper, we report the first validated liquid chromatography-tandem mass spectrometric method for simultaneous quantification of curcumin and its major metabolite: curcumin-O-glucuronide (COG), in the linear range of 2.0–2000 ng/mL in human plasma. The intra-day and inter-day accuracies of curcumin and COG in human plasma were in the range of 91.3–111.5% and 82.7–109.2% and their co-efficiency of variations were in the range of 3.5–12.7% and 3.1–11.3%, respectively. This method was capable of detecting only COG in human plasma samples from two healthy volunteers after an oral ingestion of curcumin. PMID:22682887

  19. In Vivo-Formed versus Preformed Metabolite Kinetics of trans-Resveratrol-3-sulfate and trans-Resveratrol-3-glucuronide

    PubMed Central

    Sharan, Satish; Iwuchukwu, Otito F.; Canney, Daniel J.; Zimmerman, Cheryl L.

    2012-01-01

    Metabolites in safety testing have gained a lot of attention recently. Regulatory agencies have suggested that the kinetics of preformed and in vivo-formed metabolites are comparable. This subject has been a topic of debate. We have compared the kinetics of in vivo-formed with preformed metabolites. trans-3,5,4?-Trihydroxystilbene [trans-resveratrol (RES)] and its two major metabolites, resveratrol-3-sulfate (R3S) and resveratrol-3-glucuronide (R3G) were used as model substrates. The pharmacokinetics (PK) of R3S and R3G were characterized under two situations. First, the pharmacokinetics of R3S and R3G were characterized (in vivo-formed metabolite) after administration of RES. Then, synthetic R3S and R3G were administered (preformed metabolite) and their pharmacokinetics were characterized. PK models were developed to describe the data. A three-compartment model for RES, a two-compartment model for R3S (preformed), and an enterohepatic cycling model for R3G (preformed) was found to describe the data well. These three models were further combined to build a comprehensive PK model, which was used to perform simulations to predict in vivo-formed metabolite kinetics. Comparisons were made between in vivo-formed and preformed metabolite kinetics. Marked differences were observed in the kinetics of preformed and in vivo-formed metabolites. PMID:22807110

  20. A comparison of the thermal degradation behaviour of ethylene-ethyl acrylate copolymer, low density polyethylene and poly(ethyl acrylate)

    Microsoft Academic Search

    Ian C. McNeill; Musarrat H. Mohammed

    1995-01-01

    The thermal stability of low density polyethylene (LDPE), poly(ethyl acrylate) (PEA) and ethylene-ethyl acrylate (EEA) copolymer has been investigated in an inert atmosphere using thermogravimetry-differential thermogravimetry (TG-DTG) and under vacuum by thermal volatilisation analysis (TVA). EEA copolymer was also investigated in nitrogen by differential scanning calorimetry (DSC), and LDPE and EEA copolymer have also been examined in air using TG-DTG.

  1. Vapour pressures and osmotic coefficients of binary mixtures of 1-ethyl-3-methylimidazolium ethylsulfate and 1-ethyl-3-methylpyridinium ethylsulfate with alcohols at T = 323.15 K

    Microsoft Academic Search

    Noelia Calvar; Begoña González; Ángeles Domínguez; Eugénia A. Macedo

    2009-01-01

    Osmotic coefficients of binary mixtures containing alcohols (ethanol, 1-propanol, and 2-propanol) and the ionic liquids 1-ethyl-3-methylimidazolium ethylsulfate and 1-ethyl-3-methylpyridinium ethylsulfate were determined at T=323.15K. Vapour pressure and activity coefficients of the studied systems were calculated from experimental data. The extended Pitzer model modified by Archer, and the modified NRTL model (MNRTL) were used to correlate the experimental data, obtaining standard

  2. STRUCTURAL CHARACTERIZATION OF ASPHALTENES AND ETHYL ACETATE INSOLUBLE FRACTIONS OF PETROLEUM VACUUM RESIDUES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asphaltenes and insoluble fractions of vacuum residues (VRs) of two Indian crude oils (viz. Heera and Jodhpur) of different specific gravity were obtained by precipitation of VRs in n-hexane, n-heptane and ethyl acetate, and also by subsequent reprecipitation of n-heptane and ethyl acetate soluble f...

  3. Controlled Degradation of Poly(Ethyl Cyanoacrylate-Co-Methyl Methacrylate)(PECA-Co-PMMA) Copolymers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper describes a method for modifying poly(ethyl cyanoacrylate) in order to control the degradation and the stability as well as the glass transition temperatures. Copolymers of poly(ethyl cyanoacrylate-co-methyl methacrylate) (PECA-co-PMMA) with various compositions were synthesized by free ...

  4. The effect of benzoic acid or its ethyl ester on rumen fermentation parameters

    E-print Network

    Paris-Sud XI, Université de

    The effect of benzoic acid or its ethyl ester on rumen fermentation parameters J Nousiainen Valio response of BA or its ethyl ester (EB) on the rumen fermentation parameters in the continuous culture to represent the maximum amount in vivo. The fermentation apparatus and the design of trials as well

  5. Photodissociation dynamics of ethyl ethynyl ether: A new ketenyl radical precursor

    E-print Network

    Butler, Laurie J.

    Photodissociation dynamics of ethyl ethynyl ether: A new ketenyl radical precursor M. J. Krisch, J that only cleavage of the C­O bond to form a C2HO radical and a C2H5 ethyl radical occurs. We observed radical is formed in two distinct product channels, with 37% of the radicals formed from a channel

  6. Survey of ethyl carbamate in fermented foods sold in the United Kingdom in 2004.

    PubMed

    Hasnip, Sarah; Crews, Colin; Potter, Nicholas; Christy, Julie; Chan, Danny; Bondu, Thomas; Matthews, Wendy; Walters, Barry; Patel, Krishna

    2007-04-01

    Results are presented of a survey of fermented foods and beverages sold in the United Kingdom for levels of ethyl carbamate (urethane) carried out to expand the range of food types sold in the United Kingdom for which data regarding ethyl carbamate are available. Samples were analyzed by in-house validated methods, which included measurement uncertainty estimates. The samples comprised 75 fermented liquids (beers, wines, fortified wines, spirits, liqueurs, soy sauces, and vinegars) and 25 fermented solid foods (cheeses, yogurts, soybean products, sauerkraut, yeast extract, olives, and Christmas pudding). Ethyl carbamate was not detected in the beers or the cider. Wines contained between 11 and 24 microg/kg and sake between 81 and 164 microg/kg. Fortified wines contained ethyl carbamate at levels between 14 and 60 microg/kg. Only two of five liqueurs contained ethyl carbamate. Most soy sauces and vinegars did not contain ethyl carbamate. No ethyl carbamate was detected in cheeses, yogurts, olives, or soybean-based products. Single samples of sauerkraut, yeast extract, and Christmas pudding contained low levels (29, 41, and 20 microg/kg ethyl carbamate, respectively). PMID:17328558

  7. Fungal degradation of an acetolactate synthase (ALS) inhibitor pyrazosulfuron-ethyl in soil.

    PubMed

    Sondhia, Shobha; Waseem, Uzma; Varma, R K

    2013-11-01

    Owing to reported phytotoxicity of some sulfonylurea class of herbicides in number of sensitive crops and higher persistence in soil, present study was conducted to isolate and identify pyrazosulfuron-ethyl degrading fungi from soil of rice field. Penicillium chrysogenum and Aspergillus niger, were isolated and identified from rhizospere soil of rice field, as potent pyrazosulfuron-ethyl degrading fungi. Degradation of pyrazosulfuron-ethyl by P. chrysogenum and A. niger, yielded transformation products/metabolites which were identified and characterized by LC/MS/MS. The rate of dissipation of pyrazosulfuron-ethyl was found higher in soil of rice field and soil inoculated with P. chrysogenum. This showed important route of degradation of pyrazosulfuron-ethyl by microbes apart from chemical degradation. PMID:23993642

  8. Production of ethyl acetate from dilute ethanol solutions by Candida utilis

    SciTech Connect

    Armstrong, D.W.; Martin, S.M.; Yamazaki, H.

    1984-01-01

    The conversion of ethanol to ethyl acetate has an advantage as a method of ethanol recovery since ethyl acetate is amenable to simple solvent extraction. The potential of Candida utilis in this conversion was studied. The kinetics of accumulation of ethanol and ethyl acetate in glucose-grown C. utilis showed that ester formation resulted from ethanol utilization under appropriate aeration and was inhibited by Fe/sup 3 +/ supplementation. Candida utilis converted ethanol to ethyl acetate optimally at pH 5.0-7.0. The five-hour rate of ester production increased as the ethanol concentration increased to 10 g/L, and rapidly declined to zero at concentrations exceeding 35 g/L. Thus, C. utilis has potential to recover dilute ethanol in the form of ethyl acetate.

  9. The effects of pH on the enzymatic formation of ?-glucuronides of various retinoids by induced and noninduced microsomal UDPGA-glucuronosyltransferases of several rat tissues in vitro 1 1 Abbreviations used: acitretin, 9-(2?,3?,6? trimethyl, 4?methoxybenzyl1?) 3,7 dimethyl, nona-2,4,6,8 tetraenoic acid; acitretin-G, acitretin-glucuronide; BHT, butylated hydroxytoluene; CD367, tetramethyl, tetrahydro-anthracenyl-benzoic acid; CD367-G, CD367 glucuronide; HPLC, high-performance liquid chromatography; 3MC, 3-methylcholanthrene; MES, 2-[N-morpholino]ethanesulfonic acid; NEM, N-ethylmaleimide; 4-oxo-RA, 4-oxoretinoic acid; 4-oxo-RAG, 4-oxoretinoyl ?-glucuronide; RA, retinoic acid; RAG, retinoyl ?-glucuronide; RAR, retinoic acid receptor; ROL, retinol; RXR, retinoid X receptor; Tris, tris [hydroxymethyl] aminomethane; TTNPB, tetramethyl, tetrahydronaphthenyl-propenyl-benzoic acid; TTNPB-G, TTNPB glucuronide; UDPGA, UDP-glucuronic acid; UGT, UDPGA-glucuronosyl transferase

    Microsoft Academic Search

    Giuseppe Genchi; Arun B Barua; Wei Wang; Wayne R Bidlack; James A Olson

    1998-01-01

    All-trans retinoyl-?-glucuronide, a prominent water-soluble metabolite of all-trans retinoic acid (RA) in animals, is formed by the enzymic transfer of the glucuronyl moiety of uridine diphosphoglucuronic acid to RA. Uridine diphosphoglucuronic acid glucuronosyl transferases (UGTs) of microsomal preparations catalyze this reaction. In noninduced rat liver microsomes, maximal activity was observed in the physiologic range (pH 6.9–7.5) for all-trans-RA, 9-cis-RA, all-trans-4-oxo-RA,

  10. 40 CFR 180.217 - Ammoniates for [ethylenebis-(dithiocarbamato)] zinc and ethyl-enebis [dithiocarbamic acid...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...for [ethylenebis-(dithiocarbamato)] zinc and ethyl-enebis [dithiocarbamic acid...for [ethylenebis-(dithiocarbamato)] zinc and ethyl-enebis [dithiocarbamic acid...of [ethylenebis (dithiocarbamato)] zinc with 1 part by weight ethylenebis...

  11. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol. 721.10111 Section...Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed diesters with...

  12. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol. 721.10110 Section...Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed diesters with...

  13. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol. 721.10110 Section...Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed diesters with...

  14. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol. 721.10110 Section...Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed diesters with...

  15. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol. 721.10111 Section...Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed diesters with...

  16. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol. 721.10111 Section...Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed diesters with...

  17. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol. 721.10110 Section...Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed diesters with...

  18. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol. 721.10111 Section...Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed diesters with...

  19. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol. 721.10110 Section...Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed diesters with...

  20. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol. 721.10111 Section...Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed diesters with...

  1. General and cerebral haemodynamic activity of ethyl apovincaminate.

    PubMed

    Kárpáti, E; Szporny, L

    1976-01-01

    Systemic and cerebral haemodynamic effects of ethyl apovincaminate (RGH-4405, Cavinton), a new compound, have been investigated in anaesthetized dogs. The compound was administered i.v. and produced an increase in cerebral blood flow accompanied by a decrease in cerebral vascular resistance which persisted for 15 min. The effective dose was 0.2-0.5 mg/kg. Mean arterial blood pressure, total peripheral resistance and cardiac work were decreased, heart rate and cardiac output were increased. Cerebral metabolic rate of oxygen was enhanced. It is assumed that the compound has a direct effect on cerebral metabolism. RGH-4405 has a weak antiarrhythmic and coronary dilating activity. Its effect on smooth muscle is more marked than that of papaverine. RGH-4405 appears to be a potent cerebral vasodilator enhancing cerebral metabolism. PMID:1037212

  2. Reactions of ethyl diazoacetate catalyzed by methylrhenium trioxide

    SciTech Connect

    Zhu, Z.; Espenson, H. [Iowa State Univ., Ames, IA (United States)

    1995-11-03

    Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) has found wise use in catalysis, including the epoxidation and metathesis of olefins, aldehyde olefination, and oxygen transfer. Extensive reports have now appeared in the area of MTO-catalyzed substrate oxidations with hydrogen peroxide. Certain catalytic applications of MTO for organic reactions that do not utilize peroxide have now been realized. In particular, a catalytic amount of MTO with ethyl diazoacetate (EDA) will convert aromatic imines to aziridines and convert aldehydes and ketones to epoxides. The aziridine preparation proceeds in high yields under anaerobic conditions more conveniently than with existing methods. Compounds with a three-membered heterocyclic ring can be obtained with the EDA/MTO catalytic system. Aromatic imines undergo cycloaddition reactions to give aziridines under mild conditions.

  3. Photochemistry of ethyl chloride caged in amorphous solid water.

    PubMed

    Ayoub, Yousif; Asscher, Micha

    2008-11-21

    Caging and photo-induced decomposition of ethyl chloride molecules (EC) within a layer of amorphous solid water (ASW) on top of clean and oxygen-covered Ru(001) under ultra-high vacuum (UHV) conditions are presented. The caged molecules were estimated to reside 1.5 +/- 0.2 nm above the solid surface, based on parent molecule thermal decomposition on the clean ruthenium. Dissociative electron attachment (DEA) of the caged molecules following 193 nm laser irradiation, result in initial fragmentation to ethyl radical and chloride anion. It was found that photoreactivity on top of the clean ruthenium surface (Ru) is twenty times faster than on the oxygen-covered surface (O/Ru), with DEA cross sections: sigma(Ru) = (3.8 +/- 1) x 10(-19) cm(2) and sigma(O/Ru) = (2.1 +/- 0.3) x 10(-20) cm(2). This difference is attributed to the higher work function of oxygen-covered ruthenium, leading to smaller electron attachment probability due to mismatch of the ruthenium photo-electron energy with the adsorbed EC excited electron affinity levels. EC molecules fragmented within the cage, result in post-irradiation TPD spectra that reveal primarily C(4)H(8), C(3)H(5) and C(3)H(3), without any oxygen-containing molecules. Unique stabilization of the photoproducts has been observed with the first layer of water molecules in direct contact with the substrate, desorbing near 180 K, a significantly higher temperature than the desorption of fully caged molecules. This study may contribute for understanding stratospheric photochemistry and processes in interstellar space. PMID:18979033

  4. Clinical (Non-forensic) Application Of Ethylglucuronide Measurement: Are We Ready?

    PubMed Central

    Jatlow, Peter; O'Malley, Stephanie S.

    2013-01-01

    Ethyl glucuronide (Etg) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary drug abuse screening, has largely been restricted to forensic and law enforcement situations. Despite a real need for an objective and possibly quantitative marker of ethanol exposure for use in conjunction with outpatient clinical trials and treatment programs, measurement of these metabolites has seen only limited clinical application. The barriers to more extensive clinical use of EtG/EtS testing, particularly misleading assay results that can occur as a consequence of inadvertent exposure to non-beverage ethanol containing substances, are reviewed and put into perspective. Additional information needed to develop guidelines for optimal clinical utilization of EtG/EtS measurements is discussed. PMID:20374218

  5. Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene.

    PubMed

    James, Margaret O; Stuchal, Leah D; Nyagode, Beatrice A

    2008-01-31

    The organochlorine pesticide, methoxychlor (MXC), is metabolized in animals to phenolic mono- and bis-demethylated metabolites (OH-MXC and HPTE, respectively) that interact with estrogen receptors and may be endocrine disruptors. The phase II detoxication of these compounds will influence the duration of action of the estrogenic metabolites, but has not been investigated extensively. In this study, the glucuronidation and sulfonation of OH-MXC and HPTE were investigated in subcellular fractions of liver and intestine from untreated, MXC-treated and 3-methylcholanthrene (3-MC)-treated channel catfish, Ictalurus punctatus. MXC-treated fish were given i.p. injections of 2mg MXC/kg daily for 6 days and sacrificed 24h after the last dose. The 3-MC treatment was a single 10mg/kg i.p. dose 5 days prior to sacrifice. In hepatic microsomes from control fish, the V(max) value (mean+/-S.D., n=4) for glucuronidation of OH-MXC was 270+/-50pmol/min/mg protein, higher than found for HPTE (110+/-20pmol/min/mg protein). For each substrate, the V(max) values observed in intestinal microsomes were approximately twice those found in the liver. The K(m) values for OH-MXC and HPTE glucuronidation in control liver were not significantly different and were 0.32+/-0.04mM for OH-MXC and 0.26+/-0.06mM for HPTE. The K(m) for the co-substrate, UDPGA, was higher in liver (0.28+/-0.09mM) than intestine (0.04+/-0.02mM). Treatment with 3-MC but not MXC increased the V(max) for glucuronidation in liver and intestine. Glucuronidation was a more efficient pathway than sulfonation for both substrates, in both tissues. The V(max) values for sulfonation of OH-MXC and HPTE, respectively, in liver cytosol were 7+/-3 and 17+/-4pmol/min/mg protein and in intestinal cytosol were 13+/-3 and 30+/-5pmol/min/mg protein. Treatment with 3-MC but not MXC increased rates of sulfonation of OH-MXC and HPTE and the model substrate, 3-hydroxy-benzo(a)pyrene in both intestine and liver. Comparison of the kinetics of the conjugation pathways with those published for the demethylation of MXC showed that formation of the endocrine-active metabolites was more efficient than either conjugation pathway. Residues of OH-MXC and HPTE were detected in extracts of liver microsomes from MXC-treated fish. This work showed that although OH-MXC and HPTE could be eliminated by glucuronidation and sulfonation, the phase II pathways were less efficient than the phase I pathway leading to formation of these endocrine-active metabolites. PMID:18078677

  6. 40 CFR 180.221 - O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 false O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances...Tolerances § 180.221 O -Ethyl S -phenyl ethylphos-phonodithioate; tolerances...its oxygen analog (O -ethyl S -phenyl ethylphosphonothioate, in or on the...

  7. 40 CFR 180.221 - O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 false O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances...Tolerances § 180.221 O -Ethyl S -phenyl ethylphos-phonodithioate; tolerances...its oxygen analog (O -ethyl S -phenyl ethylphosphonothioate, in or on the...

  8. 40 CFR 180.221 - O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 false O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances...Tolerances § 180.221 O -Ethyl S -phenyl ethylphos-phonodithioate; tolerances...its oxygen analog (O -ethyl S -phenyl ethylphosphonothioate, in or on the...

  9. Development of LC-MS/MS methodology for the detection/determination and confirmation of chloramphenicol, chloramphenicol 3-O-?-d-glucuronide, florfenicol, florfenicol amine and thiamphenicol residues in bovine, equine and porcine liver.

    PubMed

    Fedeniuk, Rick W; Mizuno, Massey; Neiser, Connie; O'Byrne, Collin

    2015-06-01

    A method for the detection and confirmation of organic solvent extractable residues of the neutral, acidic, and basic analytes of the amphenicol class veterinary drugs and selected metabolites was developed and validated. Using a modified QuEChERS extraction with SPE cleanup and LC-MS/MS analysis, limits of detection and confirmation for the different analytes in bovine, equine, and porcine liver ranged from 0.1ng/g for chloramphenicol to 1ng/g for florfenicol amine. Tissue homogenization with an ammonium formate/EDTA solution and subsequent analyte partitioning against 7:3 acetonitrile:isopropanol solution and mixed-mode strong-cation exchange solid-phase extraction cartridge cleanup allowed for the extraction of all compounds from tissues with mean recoveries ranging from 50% (chloramphenicol 3-O-?-d-glucuronide) to 90% (thiamphenicol). Matrix effects ranged from greater than 85% suppression for florfenicol amine to 70% matrix enhancement for chloramphenicol 3-O-?-d-glucuronide. Quantitation and confirmation were accomplished using commercially available penta-deuterated chloramphenicol as internal standard and multiple reaction monitoring (MRM) of two or three transitions per target analyte. Method accuracy was greater than 15% for all compounds except the glucuronide metabolite. Intra-lab method repeatability estimates ranged from 73% RSD for chloramphenicol 3-O-?-d-glucuronide to 14% RSD for chloramphenicol. Only chloramphenicol 3-O-?-d-glucuronide and florfenicol amine at the low end of their calibration ranges (0.25 and 1ng/g, respectively) did not meet AOAC recommended HorRatr guidelines for intra-lab repeatabilities. Preliminary tests show that the method's extraction protocol can be used to recover analytes of the ?-agonists, corticosteroids, fluoroquinolones, sulfonamides, and tetracycline drug classes from the same matrices. Requirements for use in national chemical monitoring programs as a detection/confirmatory (florfenicol amine and chloramphenicol 3-O-?-d-glucuronide) and determinative/confirmatory (chloramphenicol, florfenicol, thiamphenicol) analytical methodology are met. PMID:25913426

  10. In vitro glucuronidation of the primary metabolite of 10-chloromethyl-11-demethyl-12-oxo-calanolide A by human liver microsomes and its interactions with UDP-glucuronosyltransferase substrates.

    PubMed

    Liu, Xin; Sheng, Li; Zhao, Manman; Mi, Jiaqi; Liu, Zhihao; Li, Yan

    2015-02-01

    F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide), an analog of (+)-Calanolide A, is a novel small-molecule nonnucleoside reverse transcriptase inhibitor for the therapy of human immunode?ciency virus (HIV) infection. M3, the most abundant primary metabolite of F18 in human liver microsomes (HLMs) and rat liver microsomes (RLMs), is mainly excreted in bile as a glucuronide conjugate in rats after oral administration. The aim of this study was to identify the UDP glucuronosyltransferase (UGT) isoforms involved in the glucuronidation of M3 by HLMs and recombinant human UGTs and investigate the metabolic interactions of M3 with the substrates of UGTs in HLMs. As a result, UGT1A1 was the major isozyme responsible for the glucuronidation of M3, followed by UGT1A4, UGT1A9 and UGT2B7. M3 exhibited significant inhibition against UGT1A9 and UGT2B7 in both HLMs and recombinant human UGTs. In addition, M3 inhibited UGT1A9 catalyzed mycophenolic acid (MPA) glucuronidation with Ki of 0.39 ?M, and M3 also inhibited the glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by a "mixed-type" mechanism with Ki of 16.8 ?M. The results suggest that UGT1A1 provides the major contribution to M3 glucuronidation in vitro and M3 has the potential to interact with xenobiotics and endogenous chemicals that are UGT1A9 and UGT 2B7 substrates. PMID:25760535

  11. The human UDP-glucuronosyltransferase UGT2A1 and UGT2A2 enzymes are highly active in bile acid glucuronidation

    PubMed Central

    Perreault, Martin; Gauthier-Landry, Louis; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Finel, Moshe; Barbier, Olivier

    2013-01-01

    Bile acids (BA) are essential modulators of lipid, glucose and cholesterol homeostasis, but exert cytotoxic effects in the cholestatic liver. Glucuronidation, catalyzed by the UDP-glucuronosyltransferase (UGT) enzymes is a pharmacologically-relevant BA detoxification process. The present study aimed at characterizing the BA-conjugating activity of the little-studied human UGTs of subfamily 2A, UGT2A1, 2A2 and 2A3. Recombinant UGT2As, expressed in baculovirus-infected insect cells, were assayed for the glucuronidation of 6 major bile acids, chenodeoxycholic (CDCA), cholic (CA), lithocholic (LCA), deoxycholic (DCA), hyocholic (HCA) and hyodeoxycholic (HDCA) acids. UGT2A3 exhibited detectable, but very low, activity with all the tested BAs substrates. UGT2A1 was highly efficient in forming LCA-3 and -24G, CDCA-24, DCA-24, HCA-24 and HDCA-24G, while UGT2A2 was the most active enzyme for CA-24G and CDCA-24G formation, and was also able to generate HDCA-6G, HDCA-24G, LCA-24G and HCA-24G. The Km values of UGT2A1 varied between 102.2 ± 14.3 ?M and 2.4 ± 1.2 mM. With the exception of CA-24G, a low affinity substrate for UGT2A2, all the Km values for UGT2A2 were in the 100 to 400 ?M range. In conclusion, the present study demonstrates the high reactivity of the human UGT2A1 and UGT2A2 for bile acid glucuronidation. The physiological importance of these reactions to BA disposition remains, however, to be clarified in vivo. PMID:23756265

  12. Stir bar sorptive extraction with in situ de-conjugation and thermal desorption gas chromatography-mass spectrometry for measurement of 4-nonylphenol glucuronide in human urine sample

    Microsoft Academic Search

    Migaku Kawaguchi; Rie Ito; Yoshio Hayatsu; Hisao Nakata; Norihiro Sakui; Noriya Okanouchi; Koichi Saito; Hiroshi Yokota; Shun-ichiro Izumi; Tsunehisa Makino; Hiroyuki Nakazawa

    2006-01-01

    4-Nonylphenol glucuronide (NP-G) in human urine samples was analyzed using stir bar sorptive extraction (SBSE) with in situ de-conjugation by ?-glucuronidase and thermal desorption (TD)-gas chromatography-mass spectrometry (GC-MS). Distilled water (1ml), 1.0M ammonium acetate solution (100?l) and ?-glucuronidase (10,000unitsml?1, 10?l) were added to human urine sample (1ml), and extraction was commenced for 90min at 37°C while stirring at 250rpm with

  13. Manual and automated (robotic) high-performance liquid chromatography methods for the determination of mycophenolic acid and its glucuronide conjugate in human plasma

    Microsoft Academic Search

    Tsina Irene; Chu Frances; Kyle Hama; Martin Kaloostian; Ling Tam Yuen; Thomas Tarnowski; Wong Belinda

    1996-01-01

    A manual and an automated (Zymark PyTechnology robot) HPLC method for simultaneous determination of plasma mycophenolic acid (MPA) and its glucuronide conjugate (MPAG) are described here. Both methods are reproducible and accurate, and both are equivalent in all respects, including quantification limits (MPA, 0.100 ?g\\/ml; MPAG, 4.00 ?g\\/ml), range (using 0.05–0.5 ml of plasma: MPA, 0.0500–20.0 ?g\\/aliquot; MPAG, 2.00–200 ?g\\/aliquot),

  14. Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity toward Endogenous Substances in Humanized UGT1 Mouse Brain.

    PubMed

    Kutsuno, Yuki; Hirashima, Rika; Sakamoto, Masaya; Ushikubo, Hiroko; Michimae, Hirofumi; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2015-07-01

    Although UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, they are also involved in the metabolism of endogenous compounds. Certain substrates of UGTs, such as serotonin and estradiol, play important roles in the brain. However, the expression of UGTs in the human brain has not been fully clarified. Recently, humanized UGT1 mice (hUGT1 mice) in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus have been developed. In the present study, the expression pattern of UGT1As in brains from humans and hUGT1 mice was examined. We found that UGT1A1, 1A3, 1A6, and 1A10 were expressed in human brains. The expression pattern of UGT1As in hUGT1 mouse brains was similar to that in human brains. In addition, we examined the expression of UGT1A1 and 1A6 in the cerebellum, olfactory bulbs, midbrain, hippocampus, and cerebral cortex of hUGT1 mice. UGT1A1 in all brain regions and UGT1A6 in the cerebellum and cerebral cortex of 6-month-old hUGT1 mice were expressed at a significantly higher rate than those of 2-week-old hUGT1 mice. A difference in expression levels between brain regions was also observed. Brain microsomes exhibited glucuronidation activities toward estradiol and serotonin, with mean values of 0.13 and 5.17 pmol/min/mg, respectively. In conclusion, UGT1A1 and UGT1A6 might play an important role in function regulation of endogenous compounds in a region- and age-dependent manner. Humanized UGT1 mice might be useful to study the importance of brain UGTs in vivo. PMID:25953521

  15. Synthesis and characterization of biodegradable and thermosensitive polymeric micelles with covalently bound doxorubicin-glucuronide prodrug via click chemistry.

    PubMed

    Talelli, M; Morita, K; Rijcken, C J F; Aben, R W M; Lammers, T; Scheeren, H W; van Nostrum, C F; Storm, G; Hennink, W E

    2011-12-21

    Doxorubicin is an anthracycline anticancer agent that is commonly used in the treatment of a variety of cancers, but its application is associated with severe side effects. Biodegradable and thermosensitive polymeric micelles based on poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b-p(HPMAmLac(n))) have been studied as drug delivery systems for therapeutic and imaging agents and have shown promising in vitro and in vivo results. The purpose of this study was to investigate the covalent coupling of a doxorubicin-glucuronide prodrug (DOX-propGA3) to the core of mPEG-b-p(HPMAmLac(2)) micelles. This prodrug is specifically activated by human ?-glucuronidase, an enzyme that is overexpressed in necrotic tumor areas. To this end, an azide modified block copolymer (mPEG(5000)-b-p(HPMAmLac(2)-r-AzEMA)) was synthesized and characterized, and DOX-propGA3 was coupled to the polymer via click chemistry with a high (95%) coupling efficiency. Micelles formed by this DOX containing polymer were small (50 nm) and monodisperse and released 40% of the drug payload after 5 days incubation at 37 °C in the presence of ?-glucuronidase, but less than 5% in the absence of the enzyme. In vitro cytotoxicity experiments demonstrated that DOX micelles incubated with 14C cells showed the same cytotoxicity as free DOX only in the presence of ?-glucuronidase, indicating full conversion of the polymer-bound DOX into the parent drug. Overall, this novel system is very promising for enzymatically responsive anticancer therapy. PMID:22017211

  16. Morphine-6beta-glucuronide-induced hyperphagia: characterization of opioid action by selective antagonists and antisense mapping in rats.

    PubMed

    Leventhal, L; Silva, R M; Rossi, G C; Pasternak, G W; Bodnar, R J

    1998-11-01

    Opiate drugs such as morphine stimulate food intake in rats. The morphine metabolite, morphine-6beta-glucuronide (M6G), is more active than morphine in analgesic assays, and appears to act through distinct receptors. Thus, although morphine analgesia is decreased by antisense oligodeoxynucleotides (AS ODNs) targeting exons 1 and 4 of the MOR-1 clone, M6G analgesia is reduced by probes targeting exons 2 and 3 of the MOR-1 clone. Our study examined whether central administration of M6G increased food intake in rats, and characterized this response using either selective mu, kappa1, delta1 and delta2 antagonists, or antisense directed against the various cloned opioid receptors. Central M6G (10-1000 ng) significantly and dose-dependently increased intake after 4 hr. Whereas mu antagonism with betaFNA significantly and dose-dependently reduced M6G-induced hyperphagia, equimolar doses of delta1, delta2, and kappa1 antagonists were ineffective. AS ODNs directed against either exons 2 or 3 of the MOR-1 clone blocked M6G-induced hyperphagia, whereas either AS ODNs directed against exons 1 or 4, or a MS ODN directed against exon 2 were ineffective. In contrast, an AS ODN probe directed against exon 1, but not exon 2, of the MOR-1 clone reduced morphine-induced hyperphagia, an effect identical to DAMGO-induced hyperphagia. Whereas M6G-induced hyperphagia was insensitive to antisense probes directed against the DOR-1, KOR-1 and KOR-3/ORL1 clones, these probes respectively reduced hyperphagia induced by deltorphin II, U50488H and nociceptin. Although pharmacological data indicate that M6G-induced hyperphagia acts through mu receptors, antisense data imply that the hyperphagic actions of M6G are mediated by a receptor distinct from traditional mu agonists, either as an alternative splice variant of the MOR-1 clone or a distinct gene. PMID:9808678

  17. Ethyl benzene should be considered ototoxic at occupationally relevant exposure concentrations.

    PubMed

    Vyskocil, A; Leroux, T; Truchon, G; Lemay, F; Gendron, M; Gagnon, F; El Majidi, N; Viau, C

    2008-05-01

    Organic solvents can produce ototoxic effects in both man and experimental animals. The objective of this study was to review the literature on the effects of low-level exposure to ethyl benzene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible exposure limits. In Quebec, the Time-Weighed Average Exposure Value for 8A h (TWAEV) is 100A ppm (434A mg/m(3)) and the Short-Term Exposure Value for 15A min (STEV) is 125A ppm (543A mg/m(3)). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. In workers, there is no evidence of either ethyl benzene-induced hearing losses or ototoxic interaction after combined exposure to ethyl benzene and noise. In rats, ethyl benzene affects the auditory function mainly in the cochlear mid-frequency range and ototoxic interaction was observed after combined exposure to noise and ethyl benzene. Further studies with sufficient data on the ethyl benzene exposure of workers are necessary to make a definitive conclusion. Given the current evidence from animal studies, we recommend considering ethyl benzene as an ototoxic agent. PMID:19022877

  18. Mechanism of quizalofop-ethyl selectivity in monocotyledonous and dicotyledonous species

    SciTech Connect

    Ruizzo, M.A.

    1986-01-01

    Cucumber (Cucumis sativus L.) susceptibility to quizalofop-ethyl herbicide was investigated under field and greenhouse conditions. Yield of cucumber cultivars was significantly reduced under field conditions with a single or repeat application of the ethyl ester of quizalofop at 0.14 or 0.28 kg ai/ha. Under greenhouse conditions, quialofop-ethyl significantly suppressed cucumber plant fresh weight with or without the presence of an adjuvant. Enhancement of herbicide activity was directly related to concentration of adjuvant. Microliter droplet application of quizalofop-ethyl at a 10/sup -3/ M concentration, inhibited the relative growth (RGR) and net assimilation rate (NAR) of the treated cucumber leaf 45% and 52%, respectively. Expression of herbicidal injury was localized on the treated leaf with no visible symptoms observed on adjacent leaves. Radiolabeled /sup 14/C-quizalofop-ethyl was applied to leaves of cucumber and corn (Zea mays L.) to compare translocation patterns between two susceptible plant species and relate this information to the observed selectivity of the herbicide. Cucumber autoradiographs showed minimal translocation of /sup 14/C-quizalofop-ethyl 192 hours after treatment. In contrast, corn autoradiographs showed both apoplastic and symplastic transport of quizalofop-ethyl 3 and 24 hours after treatment. Quantification of /sup 14/C in cucumber revealed 96% of absorbed /sup 14/C was confined to the treated leaf after 192h of exposure.

  19. X-ray structural characterization of the bis-guanine derivative of a cisplatin analogue having just one proton on each coordinated nitrogen and a head-to-head conformation: [Pt{(+/-)-N,N'-dimethyl-2,3-diaminobutane}(9-ethyl-guanine)2]dinitrate.

    PubMed

    Intini, Francesco P; Cini, Renzo; Tamasi, Gabriella; Hursthouse, Michael B; Marzilli, Luigi G; Natile, Giovanni

    2010-09-01

    The X-ray structural and NMR characterization of a bis-guanine derivative of a cisplatin analogue designed to reduce the rate of the Pt-N7 rotation of the coordinated guanine nucleobases by more than 1-million-fold is reported. The [Pt{(+/-)-Me(2)dab}(9-EtG)(2)](NO(3))(2) (Me(2)dab = N,N'-dimethyl-2,3-diaminobutane, 9-EtG = 9-ethyl-guanine) complex crystallizes in the P2(1)/n space group, and the crystal contains a racemic mixture of complex molecules. The data were collected at 120 +/- 2 K, and the crystal and molecular structure (comprising one disordered nitrate) were resolved and refined to conventional agreement factors of R1 = 0.0270 and wR2 = 0.0565. The guanine ligands assume the less common head-to-head (HH) orientation, disclosing full details of the intramolecular relationships between cis guanines and between guanine and cis amine. Moreover, an understanding has been gained of the steric factors determining induction of asymmetry (from carbons to adjacent nitrogen atoms) and puckering of the chelate ring (delta or lambda for R,S,S,R or S,R,R,S configurations at the N,C,C,N chelate-ring atoms, respectively) within the Me(2)dab ligand. The chemical shift separation between H8 signals of the two HT atropisomers and between the two H8 signals of the single HH atropisomer can be explained in terms of canting of the nucleobases relative to the coordination plane and in terms of the different relationships between the H8 proton of one guanine and the shielding zone of the cis guanine. Furthermore, for each configuration of the Me(2)dab ligand (R,S,S,R or S,R,R,S), the NMR data indicate that the handedness of canting is similar for the two guanines in all three (two HT and one HH) conformers (R canting for R,S,S,R and L canting for S,R,R,S configuration). PMID:20799737

  20. Reactions of Ethyl Groups on a Model Chromia Surface: Ethyl Chloride on Stoichiometric Alpha-Cr2O3(1012)

    SciTech Connect

    Brooks, J.; Ma, Q; Cox, D

    2009-01-01

    The reaction of CH3CH2Cl over the nearly-stoichiometric ?-Cr2O3 (1 0 View the MathML source 2) surface yields gas phase CH2double bond; length as m-dashCH2, CH3CH3, H2 and surface chlorine adatoms. The decomposition reaction is initiated via C-Cl bond cleavage to give a surface ethyl (CH3CH2-) intermediate. A rate-limiting ?-hydride elimination from the surface ethyl species produces gas phase CH2double bond; length as m-dashCH2 and surface hydrogen atoms. Two parallel competing reactions form CH3CH3, via ?-hydride addition to remaining surface ethyl species (reductive elimination), and H2, via the combination of two surface hydrogen atoms. The chlorine freed from the dissociation of CH3CH2Cl binds at the five-coordinate surface Cr3+ sites on the stoichiometric surface and inhibits the surface chemistry via simple site blocking. No surface carbon deposition is observed from the thermal reaction of ethyl chloride, suggesting that ethyl intermediates are not primary coke forming intermediates in the dehydrogenation of ethane over (1 0 View the MathML source 2) facets of ?-Cr2O3.

  1. The synthesis and purification of aromatic hydrocarbons V : 1-ethyl-3-methylbenzene

    NASA Technical Reports Server (NTRS)

    Ebersole, Earl R

    1946-01-01

    The method used for the synthesis and purification of an 8-gallon quantity of 1-ethyl-3-methylbenzene from m-creosol consists in obtaining m-methylcyclohexanone from m-creosol by hydrogenation followed by oxidation, condensation of the ketone with ethylmagnesium bromide, dehydration of the tertiary alcohol obtained, and the dehydration of the olefins to 1-ethyl-3-methylbenzene. A yield of 28 percent of the theoretical was obtained from 98 percent commercial m-creosol. The physical properties of the 1-ethyl-3-methylbenzene are compared with selected values from the literature.

  2. Subchronic inhalation neurotoxicity studies of ethyl acetate in rats.

    PubMed

    Christoph, Greg R; Hansen, John F; Leung, Hon-Wing

    2003-12-01

    Rats were exposed to 0, 350, 750 or 1500 ppm of ethyl acetate by inhalation for 6 h per day, 5 days per week for 13 weeks. Functional observational battery (FOB) and motor activity tests occurred on non-exposure days during weeks 4, 8 and 13, after which tissues were microscopically examined for neuropathology. A subset of rats was monitored during a 4-week recovery period. Exposure to 750 and 1500 ppm, diminished behavioral responses to unexpected auditory stimuli during the exposure session and appeared to be an acute sedative effect. There were no signs of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750 and 1500 ppm had reduced body weight, body weight gain, feed consumption, and feed efficiency, which fully or partially recovered within 4 weeks. Reductions in body weight gain and feed efficiency were observed in male rats exposed to 350 ppm. The principal behavioral effect of subchronic exposure was reduced motor activity in the 1500 ppm females, an effect that was not present after the 4-week recovery period. All other FOB and motor activity parameters were unaffected, and no pathology was observed in nervous system tissues. Operant sessions were conducted in another set of male rats preconditioned to a stable operant baseline under a multiple fixed ratio-fixed interval (FR-FI) schedule of food reinforcement. FR response rate, FR post-reinforcement pause duration, and the pattern of FI responding were not affected during or after the exposure series. In contrast, within-group FI rate for the treatment groups increased over time whereas those of the controls decreased. A historical control group, however, also showed a similar pattern of increase, indicating that these changes did not clearly represent a treatment-related effect. Results from these studies indicate a LOEL of 350 ppm for systemic toxicity based on the decreased body weight gain in male rats, and a LOEL of 1500 ppm for neurotoxicity based on the transient reduction in motor activity in female rats. In conclusion, there was no evidence that subchronic exposure up to 1500 ppm ethyl acetate produced any enduring neurotoxic effects in rats. PMID:14637381

  3. Replication across Regioisomeric Ethylated Thymidine Lesions by Purified DNA Polymerases

    PubMed Central

    Andersen, Nisana; Wang, Pengcheng; Wang, Yinsheng

    2013-01-01

    Causal links exist between smoking cigarettes and cancer development. Some genotoxic agents in cigarette smoke are capable of alkylating nucleobases in DNA and higher levels of ethylated DNA lesions were observed in smokers than non-smokers. In this study, we examined comprehensively how the regioisomeric O2-, N3- and O4-ethylthymidine (O2-, N3- and O4-EtdT) perturb DNA replication mediated by purified human DNA polymerases (hPol) ?, ?, and ?, yeast DNA polymerase ? (yPol ?), and the exonuclease-free Klenow fragment (Kf?) of Escherichia coli DNA polymerase I. Our results showed that hPol ? and Kf? could bypass all three lesions and generate full-length replication products, whereas hPol ? stalled after inserting a single nucleotide opposite the lesions. Bypass carried out by hPol ? and yPol ? differed markedly amongst the three lesions: Consistent with its known capability in bypassing efficiently the minor-groove N2-substituted 2?-deoxyguanosine lesions, hPol ? was able to bypass O2-EtdT, though it experienced great difficulty in bypassing N3-EtdT and O4-EtdT; yPol ? was only modestly blocked by O4-EtdT, but the polymerase was highly hindered by O2-EtdT and N3-EtdT. LC-MS/MS analysis of the replication products revealed that DNA synthesis opposite O4-EtdT was highly error-prone, with dGMP being preferentially inserted, while the presence of O2-EtdT and N3-EtdT in template DNA directed substantial frequencies of misincorporation of dGMP and, for hPol ? and Kf?, dTMP. Thus, our results suggested that O2-EtdT and N3-EtdT may also contribute to the AT?TA and AT?GC mutations observed in cells and tissues of animals exposed to ethylating agents. PMID:24134187

  4. Impact of trans-resveratrol-sulfates and -glucuronides on endothelial nitric oxide synthase activity, nitric oxide release and intracellular reactive oxygen species.

    PubMed

    Ladurner, Angela; Schachner, Daniel; Schueller, Katharina; Pignitter, Marc; Heiss, Elke H; Somoza, Veronika; Dirsch, Verena M

    2014-01-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings. PMID:25329867

  5. Synthesis and application of resorufin ?-D-glucuronide, a low-cost chromogenic substrate for detecting Escherichia coli in drinking water.

    PubMed

    Magro, Germinal; Bain, Robert E S; Woodall, Claire A; Matthews, Robert L; Gundry, Stephen W; Davis, Anthony P

    2014-08-19

    The development of low-cost tests for Escherichia coli is hampered by the expense and limited choice of enzyme substrates. Most chromogenic substrates are required in costly amounts, while fluorogenic substrates require an additional apparatus (e.g., an ultraviolet lamp) to be detected. Herein, we propose an alternative chromogenic substrate, resorufin ?-d-glucuronide (REG), which is exceptionally sensitive and may be employed in very small amounts. We show that REG can be produced similarly to other simple glucuronides and should therefore be no more expensive. The compound is used by both healthy and injured E. coli, resulting in a pronounced color change from orange to a bright pink. Because the released dye (resorufin) has a high extinction coefficient, substantially lower amounts are needed than for commercially available substrates. The potential of this substrate is demonstrated by a presence/absence test requiring just 0.1 mg of REG/100 mL of water sample, one hundredth of the quantity needed for common chromogenic substrates, with an estimated bulk cost of ?0.1 U.S. cents/test. REG shows promise as a chromogenic substrate for E. coli detection and should be considered in the development of new water tests, especially for low-income settings. PMID:25035967

  6. Impact of Trans-Resveratrol-Sulfates and -Glucuronides on Endothelial Nitric Oxide Synthase Activity, Nitric Oxide Release and Intracellular Reactive Oxygen Species

    PubMed Central

    Ladurner, Angela; Schachner, Daniel; Schueller, Katharina; Pignitter, Marc; Heiss, Elke H.; Somoza, Veronika; Dirsch, Verena M.

    2015-01-01

    Resveratrol (3,5,4?-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings. PMID:25329867

  7. Tris(ethyl-enedi-amine)-cobalt(II) dichloride.

    PubMed

    Cooke, Kristin; Olenev, Andrei V; Kovnir, Kirill

    2013-06-01

    The title compound, [Co(II)(C2H8N2)3]Cl2, was obtained unexpectedly as the product of an attempted solvothermal synthesis of cobalt selenide from the elements in the presence of NH4Cl in ethyl-enedi-amine solvent. The three chelate rings of the distorted octa-hedral [Co(C2H8N2)3](2+) complex cation adopt twisted conformations about their C-C bonds. The spread of cis-N-Co-N bond angles [80.17?(6)-98.10?(6)°] in the title compound is considerably greater than the equivalent data for [Co(III)(C2H8N2)3]Cl3 [Takamizawa et al. (2008 ?). Angew. Chem. Int. Ed. 47, 1689-1692]. In the crystal, the components are linked by numerous N-H?Cl hydrogen bonds, generating a three-dimensional network in which the cationic complexes are stacked in columns along [010] and separated by columns of chloride anions. PMID:23794994

  8. Determination of acetone and methyl ethyl ketone in water

    USGS Publications Warehouse

    Tai, D.Y.

    1978-01-01

    Analytical procedures for the determination of acetone and methyl ethyl ketone in water samples were developed. Concentrations in the milligram-per-liter range were determined by injecting an aqueous sample into the analysis system through an injection port, trapping the organics on Tenax-GC at room temperature, and thermally desorbing the organics into a gas chromatograph with a flame ionization detector for analysis. Concentrations in the microgram-per-liter range were determined by sweeping the headspace vapors over a water sample at 50C, trapping on Tenax-GC, and thermally desorbing the organics into the gas chromatograph. The precision for two operators of the milligram-per-liter concentration procedure, expressed as the coefficient of variation, was generally less than 2 percent for concentrations ranging from 16 to 160 milligrams per liter. The precision from two operators of the microgram-per-liter concentration procedure was between 2 and 4 percent for concentrations of 20 and 60 micrograms per liter. (Woodard-USGS)

  9. Electronic properties of N(5)-ethyl flavinium ion.

    PubMed

    Sichula, Vincent; Kucheryavy, Pavel; Khatmullin, Renat; Hu, Ying; Mirzakulova, Ekaterina; Vyas, Shubham; Manzer, Samuel F; Hadad, Christopher M; Glusac, Ksenija D

    2010-11-25

    We investigated the electronic properties of N(5)-ethyl flavinium perchlorate (Et-Fl(+)) and compared them to those of its parent compound, 3-methyllumiflavin (Fl). Absorption and fluorescence spectra of Fl and Et-Fl(+) exhibit similar spectral features, but the absorption energy of Et-Fl(+) is substantially lower than that of Fl. We calculated the absorption signatures of Fl and Et-Fl(+) using time-dependent density functional theory (TD-DFT) methods and found that the main absorption bands of Fl and Et-Fl(+) are (?,?*) transitions for the S(1) and S(3) excited states. Furthermore, calculations predict that the S(2) state has (n,?*) character. Using cyclic voltammetry and a simplistic consideration of the orbital energies, we compared the HOMO/LUMO energies of Fl and Et-Fl(+). We found that both HOMO and LUMO orbitals of Et-Fl(+) are stabilized relative to those in Fl, although the stabilization of the LUMO level was more pronounced. Visible and mid-IR pump-probe experiments demonstrate that Et-Fl(+) exhibits a shorter excited-state lifetime (590 ps) relative to that of Fl (several nanoseconds), possibly due to faster thermal deactivation in Et-Fl(+), as dictated by the energy gap law. Furthermore, we observed a fast (23-30 ps) S(2) ? S(0) internal conversion in transient absorption spectra of both Fl and Et-Fl(+) in experiments that utilized pump excitations with higher energy. PMID:21043534

  10. The pharmacological actions of pempidine and its ethyl homologue

    PubMed Central

    Spinks, A.; Young, E. H. P.; Farrington, J. A.; Dunlop, D.

    1958-01-01

    Pempidine, and other highly active ganglion blocking agents of the polyalkylpiperidine series, were developed from tertiary alkylamines, themselves weakly active, on the hypothesis that high activity was conferred by the presence in the molecule of a sterically hindered secondary or tertiary nitrogen atom. Pempidine and its N-ethyl homologue (26539) resembled mecamylamine qualitatively. All three drugs blocked sympathetic and parasympathetic ganglia; this action was slow in onset and protracted. They blocked neuromuscular transmission, but only about one hundredth as powerfully as ganglionic transmission. They caused a fall in amplitude and rate of the isolated heart, and reduced coronary flow. They had local anaesthetic properties in one of four tests used. They caused tremor. All were well absorbed when administered orally. Pempidine was about twice as active as mecamylamine on ganglia, but only about one half to one quarter as toxic as judged by death, growth, induction of tremor, or cardiotoxicity. Compound 26539 was also quantitatively superior to mecamylamine in respect of these safety margins, but unlike pempidine or mecamylamine damaged the pituitary gland and testis when administered daily for several months. The mode of action of the three drugs is discussed: the results give tentative support for the hypothesis that their action is intracellular. PMID:13618559

  11. Theoretical Study of the Vibrational Spectroscopy of the Ethyl Radical

    NASA Astrophysics Data System (ADS)

    Tabor, Daniel P.; Sibert, Edwin. L. Sibert, Iii

    2013-06-01

    The rich spectroscopy of the ethyl radical has attracted the attention of several experimental and theoretical investigations. The purpose of these studies was to elucidate the signatures of hyperconjugation, torsion, inversion, and Fermi coupling in the molecular spectra. Due to the number of degrees of freedom in the system, previous theoretical studies have implemented reduced-dimensional models. Our ultimate goal is a full-dimensional theoretical treatment of the vibrations using both Van Vleck and variational approaches. The methods will be combined with the potential that we have calculated using the CCSD(T) method on the cc-pVTZ basis set. In this talk we will discuss our initial work, which builds up from these reduced-dimensional models. Our calculations use coordinates that exploit the system's G_{12} PI symmetry in a simple fashion. By systematically adding more degrees of freedom to our model, we can determine the effects of specific couplings on the spectroscopy. T. Häber, A. C. Blair, D. J. Nesbitt and M. D. Schuder J. Chem. Phys. {124}, 054316, (2006). G .E. Douberly, unpublished. R. S. Bhatta, A. Gao and D. S. Perry J. Mol. Struct.: THEOCHEM {941}, 22, (2010).

  12. Orientational dynamics of the ionic organic liquid 1-ethyl-3-methylimidazolium nitrate

    E-print Network

    Fayer, Michael D.

    Orientational dynamics of the ionic organic liquid 1-ethyl-3-methylimidazolium nitrate Hu Cang, Jie-methylimidazolium nitrate (EMIM NO3 ) over time scales from 1 ps to 2 ns, and the temperatures range from 410 to 295

  13. 40 CFR 180.212 - S-Ethyl cyclohexylethylthio-carbamate; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...cyclohexylethylthio-carbamate; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide S -ethyl cyclohexylethylthiocarbamate in or on the following food commodities: Commodity Parts per million...

  14. 40 CFR 180.212 - S-Ethyl cyclohexylethylthio-carbamate; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...cyclohexylethylthio-carbamate; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide S -ethyl cyclohexylethylthiocarbamate in or on the following food commodities: Commodity Parts per million...

  15. [Synthesis and properties of the N-ethyl derivatives of carminomycin and rubomycin].

    PubMed

    Olsuf'eva, E N; Povarov, L S; Potapova, N P

    1982-01-01

    N-Monoethyl derivatives of carminomycin, rubomycin, 13-dihydrocarminomycin and 13-dihydrorubomycin were synthesized by condensation of their amino groups with acetic aldehyde in the presence of sodium boron hydride. The respective N,N-diethyl derivatives of the antibiotics were formed as by-products of the reaction. New compounds such as N-ethylcarminomycin, N,N-diethylcarminomycin, N-ethyl-13-dihydrocarminomycin, N,N-diethyl-13-dihydrocarminomycin, N-ethylrubomycin and N-ethyl-13-dihydrorubomycin were synthesized. Antibacterial activity of N-ethyl- and N,N-diethyl derivatives of carminomycin and rubomycin determined with the use of Bac. mycoides as the test microbe was 40-50 per cent and that of N-ethyl- and N,N-diethyl-13-dihydro-derivatives was 15-30 per cent of the activity of the respective antibiotics, carminomycin and rubomycin. PMID:6814352

  16. The Wolfe Institute The Ethyle R.Wolfe Institute for the Humanities,

    E-print Network

    Rosen, Jay

    The Wolfe Institute The Ethyle R.Wolfe Institute for the Humanities, in cooperation.951.5847 wolfeinstitute@brooklyn.cuny.edu Twitter: twitter.com/Wolfe_Institute Every year police officers detain hundreds

  17. 5-Isopropylidene-3-ethyl rhodanine induce growth inhibition followed by apoptosis in leukemia cells.

    PubMed

    Ravi, Subban; Chiruvella, Kishore K; Rajesh, K; Prabhu, V; Raghavan, Sathees C

    2010-07-01

    5-Isopropylidene-3-ethyl rhodanine II was prepared by conventional and Microwave assisted synthesis. For the first time, we found that rhodanine II treatment led to cytotoxicity in leukemic cell line, CEM by inducing apoptosis. PMID:20236736

  18. Rapeseed ethyl ester as bio-lube in 2-cycle engine

    SciTech Connect

    NONE

    1996-12-31

    The performance of four blends of gasoline with rapeseed ethyl ester (REE) and three commercial 2-cycle oils has been evaluated in engine tests by the University of Idaho. Details and results of the tests are given in the article.

  19. Phase behaviour and physico-chemical properties of the binary systems {1-ethyl-3-methylimidazolium thiocyanate, or 1-ethyl-3-methylimidazolium tosylate + water, or + an alcohol}

    Microsoft Academic Search

    Urszula Doma?ska; Marta Królikowska; Marek Królikowski

    2010-01-01

    Phase diagrams for the binary systems {1-ethyl-3-methylimidazolium thiocyanate, [EMIM][SCN], or 1-ethyl-3-methylimidazolium tosylate [EMIM][TOS]+water, or +an alcohol (C7–C10)} have been determined at atmospheric pressure using a dynamic method. Water shows complete miscibility with [EMIM][SCN] in the liquid phase in the temperature range (298.15–438.15) K. (Liquid+liquid) phase equilibria and (solid+liquid) phase equilibria with complete miscibility in the liquid phase region were observed

  20. Hepatic studies of intraperitoneally administered tris(2-ethyl hexyl)trimellitate (TOTM) and di(2-ethyl hexyl)phthalate in rats.

    PubMed

    Rathinam, K; Srivastava, S P; Seth, P K

    1990-02-01

    Adult male rats receiving tris(2-ethyl hexyl)trimellitate (TOTM) intraperitoneally for seven days exhibited no significant changes in the activities of hepatic aminopyrine-N-demethylase, aryl hydrocarbon hydroxylase or glutathione-S-transferase, or in the glutathione contents. However, except for the glutathione level, the di(2-ethyl hexyl)phthalate (DEHP)-treated group showed significant increases in the activities of these enzymes. Changes in the body weight and the absolute and relative liver weights were also observed among the DHEP-treated group. PMID:2335710

  1. Highly unsaturated fatty acids. III. Isolation of methyl eicosapentaenoate, ethyl docosapentaenoate, and ethyl docosahexaenoate from cod liver oil esters by chromatography

    Microsoft Academic Search

    Ahmed M. Abu-Nasr; Ralph T. Holman

    1954-01-01

    Summary  a) Displacement chromatography using a charcoal-isopropanol-methyl behenate system has been successfully applied to the isolation\\u000a of docosahexaenoic acid and ethyl docosahexaenoate from cod liver oil concentrates.\\u000a \\u000a b) Methyl eicosapentaenoate was isolated from cod liver oil methyl esters by combined elution chromatography on silicic acid\\u000a and displacement chromatography.\\u000a \\u000a \\u000a \\u000a c) Using silicic acid as adsorbent and petroleum ether-chloroform as solvent, ethyl docosapentaenoate

  2. Spray Application Parameters That Influence the Growth Inhibiting Effects of Trinexapac-Ethyl

    Microsoft Academic Search

    Matthew James Fagerness; Donald Penner

    1998-01-01

    identifies a broad range of effective spray carrier vol- umes (187-1683 L ha2 1 ), achievement of rainfastness Trinexapac-ethyl (4-(cyclopropyl-a-hydroxy-methylene)-3,5-diox- within 1 h after application, and no need for an adjuvant ocyclohexanecarboxylic acid ethyl ester) is a foliar absorbed, cyclohex- to enhance efficacy. There is little evidence available to anedione turfgrass growth regulator that can inhibit shoot growth in numerous

  3. Aspects of Thermal Graft Copolymerization of Methyl Methacrylate onto Ethyl Cellulose in Homogeneous Media

    Microsoft Academic Search

    E. A. Abdel-Razik

    1997-01-01

    Homogeneous graft copolymerization of methyl methacrylate (MMA) onto ethyl cellulose (EC) using radical initiators such as ammonium persulfate (APS), potassium persulfate (KPS), and benzoyl peroxide (BPO) was carried out in benzene\\/DMSO (1\\/1 v\\/v) mixed-solvent system. The grafting yield (GY%) was determined as functions of the polymerization temperature and of the concentrations of a monomer, ethyl cellulose, and an initiator. Several

  4. Solubility of carbon dioxide in 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate

    Microsoft Academic Search

    Allan N. Soriano; Bonifacio T. Doma; Meng-Hui Li

    2008-01-01

    Experimental results for the solubility of carbon dioxide in the ionic liquid 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate are not reported in the literature. To this end, we present in this work new solubility data for carbon dioxide in 1-ethyl-3-methylimidazolium 2-(2-methoxyethoxy) ethylsulfate for temperatures ranging from (303.2 to 343.2)K and pressures up to 6.7MPa using a thermogravimetric microbalance. The carbon dioxide solubility was

  5. The room temperature ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate: Electrochemical couples and physical properties

    Microsoft Academic Search

    Joan Fuller; R. T. Carlin; R. A. Osteryoung

    1997-01-01

    Room temperature molten salts composed of the 1-ethyl-3-methylimidazolium cation and a chloroaluminate anion have received much attention for use in a variety of commercial applications such as batteries, photovoltaics, metal deposition, and capacitors. The room temperature ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBFâ) was demonstrated as a versatile electrolyte by examining three representative electrochemical couples: ferrocene and tetrathiafulvalene oxidations and lithium ion

  6. Electrochemical study of copper in a basic 1-ethyl-3-methylimidazolium tetrafluoroborate room temperature molten salt

    Microsoft Academic Search

    Po-Yu Chen; I-Wen Sun

    1999-01-01

    The electrochemistry and electrodeposition of copper was investigated on polycrystalline tungsten, platinum and on glassy carbon electrodes in 1-ethyl-3-methylimidazolium tetrafluoroborate room temperature molten salt containing excess 1-ethyl-3-methylimidazolium chloride. Experiments performed in a N2-filled dry box show that Cu(I) can be oxidized to Cu(II) or reduced to Cu metal. The Cu(I)\\/Cu(II) redox couple exhibits a quasi-reversible charge-transfer behavior. The electrodeposition of

  7. Pervaporation separation of ethyl acetate–ethanol binary mixtures using polydimethylsiloxane membranes

    Microsoft Academic Search

    A. Hasano?lu; Y. Salt; S. Kele?er; S. Özkan; S. Dinçer

    2005-01-01

    Pervaporation separation of azeotrope forming ethyl acetate–ethanol mixtures was investigated by using a selfmade polydimethylsiloxane (PDMS) membrane. Sorption, desorption and pervaporation experiments for ethyl acetate–ethanol mixture with different concentrations were conducted at 30, 40 and 50°C. The effect of process parameters such as feed concentration and temperature on flux and selectivity is discussed. Equilibrium curves are determined by vapor–liquid equilibrium

  8. Heat release and engine performance effects of soybean oil ethyl ester blending into diesel fuel

    Microsoft Academic Search

    Andre Valente Bueno; José Antonio Velásquez; Luiz Fernando Milanez

    2011-01-01

    The engine performance impact of soybean oil ethyl ester blending into diesel fuel was analyzed employing heat release analysis, in-cylinder exergy balances and dynamometric tests. Blends with concentrations of up to 30% of soybean oil ethyl ester in volume were used in steady-state experiments conducted in a high speed turbocharged direct injection engine. Modifications in fuel heat value, fuel–air equivalence

  9. Quizalofop-p-ethyl-induced phytotoxicity and genotoxicity in Lemna minor and Lemna gibba

    Microsoft Academic Search

    Zeynep B. Doganlar

    2012-01-01

    In this study, the effects of the herbicide, quizalofop-p-ethyl, on pigment contents (total chlorophyll, chlorophyll a\\/b, carotenoid), antioxidant enzyme [superoxide dismutase (SOD) and guaiacol peroxidase (POD)] activities, lipid peroxidation product (malondialdehyde: MDA) and DNA profiles were investigated in Lemna gibba and Lemna minor. Laboratory-acclimatized plants were treated with quizalofop-p-ethyl at 31.375, 62.75, 125 and 250 mg L for 24 and 96 h.

  10. REPEATED INTRAVENOUS DOSES OF ALL-TRANS-RETINOYL BETA-D-GLUCURONIDE IS NOT EFFECTIVE IN THE TREATMENT OF BACTERIAL BRONCHOPNEUMONIA IN LAMBS BUT IS DEVOID OF GROSS AND ACUTE TOXICITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All-trans-retinoyl beta-D-glucuronide is a water-soluble conjugate of all-trans-retinoic acid. It has low toxicity yet high reparative effects on epithelium in many in vitro and in vivo models. In this study we assessed the effect(s) of intravenously-administered all-trans-retinoyl beta-D-glucuron...

  11. Formation of ethyl acetate by Kluyveromyces marxianus on whey: studies of the ester stripping.

    PubMed

    Urit, Thanet; Löser, Christian; Wunderlich, Martin; Bley, Thomas

    2011-06-01

    Kluyveromyces marxianus is capable of converting lactose into ethyl acetate offering a chance for an economical reuse of whey. The microbial formation of ethyl acetate as a bulk product calls for an aerobic process and, thus, the highly volatile ethyl acetate is discharged from the aerated bioreactor. This stripping process was modeled and investigated experimentally. The stripping rate was proportional to the gas flow and nearly independent of the stirring rate since the stripping was governed by the absorption capacity of the exhaust gas rather than the phase transfer. Cooling the exhaust gas did not noticeably influence the stripping. One batch experiment is presented in detail to demonstrate the formation of ethyl acetate by K. maxianus DSM 5422 on whey. Further batch experiments showed that a substantial formation of ethyl acetate only occurred when the yeast growth was limited by a lack of trace elements. The highest product yield observed was 0.25 g ethyl acetate per g lactose which is nearly 50% of the theoretical maximum. PMID:21191616

  12. Effect of ethyl pyruvate on skeletal muscle metabolism in rats fed on a high fat diet.

    PubMed

    Olek, Robert A; Ziolkowski, Wieslaw; Wierzba, Tomasz H; Kaczor, Jan J

    2013-07-01

    Impaired mitochondrial capacity may be implicated in the pathology of chronic metabolic diseases. To elucidate the effect of ethyl pyruvate supplementation on skeletal muscles metabolism we examined changes in activities of mitochondrial and antioxidant enzymes, as well as sulfhydryl groups oxidation (an indirect marker of oxidative stress) during the development of obesity. After 6 weeks feeding of control or high fat diet, Wistar rats were divided into four groups: control diet, control diet and ethyl pyruvate, high fat diet, and high fat diet and ethyl pyruvate. Ethyl pyruvate was administered as 0.3% solution in drinking water, for the following 6 weeks. High fat diet feeding induced the increase of activities 3-hydroxyacylCoA dehydrogenase, citrate synthase, and fumarase. Moreover, higher catalase and superoxide dismutase activities, as well as sulfhydryl groups oxidation, were noted. Ethyl pyruvate supplementation did not affect the mitochondrial enzymes' activities, but induced superoxide dismutase activity and sulfhydryl groups oxidation. All of the changes were observed in soleus muscle, but not in extensor digitorum longus muscle. Additionally, positive correlations between fasting blood insulin concentration and activities of catalase (p = 0.04), and superoxide dismutase (p = 0.01) in soleus muscle were noticed. Prolonged ethyl pyruvate consumption elevated insulin concentration, which may cause modifications in oxidative type skeletal muscles. PMID:23857218

  13. Organic reactions catalyzed by methylrhenium trioxide: Reactions of ethyl diazoacetate and organic azides

    SciTech Connect

    Zhu, Z.; Espenson, J.H. [Ames Lab., IA (United States)] [Ames Lab., IA (United States); [Iowa State Univ., Ames, IA (United States)

    1996-10-16

    Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) catalyzes several classes of reactions of ethyl diazoacetate, EDA. It is the first high valent oxo complex for carbene transfer. Under mild conditions and in the absence of other substrates, EDA was converted to a 9:1 mixture of diethyl maleate and diethyl fumarate. In the presence of alcohols, {alpha}-alkoxy ethyl acetates were obtained in good yield. The yields dropped for the larger and more branched alcohols, the balance of material being diethyl maleate and fumarate. An electron-donating group in the para position of phenols favors the formation of {alpha}-phenoxy ethyl acetates. The use of EDA to form {alpha}-thio ethyl acetates and N-substituted glycine ethyl esters, on the other hand, is hardly affected by the size or structure of the parent thiol or amine, with all of these reactions proceeding in high yield. MTO-catalyzed cycloaddition reactions occur between EDA and aromatic imines, olefins, and carbonyl compounds. Three-membered ring products are formed: aziridines, cyclopropanes, and epoxides, respectively. The reactions favor the formation of trans products, and provide a convenient route for the preparation of aziridines. Intermediate carbenoid and nitrenoid species have been proposed. In the presence of an oxygen source such as an epoxide, ethyl diazoacetate and azibenzil are converted to an oxalic acid monoethyl ester and to benzil; at the same time the epoxide was converted to an olefin. 75 refs., 1 fig., 7 tabs.

  14. EtG/EtS in Urine from sexual assault victims determined by UPLC-MS-MS.

    PubMed

    Hegstad, Solfrid; Helland, Arne; Hagemann, Cecilie; Michelsen, Lisbeth; Spigset, Olav

    2013-05-01

    In cases of sexual assault, victims often present too late for the detection of ethanol in biological samples. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Sample preparation prior to UPLC-MS-MS analysis was a simple sample dilution. The calibration ranges were 0.2-20 mg/L, and between-assay relative standard deviations were in the range of 0.7-7.0% at concentrations of 0.3, 3.0 and 7.0 mg/L. Urine samples were analyzed from 59 female patients presenting to the Sexual Assault Centre at St. Olav University Hospital in Trondheim, Norway between November 2010 and October 2011. EtG and EtS results were fully concordant, and positive in 45 of the 48 cases with self-reported alcohol intake. In contrast, ethanol was detectable in only 20 of these cases, corresponding to sensitivities of 94 and 42%, respectively. Of the patients reporting no alcohol intake, none had positive EtG/EtS findings. These data show that analysis of EtG and EtS greatly increases the detection window of alcohol ingestion in cases of sexual assault, and may shed additional light on the involvement of ethanol in such cases. The victims' self-reported intake of alcohol seems to be reliable in this study, according to the EtG/EtS findings. PMID:23467259

  15. Considerations regarding a permitted daily exposure calculation for ethyl methanesulfonate.

    PubMed

    Müller, Lutz; Gocke, Elmar

    2009-11-12

    Specification of human exposure limits to compounds with toxicities based on modes of action that allow considerations of a threshold and the safe estimation of a no-observed-effect level (NOEL) is normally based on acceptable daily intake (ADI) or permitted daily exposure (PDE) calculations using appropriate safety factors to account for differences between species, populations, length of observation and severity of lesions. In view of the reliable experimental evidence for a thresholded dose response of the genotoxicity of ethyl methanesulfonate (EMS) as reported in this special issue of Toxicology Letters such an acceptable daily intake proposal is made using the approach for setting permitted daily exposure limits outlined in appendix 3 of the ICH Q3C consensus guideline on residual solvents in pharmaceuticals (ICH, 2005). Up to now the specification of EMS exposure limits was based on the generic threshold of toxicological concern (TTC)-derived limit of 1.5mug/person/day as advocated by the CHMP [CHMP, 2006. Guideline on the limits of genotoxic impurities. www.emea.europa.eu/pdfs/human/swp/519902en.pdf (June 28, 2006) with Q&A www.emea.europa.eu/pdfs/human/swp/43199407en.pdf (June 25, 2008)] or on as low as technically achievable criteria. Such limits have been based on conservative linear dose-effect extrapolations corresponding to an excess cancer risk of 1 in 100,000. We now present an EMS-specific PDE based on the reliable demonstration of a NOEL for induction of mutations in vivo of 25mg/kg/day. Using the most conservative safety factors described in ICH Q3C we derive a PDE of approximately 100 microg/person/day using product safety factors still amounting to 12,000. PMID:19857798

  16. Reverse-phase h.p.l.c. separation, quantification and preparation of bilirubin and its conjugates from native bile. Quantitative analysis of the intact tetrapyrroles based on h.p.l.c. of their ethyl anthranilate azo derivatives.

    PubMed Central

    Spivak, W; Carey, M C

    1985-01-01

    We describe a facile and sensitive reverse-phase h.p.l.c. method for analytical separation of biliary bile pigments and direct quantification of unconjugated bilirubin (UCB) and its monoglucuronide (BMG) and diglucuronide (BDG) conjugates in bile. The method can be 'scaled up' for preparative isolation of pure BDG and BMG from pigment-enriched biles. We employed an Altex ultrasphere ODS column in the preparative steps and a Waters mu-Bondapak C18 column in the separatory and analytical procedures. Bile pigments were eluted with ammonium acetate buffer, pH 4.5, and a 20 min linear gradient of 60-100% (v/v) methanol at a flow rate of 2.0 ml/min for the preparative separations and 1.0 ml/min for the analytical separations. Bile pigments were eluted in order of decreasing polarity (glucuronide greater than glucose greater than xylose conjugates greater than UCB) and were chemically identified by t.l.c. of their respective ethyl anthranilate azo derivatives. Quantification of UCB was carried out by using a standard curve relating a range of h.p.l.c. integrated peak areas to concentrations of pure crystalline UCB. A pure crystalline ethyl anthranilate azo derivative of UCB (AZO . UCB) was employed as a single h.p.l.c. reference standard for quantification of BMG and BDG. We demonstrate that: separation and quantification of biliary bile pigments are rapid (approximately 25 min); bile pigment concentrations ranging from 1-500 microM can be determined 'on line' by using 5 microliters of bile without sample pretreatment; bilirubin conjugates can be obtained preparatively in milligram quantities without degradation or contamination by other components of bile. H.p.l.c. analyses of a series of mammalian biles show that biliary UCB concentrations generally range from 1 to 17 microM. These values are considerably lower than those estimated previously by t.l.c. BMG is the predominant, if not exclusive, bilirubin conjugate in the biles of a number of rodents (guinea pig, hamster, mouse, prairie dog) that are experimental models of both pigment and cholesterol gallstone formation. Conjugated bilirubins in the biles of other animals (human, monkey, pony, cat, rat and dog) are chemically more diverse and include mono-, di- and mixed disconjugates of glucuronic acid, xylose and glucose in proportions that give distinct patterns for each species. PMID:3919713

  17. Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

    PubMed Central

    Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

    2012-01-01

    Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 ?g/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 ?g/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

  18. Ethyl Pyruvate Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Intrinsic Pathway of Apoptosis and Autophagy

    PubMed Central

    Shen, Miao; Lu, Jie; Dai, Weiqi; Wang, Fan; Xu, Ling; Chen, Kan; He, Lei; Cheng, Ping; Zhang, Yan; Wang, Chengfen; Wu, Dong; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zhou, Yinqun; Guo, Chuanyong

    2013-01-01

    Background. Hepatic ischemia-reperfusion (I/R) injury is a pivotal clinical problem occurring in many clinical conditions such as transplantation, trauma, and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable and simple lipophilic ester, has been shown to have anti-inflammatory properties. In this study, the purpose is to explore both the effect of ethyl pyruvate on hepatic I/R injury and regulation of intrinsic pathway of apoptosis and autophagy. Methods. Three doses of ethyl pyruvate (20?mg/kg, 40?mg/kg, and 80?mg/kg) were administered 1?h before a model of segmental (70%) hepatic warm ischemia was established in Balb/c mice. All serum and liver tissues were obtained at three different time points (4?h, 8?h, and 16?h). Results. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and pathological features were significantly ameliorated by ethyl pyruvate (80?mg/kg). The expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, was also obviously decreased by ethyl pyruvate (80?mg/kg). Furthermore, ethyl pyruvate inhibited the HMGB1/TLR4/ NF-?b axis and the release of cytokines (TNF-? and IL-6). Conclusion. Our results showed that ethyl pyruvate might attenuate to hepatic I/R injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated partly through downregulation of HMGB1/TLR4/ NF-?b axis and the competitive interaction with Beclin-1 of HMGB1. PMID:24453420

  19. Three-component phase behavior of the sclareol–ethyl lactate–carbon dioxide system for GAS applications

    Microsoft Academic Search

    Xenia C. Tombokan; Remil M. Aguda; David A. Danehower; Peter K. Kilpatrick; Ruben G. Carbonell

    2008-01-01

    This paper focuses on the extraction of sclareol from the leaves of Salvia sclarea Lamiaceae, more commonly known as Clary sage. The process involves the extraction of sclareol using a CO2-soluble GRAS solvent such as ethyl lactate, followed by GAS anti-solvent precipitation from ethyl lactate solution with carbon dioxide. The three-component phase behavior of the sclareol–ethyl lactate–CO2 system at various

  20. Enzymatic synthesis of fatty acid ethyl esters by utilizing camellia oil soapstocks and diethyl carbonate.

    PubMed

    Wang, Yingying; Cao, Xuejun

    2011-11-01

    This study was reported on a novel process for fatty acid ethyl esters preparation by transesterification and esterification from renewable low-cost feedstock camellia oil soapstocks and friendly acyl acceptor diethyl carbonate. The main components of product were 83.9% ethyl oleate, 8.9% ethyl palmitate, 4.7% ethyl linoleate and 2.1% ethyl stearate, which could be used as eco-friendly renewable resources or additives of industrial solvent and fossil fuel. The effects of molar ratio of diethyl carbonate to soapstocks oil, lipases, organic solvent, reaction temperature and time were investigated, and process conditions were optimized. The yield was up to 98.4% in solvent-free system with molar ratio of diethyl carbonate to soapstocks oil 3:1 and 5% Novozym 435 (based on the weight of soapstocks oil) at 50 °C and 180 rpm for 24 h. Moreover, there was no obvious loss in the yield after lipases were reused for 10 batches without treatment under optimized conditions. PMID:21958524

  1. Lignin is linked to ethyl-carbamate formation in ume (Prunus mume) liqueur.

    PubMed

    Hashiguchi, Tomokazu; Izu, Hanae; Sudo, Shigetoshi

    2012-01-01

    Ethyl carbamate concentrations in oak barrel-aged ume (Prunus mume) liqueurs were measured, and possible explanations for elevated levels were examined. The average concentration was 0.30 mg/L, significantly higher than in ume liqueurs not aged in oak (0.08 mg/L). Oak powder extracts were prepared from both untoasted and toasted oak powder by extraction with aqueous ethanol, and these were used to make ume liqueurs. Relative to a no-oak control, the ethyl carbamate concentrations were 3.8 and 11 times higher in the ume liqueur made with the untoasted and toasted oak powder extracts respectively. The extracts were loaded onto a C18 column, washed with water, and eluted with methanol. The (13)C-NMR spectra for the main constituents of the methanol elution fractions were consistent with those for lignin or fragments thereof. The methanol fractions were added to ume liqueur which was stored for 3 months. Relative to a control, the ethyl carbamate concentrations in the 3-month old liqueurs were found to be 1.2 and 4.6 higher for the untoasted oak-powder and the toasted oak-powder respectively. Ethyl carbamate was formed when lignin was added to a 40% aqueous ethanol solution that contained potassium cyanide. These observations suggest that lignin or fragments thereof promote the formation of ethyl carbamate. PMID:22232267

  2. The effect of ethyl apovincaminate on vasospasm of the circulatory isolated internal carotid artery in dogs.

    PubMed

    Mchedlishvili, G I; Ormotsadze, L G

    1981-01-01

    The vasodilator effect of ethyl apovincaminate (Cavinton) was studied upon the circulatory isolated internal carotid arteries (in dogs), which had been proved to be a typical locus of vasospasm in the cerebral arterial system. The effects of ethyl apovincaminate were studied under conditions of experimental spasm produced in the artery. The drug caused a dilator effect which was considerably greater and longer-lasting than that of theophylline. The dilatory effect of ethyl apovincaminate was the greater the higher was the initial tone of the arterial smooth muscles. Neither accumulation of the drug nor habituation of the vascular wall was observed when ethyl apovincaminate was administered repeatedly. The effects of the drug considerably decreased when Ca++ was eliminated from the arterial wall. It regularly decreased the vasoconstrictor effects of serotonin and increased K+ in the perfusion fluid and boosted the vasodilatory effect of theophylline upon the artery. On the other hand, increase of cyclic AMP in the vascular wall potentiated the effect of ethyl apovincaminate, while PGE2 decreased the latter. PMID:7194665

  3. Formation of ethyl acetate from whey by Kluyveromyces marxianus on a pilot scale.

    PubMed

    Löser, Christian; Urit, Thanet; Stukert, Anton; Bley, Thomas

    2013-01-10

    Whey arising in huge amounts during milk processing is a valuable renewable resource in the field of White Biotechnology. Kluyveromyces marxianus is able to convert whey-borne lactose into ethyl acetate, an environmentally friendly solvent. Formation of ethyl acetate as a bulk product is triggered by iron (Fe). K. marxianus DSM 5422 was cultivated aerobically in whey-borne medium originally containing 40 ?g/L Fe, supplemented with 1, 3 or 10 mg/L Fe in the pre-culture, using an 1 L or 70 L stirred reactor. The highest Fe content in the pre-culture promoted yeast growth in the main culture causing a high sugar consumption for growth and dissatisfactory formation of ethyl acetate, while the lowest Fe content limited yeast growth and promoted ester synthesis but slowed down the process. An intermediate Fe dose (ca. 0.5 ?g Fe/g sugar) lastly represented a compromise between some yeast growth, a quite high yield of ethyl acetate and an acceptable duration of the process. The mass of ethyl acetate related to the sugar consumed amounted to 0.113, 0.265 and 0.239 g/g in the three processes corresponding to 21.9%, 51.4% and 46.3% of the theoretically maximum yield. The performance on a pilot scale was somewhat higher than on lab scale. PMID:23089728

  4. Sorption and catalytic hydrolysis of diethatyl-ethyl on homoionic clays.

    PubMed

    Liu, W; Gan, J; Papiernik, S K; Yates, S R

    2000-05-01

    Sorption and catalytic hydrolysis of the herbicide diethatyl-ethyl [N-chloroacetyl-N-(2,6-diethylphenyl)glycine ethyl ester] on homoionic Na(+)-, K(+)-, Ca(2+)-, and Mg(2+)-montmorillonite clays were studied in aqueous media. The Freundlich sorption coefficient, K(f), measured from isotherms on clay followed the order of Na(+) approximately K(+) > Mg(2+) approximately Ca (2+). Analysis of FT-IR spectra of diethatyl-ethyl sorbed on clay suggests probable bonding at the carboxyl and amide carbonyl groups of the herbicide. The rate of herbicide hydrolysis in homoionic clay suspensions followed the same order as that for sorption, indicating that sorption may have preceded and thus caused hydrolysis. Preliminary product identification showed that hydrolysis occurred via nucleophilic substitution at the carboxyl carbon, causing cleavage of the ester bond and formation of diethatyl and its dechlorinated derivative, and at the amide carbon, yielding an ethyl ester derivative and its acid. These pathways also suggest that hydrolysis of diethatyl-ethyl was catalyzed by sorption on the clay surface. PMID:10820118

  5. Enzymatic production of biodiesel from microalgal oil using ethyl acetate as an acyl acceptor.

    PubMed

    Alavijeh, Razieh Shafiee; Tabandeh, Fatemeh; Tavakoli, Omid; Karkhane, Aliasghar; Shariati, Parvin

    2015-01-01

    Microalgae have become an important source of biomass for biodiesel production. In enzymatic transesterification reaction, the enzyme activity is decreased in presence of alcohols. The use of different acyl acceptors such as methyl/ethyl acetate is suggested as an alternative and effective way to overcome this problem. In this study, ethyl acetate was used for the first time in the enzymatic production of biodiesel by using microalga, Chlorella vulgaris, as a triglyceride source. Enzymatic conversion of such fatty acids to biodiesel was catalyzed by Novozym 435 as an efficient immobilized lipase which is extensively used in biodiesel production. The best conversion yield of 66.71% was obtained at the ethyl acetate to oil molar ratio of 13:1 and Novozym 435 concentration of 40%, based on the amount of oil, and a time period of 72 h at 40?. The results showed that ethyl acetate have no adverse effect on lipase activity and the biodiesel amount was not decreased even after seven transesterification cycles, so ethyl acetate has a great potential to be substituted for short-chain alcohols in transesterification reaction. PMID:25742923

  6. Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats

    PubMed Central

    Arokiyaraj, S; Balamurugan, R; Augustian, P

    2011-01-01

    Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats. PMID:23569798

  7. Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-?-Glucuronide.

    PubMed

    Varma, Manthena V S; Lin, Jian; Bi, Yi-An; Kimoto, Emi; Rodrigues, A David

    2015-07-01

    Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-O-?-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-O-?-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs. PMID:25941268

  8. Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

    PubMed

    Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

    2013-11-01

    The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 ?l of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. PMID:23973631

  9. Semi-preparative isolation of dihydroresveratrol-3-O-?-d-glucuronide and four resveratrol conjugates from human urine after oral intake of a resveratrol-containing dietary supplement.

    PubMed

    Radko, Yulia; Christensen, Kathrine B; Christensen, Lars P

    2013-07-01

    A method for semi-preparative isolation of major resveratrol metabolites from human urine after oral intake of a trans-resveratrol-containing dietary supplement was developed. Pretreatment of the urine (6L) by using solid-phase extraction gave a brown oily residue (9.3g), which was separated using a combination of normal phase column chromatography and reversed-phase flash column chromatography resulting in fractions containing 1.1g crude trans-resveratrol-3-O-sulfate (M1), 86mg of a crude mixture of trans-resveratrol-3,5-O-disulfate (M2) and trans-resveratrol-3,4'-O-disulfate (M3), and 568mg of a crude mixture of trans-resveratrol-3-O-?-d-glucuronide (M4) and dihydroresveratrol-3-O-?-d-glucuronide (M5). Purification of the crude metabolites was performed by semi-preparative reversed-phase HPLC using a gradient of aqueous ammonium acetate (2.5mmol/L, pH 6.7)/acetonitrile for purification of M1, M2 and M3 or trifluoroacetic acid in water (pH 2.5)/acetonitrile for purification of M4 and M5. From a part of the crude metabolites (50-75mg), 47mg M1 (purity 98.7%), 14mg M2 (purity 96.1%), 10mg M3 (purity 96.3%), 38mg M4 (purity 98.2%) and 18mg M5 (purity 97.8%) were obtained. The structures of all isolated resveratrol metabolites were elucidated by spectroscopic and spectrometric methods such as 1D and 2D NMR, UV, and LC-MS. This method represents a novel approach to obtain resveratrol metabolites being the first method describing the direct isolation of pure resveratrol metabolites from urine samples in quantities sufficient for full chemical characterization and testing in vitro and in preclinical trials. PMID:23727867

  10. Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS)

    Microsoft Academic Search

    F. Pragst; V. Auwaerter; F. Sporkert; K. Spiegel

    2001-01-01

    Fatty acid ethyl esters (FAEE) are products of the nonoxidative ethanol metabolism, which are known to be detectable in blood only about 24h after the last alcohol intake. After deposition in hair they should be suitable long-term markers of chronically elevated alcohol consumption. Therefore, a method for the analysis of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate from

  11. Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10.

    PubMed

    Ramírez, Jacqueline; Mirkov, Snezana; House, Larry K; Ratain, Mark J

    2015-07-01

    OTS167 is a potent maternal embryonic leucine zipper kinase inhibitor undergoing clinical testing as antineoplastic agent. We aimed to identify the UDP-glucuronosyltransferases (UGTs) involved in OTS167 metabolism, study the relationship between UGT genetic polymorphisms and hepatic OTS167 glucuronidation, and investigate the inhibitory potential of OTS167 on UGTs. Formation of a single OTS167-glucuronide (OTS167-G) was observed in pooled human liver (HLM) (Km = 3.4 ± 0.2 µM), intestinal microsomes (HIM) (Km = 1.7 ± 0.1 µM), and UGTs. UGT1A1 (64 µl/min/mg) and UGT1A8 (72 µl/min/mg) exhibited the highest intrinsic clearances (CLint) for OTS167, followed by UGT1A3 (51 µl/min/mg) and UGT1A10 (47 µl/min/mg); UGT1A9 was a minor contributor. OTS167 glucuronidation in HLM was highly correlated with thyroxine glucuronidation (r = 0.91, P < 0.0001), SN-38 glucuronidation (r = 0.79, P < 0.0001), and UGT1A1 mRNA (r = 0.72, P < 0.0001). Nilotinib (UGT1A1 inhibitor) and emodin (UGT1A8 and UGT1A10 inhibitor) exhibited the highest inhibitory effects on OTS167-G formation in HLM (68%) and HIM (47%). We hypothesize that OTS167-G is an N-glucuronide according to mass spectrometry. A significant association was found between rs6706232 and reduced OTS167-G formation (P = 0.03). No or weak UGT inhibition (range: 0-21%) was observed using clinically relevant OTS167 concentrations (0.4-2 µM). We conclude that UGT1A1 and UGT1A3 are the main UGTs responsible for hepatic formation of OTS167-G. Intestinal UGT1A1, UGT1A8, and UGT1A10 may contribute to first-pass OTS167 metabolism after oral administration. PMID:25870101

  12. Experimental Autoignition of C4-C6 Saturated and Unsaturated Methyl and Ethyl Esters

    E-print Network

    Bennadji, Hayet; Coniglio-Jaubert, Lucie; Billaud, Francis; Glaude, Pierre-Alexandre; Battin-Leclerc, Frédérique

    2009-01-01

    Autoignition delay times, ?, of methyl crotonate, methyl acrylate, ethyl butanoate, ethyl crotonate, and ethyl acrylate were studied in shock tube experiments. A series of mixtures diluted with argon, of varying fuel/oxygen equivalence ratios (?=0.25, 0.4, 1.0, and 2.0), were measured behind reflected shock waves over the temperature range of 1280-1930 K, pressure range of 7-9.65 atm, during which the logarithm of ? varies linearly as a function of the inverse temperature for all equivalence ratios. The ignition delay time decreases as temperature rises. The dependence of ? on temperature, and reactant concentrations is given in an empirical correlation. The results provide a database for the validation of small saturated and unsaturated esters kinetic mechanisms at elevated temperatures and pressure combustion.

  13. Ethyl carbamate levels in wine and spirits from markets in Hebei Province, China.

    PubMed

    Liu, Y P; Dong, B; Qin, Z S; Yang, N J; Lu, Y; Yang, L X; Chang, F Q; Wu, Y N

    2011-01-01

    Ethyl carbamate (EC) in wine, grain spirits and wine sauce (145 samples) was analysed using solid-phase extraction and stable isotope dilution GC/MS. Samples were obtained from markets in eight areas (Shijiazhuang, Baoding, Handan, Qinhuangdao, Langfang, Zhangjiakou, Xingtai and Cangzhou) of Hebei Province, China. The method had a limit of detection of 2 µg kg?¹, with recoveries varying from 95.7 to 102% and RSD ranging 2.3-5.6%. The average concentrations of ethyl carbamate in wines, grain spirits and wine sauce were 14.7 (<2.0-44.5) µg kg?¹, 33.8 (2.9-129) µg kg?¹ and 8.7 (<2.0-63.3) µg kg?¹, respectively. The results led to the development of limit standards that can be used to predict the concentration of ethyl carbamate in Chinese fermented wines. PMID:24779655

  14. Synthesis of inorganic-organic hybrids from metal alkoxides and ethyl cellulose

    SciTech Connect

    Yoshinaga, Ikuko; Yamada, Noriko; Katayama, Shingo [Nippon Steel Corp., Kawasaki (Japan). Advanced Technology Research Labs.

    1996-12-31

    Inorganic-organic hybrids were synthesized by the reaction of inorganic species of Ti(OC{sub 2}H{sub 5}){sub 4}, Nb(OC{sub 2}H{sub 5}){sub 5}, Ta(OC{sub 2}H{sub 5}){sub 5} and Fe(OC{sub 2}H{sub 5}){sub 3} with an organic polymer of ethyl cellulose. The studies of FT-IR spectroscopy revealed that m-O-cellulose bonds were formed by the reaction of ethoxy groups of metal ethoxides with hydroxy groups of ethyl cellulose. The dielectric constants of the resulting Ti-O-, Nb-O- and Ta-O-cellulose hybrids were higher than that of ethyl cellulose. The molar magnetic susceptibility of the Fe-O-cellulose hybrid was independent of iron content and was lower than that of Fe(OC{sub 2}H{sub 5}){sub 3}.

  15. A one-pot glycerol-based additive-blended ethyl biodiesel production: a green process.

    PubMed

    Zanin, Fabio G; Macedo, Alexandra; Archilha, Marcos Vinicios L R; Wendler, Edison P; Dos Santos, Alcindo A

    2013-09-01

    N-methyl-2-pyrrolidonium methyl sulfonate, a Brønsted acid ionic liquid, promoted the transesterification of soybean oil with ethanol giving a high quality fatty acid ethyl ester. At the end of the reaction, after distillation of excess of ethanol, spontaneous phase separation took place. While the clear upper phase corresponded to the ethyl ester, the lower phase was composed of a mixture of glycerol byproduct and the catalyst. By addition of a stoichiometric amount of appropriated reagents to the resulting mixture, a new ionic liquid-catalyzed process allows the conversion of the glycerol into less polar derivatives, and consequent migration to the ethyl esters phase. This work demonstrated that emulsion, phase separation and contamination problems were completely avoided and the glycerol could be incorporated into the biodiesel as additives in a single step. The whole process involves two renewable starting materials, ethanol and vegetable oil, allowing a total green additive-blended biodiesel production process. PMID:23792662

  16. Reaction Rate Coefficients of OH Radicals and Cl Atoms with Ethyl Propanoate, n-Propyl Propanoate, Methyl 2-Methylpropanoate, and Ethyl n-Butanoate

    NASA Astrophysics Data System (ADS)

    Cometto, Pablo M.; Daële, Véronique; Idir, Mahmoud; Lane, Silvia I.; Mellouki, Abdelwahid

    2009-09-01

    Kinetics of the reactions of OH radicals and Cl atoms with four saturated esters have been investigated. Rate coefficients for the gas-phase reactions of OH radicals with ethyl propanoate (k1), n-propyl propanoate (k2), methyl 2-methylpropanoate (k3), and ethyl n-butanoate (k4) were measured using a conventional relative rate method and the pulsed laser photolysis-laser induced fluorescence technique. At (296 ± 2) K, the rate coefficients obtained by the two methods were in good agreement. Significant curvatures in the Arrhenius plots have been observed in the temperature range 243-372 K for k1, k3, and k4. The rate coefficients for the reactions of the four esters with Cl atoms were determined using the relative rate method at (296 ± 2) K and atmospheric pressure. The values obtained are presented, compared with the literature values when they exist, and discussed. Reactivity trends and atmospheric implications for these esters are also presented.

  17. Molecular Model of trans-3-(9-Anthryl)-2-Propenoic Acid Ethyl Ester

    NSDL National Science Digital Library

    The Featured Molecules this month come from the paper by Nguyen and Weisman on solvent-free Wittig reactions and the stereochemical consequences of crowding in the transition state. The molecules include those pictured in the paper as well as the cis-isomer of 3-(9-anthryl)-2-propenoic acid ethyl ester. All structures were optimized at the B3LPY/6-31G* level. In the case of ethyl cinnamate, the cis-isomer is slightly more stable thermodynamically than the trans isomer, lending further support for the argument that the observed product distribution arises from the energetics of the transition state.

  18. Diastereoselective Synthesis of a Strawberry Flavoring Agent by Epoxidation of Ethyl trans-b-Methylcinnamate

    NASA Astrophysics Data System (ADS)

    Pageau, Gayle J.; Mabaera, Rodwell; Kosuda, Kathryn M.; Sebelius, Tamara A.; Ghaffari, Ali H.; Kearns, Kenneth A.; McIntyre, Jean P.; Beachy, Tina M.; Thamattoor, Dasan M.

    2002-01-01

    The diastereoselective synthesis of ethyl (E)-3-methyl-3-phenylglycidate, a strawberry flavoring agent, is carried out by epoxidizing ethyl trans-b-methylcinnamate with m-chloroperbenzoic acid. This epoxidation is appropriate for the introductory organic laboratory and augments the small number of such experiments currently available for undergraduate education. In the course of performing this exercise, students are exposed to many important facets of organic chemistry such as synthesis, reaction mechanism, stereochemistry, chromatography, quantitative analysis, spectroscopy, and computational chemistry. The 1H NMR spectrum of this compound is especially interesting and presents instructive examples of diastereotopic protons and shielding effects of the aromatic ring current.

  19. Crystal structure of ?-ethyl-l-glutamate N-carb­oxy anhydride

    PubMed Central

    Kanazawa, Hitoshi; Inada, Aya

    2015-01-01

    In the title compound (alternative name N-carboxy-l-glutamic anhydride ?-ethyl ester), C8H11NO5, the oxazolidine ring is essentially planar, with a maximum deviation of 0.019?(2)?Å. In the crystal, mol­ecules are linked by N—H?O hydrogen bonds between the imino group and the carbonyl O atom in the ethyl ester group, forming a tape structure along the c-axis direction. The oxazolidine rings of adjacent tapes are arranged into a layer parallel to the ac plane. This arrangement is favourable for the polymerization of the title compound in the solid state. PMID:25705466

  20. Photostability of Isovaline and its Precursor 5-Ethyl-5- methylhydantoin Exposed to Simulated Space Radiations

    PubMed Central

    Sarker, Palash K.; Takahashi, Jun-ichi; Kawamoto, Yukinori; Obayashi, Yumiko; Kaneko, Takeo; Kobayashi, Kensei

    2012-01-01

    Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and ?-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5-methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under ?-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected. PMID:22312300

  1. Synthesis and characterization of original 2-(dimethylamino)ethyl methacrylate\\/poly(ethyleneglycol) star-copolymers

    Microsoft Academic Search

    Yong-Ho Shim; François Bougard; Olivier Coulembier; Roberto Lazzaroni; Philippe Dubois

    2008-01-01

    Novel synthetic transfection vectors with linear triblock and star-shaped diblock copolymer architectures have been synthesized by atom transfer radical polymerization (ATRP). Based on 2-(dimethylamino)ethyl methacrylate (DMAEMA) and copolymerization with poly(ethyleneglycol) ?-methoxy, ?-methacrylate (MAPEG), the synthesis was realized using CuBr ligated with 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA) as catalytic complex and either ethyl 2-bromoisobutyrate (EBiB) or bis(?-bromoisobutyryl) N-methyl diethanolamine (DEA) or tris(?-bromoisobutyryl) triethanolamine (TEA)

  2. Binary and ternary LLE data of the system (ethylbenzene + styrene + 1-ethyl-3-methylimidazolium thiocyanate) and binary VLE data of the system (styrene + 1-ethyl-3-methylimidazolium thiocyanate)

    Microsoft Academic Search

    Mark T. G. Jongmans; Boelo Schuur; André B. de Haan

    2012-01-01

    The distillation of close boiling mixtures may be improved by adding a proper affinity solvent, and thereby creating an extractive distillation process. An example of a close boiling mixture that may be separated by extractive distillation is the mixture ethylbenzene\\/styrene. The ionic liquid 1-ethyl-3-methylimidazolium thiocyanate ([EMIM][SCN]) is a promising solvent to separate ethylbenzene and styrene by extractive distillation. In this

  3. Effect of anion fluorination in 1-ethyl-3-methylimidazolium as solvent for the liquid extraction of ethanol from ethyl tert-butyl ether

    Microsoft Academic Search

    Alberto Arce; Héctor Rodríguez; Ana Soto

    2006-01-01

    In this work, we have studied the use of homologous imidazolium-based ionic liquids (i.e. with the same fluorinated and non-fluorinated anion) to perform the separation of an ether and an alcohol. Concretely, we have selected ethyl tert-butyl ether (ETBE) and ethanol due to the capital interest of their industrial separation. Liquid–liquid equilibrium (LLE) data for the ternary systems involved are

  4. Highly sensitive sites for guanine-O6 ethylation in rat brain DNA exposed to N-ethyl-N-nitrosourea in vivo.

    PubMed Central

    Nehls, P; Rajewsky, M F; Spiess, E; Werner, D

    1984-01-01

    Brain chromosomal DNA isolated from fetal BDIX-rats 1 h after i.v. administration of the ethylating N-nitroso carcinogen N-ethyl-N-nitrosourea (75 micrograms/g body weight), statistically contained one molecule of O6-ethyl-2'-deoxyguanosine (O6-EtdGuo) per 81 micron of DNA, as determined in enzymatic DNA hydrolysates by competitive radio-immunoassay using a high-affinity anti-(O6-EtdGuo) monoclonal antibody (ER-6). After fragmentation of the DNA by the restriction enzyme AluI (average fragment length, Lav = 0.28 micron = 970 bp; length range, Lr = 1.87-0.02 micron = 6540 - 60 bp), a small (approximately 2%) fraction of DNA enriched in specific polypeptides tightly associated with DNA was separated from the bulk DNA by a glass fiber binding technique. As analyzed by immune electron microscopy, approximately 1% of the DNA molecules in this fraction contained clusters of 2-10 (O6-EtdGuo)-antibody binding sites (ABS). On the cluster-bearing fragments (Lav, 0.85 micron +/- 0.50 micron S.D.; corresponding to 2970 +/- 1760 bp) the average ABS-ABS interspace distance was 110 nm (= 390 bp; range approximately 9-600 nm), indicating a highly non-random distribution of O6-EtdGuo in target cell DNA. Images Fig. 2. PMID:6370677

  5. Synthesis, characterization and biocompatibility of poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-poly(2-ethyl-2-oxazoline) hydrogels.

    PubMed

    Wang, X; Li, X; Li, Y; Zhou, Y; Fan, C; Li, W; Ma, S; Fan, Y; Huang, Y; Li, N; Liu, Y

    2011-12-01

    A novel thermoreversible hydrogel based on poly(2-ethyl-2-oxazoline)-derived amphiphilic triblock copolymer, poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-poly(2-ethyl-2-oxazoline) (PEOz-PLA-PEOz), was developed. The synthesis of PEOz-PLA-PEOz was carried out by coupling monohydroxylated PEOz-PLA diblocks with adipoyl chloride as coupling agent and dimethylamino pyridine as catalyst. The tube inverting and rheological tests showed that triblock copolymers had sol-gel-sol transition behavior with increasing temperature, and the gelation was found to be thermoreversible. The critical gelation concentration, the sol-gel transition temperature at a given concentration depended on the EOz/LA ratio and the molecular weight of PEOz. Scanning electron microscopy observation revealed that the resultant bulky gel exhibited an interconnected porous three-dimensional (3D) microstructure after freeze-drying. In addition, the hydrogels showed good cytocompatibility in vitro. MTT assays revealed that the human skin fibroblast cells encapsulated within the hydrogels were viable and proliferated inside the 3D scaffold. This newly described thermoreversible hydrogel demonstrated attractive properties to serve as cell matrix for a variety of tissue engineering applications or pharmaceutical delivery vehicles. PMID:21810488

  6. Small angle neutron scattering study of deuterated sodium dodecylsulfate micellization in dilute poly((2edimethylamino)ethyl methacrylate) solutions

    E-print Network

    Kofinas, Peter

    Small angle neutron scattering study of deuterated sodium dodecylsulfate micellization in dilute 2010 Keywords: Poly((2edimethylamino)ethyl methacrylate) Micelle Small angle neutron scattering a b angle neutron scattering. We found three transitions of the poly ((2edimethylamino)ethyl methacrylate

  7. In vitro antiperoxidative, free radical scavenging and xanthine oxidase inhibitory potentials of ethyl acetate fraction of Saraca ashoka flowers

    Microsoft Academic Search

    A. Prathapan; O. Lijo Cherian; Suresh V. Nampoothiri; S. Mini; K. G. Raghu

    2011-01-01

    Saraca ashoka is a widely used medicinal herb claimed to cure many diseases. This study investigated the antiperoxidative, free radical scavenging and xanthine oxidase (XO) inhibitory potential of the ethyl acetate fraction of S. ashoka flowers (SAF) and compared it with standard compounds like gallic acid, ascorbic acid, butylated hydroxyl toluene and allopurinol. The ethyl acetate fraction of SAF exhibited

  8. On using film boiling to thermally decompose liquid organic chemicals: Application to ethyl acetate as a model compound

    E-print Network

    Walter, M.Todd

    flux (CHF) Leidenfrost point a b s t r a c t Film boiling on a horizontal tube is used to studyOn using film boiling to thermally decompose liquid organic chemicals: Application to ethyl acetate 21 August 2013 Keywords: Film boiling Thermal decomposition Pyrolysis Ethyl acetate Critical heat

  9. Disappearance of Chlorpyrifos Ethyl Pesticide Residues on Tomatoes, Citrus Fruits and Sugar Beet Grown in the Open Field

    Microsoft Academic Search

    R. Salghi; H. Zerouali; M. Zougagh; A. Hormatallah; L. Bazzi; A. Chakir; A. Rios

    In this study, the prevalence of chlorpyrifos ethyl in tomatoes, citrus fruit and sugar beet produced in an area of Northern Morocco (Berkane) was investigated. Samples were taken from the major production areas during 2005-2006. Another objective of this work was to evaluate the degradation behaviour and residue levels of chlorpyrifos ethyl in tomatoes, citrus fruits, and sugar beet grown

  10. 40 CFR 180.228 - S-Ethyl hexahydro-1H-aze-pine-1-carbothioate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false S-Ethyl hexahydro-1H-aze-pine-1-carbothioate; tolerances for residues. 180.228 ...Tolerances § 180.228 S -Ethyl hexahydro-1H -aze-pine-1-carbothioate; tolerances for residues. (a)...

  11. Microbial Community Dynamics during the Bioremediation Process of Chlorimuron-Ethyl-Contaminated Soil by Hansschlegelia sp. Strain CHL1

    PubMed Central

    Yang, Liqiang; Li, Xinyu; Li, Xu; Su, Zhencheng; Zhang, Chenggang; Zhang, Huiwen

    2015-01-01

    Long-term and excessive application of chlorimuron-ethyl has led to a series of environmental problems. Strain Hansschlegelia sp. CHL1, a highly efficient chlorimuron-ethyl degrading bacterium isolated in our previous study, was employed in the current soil bioremediation study. The residues of chlorimuron-ethyl in soils were detected, and the changes of soil microbial communities were investigated by phospholipid fatty acid (PLFA) analysis. The results showed that strain CHL1 exhibited significant chlorimuron-ethyl degradation ability at wide range of concentrations between 10?g kg-1 and 1000?g kg-1. High concentrations of chlorimuron-ethyl significantly decreased the total concentration of PLFAs and the Shannon-Wiener indices and increased the stress level of microbes in soils. The inoculation with strain CHL1, however, reduced the inhibition on soil microbes caused by chlorimuron-ethyl. The results demonstrated that strain CHL1 is effective in the remediation of chlorimuron-ethyl-contaminated soil, and has the potential to remediate chlorimuron-ethyl contaminated soils in situ. PMID:25689050

  12. 40 CFR 721.10225 - Quino[2,3-b] acridine-7,14-dione, 2,9-dichloro-5,12-dihydro [4-[[2-(sulfooxy) ethyl] substituted...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...ethyl] substituted] phenyl]-, sodium salt (1:1) (generic). 721.10225...ethyl] substituted] phenyl]-, sodium salt (1:1) (generic). (a) Chemical...ethyl] substituted] phenyl]-, sodium salt (1:1) (PMN P-10-14) is...

  13. 40 CFR 721.10225 - Quino[2,3-b] acridine-7,14-dione, 2,9-dichloro-5,12-dihydro [4-[[2-(sulfooxy) ethyl] substituted...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (PMN...

  14. 40 CFR 721.10225 - Quino[2,3-b] acridine-7,14-dione, 2,9-dichloro-5,12-dihydro [4-[[2-(sulfooxy) ethyl] substituted...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (PMN...

  15. 40 CFR 721.10225 - Quino[2,3-b] acridine-7,14-dione, 2,9-dichloro-5,12-dihydro [4-[[2-(sulfooxy) ethyl] substituted...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (generic...2-(sulfooxy) ethyl] substituted] phenyl]-, sodium salt (1:1) (PMN...

  16. Influence of Phenobarbital on Morphine Metabolism and Disposition:LCMS\\/MS Determination of Morphine (M) and Morphine3Glucuronide (M3G) in Wistar-Kyoto Rat Serum, Bile, and Urine

    Microsoft Academic Search

    Yazen M. Alnouti; Melinda K. Shelby; Chuan Chen; Curtis D. Klaassen

    2007-01-01

    A simple LC-MS\\/MS method has been developed and validated for the simultaneous determination of mor- phine (M) and morphine-3-glucuronide (M3G) in rat serum, bile, and urine. Deuterated D3-M and D3-M3G were used as internal standards (IS) for M and M3G, respectively. Serum samples were processed by acetonitrile precipitation. Bile samples were prepared by solid-phase extraction (SPE) using Oasis MCX cartridges.

  17. ECHINACEA SANGUINEA AND ECHINACEA PALLIDA EXTRACTS STIMULATE GLUCURONIDATION AND BASOLATERAL TRANSFER OF BAUER ALKAMIDES 8 AND 10 AND KETONE 24 AND INHIBIT P-GLYCOPROTEIN TRANSPORTER IN CACO-2 CELLS

    PubMed Central

    Qiang, Zhiyi; Hauck, Cathy; McCoy, Joe-Ann; Widrlechner, Mark P.; Reddy, Manju B.; Murphy, Patricia A.; Hendrich, Suzanne

    2013-01-01

    The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator. We hypothesized that Bauer alkamides 8, 10 and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit P-glycoprotein transporter (P-gp) in Caco-2 human intestinal epithelial cells. Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix. Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11. Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts. Bauer alkamides 8, 10 and 11 (175–230 ?M) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~90 ?M total alkamides) and E. pallida (5 mg/mL, containing 285 ?M total alkamides) decreased the efflux of the P-gp probe calcein-AM from Caco-2 cells. These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits. Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics which are substrates for P-gp. PMID:23408271

  18. Genotoxic effects of two industrial effluents and ethyl methane sulfonate in Clarias lazera

    Microsoft Academic Search

    P. G. C. Odeigah; A. O. Osanyipeju

    1995-01-01

    The genotoxic effects of industrial effluents from a brewery and a textile mill and of ethyl methane sulfonate (EMS) were investigated by the micronucleus test in Clarias lazera, a tropical freshwater fish. Fish obtained from a local market were kept in laboratory aquaria for 3 wk and then exposed to different concentrations (0.5 to 8 mg\\/litre) of EMS or brewery

  19. Carfentrazone-ethyl Pond Dissipation and Efficacy on Floating Plants 1

    Microsoft Academic Search

    TYLER J. KOSCHNICK; W. T. HALLER; A. W. CHEN

    Carfentrazone-ethyl (CE) is a reduced risk herbicide that is currently being evaluated for the control of aquatic weeds. Greenhouse trials were conducted to determine efficacy of CE on water hyacinth ( Eichhornia crassipes (Mart.) Solms- Laub.), water lettuce ( Pistia stratiotes L.), salvinia ( Salvinia minima Baker) and landoltia (Landoltia punctata (G. Mey.) Les & D. J. Crawford ) .

  20. Development and validation of analytical methods for ethyl carbamate in various fermented foods

    Microsoft Academic Search

    Hyo-Shin Lim; Kwang-Geun Lee

    2011-01-01

    The aim of this work was to develop and validate analytical methods for ethyl carbamate (EC) in various food matrices. Column chromatography was used for the analysis of EC in kimchi, a fermented soybean paste (doenjang), a fermented fish product (jeotgal), yoghurt, bread, and cheese. To remove the fat in the bread and cheese, a Florisil cartridge was selected. The

  1. Ethyl ester of rapeseed used as a biodiesel fuel—a case study

    Microsoft Academic Search

    Charles L. Peterson; Daryl L. Reece; Joseph C. Thompson; Sidney M. Beck; Craig Chase

    1996-01-01

    A 1994 Dodge 2500 turbocharged and intercooled diesel pickup fueled with 100% ethyl ester of rapeseed oil was driven by personnel representing the University of Idaho, Agricultural Engineering Department from Moscow, Idaho to Los Angeles, California and back to Moscow and then from Moscow to Ocean City, Maryland, east of Washington, D.C. and back to Moscow, Idaho. These trips covered

  2. Synthesis of antibacterial polymers from 2-dimethylamino ethyl methacrylate quaternized by dimethyl sulfate

    Microsoft Academic Search

    Huajiang Zuo; Dingcai Wu; Ruowen Fu

    2010-01-01

    An antibacterial quaternary ammonium acrylic monomer (1) was synthesized by quaternization of 2-dimethylamino ethyl methacrylate with dimethyl sulfate. This synthetic route to quaternary ammonium salt monomer proved to be of high yield and lower cost than that used to synthesize alkyl halide. The corresponding homopolymers (2) were then obtained by free radical polymerization using potassium persulfate as the initiator. The

  3. The effects of two internal rotations in the microwave spectrum of ethyl methyl ketone.

    PubMed

    Nguyen, Ha Vinh Lam; Van, Vinh; Stahl, Wolfgang; Kleiner, Isabelle

    2014-06-01

    The rotational spectra of ethyl methyl ketone, CH3CH2COCH3, were measured in the microwave region from 2 to 40 GHz using two molecular beam Fourier transform microwave spectrometers. Splittings due to internal rotations of both, the acetyl methyl group -COCH3 and the ethyl methyl group CH3CH2CO-, could be completely resolved. All measured transitions were fitted using two different codes, XIAM and BELGI-Cs-2Tops. Molecular parameters like the rotational constants and the centrifugal distortion constants were determined with very high accuracy. The barrier to internal rotation of the acetyl methyl group was fitted to 181.502(98) cm(-1), much lower than the value of 763.87(65) cm(-1) found for the ethyl methyl group. The splittings in the spectrum due to internal rotation of the acetyl methyl group are accordingly much larger, up to 1.2 GHz, whereas for the ethyl methyl group only splittings from a few hundreds of kHz up to 4 MHz were observed. PMID:24908004

  4. Acidic 1-ethyl-3-methylimidazolium fluoride: a new room temperature ionic liquid

    Microsoft Academic Search

    Rika Hagiwara; Takayuki Hirashige; Tetsuya Tsuda; Yasuhiko Ito

    1999-01-01

    Reaction of 1-ethyl-3-methyl imidazolium chloride (EMIC) and hydrogen fluoride gives an yellow, involatile liquid, EMIF·2.3HF. The liquid is stable in air and able to be stored in a glass container. The specific conductivity was about 12Sm?1 at 298K.

  5. Diffusion of oxygen (1); 1-ethyl-3-methylimidazolium bis-((trifluoromethyl)-sulfonyl)-imide (2)

    Microsoft Academic Search

    J. Winkelmann

    2007-01-01

    This document is part of Subvolume A `Gases in Gases, Liquids and their Mixtures' of Volume 15 `Diffusion in Gases, Liquids and Electrolytes' of Landolt-Börnstein Group IV `Physical Chemistry'. It is part of the chapter of the chapter `Diffusion in Pure Gases' and contains data on diffusion of (1) oxygen; (2) 1-ethyl-3-methylimidazolium bis-((trifluoromethyl)-sulfonyl)-imide

  6. TEMPERATURE AND TRINEXAPAC-ETHYL EFFECTS ON BERMUDAGRASS GROWTH, DORMANCY AND FREEZING TOLERANCE.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the transition zone in the southeastern U.S., growth regulators are being applied to bermudagrass in summer months and, recently, also in the fall. The purpose of this study was to investigate the role of temperature and trinexapac-ethyl (TE) interactions in bermudagrass growth responses, dormanc...

  7. Combustion chemical kinetics of biodiesel and related compounds (methyl and ethyl esters): Experiments and

    E-print Network

    Paris-Sud XI, Université de

    1 Combustion chemical kinetics of biodiesel and related compounds (methyl and ethyl esters and reduced exhaust emissions have led to the emergence of new fuels and combustion devices. Over the past ten years, considerable effort has gone into understanding combustion phenomena in relation to emerging fuel

  8. Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC, Sodium CMC, Ethyl Cellulose.

    PubMed

    Sirisolla, Janakidevi; Ramanamurthy, K V

    2015-01-01

    The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method. PMID:26180278

  9. Separation of n-hexane–ethyl acetate mixtures by azeotropic batch distillation with heterogeneous entrainers

    Microsoft Academic Search

    I. Rodriguez-Donis; J. Acosta-Esquijarosa; V. Gerbaud; E. Pardillo-Fondevila; X. Joulia

    2005-01-01

    In this article, a systematic study of the separation of the n-hexane–ethyl acetate mixture with an entrainer by heterogeneous azeotropic batch distillation is performed. Based upon the thermodynamic behaviour of the ternary mixtures, potential entrainers partially miscible with one or two original azeotropic components are chosen. In all cases, the entrainer adds a heterogeneous binary or ternary azeotrope that is

  10. Sugars, acids, ethyl ?- d-glucopyranose and a methyl inositol in sea buckthorn ( Hippophaë rhamnoides) berries

    Microsoft Academic Search

    Baoru Yang

    2009-01-01

    Sea buckthorn berry is a rich source of nutrients and bioactive components beneficial for human health. Sugars and acids play an important role in determining the sensory properties of the berry. Sugars, acids, ethyl ?-d-glucopyranose and a methyl inositol were analysed in berries of three subspecies (Hippophaë rhamnoides ssp. sinensis, rhamnoides and mongolica) collected from China, Finland and Russia over

  11. Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC, Sodium CMC, Ethyl Cellulose

    PubMed Central

    Sirisolla, Janakidevi; Ramanamurthy, K. V.

    2015-01-01

    The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method. PMID:26180278

  12. Interest of ferulic acid ethyl ester in photoprotective creams: Measure of efficacy by in vitro method

    Microsoft Academic Search

    Benjamin Choquenet; Celine Couteau; Eva Paparis; Laurence J. M. Coiffard

    2008-01-01

    Topical sunscreens have been used for many years on exposed areas to protect the skin from the damaging effects of ultraviolets. If the sunscreens were essential, it is suggested that they have adverse effects. We chose to study ferulic acid ethyl ester (FAEE) as agent which could potentially be used in sunscreen products. FAEE was incorporated at various concentrations into

  13. Release of drugs from ethyl cellulose microcapsules (diffusion pellets) with pore formers and pore fusion

    Microsoft Academic Search

    W. Gunder; B. H. Lippold; B. C. Lippold

    1995-01-01

    By adding hydroxypropyl methyl cellulose (HPMC) to aqueous ethyl cellulose (EC) dispersions with 20% dibutyl sebacate (DBS) as plasticizer, it is possible to manufacture diffusion pellets (coated pellets) which contain water-filled pores in the release-controlling membrane after extraction of the HPMC at the beginning of the release process. In the case of 25% HPMC and an acidic medium, these pores

  14. Amino acids and glycine ethyl ester as new crystallization reagents for lysozyme

    PubMed Central

    Ito, Len; Shiraki, Kentaro; Yamaguchi, Hiroshi

    2010-01-01

    Several amino acids and their derivatives are prominent additives in the field of protein chemistry. This study reports the use of charged amino acids and glycine ethyl ester as precipitants in protein crystallization, using hen egg-white lysozyme (HEWL) as a model. A discussion of the crystallization of HEWL using these reagents as precipitating agents is given. PMID:20516616

  15. The use of near-infrared spectroscopy for the cure monitoring of an ethyl cyanoacrylate adhesive

    Microsoft Academic Search

    S. K. Tomlinson; O. R. Ghita; R. M. Hooper; K. E. Evans

    2006-01-01

    Near-IR reflectance spectroscopy has been used to study the curing of ethyl cyanoacrylate adhesive on polished dental glass and microscope slide substrates. The effects of changing the glue film thickness and the type of substrate on the curing rate have been investigated whilst maintaining a constant humidity. The FTIR spectral data has been used to calculate and plot the extents

  16. Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: a review.

    PubMed

    Joya, X; Friguls, B; Ortigosa, S; Papaseit, E; Martínez, S E; Manich, A; Garcia-Algar, O; Pacifici, R; Vall, O; Pichini, S

    2012-10-01

    The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioural and/or learning disabilities that are included in the term fetal alcohol spectrum disorder (FASD). Objective assessment of exposure to ethanol at both prenatal and postnatal stages is essential for early prevention and intervention. Since pregnant women tend to underreport alcohol drinking by questionnaires, a number of biological markers have been proposed and evaluated for their capability to highlight gestational drinking behaviour. These biomarkers include classical biomarkers (albeit indirect) of alcohol-induced pathology (mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) acetaldehyde-derived conjugates, and finally derivatives of non-oxidative ethanol metabolism (fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphaditylethanol (PEth)). Since ethanol itself and acetaldehyde are only measured few hours after ethanol intake in conventional matrices such as blood, urine and sweat, they are only useful to detect recent ethanol exposure. In the past few years, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and in some case wide time-window of detection in non-conventional matrices from the pregnant mother (oral fluid and hair) and fetus-newborn (neonatal hair, meconium, placenta and umbilical cord). This article reviews bioanalytical procedures for the determination of these markers of ethanol consumption during pregnancy and related prenatal exposure. In addition, clinical toxicological applications of these procedures are presented and discussed. PMID:22300909

  17. Toxicological investigation of liquid petroleum gas explosion: human model for propane/ethyl mercaptan exposures.

    PubMed

    Lowry, W T; Gamse, B; Armstrong, A T; Corn, J M; Juarez, L; McDowell, J L; Owens, R

    1991-03-01

    Four individuals died as the result of a propane explosion. As with many propane explosions, the question was raised as to the adequacy of the product's odorization after the autopsy studies had been conducted. In most cases, this question leads to litigation. Ethyl mercaptan is a widely used odorant for propane and was used in this instance. Three of the four victims had blood available at autopsy for study. Quantitative analyses of the victims' blood, obtained during autopsy, were performed using gas chromatography/mass spectrometry, without subjecting the samples to hydrolysis. These analyses determined the relative amounts of propane and ethyl mercaptan in the blood to be 90, 63, and 175 mL/m3 headspace, and 0.36, 0.34, and 0.77 microgram/L blood, respectively. Since mercaptans have been reported in human blood as products of metabolism, modeling studies were conducted to establish the validity of the autopsy data and to develop an autopsy toxicology protocol for investigating explosion deaths. When subjects were not exposed to an atmosphere containing ethyl mercaptan, dimethylsulfide was the only mercaptan detectable in their blood without severe hydrolysis prior to analysis. Metabolic ethyl mercaptan is sufficiently bound to be undetectable by the methods used without hydrolysis. Human subjects were exposed to a flammable mixture of air and propane odorized with ethyl mercaptan. The analyses of the blood from these subjects produced results which were comparable with those for the explosion victims, establishing that the question of odorant adequacy can be addressed at the autopsy of propane explosion victims. It is extremely important that the pathologist and toxicologist investigating gas explosion deaths recognize the valuable evidence existing in the victim's blood. PMID:2066720

  18. Quantification of Hepatic UDP Glucuronosyltransferase 1A Splice Variant Expression and Correlation of UDP Glucuronosyltransferase 1A1 Variant Expression with Glucuronidation Activity

    PubMed Central

    Jones, Nathan R.; Sun, Dongxiao; Freeman, Willard M.

    2012-01-01

    The UDP glucuronosyltransferase (UGT) 1A gene cluster encodes nine UGT1A family members via splicing of individual first exons to common exons 2 through 5. Each of these nine UGT1As can also undergo alternative splicing at their 3? ends by using an alternate exon 5, resulting in 27 different UGT1A mRNA species with each UGT1A gene encoding three different combinations of 5A and 5B UGT1A exons. To examine the importance of UGT1A exon 5 splice variants on overall UGT1A activity, a nested quantitative polymerase chain reaction assay was developed to accurately assess the combined expression of exon 5 splice variants (termed v2/v3) versus the expression of wild-type (termed v1) for each specific UGT1A. v1 expression was 16-, 17-, 57- and 29-fold higher than that observed for the levels of v2/v3 for UGTs 1A1, 1A4, 1A6, and 1A9, respectively, in normal human liver specimens. In a series of 58 normal human liver specimens, the expression of both UGT1A1 v1 and v2/v3 mRNAs was positively correlated with raloxifene glucuronidation activity in corresponding microsomes prepared from the same specimens (p < 0.0001, r2 = 0.720; p = 0.0002, r2 = 0.241, respectively), with expression of both variants lower in individuals homozygous for the UGT1A1*28 allele (42% for v1, p = 0.041; 53% for v2/v3, p = 0.0075). The expression of UGT1A1 v2/v3 was 1.6-fold higher than v1 (p = 0.03) in HepG2 cells, and short interfering RNA knockdown of HepG2 v2/v3 increased raloxifene glucuronidation activity by 83%. Together, these data suggest that hepatic UGT1A v2/v3 mRNA species are minor form variants in human livers from most individuals. PMID:22661630

  19. Three-step synthesis of ethyl canthinone-3-carboxylates from ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3-carboxylate via a Pd-catalyzed Suzuki-Miyaura coupling and a Cu-catalyzed amidation reaction.

    PubMed

    Ioannidou, Heraklidia A; Martin, Aaron; Gollner, Andreas; Koutentis, Panayiotis A

    2011-06-17

    Ethyl canthin-6-one-1-carboxylate (1b) and nine analogues 1c-k were prepared from readily prepared ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3-carboxylate (2b) via a three-step non-classical approach that focused on construction of the central pyrrole (ring B) using Pd-catalyzed Suzuki-Miyaura coupling followed by Cu-catalyzed C-N coupling. Furthermore, treatment of the ethyl canthinone-1-carboxylate 1b with NaOH in DCM/MeOH (9:1) gave the canthin-6-one-1-carboxylic acid (6) in high yield. All compounds are fully characterized. PMID:21563779

  20. [Activity of new iminium compounds against bacteria and fungi. 28. Synthesis of 1-ethyl-, 1-n-dodecyl-2-phenyl-3-(n-alkylthiomethyl)- and 1-ethyl-, 1-n-dodecyl-2-phenyl-3-(n-alkoxymethyl)imidazolium chlorides].

    PubMed

    Pernak, J; Krysi?ski, J; Skrzypczak, A

    1992-08-01

    The synthesis of quaternary imidazolium compounds was performed by reaction of 1-ethyl- or 1-n-dodecyl-2-phenylimidazole with chloromethyl-n-alkyl ether or chloromethyl-n-alkyl sulfid. The antibacterial properties of the compounds obtained were tested on 13 strains of bacteria and fungi. 1-Ethyl-2-phenyl-3-(n-decylthiomethyl)-, 1-ethyl-2-phenyl-3-(n-dodecylthiomethyl)imidazolium chloride and 1-n-dodecyl-2-phenyl-3-(n-butylthiomethyl)-, 1-n-dodecyl-2-phenyl-3-(n-hexylthiomethyl)imidazolium chloride indicated the best antibacterial activity. PMID:1438516