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Sample records for ethyl glucuronide determination

  1. Determination of ethyl glucuronide in hair: a rapid sample pretreatment involving simultaneous milling and extraction.

    PubMed

    Mönch, Bettina; Becker, Roland; Nehls, Irene

    2014-01-01

    A combination of simultaneous milling and extraction known as micropulverized extraction was developed for the quantification of the alcohol marker ethyl glucuronide (EtG) in hair samples using a homogeneous reference material and a mixer mill. Best extraction results from 50 mg of hair were obtained with 2-mL plastic tubes containing two steel balls (? = 5 mm), 0.5 mL of water and with an oscillating frequency of 30 s(-1) over a period of 30 min. EtG was quantified employing a validated GC-MS procedure involving derivatization with pentafluoropropionic acid anhydride. This micropulverization procedure was compared with dry milling followed by separate aqueous extraction and with aqueous extraction after manual cutting to millimeter-size snippets. Micropulverization yielded 28.0?±?1.70 pg/mg and was seen to be superior to manually cutting (23.0?±?0.83 pg/mg) and equivalent to dry grinding (27.7?±?1.71 pg/mg) with regard to completeness of EtG extraction. The option to process up to 20 samples simultaneously makes micropulverization especially valuable for the high throughput of urgent samples. PMID:24221575

  2. Determination of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in hair: a promising way for retrospective detection of alcohol abuse during pregnancy?

    PubMed

    Pragst, Fritz; Yegles, Michel

    2008-04-01

    The retrospective detection of alcohol consumption during pregnancy is an important part of the diagnosis of the fetal alcohol syndrome. A promising way to solve this problem can be the determination of fatty acid ethyl esters (FAEE) or/and ethyl glucuronide (EtG) in hair of the mothers. In this article, the present state in analytical determination and interpretation of FAEE and EtG concentrations in hair are reviewed. Both FAEE and EtG are minor metabolites of ethanol and as direct alcohol markers very specific for alcohol. They are durably deposited in hair, which enables taking advantage of the long diagnostic time window of this sample material. In the last years, specific and sensitive methods for determination of both alcohol markers in hair were developed. Headspace solid phase microextraction in combination with gas chromatography-mass spectroscopy after hair extraction with an n-heptane/dimethylsulfoxide mixture proved to be a favorable technique for determination of four characteristic FAEE (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate). EtG is extracted from hair by water and analyzed either by gas chromatography-mass spectroscopy with negative chemical ionization after cleanup with solid phase extraction and derivatization with pentafluoropropionic anhydride or by liquid chromatography-mass spectroscopy-mass spectroscopy. The detection limits of the single FAEE as well as of EtG are in the range of 1 to 10 pg/mg. FAEE as well as EtG were determined in a larger number of hair samples of teetotalers, social drinkers, patients in alcohol withdrawal treatment, and death cases with previous known heavy drinking. From the results, the following criteria were derived: strict abstinence is excluded or improbable at C FAEE >0.2 ng/mg or C EtG >7 pg/mg. Moderate social drinkers should have C FAEE <0.5 ng/mg and C EtG <25 pg/mg; above these values, alcohol abuse is probable. Until now, there has been no evaluation in context of FAS diagnosis; however, a successful application for this purpose can be expected from the good experience in driving ability examination. PMID:18367991

  3. Ethyl Glucuronide Positivity Rate in a Pain Management Population.

    PubMed

    Johnson-Davis, Kamisha L; Slawson, Matthew H

    2015-11-01

    Ethanol may be consumed by some patients as a means to manage their pain or psychiatric disorder. Consequently, there is the potential to consider ethanol a co-therapeutic in pain management. The purpose of this study was to perform a retrospective analysis to evaluate the rate of ethanol use in a population of patients in pain management programs that were evaluated by our in-house pain management drug panel test. Results from this retrospective study showed that 12.6% of patients in a pain management population were positive for the direct ethanol metabolite, ethyl glucuronide (EtG), by immunoassay. Furthermore, 86% of the individuals positive for EtG were also positive for prescription pain medication and illicit drugs. Results presented here suggest that ethanol use should be routinely monitored in pain management populations in an effort to determine any potential adverse effects of ethanol-drug interactions and as a way to further evaluate the effect of ethanol on pain management outcomes. Testing this population of patients suggests that ethanol use is prevalent and the risk of drug-ethanol adverse effects should be monitored in a pain management population. PMID:26324207

  4. Detection of ethyl glucuronide in blood spotted on different surfaces.

    PubMed

    Winkler, M; Kaufmann, E; Thoma, D; Thierauf, A; Weinmann, W; Skopp, G; Alt, A

    2011-07-15

    This study aims to show that sensitive detection of ethyl glucuronide in dried blood spotted onto various surfaces after a period of 24h is feasible. At present, there is insufficient information how tightly ethyl glucuronide (EtG) binds to various materials and how easily it can be eluted. 4ml aliquots of blood samples obtained from seven volunteers after consumption of alcoholic beverages were applied to six different surfaces. After drying and a 24h-storage at 20±2°C the samples were re-dissolved in water, and EtG was subsequently analyzed by a LC-MS Paul-type ion trap. A comparison was made between dried and corresponding fluid samples. EtG was detectable in all subjects' samples following consumption of alcohol. EtG was also detectable after a storage time of four weeks at 4°C in whole blood that had been preserved with EDTA. EtG was detectable in all samples dried on different surfaces and its concentration remained relatively constant irrespective of the particular condition of the material. Detection of EtG in blood spots from the scene may indicate recent alcohol consumption in cases where collection of blood remained undone or could not be performed. PMID:21641739

  5. 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.…

  6. Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair of alcoholics, social drinkers and teetotallers.

    PubMed

    Yegles, M; Labarthe, A; Auwärter, V; Hartwig, S; Vater, H; Wennig, R; Pragst, F

    2004-10-29

    In previous investigations hair analysis for ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) proved to be suitable for the detection of excessive alcohol consumption. The aim of this study was to compare EtG and FAEE concentrations in hair of alcoholics, social drinkers and teetotallers. Hair samples from 10 alcoholics in withdrawal treatment, 11 fatalities with documented excessive alcohol consumption, four moderate social drinkers who consumed up to 20 g ethanol per day, and three strict teetotallers were analysed. After external degreasing with n-heptane, extraction with a dimethyl sulfoxide/n-heptane mixture and headspace solid-phase microextraction of the extracts, four fatty acid ethyl esters (FAEEs) (ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) were analysed by gas chromatography-mass spectrometry (GC-MS) with deuterated internal standards. EtG was determined by GC-MS/NCI after ultrasonication of the samples with H2O, cleanup by SPE with aminopropyl columns and PFP derivatisation. The following concentrations were measured for the four groups: teetotallers EtG < 0.002 ng/mg, FAEE 0.05-0.37 ng/mg, moderate social drinkers EtG < 0.002 ng/mg, FAEE 0.26-0.50 ng/mg, alcoholic patients EtG 0.030-0.415 ng/mg, FAEE 0.65-20.50 ng/mg and the fatalities with alcohol history EtG 0.072-3.380 ng/mg, FAEE 1.30-30.60 ng/mg. The results confirm that by using a cut-off value of the sum of FAEE > 1 ng/mg and/or a positive EtG result in hair, excessive alcohol consumption can be identified using hair analysis. However, no significant correlation between the EtG and FAEE concentrations in the positive cases could be shown. Segmental analysis of some of the specimens did not reveal the same distribution for EtG compared to FAEE in hair, and no chronological accordance compared to the self-reported alcohol consumption could be observed for both parameters. These different results of both methods are discussed in terms of differences between EtG and FAEE in mechanism of formation and incorporation into hair and elimination from hair. PMID:15451089

  7. Quantitation of Ethyl Glucuronide and Ethyl Sulfate in Urine Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

    PubMed

    Slawson, Matthew H; Johnson-Davis, Kamisha L

    2016-01-01

    Ethyl glucuronide and ethyl sulfate are minor conjugated metabolites of ethanol that can be detected in urine for several days after last ingestion of ethanol. The monitoring of ethanol use has both clinical and forensic applications and a longer detection window afforded by monitoring these metabolites is obvious. LC-MS/MS is used to analyze diluted urine with deuterated analogs of each analyte as internal standards to ensure accurate quantitation and control for any potential matrix effects. High aqueous HPLC is used to chromatograph the metabolites. Negative ion electrospray is used to introduce the metabolites into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each metabolite, while a matrix-matched calibration curve is used for quantitation. PMID:26660185

  8. Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide.

    PubMed

    Schwab, Nicole; Skopp, Gisela

    2014-04-01

    Ethyl glucuronide (EtG), a minor metabolite of ethanol, is used as a marker of alcohol consumption in a variety of clinical and forensic settings. At present there are very few studies of UDP-glucuronosyltransferases (UGT), responsible for catalyzing EtG formation, and the possible effect of nutritional components, e.g. flavonoids, which are extensively glucuronidated, on EtG formation has not been addressed at all. The following incubation conditions were optimized with regard to previously published conditions: buffer, substrate concentration, and incubation time. Isolation of EtG from the incubation mixture was also optimized. Recombinant UGT enzymes (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 2B10, 2B15) were screened for their activity towards ethanol, and kinetic data were then established for all enzymes. It was decided to study the effect of the flavonoids quercetin and kaempferol on glucuronidation of ethanol. Isolation was by solid-phase extraction (SPE) to minimize matrix effects. Analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS-MS), with EtG-d5 as the internal standard. SPE was vital to avoid severe ion suppression after direct injection of the incubation solution. EtG formation was observed for all enzymes under investigation; their kinetics followed the Michaelis-Menten model, meaning the maximum reaction rate achieved at saturating substrate concentrations (V(max)) and the substrate concentration at which the reaction rate is half of V(max) (Michaelis-Menten constant, K(m)) could be calculated. The highest rate of glucuronidation was observed with UGT1A9 and 2B7. After co-incubation with both flavonoids, formation of EtG was significantly reduced for all enzymes except for UGT2B15, whose activity did not seem to be affected. Results reveal that multiple UGT isoforms are capable of catalyzing glucuronidation of ethanol; nevertheless, the effect of UGT polymorphism on glucuronidation of ethanol needs further study. Formation of EtG is inhibited by the flavonoids under investigation. Obviously, nutritional components affect conversion of ethanol to EtG. This observation may serve as a partial explanation of its variable formation in man. PMID:24553666

  9. Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker

    PubMed Central

    Berger, Lisa; Fendrich, Michael; Jones, Joseph; Fuhrmann, Daniel; Plate, Charles; Lewis, Douglas

    2014-01-01

    Aims This study aimed to evaluate the performance of ethyl glucuronide (EtG) in hair and fingernails as a long-term alcohol biomarker. Design Cross-sectional survey with probability sampling. Setting Midwestern United States. Participants Participants were 606 undergraduate college students between the ages of 18 and 25 years at the time of selection for potential study participation. Measurements EtG concentrations in hair and fingernails were measured by liquid chromatography-tandem mass spectrometry at three thresholds [30 picograms (pg) per milligram (mg); 20 pg/mg; and 8 pg/mg]. Any weekly alcohol use, increasing-risk drinking and high-risk drinking on average during the past 12 weeks was assessed by participant interview using the time-line follow-back method. Findings In both hair and fingernails at all three EtG thresholds, sensitivity was greatest for the high-risk drinking group [hair: 0.43, confidence interval (CI) = 0.17, 0.69 at 30 pg/mg, 0.71, CI = 0.47, 0.95 at 20 pg/mg; 0.93, CI = 0.79, 1.00 at 8 pg/mg; fingernails: 1.00, CI = 1.00–1.00 at 30, 20 and 8 pg/mg] and specificity was greatest for any alcohol use (hair: 1.00, CI = 1.00, 1.00 at 30 and 20 pg/mg; 0.97, CI = 0.92–0.99 at 8 pg/mg; fingernails: 1.00, CI = 1.00–1.00 at 30, 20 and 8 pg/mg). Areas under the receiver operating characteristic curves were significantly higher for EtG concentration in fingernails than hair for any weekly alcohol use (P = 0.02, DeLong test, two-tailed) and increasing-risk drinking (P = 0.02, DeLong test, two-tailed). Conclusions Ethyl glucuronide, especially in fingernails, may have potential as a quantitative indicator of alcohol use. PMID:24524319

  10. A Highly Specific, Fully Validated Urinary Ethyl Glucuronide Analysis Using Solid Phase Extraction-Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry.

    PubMed

    Acikkol, Munevver; Ozdemir, Ali Acar; Anilanmert, Beril; Mirsal, Hasan

    2015-01-01

    A highly specific and selective analytical method using LC/MS/MS for the quantitative determination of ethyl glucuronide (EtG) in urine was developed and fully validated. Since the determination of EtG in urine may be possible days after the elimination of alcohol, it is an indication of alcohol use in alcohol treatment programs and antemortem and postmortem toxicological investigations. Propyl glucuronide (PrG), which increased the selectivity of the method, was used as an internal standard. The method was validated in terms of selectivity, linearity, LOD, LOQ, intraday and interday precision, and recovery. The analyte and PrG in the SPE cleaned up extract were separated on a 150 mm C18 column in 3.3 min with high resolution. The rest of the peaks from the matrix were eluted in 9.0 min. The LOD was 90.8 ng/mL and the LOQ was calculated using the EURACHEM method as 185.0 ng/mL. The intraday and the intermediate precision of the method was calculated using analysis of variance and confirmed with calculation of HorRat values, which were found within acceptable limits. The method provided a reliable solution for monitoring patients under alcohol addiction treatment and was successfully applied to real samples. PMID:26086255

  11. 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

  12. Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation[S

    PubMed Central

    Jarrar, Yazun Bashir; Cha, Eun-Young; Seo, Kyung-Ah; Ghim, Jong-Lyul; Kim, Hyo-Ji; Kim, Dong-Hyun; Lee, Su-Jun; Shin, Jae-Gook

    2014-01-01

    The compound 20-HETE is involved in numerous physiological functions, including blood pressure and platelet aggregation. Glucuronidation of 20-HETE by UDP-glucuronosyltransferases (UGTs) is thought to be a primary pathway of 20-HETE elimination in humans. The present study identified major UGT enzymes responsible for 20-HETE glucuronidation and investigated their genetic influence on the glucuronidation reaction using human livers (n = 44). Twelve recombinant UGTs were screened to identify major contributors to 20-HETE glucuronidation. Based on these results, UGT2B7, UGT1A9, and UGT1A3 exhibited as major contributors to 20-HETE glucuronidation. The Km values of 20-HETE glucuronidation by UGT1A3, UGT1A9, and UGT2B7 were 78.4, 22.2, and 14.8 ?M, respectively, while Vmax values were 1.33, 1.78, and 1.62 nmol/min/mg protein, respectively. Protein expression levels and genetic variants of UGT1A3, UGT1A9, and UGT2B7 were analyzed in human livers using Western blotting and genotyping, respectively. Glucuronidation of 20-HETE was significantly correlated with the protein levels of UGT2B7 (r2 = 0.33, P < 0.001) and UGT1A9 (r2 = 0.31, P < 0.001), but not UGT1A3 (r2 = 0.02, P > 0.05). A correlation between genotype and 20-HETE glucuronidation revealed that UGT2B7 802C>T, UGT1A9 ?118T9>T10, and UGT1A9 1399T>C significantly altered 20-HETE glucuronide formation (P < 0.05–0.001). Increased levels of 20-HETE comprise a risk factor for cardiovascular diseases, and the present data may increase our understanding of 20-HETE metabolism and cardiovascular complications. PMID:25249502

  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. 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

  15. 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

  16. Quantitative determination of common urinary odorants and their glucuronide conjugates in human urine.

    PubMed

    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

  17. 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

  18. Identifying and applying a highly selective probe to simultaneously determine the O-glucuronidation activity of human UGT1A3 and UGT1A4

    PubMed Central

    Jiang, Li; Liang, Si-Cheng; Wang, Chao; Ge, Guang-Bo; Huo, Xiao-Kui; Qi, Xiao-Yi; Deng, Sa; Liu, Ke-Xin; Ma, Xiao-Chi

    2015-01-01

    Glucuronidation mediated by uridine 5?-diphospho (UDP)-glucuronosyltransferase is an important detoxification pathway. However, identifying a selective probe of UDP- glucuronosyltransferase is complicated because of the significant overlapping substrate specificity displayed by the enzyme. In this paper, desacetylcinobufagin (DACB) 3-O- and 16-O-glucuronidation were found to be isoform-specific probe reactions for UGT1A4 and UGT1A3, respectively. DACB was well characterized as a probe for simultaneously determining the catalytic activities of O-glucuronidation mediated by UGT1A3 and UGT1A4 from various enzyme sources, through a sensitive analysis method. PMID:25884245

  19. Bisphenol A glucuronide deconjugation is a determining factor of fetal exposure to bisphenol A.

    PubMed

    Gauderat, Glenn; Picard-Hagen, Nicole; Toutain, Pierre-Louis; Corbel, Tanguy; Viguié, Catherine; Puel, Sylvie; Lacroix, Marlčne Z; Mindeguia, Pierre; Bousquet-Melou, Alain; Gayrard, Véronique

    2016-01-01

    Previous studies in experimental animals have shown that maternal exposure to bisphenol A (BPA) during late pregnancy leads to high plasma concentrations of BPA glucuronide (BPAG) in fetus compared to mother due to the inability of BPAG to cross the placental barrier. A recent in vitro study has reported that BPAG can exert adipogenic effect underlining the need for characterization of the fetal disposition of BPAG. Experiments were conducted in chronically catheterized fetal sheep to determine the contribution of BPAG hydrolysis to BPA to the elimination of BPAG from the fetal compartment and its resulting effect on the overall fetal exposure to free BPA. Serial sampling of fetal arterial blood, amniotic fluid, maternal venous blood and urine was performed following separate single doses of BPA and BPAG administered intravenously to eight fetal/maternal pairs after cesarean section, and repeated BPAG doses given to two fetal sheep. On average 67% of the BPA entering the fetal circulation was rapidly eliminated through fetal to maternal clearance, with a very short half-life (20min), while the remaining fraction (24%) was glucuronoconjugated. BPA conjugation-deconjugation cycling was responsible for a 43% increase of the overall fetal exposure to free BPA. A very specific pattern of fetal exposure to free BPA was observed due to its highly increased persistence with a hydrolysis-dependent plasma terminal free BPA half-life of several tens of hours. These findings suggest that although the high fetal to maternal clearance of free BPA protects the fetus from transient increases in free BPA plasma concentrations associated with maternal BPA intake, low but sustained basal free BPA concentrations are maintained in the fetus through BPA conjugation-deconjugation cycling. The potential health implications of these low but sustained basal concentrations of free BPA in fetal plasma should be addressed especially when considering time-dependent effects. PMID:26540084

  20. 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.

  1. Electrospray LC-MS method with solid-phase extraction for accurate determination of morphine-, codeine-, and ethylmorphine-glucuronides and 6-acetylmorphine in urine.

    PubMed

    Svensson, J-O; Andersson, M; Gustavsson, E; Beck, O

    2007-03-01

    A method for the identification and quantification of morphine-3-glucuronide, codeine-6-glucuronide, ethylmorphine-6-glucuronide, and 6-acetylmorphine in human urine based on solid-phase extraction (SPE) and electrospray ionization liquid chromatography-mass spectrometry (LC-MS) was validated for use as a confirmation procedure in combination with immunochemical screening for opiates. Three deuterium-labelled analogues were used as internal standards: morphine-3-glucuronide-d3, codeine-d3, and 6-acetylmorphine-d3. Fifty-microliter aliquots of urine were prepared by SPE using 30-mg Oasis HLB cartridges. The chromatographic system consisted of a 2.0 x 100-mm C18 column and the gradient elution buffers used acetonitrile and 25 mmol/L formic acid. The protonated molecular ions were monitored in the selected ion monitoring mode together with one qualifier ion for each analyte. The interassay variability was less than 10% at the reporting limit 30 ng/mL for 6-acetylmorphine and 300 ng/mL for the other analytes. The method was validated by comparison with a reference gas chromatographic (GC)-MS method using authentic urine samples. The two methods agreed completely regarding identified analytes, and for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by GC-MS. This result was to be expected because the free compounds are not measured with the LC-MS method. This study concludes that the presented LC-MS method is robust and reliable, and suitable for use as a confirmation method in clinical urine drug testing for opiates. PMID:17536742

  2. Autism and Phthalate Metabolite Glucuronidation

    ERIC Educational Resources Information Center

    Stein, T. Peter; 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…

  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. 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)

  5. 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

    ... recent previous determination for the 2012 amount in the Federal Register on December 30, 2011 (76 FR... Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports AGENCY: United States... is equal to 7 percent of the U.S. domestic market for fuel ethyl alcohol during the 12-month...

  6. Involvement of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 in ethanol glucuronidation, and interactions with common drugs of abuse.

    PubMed

    Al Saabi, Alaa; Allorge, Delphine; Sauvage, François-Ludovic; Tournel, Gilles; Gaulier, Jean-Michel; Marquet, Pierre; Picard, Nicolas

    2013-03-01

    Ethyl glucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Activities of human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as of 12 major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol, and cannabidiol (5, 10, 15 mg/l) with ethanol (1.15, 4.6, 11.5 g/l; i.e., 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Ethanol glucuronidation intrinsic clearance (Cl(int)) was 4 and 12.7 times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6, and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17 and 33% of HLM Cl(int), respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentration-dependent manner, whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner (IC(50) = 1.17 mg/l; inhibition constant (K(i)) = 3.1 mg/l). UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation. PMID:23230132

  7. 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

  8. 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

    ... its notice instituting this investigation in the Federal Register of March 21, 1990 (55 FR 10512), and..., 2010 (75 FR 82069). By order of the Commission. James R. Holbein, Secretary. BILLING CODE 7020-02-P ... Ethyl Alcohol for Fuel Use: Determination of the Base Quantity of Imports AGENCY: United...

  9. Stable knock-down of efflux transporters leads to reduced glucuronidation in UGT1A1-overexpressing HeLa cells: the evidence for glucuronidation-transport interplay.

    PubMed

    Zhang, Xingwang; Dong, Dong; Wang, Huailing; Ma, Zhiguo; Wang, Yifei; Wu, Baojian

    2015-04-01

    Efflux of glucuronide is facilitated by the membrane transporters including BCRP and MRPs. In this study, we aimed to determine the effects of transporter expression on glucuronide efflux and cellular glucuronidation. Single efflux transporter (i.e., BCRP, MRP1, MRP3, or MRP4) was stably knocked-down in UGT1A1-overexpressing HeLa cells. Knock-down of transporters was performed by stable transfection of short-hairpin RNA (shRNA) using lentiviral vectors. Glucuronidation and glucuronide transport in the cells were characterized using three different aglycones (i.e., genistein, apigenin, and emodin) with distinct metabolic activities. BCRP knock-down resulted in significant reductions in excretion of glucuronides (42.9% for genistein glucuronide (GG), 21.1% for apigenin glucuronide (AG) , and 33.7% for emodin glucuronide (EG); p < 0.01) and in cellular glucuronidation (38.3% for genistein, 38.6% for apigenin, and 34.7% for emodin; p < 0.01). Knock-down of a MRP transporter led to substantial decreases in excretion of GG (32.3% for MRP1, 36.7% for MRP3, and 36.6% for MRP4; p < 0.01) and AG (59.3% for MRP1, 24.7% for MRP3, and 34.1% for MRP4; p < 0.01). Also, cellular glucuronidation of genistein (38.3% for MRP1, 32.3% for MRP3, and 31.1% for MRP4; p < 0.01) and apigenin (40.6% for MRP1, 32.4% for MRP3, and 34.6% for MRP4; p < 0.001) was markedly suppressed. By contrast, silencing of MRPs did not cause any changes in either excretion of EG or cellular glucuronidation of emodin. In conclusion, cellular glucuronidation was significantly altered by decreasing expression of efflux transporters, revealing a strong interplay of glucuronidation with efflux transport. PMID:25741749

  10. 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

  11. Determination of ?- and ?-boldenone sulfate, glucuronide and free forms, and androstadienedione in bovine urine using immunoaffinity columns clean-up and liquid chromatography tandem mass spectrometry analysis.

    PubMed

    Chiesa, Luca; Pavlovic, Radmila; Dusi, Guglielmo; Pasquale, Elisa; Casati, Alessio; Panseri, Sara; Arioli, Francesco

    2015-01-01

    The debate about the origins of boldenone in bovine urine is ongoing for two decades in Europe. Despite the fact that its use as a growth promoter has been banned in the European Union (EU) since 1981, its detection in bovine urine, in the form of ?-boldenone conjugate, is considered fully compliant up to 2 ng mL(-1). The conjugated form of ?-boldenone must be absent. In recent years, the literature about boldenone has focused on the identification of biomarkers that can indicate an illicit treatment. ?-boldenone sulfate is a candidate molecule, even if the only studies currently available have taken place in small populations. In this study, a method for the determination of sulfate and glucuronate conjugates of ?-boldenone was developed and validated according to the European Commission Decision 2002/657/EC and applied to ?-boldenone sulfate and glucuronide, ?- and ?-boldenone free forms and androstadienedione (ADD), too. The clean-up with immunoaffinity columns enabled the direct determination of the conjugates and free forms and allowed specific and sensitive analyses of urine samples randomly selected to verify this method. The decision limits (CC?) ranged between 0.07 and 0.08 ng mL(-1), the detection capabilities (CC?) between 0.08 and 0.1 ng mL(-1). Recovery was higher than 92% for all the analytes. Intra-day repeatability was between 5.8% and 17.2%, and inter-day repeatability was between 6.0% and 21.8% for the studied free and conjugated forms. This method has been developed as a powerful tool with the aim to study the origin of boldenone in a trial on a significant number of animals. PMID:25281088

  12. Detection and quantitative determination of diethylene glycol in ethyl alcohol using gamma- ray spectroscopy.

    PubMed

    Udagani, Chikkappa; Ramesh, Thimmasandra Narayan

    2015-08-01

    Determination of the toxic diethylene glycol contamination in ethyl alcohol demands a rapid, accurate and reliable method. Diethylene glycol (DEG) ingestion, accidental or intentional, can lead to death. Clinical and analytical methods used to detect diethylene glycol in alcohol require several hours to days due to tedious instrument handling and measurements. Enzymatic assays face difficulty due to analytic problems. As an alternative method of data analysis, we have used ?-ray spectroscopic method to estimate the diethylene glycol contamination in alcohol by monitoring the variation in the linear and mass attenuation coefficients. This method is simple, robust, portable and can provide reliable and quantitative information about the ethyl alcohol adulterated with diethylene glycol which is of broader interest to society. PMID:26243958

  13. Gas chromatographic method for the determination of residual monomers, 2-(acryloyloxy)ethyl isocyanate and 2-(methacryloyloxy)ethyl isocyanate, as curing agents in an ultraviolet curable adhesive.

    PubMed

    Kim, Byoung-Hyoun; Kim, Nosun; Moon, Dong Cheul

    2014-02-01

    A gas chromatographic method is described for the determination of residual 2-(acryloyloxy)ethyl isocyanate (AOI) and 2-(methacryloyloxy)ethyl isocyanate (MOI) as curing agents in an ultraviolet curable adhesive. Pre-column derivatization was employed in the determination of AOI and MOI as a means of enhancing the response of the flame ionization detector. Urethane derivatives of AOI and MOI were derived using methanol for 30 min at room temperature. The accuracies (n = 5, three concentration levels) were in the range of 113.4 to 126.7%, and precisions (n = 5, three concentration levels) were in the range of 0.8 to 4.3% for AOI-OMe. Furthermore, the accuracies were in the range of 79.5 to 108.6% and the precisions were in the range of 1.0 to 2.4% for MOI-OMe. The correlation coefficients of six calibration standards were all greater than 0.9999 for AOI-OMe and greater than 0.9998 for MOI-OMe over the range from 10 to 100 µg/mL. PMID:23357043

  14. Validation of an Efficient Method for the Determination of Pesticide Residues in Fruits and Vegetables Using Ethyl Acetate for Extraction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, a version of the “quick, easy, cheap, effective, rugged, and safe” (QuEChERS) method was modified to use ethyl acetate (EtOAc) rather than acetonitrile (MeCN) for extraction in the determination of multiple pesticide residues in fruits and vegetables. EtOAc is better suited than MeCN...

  15. Ultrasound-assisted emulsification-microextraction for the sensitive determination of ethyl carbamate in alcoholic beverages.

    PubMed

    Liao, Qie Gen; Li, Wei Hong; Luo, Lin Guang

    2013-08-01

    A method based on ultrasound-assisted emulsification-microextraction (USAEME) was proposed in this contribution for the determination of ethyl carbamate (EC) in alcoholic beverages using gas chromatography coupled to triple quadrupole mass spectrometry. To achieve the determination of EC in alcoholic beverages, the influences on the extraction efficiency of type and volume of extraction solvent, temperature, ionic strength, alcohol content, and extraction time were studied, once the extraction solvent had been selected. The optimized conditions were 200.0 ?L of chloroform at 30 °C during 5 min with 15% (m/v) sodium chloride addition. The detection limit, relative standard deviations, linear range, and recoveries under the optimized conditions were 0.03 ?g L(-1), 4.2-6.1%, 0.1-50.0 ?g L(-1), and 80.5-87.9%, respectively. Moreover, the feasibility of the present method was also validated by real samples. To the best of our knowledge, this is the first time that USAEME has been applied to determine a strongly hydrophilic compound in alcoholic beverages. PMID:23820951

  16. In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin.

    PubMed

    Fisher, M B; Campanale, K; Ackermann, B L; VandenBranden, M; Wrighton, S A

    2000-05-01

    The UDP-glucuronosyltransferases (UGTs) are a superfamily of membrane-bound enzymes whose active site is localized inside the endoplasmic reticulum. Glucuronidation using human liver microsomes has traditionally involved disruption of the membrane barrier, usually by detergent treatment, to attain maximal enzyme activity. The goals of the current work were to develop a universal method to glucuronidate xenobiotic substrates using microsomes, and to apply this method to sequential oxidation-glucuronidation reactions. Three assays of UGT catalytic activity estradiol-3-glucuronidation, acetaminophen-O-glucuronidation, and morphine-3-glucuronidation, which are relatively selective probes for human UGT1A1, 1A6, and 2B7 isoforms, respectively, were developed. Treatment of microsomes with the pore-forming peptide alamethicin (50 microg/mg protein) resulted in conjugation rates 2 to 3 times the rates observed with untreated microsomes. Addition of physiological concentrations of Mg(2+) to the alamethicin-treated microsomes yielded rates that were 4 to 7 times the rates with untreated microsomes. Optimized assay conditions were found not to detrimentally affect cytochrome P450 activity as determined by effects on testosterone 6beta-hydroxylation and 7-ethoxycoumarin deethylation. Formation of estradiol-3-glucuronide displayed atypical kinetics, and data best fit the Hill equation, yielding apparent kinetic parameters of K(m)(app) = 0.017 mM, V(max)(app) = 0.4 nmol/mg/min, and n = 1.8. Formation of acetaminophen-O-glucuronide also best fit the Hill equation, with K(m)(app) = 4 mM, V(max)(app) = 1.5 nmol/mg/min, and n = 1.4. Alternatively, morphine-3-glucuronide formation displayed Michaelis-Menten kinetics, with K(m)(app) = 2 mM and V(max)(app) = 2. 5 nmol/mg/min. Finally, alamethicin treatment of microsomes was found to be effective in facilitating the sequential oxidation-glucuronidation of 7-ethoxycoumarin. PMID:10772635

  17. Simultaneous determination of baicalin, oroxylin A-7-O-glucuronide and wogonoside in rat plasma by UPLC-DAD and its application in pharmacokinetics of pure baicalin, Radix Scutellariae and Yinhuang granule.

    PubMed

    Chen, Hui; Li, Zheng; Li, Yin-Jie; Wu, Xiao-Wen; Wang, Shi-Rui; Chen, Kai; Zheng, Xiao-Xiao; Du, Qian; Tang, Dao-Quan

    2015-12-01

    A novel UPLC-DAD method was developed and validated for the simultaneous determination of baicalin (baicalein-7-glucuronide, BG), oroxylin A-7-O-glucuronide (OAG) and wogonoside (WG) in rat plasma using rutin as the internal standard. Plasma samples were precipitated using acetonitrile containing 0.1% formic acid. Separation was performed on an Agilent Eclipse Plus C18 column (2.1 × 50 mm, 1.8 µm) using gradient acetonitrile and 0.2% formic acid water solution as mobile phase. The flow-rate was set at 0.4 mL/min and the eluate was detected at 275 nm. The method was linear over the ranges of 0.075-17.50, 0.050-12.60 and 0.056-14.10 µg/mL for BG, OAG and WG, respectively. The intra- and inter-day precisions were respectively <4.8% and 6.4%. All of the limits of detection of three analytes in rat plasma were 0.01 µg/mL, whereas the limits of quantification were, respectively, 0.035, 0.025 and, 0.025 µg/mL. This assay has been successfully applied to pharmacokinetics of BG, OAG and WG in rats after oral administration of Yinhuang granule (YHG) and comparative pharmacokinetics of BG in rats following oral administration of the pure BG, Radix Scutellariae (RS) or YHG. We speculate that some co-existing ingredients in RS or YHG may increase the absorption and elimination of BG in rat. This work may be helpful for the quality control of Yinhuang granule. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26018907

  18. LC-MS/MS method for the simultaneous determination of ethyl gallate and its major metabolite in rat plasma.

    PubMed

    Gao, Shouhong; Zhan, Qin; Li, Jingxian; Yang, Qi; Li, Xia; Chen, Wansheng; Sun, Lianna

    2010-05-01

    A simple, rapid and sensitive liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed and validated for the determination of ethyl gallate, a pharmacologically active constituent isolated from Lagerstroemia speciosa (Linn.) Pers. This method was used to examine the pharmacokinetics of ethyl gallate and its major metabolite gallic acid in rat plasma using propyl gallate as an internal standard. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a Zorbax SB-C(18) column (3.5 microm, 2.1 x 50 mm) with an isocratic mobile phase consisted of methanol-acetonitrile-10 mM ammonium acetate (10 : 25 : 65, v/v/v) containing 0.1% formic acid at a flow rate of 0.25 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple-reaction monitoring mode using the electrospray ionization technique in negative mode. The lower limits of quantification of gallic acid and ethyl gallate of the method were 0.5 and 1.0 ng/mL. The intra-day and inter-day accuracy and precision of the assay were less than 8.0%. This method has been applied successfully to a pharmacokinetic study involving the intragastric administration of ethyl gallate to rats. PMID:19688816

  19. Gas chromatographic-mass spectrometric assay for 6-hydroxymelatonin sulfate and 6-hydroxymelatonin glucuronide in urine

    SciTech Connect

    Francis, P.L.; Leone, A.M.; Young, I.M.; Stovell, P.; Silman, R.E.

    1987-04-01

    Circulating melatonin is hydroxylated to 6-hydroxymelatonin and excreted in urine as the sulfate and glucuronide conjugates. We extracted these two compounds from urine by using octadecylsilane-bonded silica cartridges to eliminate most of the urea and electrolytes, and silica cartridges to separate the sulfate and glucuronide conjugates. After hydrolyzing the separated conjugates enzymically, we determined the free hydroxymelatonin by gas chromatography-mass spectrometry. Though recoveries were low and variable, we were able to quantify the analyte in the original sample by adding deuterated sulfate and glucuronide conjugates to the urines before extraction.

  20. The Determination of Pesticidal and Non-Pesticidal Organotin Compounds by in situ Ethylation and Capillary Gas Chromatography with Pulsed Flame Photometric Detection

    EPA Science Inventory

    The concurrent determination of pesticidal and non-pesticidal organotin compounds in several water matrices, using a simultaneous in situ ethylation and liquid-liquid extraction followed by splitless injection mode capillary gas chromatography with pulsed flame photometric detect...

  1. The Determination of Pesticidal and Non-Pesticidal Organotin Compounds in Water Matrices by in situ Ethylation and Gas Chromatography with Pulsed Flame Photometric Detection

    EPA Science Inventory

    The concurrent determination of pesticidal and non-pesticidal organotin compounds in several water matrices, using a simultaneous in situ ethylation and liquid-liquid extraction followed by splitless injection mode capillary gas chromatography with pulsed flame photometric detect...

  2. The chemiluminescence determination of 2-chloroethyl ethyl sulfide using luminol-AgNO3-silver nanoparticles system.

    PubMed

    Maddah, Bozorgmehr; Shamsi, Javad; Barsang, Mehran Jam; Rahimi-Nasrabadi, Mehdi

    2015-05-01

    A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1ngmL(-1), with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6×10(-6)ngmL(-1). Also, the relative standard deviation (RSD, n=5) for determination of 2-CEES (0.50ngmL(-1)) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples. PMID:25703367

  3. The chemiluminescence determination of 2-chloroethyl ethyl sulfide using luminol-AgNO3-silver nanoparticles system

    NASA Astrophysics Data System (ADS)

    Maddah, Bozorgmehr; Shamsi, Javad; Barsang, Mehran Jam; Rahimi-Nasrabadi, Mehdi

    2015-05-01

    A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1 ng mL-1, with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6 × 10-6 ng mL-1. Also, the relative standard deviation (RSD, n = 5) for determination of 2-CEES (0.50 ng mL-1) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples.

  4. [Simultaneous determination of ethyl carbamate and chloropropanols in flavorings by gas chromatography-triple quadrupole tandem mass spectrometry].

    PubMed

    Xu, Xiaomin; He, Huali; Ruan, Yudi; Huang, Baifen; Zhang, Jingshun; Cai, Zengxuan; Ren, Yiping

    2013-11-01

    A simultaneous determination method for ethyl carbamate (EC) and chloropropanols (3-monochloropropane-1, 2-diol (3-MCPD) and 2-monochloropropane-1, 3-diol (2-MCPD)) in flavorings was developed by gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After spiked with internal standard, the sample was extracted by matrix solid-phase dispersion extraction technique with an Extrelut NT column. Hexane was used to wash the fat soluble matrix interferences and then an ethyl acetate-ethyl ether (20: 80, v/v) mixture was added to elute the analytes. The concentrated extract was detected by GC-MS/MS in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) were 2, 5 and 5 microg/kg for EC, 3-MCPD and 2-MCPD, respectively. The linear ranges were 5 - 1 000 microg/kg (r = 0.9997), 10-1000 microg/kg (r = 0.999 1) and 10-1000 microg/kg (r = 0.999 5) for EC, 3-MCPD and 2-MCPD, respectively. In soy sauce, yellow rice wine, salami sauce and flavoring of instant noodle matrices, the recoveries (RSDs, n = 7) in MRM mode at the levels of 20, 100 and 400 microg/kg were 87.7%-104% (4.3%-10.7%), 90.1%-109% (2.6%-10.2%), and 90.9%-103% (3.0%-9.5%), respectively. EC, 3-MCPD and 2-MCPD were found in some real samples of the soy sauce, wine and flavoring of instant noodle. EC or 3-MCPD was found in some of the salami samples. The method is accurate, fast and suitable for the simultaneous determination of EC, 3-MCPD and 2-MCPD in flavorings. PMID:24558851

  5. Comparing the glucuronidation capacity of the feline liver with substrate-specific glucuronidation in dogs.

    PubMed

    van Beusekom, C D; Fink-Gremmels, J; Schrickx, J A

    2014-02-01

    This study aimed to assess the overall glucuronidation capacity of cats, using prototypic substrates identified for human UDP-glucuronosyltransferases (UGTs). To this end, Michaelis-Menten kinetics were established for the substrates using feline hepatic microsomal fractions, and results were compared with similar experiments carried out with dog liver microsomes. Cats are known for their low capacity of glucuronide formation, and UGT1A6 was found to be a pseudogene. However, functional studies with typical substrates were not performed and knowledge of the enzymology and genetics of other glucuronidation enzymes in felidae is lacking. The results of this study showed extremely low formation of naphthol-1-glucuronide (1.7 ± 0.4 nmol/mg protein/min), estradiol-17-glucuronide (<0.7 nmol/mg protein/min), and morphine-3-glucuronide (0.2 ± 0.03 nmol/mg protein/min), suggesting a lack of functional UGT1A6 and UGT2B7 homologues in the cat's liver. Dog liver microsomes were producing these glucuronides in much higher amounts. Glucuronide capacity was present for the substrates 17?-estradiol (estradiol-3-glucuronide, 2.9 ± 0.2 nmol/mg protein/min) and 4-methylumbelliferone (31.3 ± 3.3 nmol/mg protein/min), assuming that cats have functional homologue enzymes to at least the human UGT1A1 and probably other UGT1A isozymes. This implies that for new drugs, glucuronidation capacity has to be investigated on a substance-to-substance base. Knowledge of the glucuronidation rate of a drug provides the basis for pharmacokinetic modeling and as a result proper dosage regimens can be established to avoid undesirable drug toxicity in cats. PMID:23888985

  6. Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea.

    PubMed

    Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-Il; Lee, Jee-Yeon; Yoon, Hae Jung; Koh, Eunmi

    2015-09-01

    Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods. PMID:26483888

  7. Determination of Ethyl Carbamate in Alcoholic Beverages and Fermented Foods Sold in Korea

    PubMed Central

    Ryu, Dayeon; Choi, Bogyoung; Kim, Eunjoo; Park, Seri; Paeng, Hwijin; Kim, Cho-il; Lee, Jee-yeon; Yoon, Hae Jung

    2015-01-01

    Ethyl carbamate (EC) classified as a probable human carcinogen (Group 2A) is naturally formed in alcoholic beverages and fermented foods during fermentation process and/or during storage. The objective of this study was to analyze EC in 34 food items including 14 alcoholic beverages and 20 fermented foods sold in Korea. Each food was collected from 18 supermarkets in 9 metropolitan cities in Korea, and then made into composite. According to food composition and alcohol content, samples were divided into four matrices such as apple juice, milk, Soju (liquor containing about 20% alcohol), and rice porridge. The maximum EC value of 151.06 µg/kg was found in Maesilju (liquor made from Maesil and Soju). Whisky and Bokbunjaju (Korean black raspberry wine) contained 9.90 µg/kg and 6.30 µg/kg, respectively. EC was not detected in other alcoholic beverages. Of 20 fermented foods, Japanese-style soy sauce had highest level of 15.59 µg/kg and traditional one contained 4.18 µg/kg. Soybean paste had 1.18 µg/kg, however, EC was not found in other fermented foods. PMID:26483888

  8. A new chemiluminescence method for determination of clonazepam and diazepam based on 1-Ethyl-3-Methylimidazolium Ethylsulfate/copper as catalyst

    NASA Astrophysics Data System (ADS)

    Chaichi, M. J.; Alijanpour, S. O.

    2014-01-01

    A novel chemiluminescence (CL) reaction, Benzodiazepines-H2O2-1-Ethyl-3-Methylimidazolium Ethylsulfate/copper, for determination of clonazepam and diazepam at nanogram per milliliter level in batch-type system have been described. The method relies on the catalytic effect of 1-Ethyl-3-Methylimidazolium Ethylsulfate/copper on the chemiluminescence reaction of Benzodiazepines, the oxidation of Benzodiazepines with hydrogen peroxide in natural medium. The influences of various experimental parameters such as solution pH, the ratio of 1-Ethyl-3 Methylimidazolium ethylsulfate concentration to copper ion, the type of buffer and the concentration of CL reagents were investigated. Under the optimum condition, the proposed method was satisfactorily applied for the determination of these drugs in tablets and urine without the interference of their potential impurities.

  9. 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

  10. 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

    ... International Trade Commission. ACTION: Notice of determination. SUMMARY: Section 423(c) of the Tax Reform Act... administration of the law is the greater of 60 million gallons or 7 percent of U.S. consumption, as determined by... March 21, 1990 (55 FR 10512), and published its most recent previous determination for the 2010...

  11. 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...

  12. Systematic Studies of Sulfation and Glucuronidation of 12 Flavonoids in the Mouse Liver S9 Fraction Reveals both Unique and Shared Positional Preferences

    PubMed Central

    Tang, Lan; Zhou, Juan; Yang, Cai-Hua; Xia, Bi-Jun; Hu, Ming; Liu, Zhong-Qiu

    2012-01-01

    Sulfation and glucuronidation are the principal metabolic pathways of flavonoids, and extensive phase II metabolism is the main reason for their poor bioavailabilities. The purpose of this study was to compare the similarities and differences in the positional preference of glucuronidation versus sulfation in the mouse liver S9 fraction. The conjugating rates of seven mono-hydroxyflavones (HFs) (i.e., 2’-, 3’-, 4’-, 3-, 5-, 6-, and 7-HF), and five di-hydroxyflavones (diHFs), (i.e., 6,7-, 4’,7-, 3,7-, 5,7-, and 3,4’-diHF) were determined in three separate enzymatic reaction systems: (A) sulfation only, (B) glucuronidation only, or (C) simultaneous sulfation and glucuronidation (i.e., Sult-Ugt co-reaction). In general, glucuronidation rates were much faster than the sulfation rates. Among the HFs, 7-HF was the best substrate for both conjugation reactions, whereas 3-HF was rapidly glucuronidated but was not sulfated. As a result, the rank order of sulfation was very different from that of glucuronidation. Among the diHFs, regiospecific glucuronidation was limited to 7-OH and 3-OH positions, whereas regiospecific sulfation was limited to 7-OH and 4’-OH positions. Other positions (i.e., 6-OH and 5-OH) in diHFs were not conjugated. The positional preferences were essentially maintained in a Sult-Ugt co-reaction system, although sulfation was surprisingly enhanced. Lastly, sulfation and glucuronidation displayed different regiospecific- and substrate-dependent characteristics. In conclusion, glucuronidation and sulfation shared the same preference for 7-OH position (of flavonoids) but displayed unique preference in other positions in that glucuronidation preferred 3-OH position whereas sulfation preferred 4’-OH position. PMID:22352802

  13. Determination of Ethyl Carbamate in Chinese Yellow Rice Wine by Diatomaceous Earth Extraction and GC/MS Method.

    PubMed

    Wu, Pinggu; Zhang, Liqun; Shen, Xianghong; Wang, Liyuan; Zou, Yan; Zhang, Jing; Tan, Ying; Tang, Jun; Ma, Bingjie; Pan, Xiaodong; Jiang, Wei

    2015-01-01

    A sensitive and rapid analytical method based on alkaline diatomaceous earth extraction followed by GC/MS was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC) in yellow rice wines. The optimal extraction conditions were investigated. With the application of diatomaceous earth extraction, the damage of organic acids to the capillary column was greatly reduced. By using d5-EC as an internal standard for quantitative analysis of EC, the linearity of the calibration curves was good between 10 and 1000 ng/mL. The LOD and LOQ were 1.7 and 5.0 ?g/kg, respectively. The spiked level of EC was 5.0-300 ?g/kg, and the average recovery of the spikes was between 78.4 and 98.2%, with an RSD between 4.3 and 8.3%. Upon validation by five laboratories when spiked with 50, 100, and 300 ?g/kg, the average respective recoveries were 102.9, 102.2, and 98.7% with a RSD between 0.7 and 8.1%. The validation results demonstrated that the method is fast, simple, selective, and suitable for the determination of EC in yellow rice wines. PMID:26086264

  14. Ethyl acetate

    Integrated Risk Information System (IRIS)

    Ethyl acetate ; CASRN 141 - 78 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  15. Ethyl chloride

    Integrated Risk Information System (IRIS)

    Ethyl chloride ; CASRN 75 - 00 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  16. Ethyl ether

    Integrated Risk Information System (IRIS)

    Ethyl ether ; CASRN 60 - 29 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  17. Icosapent Ethyl

    MedlinePLUS

    Icosapent ethyl is used together with lifestyle changes (diet, weight loss, exercise) to reduce the amount of ... Eat a low-fat, low-cholesterol diet. Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. You can also visit the National Cholesterol ...

  18. Ethyl carbamate

    Integrated Risk Information System (IRIS)

    Ethyl carbamate ; CASRN 51 - 79 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  19. Evaluation of the DNA damaging potential of cannabis cigarette smoke by the determination of acetaldehyde derived N2-ethyl-2'-deoxyguanosine adducts.

    PubMed

    Singh, Rajinder; Sandhu, Jatinderpal; Kaur, Balvinder; Juren, Tina; Steward, William P; Segerbäck, Dan; Farmer, Peter B

    2009-06-01

    Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer. The method required 50 microg of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes. No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development. PMID:19449825

  20. 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

    ...be used to establish the ``base quantity'' of imports of fuel...CBERA-beneficiary countries. The base quantity to be used by U.S...been rounded). Therefore, the base quantity for 2011 should be 875...determination is based on official data of the U.S. Department...

  1. 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

    ...be used to establish the ``base quantity'' of imports of fuel...CBERA-beneficiary countries. The base quantity to be used by U.S...been rounded). Therefore, the base quantity for 2012 should be 906...determination is based on official data of the U.S. Department...

  2. 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

  3. Determination of benazolin-ethyl residues in soil and rape seed by SPE clean-up and GC with electron capture detection.

    PubMed

    Liu, Xiaolu; Yang, Tao; Hu, Jiye

    2013-01-01

    A method has been developed and established for residue determination of benazolin-ethyl in soil and rape seed samples by gas chromatography with electron capture detection (GC-ECD). Limits of quantification of the method are 0.005 mg/kg for both soil and rape seed, which are sufficiently below the maximum residue limit, and the limit of detection is 0.0023 ng. The average recoveries of the analyte range from 85.89 to 105.84% with relative standard deviations (coefficient of variation) less than 5.53% at the three spike levels (0.005, 0.1 and 0.5 mg/kg). The half-life of benazolin-ethyl in soil from the experimental field is 4.62 days. The final residues of benazolin-ethyl in soil and rape seed samples are lower than 0.005 mg/kg at harvest time. Direct confirmation of the analyte in real samples is achieved by GC-mass spectrometry. It is demonstrated that the proposed method is simple, rapid and efficient, and reliable to detect benazolin-ethyl residues in soil and rape seed samples. PMID:22718745

  4. In Vitro Glucuronidation of 2,2-Bis(bromomethyl)-1,3-propanediol by Microsomes and Hepatocytes from Rats and Humans

    PubMed Central

    Rad, Golriz; Hoehle, Simone I.; Kuester, Robert K.

    2010-01-01

    2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant used in unsaturated polyester resins. In a 2-year bioassay BMP was shown to be a multisite carcinogen in rats and mice. Because glucuronidation is the key metabolic transformation of BMP by rats, in this study the in vitro hepatic glucuronidation of BMP was compared across several species. In addition, the glucuronidation activities of human intestinal microsomes and specific human hepatic UDP-glucuronosyltransferase (UGT) enzymes for BMP were determined. To explore other possible routes of metabolism for BMP, studies were conducted with rat and human hepatocytes. Incubation of hepatic microsomes with BMP in the presence of UDP-glucuronic acid resulted in the formation of a BMP monoglucuronide. The order of hepatic microsomal glucuronidation activity of BMP was rats, mice ? hamsters > monkeys ? humans. The rate of glucuronidation by rat hepatic microsomes was 90-fold greater than that of human hepatic microsomes. Human intestinal microsomes converted BMP to BMP glucuronide at a rate even lower than that of human hepatic microsomes. Among the human UGT enzymes tested, only UGT2B7 had detectable glucuronidation activity for BMP. BMP monoglucuronide was the only metabolite formed when BMP was incubated with suspensions of freshly isolated hepatocytes from male F-344 rats or with cryopreserved human hepatocytes. Glucuronidation of BMP in human hepatocytes was extremely low. Overall, the results support in vivo studies in rats in which BMP glucuronide was the only metabolite found. The poor glucuronidation capacity of humans for BMP suggests that the pharmacokinetic profile of BMP in humans will be dramatically different from that of rodents. PMID:20200232

  5. 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

  6. Disruption of thyroid hormone homeostasis in Ugt1a-deficient Gunn rats by microsomal enzyme inducers is not due to enhanced thyroxine glucuronidation?

    PubMed Central

    Richardson, Terrilyn A.; Klaassen, Curtis D.

    2011-01-01

    Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) are thought to increase glucuronidation of thyroxine (T4), thus reducing serum T4, and subsequently increasing thyroid stimulating hormone (TSH). Ugt1a1 and Ugt1a6 mediate T4 glucuronidation. Therefore, this experiment determined the involvement of Ugt1a enzymes in increased T4 glucuronidation, decreased serum T4, and increased TSH after MEI treatment. Male Wistar and Ugt1a-deficient Wistar (Gunn) rats were fed a control diet or diet containing pregnenolone-16?-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum T4, triiodothyronine (T3), and TSH concentrations, hepatic T4/T3 glucuronidation, and thyroid histology and follicular cell proliferation were investigated. PCN, 3-MC, and PCB treatments decreased serum T4, whereas serum T3 was maintained in both Gunn and Wistar rats (except for PCB treatment). TSH was increased in Wistar and Gunn rats after PCN (130 and 277%) or PCB treatment (72 and 60%). T4 glucuronidation in Wistar rats was increased after PCN (298%), 3-MC (85%), and PCB (450%), but was extremely low in Gunn rats, and unchanged after MEI. T3 glucuronidation was increased after PCN (121%) or PCB (58%) in Wistar rats, but only PCN increased T3 glucuronidation in Gunn rats (43%). PCN treatment induced thyroid morphological changes and increased follicular cell proliferation in both strains. These data demonstrate that T4 glucuronidation cannot be increased in Ugt1a-deficient Gunn rats. Thus, the decrease in serum T4, increase in TSH, and increase in thyroid cell proliferation after MEI are not dependent on increased T4 glucuronidation, and cannot be attributed to Ugt1a enzymes. PMID:20655938

  7. Characterization of chrysin glucuronidation in UGT1A1-overexpressing HeLa cells: elucidating the transporters responsible for efflux of glucuronide.

    PubMed

    Quan, Enxi; Wang, Huailing; Dong, Dong; Zhang, Xingwang; Wu, Baojian

    2015-04-01

    Active transport of glucuronide out of cells is a critical process in elimination of drugs via the glucuronidation pathway. Here, HeLa cells were stably transfected with UGT1A1 and the contributions of BCRP and MRP family transporters to the cellular efflux of chrysin glucuronide (CG) were determined. The cDNA of UGT1A1 was introduced into HeLa cells using the lentiviral transfection method. The modified cells were functional in generation of the glucuronide from chrysin. Ko143 at 10-20 ?M (a dual inhibitor of BCRP and UGT1A1) caused a marked decrease (51.3%-59.7%, P < 0.01) in the excretion rate and efflux clearance of CG. Likewise, MK-571 at 5-20 ?M (an inhibitor of MRPs but an activator of UGT1A1) resulted in a significant reduction in the excretion rate (18.2%-64.0%, P < 0.01) and efflux clearance (37.0%-90.2%, P < 0.001). By contrast, dipyridamole and leukotriene C4 showed no inhibitory effects on CG excretion. The chemical inhibition indicated that excretion of CG was contributed by the MRP family transporters, whereas the role of BCRP was unclear. Furthermore, short hairpin RNA-mediated silencing of a target transporter led to a marked reduction in the excretion rate of CG (38.6% for BCRP, 39.3% for MRP1, 36.4% for MRP3, and 28.7% for MRP4; P < 0.01). Transporter silencing also led to substantial decreases in the efflux clearance (44.7% for BCRP, 60.4% for MRP1, 36.7% for MRP3, and 28.7% for MRP4; P < 0.01). The gene silencing results suggested that BCRP, MRP1, MRP3, and MRP4 were significant contributors to excretion of CG. PMID:25595598

  8. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate....

  9. 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

  10. Optimization of an analytical method for determining organotin compounds in fish tissue by base-hydrolysis pretreatment and simultaneous ethylation-extraction procedures.

    PubMed

    Tang, Chuan-Ho; Wang, Wei-Hsien

    2007-01-01

    To determine butyl- and phenyl-tins in fish muscle, a method including base digestion pretreatment, followed by a simultaneous ethylation-extraction procedure and gas chromatograph-flame photometric detector (GC-FPD) analysis is outlined. Key parameters that influence analyte recovery were investigated and optimized. A solution of 3% (w/v) potassium hydroxide (KOH) and 1 h digestion time at 60 degrees C were chosen in the base digestion step, to ensure complete solubilization of fish muscle and the decomposition of organotins was found to be insignificant. We found that the ratio of fish muscle/reaction solution should not exceed 0.2 g (dry weight) per 100 mL in order to avoid the matrix effect caused by the binding of hydrolyzed fish tissue with organotin ions. Ethylation of organotins were conducted at pH 6-7 with a 1% (w/v) sodium tetraethylborate (NaBEt(4)) solution for 1 h. This simple and timesaving procedure should be able to be applied to the routine analysis of organotins in other bio-tissues. PMID:17386465

  11. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... prescribed for polyethylene in § 177.1520. (1) Specifications—(i) Infrared identification. Ethylene-ethyl acrylate copolymers can be identified by their characteristic infrared spectra. (ii) Quantitative determination of ethyl acrylate content. The ethyl acrylate can be determined by the infrared spectra. Prepare...

  12. Simultaneous determination of organotin compounds in textiles by gas chromatography-flame photometry following liquid/liquid partitioning with tert-butyl ethyl ether after reflux-extraction.

    PubMed

    Hamasaki, Tetsuo

    2013-10-15

    A rapid and relatively clean method for determining six organotin compounds (OtC) in textile goods with a gas chromatograph equipped with a conventional flame photometric detector (GC-FPD) has been developed. After the reflux-extraction to use methanol containing 1% (v/v) of hydrochloric acid, five hydrophobic OtC (e.g. tributyltin: TBT) and slightly less hydrophobic dibutyltin (DBT) could be drawn out through partitioning between the methanolic buffer solution and tert-butyl ethyl ether instead of hazardous dichloromethane, of which usage is provided by the official-methods notified in Japan, and following the ethylation procedure to use sodium tetraethylborate, the OtC were determined with the GC-FPD. The recoveries of DBT, TBT, tetrabutyltin, triphenyltin, dioctyltin, and trioctyltin from textile products (cloth diaper, socks, and undershirt) were 60-77, 89-98, 86-94, 71-78, 85-109, and 70-79% respectively, and their coefficients of variation were 2.5-16.5%. Calibration curves for OtC were linear (0.01-0.20 ?g as Sn mL(-1)), and the correlation coefficients were 0.9922-1.0000. Their detection limits were estimated to be 2.7-9.7 n gas Sn g(-1). These data suggested that this method would be applicable to their simultaneous determination. Five retailed textile goods were analyzed by this proposed method, and 0.013-0.65 µg as Sn g(-1) of OtC (e.g. DBT) were determined in three. Moreover, a possibility that various OtC including non-targeted species in textile would be specifically detected by applying the studying speciation-technique of controlling signal intensity-flame fuel gas pressures of the GC-FPD was found. PMID:24054605

  13. Identification of sulfur interferences during organotin determination in harbour sediment samples by sodium tetraethyl borate ethylation and gas chromatography-pulsed flame photometric detection.

    PubMed

    Bravo, Manuel; Lespes, Gäetane; De Gregori, Ida; Pinochet, Hugo; Potin-Gautier, Martine

    2004-08-13

    Because of the high toxicity of organotin compounds and the current regulation about their applications, analytical method usable in routine analysis is required. A speciation procedure based on NaBEt4 ethylation and GC-PFPD analysis has shown to be suitable for the organotin determination. Unfortunately, some matrix effects were observed during the analysis of harbour sediments from Chile. These effects were identified as the alkylation of elemental sulfur and the coelution between the organotin compounds and some dialkylsulfides. The re-optimization of GC parameters and application of solid phase microextraction (SPME) were proposed to solve these analytical problems. Certified reference materials and different harbour sediment samples were analysed in order to evaluate the suitability of the methods for organotin control in complex environment samples. PMID:15387191

  14. Determining the degradation efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS

    PubMed Central

    2012-01-01

    Background The discharge of wastewater that contains high concentrations of reactive dyes is a well-known problem associated with dyestuff activities. In recent years, semiconductor photocatalysis has become more and more attractive and important since it has a great potential to contribute to such environmental problems. One of the most important aspects of environmental photocatalysis is in the selection of semiconductor materials like ZnO and TiO2, which are close to being two of the ideal photocatalysts in several respects. For example, they are relatively inexpensive, and they provide photo-generated holes with high oxidizing power due to their wide band gap energy. In this work, nanostructural ZnO film on the Zn foil of the Alkaline-Manganese Dioxide-Zinc Cell was fabricated to degrade EV dye. The major innovation of this paper is to obtain the degradation mechanism of ethyl violet dyes resulting from the HPLC-PDA-ESI-MS analyses. Results The fabrication of ZnO nanostructures on zinc foils with a simple solution-based corrosion strategy and the synthesis, characterization, application, and implication of Zn would be reported in this study. Other objectives of this research are to identify the reaction intermediates and to understand the detailed degradation mechanism of EV dye, as model compound of triphenylmethane dye, with active Zn metal, by HPLC-ESI-MS and GC-MS. Conclusions ZnO nanostructure/Zn-foils had an excellent potential for future applications on the photocatalytic degradation of the organic dye in the environmental remediation. The intermediates of the degradation process were separated and characterized by the HPLC-PDA-ESI-MS and GC-MS, and twenty-six intermediates were characterized in this study. Based on the variation of the amount of intermediates, possible degradation pathways for the decolorization of dyes are also proposed and discussed. PMID:22748361

  15. Testosterone sulphation and glucuronidation in the human liver: interindividual variability.

    PubMed

    Pacifici, G M; Gucci, A; Giuliani, L

    1997-01-01

    Presystemic sulphation and glucuronidation at OH-C17 limits the bioavailability of testosterone; the aim of this investigation was to describe the variability in testosterone sulphation and glucuronidation rates in the human liver. Liver samples were obtained from 61 women and 40 men of similar age (mean 53 and 55 years, respectively) submitted to surgery. The mean rate of testosterone sulphation was significantly (P = 0.002) higher in men (22.4 pmol/min/mg) than in women (17.5 pmol/min/mg), was not age-dependent, followed bimodal distribution and varied over 7-fold in men and women. There was a weak, but significant negative correlation (r = -0.380; P = 0.003), between the rate of testosterone glucuronidation and age in the liver of women but not in that of men. The mean rate (pmol/min/mg) of testosterone glucuronidation was 155 (men) and 105 (women) (NS) and varied over 20-fold. When the rate of testosterone glucuronidation was expressed on the basis of g liver equivalent, the mean estimates were significantly (P = 0.003) greater in men (3323 pmol/min/g) than in women (1841 pmol/min/g). The present findings are consistent with the view that the hepatic activities of sulphotransferase and glucuronosyltransferase are higher in men than in women and that they vary in the human liver. PMID:9358207

  16. 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

  17. A high throughput assay for the glucuronidation of 7-hydroxy-4-trifluoromethylcoumarin by recombinant human UDP-glucuronosyltransferases and liver microsomes.

    PubMed

    Rahikainen, Tuomas; Häkkinen, Merja R; Finel, Moshe; Pasanen, Markku; Juvonen, Risto O

    2013-10-01

    1. UDP-glucuronosyltransferases (UGTs) are versatile and important conjugation enzymes in the metabolism of drugs and other xenobiotics. 2. We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of 7-hydroxy-4-trifluoromethylcoumarin (HFC) for several UGTs. 3. We have used this method to screen 11 recombinant human UGTs for HFC glucuronidation activity and studied the reaction kinetics with the most active enzymes. We have also examined the HFC glucuronidation activity of liver microsomes from human, pig, rabbit and rat. 4.? At a substrate concentration of 20?µM, the most active HFC glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300?µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs. The activities of UGTs 1A3, 1A8, 1A9, 2B4 and 2B7 were low, whereas UGT1A1 and UGT2B17 exhibited no HFC glucuronidation activity. UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-glucuronic acid than the other UGTs. 5. Human, pig and rabbit, but not rat liver microsomes, catalyzed HFC glucuronidation at high rates. 6. This new method is particularly suitable for fast activity screenings of UGTs 1A6, 1A7, 1A10 and 2A1 and HFC glucuronidation activity determination from various samples. PMID:23551063

  18. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    PubMed

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine.This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS. PMID:26660175

  19. A sensitive high performance liquid chromatography-positive electrospray tandem mass spectrometry method for N7-[2-[(2-hydroxyethyl)thio]-ethyl]guanine determination.

    PubMed

    Wei, Yuxia; Yue, Lijun; Liu, Qin; Chen, Jia; Xie, Jianwei

    2011-06-01

    A simple, fast, sensitive and robust method for the determination of the sulfur mustard (SM) exposure biomarker-N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (HETEG) was reported using high-performance liquid chromatography-positive electrospray tandem mass spectrometry (HPLC-ESI-MS/MS), working in multiple reaction monitor (MRM) mode. The method provided limit of detection of 0.330 ng/mL and lower limit of quantitation of 0.940 ng/mL. The method was linearly calibrated from 0.940 ng/mL to 587 ng/mL with precisions of 3.5-14.5%, and accuracies of 88-112%. The recovery varied from 102% to 118%. HETEG spiked in DNA hydrolytes isolated from the human whole blood was stable after five freeze/thaw cycles and 35-day frozen at -20°C. For the exposed biological samples, alkylated DNA was isolated from SM-treated human whole blood, followed by DNA digestion and adducts enrichment, the resulting alkylation base was determined. By the procedure, the HETEG level in DNA hydrolytes isolated from the human whole blood exposure to 312 ng/mL SM was detected successfully. PMID:21515093

  20. Determination of ethyl carbamate in fermented liquids by ultra high performance liquid chromatography coupled with a Q Exactive hybrid quadrupole-orbitrap mass spectrometer.

    PubMed

    Zhao, Xirong; Jiang, Changxing

    2015-06-15

    In this study, the determination of ethyl carbamate (EC) in fermented liquids (red wines, Chinese liquors and yellow wines) was carried by using ultra high performance liquid chromatography coupled with a Q Exactive hybrid quadrupole-orbitrap mass spectrometer (UHPLC-MS/MS). The parameters usually examined in the method validation were firstly evaluated. Good linearity was obtained with a correlation coefficient of 0.9999. The limits of detection (LOD) and quantitation (LOQ) of EC in sample were 1.8 and 4.0 ?g/L, respectively. Recoveries ranged between 107.19% and 110.98%. The precision (relative standard deviation, RSD) of the method was <5%. Furthermore, red wines, Chinese liquors and yellow wines for sale were detected using this method. The results showed that the red wines and Chinese liquors had the normal EC level that was within the limits of the Canadian legislation. The proposed method was simple in sample preparation without using organic solvents in pre-treatment and could be used for the determination of the content of EC in fermented liquids. PMID:25660859

  1. Disruption of thyroid hormone homeostasis in Ugt1a-deficient Gunn rats by microsomal enzyme inducers is not due to enhanced thyroxine glucuronidation

    SciTech Connect

    Richardson, Terrilyn A.; Klaassen, Curtis D.

    2010-10-01

    Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) are thought to increase glucuronidation of thyroxine (T{sub 4}), thus reducing serum T{sub 4}, and subsequently increasing thyroid stimulating hormone (TSH). Ugt1a1 and Ugt1a6 mediate T{sub 4} glucuronidation. Therefore, this experiment determined the involvement of Ugt1a enzymes in increased T{sub 4} glucuronidation, decreased serum T{sub 4}, and increased TSH after MEI treatment. Male Wistar and Ugt1a-deficient Wistar (Gunn) rats were fed a control diet or diet containing pregnenolone-16{alpha}-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum T{sub 4}, triiodothyronine (T{sub 3}), and TSH concentrations, hepatic T{sub 4}/T{sub 3} glucuronidation, and thyroid histology and follicular cell proliferation were investigated. PCN, 3-MC, and PCB treatments decreased serum T{sub 4}, whereas serum T{sub 3} was maintained in both Gunn and Wistar rats (except for PCB treatment). TSH was increased in Wistar and Gunn rats after PCN (130 and 277%) or PCB treatment (72 and 60%). T{sub 4} glucuronidation in Wistar rats was increased after PCN (298%), 3-MC (85%), and PCB (450%), but was extremely low in Gunn rats, and unchanged after MEI. T{sub 3} glucuronidation was increased after PCN (121%) or PCB (58%) in Wistar rats, but only PCN increased T{sub 3} glucuronidation in Gunn rats (43%). PCN treatment induced thyroid morphological changes and increased follicular cell proliferation in both strains. These data demonstrate that T{sub 4} glucuronidation cannot be increased in Ugt1a-deficient Gunn rats. Thus, the decrease in serum T{sub 4}, increase in TSH, and increase in thyroid cell proliferation after MEI are not dependent on increased T{sub 4} glucuronidation, and cannot be attributed to Ugt1a enzymes.

  2. Fate of glucuronide conjugated estradiol in the environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

  3. Application of 10-ethyl-acridine-3-sulfonyl chloride for HPLC determination of aliphatic amines in environmental water using fluorescence and APCI-MS.

    PubMed

    You, Jinmao; Zhao, Huaixin; Sun, Zhiwei; Xia, Lian; Yan, Tao; Suo, Yourui; Li, Yulin

    2009-05-01

    A simple, sensitive method for the determination of aliphatic amines based on a sulfonylation reaction using 10-ethyl-acridine-3-sulfonyl chloride (EASC) as pre-column labeling reagent with fluorescence detection and APCI-MS identification has been developed. The labeled derivatives exhibited high stability and were enough to be efficiently analyzed by HPLC with an excitation maximum at lambda(ex) 270 nm and an emission maximum at lambda(em) 430 nm. Identification of derivatives was carried out by online post-column MS in positive-ion mode. Comparing with the widely used 5-dimethylaminonaphthalene-1-sulfonylchloride (Dansyl-Cl), EASC-amine derivatives not only exhibited high fluorescence but also exhibited excellent MS ionizable potential. Detection limits obtained from 0.10 pmol injection, at a S/N of 3, were 4.0-12.7 fmol. The mean intra- and inter-assay precision for all aliphatic amine levels were <3.84 and 3.21%, respectively. Excellent linear responses were observed with coefficients of >0.9995. PMID:19350582

  4. Synthesis of an estradiol glucuronide derivative and investigation of its radiopharmaceutical potential.

    PubMed

    Biber, F Z; Unak, P; Ertay, T; Medine, E I; Zihnioglu, F; Tasci, C; Durak, H

    2006-07-01

    The aim of the current study was to synthesize a derivative of estradiol glucuronide, which is able to be labeled with 99mTc and to investigate its radiopharmaceutical potential using imaging and biodistribution studies. An estrogen derivative, beta-estradiol (1,3,5,[10]-estratriene-3,17beta-diol) attached to diethylenetriamine pentaacetic acid (DTPA) was synthesized in six steps. At the end of these steps a compound of estradiol and DTPA derivative called deoxy demethyl homoestradiolyl diethylenetriamine pentaacetic acid (ESTDTPA) was synthesized. Afterwards, this compound was reacted with UDP-glucuronyl transferase (UDPGT). Following the glucuronidation reaction, the product called deoxy demethyl homoestradiolyl diethylenetriamine pentaaceticacid-glucuronide (ESTDTPAG) was obtained. Synthesized products were purified using high performance liquid chromatography (HPLC). The identification of the purified products and impurities were also established using HPLC. Synthesized compound was labeled with 99mTc. Thin layer radio chromatography (TLRC) technique was used to determine their radiochemical yields and stabilities. Labeling yield was over 96%. The biodistribution studies were performed on female Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were plotted. The target organs (tumor, as well as uterus, ovaries, adrenals and other ER containing tissues) retain the estradiol derivative longer than nontarget organs, but even these lost most of their activity within a few hours. In addition, the imaging studies were performed on normal and tumor bearing female Albino Wistar rats using Camstar XR/T gamma camera. In gamma-scintigraphic imaging studies with 99mTc-ESTDTPAG the breast tumors could be well visualized up to 24 h. PMID:16531048

  5. The effect of glucuronidation on isoflavone induced estrogen receptor (ER)? and ER? mediated coregulator interactions.

    PubMed

    Beekmann, Karsten; de Haan, Laura H J; Actis-Goretta, Lucas; Houtman, René; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2015-11-01

    Non-prenylated isoflavone aglycones are known to have phyto-estrogenic properties and act as agonistic ligands on ER? and ER? due to their structural resemblance to 17?-estradiol (E2). Genistein and daidzein are the two main dietary isoflavones; upon uptake they are extensively metabolized and exist nearly exclusively as their conjugated forms in biological fluids. Little is known about the effect of conjugation on the intrinsic estrogenic activities of these isoflavones. To characterize and compare the intrinsic estrogenic activities of genistein and daidzein, and their respective 7-O-glucuronide metabolites a cell-free assay system was employed that determines the ligand-induced changes in ER?- and ER?-ligand binding domain (LBD) interactions with 154 different binding motifs derived from 66 different nuclear receptor coregulators. The glucuronides were 8 to 4400 times less potent than their respective aglycones to modulate ER?-LBD and ER?-LBD-coregulator interactions. Glucuronidation changed the preferential activation of genistein from ER?-LBD to ER?-LBD and further increased the slightly preferential activation of daidzein for ER?-LBD. The tested isoflavone compounds were less potent than E2 (around 5 to 1580 times for the aglycones) but modulated the LBD-coregulator interactions in a manner similar to E2. Our results show that genistein and daidzein remain agonistic ligands of ER?-LBD and ER?-LBD in their conjugated form with a higher relative preference for ER?-LBD than the corresponding aglycones. This shift in receptor preference is of special interest as the preferential activation of ER? is considered one of the possible modes of action underlying the supposed beneficial instead of adverse health effects of isoflavones. PMID:26361015

  6. New Spectrophotometric Method for Determining Nitrogen Dioxide in Air Using 2,2-azino-bis(3-ethyl benzothiazoline)-6-Sulfonic Acid-Diammonium Salt and Passive Sampling

    PubMed Central

    Salem, Alaa A.; Soliman, Ahmed A.; El-Haty, Ismail A.

    2011-01-01

    A new simple and highly sensitive spectrophotometric method for determining nitrogen dioxide in air was developed. The method is based on converting atmospheric nitrogen dioxide to nitrite ions within the IVL passive samplers used for samples collection. Acidifying nitrite ions with concentrated HCl produced the peroxynitrous acid oxidizing agent which was measured using 2, 2-azino-bis(3-ethyl benzothiazoline)-6-sulfonic acid-diammonium salt (ABTS) as reducing coloring agent. A parallel series of collected samples were measured for its nitrite content using a validated ion chromatographic method. The results obtained using both methods were compared in terms of their sensitivity and accuracy. Developed spectrophotometric method was shown to be one order of magnitude higher in sensitivity compared to the ion chromatographic method. Quantitation limits of 0.05 ppm and 0.55 ?g/m3 were obtained for nitrite ion and nitrogen dioxid, respectively. Standard deviations in the ranges of 0.05–0.59 and 0.63–7.92 with averages of 0.27 and 3.11 were obtained for determining nitrite and nitrogen dioxide, respectively. Student-t test revealed t-values less than 6.93 and 4.40 for nitrite ions and nitrogen dioxide, respectively. These values indicated insignificant difference between the averages of the newly developed method and the values obtained by ion chromatography at 95% confidence level. Compared to continuous monitoring techniques, the newly developed method has shown simple, accurate, sensitive, inexpensive and reliable for long term monitoring of nitrogen dioxide in ambient air. PMID:21760708

  7. 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

  8. Sequence, specificity and crystallization of an oestrone-3-glucuronide antibody (3910).

    PubMed

    He, M; Gani, M; Livnah, O; Stura, E A; Beale, D; Coley, J; Wilson, I A; Taussig, M J

    1997-04-01

    We describe the specificity profile and V region sequences of a high-affinity monoclonal antibody (mAb), 3910, directed against oestrone-3-glucuronide (E3G). Inhibition studies show that the D-ring is critical for steroid specificity, while the glucuronic acid attached to the A ring is required for high binding affinity, suggesting that both 'ends' of the E3G ligand are recognized. The VH domain is encoded by a gene from the VH7183 family, while VL appears to be encoded by the Vk5.1 gene (kappa II subgroup) with a deletion of six residues from complementarity-determining region-1 (CDR1). The VH CDR3 is 10 amino acid residues in length, of which D/N contributes five residues. Comparison of VH CDR of 3910 with those of mAb against progesterone (DB3) and digoxin (26-10, 40-50), for which crystal structures have been determined, suggests that aromatic side chains are important for E3G binding and that tyrosine residues H50, H97 and H100 may interact with the ligand. The Fab fragment of 3910 has been crystallized in its native and steroid (E3G and oestriol-3-glucuronide) complexed forms. An X-ray diffraction data set to 3 A resolution has been collected for the native Fab. PMID:9176119

  9. 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; Sřrlie, 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

  10. Human UDP-Glucuronosyltransferase 1A1 is the Primary Enzyme Responsible for the N-glucuronidation of N-hydroxy-PhIP in vitro

    SciTech Connect

    Malfatti, M A; Felton, J S

    2004-04-06

    UDP-Glucuronosyltransferase 1A proteins (UGT1A) catalyze the glucuronidation of many endogenous and xenobiotic compounds including heterocyclic amines and their hydroxylated metabolites (the main topic of this study). Studies have shown that in humans UGT1A mediated glucuronidation is an important pathway in the detoxification of food-borne carcinogenic heterocyclic amines. The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant heterocyclic amine found in cooked meats, is highly dependent on cytochrome P4501A2 hydroxylation followed by UGT catalyzed glucuronidation of the N-hydroxy-PhIP reactive intermediate. To determine which UGT1A proteins are involved in the glucuronidation of N-hydroxy-PhIP, microsomal preparations from baculovirus infected insect cells that express all of the known functional human UGT1A isozymes (UGT1A1, -1A3, -1A4, -1A6, -1A7, -1A8, -1A9, -1A10) were exposed to N-hydroxy-PhIP and the reaction products were isolated by HPLC. All UGT1A proteins except UGT1A6 showed some degree of activity towards N-hydroxy-PhIP. The formation of both N-hydroxy-PhIP-N{sup 2}-glucuronide and N-hydroxy-PhIP-N3-glucuronide was both time and substrate concentration dependent in all the microsomal incubations that showed appreciable activity. UGT1A1 was the most efficient in converting N-hydroxy-PhIP to both conjugates producing 5 times more of the N{sup 2}-conjugate than UGT1A4, the next active UGT, and 286 times more than UGT1A7, the least active UGT. With an apparent Km of 52 {micro}M and a K{sub cat} of 114 min-1, UGT1A1 was also the most catalytically efficient in forming N-hydroxy-PhIP-N{sup 2}-glucuronide. Catalytic constants for UGT1A4, UGT1A8 and UGT1A9 were 52 min-1, 35 min{sup -1} and 3.7 min{sup -1}, respectively. The catalytic efficiency for N-hydroxy-PhIP-N3-glucuronide formation was 8, 10, and 6 times lower for UGT1A1, -1A4, and -1A8, respectively, when compared to the k{sub cat} values for N-hydroxy-PhIP-N{sup 2}-glucuronide formation. These results clearly show that UGT1A1 is mainly responsible for glucuronidating N-hydroxy-PhIP. Polymorphic expression resulting in decreased UGT1A1 activity in humans can cause reduced rates of glucuronidation which can change the metabolic ratio between bioactivation and detoxification to favor bioactivation. This change will increase the susceptibility to the deleterious effects from PhIP exposure because the capacity to form nontoxic N-hydroxy-PhIP glucuronide conjugates will be diminished.

  11. An immunoassay for the detection of triclosan-O-glucuronide, a primary human urinary metabolite of triclosan.

    PubMed

    Ranganathan, Anupama; Gee, Shirley J; Hammock, Bruce D

    2015-09-01

    Triclosan-O-glucuronide (TCSG) is one of the primary urinary metabolites of the antibacterial compound triclosan or TCS that is found in many personal care products and consumer goods. We have developed a competitive, indirect heterologous ELISA for the detection of the target TCSG in urine. Such an ELISA for TCSG could be developed as a useful tool to measure this important biomarker of human exposure to TCS. Immunogens were prepared by conjugating TCSG to thyroglobulin, via heterobifunctional cross-linkers AEDP or 3-[(2-aminoethyl)dithio] propionic acid•hydrochloride and TFCS or N-[?-trifluoroacetylcaproyloxy]succinimide ester. The coating antigen was prepared by the direct conjugation of TCSG to bovine serum albumin. Antibodies raised in rabbits 2619, 2621 (immunogen TCSG-AEDP-Thy), and 2623 (immunogen TCSG-TFCS-Thy), and the coating antigen were screened and characterized to determine their optimal concentrations. The optimized ELISA, developed with antibody 2621, gave an IC50 value of 2.85 ng/mL, with the linear range (IC20-IC80) determined to be 2.6-24.8 ng/mL. Selectivity of the assay was assessed by measuring cross-reactivity of antibody 2621 to related congeners such as the aglycone TCS, triclosan-O-sulfate, triclocarban, a polybrominated diphenyl ether derivative, and 3-phenoxybenzyl alcohol glucuronide. There was virtually no recognition by antibody 2621 to any of these cross-reactants. Graphical Abstract Urinary biomarker analysis of triclosan glucuronide. PMID:26255293

  12. 99mTc-d-penicillamine-glucuronide: synthesis, radiolabeling, in vitro and in vivo evaluation.

    PubMed

    Teksöz, Serap; Içhedef, Ci?dem Acar; Ozyüncü, Seniha; Müftüler, Fazilet Zümrüt Biber; Unak, Perihan; Medine, Ilker Emin; Ertay, Türkan; Eren, Mine ?encan

    2011-10-01

    The current study was aimed at synthesizing a glucuronide derivative of D-penicillamine (D-PA) to be used for imaging purposes. First of all, D-PA-glucuronide (D-PA-Glu) was synthesized by experimental treatments starting with uridine 5'-diphospho-glucuronosyltransferase enzyme rich microsome preparate. Then, the synthesized compound was labeled with technetium ((99m)Tc) by using a reduction method with stannous chloride. Quality controls were performed by using high-performance liquid chromatography and thin-layer radio chromatography (TLRC). Radiolabeling yield of (99m)Tc-D-PA-Glu was more than 98% according to TLRC results. In vitro evaluations of radiolabeled complexes were investigated on PC-3 human prostate cancer cells. (99m)Tc-D-PA-Glu exhibited more accumulation on PC-3 cells versus (99m)Tc-D-PA at 240 minutes. In order to determine its radiopharmaceutical potential, biodistribution studies were carried out in male Albino Wistar rats. The biodistribution results of (99m)Tc-D-PA-Glu, showed the highest uptake in prostate at 120 minutes postinjection with the main excretion route being through kidneys and bladder. (99m)Tc-D-PA-Glu and (99m)Tc-D-PA have exhibited different biodistribution results. PMID:21950558

  13. Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-?-Glucuronide.

    PubMed

    Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

    2015-11-01

    Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-?-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 ?M, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1. PMID:26378985

  14. DETERMINATION OF KOW VALUES FOR A SERIES OF ARYL GLUCURONIDES

    EPA Science Inventory

    An important perameter in toxicokinetic modeling is the octanol/water partition coefficient (Kow). This parameter has often been used to predict the accumulation of contaminants from water to fish (Klamer and Beekman 1995); however, few Kow values are available for modeling the b...

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

    SciTech Connect

    Chan, Tom S. Wilson, John X.; Selliah, Subajini; Bilodeau, Marc; Zwingmann, Claudia; Poon, Raymond; O'Brien, Peter J.

    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.

  16. Structure-Dependent Deconjugation of Flavonoid Glucuronides by Human ?-Glucuronidase - In Vitro and In Silico Analyses.

    PubMed

    Untergehrer, Monika; Bücherl, Daniel; Wittmann, Hans-Joachim; Strasser, Andrea; Heilmann, Jörg; Jürgenliemk, Guido

    2015-08-01

    Flavonoid glycosides are extensively metabolized to glucuronidated compounds after oral intake. Recently, a cleavage of quercetin glucuronides by ?-glucuronidase has been found. To characterize the deglucuronidation reaction and its structural prerequisites among the flavonoid subtypes more precisely, four flavonol glucuronides with varying glucuronidation positions, five flavone 7-O-glucuronides with varying A- and B-ring substitution as well as one flavanone- and one isoflavone-7-O-glucuronide were analyzed in a human monocytic cell line. Investigation of the deglucuronidation rates by HPLC revealed a significant influence of the glucuronidation position on enzyme activity for flavonols. Across the flavonoid subtypes, the C-ring saturation also showed a significant influence on deglucuronidation, whereas A- and B-ring variations within the flavone-7-O-glucuronides did not affect the enzymes' activity. Results were compared to computational binding studies on human ?-glucuronidase. Additionally, molecular modeling and dynamic studies were performed to obtain detailed insight into the binding and cleavage mode of the substrate at the active site of the human ?-glucuronidase. PMID:26018917

  17. UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation

    SciTech Connect

    Nishiyama, Takahito; Ohnuma, Tomokazu; Inoue, Yuu; Kishi, Takehiko; Ogura, Kenichiro; Hiratsuka, Akira

    2008-06-27

    Menadione (2-methyl-1,4-naphthoquine), also known as vitamin K3, has been widely used as a model compound in the field of oxidative stress-related research. The metabolism of menadione has been studied, and it is known that menadione undergoes a two-electron reduction by NAD(P)H:Quinone oxidoreductase 1 (NQO1) after which the reduced form of menadione (2-methyl-1,4-naphthalenediol, menadiol) is glucuronidated and excreted in urine. To investigate which human UDP-glucuronosyltransferase (UGT) isoforms participate in the glucuronidation of menadiol reduced by NQO1 from menadione, we first constructed heterologously expressed NQO1 in Sf9 cells and tested the menadiol glucuronidating activity of 16 human recombinant UGT isoforms. Of the 16 UGT isoforms, UGTs 1A6, 1A7, 1A8, 1A9, and 1A10 catalyzed menadiol glucuronidation, and, of these, UGTs 1A6 and 1A10 catalyzed menadiol glucuronidation at much higher rates than the other UGTs. Menadiol was regioselectively glucuronidated in the manner of 4-position > 1-position by UGTs 1A7, 1A8, 1A9, and 1A10. In contrast to these UGTs, only UGT1A6 exhibited 1-menadiol-preferential glucuronidating activity. The results suggest possible detoxification pathways for quinones via NQO1 reduction followed by UGT glucuronidation.

  18. Methyl ethyl ketone (MEK)

    Integrated Risk Information System (IRIS)

    EPA 635 / R - 03 / 009 www.epa.gov / iris TOXICOLOGICAL REVIEW OF METHYL ETHYL KETONE ( CAS No . 78 - 93 - 3 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) September 2003 U.S . Environmental Protection Agency Washington , DC DISCLAIMER This document has been r

  19. Chlorimuron-ethyl

    Integrated Risk Information System (IRIS)

    Chlorimuron - ethyl ; CASRN 90982 - 32 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  20. 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.

  1. Marshall University Ethyl Alcohol

    E-print Network

    Sanyal, Suman

    Marshall University Guide for Use of Tax Free Ethyl Alcohol Including Excerpts from The Code of Federal Regulations TITLE 27--ALCOHOL, TOBACCO PRODUCTS AND FIREARMS CHAPTER I PART 22_DISTRIBUTION AND USE OF TAX-FREE ALCOHOL NOVEMBER 15, 2006 Brian Carrico, Director Health and Safety Office Marshall

  2. Urinary bromophenol glucuronide and sulfate conjugates: Potential human exposure molecular markers for polybrominated diphenyl ethers.

    PubMed

    Ho, Ka-Lok; Yau, Man-Shan; Murphy, Margaret B; Wan, Yi; Fong, Bonnie M-W; Tam, Sidney; Giesy, John P; Leung, Kelvin S-Y; Lam, Michael H-W

    2015-08-01

    One possible source of urinary bromophenol (BP) glucuronide and sulfate conjugates in mammalian animal models and humans is polybromodiphenyl ethers (PBDEs), a group of additive flame-retardants found ubiquitously in the environment. In order to study the correlation between levels of PBDEs in human blood plasma and those of the corresponding BP-conjugates in human urine, concentrations of 17 BDE congeners, 22 OH-BDE and 13 MeO-BDE metabolites, and 3 BPs in plasma collected from 100 voluntary donors in Hong Kong were measured by gas chromatograph tandem mass spectrometry (GC-MS). Geometric mean concentration of ?PBDEs, ?OH-BDEs, ?MeO-BDEs and ?BPs in human plasma were 4.45 ng g(-1) lw, 1.88 ng g(-1) lw, 0.42 ng g(-1) lw and 1.59 ng g(-1) lw respectively. Concentrations of glucuronide and sulfate conjugates of 2,4-dibromophenol (2,4-DBP) and 2,4,6-tribromophenol (2,4,6-TBP) in paired samples of urine were determined by liquid chromatography tandem triple quadrupole mass spectrometry (LC-MS/MS). BP-conjugates were found in all of the parallel urine samples, in the range of 0.08-106.49 ?g g(-1)-creatinine. Correlations among plasma concentrations of ?PBDEs/?OH-BDEs/?MeO-BDEs/?BPs and BP-conjugates in urine were evaluated by multivariate regression and Pearson product correlation analyses. These urinary BP-conjugates were positively correlated with ?PBDEs in blood plasma, but were either not or negatively correlated with other organobromine compounds in blood plasma. Stronger correlations (Pearson's r as great as 0.881) were observed between concentrations of BDE congeners having the same number and pattern of bromine substitution on their phenyl rings in blood plasma and their corresponding BP-conjugates in urine. PMID:25817024

  3. 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.

  4. Comparison of the hydrolysis rates of morphine-3-glucuronide and morphine-6-glucuronide with acid and beta-glucuronidase.

    PubMed

    Romberg, R W; Lee, L

    1995-01-01

    The acid and enzymatic hydrolysis rates for two morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were compared. Urine fortified with M3G or M6G was hydrolyzed in a boiling water bath or with beta-glucuronidases. Optimal temperatures for beta-glucuronidases were 60 degrees C for Helix pomatia and abalone and 50 degrees C for Escherichia coli. A 3-h incubation with 1,000-1,500 Fishman units of enzyme gave complete hydrolysis of M3G. The enzymatic hydrolysis rate of M6G was approximately 25% of the hydrolysis rate of M3G and required 24 h for completion. The acid hydrolysis rate of M6G was slower than M3G and required a 0.5-h incubation with a 1:1 mixture of concentrated HCl in a boiling water bath for completion. For comparison, the acid hydrolysis rate of codeine conjugates was found to be similar to the rate of M6G, but the enzymatic rate of codeine conjugates appeared slower than the rate of M6G. PMID:7564293

  5. Enzymatic synthesis of uracil glucuronide, labeling with 125/131I, and in vitro evaluation on adenocarcinoma cells.

    PubMed

    Medine, Ilker Emin; Unak, Perihan; Sakarya, Serhan; Toksöz, Feriha

    2010-06-01

    Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% +/- 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled (125/131)I-UNG and (125/131)I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of (125/131)I-UOG were higher than those of (125/131)I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of (125/131)I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I-125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages. PMID:20578839

  6. Morphine-3-glucuronide: silent regulator of morphine actions.

    PubMed

    Lipkowski, A W; Carr, D B; Langlade, A; Osgood, P F; Szyfelbein, S K

    1994-01-01

    To assess whether stoichiometric manipulation of morphine (M) metabolism can enhance analgesia or slow the development of M tolerance we co-administered M-3- glucuronide (M3G) during single or repeated doses of morphine in rats. Although M3G itself lacked analgesic activity, co-injection of M3G with M increased and prolonged analgesia beyond that seen with M. In addition, diminution of the acute analgesic effect of M after 3 once-daily doses of M did not occur after daily co-injection of M3G and M. Thus the traditional view that tolerance to the effects of M is due solely to effects mediated through opioid receptors must be broadened to include the contributions of enzyme induction or stoichiometric equilibration of M3G in this process. PMID:8015358

  7. Investigation of therapeutic efficiency of bleomycin and bleomycin-glucuronide labeled with (131)I on the cancer cell lines.

    PubMed

    Ediz, Melis; Avc?ba??, U?ur; Unak, Perihan; Müftüler, Fazilet Zümrüt Biber; Medine, Emin ?lker; Yurt K?lçar, Ayfer; Demiro?lu, Hasan; Gümü?er, Fikriye Gül; Sakarya, Serhan

    2013-05-01

    The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ?-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells. PMID:23350895

  8. The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure.

    PubMed

    Court, Michael H; Freytsis, Marina; Wang, Xueding; Peter, Inga; Guillemette, Chantal; Hazarika, Suwagmani; Duan, Su X; Greenblatt, David J; Lee, William M

    2013-05-01

    Acetaminophen is cleared primarily by hepatic glucuronidation. Polymorphisms in genes encoding the acetaminophen UDP-glucuronosyltransferase (UGT) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose. In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen-glucuronidating enzymes (UGTs 1A1, 1A6, 1A9, and 2B15). Of these, only three linked single nucleotide polymorphisms (SNPs) located in the shared UGT1A-3'UTR region (rs10929303, rs1042640, rs8330) were associated with acetaminophen glucuronidation activity, with rs8330 consistently showing higher acetaminophen glucuronidation at all the tested concentrations of acetaminophen. Mechanistic studies using luciferase-UGT1A-3'UTR reporters indicated that these SNPs do not alter mRNA stability or translation efficiency. However, there was evidence for allelic imbalance and a gene-dose proportional increase in the amount of exon 5a versus exon 5b containing UGT1A mRNA spliced transcripts in livers with the rs8330 variant allele. Cotransfection studies demonstrated an inhibitory effect of exon 5b containing cDNAs on acetaminophen glucuronidation by UGT1A1 and UGT1A6 cDNAs containing exon 5a. In silico analysis predicted that rs8330 creates an exon splice enhancer site that could favor exon 5a (over exon 5b) utilization during splicing. Finally, the prevalence of rs8330 was significantly lower (P = 0.027, ?(2) test) in patients who had acute liver failure from unintentional acetaminophen overdose compared with patients with acute liver failure from other causes or a race- or ethnicity-matched population. Together, these findings suggest that rs8330 is an important determinant of acetaminophen glucuronidation and could affect an individual's risk for acetaminophen-induced liver injury. PMID:23408116

  9. Identification and characterization of human UDP-glucuronosyltransferases responsible for the glucuronidation of fraxetin.

    PubMed

    Xia, Yang-Liu; Liang, Si-Cheng; Zhu, Liang-Liang; Ge, Guang-Bo; He, Gui-Yuan; Ning, Jing; Lv, Xia; Ma, Xiao-Chi; Yang, Ling; Yang, Sheng-Li

    2014-01-01

    Fraxetin, a major constituent of the traditional medicine plant Fraxinus rhynchophylla Hance (Oleaceae), has been found to possess multiple bioactivities. However, the metabolic pathway(s) of fraxetin in human tissues has not been reported yet. This study aimed to characterize the glucuronidation pathway(s) of fraxetin in human tissues. Fraxetin could be metabolized to two glucuronides in human liver microsomes (HLMs). These two glucuronides were biosynthesized and characterized as 7-O-glucuronide (7-O-G) and 8-O-glucuronide (8-O-G). UGT1A1, -1A6, -1A7, -1A8, -1A9 and -1A10 participated in the formation of 7-O-G, while the formation of 8-O-G was catalyzed selectively by UGT1A6 and UGT1A9. UGT1A9 showed the highest catalytic activities in the formation of 7-O-G and 8-O-G. Both kinetic characterization and inhibition assays demonstrated that UGT1A9 played important roles in fraxetin glucuronidations in HLMs, especially in the formation of the major metabolite 8-O-G. Furthermore, the intrinsic clearance of fraxetin in both human liver microsomes and UGT1A9 was greater than that of 7,8-dihydroxylcoumarin, revealing that the addition of a C-6 methoxy group led to the higher metabolic clearance. In summary, the glucuronidation pathways of fraxetin in human liver microsomes were well-characterized, and UGT1A9 was the major isoform responsible for the glucuronidations of fraxetin. PMID:24025985

  10. 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

  11. Glucuronidation of Drugs and Drug-Induced Toxicity in Humanized UDP-Glucuronosyltransferase 1 Mice

    PubMed Central

    Kutsuno, Yuki; Itoh, Tomoo; Tukey, Robert H.

    2014-01-01

    UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that catalyze glucuronidation of various drugs. Although experimental rodents are used in preclinical studies to predict glucuronidation and toxicity of drugs in humans, species differences in glucuronidation and drug-induced toxicity have been reported. Humanized UGT1 mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice) were recently developed. In this study, acyl-glucuronidations of etodolac, diclofenac, and ibuprofen in liver microsomes of hUGT1 mice were examined and compared with those of humans and regular mice. The kinetics of etodolac, diclofenac, and ibuprofen acyl-glucuronidation in hUGT1 mice were almost comparable to those in humans, rather than in mice. We further investigated the hepatotoxicity of ibuprofen in hUGT1 mice and regular mice by measuring serum alanine amino transferase (ALT) levels. Because ALT levels were increased at 6 hours after dosing in hUGT1 mice and at 24 hours after dosing in regular mice, the onset pattern of ibuprofen-induced liver toxicity in hUGT1 mice was different from that in regular mice. These data suggest that hUGT1 mice can be valuable tools for understanding glucuronidations of drugs and drug-induced toxicity in humans. PMID:24764149

  12. Analytical procedure for the determination of Ethyl Lauroyl Arginate (LAE) to assess the kinetics and specific migration from a new antimicrobial active food packaging.

    PubMed

    Pezo, Davinson; Navascués, Beatriz; Salafranca, Jesús; Nerín, Cristina

    2012-10-01

    Ethyl Lauroyl Arginate (LAE) is a cationic tensoactive compound, soluble in water, with a wide activity spectrum against moulds and bacteria. LAE has been incorporated as antimicrobial agent into packaging materials for food contact and these materials require to comply with the specific migration criteria. In this paper, one analytical procedure has been developed and optimized for the analysis of LAE in food simulants after the migrations tests. It consists of the formation of an ionic pair between LAE and the inorganic complex Co(SCN)(4)(2-) in aqueous solution, followed by a liquid-liquid extraction in a suitable organic solvent and further UV-Vis absorbance measurement. In order to evaluate possible interferences, the ionic pair has been also analyzed by high performance liquid chromatography with UV-Vis detection. Both procedures provided similar analytical characteristics, with linear ranges from 1.10 to 25.00 mg kg(-1), linearity higher than 0.9886, limits of detection and quantification of 0.33 and 1.10 mg kg(-1), respectively, accuracy better than 1% as relative error and precision better than 3.6% expressed as RSD. Optimization of analytical techniques, thermal and chemical stability of LAE, as well as migration kinetics of LAE from experimental active packaging are reported and discussed. PMID:22938611

  13. Optical on-line method of ethyl mercaptan detection in liquid phase in motor fuels

    NASA Astrophysics Data System (ADS)

    Kireev, S. V.; Shnyrev, S. L.

    2015-11-01

    The letter reports on the experimental research of the absorption spectra of ethyl mercaptan in liquid phase in various motor fuels (petrol, kerosene, and diesel fuel). The values of ethyl mercaptan absorption sections were obtained in the above-mentioned fuels in the spectral range of 280–475?nm, and the dependences of ethyl mercaptan absorption coefficients on its part in the analyzed mixture with motor fuels were researched. On the basis of the obtained results we propose an optical on-line method of ethyl mercaptan detection in motor fuels. The optimal spectral ranges for the highest sensitivity of ethyl mercaptan detection in various motor fuels were determined.

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SAFE IN FEED AND DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.200... the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  15. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SAFE IN FEED AND DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.200... the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  16. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... SAFE IN FEED AND DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.200... the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  17. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SAFE IN FEED AND DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.200... the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  18. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...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,...

  19. 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}

  20. Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

    SciTech Connect

    Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

    1980-06-15

    Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were noted in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.

  1. 5?-Androst-16-en-3?-ol ?-D-glucuronide, precursor of 5?-androst-16-en-3?-ol in human sweat.

    PubMed

    Starkenmann, Christian; Mayenzet, Fabienne; Brauchli, Robert; Troccaz, Myriam

    2013-12-01

    5?-Androst-16-en-3?-ol (?-androstenol) is an important contributor to human axilla sweat odor. It is assumed that ?-andostenol is excreted from the apocrine glands via a H2 O-soluble conjugate, and this precursor was formally characterized in this study for the first time in human sweat. The possible H2 O-soluble precursors, sulfate and glucuronide derivatives, were synthesized as analytical standards, i.e., ?-androstenol, ?-androstenol sulfates, 5?-androsta-5,16-dien-3?-ol (?-androstadienol) sulfate, ?-androstenol ?-glucuronide, ?-androstenol ?-glucuronide, ?-androstadienol ?-glucuronide, and ?-androstenol ?-glucuronide furanose. The occurrence of ?-androstenol ?-glucuronide was established by ultra performance liquid chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative-ion mode in pooled human sweat, containing eccrine and apocrine secretions and collected from 25 female and 24 male underarms. Its concentration was of 79?ng/ml in female secretions and 241?ng/ml in male secretions. The release of ?-androstenol was observed after incubation of the sterile human sweat or ?-androstenol ?-glucuronide with a commercial glucuronidase enzyme, the urine-isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium acnes ATCC 6919, reported to have ?-glucuronidase activities. We demonstrated that if ?- and ?-androstenols and androstadienol sulfates were present in human sweat, their concentrations would be too low to be considered as potential precursors of malodors; therefore, the H2 O-soluble precursor of ?-androstenol in apocrine secretion should be a ?-glucuronide. PMID:24327440

  2. In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole

    PubMed Central

    Kamdem, Landry K; Liu, Yong; Stearns, Vered; Kadlubar, Susan A; Ramirez, Jacqueline; Jeter, Stacie; Shahverdi, Karineh; Ward, Bryan A; Ogburn, Evan; Ratain, Mark J; Flockhart, David A; Desta, Zeruesenay

    2010-01-01

    AIMS Little information is available regarding the metabolic routes of anastrozole and the specific enzymes involved. We characterized anastrozole oxidative and conjugation metabolism in vitro and in vivo. METHODS A sensitive LC-MS/MS method was developed to measure anastrozole and its metabolites in vitro and in vivo. Anastrozole metabolism was characterized using human liver microsomes (HLMs), expressed cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs). RESULTS Hydroxyanastrozole and anastrozole glucuronide were identified as the main oxidative and conjugated metabolites of anastrozole in vitro, respectively. Formation of hydroxyanastrozole from anastrozole was markedly inhibited by CYP3A selective chemical inhibitors (by >90%) and significantly correlated with CYP3A activity in a panel of HLMs (r = 0.96, P = 0.0005) and mainly catalyzed by expressed CYP3A4 and CYP3A5. The Km values obtained from HLMs were also close to those from CYP3A4 and CYP3A5. Formation of anastrozole glucuronide in a bank of HLMs was correlated strongly with imipramine N-glucuronide, a marker of UGT1A4 (r = 0.72, P < 0.0001), while expressed UGT1A4 catalyzed its formation at the highest rate. Hydroxyanastrozole (mainly as a glucuronide) and anastrozole were quantified in plasma of breast cancer patients taking anastrozole (1 mg day?1); anastrozole glucuronide was less apparent. CONCLUSION Anastrozole is oxidized to hydroxyanastrozole mainly by CYP3A4 (and to some extent by CYP3A5 and CYP2C8). Once formed, this metabolite undergoes glucuronidation. Variable activity of CYP3A4 (and probably UGT1A4), possibly due to genetic polymorphisms and drug interactions, may alter anastrozole disposition and its effects in vivo. PMID:21175441

  3. The C-glycosyl flavonoid, aspalathin, is absorbed, methylated and glucuronidated intact in humans.

    PubMed

    Courts, Fraser L; Williamson, Gary

    2009-09-01

    Human bioavailability of the flavonoid dihydrochalcones is little understood, and no evidence exists for C-glycosyl flavonoid absorption in humans. The present study uses catechol-O-methyltransferase to generate methylated metabolites of aspalathin (a C-glycosyl dihydrochalcone from rooibos tea). One of the methylated forms, both with and without glucuronidation, was detected using LC-MS/MS in the urine of human subjects (n = 6), demonstrating that deglycosylation is not a prerequisite for C-glycosyl flavonoid absorption. Methylation is catalysed by both intestine and liver cytosolic extracts. The results show that flavonoid C-glycosides are methylated and glucuronidated in vivo in an intact form in humans. PMID:19653227

  4. Determining the Partial Photoionization Cross-Sections of Ethyl Radicals B. L. FitzPatrick, M. Maienschein-Cline, and L. J. Butler*

    E-print Network

    Butler, Laurie J.

    on the internal energy10 and electronic state11 of the radical being ionized. Thus, it is important of China ReceiVed: May 17, 2007; In Final Form: June 20, 2007 Using a crossed laser-molecular beamH5 + , C2H4 + , and C2H3 + at 12.1 and 13.8 eV. The data also determine the internal energy

  5. Ethyl diazoacetate synthesis in flow

    PubMed Central

    Delville, Mariëlle M E; van Hest, Jan C M

    2013-01-01

    Summary Ethyl diazoacetate is a versatile compound in organic chemistry and frequently used on lab scale. Its highly explosive nature, however, severely limits its use in industrial processes. The in-line coupling of microreactor synthesis and separation technology enables the synthesis of this compound in an inherently safe manner, thereby making it available on demand in sufficient quantities. Ethyl diazoacetate was prepared in a biphasic mixture comprising an aqueous solution of glycine ethyl ester, sodium nitrite and dichloromethane. Optimization of the reaction was focused on decreasing the residence time with the smallest amount of sodium nitrite possible. With these boundary conditions, a production yield of 20 g EDA day?1 was achieved using a microreactor with an internal volume of 100 ?L. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. PMID:24062847

  6. 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,...

  7. URINARY PHARMACOKINETICS OF THE GLUCURONIDE AND SULFATE CONJUGATES OF GENISTEIN AND DAIDZEIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of soybean-rich diets is thought to provide to provide significant health benefits such as prevention of cancer, primarily because of the high contents of factors such as the isoflavones genistein and diadzein. Isoflavones circulate and are excreted into the urine mainly as glucuronide ...

  8. 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...

  9. 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 Development of Sensitive Immunoassays for the Detection of the Glucuronide Conjugate of 3-Phenoxybenzyl Alcohol, a

    E-print Network

    Hammock, Bruce D.

    the benzyl alcohol and the benzoic acid may undergo further metabolism to glucuronide, glycine, taurine- benzyl alcohol (3-PBAlc-Gluc) should be a useful biomarker for exposure to type I pyrethroids-Phenoxybenzyl Alcohol, a Putative Human Urinary Biomarker for Pyrethroid Exposure HEE-JOO KIM, KI CHANG AHN

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

    PubMed Central

    Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

    2014-01-01

    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

  11. 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

  12. 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

  13. S-Ethyl dipropylthiocarbamate (EPTC)

    Integrated Risk Information System (IRIS)

    S - Ethyl dipropylthiocarbamate ( EPTC ) ; CASRN 759 - 94 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessme

  14. Ethyl levulinate: A potential bio-based diluent for biodiesel which improves cold flow properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The physical properties of biodiesel from soybean, canola, cottonseed and poultry fat methyl esters were improved with addition of ethyl levulinate with increasing concentration. The effect of adding ethyl levulinate was determined by studying its influence on the acid value, cloud point, pour point...

  15. Simultaneous Determination of Six Active Compounds in Yixin Badiranjibuya Granules, a Traditional Chinese Medicine, by RP-HPLC-UV Method

    PubMed Central

    Yu, Ning; He, ChenHui; Awuti, Gulistan; Zeng, Cheng; Xing, JianGuo; Huang, Wei

    2015-01-01

    In this study, a sensitive, precise, and accurate HPLC-UV method was developed and validated to simultaneously determine the six analytes (luteolin-7-O-?-D-glucuronide, apigenin-7-O-?-D-glucuronide, diosmetin-7-O-?-D-glucuronide, acacetin-7-O-?-D-glucuronide, tilianin, and rosmarinic acid) in Yixin Badiranjibuya Granules, in which five analytes (i.e., luteolin-7-O-?-D-glucuronide, apigenin-7-O-?-D-glucuronide, diosmetin-7-O-?-D-glucuronide, acacetin-7-O-?-D-glucuronide, and rosmarinic acid) were determined for the first time in Yixin Badiranjibuya Granules, the content of tilianin in Yixin Badiranjibuya Granules was reported in other literatures, and the content of tilianin in our work was higher than that of the literature reports. The quality of 11 batch samples from four different manufacturers was evaluated using the proposed determination method. The contents of the six analytes were largely different among samples from various manufacturers. Therefore, this determination method can provide a scientific basis for quality evaluation and control of Yixin Badiranjibuya Granules. PMID:26587308

  16. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  17. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  18. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  19. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  1. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  2. Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

    PubMed

    Tephly, T R; Coffman, B; Styczynski, P; Rios, G; Charkowski, D M; Vanrollins, M; McQuade, R D; Tedford, C E

    1994-01-01

    Dopamine D-1 receptor antagonists are currently under investigation for use as antipsychotic agents. Two potent and selective D-1 receptor antagonists, SCH 39166 and SCH 23390, have been studied extensively in various experimental animal models. SCH 39166 has a more prolonged duration of action in primates in vivo and a lower rate of in vitro glucuronidation by microsomes from squirrel monkey liver. Because the rate of glucuronidation seems to govern the duration of action and may limit the use of these agents in humans, the glucuronidation of SCH 39166 and SCH 23390 by microsomes isolated from human liver was studied. The rates of glucuronide formation (Vmax) for SCH 39166 were much lower than those of SCH 23390, yet the KM values were similar. Therefore, the average efficiency (Vmax/KM) of SCH 39166 glucuronidation was only 14% that of SCH 23390. These results agree with previous studies in hepatic microsomes from squirrel monkeys. Marked inhibition of SCH 39166 glucuronidation by SCH 23390 and its pharmacologically inactive stereoisomer, SCH 23388, was observed. The inactive stereoisomer of SCH 39166, SCH 39165, was a weak inhibitor. In contrast, substrates for morphine UDP-glucuronosyltransferase (UGT), and p-nitrophenol, an alternative substrate for numerous human hepatic UGTs, did not inhibit SCH 39166 glucuronidation. Further separation of human hepatic UGTs activities using chromatofocusing chromatography indicated that SCH 39166 UGT activity was distinct from human hepatic UGT2B15 and human hepatic pI 6.2 UGT activity. Thus, a unique human hepatic UGT may be involved in SCH 39166 glucuronidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7835222

  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. 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

  5. Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation.

    PubMed

    Cong, Ming; Hu, Cui-Min; Cao, Yun-Feng; Fang, Zhong-Ze; Tang, Shu-Hong; Wang, Jia-Rui; Luo, Jun-Sheng

    2013-03-01

    Danshen is one of the most famous herbs in the world, and more and more danshen-prescribed drugs interactions have been reported in recent years. Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro the human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0.4 and 1.7?M, respectively. Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol. PMID:23333907

  6. In Vitro Effects of Bisphenol A ?-D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes

    PubMed Central

    Boucher, Jonathan G.; Boudreau, Adčle; Ahmed, Shaimaa

    2015-01-01

    Background Exposure to common environmental substances, such as bisphenol A (BPA), has been associated with a number of negative health outcomes. In vivo, BPA is rapidly converted to its predominant metabolite, BPA-glucuronide (BPA-G), which has long been believed to be biologically inactive because it lacks estrogenic activity. However, the effects of BPA-G on cellular metabolism have not been characterized. In the present study we examined the effect of BPA-G on adipogenesis. Methods The effect of BPA-G on the differentiation of human and 3T3L1 murine preadipocytes was evaluated in vitro by quantifying lipid accumulation and the expression of adipogenic markers. Results Treatment of 3T3L1 preadipocytes with 10 ?M BPA-G induced a significant increase in lipid accumulation, mRNA expression of the adipogenic markers sterol regulatory element binding factor 1 (SREBF1) and lipoprotein lipase (LPL), and protein levels of LPL, aP2, and adipsin. Treatment of primary human preadipocytes with BPA-G also induced adipogenesis as determined by aP2 levels. Co-treatment of cells with the estrogen receptor (ER) antagonist fulvestrant (ICI) significantly inhibited the BPA-G–induced increase in LPL and aP2 levels, whereas treatment with ICI alone had no effect. Moreover, BPA-G did not display any significant estrogenic activity. Conclusions To our knowledge, this study is the first to report that BPA-G induces adipocyte differentiation and is not simply an inactive metabolite. The fact that BPA-G induced adipogenesis and was inhibited by an ER antagonist yet showed no estrogenic activity suggests that it has no classical ER transcriptional activation function and acts through a pathway that remains to be determined. Citation Boucher JG, Boudreau A, Ahmed S, Atlas E. 2015. In vitro effects of bisphenol A ?-D-glucuronide (BPA-G) on adipogenesis in human and murine preadipocytes. Environ Health Perspect 123:1287–1293;?http://dx.doi.org/10.1289/ehp.1409143 PMID:26018136

  7. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  8. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  9. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  10. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the National Academy Press, Box... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and....1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH. (b) The ingredient meets...

  11. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  12. Enantioselective Metabolism of Quizalofop-Ethyl in Rat

    PubMed Central

    Liang, Yiran; Wang, Peng; Liu, Donghui; Shen, Zhigang; Liu, Hui; Jia, Zhixin; Zhou, Zhiqiang

    2014-01-01

    The pharmacokinetic and distribution of the enantiomers of quizalofop-ethyl and its metabolite quizalofop-acid were studied in Sprague-Dawley male rats. The two pairs of enantiomers were determined using a validated chiral high-performance liquid chromatography method. Animals were administered quizalofop-ethyl at 10 mg kg?1 orally and intravenously. It was found high concentration of quizalofop-acid in the blood and tissues by both intragastric and intravenous administration, and quizalofop-ethyl could not be detected through the whole study which indicated a quick metabolism of quizalofop-ethyl to quizalofop-acid in vivo. In almost all the samples, the concentrations of (+)-quizalofop-acid exceeded those of (?)-quizalofop-acid. Quizalofop-acid could still be detected in the samples even at 120 h except in brain due to the function of blood-brain barrier. Based on a rough calculation, about 8.77% and 2.16% of quizalofop-acid were excreted through urine and feces after intragastric administration. The oral bioavailability of (+)-quizalofop-acid and (?)-quizalofop-acid were 72.8% and 83.6%. PMID:24964043

  13. [Analysis of the reaction solution for dehydroacetic acid by ethyl acetoacetate using high formance liquid chromatography].

    PubMed

    Chen, Qiuyun; Duan, Zhengkang; Li, Haitao; Yan, Zhixiang; Peng, Ye; Zeng, Hangri

    2013-05-01

    A way of ethyl acetoacetate by the Claisen condensation reaction is one of the main methods of the industrial production of dehydroacetic acid. There are the problems of the differences in absorbance value and the maximum absorption wavelength, and the chromatographic peak is prone to the phenomena such as bifurcation and tailing when using liquid chromatography to the analysis of ethyl acetoacetate. To avoid the interference of the enol of ethyl acetoacetate, and making the peak shape of ethyl acetoacetate better and quantitatively more accurate, we converted the enol to ketone through optimizing the chromatographic conditions. As a result, qualitative and quantitative analyses of ethyl acetoacetate were replaced by those of the ethyl acetoacetate ketone. A method was developed for the simultaneous determination of dehydroacetic acid and ethyl acetoacetate by HPLC in the reaction mixture for producing dehydroacetic acid. An Agilent HC-C18 column (250 mm x 4.6 mm, 5 microm) was used for the separation. The ultraviolet wavelength was 290 nm and the column temperature was 35 degrees C, and methanol-0.3% ammonium acetate buffer (5: 95, v/v) with pH 6.0 adjusted by acetic acid as mobile phase, and the flow rate was 0.6 mL/min. The correlation coefficients of dehydroacetic acid and ethyl acetoacetate were 0.99995 and 0.99992, and the spiked recoveries were 98.5% and 101.3%, respectively; and the relative standard deviations were less than 1.0%. This meth- od has the advantages of good accuracy and high sensitivity, and it can analyse both qualitatively and quantitatively dehydroacetic acid and ethyl acetoacetate rapidly and simply. And it can provide the reference for producing dehydroacetic acid by the way of ethyl acetoacetate. PMID:24010347

  14. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... methanoate. It is an ester of formic acid and is prepared by esterification of formic acid with ethyl alcohol or by distillation of ethyl acetate and formic acid in the presence of concentrated sulfuric acid... as defined in § 170.3(n)(6), hard candy as defined in § 170.3(n)(25), and soft candy as defined...

  15. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether...

  16. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether...

  17. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction.

    PubMed

    Gufford, Brandon T; Chen, Gang; Vergara, Ana G; Lazarus, Philip; Oberlies, Nicholas H; Paine, Mary F

    2015-09-01

    Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine. Key constituents in milk thistle, flavonolignans, were previously shown to be potent inhibitors of intestinal UDP-glucuronosyl transferases (UGTs), with IC50s ? 10 ?M. Taken together, milk thistle preparations may perpetrate unwanted interactions with raloxifene. The objective of this work was to evaluate the inhibitory effects of individual milk thistle constituents on the intestinal glucuronidation of raloxifene using human intestinal microsomes and human embryonic kidney cell lysates overexpressing UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine that are critical to raloxifene clearance. The flavonolignans silybin A and silybin B were potent inhibitors of both raloxifene 4'- and 6-glucuronidation in all enzyme systems. The Kis (human intestinal microsomes, 27-66 µM; UGT1A1, 3.2-8.3 µM; UGT1A8, 19-73 µM; and UGT1A10, 65-120 µM) encompassed reported intestinal tissue concentrations (20-310 µM), prompting prediction of clinical interaction risk using a mechanistic static model. Silibinin and silymarin were predicted to increase raloxifene systemic exposure by 4- to 5-fold, indicating high interaction risk that merits further evaluation. This systematic investigation of the potential interaction between a widely used herbal product and chemopreventive agent underscores the importance of understanding natural product-drug interactions in the context of cancer prevention. PMID:26070840

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

    PubMed Central

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueńas, 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

  19. Vibrational spectroscopic studies of N1-ethyl-5?-bromo-7-azaindirubin-3?-oxime and N1-ethyl-indirubin-3?-monooxime

    NASA Astrophysics Data System (ADS)

    Li, Ying-Sing; Yao, Qi-Zheng; Wang, Zhao-Hui; Cheng, Jingcai; Truong, Tuyen Thi T.

    2015-05-01

    We have prepared N1-ethyl-5?-bromo-7-azaindirubin-3?-oxime due to its potential for being a pharmaceutical. Infrared and Raman spectra have been recorded and vibrational assignments have been suggested based mainly on our previous vibrational investigation of N1-isopropyl-5?-chloro-7-azaindirubin-3?-oxime and on group characteristic frequencies. Temperature variation study has revealed the presence of conformers due to the internal rotation of ethyl group. IR spectra collected for N1-ethyl-7-azaindirubin-3?-oxime have shown rather similar spectral features with that of N1-ethyl-5?-bromo-7-azaindirubin-3?-oxime. IR spectra of these compounds have revealed the association through hydrogen bonding in the solid state. IR spectra recorded for these samples after annealing at high temperatures indicated the thermal conversion temperature to be lowered than 270 °C. Results from thermal analyses have determined the beginning decomposition temperatures to be 250 °C and the decomposition enthalpies to be 94 kJ/mol for both N1-ethyl-5?-bromo-7-azaindirubin-3?-oxime and N1-ethyl-7-azaindirubin-3?-oxime.

  20. The in vitro formation of sulfates and glucuronides of estrogens by adult and fetal ovine tissues.

    PubMed

    Hobkirk, R; Cardy, C A

    1985-08-01

    Incubation of nanomolar concentrations of [3H]estrone with ovine liver slices from adult and fetal animals demonstrated, in particular, the production of estrogen sulfates together with smaller amounts of glucuronides, even although microsomal estrogen glucuronyltransferase (GT) and sulfatase activities were high, especially in adult tissue. [3H]Estriol was conjugated almost exclusively as sulfate under the same experimental conditions. Slices of maternal and fetal kidney medulla were also strikingly active in promoting estrogen sulfate production as were slices of fetal kidney cortex. Adult kidney cortex conjugated estrogen only in the glucuronide form. These data indicate the possibility that maternal and fetal liver and kidney might contribute to the high circulating level of estrone sulfate in the pregnant sheep. Through the use of [3H]estrone and [3H]estrone sulfate as substrates, it was possible to demonstrate that adult slices of kidney medulla possessed relatively low sulfatase, considerable sulfotransferase (ST), and virtually no GT activity, whereas cortex had high sulfatase, little or no ST, and low, though demonstrable, GT activity. The ST activity of kidney high-speed supernatants was stimulated by the presence of sulfhydryl groups, whereas that in liver was not. Enzymic reduction of estrone and (or) estrone sulfate by liver and kidney slices indicated that, in the former, 17 alpha-reduction prevailed and, in the latter with the exception of the maternal medulla, 17 beta-reduction was the main pathway, particularly in the fetus. PMID:2998578

  1. Extraction of aromatics with ethyl acetoacetate

    SciTech Connect

    Hosler, P.

    1986-06-10

    A liquid phase extraction process is described for the dearomatization of a mixed hydrocarbon feed containing aromatic and nonaromatic hydrocarbons consisting of: (a) contacting the mixed feed in an extraction zone with the solvent ethyl acetoacetate at an elevated temperature to provide an aromatic-rich ethyl acetoacetate solvent phase containing the aromatic hydrocarbons, and a raffinate containing primarily non-aromatic hydrocarbons; (b) recovering and cooling the aromatic-rich solvent phase to form an upper phase comprising an aromatic-rich extract containing solvent and aromatic hydrocarbons, and a lower solvent-rich phase containing primarily the ethyl acetoacetate, and residual hydrocarbons; and (c) recovering the aromatic hydrocarbons and the raffinate.

  2. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl ethyl cellulose. 172.872 Section 172.872... CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose... of methyl groups and y is the number of ethyl groups. The average value of x is 0.3 and the...

  3. [Toxicology of ethyl gasoline 78 and 94].

    PubMed

    Starzy?ski, Z; Szyma?ska, S; Jaraczewska, W; My?lak, Z

    1978-01-01

    The authors have described clinical pictures of acute and chronic intoxication, especially toxic effect of ethyl gasoline upon nervous sytem, parenchymatous organs, and irritating effect on skin and mucous membranes. PMID:723613

  4. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...sulfuric acid. Ethyl formate occurs naturally in some plant oils, fruits, and juices but does not occur naturally in the animal kingdom. (b) The ingredient meets the specifications of the “Food Chemicals Codex,” 3d Ed. (1981),...

  5. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...sulfuric acid. Ethyl formate occurs naturally in some plant oils, fruits, and juices but does not occur naturally in the animal kingdom. (b) The ingredient meets the specifications of the “Food Chemicals Codex,” 3d Ed. (1981),...

  6. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, Jr., Lawrence A. (Houston, TX); Arganbright, Robert P. (Houston, TX); Hearn, Dennis (Houston, TX)

    1995-01-01

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50.degree. C. to 300.degree. C., using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered.

  7. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1995-12-19

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50 C to 300 C, using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered. 2 figs.

  8. Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition.

    PubMed

    Baer, Brian R; DeLisle, Robert Kirk; Allen, Andrew

    2009-07-01

    Gemfibrozil-1-O-beta-glucuronide (GEM-1-O-gluc), a major metabolite of the antihyperlipidemic drug gemfibrozil, is a mechanism-based inhibitor of P450 2C8 in vitro, and this irreversible inactivation may lead to clinical drug-drug interactions between gemfibrozil and other P450 2C8 substrates. In light of this in vitro finding and the observation that the glucuronide conjugate does not contain any obvious structural alerts, the current study was conducted to determine the potential site of GEM-1-O-gluc bioactivation and the subsequent mechanism of P450 2C8 inhibition (i.e., modification of apoprotein or heme). LC/MS analysis of a reaction mixture containing recombinant P450 2C8 and GEM-1-O-gluc revealed that the substrate was covalently linked to the heme prosthetic heme group during catalysis. A combination of mass spectrometry and deuterium isotope effects revealed that a benzylic carbon on the 2',5'-dimethylphenoxy group of GEM-1-O-gluc was covalently bound to the heme of P450 2C8. The regiospecificity of substrate addition to the heme group was not confirmed experimentally, but computational modeling experiments indicated that the gamma-meso position was the most likely site of modification. The metabolite profile, which consisted of two benzyl alcohol metabolites and a 4'-hydroxy-GEM-1-O-gluc metabolite, indicated that oxidation of GEM-1-O-gluc was limited to the 2',5'-dimethylphenoxy group. These results are consistent with an inactivation mechanism wherein GEM-1-O-gluc is oxidized to a benzyl radical intermediate, which evades oxygen rebound, and adds to the gamma-meso position of heme. Mechanism-based inhibition of P450 2C8 can be rationalized by the formation of the GEM-1-O-gluc-heme adduct and the consequential restriction of additional substrate access to the catalytic iron center. PMID:19445523

  9. IDENTIFICATION OF TWO GLUCURONIDE METABOLITES OF DOXYLAMINE VIA THERMOSPRAY/MASS SPECTROMETRY AND THERMOSPRAY/MASS SPECTROMETRY/MASS SPECTROMETRY

    EPA Science Inventory

    Analysis of a high-pressure liquid chromatography fraction containing two urinary glucuronide metabolites of doxylamine by thermospray mass spectrometry (TSP/MS) provided (MH)+ ions for each metabolite. TSP/MS/MS of the (MH)+ ions provided a fragment ion characteristic of these m...

  10. Multiple UDP- Glucuronosyltransferases in Human Liver Microsomes Glucuronidate Both R- and S-7-Hydroxywarfarin into Two Metabolites

    PubMed Central

    Pugh, C. Preston; Pouncey, Dakota L; Hartman, Jessica H.; Nshimiyimana, Robert; Desrochers, Linda P.; Goodwin, Thomas E.; Boysen, Gunnar; Miller, Grover P.

    2014-01-01

    The widely used anticoagulant Coumadin (R/S-warfarin) undergoes oxidation by cytochromes P450 into hydroxywarfarins that subsequently become conjugated for excretion in urine. Hydroxywarfarins may modulate warfarin metabolism transcriptionally or through direct inhibition of cytochromes P450 and thus, UGT action toward hydroxywarfarin elimination may impact levels of the parent drugs and patient responses. Nevertheless, relatively little is known about conjugation by UDP-glucuronosyltransferases in warfarin metabolism. Herein, we identified probable conjugation sites, kinetic mechanisms and hepatic UGT isoforms involved in microsomal glucuronidation of R- and S-7-hydroxywarfarin. Both compounds underwent glucuronidation at C4 and C7 hydroxyl groups based on elution properties and spectral characteristics. Their formation demonstrated regio- and enantioselectivity by UGTs and resulted in either Michaelis-Menten or substrate inhibition kinetics. Glucuronidation at the C7 hydroxyl group occurred more readily than at the C4 group, and the reaction was overall more efficient for R-7-hydroxywarfarin due to higher affinity and rates of turnover. The use of these mechanisms and parameters to model in vivo clearance demonstrated that contributions of substrate inhibition would lead to underestimation of metabolic clearance than that predicted by Michaelis-Menten kinetics. Lastly, these processes were driven by multiple UGTs indicating redundancy in glucuronidation pathways and ultimately metabolic clearance of R- and S-7-hydroxywarfarin. PMID:25447818

  11. 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...

  12. Mouse hepatoma cell lines differing in aryl hydrocarbon receptor-mediated signaling have different activities for glucuronidation.

    PubMed

    Burkhardt, B; Jung, S A; Pfeiffer, E; Weiss, C; Metzler, M

    2012-04-01

    For studies on the aryl hydrocarbon receptor (AhR)-dependent toxicity of the mycotoxins alternariol (AOH) and alternariol methyl ether (AME), three mouse hepatoma (Hepa-1) cell lines with intact and with compromised AhR signaling were compared with respect to their activities for hydroxylation, methylation, and glucuronidation. Whereas the activities of cytochrome P450-mediated monooxygenase and catechol-O-methyl transferase were very low and did not differ between the three cell lines, a pronounced difference was observed for UDP-glucuronosyl transferase activity, which was much higher in Hepa-1c1c4 than in c1c7 and c1c12 cells. In all three cell types, the rate of glucuronidation of AOH was about four times higher than that of AME. Whereas AME caused a concentration-dependent G2/M arrest in each cell line, AOH arrested Hepa-1c1c7 and c1c12 cells but not c1c4 cells. However, Hepa-1c1c4 cells were arrested by AOH when ?-glucuronidase was added to the incubation medium in order to reverse the formation of AOH glucuronides. We conclude that the failure of AOH to cause cell cycle inhibition in Hepa-1c1c4 cells is due to its efficient glucuronidation. The considerable UDP-glucuronosyl transferase activity of Hepa-1c1c4 cells should be taken into account when other compounds are studied in this cell line. Moreover, we demonstrate that differences in glucuronide formation between cell types can be overcome by the addition of ?-glucuronidase to the cell culture medium. PMID:22143556

  13. Enhanced potency of intravenous, but not intrathecal, morphine and morphine-6-glucuronide after burn trauma.

    PubMed

    Langlade, A; Carr, D B; Serrie, A; Silbert, B S; Szyfelbein, S K; Lipkowski, A W

    1994-01-01

    We examined the analgesic effect of morphine (M) and its metabolite morphine-6-glucuronide (M6G) in a rat model of acute thermal trauma. M or M6G were given by intrathecal (IT) or intravenous (i.v.) routes after brief burn or sham burn delivered during inhalational anesthesia. In the sham group, M6G was significantly less potent than M when given i.v., yet tended to be more potent than M when given IT. For both drugs, thermal injury increased i.v. potency, yet decreased (for M) or displayed a trend to decrease (for M6G) It potency. The increased potency seen with i.v. but not IT opioid administration may reflect pharmacokinetic (e.g., diminished clearance) and/or pharmacodynamic responses (e.g., activation of peripheral opioid receptors) after thermal injury. PMID:8177011

  14. Skin of the male African catfish, Clarias gariepinus: a source of steroid glucuronides

    SciTech Connect

    Ali, S.A.; Schoonen, W.G.; Lambert, J.G.; Van den Hurk, R.; Van Oordt, P.G.

    1987-06-01

    Steroid metabolism in the skin of mature male African catfish, Clarias gariepinus, reared in the laboratory, was studied in vitro by tissue incubations with (/sup 3/H)pregnenolone, (/sup 3/H)dehydroepiandrosterone, (/sup 3/H)17 alpha-hydroxyprogesterone, (/sup 3/H)androstenedione, (/sup 14/C)11 beta-hydroxyandrostenedione, and (/sup 3/H)testosterone as precursors. While pregnenolone was not converted to any other steroid, dehydroepiandrosterone was transformed mainly to 5-androstene-3 beta, 17 beta-diol. The products of 17 alpha-hydroxyprogesterone incubations were 5 beta-pregnane-3 alpha,17 alpha-diol-20-one, 5 beta-pregnane-3 alpha,17 alpha, 20 beta-triol, and 5 beta-pregnan-17 alpha-o1-3,20-dione. The major steroids of androstenedione incubations were etiocholanolone, testosterone, and androsterone. Testosterone was converted mainly to etiocholanolone and androstenedione, and only small quantities of 11 beta-hydroxytestosterone, 11-ketotestosterone, and 11-ketoandrostenedione were the metabolites found in 11 beta-hydroxyandrostenedione incubation. These results demonstrated the presence of the enzymes 5 alpha- and 5 beta-reductases and 3 alpha-, 11 beta-, 17 beta-, and 20 beta-hydroxysteroid dehydrogenases in the skin. From enzymehistochemical results it appeared that the steroid conversions take place in the epithelial cells. Moreover, the presence of UDP-glucose dehydrogenase, an enzyme involved in the synthesis of glucuronic acid, in these cells indicates the possibility of steroid glucuronide formation. Indeed significant amounts of water-soluble steroid conjugates, particularly 5 beta-dihydrotestosterone- and testosterone-glucuronide, were found in the incubations with androstenedione and testosterone, indicating the presence of the UDP-glucuronosyl transferase in the catfish skin.

  15. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS...

  16. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS...

  17. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS...

  18. Fenfluramine hydrochloride, (+-)-N-ethyl-m-(trifluoromethyl)amphetamine hydrochloride

    E-print Network

    Grunewald, Gary L.; Creese, Mary W.; Extine, Michael W.

    1981-01-01

    . 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...

  19. 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

  20. 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. PMID:25952649

  1. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong...

  2. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong...

  3. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong...

  4. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong...

  5. 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)...

  6. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease.

    PubMed

    Ho, Lap; Ferruzzi, Mario G; Janle, Elsa M; Wang, Jun; Gong, Bing; Chen, Tzu-Ying; Lobo, Jessica; Cooper, Bruce; Wu, Qing Li; Talcott, Stephen T; Percival, Susan S; Simon, James E; Pasinetti, Giulio Maria

    2013-02-01

    Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of ?-amyloid (A?) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on A? generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of A?(1-40) and A?(1-42) that is necessary for the formation of neurotoxic oligomeric A? species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD. PMID:23097297

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl...

  8. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl...

  9. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl...

  10. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl...

  11. Ethyl p-nitrophenyl phenylphosphorothioate (EPN)

    Integrated Risk Information System (IRIS)

    Ethyl p - nitrophenyl phenylphosphorothioate ( EPN ) ; CASRN 2104 - 64 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Ha

  12. 21 CFR 172.868 - Ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl cellulose. 172.868 Section 172.868 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

  13. 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.

  14. 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.

  15. Perylenetetracarboxylic diimide (PTCDI) nanowires for sensing ethyl acetate in wine.

    PubMed

    Khopkar, Yashdeep; Kojtari, Arben; Swearer, Dayne; Zivanovic, Sandra; Ji, Hai-Feng

    2014-09-01

    We report the application of perylenetetracarboxylic diimide (PTCDI) nanowires for sensing ethyl acetate. The conductivity of the crystalline nano/microwires increases quickly and selectively in the presence of ethyl acetate vapor, but not with water, acid and alcohol vapors, suggesting that the nanowires of PTCDI may be used for monitoring ethyl acetate during a wine manufacturing process. PMID:25924331

  16. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl,...

  17. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl,...

  18. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl,...

  19. The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide.

    PubMed

    Karbownik, Agnieszka; Sza?ek, Edyta; Soba?ska, Katarzyna; Po?om, Wojciech; Grabowski, Tomasz; Biczysko-Murawa, Anna; Matuszewski, Marcin; Wolc, Anna; Grze?kowiak, Edmund

    2015-06-01

    The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0-t , AUC0-? , and C max and lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 ?g/mL (90 % CI 1.06, 1.25; p = 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p = 0.0375). The mean t max of paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean t max of sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p = 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol. PMID:24676873

  20. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease

    PubMed Central

    Ho, Lap; Ferruzzi, Mario G.; Janle, Elsa M.; Wang, Jun; Gong, Bing; Chen, Tzu-Ying; Lobo, Jessica; Cooper, Bruce; Wu, Qing Li; Talcott, Stephen T.; Percival, Susan S.; Simon, James E.; Pasinetti, Giulio Maria

    2013-01-01

    Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of ?-amyloid (A?) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on A? generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of A?1–40 and A?1–42 that is necessary for the formation of neurotoxic oligomeric A? species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.—Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T.-Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., Pasinetti, G. M. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. PMID:23097297

  1. Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds.

    PubMed

    Wang, Meiyu; Qi, Huixin; Li, Jiajun; Xu, Yunting; Zhang, Hongjian

    2015-12-01

    Steviol glucuronide (SVG) is the major metabolite derived from steviol, the aglycone of stevioside and rebaudioside A. After the ingestion of stevioside and rebaudioside A, SVG is formed and excreted into the urine in humans. In the present study, transporter mediated efflux and uptake of SVG was investigated in order to understand molecular mechanisms underlying its renal clearance. Results showed that SVG was not a substrate of efflux transporters BCRP, MRP2, MATE1 or P-gp. In contrast, OAT3 played a predominant role in the uptake of SVG in comparison to OATP1B1, OATP1B3, or OATP2B1. Quercetin, telmisartan, diclofenac, and mulberrin displayed a relatively strong inhibition against OAT3 mediated uptake of SVG with IC50 values of 1.8, 2.9, 8.0, and 10.0 ?M, respectively. Because OAT3 is a major uptake transporter in the kidney, inhibition of OAT3 activity may alter SVG's renal clearance by drugs and natural compounds that are used concomitantly with stevia leaf extracts. PMID:26525112

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

    SciTech Connect

    Ohara, Kazuaki; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa; Shindo, Kazutoshi; Yajima, Hiroaki; Yoshida, Aruto

    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.

  3. Degradation behaviour of pyrazosulfuron-ethyl in water as affected by pH.

    PubMed

    Singh, Shashi B; Singh, Neera

    2013-01-01

    Pyrazosulfuron-ethyl, a new herbicide belonging to the sulfonylurea group, is used for weed control in rice crops growing in areas varying from acidic to alkaline soils. This study was undertaken to determine the degradation behaviour of pyrazosulfuron-ethyl in distilled water and buffer solutions at pH 4, 7 and 9. Degradation was pH-dependent and herbicide was least persistent in acidic pH followed by alkaline and neutral pH. The half-life of pyrazosulfuron-ethyl varied from 2.6 days (pH 4) to 19.4 days (pH 7) and half-life in distilled water was comparable to half-life at pH 7 buffer. HPLC analysis of different pH samples showed the formation of three metabolites viz., 5-(aminosulfonyl)-1-methyl-1H-pyrazole-4-carboxylic acid; ethyl 5-(aminosulfonyl)-1-methyl-1H-pyrazole-4-carboxylate and 2-amino-4,6-dimethoxy pyrimidine. The formation of pyrazosulfuron acid [5-([([(4,6-dimethoxy-2 pyrimidinyl)-amino]-carbonyl) amino]-sulfonyl)-1-methyl-1H-pyrazole-4-carboxylic acid] was not observed at any pH. The study indicated that the herbicide was least stable under acidic conditions and the predominant degradation route of pyrazosulfuron-ethyl in water is hydrolysis of sulfonamide linkage. PMID:23374044

  4. The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential.

    PubMed

    Miners, John O; Mackenzie, Peter I; Knights, Kathleen M

    2010-02-01

    Major advances in the characterization of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) enzyme substrate and inhibitor selectivities and the development of experimental paradigms to investigate xenobiotic glucuronidation in vitro now permit the prediction of a range of drug-glucuronidation parameters in humans. In particular, the availability of substrate and inhibitor "probes" for the major hepatic drug metabolizing UGTs together with batteries of recombinant enzymes allow the reaction phenotyping of drug glucuronidation reactions. Additionally, in vitro experimental approaches and scaling strategies have been successfully applied to the quantitative prediction of in vivo clearance via glucuronidation and drug-drug interaction potential. PMID:19795925

  5. Glucuronidation of bavachinin by human tissues and expressed UGT enzymes: Identification of UGT1A1 and UGT1A8 as the major contributing enzymes.

    PubMed

    Lv, Xia; Hou, Jie; Xia, Yang-Liu; Ning, Jing; He, Gui-Yuan; Wang, Ping; Ge, Guang-Bo; Xiu, Zhi-Long; Yang, Ling

    2015-10-01

    Bavachinin (BCI), a major bioactive compound in Chinese herbal Psoralea corylifolia, possesses a wide range of biological activities. In this study, the glucuronidation pathway of BCI was characterized for the first time, by using pooled human liver microsomes (HLM), pooled human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). One mono-glucuronide was detected in HLM in the presence of uridine-diphosphate glucuronic acid (UDPGA), and it was biosynthesized and well-characterized as BCI-4'-O-glucuronide (BCIG). Reaction phenotyping assay showed that UGT1A1, UGT1A3 and UGT1A8 were involved in BCI-4'-O-glucuronidation, while UGT1A1 and UGT1A8 displayed the higher catalytic ability among all tested UGT isoforms. Kinetic analysis demonstrated that BCI-4'-O-glucuronidation in both HLM and UGT1A1 followed sigmoidal kinetic behaviors and displayed much close Km values (12.4 ?M in HLM & 9.7 ?M in UGT1A1). Both chemical inhibition assays and correlation analysis demonstrated that UGT1A1 displayed a predominant role in BCI-4'-O-glucuronidation in HLM. Both HIM and UGT1A8 exhibited substrate inhibition at high concentrations, and Km values of HIM and UGT1A8 were 3.6 and 2.3 ?M, respectively. Similar catalytic efficiencies were observed for HIM (199.3 ?L/min/mg) and UGT1A8 (216.2 ?L/min/mg). These findings suggested that UGT1A1 and UGT1A8 were the primary isoforms involved in BCI-4'-O-glucuronidation in HLM, and HIM, respectively. PMID:26320626

  6. Persistence of pyrazosulfuron-ethyl and halosulfuron-methyl in aqueous solutions: Comparing hydrolytic dissipation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrazosulfuron-ethyl and halosulfuron-methyl are two new highly active sulfonylurea herbicides that have been widely used for weed control in many crops. Chemical hydrolysis is a primary process to determine the environmental fates of this group of pesticides. The hydrolytic dissipation of two herbi...

  7. Deuterium Exchange in Ethyl Acetoacetate: An Undergraduate GC-MS [Gas Chromatography-Mass Spectroscopy] Experiment

    ERIC Educational Resources Information Center

    Heinson, C. D.; Williams, J. M.; Tinnerman, W. N.; Malloy, T. B.

    2005-01-01

    The role of ethanol O-d in nullifying the deuterolysis may be demonstrated by determining that transesterification of methyl acetoacetate of the ethyl ester occurs as well as deuterium exchange of the five acetoacetate hydrogens. The significant acidity of the methylene protons in the acetoacetate group, the efficacy of base catalysis, the role of…

  8. Centrifugal distortion and internal rotation analysis of the microwave spectrum of ethyl fluoride

    SciTech Connect

    Fliege, E.; Dreizler, H.; Demaison, J.; Boucher, D.; Burie, J.; Dubrulle, A.

    1983-03-15

    The internal rotation fine structure of the microwave spectrum of ethyl fluoride CH/sub 3/CH/sub 2/F was resolved and analyzed in the ground state. The assignment of the high J lines was checked by a centrifugal distortion analysis. The barrier height V/sub 3/ determined from the ground state is 3349 +- 4 cal/mol.

  9. Production of ethyl alcohol from bananas

    SciTech Connect

    Jones, R.L.; Towns, T.

    1983-12-01

    The production of ethyl alcohol from waste bananas presents many special problems. During cooking, matting of the latex fibers from the banana peel recongeal when cooled and left untreated. This problem has been addressed by Alfaro by the use of CaC1/sub 2/. Separation of solids prior to distillation of the mashes in an economical fashion and use of the by product are also of concern to banana processors.

  10. Synthesis of Ethyl Salicylate Using Household Chemicals

    NASA Astrophysics Data System (ADS)

    Solomon, Sally; Hur, Chinhyu; Lee, Alan; Smith, Kurt

    1996-02-01

    Ethyl salicylate is synthesized, isolated, and characterized in a three-step process using simple equipment and household chemicals. First, acetylsalicylic acid is extracted from aspirin tablets with isopropyl alcohol, then hydrolyzed to salicylic acid with muriatic acid, and finally, the salicylic acid is esterified using ethanol and a boric acid catalyst. The experiment can be directed towards high school or university level students who have sufficient background in organic chemistry to recognize the structures and reactions that are involved.

  11. 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.

    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].

  12. 1-Hydroxypyrene glucuronide as the major aqueous pyrene metabolite in tissue and gut fluid from the marine deposit-feeding polychaete Nereis diversicolor.

    PubMed

    Giessing, Anders M B; Mayer, Lawrence M; Forbes, Thomas L

    2003-05-01

    Both 1-hydroxypyrene and 1-hydroxypyrene glucuronide are identified as the primary phase I and phase II metabolites of the four-ringed polycyclic aromatic hydrocarbon (PAH) pyrene in the marine deposit-feeding polychaete Nereis diversicolor. Identification of pyrene and primary metabolites was performed using high-pressure liquid chromatography (HPLC) with diode-array detection and fluorescence detection (HPLC/DAD/F) and an ion-trap mass spectrometer for positive identification of 1-hydroxypyrene glucuronide. Besides 1-hydroxypyrene and 1-hydroxypyrene glucuronide, the HPLC/F trace of tissue samples from pyrene-exposed worms showed three additional low-intensity peaks that may be related to pyrene metabolism based on similar excitation/emission wavelengths. The peaks were all too low in intensity to be positively identified. Of the total PAH in tissue, 1-hydroxypyrene glucuronide, 1-hydroxypyrene, and pyrene constituted 73%, 2%, and 25% respectively. Gut elimination of metabolic products is supported by the identification of 1-hydroxypyrene and 1-hydroxypyrene glucuronide in both gut fluid and defecation water. Being the only phase I metabolite of pyrene, 1-hydroxypyrene becomes a useful marker for PAH exposure, and it may serve as a valuable model compound for assessing species-specific PAH metabolic capabilities. PMID:12729221

  13. 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.

  14. KEY COMPARISON: Final report on CCQM-K69 key comparison: Testosterone glucuronide in human urine

    NASA Astrophysics Data System (ADS)

    Liu, Fong-Ha; Mackay, Lindsey; Murby, John

    2010-01-01

    The CCQM-K69 key comparison of testosterone glucuronide in human urine was organized under the auspices of the CCQM Organic Analysis Working Group (OAWG). The National Measurement Institute Australia (NMIA) acted as the coordinating laboratory for the comparison. The samples distributed for the key comparison were prepared at NMIA with funding from the World Anti-Doping Agency (WADA). WADA granted the approval for this material to be used for the intercomparison provided the distribution and handling of the material were strictly controlled. Three national metrology institutes (NMIs)/designated institutes (DIs) developed reference methods and submitted data for the key comparison along with two other laboratories who participated in the parallel pilot study. A good selection of analytical methods and sample workup procedures was displayed in the results submitted considering the complexities of the matrix involved. The comparability of measurement results was successfully demonstrated by the participating NMIs. Only the key comparison data were used to estimate the key comparison reference value (KCRV), using the arithmetic mean approach. The reported expanded uncertainties for results ranged from 3.7% to 6.7% at the 95% level of confidence and all results agreed within the expanded uncertainty of the KCRV. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  15. 17alpha- and 17beta-boldenone 17-glucuronides: synthesis and complete characterization by 1H and 13C NMR.

    PubMed

    Casati, Silvana; Ottria, Roberta; Ciuffreda, Pierangela

    2009-02-01

    Boldenone is an androgenic anabolic steroid intensively used for growth promoting purposes in animals destined for meat production and as a performance enhancer in athletics. Therefore its use is officially banned either in animals intended for consumption or in humans. Because most anabolic steroids are completely metabolized and usually no parent steroid is excreted, metabolite identification is crucial to detect the illegal use of anabolic steroids either in humans or in livestock. 17alpha- and 17beta-boldenone 17-glucuronides were synthesized, purified and characterized in order to provide suitable standards for the identification and quantification of these metabolites. PMID:19071152

  16. 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

  17. Torsional barrier and equilibrium structure of ethyl cyanide

    NASA Astrophysics Data System (ADS)

    Demaison, J.; Margulčs, L.; Mäder, H.; Sheng, M.; Rudolph, H. D.

    2008-12-01

    The quadratic, cubic and semi-diagonal quartic force field of ethyl cyanide has been calculated at the B3LYP level of theory employing a basis set of triple-? quality. A semi-experimental equilibrium structure has been derived from experimental ground state rotational constants and rovibrational interaction parameters calculated from the ab initio force field. This structure is in excellent agreement with the ab initio structure calculated at the CCSD(T) level of theory using a basis set of quadruple-? quality and a core correlation correction. The empirical structures are also determined and their accuracy is discussed. The potential barrier V3 hindering internal rotation of the methyl group has been calculated from 23 rotational transitions of CH 3CH 2C 15N which were found split into doublets, giving V3 = 3074(27) cal mol -1.

  18. Interaction of Ethyl Alcohol Vapor with Sulfuric Acid Solutions

    NASA Technical Reports Server (NTRS)

    Leu, Ming-Taun

    2006-01-01

    We investigated the uptake of ethyl alcohol (ethanol) vapor by sulfuric acid solutions over the range approx.40 to approx.80 wt % H2SO4 and temperatures of 193-273 K. Laboratory studies used a fast flow-tube reactor coupled to an electron-impact ionization mass spectrometer for detection of ethanol and reaction products. The uptake coefficients ((gamma)) were measured and found to vary from 0.019 to 0.072, depending upon the acid composition and temperature. At concentrations greater than approx.70 wt % and in dilute solutions colder than 220 K, the values approached approx.0.07. We also determined the effective solubility constant of ethanol in approx.40 wt % H2SO4 in the temperature range 203-223 K. The potential implications to the budget of ethanol in the global troposphere are briefly discussed.

  19. Determination of 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene and related compounds in marine pore water by automated thermal desorption-gas chromatography/mass spectrometry using disposable optical fiber.

    PubMed

    Eganhouse, Robert P; DiFilippo, Erica L

    2015-10-01

    A method is described for determination of ten DDT-related compounds in marine pore water based on equilibrium solid-phase microextraction (SPME) using commercial polydimethylsiloxane-coated optical fiber with analysis by automated thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS). Thermally cleaned fiber was directly exposed to sediments and allowed to reach equilibrium under static conditions at the in situ field temperature. Following removal, fibers were rinsed, dried and cut into appropriate lengths for storage in leak-tight containers at -20°C. Analysis by TD-GC/MS under full scan (FS) and selected ion monitoring (SIM) modes was then performed. Pore-water method detection limits in FS and SIM modes were estimated at 0.05-2.4ng/L and 0.7-16pg/L, respectively. Precision of the method, including contributions from fiber handling, was less than 10%. Analysis of independently prepared solutions containing eight DDT compounds yielded concentrations that were within 6.9±5.5% and 0.1±14% of the actual concentrations in FS and SIM modes, respectively. The use of optical fiber with automated analysis allows for studies at high temporal and/or spatial resolution as well as for monitoring programs over large spatial and/or long temporal scales with adequate sample replication. This greatly enhances the flexibility of the technique and improves the ability to meet quality control objectives at significantly lower cost. PMID:26346188

  20. 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

  1. Distribution and Organoleptic Impact of Ethyl 3-Hydroxybutanoate Enantiomers in Wine.

    PubMed

    Lytra, Georgia; Cameleyre, Margaux; Tempere, Sophie; Barbe, Jean-Christophe

    2015-12-01

    Enantiomers of ethyl 3-hydroxybutanoate were assayed in 87 commercial wines from various vintages and origins, using chiral gas chromatography (?-cyclodextrin). Generally, ethyl 3-hydroxybutanoate levels were higher in red than in white wines of the same age. The average S/R enantiomeric ratio of this compound in red wine was approximately 75:25 (±13), with an average total concentration of ?450 (±150) ?g/L. In red wines, R-form levels increased gradually during aging, but no variations were observed in S-form concentrations. To our knowledge, no previous research had determined the enantiomeric distribution of this compound in wine. The olfactory threshold of the S-form in dilute alcohol solution was 21 mg/L, one-third that of the R-form: 63 mg/L. The S- and R-forms had different aromatic nuances. The olfactory threshold of their mixture (85:15, m/m) was 14 mg/L, indicating a simple additive effect in this binary mixture. Furthermore, the concentrations found in red wines were considerably below the olfactory threshold under the same experimental conditions. Sensory analysis revealed that ethyl 3-hydroxybutanoate (S/R, 85:15, m/m) had an enhancing effect on the perception of fruity aromas in the matrices studied. Sensory profiles highlighted the contribution of ethyl 3-hydroxybutanoate to red-berry and fresh-fruit descriptors, despite its subthreshold concentrations. PMID:26587875

  2. 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,...

  3. 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.

  4. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Ethyl ether. 151.50-42 Section 151.50-42 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-42 Ethyl ether. (a)(1) Gravity tanks shall be designed and tested to meet the...

  5. Metabolism of ethyl tiglate in apple fruits leads to the formation of small amounts of (R)-ethyl 2-methylbutanoate.

    PubMed

    Hauck, T; Weckerle, B; Schwab, W

    2000-01-01

    (S)-Ethyl 2-methylbutanoate is an important aroma compound in apples and serves as an indicator for genuineness of apple products due to its high optical purity of greater than 98% enantiomeric excess [T. Koenig and P. Schreier, Zeitsch. Lebensm.-Unters. Forsch. A, 1999, 208, 130-133; K. Schumacher et al., J. Agric. Food Chem., 1998, 46, 4496-4500]. The origin of minor amounts of (R)-ethyl 2-methylbutanoate is unknown as naturally occurring (+)-isoleucine, the proposed precursor of (S)-ethyl 2-methylbutanoate is enantiomerically pure. Since ethyl (E)-2-methyl-2-butenoate (ethyl tiglate) was recently discovered as a natural apple constituent and hydrogenation activity in apples was demonstrated we proposed ethyl tiglate as a precursor of (R)-ethyl 2-methylbutanoate. D4-3,4,4,4-ethyl tiglate was synthesized and was injected into ripe apple fruits (cv. Golden Delicious, Red Delicious and Granny Smith). After 3, 6, and 12 days apple volatiles were isolated by solid phase extraction on XAD-2 and the metabolites formed from D4-3,4,4,4-ethyl tiglate were analyzed by capillary gas chromatography-mass spectrometry (GC-MS). Ethyl 2-methylbutanoate, 2-methylbutyl acetate, 2-methylbutanol, and 2-methylbutanoic acid were identified as major transformation products. Chiral evaluation of the metabolites by multidimensional GC-MS revealed enantiomeric excesses ranging from 43% (S) to 30% (R) depending on the apple cultivar, sampling date and metabolite. The data show for the first time that the natural apple constituent ethyl tiglate can serve as a source for (R)-2-methylbutanol derivatives. PMID:11143814

  6. 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

  7. 40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethanaminium, N-ethyl-2-hydroxy-N,N... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

  8. Non-steroidal anti-inflammatory drugs do not influence the urinary testosterone/epitestosterone glucuronide ratio.

    PubMed

    Lundmark, Jonas; Gĺrevik, Nina; Thörngren, John-Olof; Garle, Mats; Ekström, Lena; Rane, Anders; Schulze, Jenny J

    2013-01-01

    The UDP Glucuronosyl Transferase (UGT) enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) as well as anabolic androgenic steroids (AAS). Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In vitro studies show inhibitory potential on UGT2B7, 2B15, and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG) as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test. The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 male healthy volunteers, with either two, one or no allele (ins/ins, ins/del, or del/del) of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac) for 6?days. On day three, 500?mg of testosterone enanthate was administered. Spot urine samples were collected for 17?days. After a wash-out period of 4?months the volunteers received 500?mg testosterone enanthate only, with subsequent spot urine collection for 14?days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs. PMID:23720652

  9. The gelation of oil using ethyl cellulose.

    PubMed

    Davidovich-Pinhas, M; Barbut, S; Marangoni, A G

    2015-03-01

    The characterization of the thermo-gelation mechanism and properties of ethyl cellulose/canola oil oleogels was performed using rheology and thermal analysis. Thermal analysis detected no evidence for thermal transitions contributed to secondary conformational changes, suggesting a gelation mechanism that does not involve secondary ordered structure formation. Rheological analysis demonstrated a relationship between the polymer molecular weight and the final gel strength, the cross-over behavior as well as the gel point temperature. Increasing polymer molecular weight led to an increase in final gel strength, the modulus at cross-over, and the gel point temperature. Cooling/heating rates affect gel modulus only for the low molecular weight samples. A decrease in gel strength with increasing cooling rate was detected. The cross-over temperature was not affected by the cooling/heating rates. Cooling rate also affected the gelation setting time where slow cooling rates produced a stable gel faster. PMID:25498711

  10. Protective Effect of Ethyl Acetate Fraction of Stereospermum Suaveolens Against Hepatic Oxidative Stress in STZ Diabetic Rats

    PubMed Central

    Balasubramanian, Thirumalaiswamy; Senthilkumar, G. P; Karthikeyan, M.; Chatterjee, Tapan Kumar

    2013-01-01

    Stereospermum suaveolens is a folk remedy for the treatment of diabetes and liver disorders in southern parts of India. In the present study, the protective effect of the ethyl acetate fraction of ethanol extract from S. suaveolens against hepatic oxidative stress was evaluated in streptozotocin (STZ)-induced diabetic rats for 14 days. The ethyl acetate fraction was administered orally to the STZ diabetic rats at the doses of 200 and 400 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine hepatoprotective activity, changes in the levels of serum biomarker enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), and serum alkaline phosphatase (SALP) were assessed in the ethyl acetate fraction treated diabetic rats and were compared with the levels in diabetic control rats. In addition, the antioxidant activity of ethyl acetate fraction was evaluated using various hepatic parameters such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). It was found that administration of ethyl acetate fraction (200 and 400 mg/kg) produced a significant (P < 0.001) fall in fasting blood glucose level, TBARS, bilirubin, AST, ALT, and SALP, while elevating the GSH levels, and SOD and CAT activities in diabetic rats. Histopathologic studies also revealed the protective effect of ethyl acetate fraction on the liver tissues of diabetic rats. It was concluded from this study that the ethyl acetate fraction from ethanol extract of S. suaveolens modulates the activity of enzymatic and nonenzymatic antioxidants and enhances the defense against hepatic oxidative stress in STZ-induced diabetic rats. PMID:24716175

  11. Two new cucurbitane-type triterpenoid saponins isolated from ethyl acetate extract of Citrullus colocynthis fruit.

    PubMed

    Song, Fei; Dai, Bin; Zhang, Hai-Yan; Xie, Jian-Wei; Gu, Cheng-Zhi; Zhang, Jie

    2015-01-01

    Two new cucurbitacins I (1 and 2), together with eight known compounds (3-10), were isolated from the ethyl acetate extract of the fruit of Citrullus colocynthis. Compounds 3, 5-9 were isolated from C. colocynthis for the first time. The structures of new compounds were determined primarily from IR, HR-MS, 1D-, and 2D-NMR analysis. PMID:25761128

  12. Mechanistic insight into alkylation of the ethyl acetoacetate anion with different ethyl halides

    NASA Astrophysics Data System (ADS)

    Markovi?, S.; ?ur?evi?, J.; Vukosavljevi?, M.; Petrovi?, Z.

    2013-12-01

    The alkylation reactions of the ambident ethyl acetoacetate anion with C2H5X (X = F, Cl, Br, and I) in the O2, C3, and O4 positions of the anion were investigated at the B3LYP/6-311+G( d,p) level of theory. It was found that the ethylation reaction does not occur in the position O4, as well as with ethyl fluoride in any position of the anion, due to very high activation energies and thermodynamic instability of the hypothetic products. The activation energies for the reactions in the position O2 are lower in comparison to the position C3, but the products of the reactions in the C3 position are more stable than those in the position O4, implying that the C/O products ratio is controlled by both thermodynamic and kinetic factors, leading to the O2-product with the chloride, and C3-product with the iodide as leaving group.

  13. Synthesis and Preliminary Chemotherapeutic Evaluation of the Fully C-Linked Glucuronide of N-(4-Hydroxyphenyl) retinamide (4-HPR)

    PubMed Central

    Walker, Joel R.; Alshafie, Galal; Nieves, Nirca; Ahrens, Jamie; Clagett-Dame, Margaret; Abou-Issa, Hussein; Curley, Robert W.

    2006-01-01

    All-trans retinoic acid (atRA) analogues such as N-(4-hydroxyphenyl) retinamide (4-HPR) are effective chemopreventive and chemotherapeutic agents but their utility has been hampered by dose-limiting side effects. The glucuronide derivatives of 4-HPR, the oxygen-linked 4-HPROG and the carbon-linked 4-HPRCG, have been found to be more effective agents. The synthetic route to the fully C-linked analogue of 4-HPROG (4-HBRCG), which employs Suzuki coupling and Umpolung chemistries as key methodologies, is shown. The results of this study show 4-HBRCG to be an effective chemotherapeutic agent in a rat mammary tumor model while being devoid of classical retinoid toxicities. PMID:16412653

  14. 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

  15. Glucuronide conjugation reduces the cytotoxicity but not the mutagenicity of benzo(a)pyrene in the CHO/HGPRT assay

    SciTech Connect

    Recio, L.; Hsie, A.W.

    1984-01-01

    Benzo(a)pyrene (B(a)P) is biotransformed by the mixed-function oxidase (MFO) system to numerous metabolites some of which are cytotoxic and/or mutagenic to mammalian cells. However, conjugation of B(a)P-induced metabolites with glucuronic acid in vivo is a major pathway of detoxication and elimination. The effects of glucuronide conjugation on B(a)P-induced cytotoxicity and mutagenicity were studied using the CHO-HGPRT assay with a rat liver homogenate preparation containing MFO system cofactors (S9 mix) and uridine diphosphate ..cap alpha..-D-glucuronic acid (UDPGA). B(a)P metabolites proximate to the biologically active B(a)P quinones (B(a)P 6-OH) and to the B(a)P 7,8-diol-9,10 epoxide isomers (B(a)P 7,8-diol), were also assayed with S9 mix in the absence and presence of UDPGA. The addition of UDPGA to S9 mix reduced B(a)P-induced cytotoxicity but did not affect mutagenicity. B(a)P 6-OH-mediated cytotoxicity was also reduced in the presence of UDPGA. UDPGA had no effect on B(a)P 7,8-diol-induced cytotoxicity or mutagenicity. B(a)P phenols have been shown to be the preferred B(a)P metabolite substrates for UDP-glucuronyltransferase enzymes. Thus, the reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to the elimination of cytotoxic phenols and quinones. Since B(a)P 7,8-diol is a poor substrate for UDP-glucuronyltransferase enzymes, no effects on B(a)P-induced mutagenicity or B(a)P 7,8-diol-induced cytotoxicity and mutagenicity were observed. 40 references, 3 figures, 2 tables.

  16. Species differences in sinusoidal and canalicular efflux transport of mycophenolic acid 7-O-glucuronide in sandwich-cultured hepatocytes.

    PubMed

    Tetsuka, Kazuhiro; Gerst, Nicolas; Tamura, Kouichi; Masters, Jeffrey N

    2014-04-01

    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

  17. Biodegradation of pyrazosulfuron-ethyl by Acinetobacter sp. CW17.

    PubMed

    Wang, Yanhui; Du, Liangwei; Chen, Yingxi; Liu, Xiaoliang; Zhou, Xiaomao; Tan, Huihua; Bai, Lianyang; Zeng, Dongqiang

    2012-03-01

    The pyrazosulfuron-ethyl-degrading bacterium, designated as CW17, was isolated from contaminated soil near the warehouse of the factory producing pyrazosulfuron-ethyl in Changsha city, China. The strain CW17 was identified as Acinetobacter sp. based on analyses of 94 carbon source utilization or chemical sensitivity in Biolog microplates, conventional phenotypic characteristics, and 16S rRNA gene sequencing. When pyrazosulfuron-ethyl was provided as the sole carbon source, the effects of pyrazosulfuron-ethyl concentration, pH, and temperature on biodegradation were examined. The degradation rates of pyrazosulfuron-ethyl at initial concentrations of 5.0, 20.0, and 50.0 mg/L were 48.0%, 77.0%, and 32.6%, respectively, after inoculation for 7 days. The growth of the strain was inhibited at low pH buffers. The chemical degradation occurs much faster at low pH than at neutral and basic pH conditions. The degradation rate of pyrazosulfuron-ethyl at 30°C was faster than those at 20 and 37°C by CW17 strains. Two metabolites of degradation were analyzed by liquid chromatography-mass spectroscopy (LC/MS). Based on the identified products, strain CW17 seemed to be able to degrade pyrazosulfuron-ethyl by cleavage of the sulfonylurea bridge. PMID:22388979

  18. Ethyl Esterification for MALDI-MS Analysis of Protein Glycosylation.

    PubMed

    Reiding, Karli R; Lonardi, Emanuela; Hipgrave Ederveen, Agnes L; Wuhrer, Manfred

    2016-01-01

    Ethyl esterification is a technique for the chemical modification of sialylated glycans, leading to enhanced stability when performing matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS), as well as allowing the efficient detection of both sialylated and non-sialylated glycans in positive ion mode. In addition, the method shows specific reaction products for ?2,3- and ?2,6-linked sialic acids, leading to an MS distinguishable mass difference. Here, we describe the ethyl esterification protocol for 96 glycan samples, including enzymatic N-glycan release, the aforementioned ethyl esterification, glycan enrichment, MALDI target preparation, and the MS(/MS) measurement. PMID:26700047

  19. In vitro protection of biological macromolecules against oxidative stress and in vivo toxicity evaluation of Acacia nilotica (L.) and ethyl gallate in rats

    PubMed Central

    2014-01-01

    Background Recently, enormous research has been focused on natural bioactive compounds possessing potential antioxidant and anticancer properties using cell lines and animal models. Acacia nilotica (L.) is widely distributed in Asia, Africa, Australia and Kenya. The plant is traditionally used to treat mouth, ear and bone cancer. However, reports on Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan regarding its toxicity profile is limited. Hence in this study, we investigated the antioxidant capacity and acute toxicity of ethyl gallate, a phenolic antioxidant present in the A. nilotica (L.) leaf extract. Methods The antioxidant activity of ethyl gallate against Fenton’s system (Fe3+/H2O2/ascorbic acid) generated oxidative damage to pBR322 DNA and BSA was investigated. We also studied the interaction of ethyl gallate to CT-DNA by wave scan and FTIR analysis. The amount of ethyl gallate present in the A. nilotica (L.) leaf extract was calculated using HPLC and represented in gram equivalence of ethyl gallate. The acute toxicity profile of ethyl gallate in the A. nilotica (L.) leaf extract was analyzed in albino Wistar rats. Measurement of liver and kidney function markers, total proteins and glucose were determined in the serum. Statistical analysis was done using statistical package for social sciences (SPSS) tool version 16.0. Results Ethyl gallate was found to be effective at 100 ?g/mL concentration by inhibiting the free radical mediated damage to BSA and pBR322 DNA. We also found that the interaction of ethyl gallate and A. nilotica (L.) leaf extract to CT-DNA occurs through intercalation. One gram of A. nilotica (L.) leaf extract was found to be equivalent to 20 mg of ethyl gallate through HPLC analysis. Based on the acute toxicity results, A. nilotica (L.) leaf extract and ethyl gallate as well was found to be non-toxic and safe. Conclusions Results revealed no mortality or abnormal biochemical changes in vivo and the protective effect of A. nilotica (L.) leaf extract and ethyl gallate on DNA and protein against oxidative stress in vitro. Hence, A. nilotica (L.) leaf extract or ethyl gallate could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy. PMID:25043389

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...expressed as the stoichiometric equivalent of quizalofop ethyl, in or on the commodity. Commodity Parts per million Pineapple 0.1 (d) Indirect or inadvertent residues. [Reserved] [63 FR 32759, June 16, 1998, as amended at 70 FR...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...expressed as the stoichiometric equivalent of quizalofop ethyl, in or on the commodity. Commodity Parts per million Pineapple 0.1 (d) Indirect or inadvertent residues. [Reserved] [63 FR 32759, June 16, 1998, as amended at 70 FR...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...expressed as the stoichiometric equivalent of quizalofop ethyl, in or on the commodity. Commodity Parts per million Pineapple 0.1 (d) Indirect or inadvertent residues. [Reserved] [63 FR 32759, June 16, 1998, as amended at 70 FR...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...as quizalofop-p ethyl ester, in or the raw agricultural commodities, as follows: Commodity Parts per million Pineapple 0.1 (d) Indirect or inadvertent residues. [Reserved] [63 FR 32759, June 16, 1998, as amended at 70 FR...

  4. 77 FR 26456 - Carfentrazone-ethyl; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-04

    ...carfentrazone-ethyl in target plants is through inhibition of the enzyme protoporphyrinogen oxidase (PPO) which is involved in...chlorophyll biosynthesis. In mammals, PPO is also an important enzyme in heme biosynthesis and its inhibition can lead...

  5. Orbital floor reconstruction with ethyl-2-cyanoacrylate.

    PubMed

    Nemoto, Hitoshi; Ito, Yoshinori; Kasai, Yoshiaki; Maruyama, Naoki; Kimura, Naohiro; Sumiya, Noriyoshi

    2015-02-01

    The orbital floor is one of the most frequently broken bones in maxillofacial fracture, and orbital reconstruction is needed in many cases. Various materials are used for orbital floor reconstruction. We report here orbital reconstruction using autologous orbital bone with cyanoacrylate. Entrapped soft tissues were freed and repositioned intraorbitally and bone fragments were gathered with a microscope simultaneously. The bone fragments were fixed to a board of bone with ethyl-2-cyanoacrylate and returned to the orbital fracture site. Of 96 fresh orbital floor fractures, this method was used for 31 (32.3%) patients. Simple reduction was performed in 48 patients. Bone graft with iliac crest was performed in the other 12 patients. Reconstruction with alloplastic materials was performed in 5 patients. Diplopia was corrected in 26 patients on whom this method was performed. The reconstructed bone collapsed into the maxillary sinus in 1 patient who underwent iliac bone graft on reoperation. Another 4 patients did not show diplopia preoperatively. None of the patients showed enophthalmos, foreign body reaction, or infection postoperatively. We were able to perform orbital bone reconstruction with autologous orbital bone without another donor site in 30 (62.5%) of 48 cases that required grafting. The indications for this method are that a sufficient quantity of bone fragments can be obtained and returned on a board of bone which can be stabilized in the orbit without collapsing into the maxillary sinus. Good results were obtained, and we consider this to be a safe and useful method. PMID:24149407

  6. The ethyl radical: Photoionization and theoretical studies

    SciTech Connect

    Ruscic, B.; Berkowitz, J.; Curtiss, L. A.; Pople, J. A.

    1989-07-01

    The ethyl radical has been produced by the F+C/sub 2/H/sub 6/ reaction, and studiedby photoionization mass spectrometry. The adiabatic ionization potential (IP) isfound to be 8.117+-0.008 eV. The radical and cation have been studied by the G1level of molecular orbital theory. The calculated adiabatic ionization potentialis 8.06 eV. On the basis of both experiment and theory, it is concluded that thecation in its ground state has a bridged structure. The adiabatic value resolvesa previous inconsistency involving ..delta../ital H//sup /circ///sub /ital f//(C/sub 2/H/sub 5/),..delta../ital H//sup /circ///sub /ital f//(C/sub 2/H/sup +//sub 5/) and IP (C/sub 2/H/sub 5/). Broadautoionizing structures are observed at higher energy. These features can berationalized as Rydberg states converging to the first excited state /sup 3//ital A//double prime/calculated to be at 12.05 eV.

  7. 40 CFR 180.183 - O,O-Diethyl S-[2-(ethyl-thio)ethyl] phosphorodithioate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...ethyl] phosphorothioate; calculated as disulfoton, in or on food commodities as follows: Commodity Parts per million Asparagus 0.1 (d) Indirect or inadvertent residues. [Reserved] [63 FR 2165, Jan. 14, 1998, as amended at 63 FR...

  8. Gauche Ethyl Alcohol: Laboratory Assignments and Interstellar Identification

    NASA Technical Reports Server (NTRS)

    Pearson, J. C.; Sastry, K. V. L. N.; Herbst, Eric; DeLucia, Frank C.

    1997-01-01

    Ethyl alcohol (ethanol) is known to possess a pair of closely spaced excited torsional substates (gauche+, gauche-) at an energy of approximately 57 K above the ground (trans) torsional substate. We report an extended analysis of some gauche - gauche+ Q-branch ((Delta)J = 0) transitions with a three-substate fixed frame axis method (FFAM) Hamiltonian. Our approach accounts for complex trans-gauche interactions for the first time. In addition, we are able to obtain intensities for perturbed rotational transitions, and to determine the trans to gauche+ separation to be 1185399.1 MHz. A complete ground state rotational-torsional partition function accounting for the previously neglected gauche substates is presented. Based on our analysis, a total of 14 U lines obtained towards Orion KL can now be assigned to gauche substates of ethanol. Analysis of these lines yields a rotational temperature of 223 K and a total (trans + gauche) column density of 7.0 x 10(exp 15)/sq cm. The column density is in reasonable agreement with the recent value of 2-3 x 10(exp 15)/sq cm based on observations of trans-ethanol by Ohishi et al., although there is some disparity in the rotational temperatures. Eight additional U lines in the literature are assigned to transitions of gauche ethanol.

  9. 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).

  10. Development of a fast screening and confirmatory method by liquid chromatography-quadrupole-time-of-flight mass spectrometry for glucuronide-conjugated methyltestosterone metabolite in tilapia.

    PubMed

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

    2012-05-23

    This paper describes the development of a fast method to screen and confirm methyltestosterone 17-O-glucuronide (MT-glu) in tilapia bile. The method consists of solid-phase extraction (SPE) followed by high-performance liquid chromatography-mass spectrometry. The system used was an Agilent 6530 Q-TOF with an Agilent Jet stream electrospray ionization interface. The glucuronide detected in the bile was characterized as MT-glu by comparison with a chemically synthesized standard. MT-glu was detected in bile for up to 7 days after dosing. Semiquantification was done with matrix-matched calibration curves, because MT-glu showed signal suppression due to matrix effects. This method provides a suitable tool to monitor the illegal use of methyltestosterone in tilapia culture. PMID:22548460

  11. Chemodynamics of Methyl Parathion and Ethyl Parathion: Adsorption Models for Sustainable Agriculture

    PubMed Central

    Rafique, Uzaira; Balkhair, Khaled S.; Ashraf, Muhammad Aqeel

    2014-01-01

    The toxicity of organophosphate insecticides for nontarget organism has been the subject of extensive research for sustainable agriculture. Pakistan has banned the use of methyl/ethyl parathions, but they are still illegally used. The present study is an attempt to estimate the residual concentration and to suggest remedial solution of adsorption by different types of soils collected and characterized for physicochemical parameters. Sorption of pesticides in soil or other porous media is an important process regulating pesticide transport and degradation. The percentage removal of methyl parathion and ethyl parathion was determined through UV-Visible spectrophotometer at 276?nm and 277?nm, respectively. The results indicate that agricultural soil as compared to barren soil is more efficient adsorbent for both insecticides, at optimum batch condition of pH 7. The equilibrium between adsorbate and adsorbent was attained in 12 hours. Methyl parathion is removed more efficiently (by seven orders of magnitude) than ethyl parathion. It may be attributed to more available binding sites and less steric hindrance of methyl parathion. Adsorption kinetics indicates that a good correlation exists between distribution coefficient (Kd) and soil organic carbon. A general increase in Kd is noted with increase in induced concentration due to the formation of bound or aged residue. PMID:24689059

  12. Subchronic Toxicity Study in Rats of Two New Ethyl-Carbamates with Ixodicidal Activity

    PubMed Central

    Prado-Ochoa, María Guadalupe; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muńoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    Female and male Wistar rats were used to determine the subchronic oral toxicities of two new ethyl-carbamates with ixodicidal activities (ethyl-4-bromphenyl-carbamate and ethyl-4-chlorphenyl-carbamate). The evaluated carbamates were administered in the drinking water (12.5, 25 and 50?mg/kg/day) for 90 days. Exposure to the evaluated carbamates did not cause mortality or clinical signs and did not affect food consumption or weight gain. However, exposure to these carbamates produced alterations in water consumption, hematocrit, percentages of reticulocytes, plasma proteins, some biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, cholinesterase, and creatinine activities), thiobarbituric acid reactive substances, and the relative weight of the spleen. Histologically, slight pathological alterations were found in the liver that were consistent with the observed biochemical alterations. The nonobserved adverse effect levels (NOAELs) of the evaluated carbamates were 12.5?mg/kg/day for both the female and male rats. The low severity and reversibility of the majority of the observed alterations suggest that the evaluated carbamates have low subchronic toxicity. PMID:24818142

  13. Theoretical study for OH radical-initiated atmospheric oxidation of ethyl acrylate.

    PubMed

    Sun, Yanhui; Zhang, Qingzhu; Hu, Jingtian; Chen, Jianmin; Wang, Wenxing

    2015-01-01

    OH radical-initiated atmospheric oxidation of ethyl acrylate (ethyl 2-propenoate, EA) has been investigated by performing density functional theory (DFT) calculations. Optimizations of the reactants, intermediates, transition states and products were carried out at the MPWB1K/6-31+G(d,p) level. Single-point energy calculations were performed at the MPWB1K/6-311+G(3df,2p) level of theory. The detailed oxidation mechanism was presented and discussed. The results show that the OH addition is more energetically favorable than the H abstraction. Rice-Ramsperger-Kassel-Marcus (RRKM) theory was used to predict the rate constants over the possible atmospheric temperature range of 180-370 K. The Arrhenius expression adequately describes the total rate constant: k(EA+OH)=(1.71×10(-12))exp(805.42/T)cm(3) molecule(-1) s(-1). At 298 K, the atmospheric lifetime of ethyl acrylate determined by OH radicals is about 16.2h. In order to find out the effect of alkyl substitution on the reaction activity, rate constants for the reactions of methyl acrylate, methyl methacrylate and butyl acrylate with OH radicals were also discussed. Calculation results show that the reaction activity may increase with the increased electron-donating substitution for electrophilic addition reaction. PMID:25137248

  14. 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

  15. 40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721.3152...C12-18 fatty acids, ethyl sulfates (salts). (a) Chemical substance and significant...C12-18 fatty acids, ethyl sulfates (salts) (P-94-24) is subject to...

  16. Kinetics of intramolecular acyl migration of 1beta-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acids.

    PubMed

    Hasegawa, H; Akira, K; Shinohara, Y; Kasuya, Y; Hashimoto, T

    2001-07-01

    The stereoselective acyl migration of diastereomeric 1beta-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acid [(R)-1PG and (S)-IPG, respectively] in phosphate buffer (pH 7.4) at 310K was investigated using HPLC. The disappearance of (R)-1PG was faster than that of (S)-1PG according to pseudo first-order kinetics. A kinetic model describing the degradation reactions was constructed. The rate constant for acyl migration from the 1beta-O-isomer to the 2-O-acyl isomer (k12) was about one order magnitude larger than that for hydrolysis from 1beta-O-acyl isomer to aglycone (k10). The k12 of (R)-IPG (0.377 +/- 0.005 h(-1)) was about two times larger than that of (S)-IPG (0.184 +/- 0.003 h(-1)). The results indicated that the stereoselectivity in the degradation of 1PG was apparently governed by the acyl migration from 1-isomer to 2-isomer. The kinetic parameters for acyl migration from 1-isomer to 2-isomer were estimated from temperature-dependent experiments using the transition state theory. The value of the free energy of activation at 310 K for (R)-1PG (99.67 kJ/mol) was smaller than that of (S)-IPG (101.60kJ/mol), suggesting that (R)-IPG showed thermodynamically higher reactivity in acyl migration than (S)-1PG. PMID:11456131

  17. 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

  18. A rapid and sensitive assay to quantify valproyl 1-O-acyl glucuronide in supernatants of sandwich-cultured rat hepatocytes using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Surendradoss, Jayakumar; Szeitz, András; Teng, Xiao Wei; Chang, Thomas K H; Abbott, Frank S

    2013-08-01

    A rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of valproyl-1-O-acyl glucuronide (VPA-G) levels in hepatocyte culture medium. Chromatographic separation was achieved using a Waters Acquity UPLC(®) BEH C18 column (1.7?m, 2.1mm×50mm) with gradient elution and a total run time of 4min. [(2)H6]-VPA-G was used as internal standard (IS). Quantification was performed in the multiple reaction monitoring (MRM) mode using the total ion current of the MRM transition pairs m/z 319.1?142.7 and m/z 319.1?175.2 for VPA-G, and m/z 325.1?149.3 and m/z 325.1?174.9 for the IS under negative electrospray ionization mode. The assay was linear over the VPA-G concentrations of 0.5-500ng/mL, with a r(2) value of 0.995±0.002 (mean±SD). The intra- and inter-day accuracy (% deviation) ranged from -10.2% to 11.1%, whereas the intra- and inter-day precision (% RSD) were ?7.43%. The method was applied successfully to the quantification of VPA-G levels in culture supernatants of sandwich-cultured rat hepatocytes treated with valproic acid (VPA). No significant difference in the levels of VPA-G over a culture period of 6 days was observed in an experiment that investigated the effect of the age of hepatocyte culture on the extent of VPA glucuronidation. The method presented here for the direct quantification of VPA-G is an improvement of existing methods in the literature and offers a shorter run time and greater sensitivity that enables the use of small volumes of sample. To the best of our knowledge, this is the first validated UHPLC-MS/MS method applied to the quantification of VPA-G in cell culture supernatants. PMID:23827518

  19. New Ground-State Measurements of Ethyl Cyanide

    NASA Astrophysics Data System (ADS)

    Brauer, Carolyn S.; Pearson, John C.; Drouin, Brian J.; Yu, Shanshan

    2009-09-01

    The spectrum of ethyl cyanide, or propionitrile (CH3CH2CN), has been repeatedly observed in the interstellar medium with large column densities and surprisingly high temperatures in hot core sources. The construction of new, more sensitive, observatories accessing higher frequencies such as Herschel, ALMA, and SOFIA have made it important to extend the laboratory data for ethyl cyanide to coincide with the capabilities of the new instruments. We report extensions of the laboratory measurements of the rotational spectrum of ethyl cyanide in its ground vibrational state to 1.6 THz. A global analysis of the ground state, which includes all of the previous data and 3356 newly assigned transitions, has been fitted to within experimental error to J = 132, K = 36, using both Watson A-reduced and Watson S-reduced Hamiltonians.

  20. Bis(ethyl-eneglycolato-?(2) O,O')tellurium(IV).

    PubMed

    Brooks, Neil R; Wu, Minxian; Van Meervelt, Luc; Binnemans, Koen; Fransaer, Jan

    2013-01-01

    The title compound, C4H8O4Te, crystallized from a solution of Te(4+) in ethyl-ene glycol. The Te(IV) atom is in a distorted seesaw coordination defined by four O atoms from two different ethyl-eneglycate ligands. The C atoms of the ethyl-eneglycate ligands are disorderd over two positions, with population parameters of 50.3?(6) and 49.7?(6)% indicating a statistical distribution. Due to the possibility to transform the primitive monoclinic unit cell into a metrically ortho-rhom-bic C unit cell, the data are twinned and were refined with the twin law -100/0-10/101 with the relative scale factor refining to 1.82?(4)% for the minor component. PMID:24046645

  1. Fragrance material review on 2-(p-tolyloxy)ethyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 2-(p-tolyloxy)ethyl acetate when used as a fragrance ingredient is presented. 2-(p-tolyloxy)ethyl 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 2-(p-tolyloxy)ethyl acetate were evaluated, then summarized, and includes physical properties 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:22414652

  2. Dehydration of fermentative 2,3-butanediol into methyl ethyl ketone

    SciTech Connect

    Tran, A.V.; Chambers, R.P.

    1987-01-01

    A solid acid catalyst consisted of sulfonic groups covalently bound to an inorganic matrice was developed to dehydrate 2,3-butanediol into methyl ethyl ketone. Rate constant and apparent activation energy of the dehydration reaction were determined. The decay course of the catalyst was a two-stage curve. The catalyst was deactivated more rapidly in the first stage than in the second stage. The strategy of maintaining constant degree of dehydration was employed to lengthen the lifetime of catalyst. Treatment of the 2,3-butanediol containing fermentation broth with activated carbon greatly facilitated the subsequent dehydration reaction.

  3. Synthesis and Evaluation of Benzophenone-N-ethyl Morpholine Ethers as Anti-inflammatory Agents

    PubMed Central

    Khanum, Shaukath A.; Begum, Bushra A.; Girish, V.; Khanum, Noor Fatima

    2010-01-01

    The synthesis of hydroxy benzophenones and benzophenone-N-ethyl morpholine ethers and the results of anti-inflammatory activity in vivo are described. The structures of the compounds were elucidated by IR, 1H-NMR, mass spectroscopy and the elementary analysis. The anti-inflammatory activity of the synthesized compounds were determined by carrageenan-induced hind paw oedema test in rats. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than standard drugs. In addition ulcerogenic and cyclooxygenase activities are also described. PMID:23675177

  4. Mass spectra of methyl acetate and ethyl formate

    NASA Astrophysics Data System (ADS)

    Liu, Min; Wu, Chengyin; Wu, Zhifeng; Liang, Qingqing; Deng, Yongkai; Gong, Qihuang; Sun, Yue; Xu, Yuntao; Zhao, Yujie; Shan, Xiaobin; Liu, Fuyi; Sheng, Liusi

    2009-01-01

    We experimentally investigate the ionization and dissociation of two isomers, methyl acetate (CH 3COOCH 3) and ethyl formate (CH 3CH 2COOH), irradiated by strong laser pulses with a pulse duration of 7 fs. Strong parent ions are observed for both isomers. However, main fragmental ions are CH 3CO + and CH3+ for methyl acetate and CH 3O + and CH4+ for ethyl formate. Through comparing with the single photon ionization mass spectra of these two isomers, we find that these fragments are produced by the direct dissociation of the parent ions in different excited electronic states.

  5. Synthesis and Characterization of New Optically Active Poly (ethyl L-lysinamide)s and Poly (ethyl L-lysinimide)s

    PubMed Central

    Zahmatkesh, Saeed; Vakili, Mohammad Reza

    2010-01-01

    Ethyl L-lysine dihydrochloride was reacted with three different dianhydrides to yield the poly (ethyl L-lysinimide)s (PI1?3); it was also reacted with two different diacyl chlorides to yield the poly (ethyl L-lysinamide)s (PA4-5). The resulting polymers have inherent viscosities in the range of 0.15 to 0.42?dL?g?1. These polymers are prepared from an inexpensive starting material and are optically active, potentially ion exchangeable, semicrystalline, thermally stable, and soluble in polar aprotic solvents such as DMF, DMSO, NMP, DMAc, and sulfuric acid. All of the above polymers were fully characterized by FT-IR and 1H NMR spectroscopy, elemental analysis, WAX diffraction, TGA, inherent viscosity measurement, and specific rotation. PMID:22331998

  6. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...false Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...10243 Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...identified as phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-,...

  7. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...false Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...10243 Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...identified as phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-,...

  8. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...false Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...10243 Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis...identified as phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-,...

  9. 75 FR 17769 - In the Matter of Certain Products Advertised as Containing Creatine Ethyl Ester; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ...Certain Products Advertised as Containing Creatine Ethyl Ester; Notice of Commission Issuance...the Products Advertised as Containing Creatine Ethyl Ester of Respondents Found in Default...certain products advertised as containing creatine ethyl ester by reason of false...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...2010-10-01 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, 2011 CFR

    2011-10-01

    ...2011-10-01 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. 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...

  13. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 40 CFR 721.10109 - Hexanoic acid, 2-ethyl-, mixed triesters with benzoic acid and trimethylolpropane.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...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...

  5. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide fenoxaprop-ethyl, including its metabolites and degradates, in or on the...-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including...

  6. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... residues of the herbicide fenoxaprop-ethyl, including its metabolites and degradates, in or on the...-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including...

  7. 40 CFR 180.430 - Fenoxaprop-ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... combined residues of the herbicide fenoxaprop-ethyl phenoxy]propanoate] and its metabolites (6-chloro-2... tolerances are established for combined residues of the herbicide fenoxaprop-ethyl, phenoxy]propanoic...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide fenoxaprop-ethyl, including its metabolites and degradates, in or on the...-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including...

  9. 40 CFR 180.662 - Trinexapac-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Trinexapac-ethyl; tolerances for residues. (a) General. Tolerances are established for residues of the plant growth inhibitor, trinexapac-ethyl, including its metabolites and degradates, in or on the commodities in the...

  10. 40 CFR 180.662 - Trinexapac-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Trinexapac-ethyl; tolerances for residues. (a) General. Tolerances are established for residues of the plant growth inhibitor, trinexapac-ethyl, including its metabolites and degradates, in or on the commodities in the...

  11. 40 CFR 180.662 - Trinexapac-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Trinexapac-ethyl; tolerances for residues. (a) General. Tolerances are established for residues of the plant growth inhibitor, trinexapac-ethyl, including its metabolites and degradates, in or on the commodities in the...

  12. 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...

  13. 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,...

  14. 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,...

  15. 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...

  16. 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...

  17. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...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,...

  18. 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...

  19. Intrathecal morphine-3-glucuronide-induced nociceptive behavior via Delta-2 opioid receptors in the spinal cord.

    PubMed

    Komatsu, Takaaki; Katsuyama, Soh; Nagase, Hiroshi; Mizoguchi, Hirokazu; Sakurada, Chikai; Tsuzuki, Minoru; Sakurada, Shinobu; Sakurada, Tsukasa

    2016-01-01

    Intrathecal (i.t.) injection of morphine-3-glucuronide (M3G), a major metabolite of morphine without analgesic actions, produces severe hindlimb scratching followed by biting and licking in mice. The M3G-induced behavioral response was inhibited dose-dependently by pretreatment with an antisera against dynorphin. However, the selective ?-opioid receptor antagonist, nor-BNI did not prevent the M3G-induced behavioral response. Dynorphin is rapidly degraded by a dynorphin-converting enzyme (cystein protease), to leucine-enkephalin (Leu-ENK). The M3G-induced behavioral response was inhibited dose-dependently by pretreatment with the antisera against Leu-ENK. We also showed that M3G co-administered with Leu-ENK-converting enzyme inhibitors, phosphoramidon and bestatin produced much stronger behavioral responses than M3G alone. Furthermore, the M3G-induced behavioral responses were inhibited dose-dependently by i.t. co-administration of the non-selective ?-opioid receptor antagonist, naltrindole or the selective ?2-opioid receptor antagonist, naltriben, whereas the selective ?1-opioid receptor antagonist, BNTX had no effect. An i.t. injection of M3G also produced a definite activation of ERK in the lumbar dorsal spinal cord. Western blotting analysis revealed that antisera against dynorphin, antisera against Leu-ENK, naltrindole or naltriben resulted in a significant blockade of ERK activation induced by M3G in the spinal cord. Taken together, these results suggest that M3G-induced nociceptive responses and ERK activation may be triggered via ?2-opioid receptors activated by Leu-ENK, which is formed from dynorphin in the spinal cord. PMID:26476133

  20. Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation.

    PubMed

    Lu, Hang; Fang, Zhong-Ze; Cao, Yun-Feng; Hu, Cui-Min; Hong, Mo; Sun, Xiao-Yu; Li, Hua; Liu, Yan; Fu, Xiaoguang; Sun, Hongzhi

    2013-01-01

    Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT). Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions. The results showed that 100?M of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95.2%, 76.1%, 78.9%, 87.2%, 67.2%, 94.8%, and 91.7%, respectively. The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K(i)) to be 0.7?M, 0.3?M, and 18.3?M for UGT1A1, UGT1A9, and UGT1A10, respectively. All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms. PMID:23237733

  1. 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

  2. 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

  3. 77 FR 41346 - Trinexapac-ethyl; Proposed Pesticide Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... tolerance table for trinexapac-ethyl that was published in the Federal Register on March 2, 2012 (77 FR... Planning and Review'' (58 FR 51735, October 4, 1993). Because this proposed rule has been exempted from..., Distribution, or Use'' (66 FR 28355, May 22, 2001). This proposed rule does not contain any...

  4. 78 FR 13257 - Pyraflufen-ethyl; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ...pyraflufen-ethyl and metabolite E-1 in milk and the meat by-products of cattle, goat...oil. The anticipated residue in meat, milk, fat, and meat byproducts...parent and metabolite E-1 in milk and meat by-products of cattle,...

  5. MATERIAL SAFETY DATA SHEET ETHYL ALCOHOL USP -200 PROOF

    E-print Network

    Choi, Kyu Yong

    GRAVITY: 0.7940 @ 60°/60° F VAPOR DENSITY (AIR = 1): 1.59 SOLUBILITY IN WATER: Complete APPEARANCE, "alcohol" foam, or carbon dioxide; water may be ineffective, but water should be used to keep fireMATERIAL SAFETY DATA SHEET ETHYL ALCOHOL USP - 200 PROOF AAPER MSDS NUMBER: E200 EFFECTIVE DATE

  6. 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…

  7. 77 FR 41346 - Trinexapac-ethyl; Proposed Pesticide Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ...trinexapac-ethyl in or on barley, bran; sugarcane, molasses; and wheat, bran under the...in or on barley, bran at 2.5 ppm; sugarcane, molasses at 2.5 ppm; and wheat...agricultural commodities of barley, sugarcane and wheat; however, tolerances...

  8. Dissociation of the Ethyl Radical: An Exercise in Computational Chemistry

    ERIC Educational Resources Information Center

    Nassabeh, Nahal; Tran, Mark; Fleming, Patrick E.

    2014-01-01

    A set of exercises for use in a typical physical chemistry laboratory course are described, modeling the unimolecular dissociation of the ethyl radical to form ethylene and atomic hydrogen. Students analyze the computational results both qualitatively and quantitatively. Qualitative structural changes are compared to approximate predicted values…

  9. 76 FR 31479 - Pyraflufen-ethyl; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-01

    ... Federal Register of June 23, 2010 (75 FR 35801) (FRL-8831- 3), EPA issued a notice pursuant to section 408...- ethyl. C. Revisions to Petitioned-for Tolerances In the Federal Register of December 8, 2010 (75 FR..., entitled Regulatory Planning and Review (58 FR 51735, ] October 4, 1993). Because this final rule has...

  10. 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…

  11. Estimation of alcohol consumption during "Fallas" festivity in the wastewater of Valencia city (Spain) using ethyl sulfate as a biomarker.

    PubMed

    Andrés-Costa, María Jesús; Escrivá, Úrsula; Andreu, Vicente; Picó, Yolanda

    2016-01-15

    Alcohol consumption has been increasing in the last years and it has become a sociological problem due its derived health and safety problems. Ethyl sulfate is a secondary metabolite of the alcohol degradation that is excreted through the urine (0.010-0.016%) after alcohol ingestion and it is quite stable in water. In this study, a new methodology to determine ethyl sulfate by ion-pair liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Different ion-pairs and additives were tested directly in the sample extracts or in the mobile phase. The best ion-pair was set up adding 0.5M of tributylamine and 0.1% of formic acid to the sample. The limit of quantification was 0.3?gL(-1) and the intra-day and inter-day precision of the method were ?2.8 and ?3.0%, respectively. Good linearity (r(2)<0.999) and low matrix effect (<30% corrected by using internal isotopically labelled internal standard) were achieved. The sampling campaign was from 4th to 20th March of 2014 covering the festivity of Fallas (15th to 19th March). Ethyl sulfate was determined in all influents of the 3 wastewater treatment plants (Pinedo I, Pinedo II and Quart-Benŕger) belonging to Valencia and surrounding area. Ethyl sulfate concentrations ranged from 1.46 to 19.85?gL(-1) and alcohol consumption ranged from 1.07 to 56.11mLday(-1)inhab(-1), being the highest value of alcohol consumption determined during Fallas. This study presents a reliable and alternative method to traditional ones to determine alcohol consumption by population that provides real-time information of alcohol consumption. PMID:26439652

  12. Enzymatic synthesis of (125/131)I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence.

    PubMed

    Ye?ila?aç, Reyhan; Ünak, Perihan; Medine, E ?lker; ?çhedef, Çi?dem A; Ertay, Turkan; Müftüler, F Z Biber

    2011-02-01

    8-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with (125)I to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with (125)I and (131)I. Structural analyses were performed with LC/MS/MS, (1)H NMR and (13)C-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with (125/131)I according to iodogen method. (125)I-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu- 80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). (131)I-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug. PMID:21109446

  13. The critical role of amino acid residue at position 117 of mouse UDP-glucuronosyltransfererase 1a6a and 1a6b in resveratrol glucuronidation.

    PubMed

    Uchihashi, Shinsuke; Nishikawa, Miyu; Sakaki, Toshiyuki; Ikushiro, Shin-ichi

    2012-10-01

    Mouse UDP-glucuronosyltransferase 1a6 (Ugt1a6) contains two functional copies of 1a6a and 1a6b that share high sequence homology (98%). Only 10 amino acids located around the substrate recognition region are different out of 531 total residues. Although Ugt1a6 plays important roles in conjugating phenolic compounds, the functional characteristics of these isozymes are unclear. We performed functional analyses of mouse Ugt1a6a and Ugt1a6b using two isomeric polyphenols (trans- and cis-resveratrol). The cDNAs of mouse Ugt1a6a and Ugt1a6b were cloned and constructed as recombinant proteins using a yeast expression system, and kinetic parameters were evaluated. The wild-type Ugt1a6a and Ugt1a6b proteins catalysed trans- and cis-resveratrol 3-O-glucuronidation. Although the K(m) value for trans-resveratrol was significantly lower for Ugt1a6a compared with Ugt1a6b, the K(m) values for cis-resveratrol were comparable for the isozymes. Despite high sequence homology, significant kinetic differences were observed between the isozymes. To identify the critical residues for resveratrol glucuronidation, we constructed 10 variants of Ugt1a6a (T81P, N96R, H98Q, L100V, S104P, N115S, I117L, V118T, V119L and D120E). The I117L variant had Ugt1a6b-like enzymatic properties of K(m) in trans-resveratrol, and V(max) and K(si) in cis-form, suggesting that the residues located at position 117 of Ugt1a6a and Ugt1a6b play an important role in resveratrol glucuronidation. PMID:22774205

  14. 40 CFR 721.4090 - Ethanaminium, N-[bis(diethylamino)-methylene]-N-ethyl-, bromide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethanaminium, N- -N-ethyl-, bromide... Substances § 721.4090 Ethanaminium, N- -N-ethyl-, bromide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as ethanaminium, N- -N-ethyl-, bromide (PMN...

  15. 40 CFR 721.9514 - Ethyl silicate, reaction products with modified alkoxysilane salt (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethyl silicate, reaction products with... Significant New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with.... (1) The chemical substance identified generically as Ethyl silicate, reaction products with...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Ethyl silicate, reaction products with... Significant New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with.... (1) The chemical substance identified generically as Ethyl silicate, reaction products with...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Ethyl silicate, reaction products with... Significant New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with.... (1) The chemical substance identified generically as Ethyl silicate, reaction products with...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Ethyl silicate, reaction products with... Significant New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with.... (1) The chemical substance identified generically as Ethyl silicate, reaction products with...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Ethyl silicate, reaction products with... Significant New Uses for Specific Chemical Substances § 721.9514 Ethyl silicate, reaction products with.... (1) The chemical substance identified generically as Ethyl silicate, reaction products with...

  20. 40 CFR 180.585 - Pyraflufen-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...] acetate, and its acid metabolite, E-1, 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluorophenoxyacetic acid, calculated as the stoichiometric equivalent of pyraflufen-ethyl in or on the commodity... measuring only the sum of the parent pyraflufen-ethyl, ethyl 2- -4-fluorophenoxy] acetate and its...

  1. 40 CFR 180.585 - Pyraflufen-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...] acetate, and its acid metabolite, E-1, 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H-pyrazol-3-yl)-4-fluorophenoxyacetic acid, calculated as the stoichiometric equivalent of pyraflufen-ethyl in or on the commodity... measuring only the sum of the parent pyraflufen-ethyl, ethyl 2- -4-fluorophenoxy] acetate and its...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10109 Hexanoic acid, 2-ethyl-, mixed... to reporting. (1) The chemical substance identified as hexanoic acid, 2-ethyl-, mixed triesters...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide fenoxaprop-ethyl, including its metabolites and degradates, in or on the...-limited tolerances are established for residues of the herbicide fenoxaprop-ethyl, including its... established for residues of the herbicide fenoxaprop-ethyl, including its metabolites and degradates, in or...

  4. Detection of Benzene, Toluene, Ethyl Benzene, and Xylenes (BTEX) Using Toluene Dioxygenase-Peroxidase Coupling Reactions

    E-print Network

    Chen, Wilfred

    Detection of Benzene, Toluene, Ethyl Benzene, and Xylenes (BTEX) Using Toluene Dioxygenase, whole-cell bioassay for the detection of bioavailable benzene, toluene, ethyl benzene, and xylenes (BTEX of the response obtained from the blank) of 10, 10, 20, and 50 µM was observed for benzene, toluene, ethyl benzene

  5. Identification of diet-derived constituents as potent inhibitors of intestinal glucuronidation.

    PubMed

    Gufford, Brandon T; Chen, Gang; Lazarus, Philip; Graf, Tyler N; Oberlies, Nicholas H; Paine, Mary F

    2014-10-01

    Drug-metabolizing enzymes within enterocytes constitute a key barrier to xenobiotic entry into the systemic circulation. Furanocoumarins in grapefruit juice are cornerstone examples of diet-derived xenobiotics that perpetrate interactions with drugs via mechanism-based inhibition of intestinal CYP3A4. Relative to intestinal CYP3A4-mediated inhibition, alternate mechanisms underlying dietary substance-drug interactions remain understudied. A working systematic framework was applied to a panel of structurally diverse diet-derived constituents/extracts (n = 15) as inhibitors of intestinal UDP-glucuronosyl transferases (UGTs) to identify and characterize additional perpetrators of dietary substance-drug interactions. Using a screening assay involving the nonspecific UGT probe substrate 4-methylumbelliferone, human intestinal microsomes, and human embryonic kidney cell lysates overexpressing gut-relevant UGT1A isoforms, 14 diet-derived constituents/extracts inhibited UGT activity by >50% in at least one enzyme source, prompting IC(50) determination. The IC(50) values of 13 constituents/extracts (?10 ?M with at least one enzyme source) were well below intestinal tissue concentrations or concentrations in relevant juices, suggesting that these diet-derived substances can inhibit intestinal UGTs at clinically achievable concentrations. Evaluation of the effect of inhibitor depletion on IC(50) determination demonstrated substantial impact (up to 2.8-fold shift) using silybin A and silybin B, two key flavonolignans from milk thistle (Silybum marianum) as exemplar inhibitors, highlighting an important consideration for interpretation of UGT inhibition in vitro. Results from this work will help refine a working systematic framework to identify dietary substance-drug interactions that warrant advanced modeling and simulation to inform clinical assessment. PMID:25008344

  6. Identification of Diet-Derived Constituents as Potent Inhibitors of Intestinal Glucuronidation

    PubMed Central

    Gufford, Brandon T.; Chen, Gang; Lazarus, Philip; Graf, Tyler N.; Oberlies, Nicholas H.

    2014-01-01

    Drug-metabolizing enzymes within enterocytes constitute a key barrier to xenobiotic entry into the systemic circulation. Furanocoumarins in grapefruit juice are cornerstone examples of diet-derived xenobiotics that perpetrate interactions with drugs via mechanism-based inhibition of intestinal CYP3A4. Relative to intestinal CYP3A4-mediated inhibition, alternate mechanisms underlying dietary substance–drug interactions remain understudied. A working systematic framework was applied to a panel of structurally diverse diet-derived constituents/extracts (n = 15) as inhibitors of intestinal UDP-glucuronosyl transferases (UGTs) to identify and characterize additional perpetrators of dietary substance–drug interactions. Using a screening assay involving the nonspecific UGT probe substrate 4-methylumbelliferone, human intestinal microsomes, and human embryonic kidney cell lysates overexpressing gut-relevant UGT1A isoforms, 14 diet-derived constituents/extracts inhibited UGT activity by >50% in at least one enzyme source, prompting IC50 determination. The IC50 values of 13 constituents/extracts (?10 ?M with at least one enzyme source) were well below intestinal tissue concentrations or concentrations in relevant juices, suggesting that these diet-derived substances can inhibit intestinal UGTs at clinically achievable concentrations. Evaluation of the effect of inhibitor depletion on IC50 determination demonstrated substantial impact (up to 2.8-fold shift) using silybin A and silybin B, two key flavonolignans from milk thistle (Silybum marianum) as exemplar inhibitors, highlighting an important consideration for interpretation of UGT inhibition in vitro. Results from this work will help refine a working systematic framework to identify dietary substance–drug interactions that warrant advanced modeling and simulation to inform clinical assessment. PMID:25008344

  7. Theoretical and kinetic study of the hydrogen atom abstraction reactions of ethyl esters with hydrogen radicals

    NASA Astrophysics Data System (ADS)

    Wang, Quan-De; Wang, Xing-Jian; Liu, Zi-Wu; Kang, Guo-Jun

    2014-11-01

    Ab initio and chemical kinetic study of the hydrogen abstraction reactions by the hydrogen radical on ethyl formate, ethyl acetate, ethyl propanoate, and ethyl butanoate have been performed at the CCSD(T)/CBS//B3LYP/6-311G(d, p) level of theory. High-pressure limit rate constants at temperatures from 300 to 2500 K have been calculated for all of the reaction channels using transition state theory with Eckart tunneling corrections, and the data are fitted to the modified three parameters Arrhenius expression using least-squares regression. A branching ratio analysis for each reaction site has also been investigated for all of the ethyl esters.

  8. Impact of Association Colloids on Lipid Oxidation in Triacylglycerols and Fatty Acid Ethyl Esters.

    PubMed

    Homma, Rika; Suzuki, Karin; Cui, Leqi; McClements, David Julian; Decker, Eric A

    2015-11-25

    The impact of association colloids on lipid oxidation in triacylglycerols and fatty acid ethyl esters was investigated. Association colloids did not affect lipid oxidation of high oleic safflower and high linoleic safflower triacylglycerols, but were prooxidative in fish triacylglycerols. Association colloids retarded aldehyde formation in stripped ethyl oleate, linoleate, and fish oil ethyl esters. Interfacial tension revealed that lipid hydroperoxides were surface active in the presence of the surfactants found in association colloids. The lipid hydroperoxides from ethyl esters were less surface active than triacylglycerol hydroperoxides. Stripping decreased iron and copper concentrations in all oils, but more so in fatty acid ethyl esters. The combination of lower hydroperoxide surface activity and low metal concentrations could explain why association colloids inhibited lipid oxidation in fatty acid ethyl esters. This research suggests that association colloids could be used as an antioxidant technology in fatty acid ethyl esters. PMID:26506263

  9. (1S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate: major sex pheromone component of Paulownia bagworm, Clania variegata.

    PubMed

    Gries, Regine; Khaskin, Grigori; Tan, Zhong-Xing; Zhao, Bo-Guang; Skip King, G G; Miroshnychenko, Aleksander; Lin, Guo-Qiang; Rhainds, Marc; Gries, Gerhard

    2006-08-01

    The Paulownia bagworm, Clania variegata Snell. (Lepidoptera: Psychidae), is one of the most significant forest defoliators in China. In gas chromatographic (GC)-electroantennographic detection analyses of pheromone gland extracts of female C. variegata on three GC columns (DB-5, DB-23, DB-210), two compounds (A and B) elicited strong responses from male antennae. The more abundant component B was isolated by high-performance liquid chromatography and identified as 1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate by transesterification, GC-mass spectrometry (MS), and comparison of its spectral and GC retention characteristics with those of synthetic compounds. In field trapping experiments in China, racemic and (1S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate [but not the (1R)-stereoisomer] attracted male C. variegata. The absolute configuration of B (a molecule with three chiral centers) and the structure of component A remain to be determined. PMID:16900424

  10. SPECTROSCOPIC CHARACTERIZATION AND DETECTION OF ETHYL MERCAPTAN IN ORION

    SciTech Connect

    Kolesniková, L.; Alonso, J. L.; Daly, A. M.; Tercero, B.; Cernicharo, J.; Gordon, B. P.; Shipman, S. T. E-mail: jlalonso@qf.uva.es E-mail: terceromb@cab.inta-csic.es E-mail: brittany.gordon@ncf.edu

    2014-03-20

    New laboratory data of ethyl mercaptan, CH{sub 3}CH{sub 2}SH, in the millimeter- and submillimeter-wave domains (up to 880 GHz) provided very precise values of the spectroscopic constants that allowed the detection of gauche-CH{sub 3}CH{sub 2}SH toward Orion KL. This identification is supported by 77 unblended or slightly blended lines plus no missing transitions in the range 80-280 GHz. A detection of methyl mercaptan, CH{sub 3}SH, in the spectral survey of Orion KL is reported as well. Our column density results indicate that methyl mercaptan is ? 5 times more abundant than ethyl mercaptan in the hot core of Orion KL.

  11. 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

  12. Enantioselective hydrogenation of ethyl acetoacetate on asymmetric Raney Ni catalysts

    SciTech Connect

    Zubareva, N.D.; Chernysheva, V.V.; Grigor'ev, Yu.A.; Klabunovskii, E.I.

    1987-09-10

    The properties of Raney nickel catalysts modified by (+)-tartaric acid and active in enantioselective hydrogenation of ethyl acetoacetate depend on the chemical and phase compositions of the starting Ni-Al alloys. A decrease of the Ni content in the Ni-Al alloy specimens which corresponds to an increase of the fraction of the NiAl/sub 3/ intermetallic compound in them contributes to an increase of the catalytic activity and enantioselectivity of the action of the obtained catalysts.

  13. Effects of wildlife of ethyl and methyl parathion applied to California USA rice fields

    USGS Publications Warehouse

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  14. Effects on wildlife of ethyl and methyl parathion applied to California rice fields

    USGS Publications Warehouse

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  15. Control of ethyl methacrylate exposures during the application of artificial fingernails.

    PubMed

    Spencer, A B; Estill, C F; McCammon, J B; Mickelsen, R L; Johnston, O E

    1997-03-01

    In 1990 six cases of physician-diagnosed occupational asthma in cosmetologists working with artificial fingernails prompted the Colorado Department of Health to request the assistance of National Institute for Occupational Safety and Health (NIOSH) researchers in the evaluation and control of nail salon technician exposure. A commercially available recirculating downdraft table with charcoal filters was purchased and evaluated. Researchers from NIOSH made modifications to the table that included increasing the downdraft air volume; enlarging the plenum for more consistent airflow rates at the face of the table; removing the charcoal filters while incorporating a ventilation system to the outdoors; and putting an extension around the duct leading to the perforated plate at the downdraft face of the table. An evaluation was performed using the following two configurations: the modified table with the downdraft ventilation on (vented) and without the downdraft ventilation on (unvented). Each of the two configurations was sampled for 3 days in random order. Testing included the use of XAD-2 solid sorbent tubes for determining ethyl methacrylate and methyl methacrylate concentrations. Relative concentrations of organics were examined and used to analyze work practices. The geometric mean ethyl methacrylate exposure for personal breathing zone samples when using the modified table for approximately 6 hours was 0.6 ppm; when using the unventilated conventional table, the geometric mean exposure was 8.7 ppm. The difference in the values is statistically significant (p = 0.0045). Methyl methacrylate concentrations were nondetectable on all sorbent tubes. PMID:9075312

  16. Mechanistic insights into the hydrolysis of 2-chloroethyl ethyl sulfide: the expanded roles of sulfonium salts.

    PubMed

    Bae, Su Y; Winemiller, Mark D

    2013-07-01

    The hydrolysis of 2-chloroethyl ethyl sulfide has been examined in an effort to better understand its mechanism under more concentrated conditions. Two salts formed during hydrolysis were synthesized, and an emphasis was placed on determining their effect on the reaction as it proceeded. Unexpected changes in mechanism were seen when excess chloride was added to the reaction. By measuring rates and product distributions as the products were added back into the hydrolysis, a mechanism was developed. The formation of these sulfonium salts represents additional products in the disappearance of 2-chloroethyl ethyl sulfide with k3 in particular causing a deviation away from expected first-order behavior. Sulfonium salts 3 and 4 do not appear to interconvert, and the system as a whole had fewer pathways available than previously proposed. Initial conditions for studying the hydrolysis were very important and could lead to different conclusions depending on the conditions used. This work will aid in better understanding the hydrolysis of the very toxic chemical warfare agent mustard (bis(2-chloroethyl)sulfide) in the environment and during its decontamination. PMID:23767819

  17. Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

    PubMed Central

    Guarda, Ismael Francisco Mota Siqueira; Correia, Cristiano Jesus; Breithaupt-Faloppa, Ana Cristina; Ferreira, Sueli Gomes; Moreno, Ana Carolina Ramos; Martinez, Marina Baquerizo; Rocha-e-Silva, Mauricio; Sannomiya, Paulina

    2015-01-01

    OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (?2.5-fold increase), adherent cells (?3.0-fold), and migrated cells (?3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions. CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1. PMID:26222821

  18. 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

  19. 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.

  20. GENOTOXICITY OF ACRYLIC ACID, METHYL ACRYLATE, ETHYL ACRYLATE, METHYL METHACRYLATE, AND ETHYL METHACRYLATE IN L5178Y MOUSE LYMPHOMA CELLS (JOURNAL VERSION)

    EPA Science Inventory

    A series of monomeric acrylate/methacrylate esters (methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate) as well as acrylic acid were examined for genotoxic activity in L5178Y mouse lymphoma cells without exogenous activation. All five compounds induced c...

  1. 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...

  2. Synthesis and characterization of ruthenium polypyridyl complexes with hydroxypyridine derivatives: effect of protonation and ethylation at the pyridyl nitrogen.

    PubMed

    Kim, Juyeong; Yennawar, Hemant P; Lear, Benjamin J

    2013-11-28

    A new series of ruthenium polypyridyl complexes with a hydroxypyridine ligand were prepared, and their properties were investigated spectroscopically and electrochemically. Particular focus is paid to the effects of protonation-deprotonation and ethylation of the hydroxypyridine ligand, which affects the NMR, electronic spectroscopy, and electrochemistry of the complex. The changes to the UV-vis spectrum were used to determine a pka of 10.5 for the hydroxypyridine nitrogen. In the NMR, protonation of the hydroxypyridine ligand of the complex causes changes in the chemical shifts of the protons on both the hydroxypyridine and bipyridine rings, indicating some degree of electronic communication between these ligands. In addition, it is found that deprotonation of the hydroxypyridine ligand strongly affects the redox potential of the ruthenium metal center, shifting it more negative by 0.4 V. While the electrochemistry of the protonated complex contains irreversible electrochemical events, both deprotonation and subsequent ethylation of the hydroxypyridine ligand result in reversible electrochemistry for all events within the solvent window. For the ethylated complex, we search for a ligand to ligand charge transfer band, corresponding to electron transfer between bipyridine ligands in the mixed valence state. Despite the potential for electronic coupling between ligands through the metal center, we were unable to find any spectroscopic evidence of such electronic coupling. PMID:24045324

  3. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    PubMed Central

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muńoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000?mg/kg, and the dermal LD50 of each carbamate was >5000?mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P < 0.05) and had slight nervous system manifestations. These clinical signs were evident from the 300?mg/kg dose and were reversible, whereas the 2000?mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000?mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. PMID:24883331

  4. Ethyl acetate as a substitute for diethyl ether in the formalin-ether sedimentation technique.

    PubMed Central

    Young, K H; Bullock, S L; Melvin, D M; Spruill, C L

    1979-01-01

    Ethyl acetate appears to be a satisfactory subsitute solvent for diethyl ether in the Formalin-ether sedimentation technique. In comparative studies, concentration of organisms with ethyl acetate was equal to or greater than that with diethyl ether. No distortion or alteration of morphology was observed with eigher solvent, and preparations were comparable in appearance and ease of examination. In addition, ethyl acetate is less flammable and less hazardous to use than diethyl ether. PMID:574877

  5. The mechanism of hydrothermal hydrolysis for glycyrrhizic acid into glycyrrhetinic acid and glycyrrhetinic acid 3-O-mono-?-D-glucuronide in subcritical water.

    PubMed

    Fan, Rui; Li, Nan; Xu, Honggao; Xiang, Jun; Wang, Lei; Gao, Yanxiang

    2016-01-01

    To improve the bioactivity and sweetness properties of glycyrrhizic acid (GL), the hydrothermal hydrolysis of GL into glycyrrhetinic acid (GA) and glycyrrhetinic acid 3-O-mono-?-D-glucuronide (GAMG) in subcritical water was investigated. The effects of temperature, time and their interaction on the conversion ratios were analyzed and the reactions were elaborated with kinetics and thermodynamics. The results showed that GL hydrothermal hydrolysis was significantly (P < 0.05) affected by reaction time and temperature, as well as their interaction, and could be fitted into first-order kinetics. The thermodynamic analysis indicated that the hydrolysis of GL was endergonic and non-spontaneous. The hydrolytic pathways were composed of complex consecutive and parallel reactions. It was concluded that subcritical water may be a potential medium for producing GAMG and GA. PMID:26213056

  6. Optical luminescence studies of the ethyl xanthate adsorption layer on the surface of sphalerite minerals.

    PubMed

    Todoran, R; Todoran, D; Szakács, Zs

    2016-01-01

    In this work we propose optical luminescence measurements as a method to evaluate the kinetics of adsorption processes. Measurement of the intensity of the integral optical radiation obtained from the mineral-xanthate interface layer, stimulated with a monochromatic pulsating optical signal, as a function of time were made. The luminescence radiation was obtained from the thin interface layer formed at the separation surface between the sphalerite natural mineral and potassium ethyl xanthate solution, for different solution concentrations and pH-es at the constant industry standard temperature. This method enabled us to determine the time to achieve dynamic equilibrium in the formation of the interface layer of approximately 20min, gaining information on the adsorption kinetics in the case of xanthate on mineral surface and leading to the optimization of the industrial froth flotation process. PMID:25619858

  7. CCSD(T) study of the infrared spectrum of ethyl-methyl-ether isotopic varieties

    NASA Astrophysics Data System (ADS)

    Senent, M. L.; Ruiz, R.; Villa, M.; Domínguez-Gómez, R.

    2010-02-01

    Band positions for the infrared bands of various ethyl-methyl-ether isotopomers (CH 3CH 2OCH 2D, CH 2DCH 2OCH 3, CH 3CH 2OCD 3, CD 3CH 2OCH 3, CH 3CD 2OCH 3, CH 3CH 2O 13CH 3, 13CH 3CH 2OCH 3, and CH 313CH 2OCH 3) are determined using second order perturbation theory. For species showing G18 symmetry, band position are calculated variationally from a CCSD(T)/cc-pVTZ three-dimensional potential energy surface corrected vibrationally. Potential energy barriers, fundamental frequencies, and rotational constants for excited vibrational levels, are also provided. Calculated frequencies for CH 3CH 2OCD 3 confirm experimental assignments and our predictions for the most abundant isotopomer [4].

  8. Fatty acid ethyl ester synthesis in the preparation of scotch whiskey.

    PubMed

    Goss, K A; Alharethi, R; Laposata, M

    1999-04-01

    Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites present in human organs commonly damaged by ethanol abuse, have been implicated as mediators of organ damage. FAEE are additives in various foods and beverages to provide flavor or fragrance, and therefore are common dietary lipid constituents. We hypothesized that FAEE could be generated during alcoholic beverage production because fatty acids are present within microorganisms and ethanol is generated during the fermentation process. In this report, we demonstrate that FAEE are present in commercially available scotch beverages, and that in the preparation of scotch, FAEE can be produced during the fermentation reaction as a result of FAEE synthase activity in the yeast. Following ingestion of scotch, preformed FAEE are delivered to GI tract. The consequences of ingestion of FAEE in scotch, if any, remain to be determined. PMID:10231172

  9. Optical luminescence studies of the ethyl xanthate adsorption layer on the surface of sphalerite minerals

    NASA Astrophysics Data System (ADS)

    Todoran, R.; Todoran, D.; Szakács, Zs.

    2016-01-01

    In this work we propose optical luminescence measurements as a method to evaluate the kinetics of adsorption processes. Measurement of the intensity of the integral optical radiation obtained from the mineral-xanthate interface layer, stimulated with a monochromatic pulsating optical signal, as a function of time were made. The luminescence radiation was obtained from the thin interface layer formed at the separation surface between the sphalerite natural mineral and potassium ethyl xanthate solution, for different solution concentrations and pH-es at the constant industry standard temperature. This method enabled us to determine the time to achieve dynamic equilibrium in the formation of the interface layer of approximately 20 min, gaining information on the adsorption kinetics in the case of xanthate on mineral surface and leading to the optimization of the industrial froth flotation process.

  10. Identification of glucoside and carboxyl-linked glucuronide conjugates of mycophenolic acid in plasma of transplant recipients treated with mycophenolate mofetil

    PubMed Central

    Shipkova, Maria; Armstrong, Victor William; Wieland, Eberhard; Niedmann, Paul Dieter; Schütz, Ekkehard; Brenner-Weiß, Gerald; Voihsel, Martin; Braun, Felix; Oellerich, Michael

    1999-01-01

    Mycophenolic acid (MPA), is primarily metabolized in the liver to 7-O-MPA-?-glucuronide (MPAG). Using RP-h.p.l.c. we observed three further MPA metabolites, M-1, M-2, M-3, in plasma of transplant recipients on MMF therapy. To obtain information on the structure and source of these metabolites: (A) h.p.l.c. fractions containing either metabolite or MPA were collected and analysed by tandem mass spectrometry; (B) the metabolism of MPA was studied in human liver microsomes in the presence of UDP-glucuronic acid, UDP-glucose or NADPH; (C) hydrolysis of metabolites was investigated using ?-glucosidase, ?-glucuronidase or NaOH; (D) cross-reactivity of each metabolite was tested in an immunoassay for MPA (EMIT). Mass spectrometry of M-1, M-2, MPA and MPAG in the negative ion mode revealed molecular ions of m/z 481, m/z 495, m/z 319 and m/z 495 respectively. Incubation of microsomes with MPA and UDP-glucose produced M-1, with MPA and UDP-glucuronic acid MPAG and M-2 were formed, while with MPA and NADPH, M-3 was observed. ?-Glucosidase hydrolysed M-1 completely. ?-Glucuronidase treatment led to a complete disappearance of MPAG whereas the amount of M-2 was reduced by approximately 30%. Only M-2 was labile to alkaline treatment. M-2 and MPA but not M-1 and MPAG cross-reacted in the EMIT assay. These results suggest that: (i) M-1 is the 7-OH glucose conjugate of MPA; (ii) M-2 is the acyl glucuronide conjugate of MPA; (iii) M-3 is derived from the hepatic CYP450 system. PMID:10204993

  11. Human Metabolite Lamotrigine-N(2)-glucuronide Is the Principal Source of Lamotrigine-Derived Compounds in Wastewater Treatment Plants and Surface Water.

    PubMed

    Zonja, Bozo; Pérez, Sandra; Barceló, Damiŕ

    2016-01-01

    Wastewater and surface water samples, extracted with four solid-phase extraction cartridges of different chemistries, were suspect-screened for the anticonvulsant lamotrigine (LMG), its metabolites, and related compounds. LMG, three human metabolites, and a LMG synthetic impurity (OXO-LMG) were detected. Preliminary results showed significantly higher concentrations of OXO-LMG in wastewater effluent, suggesting its formation in the wastewater treatment plants (WWTPs). However, biodegradation experiments with activated sludge demonstrated that LMG is resistant to degradation and that its human metabolite lamotrigine-N(2)-glucuronide (LMG-N2-G) is the actual source of OXO-LMG in WWTPs. In batch reactors, LMG-N2-G was transformed, following pseudo-first-order kinetics to OXO-LMG and LMG, but kinetic experiments suggested an incomplete mass balance. A fragment ion search applied to batch-reactor and environmental samples revealed another transformation product (TP), formed by LMG-N2-G oxidation, which was identified by high-resolution mass spectrometry. Accounting for all TPs detected, a total mass balance at two concentration levels in batch reactors was closed at 86% and 102%, respectively. In three WWTPs, the total mass balance of LMG-N2-G ranged from 71 to 102%. Finally, LMG-N2-G and its TPs were detected in surface water samples with median concentration ranges of 23-139 ng L(-1). The results of this study suggest that glucuronides of pharmaceuticals might also be sources of yet undiscovered, but environmentally relevant, transformation products. PMID:26606642

  12. Identification of 1-hydroxypyrene glucuronide in tissue of marine polychaete Nereis diversicolor by liquid chromatography/ion trap multiple mass spectrometry.

    PubMed

    Giessing, Anders M B; Lund, Torben

    2002-01-01

    1-Hydroxypyrene glucuronide is identified as the single major aqueous metabolite of the tetracyclic aromatic hydrocarbon pyrene, in tissue from a deposit-feeding marine polychaete, Nereis diversicolor. Identification was performed using an ion trap mass spectrometer fitted with an atmospheric pressure chemical ionization (APCI) probe and connected to a high-performance liquid chromatography/diode array detector (HPLC/DAD) system. Besides 1-hydroxypyrene, the 339-nm UV trace of tissue samples from pyrene-exposed worms showed only one dominant peak that could be related to pyrene metabolism. Negative APCI-MS of this supposed 1- hydroxypyrene conjugate gave a characteristic signal at m/z 429 corresponding to the molecular ion of 1-hydroxypyrene glucuronide plus eluent adducts ([M - H + 2H(2)O](-)). Fragmentation pathways were studied by isolating the abundant ion at m/z 429 in the ion trap and performing multiple mass spectrometric experiments (MS(n)). The fragmentations observed were consistent with the proposed identification. Two low intensity LC peaks that could be related to pyrene metabolism by their DAD absorption spectra were also present in the 339-nm UV chromatogram of tissue samples. However, these peaks could not be identified by their mass spectra in negative ion mode due to ion suppression by very abundant co-eluting impurities. The present method shows that LC/MS(n) is a fast and useful analytical tool for identification of aqueous polycyclic aromatic hydrocarbon biotransformation products in samples from relatively small marine invertebrates with limited sample preparation. PMID:12203242

  13. 4-(Dimethyl­amino)benzaldehyde 4-ethyl­thio­semicarbazone

    PubMed Central

    Salhin, Abdussalam; Razak, Norfarhah Abdul; Rahman, I. A.

    2008-01-01

    The title thio­semicarbazone derivative, C12H18N4S, features intra­molecular N—H?N and C—H?S hydrogen bonds which generate S(5) ring motifs. The dihedral angle between the benzene ring and the thio­urea unit is 6.30?(6)° indicating planarity in the mol­ecule. Inter­molecular N—H?S hydrogen bonds generate dimers with an R 2 2(8) ring motif. The methyl group of the N-ethyl residue is disordered and was refined with site occupancies of 0.521?(5) and 0.479?(5). PMID:21581327

  14. Placental Fatty Acid Ethyl Esters Are Elevated with Maternal Alcohol Use in Pregnancies Complicated by Prematurity

    PubMed Central

    Gauthier, Theresa W.; Mohan, Sowmya S.; Gross, Teresa S.; Harris, Frank L.; Guidot, David M.; Brown, Lou Ann S.

    2015-01-01

    The accumulation of fatty acid ethyl esters (FAEEs) in meconium of term newborns has been described as one potential biomarker of maternal alcohol use during pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the placenta. Limited research has focused on the identification of the premature newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use occurs in a significant proportion of premature deliveries and that this exposure can be detected as elevated placental FAEEs. The goals of this study were to 1) determine the prevalence of maternal alcohol use in the premature newborn and 2) investigate whether placental FAEEs could identify those newborns with fetal alcohol exposure. This prospective observational study evaluated 80 placentas from 80 women after premature delivery. Subjects were interviewed for alcohol intake and placental FAEEs were quantified via GC/MS. Receiver Operator Characteristic (ROC) Curves were generated to evaluate the ability of placental FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were generated to adjust for gestational age, maternal smoking, and illicit drug use. 30% of the subjects admitted to drinking alcohol during pregnancy and approximately 14% answered questions indicative of problem drinking (designated AUDIT+). The specific FAEEs ethyl stearate and linoleate, as well as combinations of oleate + linoleate + linolenate (OLL) and of OLL + stearate, were significantly (p<0.05) elevated in placentas from AUDIT+ pregnancies. Adjusted ROC Curves generated areas under the curve ranging from 88–93% with negative predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one third of premature pregnancies were alcohol-exposed, and that elevated placental FAEEs hold great promise to accurately determine maternal alcohol use, particularly heavy use, in pregnancies complicated by premature delivery. PMID:25978403

  15. Effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a statin-treated patient with elevated triglycerides.

    PubMed

    Kedia, Anurag W; Lynch, Erin

    2015-11-01

    In patients with dyslipidemia, elevated triglyceride (TG) levels, or TG-rich lipoproteins, and cardiovascular risk may remain despite statin therapy. Prescription omega-3 fatty acid formulations containing the ethyl esters of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (omega-3-acid ethyl esters; Lovaza®) or high-purity EPA ethyl ester (icosapent ethyl; Vascepa®) are TG-lowering treatments that may be administered in addition to statins. Here we describe the effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a 44-year-old obese man with dyslipidemia, hypertension, and hypothyroidism. The patient was receiving stable treatment with medications, including atorvastatin 40 mg/day and extended-release niacin 1000 mg/day. Owing to persistently elevated TG levels and other cardiovascular risk factors, the patient was initiated on omega-3-acid ethyl esters 4 g/day. After approximately 2 years on omega-3-acid ethyl esters, his total cholesterol (TC) level was 184 mg/dL, low-density lipoprotein cholesterol (LDL-C) level was 81 mg/dL, TG level was elevated at 307 mg/dL despite statin therapy, and non-high-density lipoprotein cholesterol (non-HDL-C) level was 144 mg/dL. After the switch to icosapent ethyl, TC level decreased by 34% to 121 mg/dL, LDL-C level decreased by 28% to 58 mg/dL, TG level decreased by 41% to 180 mg/dL, and non-HDL-C level decreased by 44% to 81 mg/dL. Switching from omega-3-acid ethyl esters containing both EPA and DHA to icosapent ethyl containing high-purity EPA resulted in beneficial and substantial changes in the lipid profile with a notable reduction of TG levels along with additional reductions in LDL-C levels in a statin-treated obese patient with persistently high TG levels. Treatment with icosapent ethyl was well tolerated. PMID:26453247

  16. DISCOVERY OF METHYL ACETATE AND GAUCHE ETHYL FORMATE IN ORION

    SciTech Connect

    Tercero, B.; Cernicharo, J.; Lopez, A.; Caro, G. M. Munoz; Kleiner, I.; Nguyen, H. V. L. E-mail: jcernicharo@cab.inta-csic.es E-mail: munozcg@cab.inta-csic.es E-mail: nguyen@pc.rwth-aachen.de

    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.

  17. Protective effects of ethyl pyruvate in cisplatin-induced nephrotoxicity

    PubMed Central

    Kelle, Ilker; Akkoc, Hasan; Tunik, Selcuk; Nergiz, Yusuf; Erdinc, Meral; Erdinc, Levent

    2014-01-01

    This study was performed to investigate the effect of ethyl pyruvate on changes in renal functions and oxidative stress related renal injury caused by cisplatin (cis-dichlorodiammine platinum-II; CDDP). Male Wistar albino rats were divided into four groups (n = 8): (1) control group (1 ml Ringer's lactate solution i.p.); (2) ethyl pyruvate (EP) group (50 mg/kg Ringer's EP solution (REPS) i.p.); (3) cisplatin group (a single dose of cisplatin (5 mg/kg, i.p.); and (4) cisplatin + EP group (a single dose of cisplatin (5 mg/kg, i.p.) + REPS 50 mg/kg/day, i.p.) for five days. At the sixth day, kidneys of rats were mounted to a Langendorff apparatus. Renal perfusion pressures were recorded. Blood samples were taken for serum urea, creatinine, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stres index (OSI) evaluations. Kidney tissues were obtained for malondialdehyde (MDA) analyses and histopathological examination. Perfusion pressures, serum urea, creatinine, TOS, OSI and tissue MDA levels were found significantly higher, whereas TAS was notably lower in cisplatin group. Histopathological examination showed apparent renal paranchymal injury in cisplatin group. In cisplatin + REPS group, perfusion pressures, serum urea, creatinine and tissue MDA levels were decreased. Moreover, EP co-administration provided less inflammatory cell infiltration, tubular dilatation, whereas TOS, TAS and OSI improved significantly versus cisplatin group. These findings show that EP has protective effects against cisplatin nephrotoxicity. PMID:26019553

  18. Comparison of formalin-ethyl ether sedimentation, formalin-ethyl acetate sedimentation, and zinc sulfate flotation techniques for detection of intestinal parasites.

    PubMed Central

    Truant, A L; Elliott, S H; Kelly, M T; Smith, J H

    1981-01-01

    Formalin-ethyl ether sedimentation, Formalin-ethyl acetate sedimentation, and zinc sulfate flotation techniques were compared using over 250 clinical parasitology specimens. Fifty positive specimens were identified, and a variety of parasites, including amoebae, flagellates, cestodes, nematodes, and trematodes, were encountered. The Formalin-ether and Formalin-ethyl acetate sedimentation procedures gave identical results for the detection of cysts, ova, and larvae, and these methods offered an advantage over the flotation procedure for the detection of selected ova. However, the zinc sulfate procedure was more effective for the detection of protozoan cysts, Hymenolepis nana, and hookworm eggs. The results indicate that the Formalin-ethyl acetate procedure provides a suitable alternative to the Formalin-ether method, and they demonstrate the value of using both flotation and sedimentation procedures in the analysis of fecal specimens for parasites. PMID:7240400

  19. Tetra­kis(?-4-ethyl­benzoato-?2 O:O?)­bis­[(4-ethyl­benzoic acid-?O)copper(II)

    PubMed Central

    Sunil, Abraham C.; Bezuidenhoudt, Barend C. B.; Janse van Rensburg, J. Marthinus

    2008-01-01

    The molecule of the title compound, [Cu2(C9H9O2)4(C9H10O2)2], lies on a center of inversion. It consists of four bridging ethyl­benzoate ligands, forming a cage around two Cu atoms in a syn–syn configuration, and two monodentate ethyl­benzoic acid ligands bonded apically to the square-planar Cu atoms. The Cu?Cu distance is 2.6047?(5)?Ĺ. PMID:21202792

  20. 40 CFR 721.1085 - Benzenamine,4,4?-methylenebis[N-ethyl-N-methyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenamine,4,4â˛-methylenebis[N-ethyl-N-methyl-. 721.1085 Section 721.1085 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1085 Benzenamine,4,4?-methylenebis[N-ethyl-N-methyl-. (a)...

  1. Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester Production in Saccharomyces cerevisiae

    E-print Network

    Zhao, Huimin

    Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester Production, Illinois 61801, United States *S Supporting Information ABSTRACT: Fatty acid ethyl esters (FAEEs) are a form of biodiesel that can be microbially produced via a transesterification reaction of fatty acids

  2. The mid-IR spectra of 9-ethyl guanine, guanosine, and 2-deoxyguanosine

    E-print Network

    de Vries, Mattanjah S.

    The mid-IR spectra of 9-ethyl guanine, guanosine, and 2- deoxyguanosine Ali Abo-riziq(a) , Bridgit for Complex Molecular Systems and Biomolecules, 166 10 Prague 6, Czech Republic Abstract We present the mid-IR (400-1800 cm-1 ) spectra of 9-ethyl guanine, guanosine, and 2- deoxyguanosine measured by IR-UV double

  3. Isomerization and intermolecular solutesolvent interactions of ethyl isocyanate: Ultrafast infrared vibrational echoes and linear

    E-print Network

    Fayer, Michael D.

    Isomerization and intermolecular solute­solvent interactions of ethyl isocyanate: Ultrafast induced gauche­trans isomerization and direct solute­solvent interactions of the solute, ethyl isocyanate isomerization. To describe the observations, a model is presented that involves both intramolecular dynamics

  4. Iron pentacarbonyl-halogen-initiated reaction of ethyl acetoacetate and acetylacetone with acrylic monomers

    SciTech Connect

    Amriev, R.A.; Abdulkina, Z.A.; Friedlina, R.K.; Velichko, F.K.

    1985-05-20

    The authors have found that ethyl acetoacentate (EAA) and acetylacetone add to the double bond of acrylic monomers in the presence of the initiating system Fe(CO)/sub 5/ + Br/sub 2/(IS). The iron pentacarbonyl-bromine system initiates the addition reactions of ethyl acetoacetate and acetylacetone with the double bonds of acrylic monomers.

  5. 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...

  6. Control Study of Ethyl tert-Butyl Ether Reactive Distillation Muhammad A. Al-Arfaj

    E-print Network

    Al-Arfaj, Muhammad A.

    Control Study of Ethyl tert-Butyl Ether Reactive Distillation Muhammad A. Al-Arfaj Department structures for ethyl tert-butyl ether (ETBE) reactive distillation columns are studied. Two process The use of reactive distillation has grown in recent years because it results in less expensive and more

  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. High-yield synthesis of bioactive ethyl cinnamate by enzymatic esterification of cinnamic acid.

    PubMed

    Wang, Yun; Zhang, Dong-Hao; Zhang, Jiang-Yan; Chen, Na; Zhi, Gao-Ying

    2016-01-01

    In this paper, Lipozyme TLIM-catalyzed synthesis of ethyl cinnamate through esterification of cinnamic acid with ethanol was studied. In order to increase the yield of ethyl cinnamate, several media, including acetone, isooctane, DMSO and solvent-free medium, were investigated in this reaction. The reaction showed a high yield by using isooctane as reaction medium, which was found to be much higher than the yields reported previously. Furthermore, several parameters such as shaking rate, water activity, reaction temperature, substrate molar ratio and enzyme loading had important influences on this reaction. For instance, when temperature increased from 10 to 50 °C, the initial reaction rate increased by 18 times and the yield of ethyl cinnamate increased by 6.2 times. Under the optimum conditions, lipase-catalyzed synthesis of ethyl cinnamate gave a maximum yield of 99%, which was of general interest for developing industrial processes for the preparation of ethyl cinnamate. PMID:26213020

  10. COMPARATIVE GENOTOXICITY STUDIES OF ETHYL CARBAMATE AND RELATED CHEMICALS: FURTHER SUPPORT FOR VINYL CARBAMATE AS A PROXIMATE CARCINOGENIC METABOLITE

    EPA Science Inventory

    In vivo and/or in vitro mammalian cell systems were used to evaluate sister chromatid exchange (SCE) induction and gene mutagenesis effects following exposure to ethyl carbamate (urethane), vinyl carbamate, ethyl N-hydroxycarbamate, and 2-hydroxyethyl carbamate.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Thermochemistry of Ethyl 3-Oxobutanoate Revisited: Observance of a Non-Zero Enthalpy of Mixing between Tautomers and Its Effects

    E-print Network

    Chickos, James S.

    , ethyl acetoacetate can act as a bidentate ligand and form complexes with metal ions.1 Its enthalpy, the term ethyl acetoacetate will be used when referring to the equilibrium mixture, and the terms ethyl 3 of formation of ethyl acetoacetate in liquid phase, fH°m(l, 298.15 K) ) (-640.4 ( 1.1) kJ,mol-1, has been

  3. Spectroscopic Characterization and Detection of Ethyl Mercaptan in Orion

    NASA Astrophysics Data System (ADS)

    Kolesniková, Lucie; Daly, Adam M.; Alonso, José L.; Tercero, Belén; Cernicharo, Jose; Gordon, Bri; Shipman, Steven

    2014-06-01

    The rotational spectrum of ethyl mercaptan, CH3CH2SH, has been measured in the microwave, millimeter- and submillimeter-wave regions from 8 to 880 GHz and more than 2800 distinct transition frequencies have been assigned for the gauche- and trans-conformers. Very precise values of the spectroscopic constants allowed the detection of the gauche-CH_3CH_2SH towards Orion KL. 77 unblended or slightly blended lines plus no missing transitions in the range 80 -- 280 GHz support this identification. Trans--CH_3CH_2SH has been detected tentatively. L. Kolesniková, B. Tercero, J. Cernicharo, A. M. Daly, J. L. Alonso, B. P. Gordon, S. Shipman, Astrophys. J. Lett. 2014, accepted.

  4. DETERMINATION OF DISSOLVED KEPONE BY DIRECT ADDITION OF XAD-2 RESIN TO WATER

    EPA Science Inventory

    Analytical procedures are described for the determination of Kepone in water, using benzene, toulene-ethyl acetate, or ethyl ether-hexane as solvents. The procedure is presently being used to quantify dissolved Kepone concentrations of less than 15 ng/l in the James River and thu...

  5. A long-standing mystery solved: the formation of 3-hydroxydesloratadine is catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UDP-glucuronosyltransferase 2B10 is an obligatory requirement.

    PubMed

    Kazmi, Faraz; Barbara, Joanna E; Yerino, Phyllis; Parkinson, Andrew

    2015-04-01

    Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating long-lasting antihistamine that is widely used for the treatment of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has remained a mystery as to which enzymes are responsible for the formation of 3-hydroxydesloratadine, the major active human metabolite, largely due to the inability of any in vitro system tested thus far to generate this metabolite. In this study, we demonstrated that cryopreserved human hepatocytes (CHHs) form 3-hydroxydesloratadine and its corresponding O-glucuronide. CHHs catalyzed the formation of 3-hydroxydesloratadine with a Km of 1.6 ?M and a Vmax of 1.3 pmol/min per million cells. Chemical inhibition of cytochrome P450 (P450) enzymes in CHHs demonstrated that gemfibrozil glucuronide (CYP2C8 inhibitor) and 1-aminobenzotriazole (general P450 inhibitor) inhibited 3-hydroxydesloratadine formation by 91% and 98%, respectively. Other inhibitors of CYP2C8 (gemfibrozil, montelukast, clopidogrel glucuronide, repaglinide, and cerivastatin) also caused extensive inhibition of 3-hydroxydesloratadine formation (73%-100%). Assessment of desloratadine, amodiaquine, and paclitaxel metabolism by a panel of individual CHHs demonstrated that CYP2C8 marker activity robustly correlated with 3-hydroxydesloratadine formation (r(2) of 0.70-0.90). Detailed mechanistic studies with sonicated or saponin-treated CHHs, human liver microsomes, and S9 fractions showed that both NADPH and UDP-glucuronic acid are required for 3-hydroxydesloratadine formation, and studies with recombinant UDP-glucuronosyltransferase (UGT) and P450 enzymes implicated the specific involvement of UGT2B10 in addition to CYP2C8. Overall, our results demonstrate for the first time that desloratadine glucuronidation by UGT2B10 followed by CYP2C8 oxidation and a deconjugation event are responsible for the formation of 3-hydroxydesloratadine. PMID:25595597

  6. An improved and validated sample cleanup method for analysis of ethyl carbamate in Chinese liquor.

    PubMed

    Xia, Qiang; Yuan, Huawei; Wu, Chongde; Zheng, Jia; Zhang, Suyi; Shen, Caihong; Yi, Bin; Zhou, Rongqing

    2014-09-01

    Ethyl carbamate (EC) is a potential human carcinogen widely existing in fermented foods and alcoholic beverages. The solid-phase extraction (SPE) coupled to gas chromatography mass spectrometry is a widely-used method to determine EC levels, but the accuracy varies with sample matrix and the effects of operation parameters are rarely examined. In this study, the influence factors involved in EC determination were investigated using Chinese liquor as sample matrix, and the improved method was further applied. Three types of SPE columns, including diatomite, Florisil, and primary-secondary amine, were compared in extraction efficiency, and the diatomite column exhibited the highest extraction efficiency. The optimal volumes of elution solvents with diatomite column were 15 mL for 3-mL samples solution loaded. In addition, the alcoholic strength for EC determination should be diluted below 20% (v/v) to avoid the enhancement of matrix-induced chromatographic response. Moreover, the pH neutralization could help improve EC recovery and peak resolution, reducing interfering effects. Based on these results, the improved method showed that the limit of detection, the limit of quantification, and average recoveries were 1.10 ?g/L, 3.65 ?g/L, and 93.06%, respectively. To further elucidate the underlying factors related to EC accumulation, partial least square regression analysis was conducted, and the results suggested that EC levels had the closest relationship with alcoholic strength among the remaining precursors. PMID:25124850

  7. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Chromium (Cr III) complex of N-ethyl-N... Substances for Use Only as Components of Paper and Paperboard § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium (Cr III) complex of N-ethyl -...

  8. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the...

  9. 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

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10110 Hexanoic acid, 2-ethyl-, mixed... to reporting. (1) The chemical substance identified as hexanoic acid, 2-ethyl-, mixed diesters...

  10. 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

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Hexanoic acid, 2-ethyl-, mixed... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10111 Hexanoic acid, 2-ethyl-, mixed... to reporting. (1) The chemical substance identified as hexanoic acid, 2-ethyl-, mixed diesters...

  11. 40 CFR 721.10326 - 2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl...

  12. 40 CFR 721.10326 - 2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl...

  13. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  14. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  15. 40 CFR 721.10243 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, bis(2-chloroethyl) ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, P- ethyl]-, bis(2... Specific Chemical Substances § 721.10243 Phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester. (a... phosphonic acid, P- ethyl]-, bis(2-chloroethyl) ester (PMN P-09-193; CAS No. 55088-28-3) is subject...

  16. Quantification of Hepatic UDP glucuronosyltransferase 1A splice variant expression and correlation of UDP glucuronosyltransferase 1A1 variant expression with glucuronidation activity.

    PubMed

    Jones, Nathan R; Sun, Dongxiao; Freeman, Willard M; Lazarus, Philip

    2012-09-01

    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, r˛ = 0.720; p = 0.0002, r˛ = 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

  17. 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.

  18. Valence and ionic lowest-lying electronic states of ethyl formate as studied by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy, and ab initio calculations.

    PubMed

    ?mia?ek, M A; ?abuda, M; Guthmuller, J; Hubin-Franskin, M-J; Delwiche, J; Duflot, D; Mason, N J; Hoffmann, S V; Jones, N C; Limăo-Vieira, P

    2014-09-14

    The highest resolution vacuum ultraviolet photoabsorption spectrum of ethyl formate, C2H5OCHO, yet reported is presented over the wavelength range 115.0-275.5 nm (10.75-4.5 eV) revealing several new spectral features. Valence and Rydberg transitions and their associated vibronic series, observed in the photoabsorption spectrum, have been assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of ethyl formate and are compared with a newly recorded He(I) photoelectron spectrum (from 10.1 to 16.1 eV). New vibrational structure is observed in the first photoelectron band. The photoabsorption cross sections have been used to calculate the photolysis lifetime of ethyl formate in the upper stratosphere (20-50 km). PMID:25217920

  19. Valence and ionic lowest-lying electronic states of ethyl formate as studied by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy, and ab initio calculations

    SciTech Connect

    ?mia?ek, M. A.; Duflot, D.; Mason, N. J.; Hoffmann, S. V.; Jones, N. C.; Limăo-Vieira, P.

    2014-09-14

    The highest resolution vacuum ultraviolet photoabsorption spectrum of ethyl formate, C{sub 2}H{sub 5}OCHO, yet reported is presented over the wavelength range 115.0–275.5 nm (10.75–4.5 eV) revealing several new spectral features. Valence and Rydberg transitions and their associated vibronic series, observed in the photoabsorption spectrum, have been assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of ethyl formate and are compared with a newly recorded He(I) photoelectron spectrum (from 10.1 to 16.1 eV). New vibrational structure is observed in the first photoelectron band. The photoabsorption cross sections have been used to calculate the photolysis lifetime of ethyl formate in the upper stratosphere (20–50 km)

  20. Reactions of ethyl groups on a model chromia surface: Ethyl chloride on stoichiometric ?-Cr 2O 3 (1 0 1Ż 2)

    NASA Astrophysics Data System (ADS)

    Brooks, John D.; Ma, Qiang; Cox, David F.

    2009-02-01

    The reaction of CH 3CH 2Cl over the nearly-stoichiometric ?-Cr 2O 3 (1 0 1Ż 2) surface yields gas phase CH 2dbnd CH 2, CH 3CH 3, H 2 and surface chlorine adatoms. The decomposition reaction is initiated via C-Cl bond cleavage to give a surface ethyl (CH 3CH 2-) intermediate. A rate-limiting ?-hydride elimination from the surface ethyl species produces gas phase CH 2dbnd CH 2 and surface hydrogen atoms. Two parallel competing reactions form CH 3CH 3, via ?-hydride addition to remaining surface ethyl species (reductive elimination), and H 2, via the combination of two surface hydrogen atoms. The chlorine freed from the dissociation of CH 3CH 2Cl binds at the five-coordinate surface Cr 3+ 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 1Ż 2) facets of ?-Cr 2O 3.

  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. The Millimeter- and Submillimeter-Wave Spectrum of Gauche-Ethyl Alcohol

    NASA Technical Reports Server (NTRS)

    Pearson, J. C.; Sastry, K. V. L. N.; Herbst, Eric; DeLucia, Frank C.

    1996-01-01

    We report an investigation of the rotational-torsional spectrum of the gauche rotational isomers of ethyl alcohol in the 51-505 GHz frequency region. Over a thousand transitions between rotational levels in the gauche substates of the ground OH torsional state have been measured and assigned. These transitions involve rotational quantum numbers J and K(sub a) up to 30 and 15, respectively, and are of two types: alpha-type transitions between levels in either the gauche+ or the gauche-substate, and c-type transitions between rotational levels in the different substates. The majority of these transitions have been fit satisfactorily using a two-state Hamiltonian based on the Fixed Framework Axis Method (FFAM). The rotation, distortion, and interaction constants have been determined along with the energy difference between the two gauche substates. The derived constants can be used to predict many more transitions accurately for astronomical purposes. The J and K(sub a) region where the two-state analysis can be used has been determined. The basis for a three-state analysis including the trans substate is presented and the applicability of the FFAM approach is discussed.

  3. Searching for trans ethyl methyl ether in Orion KL?

    NASA Astrophysics Data System (ADS)

    Tercero, B.; Cernicharo, J.; López, A.; Brouillet, N.; Kolesniková, L.; Motiyenko, R. A.; Margulčs, L.; Alonso, J. L.; Guillemin, J.-C.

    2015-10-01

    We report on the tentative detection of trans ethyl methyl ether (tEME), t-CH3CH2OCH3, through the identification of a large number of rotational lines from each one of the spin states of the molecule towards Orion KL. We also search for gauche-trans-n-propanol, Gt-n-CH3CH2CH2OH, an isomer of tEME in the same source. We have identified lines of both species in the IRAM 30 m line survey and in the ALMA Science Verification data. We have obtained ALMA maps to establish the spatial distribution of these species. Whereas tEME mainly arises from the compact ridge component of Orion, Gt-n-propanol appears at the emission peak of ethanol (south hot core). The derived column densities of these species at the location of their emission peaks are ?(4.0 ± 0.8) × 1015 cm-2 and ?(1.0 ± 0.2) × 1015 cm-2 for tEME and Gt-n-propanol, respectively. The rotational temperature is ~100 K for both molecules. We also provide maps of CH3OCOH, CH3CH2OCOH, CH3OCH3, CH3OH, and CH3CH2OH to compare the distribution of these organic saturated O-bearing species containing methyl and ethyl groups in this region. Abundance ratios of related species and upper limits to the abundances of non-detected ethers are provided. We derive an abundance ratio N(CH3OCH3)/N(tEME) ? 150 in the compact ridge of Orion. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2011.0.00009.SV. ALMA is a partnership of ESO (representing its member states), NSF (USA), and NINS (Japan) with NRC (Canada), NSC, and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO, and NAOJ. This work was also based on observations carried out with the IRAM 30-m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).Appendix A is available in electronic form at http://www.aanda.org

  4. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) analogs as glutaminase inhibitors

    PubMed Central

    Shukla, Krupa; Ferraris, Dana V.; Thomas, Ajit G.; Stathis, Marigo; Duvall, Bridget; Delahanty, Greg; Alt, Jesse; Rais, Rana; Rojas, Camilo; Gao, Ping; Xiang, Yan; Dang, Chi V.; Slusher, Barbara S.; Tsukamoto, Takashi

    2012-01-01

    Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has served as a molecular probe to determine the therapeutic potential of GLS inhibition. In an attempt to identify more potent GLS inhibitors with improved drug-like molecular properties, a series of BPTES analogs were synthesized and evaluated. Our structure-activity relationship (SAR) studies revealed that some truncated analogs retained the potency of BPTES, presenting an opportunity to improve its aqueous solubility. One of the analogs, N-(5-{2-[2-(5-amino-[1,3,4]thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl)-2-phenyl-acetamide, exhibited similar potency and better solubility relative to BPTES and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a mouse xenograft model. PMID:23151085

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...on the following commodities: Commodity Parts per million Corn, field, grain 0.01 Soybean, seed 0.01 Sugarcane, cane 0.01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic...

  6. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...on the following commodities: Commodity Parts per million Corn, field, grain 0.01 Soybean, seed 0.01 Sugarcane, cane 0.01 (2) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic...

  7. 40 CFR 180.515 - Carfentrazone-ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...bran 0.80 Wheat, flour 0.80 Wheat, germ 0.80 Wheat, middlings 0.80 Wheat, shorts 0.80 (b) Section 18 emergency...carfentrazone-ethyl and its chloropropionic acid metabolite in connection with use...

  8. Rapeseed ethyl ester as bio-lube in 2-cycle engine

    SciTech Connect

    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.

  9. Synthesis and bacterial biofilm inhibition studies of ethyl N-(2-phenethyl) carbamate derivatives

    E-print Network

    Rogers, Steven A.

    2010-07-08

    An 88 member library based upon the marine bacterial metabolite ethyl N-(2-phenethyl) carbamate was evaluated for bacterial biofilm inhibition against a panel of medically relevant strains. These studies culminated in the discovery of a new class...

  10. Mechanism of N(5)-ethyl-flavinium cation formation upon electrochemical oxidation of N(5)-ethyl-4a-hydroxyflavin pseudobase.

    PubMed

    Sichula, Vincent; Hu, Ying; Mirzakulova, Ekaterina; Manzer, Samuel F; Vyas, Shubham; Hadad, Christopher M; Glusac, Ksenija D

    2010-07-29

    We investigated the oxidation behavior of 5-ethyl-4a-hydroxy-3-methyl-4a,5-dihydrolumiflavin (pseudobase Et-FlOH) in acetonitrile with the aim of determining if the two-electron oxidized Et-FlOH(2+) undergoes a release of hydroxyl cation and the production of 5-ethyl-3methyllumiflavinium cation (Et-Fl(+)). The focus of this work is to investigate the possibility of using Et-FlOH as a catalyst for water oxidation. The cyclic voltammetry demonstrates that Et-FlOH exhibits two one-electron oxidation potentials at +0.95 and +1.4 V versus normal hydrogen electrode (NHE), with the second oxidation potential being irreversible. The production of Et-Fl(+) is observed in the cyclic voltammetry of Et-FlOH and has been previously assigned to the release of OH(+) from the two-electron oxidized Et-FlOH(2+). The results of our study show that this is not the case: (i) we performed bulk electrolysis of the electrolyte solution at +2 V and then added Et-FlOH to the electrolyzed solution. We found that Et-Fl(+) is produced from this solution, even though Et-FlOH itself was not oxidized; (ii) reactions of Et-FlOH with chemical oxidants (ceric ammonium nitrate, nitrosyl tetrafluoroborate, and tetrabutylammonium persulfate) demonstrate that Et-Fl(+) production occurs only in the presence of strong Lewis acids, such as Ce(4+) and NO(+) ions. On the basis of these results, we propose that the production of Et-Fl(+) in the electrochemistry of Et-FlOH occurs because of the shift in the Et-FlOH/Et-Fl(+) acid-base equilibrium in the presence of protons released during anodic oxidation. We identified two sources of protons: (i) oxidation of traces of water present in the acetonitrile releases oxygen and protons and (ii) two-electron oxidized Et-FlOH(2+) releases protons located on the N(5)-alkyl chain. The release of protons from Et-FlOH(2+) was confirmed by cyclic voltammetry of Et-FlOH in the presence of pyridine as a base. The first oxidation peak of Et-FlOH at +0.95 V is reversible in the absence of pyridine. The addition of pyridine leads to the shift of the oxidation potential to a less positive value, which is consistent with a proton-coupled electron transfer (PCET). Furthermore, the anodic current increases, and the cathodic peak becomes irreversible, giving rise to two additional reduction peaks at -0.2 and -1 V. The same reduction peaks were observed in the high scan rate cyclic voltammogram of Et-FlOH in the absence of pyridine, implying that the release of protons indeed occurs from Et-FlOH(2+). To determine which functional group of Et-FlOH(.+) is the source of protons, we performed DFT calculations at the B3LYP/6-311++G** level of theory for a reaction of Et-FlOH(.+) with pyridine and identified two proton sources: (i) the >N-CH(2)- group of the N(5) alkyl chain and (ii) the -OH group in the 4a-position of the radical cation. Because the appearance of new reduction peaks at -0.2 and -1.0 V occurs in the model compound that lacks -OH protons (Et-FlOMe), we conclude that the proton removal occurs predominantly from the >N-CH(2)- moiety. PMID:20597524

  11. Synthesis of ethyl phenylacetate by lyophilized mycelium of Aspergillus oryzae.

    PubMed

    Converti, A; Gandolfi, R; Zilli, M; Molinari, F; Binaghi, L; Perego, P; Del Borghi, M

    2005-06-01

    Lyophilized mycelia of Aspergillus oryzae CBS 102.07, Aspergillus oryzae MIM, Rhizopus oryzae CBS 112.07, Rhizopus oryzae CBS 391.34, Rhizopus oryzae CBS 260.28 and Rhizopus oryzae CBS 328.47 were tested in this study to select the best biocatalysts for ethanol acylation with phenylacetic acid. The mycelium-bound carboxylesterase activity of A. oryzae MIM, which exhibited the best performances, was initially investigated at 50 degrees C, either in 0.1 M phosphate buffer or in n-heptane to catalyse the hydrolysis or the synthesis, respectively, of ethyl phenylacetate. The results in terms of product and substrate concentrations versus time were used to estimate the maximum molar conversions at equilibrium, the equilibrium constants, and the times needed to reach half maximum conversions, thus providing sufficient information about this biotransformation. The values of the apparent equilibrium constants, estimated at 20 degrees C

  12. Ethyl Cyanide On Titan: Spectroscopic Detection and Mapping Using Alma

    NASA Astrophysics Data System (ADS)

    Cordiner, M. A.; Palmer, M. Y.; Nixon, C. A.; Irwin, P. G. J.; Teanby, N. A.; Charnley, S. B.; Mumma, M. J.; Kisiel, Z.; Serigano, J.; Kuan, Y.-J.; Chuang, Y.-L.; Wang, K.-S.

    2015-02-01

    We report the first spectroscopic detection of ethyl cyanide (C2H5CN) in Titan’s atmosphere, obtained using spectrally and spatially resolved observations of multiple emission lines with the Atacama Large Millimeter/submillimeter Array (ALMA). The presence of C2H5CN in Titan’s ionosphere was previously inferred from Cassini ion mass spectrometry measurements of C2H5CNH+. Here we report the detection of 27 rotational lines from C2H5CN (in 19 separate emission features detected at \\gt 3? confidence) in the frequency range 222-241 GHz. Simultaneous detections of multiple emission lines from HC3N, CH3CN, and CH3CCH were also obtained. In contrast to HC3N, CH3CN, and CH3CCH, which peak in Titan’s northern (spring) hemisphere, the emission from C2H5CN is found to be concentrated in the southern (autumn) hemisphere, suggesting a distinctly different chemistry for this species, consistent with a relatively short chemical lifetime for C2H5CN. Radiative transfer models show that C2H5CN is most concentrated at altitudes ? 200 km, suggesting production predominantly in the stratosphere and above. Vertical column densities are found to be in the range (1-5) × 1014 cm-2.

  13. Searching for Trans Ethyl Methyl Ether in Orion KL

    E-print Network

    Tercero, B; López, A; Brouillet, N; Kolesniková, L; Motiyenko, R A; Margulčs, L; Alonso, J L; Guillemin, J -C

    2015-01-01

    We report on the tentative detection of $trans$ Ethyl Methyl Ether (tEME), $t-CH_3CH_2OCH_3$, through the identification of a large number of rotational lines from each one of the spin states of the molecule towards Orion KL. We also search for $gauche$-$trans$-n-propanol, $Gt-n-CH_3CH_2CH_2OH$, an isomer of tEME in the same source. We have identified lines of both species in the IRAM 30m line survey and in the ALMA Science Verification data. We have obtained ALMA maps to establish the spatial distribution of these species. Whereas tEME mainly arises from the compact ridge component of Orion, Gt-n-propanol appears at the emission peak of ethanol (south hot core). The derived column densities of these species at the location of their emission peaks are $\\leq(4.0\\pm0.8)\\times10^{15} cm^{-2}$ and $\\leq(1.0\\pm0.2)\\times10^{15} cm^{-2}$ for tEME and Gt-n-propanol, respectively. The rotational temperature is $\\sim100 K$ for both molecules. We also provide maps of $CH_3OCOH$, $CH_3CH_2OCOH$, $CH_3OCH_3$, $CH_3OH$, a...

  14. Evaluation of transurethral and transperineal tin ethyl etiopurpurin-photodynamic therapy on the canine prostate one week after drug injection

    NASA Astrophysics Data System (ADS)

    Selman, Steven H.; Keck, Rick W.; Kondo, Sandy; Albrecht, Detlef

    1999-06-01

    We have been investigating the potential applicability of photodynamic therapy for the treatment of benign and malignant disease of the prostate. Both transurethral and transperineal approaches to the delivery of light to the tin ethyl etiopurpurin sensitized canine prostate have been studied. Pharmacologic studies were performed and suggested that delaying light treatment for 7 days after drug administration would maximize the desired effect on the targeted prostatic tissue while minimizing the damage to surrounding bladder and rectum. A total of 12 dogs were treated with transurethral light alone (n=6) or the combination of transurethral light and transperineal light one week after tin ethyl etiopurpurin administration. (Previous studies have shown that light alone has no effect on prostate size or histology.) Animals were euthanized 48 hours and 3 weeks after completion of treatment (drug, 1mg/kg day 0, light [400mw/750sec]day 7). Tissue response was determined by gross and microscopic examination. Additionally, pre- and post- treatment transrectal ultrasounds were compared to assess changes in prostate volume and tissue echogenicity. The combination of transurethral and transperineal light results in extensive destruction of glandular epithelium with minimal damage to surrounding structures. Prostate volumes decreased by an average of 52%. Untreated areas were found to lie greater than 0.5 cm from the light diffuser. These studies have encouraged us to continue to investigate this modality as a technique for total ablation of prostatic glandular epithelium.

  15. Targeting misuse of 2-amino-N-ethyl-1-phenylbutane in urine samples: in vitro-in vivo correlation of metabolic profiles and development of LC-TOF-MS method.

    PubMed

    Kobayashi, Masaki; Pelander, Anna; Ketola, Raimo A; Leinonen, Antti; Kuuranne, Tiia

    2015-02-01

    A phenyethylamine derivative, 2-amino-N-ethyl-1-phenylbutane (2-AEPB), has recently been detected in doping control and drugs-of-abuse samples, and identified as a non-labelled ingredient in a dietary supplement. To facilitate efficient control of this substance we have studied the in vitro metabolic behaviour of 2-AEPB with human liver preparation, compared these results with in vivo pathways in human, and finally propose an analytical strategy to target the potential misuse of 2-AEPB for toxicological, forensic and doping control purposes. The major in vitro formed metabolites originated from desethylation (M1) and monohydroxylation (M2). A minor metabolite with hydroxylation/N-oxidation was also observed (M3). In vitro-in vivo correlation was studied in an excretion study with a single, oral dose of 2-AEPB-containing supplement. An unmodified substance was the most abundant target compound and detected until the last point of sample collection (72?h), and the detection of M1 (40?h) and M2 (27?h) demonstrated good correlation to in vitro results. In the study with authentic cases (n?=?6), 2-AEPB and M1 were mainly found in free urinary fraction, whereas higher inter-individual variability was observed for M2. It was predominantly conjugated and already within this limited number of cases, the ratio between glucuronide- and sulpho-conjugated fractions varied significantly. As a conclusion, hydrolysis is not mandatory in the routine sample preparation, and as the separation can be based on either gas chromatography or liquid chromatography, this study verifies that routine mass spectrometric detection methods targeted to amphetamine derivatives can be easily extended to control the misuse of 2-AEPB. PMID:24687931

  16. Effect of citrulline, urea, ethanol, and urease on the formation of ethyl carbamate in soybean paste model system.

    PubMed

    Kim, Yong Gun; Lyu, Jihye; Kim, Mina K; Lee, Kwang-Geun

    2015-12-15

    The aim of this study was to determine the effect of urease on the formation of ethyl carbamate (EC) in the presence of previously known precursors of EC (citrulline, urea, and ethanol) using a soybean paste model system. The levels of EC were quantitatively determined by gas chromatography-mass spectrometry (GC-MS) every five days for a 30-day period. After 30 days fermentation, the concentration of EC increased significantly by 135.2%, 242.2%, and 3757.1% when the precursors (citrulline, urea and ethanol) were added to the model system, respectively (p<0.05). Urease significantly decreased the level of EC by 38.4%, 18.8%, and 17.3% when citrulline, urea, and ethanol were added to the model system, respectively (p<0.05). PMID:26190603

  17. Developing intestine is injured during absorption of oleic acid but not its ethyl ester.

    PubMed Central

    Velasquez, O R; Place, A R; Tso, P; Crissinger, K D

    1994-01-01

    Although lipids are essential nutrients in the mammalian diet, we have shown that fatty acids are injurious to epithelial cells of developing piglet intestine during luminal perfusion. Furthermore, the intestine of young animals sustains greater injury than that of older piglets. In an effort to understand the mechanism for this developmental injury, we investigated whether changes in the chemical configuration of oleic acid would alter this damage. Mucosal permeability, as quantitated by the plasma-to-lumen clearance of 51chromium EDTA, was evaluated during luminal perfusion with oleic acid as compared with its ethyl (ethyl oleate) and glyceryl (glycerol-1-mono-oleate) esters, solubilized with taurocholic acid, in jejunum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets. 51Chromium EDTA clearance increased significantly during oleic acid and glycerol-1-mono-oleate perfusion, but did not increase during perfusion with ethyl oleate or saline. This result was not secondary to failure of absorption of ethyl oleate, as [14C]oleic acid and ethyl [1-14C]oleate were absorbed to a similar extent. Furthermore, developing intestine was able to remove the ethyl group and then re-esterify the fatty acid to form triacyglycerol. These studies indicate that oleic acid-induced mucosal injury can be abolished when the carboxylic group of the fatty acid is esterified with an ethyl, but not a glycerol, group. Since the ethyl ester is also absorbed and metabolized similarly to the free fatty acid, this may provide a means of supplying long-chain fatty acids to developing intestine without causing mucosal damage. Images PMID:8113387

  18. Crude ethyl acetate extract of marine microalga, Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells

    PubMed Central

    Goh, Su Hua; Alitheen, Noorjahan Banu Mohamed; Yusoff, Fatimah Md; Yap, Swee Keong; Loh, Su Peng

    2014-01-01

    Background: Marine brown diatom Chaetoceros calcitrans and green microalga Nannochloropsis oculata are beneficial materials for various applications in the food, nutraceutical, pharmaceutical and cosmeceutical industries. Objective: This study investigated cytotoxicity of different crude solvent extracts from C. calcitrans and N. oculata against various cancer cell lines. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out to screen the cytotoxic effects of hexane (Hex), dichloromethane (DCM), ethyl acetate, and methanol extract from C. calcitrans and N. oculata toward various cancer cell lines. Flow cytometry cell cycle was used to determine the cell cycle arrest while the mode of cell death was investigated through acridine orange/propidium iodide (AOPI) staining, Annexin V-Fluorescein Isothiocyanate (FITC) and Terminal deoxynucleotidyl transferase-mediated d-UTP Nick End Labeling (TUNEL) assays. Expression profile of apoptotic and proliferative-related genes was then determined using the multiplex gene expression profiler (GeXP). Results: Crude ethyl acetate (CEA) extract of C. calcitrans inhibited growth of MDA-MB-231 cells, with IC50 of 60 ?g/mL after 72 h of treatment. Further studies were conducted to determine the mode of cell death at various concentrations of this extract: 30, 60 and 120 ?g/mL. The mode of cell death was mainly apoptosis as shown through apoptosis determination test. The expression data from GeXP showed that caspase-4 was upregulated while B-cell leukemia/lymphoma 2(Bcl-2) was down regulated. Thus, caspase-4 induction endoplasmic reticulum death pathway is believed to be one of the mechanisms underlying the induction of apoptosis while Bcl-2 induced S and G2/M cell cycle phase arrest in MDA-MB-231 cells. Conclusion: CEA extract of C. calcitrans showed the highest cytotoxicity on MDA-MB-231 via apoptosis. PMID:24696543

  19. 2,2?-Bi(9,9-di­ethyl­fluorene)

    PubMed Central

    Park, Ki-Min; Oh, Hankook; Kang, Youngjin

    2014-01-01

    The title compound, C34H34, systematic name 9,9,9?,9?-tetra­ethyl-2,2?-bi(9H-fluorene), crystallized with two crystallographically independent mol­ecules (A and B) in the asymmetric unit. These differ mainly in the orientation of the lateral ethyl chains: in mol­ecule A, they are both on the same side of the mol­ecule whereas in mol­ecule B, one di­ethyl­fluorene moiety has undergone a 180° rotation such that the two pairs of ethyl residues appear on opposite sides of the mol­ecule. The fluorene ring systems subtend dihedral angles of 31.37?(4) and 43.18?(3)° in mol­ecules A and B, respectively. Hence the two fluorene moieties are tilted slightly toward one another. This may be due to the presence of inter­molecular C—H?? inter­actions between neighboring mol­ecules. The lateral ethyl chains (excluding H atoms) are also almost planar, with each pair almost perpendicular to the plane of the fluorene system to which they are attached with dihedral angles between the ethyl and fluorene planes in the range 86.04?(8)–89.5?(1)°. PMID:24764898

  20. Ethyl Formate: A Potential Disinfestation Treatment for Eucalyptus Weevil (Gonipterus platensis) (Coleoptera: Curculionidae) in Apples.

    PubMed

    Agarwal, Manjree; Ren, Yonglin; Newman, James; Learmonth, Stewart

    2015-12-01

    Export of Pink Lady apples from Australia has been significantly affected by infestations of adult eucalyptus weevils (Gonipterus platensis Marelli). These weevils cling tenaciously to the pedicel of apple fruit when selecting overwintering sites. As a result, apples infested with live G. platensis adults lead to rejection for export. Since the Montreal Protocol restricted use of methyl bromide as postharvest treatment, it was necessary to consider alternative safer fumigants for disinfestation of eucalyptus weevil. Laboratory experiments were conducted using concentrations of 5, 10, 15, 20, 25, 30, 40, and 80?mg/liter of ethyl formate. Complete control (100% mortality) was achieved at 25-30?mg/liter of ethyl formate at 22-24°C for 24-h exposure without apples. However, with 90-95% of the volume full of apples, complete control was achieved at 40?mg/liter of ethyl formate at 22-24°C for 24-h exposure. No phytotoxicity was observed and after one day aeration, residue of ethyl formate declined to natural levels (0.05-0.2?mg/kg). Five ethyl formate field trials were conducted in cool storages (capacity from 250-900 tons) and 100% kill of eucalyptus weevils were achieved at 50-55?mg/liter at 7-10°C for 24?h. Ethyl formate has great potential for preshipment treatment of apples. Its use is considerably cheaper and safer than already existing fumigants like methyl bromide and phosphine. PMID:26470387

  1. Hypopigmentary effects of ethyl P-methoxycinnamate isolated from Kaempferia galanga.

    PubMed

    Ko, Hyun-Ju; Kim, Hae Jong; Kim, Su Yeon; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Wan Kyun Whang; Choi, Hye-Ryung; Park, Kyoung-Chan; Kim, Dong-Seok

    2014-02-01

    We isolated crystals from the chloroform fraction of an ethanol extract of Kaempferia galanga and identified it as ethyl p-methoxycinnamate through nuclear magnetic resonance analysis. In the present study, we found that ethyl p-methoxycinnamate significantly decreased melanin synthesis in B16F10 murine melanoma cells stimulated with ?-melanocyte stimulating hormone (?-MSH). In a cell-free system, however, ethyl p-methoxycinnamate did not directly inhibit tyrosinase, the rate-limiting enzyme of melanogenesis. Instead, it inhibited tyrosinase activity in B16F10 cells in a dose-dependent manner. Furthermore, Western blot analysis showed that ethyl p-methoxycinnamate decreased microphthalmia-associated transcription factor and tyrosinase levels in ?-MSH-stimulated B16F10 cells. These results indicate that the pigment-inhibitory effect of ethyl p-methoxycinnamate results from downregulation of tyrosinase. Ethyl p-methoxycinnamate isolated from K. galanga could be developed as a skin whitening agent to treat hyperpigmentary disorders. PMID:23610003

  2. Solvent exchange-induced in situ forming gel comprising ethyl cellulose-antimicrobial drugs.

    PubMed

    Phaechamud, Thawatchai; Mahadlek, Jongjan

    2015-10-15

    Solvent-exchanged in situ forming gel is a drug delivery system which is in sol form before administration. When it contacts with the body fluid, then the water miscible organic solvent dissipates and water penetrates into the system, leading the polymer precipitation as in situ gel at the site of injection. The aim of this research was to study the parameters affecting the gel properties, drug release and antimicrobial activities of the in situ forming gels prepared from ethyl cellulose (EC) dissolved in N-methyl pyrrolidone (NMP) to deliver the antimicrobial agents (doxycycline hyclate, metronidazole and benzyl peroxide) for periodontitis treatment. The gel appearance, pH, viscosity, rheology, syringeability, gel formation, rate of water diffusion into the gels, in vitro degradation, drug release behavior and antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans and Porphyrommonas gingivalis were determined. Increasing the amount of EC increased the viscosity of system while still exhibiting Newtonian flow and increased the work of syringeability whereas decreased the releasing of drug. The system transformed into the rigid gel formation after being injected into the simulated gingival crevicular fluid. The developed systems containing 5% w/w antimicrobial agent showed the antimicrobial activities against all test bacteria. Thus the developed solvent exchange-induced in situ forming gels comprising EC-antimicrobial drugs exhibited potential use for periodontitis treatment. PMID:26302862

  3. Thermal explosion analysis of methyl ethyl ketone peroxide by non-isothermal and isothermal calorimetric applications.

    PubMed

    Chi, Jen-Hao; Wu, Sheng-Hung; Shu, Chi-Min

    2009-11-15

    In the past, process incidents attributed to organic peroxides (OPs) that involved near misses, over-pressures, runaway reactions, and thermal explosions occurred because of poor training, human error, incorrect kinetic assumptions, insufficient change management, and inadequate chemical knowledge in the manufacturing process. Calorimetric applications were employed broadly to test organic peroxides on a small-scale because of their thermal hazards, such as exothermic behavior and self-accelerating decomposition in the laboratory. In essence, methyl ethyl ketone peroxide (MEKPO) is highly reactive and exothermically unstable. In recent years, it has undergone many thermal explosions and runaway reaction incidents in the manufacturing process. Differential scanning calorimetry (DSC), vent sizing package 2 (VSP2), and thermal activity monitor (TAM) were employed to analyze thermokinetic parameters and safety index. The intent of the analyses was to facilitate the use of various auto-alarm equipments to detect over-pressure, over-temperature, and hazardous materials leaks for a wide spectrum of operations. Results indicated that MEKPO decomposition is detected at low temperatures (30-40 degrees C), and the rate of decomposition was shown to exponentially increase with temperature and pressure. Determining time to maximum rate (TMR), self-accelerating decomposition temperature (SADT), maximum temperature (T(max)), exothermic onset temperature (T(0)), and heat of decomposition (DeltaH(d)) was essential for identifying early-stage runaway reactions effectively for industries. PMID:19619941

  4. The Discriminative Properties of N-ETHYL-3,4-METHYLENE Dioxyamphetamine

    NASA Astrophysics Data System (ADS)

    Boja, John William

    The goal of this dissertation was to gain insight into the discriminative effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE). In order to examine the possibility that MDE acts via both serotonergic and dopaminergic mechanisms, MDE was administered to three groups of rats trained to discriminate either (1) the serotonergic agent norfenfluramine from vehicle, (2) norfenfluramine from the dopaminergic agent amphetamine or (3) amphetamine from vehicle. The results of these discrimination studies are evidence that MDE expresses serotonergic and dopaminergic properties in a temporal pattern in which MDE initially activates the serotonergic system, followed by dopaminergic system activation. To examine additional discriminative effects of MDE, a separate group of rats was trained to discriminate 2.0 mg/kg MDE from vehicle. Various drugs were administrated to these animals to determine their similarity or dissimilarity to MDE. The results of this study are additional evidence as to a dual serotonergic/dopaminergic mediation for MDE. In addition, the related drug 3,4-methylenedioxymethamphetamine produced similar effects but this drug was more potent and possessed a longer duration of action than MDE. Subsequently, administration of the known serotonergic synthesis inhibitor para-chlorophenylalanine (PCPA) to the MDE trained rats reduced, but did not totally eliminate, MDE discrimination. This indicates that either reduced serotonin levels are still sufficient for MDE discrimination or that MDE discrimination is not solely mediated by serotonin. These experiments evidence a serotonergic/dopaminergic discriminative stimulus for MDE.

  5. Existence of optical phonons in the room temperature ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate

    PubMed Central

    Burba, Christopher M.; Frech, Roger

    2011-01-01

    The technologically important properties of room temperature ionic liquids (RTILs) are fundamentally linked to the ion–ion interactions present among the constituent ions. These ion–ion interactions in one RTIL (1-ethyl-3-methylimidazolium trifluoromethanesulfonate, [C2mim]CF3SO3) are characterized with transmission FTIR spectroscopy and polarized attenuated total reflection (ATR) FTIR spectroscopy. A quasilattice model is determined to be the best framework for understanding the ionic interactions. A novel spectroscopic approach is proposed to characterize the degree of order that is present in the quasilattice by comparing the dipole moment derivative calculated from two independent spectroscopic measurements: (1) the TO–LO splitting of a vibrational mode using dipolar coupling theory and (2) the optical constants of the material derived from polarized ATR experiments. In principle, dipole moment derivatives calculated from dipolar coupling theory should be similar to those calculated from the optical constants if the quasilattice of the RTIL is highly structured. However, a significant disparity for the two calculations is noted for [C2mim]CF3SO3, indicating that the quasilattice of [C2mim]CF3SO3 is somewhat disorganized. The potential ability to spectroscopically characterize the structure of the quasilattice, which governs the long-range ion–ion interactions in a RTIL, is a major step forward in understanding the interrelationship between the molecular-level interactions among the constituent ions of an ionic liquid and the important physical properties of the RTIL. PMID:21476760

  6. Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction of Terminalia chebula

    PubMed Central

    Wahab, Abdul; Ayub, Khurshed; Sherkheli, M. Azhar; Khan, Rafeeq Alam; Raza, Mohsin

    2013-01-01

    Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500?mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60?min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10?mg/kg; i.p., dextromethorphan 10?mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265?mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3?mg/kg; s.c.) while rimcazole (3?mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated. PMID:24024039

  7. Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction of Terminalia chebula.

    PubMed

    Ul Haq, Rizwan; Wahab, Abdul; Ayub, Khurshed; Mehmood, Khalid; Sherkheli, M Azhar; Khan, Rafeeq Alam; Raza, Mohsin

    2013-01-01

    Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500?mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60?min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10?mg/kg; i.p., dextromethorphan 10?mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265?mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3?mg/kg; s.c.) while rimcazole (3?mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated. PMID:24024039

  8. In vitro study of partially hydrolyzed poly(2-ethyl-2-oxazolines) as materials for biomedical applications.

    PubMed

    Shah, Rushita; Kronekova, Zuzana; Zahoranová, Anna; Roller, Ladislav; Saha, Nabanita; Saha, Petr; Kronek, Juraj

    2015-04-01

    Polymers based on 2-oxazoline, such as poly(2-ethyl-2-oxazolines) (PETOx), are considered to be a type of 'pseudopeptide' with the ability to form novel biomaterials. The hydrolysis of PETOx was carried out to evaluate its use in biomedical applications. In the present work, PETOx samples with a range of molar masses were prepared by living cationic polymerization. Hydrolysis was carried out at time intervals ranging from 15 to 180 min to prepare copolymers with different amounts of ethylene imine units. (1)H NMR spectroscopy was used to identify the structure of the hydrolyzed polymers. The dependence of in vitro cell viability on the degree of hydrolysis was determined using three different model cell lines, namely, mouse embryonic 3T3 fibroblasts, pancreatic ?TC3 cells, and mouse lymphoid macrophages P388.D1. It was demonstrated that increasing the degree of hydrolysis decreased cell viability for all cell types. Fibroblast cells displayed the highest tolerance; additionally, the effect of polymer size showed no observable significance. Macrophage cells, immune system representatives, displayed the highest sensitivity to contact with hydrolyzed PETOx. The effect of polymer hydrolysis, polymer concentration and the incubation time on cell viability was experimentally observed. Confocal laser-scanning microscopy provided evidence of cellular uptake of pyrene-labeled (co)polymers. PMID:25783502

  9. Crystal Structure and Desolvation Behaviour of the Tadalafil Monosolvates with Acetone and Methyl Ethyl Ketone.

    PubMed

    Miclaus, Maria O; Kacso, Irina E; Martin, Flavia A; David, Leontin; Pop, Mihaela M; Filip, Claudiu; Filip, Xenia

    2015-11-01

    Crystal structures of Tadalafil (TDF) monosolvated forms with acetone (ACE) and methyl ethyl ketone (MEK) were determined by single-crystal X-ray diffraction in which same persistent chains of TDF molecules are present as in the reported structures. The solvates crystallize in a higher orthorhombic symmetry than the known forms with monoclinic structures. Weak interactions between TDF and solvent molecules are present in both solvates, leading to slight conformational distortions of TDF molecules. The MEK solvate showed slightly higher stability than the ACE solvate, regardless of their highly similar molecular conformations and crystal packing. Desolvation into anhydrous TDF was achieved by heating, exposure to temperature and relative humidity and by mechanical stress. The high solubility of TDF in ACE and MEK solvents combined with the ease of desolvation of the resulting solvated forms indicates the viability of the solvates use as intermediates in the TDF crystallization process. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3782-3788, 2015. PMID:26211652

  10. Tautomeric equilibrium of ethyl acetoacetate in compressed CO 2+ethanol and CO 2+methanol mixtures

    NASA Astrophysics Data System (ADS)

    Li, Zhonghao; Mu, Tiancheng; Jiang, Tao; Du, Jimin; Zhao, Guoying; Zhang, Jianling; Han, Buxing; Huang, Ying

    2004-04-01

    Tautomerism equilibrium of ethyl acetoacetate (EAA) in compressed CO 2+methanol and CO 2+ethanol mixtures was studied by UV-Vis spectroscopy at 308.15 K and different pressures. The volume expansion coefficient ( ?) of the solvents at different pressures was also determined. The relative permittivity ( ?) of CO 2+methanol and CO 2+ethanol mixtures at different conditions was calculated using the K c and Onsager solvent parameter. The equilibrium constant ( K c) of EAA in the binary mixtures increases considerably with increasing pressure or volume expansion coefficient. The relative permittivity or the polarity of the binary mixtures decreases sharply with increasing volume expansion coefficient in the range of 0< ?<1.5. However, as the volume expansion coefficient exceeds 1.5, the relative permittivity decreases slowly. In other words, the dissolution of CO 2 in the polar solvents can reduce the polarity of the solvents significantly in the low volume expansion coefficient range, and the polarity of the solution is not sensitive to the volume expansion coefficient as its value is large enough. The difference in polarity of the two solvents reduces with increasing pressure and becomes negligible after volume expansion coefficient exceeds about 2.5.

  11. Neurotoxicity associated with occupational exposure to acetone, methyl ethyl ketone, and cyclohexanone.

    PubMed

    Mitran, E; Callender, T; Orha, B; Dragnea, P; Botezatu, G

    1997-01-01

    The neurotoxic effects of acetone, methyl ethyl ketone (MEK), and cyclohexanone on Romanian workers and the impact of those effects on industry environmental standards have been controversial subjects. To scientifically substantiate the standards, a study was conducted on three groups of workers to determine the changes induced by ketone solvents on the central and peripheral nervous systems. Groups of exposed workers and matched controls were studied for each solvent: acetone, 71 exposed and 86 controls from a coin printing factory; MEK, 41 exposed and 63 controls from a cable factory; and cyclohexanone, 75 exposed and 85 controls from a furniture factory. The subjects' mean age was 36 years. The mean length of exposure was 14 years. Study participants completed a questionnaire, responded to questions about alcohol consumption, submitted to a clinical examination, submitted samples for identification of biological exposure markers, and underwent motor nerve conduction velocity and neurobehavioral tests. Results showed that workers exposed to acetone were most affected in terms of human performance and evidence of neurotoxicity, followed by workers exposed to MEK and workers exposed to cyclohexanone. On the basis of the results, it was proposed that the 6-hr permissible exposure limits for acetone, MEK, and cyclohexanone be reduced to less than 500, 200, and 150 mg/m3, respectively. PMID:9311545

  12. Ethyl acetate-n-butanol gradient solvent system for high-speed countercurrent chromatography to screen bioactive substances in okra.

    PubMed

    Ying, Hao; Jiang, Heyuan; Liu, Huan; Chen, Fangjuan; Du, Qizhen

    2014-09-12

    High-speed countercurrent chromatographic separation (HSCCC) possesses the property of zero-loss of sample, which is very useful for the screening of bioactive components. In the present study, the ethyl acetate-n-butanol gradient HSCCC solvent system composed of n-hexane-ethyl acetate-n-butanol-water was investigated for the screening of bioactive substances. To screen the antiproliferative compounds in okra extract, we used the stationary phase ethyl acetate-n-butanol-water (1:1:10) as the stationary phase, and eluted the antiproliferative components by 6-steps of gradient using mobile phases n-hexane-ethyl acetate (1:2), n-hexane-ethyl acetate (1:4), n-hexane-ethyl acetate (0:4), n-butanol-ethyl acetate (1:4) n-butanol-ethyl acetate (1:2), n-butanol-ethyl acetate (2:2), and n-butanol-ethyl acetate (2:1). The fractions collected from HSCCC separation with the gradient solvent system were assayed for antiproliferative activity against cancer cells. Bioactive components were identified: a major anti-cancer compound, 4'-hydroxy phenethyl trans-ferulate, with middle activity, and a minor anti-cancer compound, carolignan, with strong activity. The result shows that the gradient solvent system is potential for the screening of bioactive compounds from natural products. PMID:25069743

  13. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

    PubMed Central

    Hammond, Thomas G.; Meng, Xiaoli; Jenkins, Rosalind E.; Maggs, James L.; Castelazo, Anahi Santoyo; Regan, Sophie L.; Bennett, Stuart N. L.; Earnshaw, Caroline J.; Aithal, Guruprasad P.; Pande, Ira; Kenna, J. Gerry; Stachulski, Andrew V.; Park, B. Kevin

    2014-01-01

    Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug-derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug-related hypersensitivities had either a single drug-derived adduct or one of five combinations of 2–8 adducts from among seven diclofenac N-acylations and three AG glycations on seven of the protein’s 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug’s AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association. PMID:24902585

  14. An improved chemo-enzymatic synthesis of 1-beta-O-acyl glucuronides: highly chemoselective enzymatic removal of protecting groups from corresponding methyl acetyl derivatives.

    PubMed

    Baba, Akiko; Yoshioka, Tadao

    2007-12-01

    An improved and widely applicable chemo-enzymatic method for the synthesis of a series of 1-beta-O-acyl glucuronides 5a-f has been developed from the corresponding methyl acetyl derivatives 3a-f, which were stereospecifically synthesized from cesium salts of carboxylic acids 1a-f and methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-alpha-D-glucopyranuronate (2). Chemoselectivity of lipase AS Amano (LAS) in the hydrolytic removal of O-acetyl groups of 3a-f to provide methyl esters 4a-f was influenced by the nature of their 1-beta-O-acyl groups; high selectivity was evident only for 3b and 3f. Carboxylesterase from Streptomyces rochei (CSR), newly screened as an alternative to LAS, showed much greater chemoselectivity toward the O-acetyl groups than LAS; 3a, 3d, and 3e were chemoselectively hydrolyzed only by CSR. The combination of CSR with LAS yielded better results in the hydrolysis of 3c and 3f than did single usage of CSR. Final deprotection of the methyl ester groups of 4a-f to provide 5a-f was chemoselectively achieved by using lipase from Candida antarctica type B (CAL-B) as well as esterase from porcine liver (PLE), although CAL-B possessed higher chemoselectivity and catalytic efficiency than did PLE. CSR also exhibited high chemoselectivity in the synthesis of (S)-naproxen 1-beta-O-acyl glucopyranoside (7) from its 2,3,4,6-tetra-O-acetyl derivative 6. PMID:17985922

  15. Development of a physiologically based pharmacokinetic model for methyl ethyl ketone in F344 rats.

    PubMed

    Thrall, Karla D; Soelberg, Jolen J; Weitz, Karl K; Woodstock, Angela D

    2002-07-12

    A physiologically based pharmacokinetic (PBPK) model to describe the absorption, distribution, metabolism, and elimination of methyl ethyl ketone (MEK) in rats was developed. Partition coefficients were experimentally determined in rat tissues and blood samples using an in vitro vial equilibration technique. These solubility ratios were in agreement with previous human-based estimates that MEK is uniformly soluble within all tissues. The in vivo metabolism of MEK was evaluated using groups of three F344 male rats exposed to 100-2000 ppm MEK in a closed, recirculating gas uptake system. An optimal fit of a family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants, Km (affinity), and Vmax (capacity) using the PBPK model. At the highest chamber concentration, the uptake curve could not be modeled without the addition of a first-order (Kfo) metabolic pathway. Pretreatment with pyrazole, an inhibitor of oxidative microsomal metabolism, decreased the slope of the gas uptake curve but did not abolish metabolism. Optimal model fit to the gas uptake curve from pyrazole-pretreated animals required the apparent Km to be increased roughly 50 times the value determined in naive rats. The completed PBPK model was evaluated against real-time exhaled breath data collected from rats receiving an intravenous (iv) injection of MEK via a jugular vein cannula. Model simulation of the iv-treated animals required alveolar ventilation to be reduced 30% in order to match the data. Exhaled breath profiles from animals treated with MEK by oral gavage or intraperitoneal (ip) injection were evaluated and absorption rates was determined. Development of a comprehensive PBPK model for MEK in rats is the first step toward future extrapolations to apply to humans. PMID:12133235

  16. Lignin biodegradation and the production of ethyl alcohol from cellulose

    SciTech Connect

    Rosenberg, S.L.; Wilke, C.R.

    1981-02-01

    During the last few years our group has been engaged in developing a biochemical process for the conversion of lignocellulosic materials to ethyl alcohol. Lignin is a barrier to complete cellulose saccharification in this process, but chemical and physical delignification steps are too expensive to be used at the present time. An enzymatic delignification process might be attractive for several reasons: little energy would be expected to be needed, enzymes could be recovered and reused, and useful chemicals might be produced from dissolved lignin. A number of thermophilic and thermotolerant fungi were examined for the ability to rapidly degrade lignocellulose in order to find an organism whcih produced an active lignin-degrading enzyme system. Chryosporium pruinosum and Sporotrichum pulverulentum were found to be active lignocellulose degraders, and C. pruinosum was chosen for further study. Lignin and carbohydrate were degraded when the substrate remained moistened by, but not submerged in, the liquid medium. Attempts were made to demonstrate a cell-free lignin degrading system by both extraction and pressing of cultures grown on moist lignocellulose. Carbohydrate-degrading activity was found but not lignin-degrading activity. This led us to ask whether diffusible lignin-degrading activity could be demonstrated in this organism. The data indicate that the lignin degradation system, or one or more of its components, produced by this organism is either unstable, non-diffusible, or inactive at small distances (about 1 mm) from growing hyphae. At present, studies are being conducted using diffusion cultures to select mutants of C. pruinosum that do produce a diffusible lignin degradation system. We are also examining a number of mesophilic lignin-degrading molds for this ability.

  17. Fatty acid ethyl esters and ethanol-induced pancreatitis.

    PubMed

    Kaphalia, B S; Ansari, G A

    2001-01-01

    Conjugation of xenobiotic alcohols with endogenous fatty acids is considered one of the mechanisms of their retention in the target organs. A number of fatty acid esters of alcohol's detected in the human tissues were found to be toxic in vivo and in vitro. Non-oxidative metabolism of ethanol resulting in the formation of fatty acid ethyl esters (FAEEs) appears to be one of the major pathways of ethanol disposition in the pancreas during chronic alcohol abuse, and could be associated with pancreatitis. In most cases, pancreatic damage occurs in alcoholics preceding the onset of clinical pancreatitis. Early markers of ethanol-induced pancreatitis could be important for early prevention of such injury. Although FAEEs have been implicated in the ethanol-induced pancreatitis, mechanism(s) of such injury is not well understood. Studies by others and by our own group have shown that plasma levels of FAEEs correlate well with plasma/blood alcohol concentration. FAEE synthase is known to catalyze the formation of FAEEs. The activity of FAEE synthase was found highest in the pancreas. Excessive synthesis of FAEEs during chronic alcohol abuse in the pancreas may be associated with pancreatic injury as supported by in vivo and cell culture studies. Human studies correlating plasma FAEE levels with that of markers of pancreatic injury could be important in developing markers of ethanol-induced toxicity. Although toxicity of exogenously administered FAEEs is shown in vivo and in vitro, the toxicity associated with endogenously formed FAEEs has not been studied. Therefore, studies regarding the role of endogenously formed FAEEs could be important in understanding the mechanism of ethanol-induced pancreatitis. PMID:11936865

  18. ETHYL CYANIDE ON TITAN: SPECTROSCOPIC DETECTION AND MAPPING USING ALMA

    SciTech Connect

    Cordiner, M. A.; Palmer, M. Y.; Nixon, C. A.; Charnley, S. B.; Mumma, M. J.; Serigano, J.; Irwin, P. G. J.; Teanby, N. A.; Kisiel, Z.; Wang, K.-S.

    2015-02-10

    We report the first spectroscopic detection of ethyl cyanide (C{sub 2}H{sub 5}CN) in Titan’s atmosphere, obtained using spectrally and spatially resolved observations of multiple emission lines with the Atacama Large Millimeter/submillimeter Array (ALMA). The presence of C{sub 2}H{sub 5}CN in Titan’s ionosphere was previously inferred from Cassini ion mass spectrometry measurements of C{sub 2}H{sub 5}CNH{sup +}. Here we report the detection of 27 rotational lines from C{sub 2}H{sub 5}CN (in 19 separate emission features detected at >3? confidence) in the frequency range 222–241 GHz. Simultaneous detections of multiple emission lines from HC{sub 3}N, CH{sub 3}CN, and CH{sub 3}CCH were also obtained. In contrast to HC{sub 3}N, CH{sub 3}CN, and CH{sub 3}CCH, which peak in Titan’s northern (spring) hemisphere, the emission from C{sub 2}H{sub 5}CN is found to be concentrated in the southern (autumn) hemisphere, suggesting a distinctly different chemistry for this species, consistent with a relatively short chemical lifetime for C{sub 2}H{sub 5}CN. Radiative transfer models show that C{sub 2}H{sub 5}CN is most concentrated at altitudes ?200 km, suggesting production predominantly in the stratosphere and above. Vertical column densities are found to be in the range (1–5) × 10{sup 14} cm{sup ?2}.

  19. Combination treatment with ethyl pyruvate and aspirin enhances neuroprotection in the postischemic brain.

    PubMed

    Kim, Seung-Woo; Jeong, Ji-Young; Kim, Hyun Ji; Seo, Ji-Seon; Han, Pyung-Lim; Yoon, Sung-Hwa; Lee, Ja-Kyeong

    2010-01-01

    Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to act as an anti-inflammatory molecule in various pathological conditions, which include sepsis or hemorrhagic shock. Recently, we showed that ethyl pyruvate has a neuroprotective effect in the postischemic brain and also in KA-induced pathogenesis in the brain. In this study, we examined whether aspirin augments neuroprotective effect of ethyl pyruvate in transient focal ischemia model by complementing the neuroprotective effects of ethyl pyruvate. Although, most of neuroprotective effect of aspirin has been attributed to the anti-platelet action, aspirin also has direct neuroprotective effects, including NF-kappaB inhibition. Ethyl pyruvate dose-dependently suppressed infarct formation in the postischemic brain, wherein intravenous administration of 5 mg/kg ethyl pyruvate 30 min after the occlusion reduced infarct volume to 34.5 +/- 15.5% (n = 6, P < 0.01) of that of the untreated control. In combination with aspirin (5 mg/kg, i.v.), the neuroprotective effect was enhanced, resulting in 16.0 +/- 5.9% (n = 6, P < 0.01) infarct volume. The time window for synergistic neuroprotection by ethyl pyruvate and aspirin extended to 9 h post-MCAO. The synergistic reduction in infarct volume was accompanied by suppression of the clinical manifestations associated with cerebral ischemia including motor impairment and neurological deficits. Inflammatory processes including microglial activation and proinflammatory cytokine expression were notably suppressed by the combination treatment in the postischemic brain and in primary microglia cultures, wherein ethyl pyruvate and aspirin modulate NF-kappaB signaling differentially. Aspirin interferes with IkappaB phosphorylation and degradation in the cytoplasm, possibly by specifically inhibiting IkappaB kinase-beta, whereas, the effect of ethyl pyruvate seems to occur in the nucleus, where it may interfere with the binding of NF-kappaB to responsive promoter elements in the target genes. Similar enhancement in neuroprotective effect was also observed in primary cortical cultures after NMDA or Zn(2+) treatment or oxygen-glucose deprivation. Together, these results indicate that combination treatment of ethyl pyruvate and aspirin affords synergistic neuroprotection in the postischemic brain with a wide therapeutic window, in part via differential modulation of the NF-kappaB signaling pathway. PMID:19636661

  20. Glutathione S-transferase pi (GST-pi) inhibition and anti-inflammation activity of the ethyl acetate extract of Streptomyces sp. strain MJM 8637

    PubMed Central

    Lee, Sung-Kwon; Lee, Dong-Ryung; Choi, Bong-Keun; Palaniyandi, Sasikumar Arunachalam; Yang, Seung Hwan; Suh, Joo-Won

    2015-01-01

    To investigate the anti-cancer properties of soil-borne actinobacteria, MJM 8637, the glutathione S-transferase pi (GST-pi) assay, anti-tumor necrosis factor (TNF)-? assay, the level of antioxidant potential by DPPH radical scavenging activity, NO scavenging activity, and ABTS radical scavenging activity in ethyl acetate extract were determined. The 16S rDNA sequencing analysis revealed that Streptomyces sp. strain MJM 8637, which was isolated from Hambak Mountain, Korea, has 99.5% similarity to Streptomyces atratus strain NBRC 3897. The physiological and the morphological characteristics of the strain MJM 8637 were also identified. The ethyl acetate extract of MJM 8637 inhibited TNF-? production approximately 61.8% at concentration 100 ?g/ml. The IC50 value of the strain MJM 8637 extract on GST-pi was identified to be 120.2 ± 1.6 ?g/ml. In DPPH, NO, and ABTS radical scavenging assays, the IC50 values of the strain MJM 8637 extract were found to be 977.2 ?g/ml, 1143.7 ?g/ml, and 454.4 ?g/ml, respectively. The ethyl acetate extract of the strain MJM 8637 showed 97.2 ± 1.3% of cell viability at 100 ?g/ml in RAW 264.7 cell viability assay. The results obtained from this study suggest that the ethyl acetate extract of Streptomyces sp. strain MJM 8637 could be considered as a potential source of drug for the cancers that have multidrug resistance with its GST-pi inhibition and anti-inflammation activities, and low cytotoxicity. PMID:26587003

  1. 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

  2. Biodegradation of pyrazosulfuron-ethyl by three strains of bacteria isolated from contaminated soils.

    PubMed

    Xu, Jun; Li, Xuesheng; Xu, Yanjun; Qiu, Lihong; Pan, Canping

    2009-02-01

    Three bacterial strains capable of transforming pyrazosulfuron-ethyl, designated as D61, D66, and D713, were isolated from pyrazosulfuron-ethyl contaminated soils. According to the sequence analysis of the partial 16S rRNA gene, it is found that the strains D61 and D66 belong to Pseudomonas sp., and the strain D713 belongs to Bacillus sp. The effects of pyrazosulfuron-ethyl concentration, pH and temperature on biodegradation were examined. At a concentration of 10.0mgL(-1), pyrazosulfuron-ethyl was completely degraded by Pseudomonas sp. D61 after 2d and by Pseudomonas sp. D66 after 5d. At a concentration of 90.0mgL(-1), pyrazosulfuron-ethyl can be completely degraded by Pseudomonas sp. D66 and D61 after 12d. More than 85.9% degradation rate was observed with Bacillus sp. D713 after 12d. The growth of these three strains was inhibited at low pH buffers. The abiotic degradation occurs much faster at low pH than at neutral and basic pH conditions. The degradation rate of pyrazosulfuron-ethyl at 28 degrees C was faster than those at 20 degrees C and 37 degrees C by these strains, except the highest degradation rate of Bacillus sp. D713 was obtained at 37 degrees C. The pyrazosulfuron-ethyl biodegradation products were identified by liquid chromatography-mass spectroscopy with positive/negative modes and tandem MS-MS techniques. The main degradation product was detected and identified as 5-(N-(4,6-dimethoxypyrimidin-2-ylcarbamoyl)sulfamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid based on mass spectral data and fragmentation patterns. PMID:19004468

  3. Interaction of ethyl chloride with amorphous solid water thin film on Ru(001) and O/Ru(001) surfaces.

    PubMed

    Ayoub, Yousif; Asscher, Micha

    2009-07-01

    The adsorption of ethyl chloride (EC) on clean and oxygen covered Ru(001) surfaces and its interaction with coadsorbed amorphous solid water (ASW) is reported based on temperature-programmed desorption (TPD) and work function change (DeltaPhi) measurements. Adsorption of EC is characterized by a decrease of 2.1 eV in work function at monolayer coverage. Flipped adsorption geometry on average (ethyl facing the surface) is found in the second layer with a 0.3 eV increase in the work function. On ruthenium substrates the orientation of EC molecules could be controlled chlorine down or up by varying the oxygen coverage, as indicated by work function change measurements. DeltaP-TPD from clean Ru(001) surface reveals a complete dissociation of the EC molecules on the clean Ru(001) surface at coverages up to 0.1 +/- 0.05 ML. At higher coverage it leads to two distinct TPD peaks: at T =175 and 120-130 K, for the monolayer and multilayer coverage, respectively. Compression of preadsorbed 0.3 ML EC molecules into small islands on the surface occurs when ASW layers at coverage in the range 0.5-6 bilayers (BL) are adsorbed on top of the EC covered surface, associated with a shift in peak desorption from 190 K down to 125 K. A Caging process of EC molecules within the layers of ASW takes place by adsorbing more than 6 BL until a fully caged system has developed above 20 ASW BL. A reversed TPD peak shift of the trapped EC molecules occurs from its compressed phase at 125 K up to 165 K, the onset for ASW transition to crystalline ice and desorption. The detachment process leads to partial flipping over the geometry of the EC at the second layer, as determined by DeltaPhi measurement. The distance of the lifted and caged EC molecules from the Ru surface has been determined to reside 1.0 +/- 0.2 nm above the solid surface, based on the thermal dissociation and hydrogen uptake measurements of sandwiched EC molecules between a variable thickness ASW film and a fixed 10 BL layer, on top of clean Ru(001). We conclude that the caged EC molecules are trapped in a micelle-like geometry with the ethyl groups pointing inward. This conclusion is based on photodecomposition studies of the caged EC molecules at 193 nm, as a function of EC initial coverage. PMID:19413356

  4. Brewing industry potential for the immediate and near-term production of fuel-grade ethyl alcohol. Final report

    SciTech Connect

    Mulloney, J.A. Jr.

    1980-04-15

    The brewing industry is described as it relates to productive facilities and potential for fuel grade ethyl alcohol production. The brewing process is compared to the fuel grade ethyl alcohol process in a brewery. A description is given for retrofitting a brewery as a distilled spirits plant. The following are included: estimated capital requirements and alcohol costs, targets of opportunity, barriers and actions affecting brewery production of ethyl alcohol, suggested action programs, and recommended program activities. (MHR)

  5. Simultaneous spectrophotometric analysis of aliphatic amines utilizing thermochromism of charge-transfer complexes with tetrabromophenolphthalein ethyl ester.

    PubMed

    Sakai, Tadao; Kato, Mitsuhiro; Teshima, Norio

    2005-12-01

    Aliphatic amines, such as n-hexylamine (primary), di-n-hexylamine (secondary) and tri-n-hexylamine (tertiary amine), react with tetrabromophenolphthalein ethyl ester molecules (TBPEH) to form reddish or red-violet charge-transfer complexes (CT complexes) in 1,2-dichloroethane (DCE). The absorption maxima of the CT complexes with all primary amines occur at around 560 nm, with secondary amines at 570 nm and, with tertiary amines at 580 nm. The CT complex formation constants with TBPEH in DCE increase in the order of the primary, secondary and tertiary amines, but their constants decrease quantitatively with an increase in temperature. This phenomenon (thermochromism) could be applied to the simultaneous spectrophotometric determination of primary amine and secondary amine, or secondary amine and tertiary amine in a mixed solution utilizing the difference of absorbance with temperature changes. PMID:16379407

  6. Ethyl rosmarinate relaxes rat aorta by an endothelium-independent pathway.

    PubMed

    Wicha, Piyawadee; Tocharus, Jiraporn; Nakaew, Archawin; Pantan, Rungusa; Suksamrarn, Apichart; Tocharus, Chainarong

    2015-11-01

    Ethyl rosmarinate is an ester derivative of rosmarinic acid, a major constituent of Hyptis suaveolens. The present study investigated the vasorelaxant mechanism of ethyl rosmarinate in isolated rat aortic rings using an organ bath system. Ethyl rosmarinate (0.1µM-3mM) produced concentration-dependent relaxation in aortic rings pre-contracted with phenylephrine (10µM), exhibiting a pD2 value of 4.56±0.08 and an Emax value of 93.82±5.00% (in endothelium-intact rings), as well as a pD2 value of 4.42±0.05 and an Emax value of 92.10±3.78% (in endothelium-denuded rings). In the endothelium-denuded rings, the vasorelaxant effect of ethyl rosmarinate was reduced by only 4-aminopyridine (1mM); however, this was not the case with tetraethylammonium (5mM), glibenclamide (10µM), barium chloride (1mM), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1µM). Ethyl rosmarinate also reduced the contraction induced by phenylephrine (10µM) and caffeine (20mM) in a Ca(2+)-free solution, and inhibited the contraction induced by increasing extracellular Ca(2+) influx, which was induced by KCl (80mM). Ethyl rosmarinate (10µM) inhibits concentration-response curves for phenylephrine, while in the same concentration of ethyl rosmarinate has no effect on contractions induced by increasing concentrations of calcium in the presence of high extracellular potassium. Our results suggests that ethyl rosmarinate induces relaxation in aortic rings via an endothelium-independent pathway, which involves the opening of voltage-gated potassium (Kv) channels and the blockade of both Ca(2+)release from intracellular stores and extracellular Ca(2+) influx. Moreover, ethyl-rosmarinate acts on the extracellular Ca(2+) influx inhibition by interacting with voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs). PMID:26362751

  7. 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

  8. Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Balasubramanian, T.; Chatterjee, Tapan Kumar; Senthilkumar, G. P.; Mani, Tamizh

    2012-01-01

    To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200?mg/kg). Administration of the ethyl acetate fraction at 200?mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine. PMID:22593683

  9. Scanning tunneling microscopy of ethylated Si(111) surfaces prepared by a chlorination/alkylation process.

    PubMed

    Yu, Hongbin; Webb, Lauren J; Solares, Santiago D; Cao, Peigen; Goddard, William A; Heath, James R; Lewis, Nathan S

    2006-11-30

    Scanning tunneling microscopy (STM) and computational modeling have been used to study the structure of ethyl-terminated Si(111) surfaces. The ethyl-terminated surface was prepared by treating the H-terminated Si(111) surface with PCl5 to form a Cl-terminated Si(111) surface with subsequent exposure to C(2)H(5)MgCl in tetrahydrofuran to produce an alkylated Si(111) surface. The STM data at 77 K revealed local, close-packed, and relatively ordered regions with a nearest-neighbor spacing of 0.38 nm as well as disordered regions. The average spot density corresponded to approximately 85% of the density of Si atop sites on an unreconstructed Si(111) surface. Molecular dynamics simulations of a Si(111) surface randomly populated with ethyl groups to a total coverage of approximately 80% confirmed that the ethyl-terminated Si(111) surface, in theory, can assume reasonable packing arrangements to accommodate such a high surface coverage, which could be produced by an exoergic surface functionalization route such as the two-step chlorination/alkylation process. Hence, it is possible to consistently interpret the STM data within a model suggested by recent X-ray photoelectron spectroscopic data and infrared absorption data, which indicate that the two-step halogenation/alkylation method can provide a relatively high coverage of ethyl groups on Si(111) surfaces. PMID:17125356

  10. Experimental and computational investigation on the gas phase reaction of ethyl formate with Cl atoms.

    PubMed

    Balaganesh, M; Dash, Manas Ranjan; Rajakumar, B

    2014-07-17

    The rate coefficient for the gas-phase reaction of Cl atoms with ethyl formate was measured over the temperature range of 268-343 K using relative rate methods, with ethyl chloride as a reference compound. The temperature dependent relative rate coefficients for the ethyl formate + Cl reaction were measured, and the modified Arrhenius expression kethyl formate(268-343) = (2.54 ± 0.57) × 10(-23) T(4.1) exp {-(981 ± 102)/T} cm(3) molecule(-1) s(-1) was obtained with 2? error limits. The room temperature rate coefficient for the title reaction is (9.84 ± 0.79) × 10(-12) cm(3) molecule(-1) s(-1), which is in good agreement with reported values. To complement the experimental measurement, computational methods were used to calculate the rate coefficient for the ethyl formate + Cl reaction atoms using canonical variational transition state theory (CVT) with small curvature tunneling (SCT) and the CCSD (T)/cc-pVDZ//M062X/6-31+g(d,p) level of theory. The temperature dependent Arrhenius expression was obtained to be 2.97 × 10(-18) T(2.4) exp[-(390/T)] cm(3) molecule(-1) s(-1) over the temperature range of 200-400 K. The thermodynamic parameters and branching ratio were calculated. Also, the atmospheric lifetime and global warming potentials (GWPs) were calculated for ethyl formate. PMID:24945822

  11. Association of exposure to polycyclic aromatic hydrocarbons (estimated from job category) with concentration of 1-hydroxypyrene glucuronide in urine from workers at a steel plant.

    PubMed Central

    Kang, D; Rothman, N; Cho, S H; Lim, H S; Kwon, H J; Kim, S M; Schwartz, B; Strickland, P T

    1995-01-01

    OBJECTIVES--Increased risk of lung cancer has been associated with employment in the steel industry. This association is thought to be due in part to increased concentrations of polycyclic aromatic hydrocarbons (PAHs) in air found in this work environment. Measurement of PAH metabolites in human urine provides a means of assessing individual internal dose of PAHs. This study examined the relative contribution of occupation and smoking to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG) among a group of workers at a steel plant. METHODS--Concentrations of 1-OHPG in urine from 44 workers with jobs associated with increased air concentrations of PAHs and 40 workers with jobs with low or no exposure to PAHs were measured. 20 workers in each group were not current smokers. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy after immunoaffinity chromatography specific for PAH metabolites. RESULTS--Mean (SEM) urinary 1-OHPG concentration was 2.16 (0.42) pmol/ml urine among the 44 occupationally exposed workers compared with 0.38 (0.05) among the 40 workers with no or low exposure (P < 0.0001). Mean urinary 1-OHPG concentration was 1.82 (0.41) pmol/ml urine among the 44 current smokers compared with 0.75 (0.20) among the 40 non-smokers (P < 0.005). Mean 1-OHPG concentrations in non-smokers were 0.26 (n = 20), 0.70 (n = 15), and 2.84 pmol/ml urine (n = 5) for strata of exposure to PAHs (no or low, mid, and high) based on job category; the corresponding values in smokers were 0.55 (n = 20), 0.94 (n = 12), and 4.91 pmol/ml (n = 12), respectively. Multiple linear regression showed significant differences between subjects in different PAH exposure with increased concentrations of 1-OHPG in urine. Amounts of foods containing PAHs ingested by this group of workers were relatively low and did not contribute significantly to urinary 1-OHPG concentrations. CONCLUSIONS--These results indicate that 1-OHPG is a common urinary metabolite in people with recent occupational exposure to PAHs and is associated with both job category and estimated stratum of PAH exposure. PMID:7550799

  12. Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ??-adrenergic signaling.

    PubMed

    Yamazaki, Shunsuke; Miyoshi, Noriyuki; Kawabata, Kyuichi; Yasuda, Michiko; Shimoi, Kayoko

    2014-09-01

    Endogenous catecholamines such as adrenaline (A) and noradrenaline (NA) are released from the adrenal gland and sympathetic nervous system during exposure to stress. The adrenergic system plays a central role in stress signaling, and excessive stress was found to be associated with increased production of reactive oxygen species (ROS). Overproduction of ROS induces oxidative damage in tissues and causes the development of diseases such as cancer. In this study, we investigated the effects of quercetin-3-O-glucuronide (Q3G), a circulating metabolite of quercetin, which is a type of natural flavonoid, on the catecholamine-induced ?2-adrenergic receptor (?2-AR)-mediated response in MDA-MB-231 human breast cancer cells expressing ?2-AR. Treatment with A or NA at concentrations above 1?M generated significant levels of ROS, and NA treatment induced the gene expression of heme oxygenase-1 (HMOX1), and matrix metalloproteinase-2 (MMP-2) and -9 (MMP9). Inhibitors of p38 MAP kinase (SB203580), cAMP-dependent protein kinase (PKA) (H-89), activator protein-1 (AP-1) transcription factor (SR11302), and NF-?B and AP-1 (Tanshinone IIA) decreased MMP2 and MMP9 gene expression. NA also enhanced cAMP induction, RAS activation and phosphorylation of ERK1/2. These results suggested that the cAMP-PKA, MAPK, and ROS-NF-?B pathways are involved in ?2-AR signaling. Treatment with 0.1?M Q3G suppressed ROS generation, cAMP and RAS activation, phosphorylation of ERK1/2 and the expression of HMOX1, MMP2, and MMP9 genes. Furthermore, Q3G (0.1?M) suppressed invasion of MDA-MB-231 breast cancer cells and MMP-9 induction, and inhibited the binding of [(3)H]-NA to ?2-AR. These results suggest that Q3G may function to suppress invasion of breast cancer cells by controlling ?2-adrenergic signaling, and may be a dietary chemopreventive factor for stress-related breast cancer. PMID:24929186

  13. Branchial and renal pathology in the fish exposed chronically to methoxy ethyl mercuric chloride

    SciTech Connect

    Gill, T.S.; Pant, J.C.; Tewari, H.

    1988-08-01

    Pathological manifestations causally related to pesticide poisoning have been described in both surficial and internal tissues of the fishes. Among the various organomercurials are phenyl mercuric acetate, methyl mercuric dicyanidiamide, methoxy ethyl mercuric chloride, methoxy ethyl mercuric silicate etc. Of these, the methoxy ethyl mercuric chloride (MEMC) is used in agriculture as an antifungal seed dressing, and its toxicity is primarily manifest in the Hg/sup 2 +/ ion. This report describes pathogenesis of branchial and renal lesions in the common freshwater fish, Puntius conchonius exposed chronically to sublethal levels of MEMC. Prior to this, alterations in the peripheral blood and metabolite levels in response to experimental MEMC poisoning have been demonstrated in this species.

  14. THE MILLIMETER- AND SUBMILLIMETER-WAVE SPECTRUM OF THE TRANS AND GAUCHE CONFORMERS OF ETHYL FORMATE

    SciTech Connect

    Medvedev, Ivan R.; De Lucia, Frank C.; Herbst, Eric

    2009-04-15

    Since methyl formate (HCOOCH{sub 3}) is found to have a high abundance in hot molecular cores and other types of clouds in the galactic center, it is reasonable to search among such sources for detectable abundances of the more complex analog ethyl formate (HCOOC{sub 2}H{sub 5}). Following a previous study of the millimeter-wave spectrum of ethyl formate, we have extended the analysis of the vibrational ground state of the trans and gauche conformers of ethyl formate into the submillimeter-wave range. Over 2200 new spectral lines have been measured and analyzed at frequencies up to 380 GHz. Fitting the data for each conformer to a Watson A-reduced asymmetric-top Hamiltonian has allowed us to predict the frequencies and intensities of many more transitions through 380 GHz.

  15. Engineering case report. Toluene and methyl ethyl ketone exposure from a commercially available contact adhesive.

    PubMed

    Mills, William J; Grigg, Benjamin J; Offermann, Francis J; Gustin, Barry E; Spingarn, Neil E

    2012-01-01

    A maintenance worker became ill after working indoors over the course of 3 days with a commercially available contact adhesive containing toluene and methyl ethyl ketone. Respiratory protection or local exhaust ventilation was not used. The worker subsequently suffered from numerous medical symptoms including tremors and elevated blood pressure. Magnetic resonance imaging documented the occurrence of encephalopathy. The worker has alleged that the cause of these effects was exposure to the vapors from the contact adhesive. The objective of this study was to characterize/estimate the level of the worker's exposure by obtaining air samples in an exposure chamber while performing similar activities under similar conditions. We found that the worker may have been exposed to approximately 159 ppm toluene and 58 ppm methyl ethyl ketone 8-hr time-weighted averages for 8 hr of adhesive application. The maximum 15-min average exposures were 233 ppm toluene and 85 ppm methyl ethyl ketone. PMID:22548642

  16. Crystal structure of N,N-di­ethyl­benzene-1,4-diaminium dinitrate

    PubMed Central

    Bouaoud, Yasmina; Smith, Graham; Merazig, Hocine; Setifi, Zouaoui

    2014-01-01

    In the structure of the title mol­ecular salt, C10H18N2 2+·2NO3 ?, the dinitrate salt of 4-(N,N-di­ethyl­amino)­aniline, the two ethyl groups lie almost perpendicular to the plane of the benzene ring [the ring-to-ethyl C—C—N—C torsion angles are ?59.5?(2) and 67.5?(3)°]. The aminium groups of the cation form inter-species N—H?O hydrogen bonds with the nitro O-atom acceptors of both anions, giving rise to chain substructures lying along c. The chains are linked via further N—H?O hydrogen bonds, forming two-dimensional networks lying parallel to (010). These sheets are linked by C—H?O hydrogen bonds, forming a three-dimensional structure. PMID:25484823

  17. Characterization and Antioxidant Properties of Six Algerian Propolis Extracts: Ethyl Acetate Extracts Inhibit Myeloperoxidase Activity

    PubMed Central

    Boufadi, Yasmina Mokhtaria; Soubhye, Jalal; Riazi, Ali; Rousseau, Alexandre; Vanhaeverbeek, Michel; Nčve, Jean; Boudjeltia, Karim Zouaoui; Van Antwerpen, Pierre

    2014-01-01

    Because propolis contains many types of antioxidant compounds such as polyphenols and flavonoids, it can be useful in preventing oxidative damages. Ethyl acetate extracts of propolis from several Algerian regions show high activity by scavenging free radicals, preventing lipid peroxidation and inhibiting myeloperoxidase (MPO). By fractioning and assaying ethyl acetate extracts, it was observed that both polyphenols and flavonoids contribute to these activities. A correlation was observed between the polyphenol content and the MPO inhibition. However, it seems that kaempferol, a flavonoid, contributes mainly to the MPO inhibition. This molecule is in a high amount in the ethyl acetate extract and demonstrates the best efficiency towards the enzyme with an inhibiting concentration at 50% of 4 ± 2 ?M. PMID:24514562

  18. Probing the microstructure of nonionic microemulsions with ethyl oleate by viscosity, ROESY, DLS, SANS, and cyclic voltammetry.

    PubMed

    Kaur, Gurpreet; Chiappisi, Leonardo; Prévost, Sylvain; Schweins, Ralf; Gradzielski, Michael; Mehta, Surinder K

    2012-07-24

    Microemulsions are important formulations in cosmetics and pharmaceutics and one peculiarity lies in the so-called "phase inversion" that takes place at a given water-to-oil concentration ratio and where the average curvature of the surfactant film is zero. In that context, we investigated the structural transitions occurring in Brij 96-based microemulsions with the cosmetic oil ethyl oleate and studied the influence of the short chain alcohol butanol on their structure and properties as a function of water addition. The characterization has been carried out by means of transport properties, spectroscopy, DLS, SANS, and electrochemical methods. The results confirm that the nonionic Brij 96 in combination with butanol as cosurfactant forms a U-type microemulsion that upon addition of water undergoes a continuous transition from swollen reverse micelles to oil-in-water (O/W) microemulsion via a bicontinuous region. After determining the structural transition through viscosity and surface tension, the 2D-ROESY studies give an insight into the microstructure, i.e., the oil component ethyl oleate mainly is located at the hydrophobic tails of surfactant while butanol molecules reside preferentially in the interface. SANS experiments show a continuous increase of the size of the structural units with increasing water content. The DLS results are more complex and show the presence of two relaxation modes in these microemulsions for low water content and a single diffusive mode only for the O/W microemulsion droplets. The fast relaxation reflects the size of the structural units while the slower one is attributed to the formation of a network of percolated microemulsion aggregates. Electrochemical studies using ferrocene have been carried out and successfully elucidated the structural transformations with the help of diffusion coefficients. An unusual behavior of ferrocene has been observed in the present microheterogeneous medium, giving a deeper insight into ferrocene electrochemistry. NMR-ROESY experiments give information regarding the internal organization of the microemulsion droplets. In general, one finds a continuous structural transition from a W/O over a bicontinuous to an O/W microemulsion, however with a peculiar network formation over an extended concentration range, which is attributed to the somewhat amphiphilic oil ethyl oleate. The detailed knowledge of the structural behavior of this type of system might be important for their future applications. PMID:22720716

  19. Contribution of ethyl methanesulfonate vapors to the yield of mutations detected in Drosophila melanogaster when the adult feeding technique is used

    SciTech Connect

    Munoz, E.R.

    1987-01-01

    Ethyl methanesulfonate (EMS) is an alkylating agent widely used in mutation research. In experiments with adult Drosophila melanogaster, EMS is either injected or fed to the flies using different feeding methods that essentially consist of placing the flies in bottles or vials with a piece of tissue paper moistened with a sucrose solution containing the desired concentration of EMS. To determine the extent to which vapors contribute to the mutagenic effect detected in Drosophila when the feeding technique is used, 7-day-old wild-type Samarkand males were fed EMS or were exposed only to its vapors.

  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. Investigating the performance of CoxOy/activated carbon catalysts for ethyl acetate catalytic combustion

    NASA Astrophysics Data System (ADS)

    Xie, Hongmei; Zhao, Xiaoping; Zhou, Guilin; He, Xiaoling; Lan, Hai; Jiang, Zongxuan

    2015-01-01

    The catalytic properties of Co-supported activated carbon (AC) catalysts for ethyl acetate catalytic elimination in air were investigated. Results showed that air atmosphere promoted the generation of high-valence state cobalt oxides, and promote the production of reactive oxygen species (ROS) in the Co3O4/AC catalyst. ROS crucially functioned in improving the catalytic activity of Co3O4/AC catalysts. Therefore, CoACA catalyst prepared in air exhibited higher catalytic activity than CoACN catalyst prepared in nitrogen, and CoACA catalyst led to high ethyl acetate conversion (>93%) and stability at a low reaction temperature (210 °C).

  2. 2-Ethyl-1H-imidazol-3-ium hemioxalate oxalic acid monohydrate

    PubMed Central

    Zhu, Run-Qiang

    2011-01-01

    In the title compound, C5H9N2 +·0.5C2O4 2?·C2H2O4·H2O, the anions, cations and water mol­eculars are linked by N—H?O and O—H?O hydrogen bonds which define a tightly bound three-dimensional structure. The title compound is a layered structure as viewed along the a or c axis; one layer contains water and oxalic acid mol­ecules, the other the imidazolium cation. The C atoms of the ethyl group of the 2-ethyl­imidazolium cation are disordered over two positions of equal occupancy. PMID:21837033

  3. Ethyl pyruvate reduces hepatic mitochondrial swelling and dysfunction in a rat model of sepsis

    PubMed Central

    Jiang, Zhiyi; Li, Xiaoyue; Lin, Zongqin; Chen, Juan; Guan, Xiangdong; Chen, Minying

    2015-01-01

    Sepsis causes mitochondrial oxidative injury and swelling. Ethyl pyruvate (EP) is a cytoprotective agent, while aquaporin-8 (AQP8) is a mitochondrial water channel that can induce mitochondrial swelling. We assessed whether EP protects mitochondria during sepsis, and whether AQP8 contributes to the underlying mechanisms. A cecal ligation and puncture (CLP) sepsis model was established in Sprague-Dawley rats, randomized to 3 groups: sham (n=20), CLP (n=59) and CLP+EP (n=51). All rats received postoperative intraperitoneal fluid resuscitation (30 ml/kg); the CLP+EP group also received intraperitoneal EP (100 mg/kg). Survival was assessed at 24 hours. Hepatic mitochondrial ultrastructure was characterized by electron microscopy. The membrane potential of isolated hepatic mitochondria was determined using JC-1 and flow cytometry. Mitochondrial AQP8 expression and cytochrome C (Cyt C) release were measured by Western blotting (values normalized to ß-actin). Survival in the sham, CLP and CLP+EP groups was 100%, 21% and 41%, respectively. Mitochondrial cross-sectional area was smaller in the CLP+EP group than in the CLP group (0.231±0.110 vs. 0.641±0.460 µm2; P<0.001), with a tendency for a lower form factor (a measure of contour irregularity) in the CLP+EP group. Mitochondrial depolarization by CLP was inhibited by EP. Mitochondrial Cyt C release was higher in the CLP group than in the sham (1.211±0.24 vs. 0.48±0.03) or CLP+EP (0.35±0.39) groups. AQP8 expression was similar between groups, with a trend for lower expression in the CLP+EP group compared with the CLP group. EP improves sepsis outcome by targeting the mitochondrion, possibly through modulation of AQP8 expression. PMID:26339342

  4. Antiviral activity of 5-ethyl-2'-deoxyuridine against herpes simplex viruses in cell culture, mice, and guinea pigs.

    PubMed Central

    Schinazi, R F; Scott, R T; Peters, J; Rice, V; Nahmias, A J

    1985-01-01

    The susceptibility of 3 laboratory strains and 24 clinical isolates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) to 5-ethyl-2'-deoxyuridine was determined in plaque reduction assays in Vero cells. The median effective doses were 8.6 and 7.8 microM, respectively. The drug was less potent than acyclovir and other related antiviral drugs, but it had a high therapeutic index against both HSV-1 and HSV-2. Drug-resistant viruses were readily produced in cell culture. These variants were cross-resistant to acyclovir, 2'-fluoro-5-iodoaracytosine, and 2'-fluoro-5-methylarauracil but were susceptible to vidarabine or phosphonoformate. These findings confirm that the selective antiviral activity of 5-ethyl-2'-deoxyuridine is mediated by the virus-induced thymidine kinase. Oral or intraperitoneal administration of the drug at nontoxic doses was ineffective in protecting mice against intracerebral challenge with virus. Using implanted osmotic minipumps or coadministering the drug with dimethyl sulfoxide failed to decrease the mortality rate. In guinea pigs infected genitally with HSV-2, topical drug treatment was more effective than placebo in reducing lesion severity and other clinical and virological variables. These effects were noted whether the drug treatment was initiated 3 or 24 h after infection (ascertained serologically). Drug-treated animals had a significantly lower herpes antibody titer than did placebo-treated guinea pigs, suggesting that the drug can also reduce the viral antigen load. In this model, the drug appeared to be as effective as topical phosphonoformate or acyclovir. PMID:3000291

  5. 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

    ...ethyl]substituted]phenyl]-, monosodium salt (generic). 721.10130 Section...ethyl]substituted]phenyl]-, monosodium salt (generic). (a) Chemical...ethyl]substituted]phenyl]-, monosodium salt (PMN P-07-140) is...

  6. 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...

  7. 40 CFR 180.228 - S-Ethyl hexahydro-1H-aze-pine-1-carbothioate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Ethyl hexahydro-1H-aze-pine-1-carbothioate; tolerances for residues. 180.228 Section 180.228 Protection of Environment ENVIRONMENTAL... FOOD Specific Tolerances § 180.228 S-Ethyl hexahydro-1H-aze-pine-1-carbothioate; tolerances...

  8. Synthesis of 10-Ethyl Flavin: A Multistep Synthesis Organic Chemistry Laboratory Experiment for Upper-Division Undergraduate Students

    ERIC Educational Resources Information Center

    Sichula, Vincent A.

    2015-01-01

    A multistep synthesis of 10-ethyl flavin was developed as an organic chemistry laboratory experiment for upper-division undergraduate students. Students synthesize 10-ethyl flavin as a bright yellow solid via a five-step sequence. The experiment introduces students to various hands-on experimental organic synthetic techniques, such as column…

  9. 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

  10. Multicomponent Synthesis of a N-Protected Alpha-Amino Ester: Ethyl 2-((4-Methoxyphenyl)Amino)-3-Phenylpropanoate

    ERIC Educational Resources Information Center

    Le Gall, Erwan; Pignon, Antoine

    2012-01-01

    This laboratory experiment describes the preparation of a N-protected phenylalanine ethyl ester by a zinc-mediated Mannich-like multicomponent reaction between benzyl bromide, "p"-anisidine, and ethyl glyoxylate. The one-step reaction involves the in situ metallation of benzyl bromide into a benzylzinc reagent and its addition onto imine (Barbier…

  11. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Chromium (Cr III) complex of N-ethyl-N... § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium... by weight of the chromium (Cr III) complex of heptadecylfluoro-octane sulfonic acid may be...

  12. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Chromium (Cr III) complex of N-ethyl-N... § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium... by weight of the chromium (Cr III) complex of heptadecylfluoro-octane sulfonic acid may be...

  13. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Chromium (Cr III) complex of N-ethyl-N... § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium... by weight of the chromium (Cr III) complex of heptadecylfluoro-octane sulfonic acid may be...

  14. 21 CFR 176.160 - Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Chromium (Cr III) complex of N-ethyl-N... § 176.160 Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane sulfonyl glycine. The chromium... by weight of the chromium (Cr III) complex of heptadecylfluoro-octane sulfonic acid may be...

  15. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-methyl-. 721.4468 Section 721.4468 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance..., 2-ethyl-4,5-dihydro-4-methyl- (PMN P-97-217; CAS No. 931-35-1) is subject to reporting under...

  16. 21 CFR 172.225 - Methyl and ethyl esters of fatty acids produced from edible fats and oils.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... from edible fats and oils. 172.225 Section 172.225 Food and Drugs FOOD AND DRUG ADMINISTRATION... Methyl and ethyl esters of fatty acids produced from edible fats and oils. Methyl esters and ethyl esters of fatty acids produced from edible fats and oils may be safely used in food, subject to...

  17. 21 CFR 172.225 - Methyl and ethyl esters of fatty acids produced from edible fats and oils.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from edible fats and oils. 172.225 Section 172.225 Food and Drugs FOOD AND DRUG ADMINISTRATION... Methyl and ethyl esters of fatty acids produced from edible fats and oils. Methyl esters and ethyl esters of fatty acids produced from edible fats and oils may be safely used in food, subject to...

  18. 21 CFR 172.225 - Methyl and ethyl esters of fatty acids produced from edible fats and oils.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... from edible fats and oils. 172.225 Section 172.225 Food and Drugs FOOD AND DRUG ADMINISTRATION... Methyl and ethyl esters of fatty acids produced from edible fats and oils. Methyl esters and ethyl esters of fatty acids produced from edible fats and oils may be safely used in food, subject to...

  19. 21 CFR 172.225 - Methyl and ethyl esters of fatty acids produced from edible fats and oils.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... from edible fats and oils. 172.225 Section 172.225 Food and Drugs FOOD AND DRUG ADMINISTRATION... Methyl and ethyl esters of fatty acids produced from edible fats and oils. Methyl esters and ethyl esters of fatty acids produced from edible fats and oils may be safely used in food, subject to...

  20. 40 CFR 721.10457 - 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol, fumaric acid and propylene glycol. 721.10457...-hexanol, fumaric acid and propylene glycol. (a) Chemical substance and significant new uses subject to... alc., cyclohexanol, 2-ethyl-1-hexanol, fumaric acid and propylene glycol (PMN P-03-154; CAS No....

  1. 40 CFR 721.10457 - 1,2-Benzenedicarboxylic acid, mixed esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... esters with benzyl alc., cyclohexanol, 2-ethyl-1-hexanol, fumaric acid and propylene glycol. 721.10457...-hexanol, fumaric acid and propylene glycol. (a) Chemical substance and significant new uses subject to... alc., cyclohexanol, 2-ethyl-1-hexanol, fumaric acid and propylene glycol (PMN P-03-154; CAS No....

  2. 40 CFR 180.217 - Ammoniates for [ethylenebis-(dithiocarbamato)] zinc and ethyl-enebis [dithiocarbamic acid...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Ammoniates for zinc and ethyl-enebis... for zinc and ethyl-enebis bimolecular and trimolecular cyclic anhydrosulfides and disulfides... mixture of 5.2 parts by weight of ammoniates of zinc with 1 part by weight ethylenebis bimolecular...

  3. 40 CFR 721.10326 - 2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ester, polymer with butyl 2-propenoate, ethyl 2-propenoate, zinc 2-methyl-2-propenoate (1:2) and zinc 2... 2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate, zinc 2-methyl-2-propenoate (1:2) and zinc 2-propenoate (1:2), 2,2'-(1,2-diazenediyl)bis - and...

  4. Comparative study of the effect of ferrocyanide and EDTA on the production of ethyl alcohol from molasses by Saccharomyces cerevisiae

    SciTech Connect

    Oderinde, R.A.; Ngoka, L.C.; Adesogan, E.K.

    1986-01-01

    The effects of potassium ferrocyanide and EDTA on ethyl alcohol production from molasses by Saccharomyces cerevisiae were investigated on simulated batch pilot-plant-scale conditions for alcoholic fermentation of molasses. Ethyl alcohol production was more sensitive to ferrocyanide than to EDTA. When ferrocyanide was introduced into the cultures at the time of inoculation, there was stimulation of ethyl alcohol production, with 261 ppm ferrocyanide producing the maximum effect, which was 3.0% more than n control cultures. When added during the propagation of the yeast, ferrocyanide depressed ethyl alcohol production by 4.0% maximum whereas EDTA stimulated ethyl alcohol production by 2.0%. Addition of ferrocyanide during the fermentation stage produced no significant effect on alcohol production, whereas over a wide range of EDTA concentration there was a steady increase in alcohol yield.

  5. Detection of chlorpyrifos-ethyl (Dursban) and its metabolites in urine samples using immunoassays with confirmation by gas chromatography/mass spectrometry 

    E-print Network

    Clewis, Suenda Beth

    1995-01-01

    Gard chlorpyrifos-ethyl plate kit) is a quantitative laboratory test traditionally used to detect chlorpyrifos-ethyl in water samples. Even though the parent compound is metabolized before being excreted in urine, the urinary traces of chlorpyrifos...

  6. Transformation kinetics and mechanism of the sulfonylurea herbicides pyrazosulfuron ethyl and halosulfuron methyl in aqueous solutions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrazosulfuron ethyl (PE) and halosulfuron methyl (HM) are two new highly active sulfonylurea herbicides which have been widely used for weed control in a variety of vegetables and other crops. These two herbicides have similar molecular structure, differing only in the substitutions on the pyrazole...

  7. IRIS Toxicological Review and Summary Documents for Tertiary Amyl Ethyl Ether (Taee)

    EPA Science Inventory

    This is EPA's first assessment of the noncancer health effects and carcinogenic potential of tertiary amyl ethyl ether (TAEE). The IRIS program is preparing an assessment that will incorporate health effects information available for TAEE, and current risk assessment methods. T...

  8. 40 CFR 180.212 - S-Ethyl cyclohexylethylthio-carbamate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Ethyl cyclohexylethylthio-carbamate; tolerances for residues. 180.212 Section 180.212 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.212...

  9. IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) (External Review Draft)

    EPA Science Inventory

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of ethyl tertiary butyl ether (ETBE) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

  10. CYTOGENETIC STUDIES OF ETHYL ACRYLATE USING C57BL/6 MICE

    EPA Science Inventory

    The clastogenicity of ethyl acrylate (EA) was examined in vivo by injecting i.p. 5 male C57BL/6 mice per dose group with either 125, 250, 500, 1000 mg/kg EA dissolved in saline. wenty-four hours after injection, the animals were anesthetized, the spleens aseptically removed, and ...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Additional requirements for carbon disulfide (carbon... Special Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl... waterways at the loading and unloading points. (f) The special requirements of § 151.50-41 for...

  12. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Additional requirements for carbon disulfide (carbon... Special Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl... waterways at the loading and unloading points. (f) The special requirements of § 151.50-41 for...

  13. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Additional requirements for carbon disulfide (carbon... Special Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl... waterways at the loading and unloading points. (f) The special requirements of § 151.50-41 for...

  14. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Additional requirements for carbon disulfide (carbon... Special Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl... waterways at the loading and unloading points. (f) The special requirements of § 151.50-41 for...

  15. 46 CFR 151.50-40 - Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Additional requirements for carbon disulfide (carbon... Special Requirements § 151.50-40 Additional requirements for carbon disulfide (carbon bisulfide) and ethyl... waterways at the loading and unloading points. (f) The special requirements of § 151.50-41 for...

  16. [Solubility of the sodium salt of novobiocin in ethyl alcohol mixtures with other solvents].

    PubMed

    Slavin, A A; Etingov, E D; Tomchina, L F; Brunshte?n, I Z

    1979-06-01

    Solubility of sodium novobiocin in binary mixtures of ethyl alcohol with ehtyl acetate, methylene chloride, diethyl ether, carbon tetrachloride or n-heptane was studied. Deviation in the sodium novobiocin solubility from the additivity was observed depending on the nature of the second component of the solvent mixture. PMID:453794

  17. Preparation, release and physicochemical characterisation of ethyl butyrate and hexanal inclusion complexes with ?- and ?-cyclodextrin.

    PubMed

    Zhang, Yang; Zhou, Yibin; Cao, Shengnan; Li, Songnan; Jin, Shanshan; Zhang, Shu

    2015-11-01

    Complexes of ethyl butyrate and hexanal encapsulated by ?-cyclodextrin (?-CD) and ?-cyclodextrin (?-CD) were prepared by coprecipitation, and gas chromatography was used to quantity the flavour compounds in the complexes. The ethyl butyrate-?-CD complex had the highest inclusion ratio (12.20%) followed by the ethyl butyrate-?-CD, hexanal-?-CD and hexanal-?-CD complexes (11.29, 4.41 and 3.33%, respectively). Release experiments were performed under different relative humidities (RH 93, 75 and 52%) and temperatures (4 and 25?°C). The flavour release behaviours of the complexes were described by the Avrami equation. The rate of flavour release was enhanced with both increasing temperature and RH, although the effect of RH was stronger. Physicochemical characterisation using FT-IR, XRD, DSC and SEM analyses demonstrated that crystalline complexes were formed. Both ?-CD and ?-CD were able to encapsulate ethyl butyrate and hexanal, and lower RH and temperature were more suitable for the storage of these complexes. PMID:26471403

  18. Antiplasmodial Properties and Bioassay-Guided Fractionation of Ethyl Acetate Extracts from Carica papaya Leaves

    PubMed Central

    Melariri, Paula; Campbell, William; Etusim, Paschal; Smith, Peter

    2011-01-01

    We investigated the antiplasmodial properties of crude extracts from Carica papaya leaves to trace the activity through bioassay-guided fractionation. The greatest antiplasmodial activity was observed in the ethyl acetate crude extract. C. papaya showed a high selectivity for P. falciparum against CHO cells with a selectivity index of 249.25 and 185.37 in the chloroquine-sensitive D10 and chloroquine-resistant DD2 strains, respectively. Carica papaya ethyl acetate extract was subjected to bioassay-guided fractionation to ascertain the most active fraction, which was purified and identified using high-pressure liquid chromatography (HPLC) and GC-MS (Gas chromatography-Mass spectrometry) methods. Linoleic and linolenic acids identified from the ethyl acetate fraction showed IC50 of 6.88??g/ml and 3.58??g/ml, respectively. The study demonstrated greater antiplasmodial activity of the crude ethyl acetate extract of Carica papaya leaves with an IC50 of 2.96 ± 0.14??g/ml when compared to the activity of the fractions and isolated compounds. PMID:22174990

  19. 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...

  20. 77 FR 75859 - Pyraflufen-Ethyl; Extension of Time-Limited Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ... dose, the Agency set time-limited tolerances (Federal Register of September 5, 2008 (73 FR 51739) until... Register of September 28, 2012 (77 FR 59576) (FRL- 9363-8), EPA issued a document pursuant to FFDCA section.... In the most recent pyraflufen-ethyl tolerance rulemaking, 76 FR 31479 (June 1, 2011) EPA...