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1

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

PubMed

The unique case of a 50-year-old known alcoholic whose corpse was exhumed 27 years after death is reported. The man apparently committed suicide by hanging, but many years later the case was questioned and homicide-linked to a long-lasting serial killer case-was suspected. Thus, the corpse was exhumed, and at the autopsy it was found to be naturally mummified. This fact permitted the analysis of body tissues with the aim to investigate the persistence of ethanol conjugates in the biological material 27 years after death. Fragments of liver and kidney, a blood clot, and a hair strand were collected and submitted to liquid chromatography tandem mass spectrometry analysis. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were identified and quantified in the liver, the kidney, and the blood clot. Hair analysis was found to be severely affected by ion suppression even after solid phase extraction. Consequently, EtG was identified in all hair segments (0-3 cm, 3-6 cm, and 6-10 cm), but no reliable quantification could be carried out. In summary, our findings demonstrate that, notwithstanding the expected conjugate degradation, EtG and EtS can be indicative of ante-mortem use of alcohol even many years after death. PMID:18661140

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

2008-11-01

2

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

PubMed Central

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

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

2013-01-01

3

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

PubMed Central

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

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

2014-01-01

4

The influence of cleansing shampoos on ethyl glucuronide concentration in hair analyzed with an optimized and validated LC-MS/MS method.  

PubMed

Ethyl glucuronide (EtG) is widely used as a marker for assessment of alcohol consumption behavior. In this study the influence of special cleansing shampoos on ethyl glucuronide concentrations in hair was investigated. For that purpose an optimized LC-MS/MS method was developed using a Hypercarb™ porous graphitic carbon (PGC) column and validated according to the guidelines of the German Society of Toxicological and Forensic Chemistry (GTFCh). Twenty-five hair samples of persons with known alcohol consumption behavior were investigated (21 positive samples and 4 blank samples). The hair samples were divided into two strands of hair and were analyzed after treatment with one out of four cleansing shampoos and without shampoo treatment. EtG concentrations in hair did not show any significant differences after a single application of the different cleansing shampoos. EtG was still detectable in all the positive hair samples without significant concentration change. These results clearly demonstrated that a single application of the tested cleansing shampoos did not remove EtG from hair and therefore had no influence on EtG concentration in analytical hair analysis. PMID:25151107

Binz, Tina M; Baumgartner, Markus R; Kraemer, Thomas

2014-11-01

5

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

PubMed

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

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

2011-02-01

6

Diagnosis of chronic alcohol consumption. Hair analysis for ethyl-glucuronide.  

PubMed

This paper describes a procedure for the detection and quantification of ethyl-glucuronide (EtG) in hair samples. During method development the efficacy of extraction of EtG from hair was compared in four extraction methods: (a) methanol; (b) methanol:water (1:1); (c) water; and (d) water:trifluoroacetic acid (9:1). In addition, three derivatizing agents were compared as well: N,O-bistrimethylsilyl-trifluoroacetamide (BSTFA): trimethylchlorosilane (TMCS) (99:1), pentafluoropropionic anhydride (PFPA) and heptafluorobutyric anhydride (HFBA). Water was found to be the best extracting solvent and PFPA the best derivatizing agent. Both provided the highest recoveries, with cleaner extracts and more stable derivatives. The final method is as follows: about 100mg of hair are sequentially washed with water and acetone. The decontaminated sample is finely cut with scissors, then the deuterated internal standard (EtG-d5) and 2 mL of water are added. After sonication for 2 h, the sample is maintained at room temperature overnight. Derivatization is performed with PFPA. Derivatives are injected into a GC-MS system in the electronic impact mode. The method shows linearity over the range of concentrations from 0.050 to 5 ng/mg. Detection and quantification limits are 0.025 and 0.050 ng/mg, respectively. Mean recoveries for the three studied concentrations (low, medium and high) are higher than 87%. The coefficients of variation in intra- and inter-assay precision are always lower than 7%. The method is being routinely applied in our lab for the diagnosis of chronic alcohol consumption. PMID:15451088

Jurado, C; Soriano, T; Giménez, M P; Menéndez, M

2004-10-29

7

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

PubMed

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

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

2010-03-20

8

Determination of ethyl glucuronide in nails by liquid chromatography tandem mass spectrometry as a potential new biomarker for chronic alcohol abuse and binge drinking behavior.  

PubMed

A liquid chromatography tandem mass spectrometry method for ethyl glucuronide (EtG) detection and quantification in nails was developed and fully validated. Nails were extracted in 700 ?L double-distilled water. EtG-d(5) was used as an internal standard. Reversed-phase separation was obtained with an isocratic mobile phase composed of 0.1% formic acid and acetonitrile (99:1) for 10 min. Quantification was performed by multiple reaction monitoring of two transitions per compound (EtG and internal standard). The assay was linear from 10 to 500 pg/mg. Validation parameters were studied at three different quality control levels (10, 50, and 300 pg/mg). Intraday, interday, and total imprecision had a coefficient of variation of less than 9.5%. Ion suppression and ion enhancement were negligible (less than 20%). No carryover was detected. The method was applied to several real cases, among teetotalers, social drinkers, and heavy drinkers. A questionnaire, together with the informed consent form, was given to all the participants in order to evaluate alcohol intake in the one month before sample collection. Nail EtG levels in a social drinker were much higher than the concentrations of EtG in hair provided by the same subject, thus suggesting potential high sensitivity in evaluating both chronic excessive alcohol consumption and binge drinking habits. PMID:22193819

Morini, Luca; Colucci, Mario; Ruberto, Maria Giovanna; Groppi, Angelo

2012-02-01

9

Simultaneous determination of GHB and EtG in hair using GCMS/MS.  

PubMed

A gas chromatographic tandem mass spectrometric (GCMS/MS) method for simultaneously determining trace concentrations of gamma-hydroxybutyrate (GHB) and ethyl glucuronide (EtG) in hair has been developed. Multiple reaction monitoring (MRM) was used to detect precursor and product ions of GHB, (233 and 147) and EtG (261 and 143) following anion exchange solid phase extraction and derivatization with N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA). Deuterated standards of GHB and EtG were used as internal standards. The assay produced excellent linearity (r(2) > 0.99) and sensitivity. The lower limit of quantitation (LLOQ) was 10 pg/mg for EtG assuming a 20 mg hair sample. The method has been used to investigate cases of suspected drug facilitated assault as well as being used to identify heavy alcohol consumption in a group of volunteers. PMID:21500364

Paul, R; Tsanaclis, L; Kingston, R; Berry, A; Guwy, A

2011-04-01

10

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

PubMed

Ethyl sulfate (EtS)--a new direct marker for ethanol intake besides ethyl glucuronide (EtG) and others--was detected in urine samples by electrospray ionization tandem mass-spectrometry (LC-ESI-MS/MS). Ethyl sulfate sodium salt was used for method development, yielding a precursor [M - H]- m/z 125 and product ions m/z 97 [HSO4]- and m/z 80 [SO3]-. Pentadeuterated EtS (D5-EtS) was synthesized by esterification of sulfuric acid with anhydrous hexadeutero ethanol ([M - H]- m/z 130, product ions m/z 98 [DSO4]- and m/z 80 [SO3]-). After addition of D5-EtS and D5-EtG, urine samples were analyzed by direct injection into the gradient LC-MS/MS system. Analysis was performed in accordance with forensic guidelines for confirmatory analysis using one precursor and two product ions. EtS has been detected (in addition to EtG) in the urine samples of nine volunteers after drinking sparkling wine containing between 9 and 49 g of ethanol. Both EtS and EtG could be detected up to 36 h after consumption of alcohol. The excretion profile was found to be similar to that of EtG. No EtS was found in teetotalers' urine samples. Method validation parameters are presented. EtS was stable in urine upon storage up to twenty days at room temperature. In addition to EtG, EtS can be used to detect recent alcohol consumption, thus providing a second marker for the time range of up to approximately one day after elimination of ethanol from urine samples. The determination of EtS can be used in addition to EtG as proof of ethanol consumption in workplace monitoring programs. PMID:15519232

Dresen, Sebastian; Weinmann, Wolfgang; Wurst, Friedrich Martin

2004-11-01

11

Flavonoid glucuronides from Helicteres isora.  

PubMed

Five flavonoid glucuronides were obtained from the fruit of Helicteres isora, three of which were previously unknown compounds: isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 6"-n-butyl ester. isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 2", 4"-disulfate and isoscutellarein 8-O-beta-D-glucuronide 2",4"-disulfate. The structures were determined on the basis of spectroscopy and hydrolysis experiments. PMID:11382247

Kamiya, K; Saiki, Y; Hama, T; Fujimoto, Y; Endang, H; Umar, M; Satake, T

2001-05-01

12

Autism and Phthalate Metabolite Glucuronidation  

PubMed Central

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

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

2013-01-01

13

Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain.  

PubMed

We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signaling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and temporomandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. PMID:25218902

Lewis, Susannah S; Hutchinson, Mark R; Frick, Morin M; Zhang, Yingning; Maier, Steven F; Sammakia, Tarek; Rice, Kenner C; Watkins, Linda R

2015-02-01

14

Electron Thermal Transport in Tokamak: ETG or TEM Turbulences?  

E-print Network

) trapped electron mode turbulence; and (3) a new finite element solver for global electromagnetic is much smaller than the experimental value and in contrast with recent findings of flux-tube simu], the electromagnetic electron temperature gradient (ETG) turbulence with a shorter scale length of the collisionless

Zonca, Fulvio

15

Efficient synthesis of flavanone glucuronides.  

PubMed

The first efficient synthesis of flavanone glucuronides as potential human metabolites is described. The synthetic strategy is based on acetyl protection, followed by a combination of chemical and enzymatic deprotection steps. As an example, the method is applied to a synthesis of 7,4'-di-O-methyleriodictyol 3'-O-beta-d-glucuronide. The aglycone is a flavanone naturally present in tarragon spice ( Artemisia dracunculus ) as well as in various Chinese, Brazilian, and Malaysian medicinal plants. PMID:19653653

Boumendjel, Ahcene; Blanc, Madeleine; Williamson, Gary; Barron, Denis

2009-08-26

16

Autism and Phthalate Metabolite Glucuronidation  

ERIC Educational Resources Information Center

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…

Stein, T. Peter; Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

2013-01-01

17

Discovery of neurosteroid glucuronides in mouse brain.  

PubMed

Neurosteroid glucuronides were found for the first time in brain samples. The intact glucuronides were extracted from the cortex, hippocampus, hypothalamus, and mid-brain tissues of nicotine- and water-treated mice, and detected with capillary liquid chromatography-electrospray-tandem mass spectrometry (CapLC-ESI-MS/MS). The glucuronides of estradiol, cortisol, corticosterone, tetrahydrodeoxycorticosterone, pregnenolone, and isopregnanolone were identified by comparing retention times in selected reaction monitoring (SRM) chromatograms and the relative abundances of two SRM transitions of each neurosteroid glucuronide between the reference and authentic samples, thus providing reliable identification. In vitro experiments, carried out by using S9 fractions from mouse and rat brains, showed a formation of glucuronides with selected test compounds (corticosterone, pregnenolone, and dehydroepiandrosterone), suggesting that biosynthesis of neurosteroid glucuronides is possible in rodent brain. PMID:19733737

Kallonen, Sirkku E; Tammimäki, Anne; Piepponen, Petteri; Raattamaa, Helena; Ketola, Raimo A; Kostiainen, Risto

2009-09-28

18

Glucuronide and sulfate conjugation in the fungal metabolism of aromatic hydrocarbons.  

PubMed Central

Cunninghamella elegans oxidized naphthalene to ethyl acetate-soluble and water-soluble metabolites. Experiments with [14C]-naphthalene indicated that 21% of the substrate was converted into metabolites. The ratio of organic-soluble metabolites to water-soluble metabolites was 76:24. The major ethyl acetate-soluble naphthalene metabolites were trans-1,2-dihydroxy-1,2-dihydro-naphthalene, 4-hydroxy-1-tetralone, and 1-naphthol. Enzymatic treatment of the aqueous phase with either arylsulfatase or beta-glucuronidase released metabolites of naphthalene that were extractable with ethyl acetate. In both cases, the major metabolite was 1-naphthol. The ratio of water-soluble sulfate conjugates to water-soluble glucuronide conjugates was 1:1. Direct analysis of the aqueous phase by high-pressure liquid and thin-layer chromatographic and mass spectrometric techniques indicated that 1-naphthyl sulfate and 1-naphthyl glucuronic acid were major water-soluble metabolites formed from the fungal metabolism of naphthalene. C. elegans oxidized biphenyl primarily to 4-hydroxy biphenyl. Deconjugation experiments with biphenyl water-soluble metabolites indicated that the glucuronide and sulfate ester of 4-hydroxy biphenyl were metabolites. The data demonstrate that sulfation and glucuronidation are major pathways in the metabolism of aromatic hydrocarbons by fungi. PMID:7103474

Cerniglia, C E; Freeman, J P; Mitchum, R K

1982-01-01

19

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

NASA Astrophysics Data System (ADS)

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

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

2014-11-01

20

Icosapent Ethyl  

MedlinePLUS

... weight loss, exercise) to reduce the amount of triglycerides (a fat-like substance) in your blood. Icosapent ... ethyl may work by decreasing the amount of triglycerides and other fats made in the liver.

21

Synthesis, structure characterization, and enzyme screening of clenbuterol glucuronides.  

PubMed

Two clenbuterol O-glucuronide diastereomers were synthesized by the Koenigs-Knorr reaction. Structures and glucuronidation sites of the glucuronides were characterized by tandem mass spectrometry and nuclear magnetic resonance spectroscopy. The two diastereomers were used as standard compounds in studies of stereoselective glucuronidation of clenbuterol with liver microsomes from different species and with 15 human recombinant UDP-glucuronosyltransferases. In this study, chemical and enzymatic reactions produced only O-glucuronides of clenbuterol, although on the basis of the chemical structure of the aglycone, both O- and N-glucuronides of clenbuterol could be formed. Differences in the production of diastereomers of clenbuterol glucuronides were observed among liver microsomes from the various animals. Dog and bovine liver microsomes were significantly active, and also stereoselective, each producing only one but a different diastereomer. Liver microsomes from rabbit and rat were also rather actively glucuronidating clenbuterol, but human, pig, and moose liver microsomes produced only minor amounts of glucuronides. Human liver microsomes produced only one clenbuterol glucuronide diastereomer, and the same was true of the human UDP-glucuronosyltransferases that were active (formation of glucuronide: 1A9 > 1A10 > 1A7). The marked differences in the stereoselective glucuronidation of clenbuterol show that UDP-glucuronosyltransferases in the livers of different animals do not have the same functions, activities, or distribution. This needs to be taken into account, particularly in toxicology testing. PMID:19447177

Alonen, Anna; Gartman, Minna; Aitio, Olli; Finel, Moshe; Yli-Kauhaluoma, Jari; Kostiainen, Risto

2009-07-12

22

Characterization of 1'-hydroxymidazolam glucuronidation in human liver microsomes.  

PubMed

Midazolam is a potent benzodiazepine derivative with sedative, hypnotic, anticonvulsant, muscle-relaxant, and anxiolytic activities. It undergoes oxidative metabolism catalyzed almost exclusively by the CYP3A subfamily to a major metabolite, 1'-hydroxymidazolam, which is equipotent to midazolam. 1'-Hydroxymidazolam is subject to glucuronidation followed by renal excretion. To date, the glucuronidation of 1'-hydroxymidazolam has not been evaluated in detail. In the current study, we identified an unreported quaternary N-glucuronide, as well as the known O-glucuronide, from incubations of 1'-hydroxymidazolam in human liver microsomes enriched with uridine 5'-diphosphoglucuronic acid (UDPGA). The structure of the N-glucuronide was confirmed by nuclear magnetic resonance analysis, which showed that glucuronidation had occurred at N-2 (the imidazole nitrogen that is not a part of the benzodiazepine ring). In a separate study, in which midazolam was used as the substrate, an analogous N-glucuronide also was detected from incubations with human liver microsomes in the presence of UDPGA. Investigation of the kinetics of 1'-hydroxymidazolam glucuronidation in human liver microsomes indicated autoactivation kinetics (Hill coefficient, n = 1.2-1.5). The apparent S(50) values for the formation of O- and N-glucuronides were 43 and 18 microM, respectively, and the corresponding apparent V(max) values were 363 and 21 pmol/mg of microsomal protein/min. Incubations with recombinant human uridine diphosphate glucuronosyltransferases (UGTs) indicated that the O-glucuronidation was catalyzed by UGT2B4 and UGT2B7, whereas the N-glucuronidation was catalyzed by UGT1A4. Consistent with these observations, hecogenin, a selective inhibitor of UGT1A4, selectively inhibited the N-glucuronidation, whereas diclofenac, a potent inhibitor of UGT2B7, had a greater inhibitory effect on the O-glucuronidation than on the N-glucuronidation. In summary, our study provides the first demonstration of N-glucuronidation of 1'-hydroxymidazolam in human liver microsomes. PMID:17998299

Zhu, Bing; Bush, David; Doss, George A; Vincent, Stella; Franklin, Ronald B; Xu, Shiyao

2008-02-01

23

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

E-print Network

Numerical Study of Electromagnetic ETG Turbulence: -dependence of Electron Heat Transport B. Labit. To this end, we have developed a 3D toroidal global fluid code that solves a non-linear electromagnetic model, that magnetic fluctuations play an important role in electron transport [1]. Electromagnetic effects

24

Reactivity considerations in the analysis of glucuronide and sulfate conjugates of diflunisal.  

PubMed

Reactivity of glucuronide and sulfate conjugates was taken into account in development of a simple isocratic HPLC method for direct assay of diflunisal (DF) and its acyl glucuronide (DAG), phenolic glucuronide (DPG), and sulfate (DS) conjugates. Whereas DPG was stable over the pH range 0-9, DAG was highly labile at neutral to slightly alkaline pH, undergoing rearrangement (isomerisation via acyl migration), hydrolysis, and in the presence of methanol, transesterification to DF methyl ester. The 2-, 3-, and 4-O-acyl positional isomers of DAG appeared as three pairs of peaks. Interconversion between partners of each pair occurred even under acidic conditions inhibitory to acyl migration, implicating mutarotation. DS was stable at neural to slightly alkaline pH, but underwent hydrolysis under relatively strongly acidic conditions. However, this hydrolysis was remarkably catalyzed (e.g., by 1,000-fold) in the presence of solvents (i.e., solvolysis) such as diethyl ether and ethyl acetate. DS (an acid) could not be extracted from aqueous solution because of this acidic solvolysis. Suitable conditions for simultaneous direct analysis (nonextractive, nonconcentrative) of DF and its reactive (DAG and DS) and unreactive (DPG) conjugates were achieved by working at pH of approximately 4.5. The procedure thus developed is suitable for plasma, urine, and bile samples, and has revealed the presence of new, as yet unidentified, metabolites of DF. PMID:2595754

Dickinson, R G; King, A R

1989-11-01

25

Curcumin Glucuronides: Assessing the Proliferative Activity against Human Cell Lines  

PubMed Central

A gram scale synthesis of the glucuronide metabolites of curcumin were completed in four steps. The newly synthesized curcumin glucuronide compounds 2 and 3 along with curcumin 1 were tested and their anti-proliferative effects against KBM-5, Jurkat cell, U266, and A549 cell lines were reported. Biological data revealed that as much as 1 ?M curcumin 1 exhibited anticancer activity and almost 100% cell kill was noted at 10 ?M on two out of four cell lines; while curcumin mono-glucuronide 2 as well as diglucuronide 3 displayed no suppression of cell proliferation. PMID:24280069

Pal, Ashutosh; Sung, Bokyung; Prasad, Basvoju A. Bhanu; Schuber, Paul T.; Prasad, Sahdeo; Aggarwal, Bharat B.; Bornmann, William G.

2014-01-01

26

Assessment of catechol induction and glucuronidation in rat liver microsomes.  

PubMed

Catechols are substances with a 1,2-dihydroxybenzene group from natural or synthetic origin. The aim of this study was to determine whether catechols (4-methylcatechol, 4-nitrocatechol, 2,3-dihydroxynaphthalene) and the antiparkinsonian drugs, entacapone and tolcapone, at doses 150 to 300 mg/kg/day, for 3 days, are able to enhance their own glucuronidation. The induction potency of catechols on rat liver UDP-glucuronosyltransferases (UGTs) was compared with that of a standard polychlorinated biphenyl (PCB) inducer, Aroclor 1254. The glucuronidation rate of these catechols was enhanced up to 15-fold in the liver microsomes of PCB-treated rats, whereas treatment with catechols had little effect. Entacapone, tolcapone, 4-methylcatechol, catechol, 2,3-dihydroxynaphthalene, and 4-nitrocatechol were glucuronidated in control microsomes at rates ranging from 0.12 for entacapone to 22.0 nmol/min/mg for 4-nitrocatechol. Using 1-naphthol, entacapone, and 1-hydroxypyrene as substrates, a 5-, 8-, and 16-fold induction was detected in the PCB rats, respectively, whereas the catechol-induced activities were 1.1- to 1.5-fold only. Entacapone was glucuronidated more efficiently by PCB microsomes than by control microsomes (Vmax/Km, 0.0125 and 0.0016 ml/min/mg protein, respectively). Similar kinetic results were obtained for 1-hydroxypyrene. The Eadie-Hofstee plots suggested the contribution of multiple UGTs for the glucuronidation of 1-hydroxypyrene (Km1, Km2, Km3 = 0.8, 9.7, and 63 microM, and Vmax1, Vmax2, Vmax3 = 11, 24, and 55 nmol/min/mg, respectively), whereas only one UGT could be implicated in the glucuronidation of entacapone (Km = 130 microM, Vmax = 1.6 nmol/min/mg). In conclusion, catechols are poor inducers of their own glucuronidation supported by several UGT isoforms. Their administration is unlikely to affect the glucuronidation of other drugs administered concomitantly. PMID:15371300

Elovaara, Eivor; Mikkola, Jouni; Luukkanen, Leena; Antonio, Laurence; Fournel-Gigleux, Sylvie; Burchell, Brian; Magdalou, Jacques; Taskinen, Jyrki

2004-12-01

27

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

PubMed

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

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

2015-03-01

28

Non-linear Dynamics in ETG Mode Saturation and Beam-Plasma Instabilities  

NASA Astrophysics Data System (ADS)

Non-linear mechanisms arise frequently in plasmas and beam-plasma systems resulting in dynamics not predicted by linear theory. The non-linear mechanisms can influence the time evolution of plasma instabilities and can be used to describe their saturation. Furthermore time and space averaged non-linear fields generated by instabilities can lead to collisionless transport and plasma heating. In the case of beam-plasma systems counter-intuitive beam defocusing and scaling behavior which are interesting areas of study for both Low-Temperature and High Energy Density physics. The non-linear mode interactions in form of phase coupling can describe energy transfer to other modes and can be used to describe the saturation of plasma instabilities. In the first part of this thesis, a theoretical model was formulated to explain the saturation mechanism of Slab Electron Temperature Gradient (ETG) mode observed in the Columbia Linear Machine (CLM), based on experimental time-series data collected through probe diagnostics [1]. ETG modes are considered to be a major player in the unexplained high levels of electron transport observed in tokamak fusion experiments and the saturation mechanism of these modes is still an active area of investigation. The data in the frequency space indicated phase coupling between 3 modes, through a higher order spectral correlation coefficient known as bicoherence. The resulting model is similar to [2], which was a treatment for ITG modes observed in the CLM and correctly predicts the observed saturation level of the ETG turbulence. The scenario is further supported by the fact that the observed mode frequencies are in close alignment with those predicted theoretical dispersion relations. Non-linear effects arise frequently in beam-plasma systems and can be important for both low temperature plasma devices commonly used for material processing as well as High Energy Density applications relevant to inertial fusion. The non-linear time averaged fields generated by beam-plasma instabilities can be responsible for defocusing and distorting beams propagating in background plasma. This can be problematic in inertial fusion applications where the beam is intended to propagate ballistically as the background plasma neutralizes the beam space charge and current. We used particle-in-cell (PIC) code LSP to numerically investigate the defocusing effects in an ion beam propagating in background plasma experiences as it is exposed to the non-linear fields generated by Two-Stream instability between beam ions and plasma electrons. Supported by theory and benchmarked by the numerical solutions of governing E&M equations, the simulations were used to find and check scaling laws for the defocusing forces in the parameter space of beam and plasma density as well as the beam ion mass. A transition region where the defocusing fields peak has been identified, which should be avoided in the design of experimental devices. We further proposed a diagnostic tool to identify the presence of the two-stream instability in a system with parameters similar to the National Drift Compression Experiment II (NDCX-II) and conducted proof-of concept simulations. In the case of electron beam propagating in background plasma instability driven collisionless scattering and plasma heating is observed. 1-D simulations conducted in EDIPIC were benchmarked in LSP to study the excitation and time-evolution of electron-electron Two-Stream instability. Coupling of electron dynamics via non-linear ponderomotive force created by instability generated fields with ion cavities and Ion-Acoustic mode excitation was observed. Furthermore 2-D simulations of an electron-beam in a background plasma was performed. Many of the effects in observed in 1-D simulations were replicated. Morever generation of oblique modes with transverse wave numbers were observed in the simulations, which resulted in significant transverse scattering of beam electrons and the time evolution of the turbulent spectrum was studied via Fourier techniques. It is plausible that the

Tokluoglu, Erinc K.

29

In vitro and in vivo glucuronidation of midazolam in humans  

PubMed Central

AIMS Midazolam (MDZ) is a benzodiazepine used as a CYP3A4 probe in clinical and in vitro studies. A glucuronide metabolite of MDZ has been identified in vitro in human liver microsome (HLM) incubations. The primary aim of this study was to understand the in vivo relevance of this pathway. METHODS An authentic standard of N-glucuronide was generated from microsomal incubations and isolated using solid-phase extraction. The structure was confirmed using proton nuclear magnetic resonance (NMR) and 1H-13C long range correlation experiments. The metabolite was quantified in vivo in human urine samples. Enzyme kinetic behaviour of the pathway was investigated in HLM and recombinant UGT (rUGT) enzymes. Additionally, preliminary experiments were performed with 1?-OH midazolam (1?-OH MDZ) and 4-OH-midazolam (4-OH MDZ) to investigate N-glucuronidation. RESULTS NMR data confirmed conjugation of midazolam N-glucuronide (MDZG) standard to be on the ?-nitrogen of the imidazole ring. In vivo, MDZG in the urine accounted for 1–2% of the administered dose. In vitro incubations confirmed UGT1A4 as the enzyme of interest. The pathway exhibited atypical kinetics and a substrate inhibitory cooperative binding model was applied to determine Km (46 µM, 64 µM), Vmax (445 pmol min?1 mg?1, 427 pmol min?1 mg?1) and Ki (58 µM, 79 µM) in HLM and rUGT1A4, respectively. From incubations with HLM and rUGT enzymes, N-glucuronidation of 1?-OH MDZ and 4-OH MDZ is also inferred. CONCLUSIONS A more complete picture of MDZ metabolism and the enzymes involved has been elucidated. Direct N-glucuronidation of MDZ occurs in vivo. Pharmacokinetic modelling using Simcyp™ illustrates an increased role for UGT1A4 under CYP3A inhibited conditions. PMID:19371318

Hyland, Ruth; Osborne, Toby; Payne, Anthony; Kempshall, Sarah; Logan, Y Raj; Ezzeddine, Khaled; Jones, Barry

2009-01-01

30

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...

31

In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats.  

PubMed

Anthraquinones naturally distribute in many plants including rhubarb and have widespread applications throughout industry and medicine. Recent studies provided new insights in potential applications of these traditional laxative constituents. Glucuronidation was the main metabolic pathway of rhubarb anthraquinones in vivo. This study examined the activity and regioselectivity of glucuronidation of rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, rhein) in liver and intestinal microsomes from rats and humans, by comparing with the core structure danthron. All anthraquinones formed mono-glucuronides and, except for rhein, the conjugation sites of the main metabolites were unambiguously identified. Two minor glucuronides of emodin were first reported together with the dominant emodin-3-O-?-d-glucuronide. The substitution on the anthraquinone ring was crucial to the activity and regioselectivity of glucuronidation. In general, the activity was decreased greatly with a ?-COOH (rhein), while enhanced dramatically with a ?-OH (emodin). Glucuronidation showed an absolute preference towards ?-OH, followed by ?-OH and ?-alcoholic OH. The glucuronidation activity and regioselectivity also varied slightly with organs and species. All glucuronides of aloe-emodin, emodin, chrysophanol and physcion were formed by multiple human UGT isoforms with 1A9 being the most prominent in most cases. The UGT2B subfamily (2B7 and 2B15) only showed high activity towards a ?-OH. In conclusion, the substitution at the anthraquinone ring was crucial to the rate and preference of glucuronidation. The high glucuronidation activity of UGT1A9 towards anthraquinones highlighted potential drug interactions. PMID:24854283

Wu, Wenjin; Hu, Nan; Zhang, Qingwen; Li, Yaping; Li, Peng; Yan, Ru; Wang, Yitao

2014-08-01

32

Regio- and stereospecific N-glucuronidation of medetomidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2B10 account for the complex kinetics of human liver microsomes.  

PubMed

Medetomidine is a chiral imidazole derivate whose dextroenantiomer is pharmacologically active. The major metabolic pathway of dexmedetomidine [(+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole] in humans is N-glucuronidation at the imidazolate nitrogens. We have purified the N3- and N1-glucuronides of dexmedetomidine, termed DG1 and DG2, respectively, according to their elution order in liquid chromatography and determined their structure by 1H nuclear magnetic resonance (NMR). Studying medetomidine glucuronidation by human liver microsomes (HLMs) and recombinant UDP glucuronosyltransferase (UGT) 1A4 indicated that another human UGT plays a major role in these activities. We now demonstrate that this enzyme is UGT2B10. HLMs catalyzed DG1 and DG2 formation, at a ratio of 3:1, with two-enzyme kinetics that contain both a high-affinity component, K(m1) values of 6.6 and 8.7 microM, and a low-affinity component, K(m2) values > 1 mM. The DG1/DG2 ratio in the case of UGT2B10 was lower, 1.4:1, whereas the substrate affinity for both reactions was high, K(m) values of 11 and 16 microM. UGT1A4 produced mainly DG1 (DG1/DG2 ratio of 6.6:1) at low substrate affinities, K(m) values above 0.6 mM, but superior expression-normalized V(max) values. Levomedetomidine [(-)-4-(R)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole] glucuronidation by HLMs yielded mostly the N3-glucuronide (LG1, structure determined by NMR), with monophasic kinetics and a K(m) value of 14 microM. The activity of UGT1A4 toward levomedetomide was low and generated both LG1 and LG2, whereas UGT2B10 exhibited relatively high activity and sharp regioselectivity, yielding only LG1, with a K(m) value of 7.4 microM. The results highlight the contribution of UGT2B10 to medetomidine glucuronidation and its potential importance for other N-glucuronidation reactions within the human liver. PMID:18474681

Kaivosaari, Sanna; Toivonen, Päivi; Aitio, Olli; Sipilä, Julius; Koskinen, Mikko; Salonen, Jarmo S; Finel, Moshe

2008-08-01

33

In Vitro Stability of Free and Glucuronidated Cannabinoids in Urine Following Controlled Smoked Cannabis  

PubMed Central

Analyte stability is an important factor in urine test interpretation, yet cannabinoid stability data are limited. A comprehensive study of ?9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide stabilities in authentic urine was completed. Urine samples after ad libitum cannabis smoking were pooled to prepare low and high pools for each study participant; baseline concentrations were measured within 24h at room temperature (RT), 4°C and ?20°C. Stability at RT, 4°C and ?20°C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT THCCOOH baseline concentrations were significantly higher than ?20°C, but not 4°C baseline concentrations. After 1 week at RT, THCCOOH increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In RT low pool, total THCCOOH (THCCOOH+THCCOOH-glucuronide) was significantly lower after 1 week. At 4°C, THCCOOH was stable 2 weeks, THCCOOH-glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable frozen for 1 year, but 6 months high pool results were significantly higher than baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total THCCOOH was stable 6 months at 4°C, and frozen 6 months (low) and 1 year (high). THC, cannabidiol and cannabinol were never detected in urine; although not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after one week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and 4°C. Analysis should be conducted within 3 months if non-hydrolyzed THCCOOH or THCCOOH-glucuronide quantification is required. PMID:24292435

Desrosiers, Nathalie A.; Lee, Dayong; Scheidweiler, Karl B.; Concheiro-Guisan, Marta; Gorelick, David A.; Huestis, Marilyn A.

2014-01-01

34

Characterization of Rat and Human UDP-Glucuronosyltransferases Responsible for the in Vitro Glucuronidation of Diclofenac  

Microsoft Academic Search

In the current study, the identification of the rat and human UDP-glucuronosyltransferase (UGT) isoforms responsible for the glucuronidation of diclofenac was determined. Recombinant hu- man UGT1A9 catalyzed the glucuronidation of diclofenac at a moderate rate of 166-pmol\\/min\\/mg protein, while UGT1A6 and 2B15 catalyzed the glucuronidation of diclofenac at low rates (<20-pmol\\/min\\/mg protein). Conversely, human UGT2B7 dis- played a high rate

C. King; W. Tang; J. Ngui; T. Tephly; M. Braun

2001-01-01

35

Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer  

Microsoft Academic Search

Some types of cancer cells have high levels of beta-glucoronidase activity. This enzyme is able to deglucuronidate a variety of glucuronide derivatives on the cell membrane. Either O- or N-glucuronides can be selectively incorporated into the cancer cells. If the aglycone is cytotoxic, the glucuronide can potentially be used as a selective anti-cancer drug in cancers with high levels of

Turan Ünak; Perihan Ünak; Binnur Ongun; Yusuf Duman

1997-01-01

36

Regioselective glucuronidation of andrographolide and its major derivatives: metabolite identification, isozyme contribution, and species differences.  

PubMed

Andrographolide (AND) and two of its derivatives, deoxyandrographolide (DEO) and dehydroandrographolide (DEH), are widely used in clinical practice as anti-inflammatory agents. However, UDP-glucuronosyltransferase (UGT)-mediated phase II metabolism of these compounds is not fully understood. In this study, glucuronidation of AND, DEO, and DEH was characterized using liver microsomes and recombinant UGT enzymes. We isolated six glucuronides and identified them using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. We also systematically analyzed various kinetic parameters (K m, V max, and CLint) for glucuronidation of AND, DEO, and DEH. Among 12 commercially available UGT enzymes, UGT1A3, 1A4, 2B4, and 2B7 exhibited metabolic activities toward AND, DEO, and DEH. Further, UGT2B7 made the greatest contribution to glucuronidation of all three anti-inflammatory agents. Regioselective glucuronidation showed considerable species differences. 19-O-Glucuronides were present in liver microsomes from all species except rats. 3-O-Glucuronides were produced by pig and cynomolgus monkey liver microsomes for all compounds, and 3-O-glucuronide of DEH was detected in mouse and rat liver microsomes (RLM). Variations in K m values were 48.6-fold (1.93-93.6 ?M) and 49.5-fold (2.01-99.1 ?M) for 19-O-glucuronide and 3-O-glucuronide formation, respectively. Total intrinsic clearances (CLint) for 3-O- and 19-O-glucuronidation varied 4.8-fold (22.7-110 ?L min(-1) mg(-1)), 10.6-fold (94.2-991 ?L min(-1) mg(-1)), and 8.3-fold (122-1,010 ?L min(-1) mg(-1)), for AND, DEH, and DEO, respectively. Our results indicate that UGT2B7 is the major UGT enzyme involved in the metabolism of AND, DEO, and DEH. Metabolic pathways in the glucuronidation of AND, DEO, and DEH showed considerable species differences. PMID:25204783

Tian, Xiangge; Liang, Sicheng; Wang, Chao; Wu, Baojian; Ge, Guangbo; Deng, Sa; Liu, Kexin; Yang, Ling; Ma, Xiaochi

2015-01-01

37

Ethyl Alcohol Production.  

E-print Network

-ooc ~ TA245.7 ~873 10.1374 The Texas A&M Un1versity System Texas Agricultural Extension Service Damel C Pfannst1el . D1rector College Station B-1374 ETHYL ALCOHOL PRODUCTION Operation of the Texas A&M University ethyl alcohol plant... is an interdisciplinary project with support from the Texas Agricultural Extension Service, Texas Agricultural Experiment Station, Center for Energy and Mineral Resources, the Texas A&M University System; and the Texas Energy Development Fund of the Texas Energy...

O'Neal, Henry

1981-01-01

38

Omega-3-acid Ethyl Esters  

MedlinePLUS

Omega-3-acid ethyl esters are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the ... triglycerides (a fat-like substance) in your blood. Omega-3-acid ethyl esters are in a class of ...

39

Rifampin induces alterations in mycophenolic acid glucuronidation and elimination: Implications for drug exposure in renal allograft recipients  

Microsoft Academic Search

Background: Exposure to mycophenolic acid (MPA) and its main metabolites (MPA 7-O-glucuronide [MPAG] and MPA acyl-glucuronide [AcMPAG]) is characterized by a large interindividual and intraindividual variability, resulting in part from variability in glucuronidation (via uridine diphosphate–glucuronosyltransferase isoforms) and excretion via multidrug resistance-associated protein 2 (MRP2). It can be hypothesized that drugs interfering with glucuronidation and excretion will alter (Ac)MPA(G) exposure.Methods:

Maarten Naesens; Dirk R. J. Kuypers; Frank Streit; Victor W. Armstrong; Michael Oellerich; Kristin Verbeke; Yves Vanrenterghem

2006-01-01

40

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

SciTech Connect

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.

Nishiyama, Takahito; Ohnuma, Tomokazu; Inoue, Yuu; Kishi, Takehiko; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)], E-mail: hiratuka@ps.toyaku.ac.jp

2008-06-27

41

Glucuronidation and sulphation of paracetamol in HIV-positive patients and patients with AIDS  

PubMed Central

Aims To gauge the effect of disease state and disease progression on the glucuronidation and sulphation of paracetamol (APAP) among HIV-positive patients and patients with AIDS. Methods The extent of APAP glucuronidation and APAP sulphation was assessed using a spot urine sample collected 4 h after the oral administration of 500 mg of APAP to 108 patients with AIDS or HIV infection. The molar concentrations of APAP and its glucuronide and sulphate metabolites were determined using a validated h.p.l.c. method and glucuronidation and sulphation indices were constructed using APAP metabolite/APAP molar concentration ratios. Results No effect of disease state, AIDS vs asymptomatic HIV positive vs control, on APAP glucuronidation or sulphation was observed. The patient population was studied over time and disease progression also did not significantly alter the calculated glucuronidation and sulphation indices. The effect of the concomitant administration of other therapeutic agents was assessed and in the cross sectional portion of the study dapsone appeared to significantly decrease APAP sulphation as did lamivudine. In the longitudinal portion of the study the latter effect was not observed but zidovudine was seen to increase APAP glucuronidation. The data also indicates that APAP glucuronidation may be reduced in patients who are >10% below their ideal body weight. PMID:10594484

O’Neil, W M; Pezzullo, J C; Di Girolamo, A; Tsoukas, C M; Wainer, I W

1999-01-01

42

Studies of the renal excretion of probenecid acyl glucuronide in man  

Microsoft Academic Search

The metabolism of probenecid has been investigated in both normal and gouty subjects. To carry out these studies, specific spectrophotometric methods were developed for the measurement of a major metabolite of probenecid, the acyl glucuronide. This conjugate was isolated in semi-pure state and its identity as a mono acyl glucuronide established. Our experiments indicate that about 25% of probenecid is

J. M. Perel; P. G. Dayton; T. F. Yü; A. B. Gutman

1971-01-01

43

Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver.  

PubMed

1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It has been shown that the compound is sulphated in human liver and the aims of the present investigation were to study resveratrol glucuronidation in human liver microsomes and to determine whether flavonoids inhibit resveratrol glucuronidation. 2. A simple and reproducible radiometric assay for resveratrol glucuronidation was developed. The assay employed uridine-5'-diphosphoglucuronic acid-[14C] and unlabelled resveratrol. Resveratrol-glucuronide was isolated by TLC. The intra- and interassays variabilities were 1 and 1.5%, respectively. 3. The rate of resveratrol glucuronidation was measured in 10 liver samples. The mean +/- SD and median of resveratrol glucuronidation rate were 0.69 +/- 0.34 and 0.80 nmol/min/mg, respectively. Resveratrol glucuronosyl transferase followed Michaelis-Menten kinetics and the Km and Vmax (mean +/- SD; n = 5) were 0.15 +/- 0.09 mM and 1.3 +/- 0.3 nmol/min/mg, respectively. The intrinsic clearance was 11 +/- 4 x 10(-3) ml/min.mg. 4. The flavonoid quercetin inhibited resveratrol glucuronidation and its IC50 (mean +/- SD; n = 3) was 10 +/- 1 microM. Myricetin, catechin, kaempferol, fisetin and apigenin (all at 20 microM) inhibited resveratrol glucuronidation and the percent of control ranged between 46% (catechin) to 72% (apigenin). 5. The present results show that resveratrol is glucuronated in the human liver. Glucuronidation may reduce the bioavailability of this compound however, flavonoids inhibit resveratrol glucuronidation and such an inhibition might improve the bioavailability of resveratrol. PMID:11197066

de Santi, C; Pietrabissa, A; Mosca, F; Pacifici, G M

2000-11-01

44

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

SciTech Connect

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.

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

1982-09-01

45

Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H(2)O(2) induced oxidative damage.  

PubMed

Hydroxytyrosol (2-(3',4'-dihydroxyphenyl)ethanol; HT), the most active ortho-diphenolic compound, present either in free or esterified form in extravirgin olive oil, is extensively metabolized in vivo mainly to O-methylated, O-sulfated and glucuronide metabolites. We investigated the capacity of three glucuronide metabolites of HT, 3'-O-?-d-glucuronide and 4'-O-?-d-glucuronide derivatives and 2-(3',4'-dihydroxyphenyl)ethanol-1-O-?-d-glucuronide, in comparison with the parent compound, to inhibit H(2)O(2) induced oxidative damage and cell death in LLC-PK1 cells, a porcine kidney epithelial cell line. H(2)O(2) treatment exerted a toxic effect inducing cell death, interacting selectively within the pro-death extracellular-signal relate kinase (ERK 1/2) and the pro-survival Akt/PKB signaling pathways. It also produced direct oxidative damage initiating the membrane lipid peroxidation process. None of the tested glucuronides exhibited any protection against the loss in renal cell viability. They also failed to prevent the changes in the phosphorylation states of ERK and Akt, probably reflecting their inability to enter the cells, while HT was highly effective. Notably, pretreatment with glucuronides exerted a protective effect at the highest concentration tested against membrane oxidative damage, comparable to that of HT: the formation of malondialdehyde, fatty acid hydroperoxides and 7-ketocholesterol was significantly inhibited. PMID:21798251

Deiana, Monica; Incani, Alessandra; Rosa, Antonella; Atzeri, Angela; Loru, Debora; Cabboi, Barbara; Paola Melis, M; Lucas, Ricardo; Morales, Juan C; Assunta Dessì, M

2011-09-30

46

In Vitro Stability of Free and Glucuronidated Cannabinoids in Blood and Plasma Following Controlled Smoked Cannabis  

PubMed Central

BACKGROUND Blood and plasma cannabinoid stability is important for test interpretation and is best studied in authentic rather than fortified samples. METHODS Low and high blood and plasma pools were created for each of 10 participants after they smoked a cannabis cigarette. The stabilities of ?9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide, and THCCOOH-glucuronide were determined after 1 week at room temperature; 1, 2, 4, 12, and 26 (±2) weeks at 4 °C; and 1, 2, 4, 12, 26 (±2), and 52 (±4) weeks at ?20 °C. Stability was assessed by Friedman test. RESULTS Numbers of THC-glucuronide and CBD-positive blood samples were insufficient to assess stability. In blood, 11-OH-THC and CBN were stable for 1 week at room temperature, whereas THC and THCCOOH-glucuronide decreased and THCCOOH increased. In blood, THC, THCCOOH-glucuronide, THCCOOH, 11-OH-THC, and CBN were stable for 12, 4, 4, 12, and 26 weeks, respectively, at 4 °C and 12, 12, 26, 26, and 52 weeks at ?20 °C. In plasma, THC-glucuronide, THC, CBN, and CBD were stable for 1 week at room temperature, whereas THCCOOH-glucuronide and 11-OH-THC decreased and THCCOOH increased. In plasma, THC-glucuronide, THC, THCCOOH-glucuronide, THCCOOH, 11-OH-THC, CBN, and CBD were stable for 26, 26, 2, 2, 26, 12, and 26 weeks, respectively, at 4 °C and 52, 52, 26, 26, 52, 52, and 52 weeks, respectively, at ?20 °C. CONCLUSIONS Blood and plasma samples should be stored at ?20 °C for no more than 3 and 6 months, respectively, to assure accurate cannabinoid quantitative results. PMID:23519966

Karschner, Erin L.; Desrosiers, Nathalie A.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

47

Ethyl anion preferred conformation  

NASA Astrophysics Data System (ADS)

Ab initio architecture and torsional barrier for ethyl anion, C2H -5 are analyzed using natural bond orbital methodology. The B3LYP/6-311++G(3df,2p) 2-kcal/mol torsional barrier between the preferred staggered and higher-energy eclipsed conformer is calculated to be one-third lower than for ethane. This decrease is largely attributed to reduced hyperconjugative stabilization of the equilibrium anion conformer compared to that for ethane. Proton removal is also predicted to cause opening of the ethane central CCH angle by 7°, attributed to decreased steric repulsion and to increased hyperconjugative stabilization accompanying angle widening in the ion.

Goodman, Lionel; Sauers, Ronald R.

48

Glucuronidation and Sulfation Kinetics of Diflunisal in Man.  

NASA Astrophysics Data System (ADS)

Diflunisal is a nonsteroidal anti-inflammatory drug used in the treatment of arthritis and musculoskeletal pain. Diflunisal exhibits concentration- and dose-dependent kinetics, the mechanism of which has not been determined. The purpose of this study was to determine the mechanism(s) responsible for non-linear disposition of diflunisal and to examine environmental factors which may affect the elimination of diflunisal. The metabolites of diflunisal, including a new metabolite, the sulphate conjugate, were purified by column and semi-preparative high pressure liquid chromatography. Assays for the quantitation of diflunisal and conjugates in urine and diflunisal in plasma were developed. Plasma protein binding of diflunisal in blank plasma and in plasma obtained following multiple doses of diflunisal was determined by equilibrium dialysis. Total body clearance of diflunisal decreased when dose increased from 100 to 750 mg. Total clearance increased when dose increased from 750 to 1000 mg. The percent of recovered dose eliminated as the acyl glucuronide decreased and the percent eliminated as the sulphate increased with increasing dose of diflunisal. Plasma protein binding of diflunisal was concentration dependent over a range of diflunisal plasma concentrations of 3 to 257 mug/ml. Total clearance, and to a lesser degree, unbound clearance of diflunisal were decreased following multiple dose administration of 250 and 500 mg diflunisal. Percent of recovered dose eliminated as the acyl glucuronide decreased and percent eliminated as the sulphate conjugate increased following multiple dosing. Plasma protein binding of diflunisal was similar in blank plasma and plasma obtained at steady state. Unbound clearance of diflunisal exceeded liver plasma flow. Frequency distributions of the elimination of the conjugates of diflunisal were normally distributed. Sex, smoking, and use of vitamins or oral contraceptives were identified as factors which may affect the elimination of diflunisal.

Loewen, Gordon Rapheal

49

Identification of UDP-glucuronosyltransferase isoforms involved in hepatic and intestinal glucuronidation of phytochemical carvacrol.  

PubMed

1. Carvacrol (2-methyl-5-(1-methylethyl)-phenol), one of the main components occurring in many essential oils of the family Labiatae, has been widely used in food, spice and pharmaceutical industries. 2. The carvacrol glucuronidation was characterized by human liver microsomes (HLMs), human intestinal microsomes (HIMs) and 12 recombinant UGT (rUGT) isoforms. 3. One metabolite was identified as a mono-glucuronide by liquid chromatography/mass spectrometry with HLMs, HIMs, rUGT1A3, rUGT1A6, rUGT1A7, rUGT1A9 and rUGT2B7. 4. The study with a chemical inhibition, rUGT, and kinetics study demonstrated that rUGT1A9 was the major isozyme responsible for glucuronidation in HLMs, and rUGT1A7 played a major role for glucuronidation in HIMs. PMID:22559213

Dong, Rui-Hua; Fang, Zhong-Ze; Zhu, Liang-Liang; Ge, Guang-Bo; Yang, Ling; Liu, Ze-Yuan

2012-10-01

50

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 ...

51

UGT2B10 genotype influences nicotine glucuronidation, oxidation and consumption  

PubMed Central

Background Tobacco exposure is routinely assessed by quantifying nicotine metabolites in plasma or urine. On average, 80% of nicotine undergoes C-oxidation to cotinine. However, interindividual variation in nicotine glucuronidation is substantial and glucuronidation accounts for from 0 to 40% of total nicotine metabolism. We report here the effect of a polymorphism in a UDP-glucuronsyl transferase, UGT2B10, on nicotine metabolism and consumption. Methods Nicotine, cotinine, their N-glucuronide conjugates, and total trans-3'-hydroxycotinine were quantified in the urine (n=327) and plasma (n =115) of smokers. Urinary nicotine N-oxide was quantified in 105 smokers. Nicotine equivalents, the sum of nicotine and all major metabolites, were calculated for each smoker. The relationship of the UGT2B10 Asp67Tyr allele to nicotine equivalents, N-glucuronidation, and C-oxidation was determined. Results Individuals heterozygous for the Asp67Tyr allele excreted less nicotine or cotinine as their glucuronide conjugates than wild-type, resulting in a 60% lower ratio of cotinine glucuronide:cotinine, a 50% lower ratio of nicotine glucuronide:nicotine and increased cotinine and trans-3'-hydroxycotinine. Nicotine equivalents, a robust biomarker of nicotine intake, were lower among Asp67Tyr heterozygotes compared to individuals without this allele; 58.2 nmol/ml (95% CI, 48.9 – 68.2) versus 69.2 nmol/ml (95% CI, 64.3 – 74.5). Conclusions Individuals heterozygous for UGT2B10 Asp67Tyr consume less nicotine than do wild type smokers. This striking observation suggests that variations in nicotine N-glucuronidation, as reported for nicotine C-oxidation, may influence smoking behavior. Impact UGT2B10 genotype influences nicotine metabolism and should be taken into account when characterizing the role of nicotine metabolism on smoking. PMID:20501767

Berg, Jeannette Zinggeler; von Weymarn, Linda; Thompson, Elizabeth A.; Wickham, Katherine M.; Weisensel, Natalie A.; Hatsukami, Dorothy K.; Murphy, Sharon E.

2010-01-01

52

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

PubMed Central

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

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

2014-01-01

53

Identification of human UGT isoforms responsible for glucuronidation of efavirenz and its three hydroxy metabolites.  

PubMed

Uridine 5'-diphosphate-glucuronosyltransferases (UGTs) involved in the glucuronide formation of efavirenz (EFV) and its three hydroxy metabolites, 8-hydroxyefavirenz (8-OH EFV), 7-hydroxyefavirenz (7-OH EFV), and 8,14-dihydroxyefavirenz (8,14-diOH EFV), were assessed. Among 12 recombinant UGT isoforms tested, only UGT2B7 showed catalytic activity in the formation of EFV-N-glucuronide (EFV-G) as previously reported. On the other hand, almost all UGT isoforms were involved in the glucuronidation of the three hydroxy metabolites, although their relative contribution is unclear. The catalytic activities in the formation of EFV-G by 17 different human liver microsomes exhibit a more than 40-fold inter-individual variability, whereas those of glucuronidation of the three hydroxy metabolites showed almost identical activity. The formation of EFV-G showed a significant correlation (r?=?0.920; p?glucuronidation in 17 different human liver microsomes. Furthermore, fluconazole, a known UGT2B7 inhibitor, potently inhibited the formation of EFV-G up to 80%. This suggests that EFV might be a specific UGT2B7 substrate in vitro. This is the first study identifying specific UGT isozymes that glucuronidate EFV and its three hydroxy metabolites. Continued identification and characterisation of these pathways may help reduce adverse effects such as CNS toxicity in EFV therapy. PMID:21319958

Bae, S K; Jeong, Y-J; Lee, C; Liu, K-H

2011-06-01

54

Disposition and pharmacology of propofol glucuronide administered intravenously to animals.  

PubMed

1. Propofol glucuronide (PG) is the major human metabolite of the i.v. anaesthetic propofol, 2,6-diisopropylphenol. 2. Bolus i.v. doses of 14C-PG (1 mg/kg) to rat and dog were eliminated in urine (40 and 66% respectively) and faeces (48 and 19%); 25 and 48% of the dose were excreted unchanged in urine. 3. In dog, PG was distributed from plasma (t 1/2 4 min) into a volume equivalent to extracellular water and eliminated with t 1/2 80 min. Total body clearance was 1.8 ml/min per kg, and renal clearance about 20% GFR. In rat, plasma 14C concentrations were about one-tenth those in dog, thus PG levels were not quantified. 4. Propofol was not detected in the plasma showing that PG is hydrolytically stable. Enterohepatic circulation of PG occurred in rat and to a lesser extent in dog. Metabolites, mainly side-chain hydroxylation products, were evident in both species from 4 h after dosing. 5. Bolus i.v. doses of PG (200 mg/kg) showed no hypnotic activity in mice. PMID:1492419

Simons, P J; Cockshott, I D; Glen, J B; Gordon, E A; Knott, S; Ruane, R J

1992-11-01

55

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

PubMed

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

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

2014-06-14

56

Molecular Structure of Ethyl maltol  

NSDL National Science Digital Library

Ethyl maltol was discovered in the 1970s. It was originally isolated from larch tree bark and is produced through fermentation-organic synthesis. Ethyl maltol occurs naturally in cereal, bread crust, coffee, and cocoa. This substance is also used as a flavor enhancer because it tends to mask bad tasting chemicals, and heightens richness and creaminess. The compound has been employed as a flavor enhancer in wine, chocolate, vanilla, fruit flavored drinks, pastries, candy, tobacco, cosmetics, and medicines.

2002-10-11

57

An orphan esterase ABHD10 modulates probenecid acyl glucuronidation in human liver.  

PubMed

Probenecid, a widely used uricosuric agent, is mainly metabolized to probenecid acyl glucuronide (PRAG), which is considered a causal substance of severe allergic or anaphylactoid reactions. PRAG can be hydrolyzed (deglucuronidated) to probenecid. The purpose of this study was to identify enzymes responsible for probenecid acyl glucuronidation and PRAG deglucuronidation in human livers and to examine the effect of deglucuronidation in PRAG formation. In human liver homogenates (HLHs), the intrinsic clearance (CLint) of PRAG deglucuronidation was much greater (497-fold) than that of probenecid acyl glucuronidation. Evaluation of PRAG formation by recombinant UDP-glucuronosyltransferase (UGT) isoforms and an inhibition study using HLHs as an enzyme source demonstrated that multiple UGT isoforms, including UGT1A1, UGT1A9, and UGT2B7, catalyzed probenecid acyl glucuronidation. We found that recombinant ?/? hydrolase domain containing 10 (ABHD10) substantially catalyzed PRAG deglucuronidation activity, whereas carboxylesterases did not. Similar inhibitory patterns by chemicals between HLHs and recombinant ABHD10 supported the major contribution of ABHD10 to PRAG deglucuronidation in human liver. Interestingly, it was demonstrated that the CLint value of probenecid acyl glucuronidation in HLHs was increased by 1.7-fold in the presence of phenylmethylsulfonyl fluoride, which potently inhibited ABHD10 activity. In conclusion, we found that PRAG deglucuronidation catalyzed by ABHD10 suppressively regulates PRAG formation via multiple UGT enzymes in human liver. The balance of activities by these enzymes is important for the formation of PRAG, which may be associated with the adverse reactions observed after probenecid administration. PMID:25217485

Ito, Yusuke; Fukami, Tatsuki; Yokoi, Tsuyoshi; Nakajima, Miki

2014-12-01

58

Direct analysis of glucuronides with liquid chromatography-mass spectrometric techniques and methods.  

PubMed

Glucuronidation is one of the main phase II metabolic reactions in humans and animals. A variety of analytical techniques and methods have been used for the detection and quantification of glucuronides of both endogenous and xenobiotic compounds from different biological samples of humans and animals. Drug metabolism has been extensively studied with both in vitro and in vivo experiments under various conditions. The purpose of this review is to explore in detail the benefits and drawbacks of different liquid chromatography-mass spectrometric (LC/MS) methods and techniques in detection and identification of all forms of glucuronide conjugates from in vitro, biological, and environmental samples. The entire analytical procedure is covered, from sample treatment, separation, and ionization to qualitative and quantitative analyses. The aim of this review is not to cover every published paper where glucuronides are identified and/or quantified, but rather to focus on special cases where a new analytical approach or technical development has led to a better, more specific, or more comprehensive detection, identification, or quantitation of glucuronide conjugates. PMID:20575759

Ketola, Raimo A; Hakala, Kati S

2010-09-01

59

Separation and Purification of Two Flavone Glucuronides from Erigeron multiradiatus (Lindl.) Benth with Macroporous Resins  

PubMed Central

Scutellarein-7-O-?-D-glucuronide (SG) and apigenin-7-O-?-D-glucuronide (AG) are two major bioactive constituents with known pharmacological effects in Erigeron multiradiatus. In this study, a simple method for preparative separation of the two flavone glucuronides was established with macroporous resins. The performance and adsorption characteristics of eight macroporous resins including AB-8, HPD100, HPD450, HPD600, D100, D101, D141, and D160 have been evaluated. The results confirmed that D141 resin offered the best adsorption and desorption capacities and the highest desorption ratio for the two glucuronides among the tested resins. Sorption isotherms were constructed for D141 resin under optimal ethanol conditions and fitted well to the Freundlich and Langmuir models (R2 > 0.95). Dynamic adsorption and desorption tests was performed on column packed with D141 resin. After one-run treatment with D141 resin, the two-constituent content in the final product was increased from 2.14% and 1.34% in the crude extract of Erigeron multiradiatus to 24.63% and 18.42% in the final products with the recoveries of 82.5% and 85.4%, respectively. The preparative separation of SG and AG can be easily and effectively achieved via adsorption and desorption on D141 resin, and the method developed can be referenced for large-scale separation and purification of flavone glucuronides from herbal raw materials. PMID:19918373

Zhang, Zhi-feng; Liu, Yuan; Luo, Pei; Zhang, Hao

2009-01-01

60

Glucuronides in mussel Mytilus galloprovincialis as a possible biomonitor of environmental carcinogens.  

PubMed

1. The in vitro incubation of mussel digestive gland with 1 mM aminofluorene resulted in the formation of glucuronides that (a) became mutagenic with carp liver S9, and (b) liberated S9-dependent mutagenic aglucones after beta-glucuronidase treatment. 2. Natural populations of mussels from unpolluted and polluted sites, as well as mussels exposed to 3 ppm of aminofluorene or to used engine oil, did not accumulate detectable amounts of premutagens, mutagens, or mutagenic glucuronides/aglucones either in digestive gland tissue or in shell-cavity water. 3. The mutagenicity testing of mussel's glucuronides/aglucones does not seem to be useful as a biomonitor of environmental carcinogens. PMID:2565191

Kurelec, B; Krca, S

1989-01-01

61

A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1 receptors.  

PubMed

Recently, hydroxylated metabolites of JWH-018, a synthetic cannabinoid found in many K2/Spice preparations, have been shown to retain affinity and activity for cannabinoid type 1 receptors (CB1Rs). The activity of glucuronidated metabolites of JWH-018 is not known; hence, this study investigated the affinity and activity of a major metabolite, JWH-018-N-(5-hydroxypentyl) ?-D-glucuronide (018-gluc), for CB1Rs. The 018-gluc binds CB1Rs (K(i) = 922 nM), has no effect on G-protein activity, but antagonizes JWH-018 activity at CB1Rs. The data suggests that hydroxylation by cytochrome P450s and subsequent glucuronidation by UDP-glucuronosyltransferases produces a metabolite, 018-gluc, which possesses antagonistic activity at CB1Rs. PMID:22404317

Seely, Kathryn A; Brents, Lisa K; Radominska-Pandya, Anna; Endres, Gregory W; Keyes, Gregory S; Moran, Jeffery H; Prather, Paul L

2012-04-16

62

Steroid and steroid glucuronide profiles in urine during pregnancy determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.  

PubMed

An ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS) method was developed for the analysis of steroids and their glucuronides in urine samples. The method provides high sensitivity and fast analysis, as both steroids and their glucuronides can be analyzed directly without hydrolysis or complex sample preparation. The method was applied in profiling of targeted and nontargeted steroids and steroid glucuronides during pregnancy. The concentrations of 11 of 27 targeted steroids and steroid glucuronides and the concentrations of 25 nontargeted steroid glucuronides increased about 10-400 fold during the pregnancy. The concentrations of most of these 36 compounds began to increase in the first days of the pregnancy, increased gradually during the pregnancy, achieved a maximum in late pregnancy, and decreased sharply after delivery. Exceptionally, the concentrations of allopregnanolone and 17-hydroxypregnenolone started to increase later than those of the other steroids. Moreover, the concentrations of E2 glucuronides began to decrease one week before the delivery, in contrast to most of the steroids and steroid glucuronides, whose concentrations dropped sharply during the delivery. Concentrations of 34 compounds decreased noticeably when the subject was on sick leave owing a series of painful contractions. The results suggest that steroids and especially steroid glucuronides may provide a valuable diagnostic tool to follow the course of pregnancy. PMID:24176505

Jäntti, Sirkku E; Hartonen, Minna; Hilvo, Mika; Nygren, Heli; Hyötyläinen, Tuulia; Ketola, Raimo A; Kostiainen, Risto

2013-11-13

63

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

PubMed

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

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

2013-12-01

64

Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytes.  

PubMed

In a previous study, we used human liver microsomes for the first time to study cytochrome P450 (P450)-mediated oxidation of the flavonoid galangin. The combination of CYP1A2 and CYP2C9 produced a V(max)/K(m) value of 13.6 +/- 1.1 microl/min/mg of protein. In the present extended study, we determined glucuronidation rates for galangin with the same microsomes. Two major and one minor glucuronide were identified by liquid chromatography/mass spectrometry. The V(max)/K(m) values for the two major glucuronides conjugated in the 7- and 3-positions were 155 +/- 30 and 427 +/- 26 microl/min/mg of protein, thus, exceeding that of oxidation by 11 and 31 times, respectively. This highly efficient glucuronidation appeared to be catalyzed mainly by the UDP-glucuronosyltransferase (UGT)1A9 isoform but also by UGT1A1 and UGT2B15. Sulfation of galangin by the human liver cytosol, mediated mainly but not exclusively by sulfotransferase (SULT) 1A1, also appeared to be efficient. These conclusions were strongly supported by experiments using the S9 fraction of the human liver, in which all three metabolic pathways could be directly compared. When galangin metabolism was examined in fresh plated hepatocytes from six donors, glucuronidation clearly predominated followed by sulfation. Oxidation occurred only to a minor extent in two of the donors. This study for the first time establishes that glucuronidation and sulfation of galangin, and maybe other flavonoids, are more efficient than P450-mediated oxidation, clearly being the metabolic pathways of choice in intact cells and therefore likely also in vivo. PMID:11950790

Otake, Yoko; Hsieh, Faye; Walle, Thomas

2002-05-01

65

Atmospheric chemistry of ethyl propionate.  

PubMed

Ethyl propionate is a model for fatty acid ethyl esters used as first-generation biodiesel. The atmospheric chemistry of ethyl propionate was investigated at 980 mbar total pressure. Relative rate measurements in 980 mbar N(2) at 293 ± 0.5 K were used to determine rate constants of k(C(2)H(5)C(O)OC(2)H(5) + Cl) = (3.11 ± 0.35) × 10(-11), k(CH(3)CHClC(O)OC(2)H(5) + Cl) = (7.43 ± 0.83) × 10(-12), and k(C(2)H(5)C(O)OC(2)H(5) + OH) = (2.14 ± 0.21) × 10(-12) cm(3) molecule(-1) s(-1). At 273-313 K, a negative Arrhenius activation energy of -3 kJ mol(-1) is observed.. The chlorine atom-initiated oxidation of ethyl propionate in 980 mbar N(2) gave the following products (stoichiometric yields): ClCH(2)CH(2)C(O)OC(2)H(5) (0.204 ± 0.031), CH(3)CHClC(O)OC(2)H(5) (0.251 ± 0.040), and C(2)H(5)C(O)OCHClCH(3) (0.481 ± 0.088). The chlorine atom-initiated oxidation of ethyl propionate in 980 mbar of N(2)/O(2) (with and without NO(x)) gave the following products: ethyl pyruvate (CH(3)C(O)C(O)OC(2)H(5)), propionic acid (C(2)H(5)C(O)OH), formaldehyde (HCHO), and, in the presence of NO(x), PAN (CH(3)C(O)OONO(2)). The lack of acetaldehyde as a product suggests that the CH(3)CH(O)C(O)OC(2)H(5) radical favors isomerization over decomposition. From the observed product yields, we conclude that H-abstraction by chlorine atoms from ethyl propionate occurs 20.4 ± 3.1%, 25.1 ± 4.0%, and 48.1 ± 8.8% from the CH(3)-, -CH(2)-, and -OCH(2)- groups, respectively. The rate constant and branching ratios for the reaction between ethyl propionate and the OH radical were investigated theoretically using quantum mechanical calculations and transition state theory. The stationary points along the reaction path were optimized using the CCSD(T)-F12/VDZ-F12//BH&HLYP/aug-cc-pVTZ level of theory; this model showed that OH radicals abstract hydrogen atoms primarily from the -OCH(2)- group (80%). PMID:22524192

Andersen, Vibeke F; Ørnsø, Kristian B; Jørgensen, Solvejg; Nielsen, Ole John; Johnson, Matthew S

2012-05-31

66

21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.  

Code of Federal Regulations, 2013 CFR

...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,...

2013-04-01

67

Diclofenac acyl glucuronide, a major biliary metabolite, is directly involved in small intestinal injury in rats  

Microsoft Academic Search

Background & Aims: Enterohepatic recirculation of nonsteroidal anti-inflammatory drugs is a critical factor in the pathogenesis of intestinal injury, but the underlying mechanism of toxicity remains obscure. The aim of this study was to examine the role of diclofenac acyl glucuronide, which is the major biliary metabolite and is chemically reactive, in the precipitation of small intestinal ulceration. Methods: Hepatocanalicular

Sven Seitz; Urs A. Boelsterli

1998-01-01

68

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...

69

Glucuronidation of bile acids by rat liver 3-OH androgen UDP-glucuronyltransferase.  

PubMed

The glucuronidation of bile acids is an important pathway for the detoxification and elimination of retained bile acids during cholestasis. A 3-OH-specific androgen UDP-glucuronyltransferase was purified from solubilized female rat liver microsomes using Chromatofocusing and UDP- hexanolamine -Sepharose 4B affinity chromatography. The purified 3-OH androgen UDP-glucuronyltransferase is reactive towards bile acids, including lithocholic acid, deoxycholic acid, and ursodeoxycholic acid, in addition to the androgenic steroids etiocholanolone and androsterone. The highest activity towards bile acids is seen with lithocholic acid-24-methyl ester, and no activity is seen with lithocholic acid-3 alpha-sulfate or 5 beta- cholanic acid-3-one. No glucuronidation activity towards bile acids was observed with either a purified 17-OH steroid UDP-glucuronyltransferase or a p-nitrophenol-UDP-glucuronyltransferase. Lithocholic acid competitively inhibits etiocholanolone glucuronidation by the purified 3-OH androgen isoenzyme. These results suggest that a UDP-glucuronyltransferase isoenzyme is present in female rat liver which is capable of specifically glucuronidating the 3-OH group of bile acids and androgenic steroids. PMID:6427209

Kirkpatrick, R B; Falany, C N; Tephly, T R

1984-05-25

70

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

Microsoft Academic Search

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

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

1999-01-01

71

Separation and characterization of carboxyl-linked glucuronides of bile acids in incubation mixture of rat liver microsomes.  

PubMed

The carboxyl-linked 24-glucuronides of common bile acids have been identified by means of liquid chromatography (LC)/atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) in an incubation mixture with a male Wistar rat liver microsomal fraction. The authentic specimens of bile acid 24-glucuronide acetate-methyl esters were synthesized unequivocally using the Mitsunobu reaction, and the APCI-mass spectrometric properties of these glucuronide derivatives were also characterized. After incubation of common unconjugated bile acids with hepatic microsomes, glucuronides were extracted and purified with a Sep-Pak C18 cartridge and lipophilic ion exchange gel, piperidino-hydroxypropyl Sephadex LH-20, and then derivatized into the acetate-methyl esters. Subsequent resolution into alpha- and beta-isomers at the glucuronosyl linkage was attained by LC on Cosmosil 5C8 and Sumichiral OA-2500 columns using 200 mM ammonium acetate (pH 7.0)-methanol (1:4, v/v), where 24-glucuronides were monitored with characteristic positive ions [M + NH4]+. The 24-glucuronides of lithocholic, chenodeoxycholic, deoxycholic, ursodeoxycholic and cholic acid were definitely characterized, in contrast to no formation of corresponding 3-glucuronides. PMID:9589552

Goto, J; Murao, N; Nakada, C; Motoyama, T; Oohashi, J; Yanagihara, T; Niwa, T; Ikegawa, S

1998-04-01

72

Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity  

PubMed Central

Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 ?M in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

2013-01-01

73

Mitochondrial Dysfunction Leads to Deconjugation of Quercetin Glucuronides in Inflammatory Macrophages  

PubMed Central

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

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

2013-01-01

74

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

PubMed Central

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

Dong, Jennifer Q.

2009-01-01

75

Structure of ethyl phenyl selenone.  

PubMed

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

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

1993-03-15

76

Determination of steroids and their intact glucuronide conjugates in mouse brain by capillary liquid chromatography-tandem mass spectrometry.  

PubMed

A method for the identification and quantitation of 10 brain steroids and their 2 sulfate and 9 glucuronide conjugates in mouse brain tissues was developed and validated. The method includes the extraction of homogenized brain by solid-phase extraction and the analysis of the extracts by capillary liquid chromatography-tandem mass spectrometry. The main advantage of the method is that steroid conjugates in brain can be analyzed as intact compounds, without derivatization, hydrolysis, or complex sample preparation procedures; thus, the true identity of the conjugates can be confirmed with tandem mass spectrometric detection. The method was validated to show its linearity (r > 0.998) and precision (<9%). The limits of detection in solution were from 6 to 80 pmol/L for steroid glucuronides, from 13 to 32 pmol/L for steroid sulfates, and from 26 pmol/L to 2.2 nmol/L for native steroids. The recovery of internal standards was 95% for d3-testosterone glucuronide and 69% for d4-allopregnanolone from spiked mouse hippocampus. Brain tissue samples from mouse hippocampus and hypothalamus were analyzed using the new method. Several steroids and glucuronides were identified and quantified from the mouse brain at concentration levels of 0.2-58 ng/g. The concentrations of steroid glucuronides were significant compared to those of their aglycons, indicating that glucuronidation might be an important metabolic pathway for some steroids in the mouse brain. The method developed in this study provides for the first time direct quantitative determination of steroids and their glucuronides and sulfates in brain without hydrolysis and, therefore, creates the possibility to study in detail the role of steroid glucuronidation and sulfation in the brain. PMID:20345173

Jäntti, Sirkku E; Tammimäki, Anne; Raattamaa, Helena; Piepponen, Petteri; Kostiainen, Risto; Ketola, Raimo A

2010-04-15

77

Nitrosation of glycine ethyl ester and ethyl diazoacetate to give the alkylating agent and mutagen ethyl chloro(hydroximino)acetate.  

PubMed

Whereas nitrosation of secondary amines produces nitrosamines, amino acids with primary amino groups and glycine ethyl ester were reported to react with nitrite to give unidentified agents that alkylated 4-(p-nitrobenzyl)pyridine to produce purple dyes and be direct mutagens in the Ames test. We report here that treatment of glycine ethyl ester at 37 degrees C with excess nitrite acidified with HCl, followed by ether extraction, gave 30-40% yields of a product identified as ethyl chloro(hydroximino)acetate [ClC(=NOH)COOEt, ECHA] and a 9% yield of ethyl chloroacetate. The ECHA was identical to that synthesized by a known method from ethyl acetoacetate, strongly alkylated nitrobenzylpyridine, and may have arisen by N-nitrosation of glycine ethyl ester to give ethyl diazoacetate, which was C-nitrosated and reacted with chloride to give ECHA. Nitrosation of ethyl diazoacetate also yielded ECHA. Ethyl nitroacetate was not an intermediate as its nitrosation did not produce ECHA. ECHA reacted with aniline to give ethyl (hydroxamino)(phenylimino)acetate [PhN=C(NHOH)CO2Et]. This product was different from ethyl [(phenylamino)carbonyl]carbamate [PhNHC(=O)NHCO2Et], which was synthesized by reacting ethyl isocyanatoformate (OCN.CO2Et) with aniline. ECHA reacted with guanosine to give a derivative, which may have been a guanine-C(=NOH)CO2Et derivative. ECHA showed moderate toxicity and weak but significant mutagenicity without activation in Salmonella typhimurium TA-100 (mean, 1.31 x control value for 12-18 microg/plats) and for V79 mammalian cells (1.5-1.7 x control value for 60-100 microM). In conclusion, gastric nitrosation of glycine derivatives such as peptides with a N-terminal glycine might produce ECHA analogues that alkylate bases of gastric mucosal DNA and thereby initiate gastric cancer. PMID:15025513

Zhou, Lin; Haorah, James; Chen, Sheng C; Wang, Xiaojie; Kolar, Carol; Lawson, Terence A; Mirvish, Sidney S

2004-03-01

78

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

SciTech Connect

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.

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

1984-11-01

79

A new oleanene glucuronide obtained from the aerial parts of Melilotus officinalis.  

PubMed

A new oleanene glucuronide called melilotus-saponin O2 (1) was isolated together with three known ones (soyasaponin I, astragaloside VIII, wistariasaponin D) from the aerial parts of Melilotus officinalis (L.) Pallas (Leguminosae). The structure of 1 was determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl- (1-->2)-beta-D-glucuronopyranosyl melilotigenin by spectroscopic and chemical methods. PMID:10705521

Hirakawa, T; Okawa, M; Kinjo, J; Nohara, T

2000-02-01

80

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

PubMed

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

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

1998-03-01

81

Formation of three types of glucuronides of 6-hydroxy bile acids by rat liver microsomes  

Microsoft Academic Search

The glucuronidation of 6-hydroxylated bile acids by rat liver microsomes was studied in vitro; for comparison, several major bile acids lacking a hydroxyl group in position 6 were also investigated. The highest reaction rates were found for lithocholic and deoxycholic acid (10.2 * 0.2 and 7.3 f 1.4 nmol\\/mg min, respectively); our results for these substrates agree well with pub-

Piotr Zimniak; Anna Radominska; Marta Zimniak; Roger Lester

82

Morphine6Glucuronide: Morphine??s Successor for Postoperative Pain Relief?  

Microsoft Academic Search

In searching for an analgesic with fewer side effects than morphine, examination of morphine's active metabolite, morphine-6-glucuronide (M6G), sug- gests that M6G is possibly such a drug. In contrast to morphine, M6G is not metabolized but excreted via the kidneys and exhibits enterohepatic cycling, as it is a substrate for multidrug resistance transporter pro- teins in the liver and intestines.

Eveline L. A. van Dorp; Raymonda Romberg; Elise Sarton; James G. Bovill; Albert Dahan

2006-01-01

83

?-Glucuronidase activity and mitochondrial dysfunction: the sites where flavonoid glucuronides act as anti-inflammatory agents  

PubMed Central

Epidemiological and experimental studies suggest that the consumption of flavonoid-rich diets decreases the risk of various chronic diseases such as cardiovascular diseases. Although studies on the bioavailability of flavonoids have been well-characterized, the tissue and cellular localizations underlying their biological mechanisms are largely unknown. The development and application of novel monoclonal antibodies revealed that macrophages could be the major target of dietary flavonoids in vivo. Using macrophage-like cell lines in vitro, we examined the molecular basis of the interaction between the macrophages and flavonoids, especially the glucuronide metabolites. We have found that extracellular ?-glucuronidase secreted from macrophages is essential for the bioactivation of the glucuronide conjugates into the aglycone, and that the enzymatic activity, which requires an acidic pH, is promoted by the increased secretion of lactate in response to the mitochondrial dysfunction. This review describes our recent findings indicating the molecular mechanisms responsible for the anti-inflammatory activity of dietary flavonoids within the inflammation sites. We propose that the extracellular activity of ?-glucuronidase associated with the status of the mitochondrial function in the target cells might be important biomarkers for the specific sites where the glucuronides of dietary flavonoids can act as anti-atherosclerotic and anti-inflammatory agents in vivo. PMID:24895476

Kawai, Yoshichika

2014-01-01

84

Mechanism of biosynthesis of thio-?-d-glucuronides and thio-?-d-glucosides  

PubMed Central

1. The thio-?-d-glucosiduronic acids (thio-?-glucuronides) of o-aminothiophenol, diethyldithiocarbamic acid, p-nitrothiophenol and thiophenol are formed biosynthetically in broken- and intact-cell preparations of mouse liver. 2. For this biosynthesis to occur in homogenates or microsomal fractions, UDP-glucuronic acid was required during incubation; glucose, glucuronic acid or UDP could not replace it. UDP was a product of the reaction. 3. The biosynthetic mechanism linking glucuronic acid to thiol and carbodithioic groups therefore requires UDP-glucuronyltransferase activity and resembles that forming the various types of O-glucuronides. 4. An analogous enzymic mechanism employing UDP-glucose synthesizes the thio-?-d-glucosides of diethyldithiocarbamic acid and thiophenol in gut preparations of the mollusc Arion ater; this mechanism resembles that forming the O-glucosides. The thio-?-d-glucosides are formed also in intact cells. 5. As expected from the distribution of O-glycosides, S-glucuronides of these aglycones were not detectable with the invertebrate, nor were the S-glucosides with the vertebrate. 6. Despite their similar biosyntheses, S- and O-?-glycosides differ in susceptibility to hydrolysis by ?-glycosidases. Rat preputial-gland ?-glucuronidase hydrolysed thioglucuronides of o-aminothiophenol, diethyldithiocarbamic acid and p-nitrothiophenol, hydrolysis being inhibited by glucarolactone; the thioglucuronide of thiophenol was not hydrolysed by preputial-gland or liver ?-glucuronidase. The two S-glucosides resisted hydrolysis by ?-glucosidase from almond emulsin. PMID:4658987

Dutton, G. J.; Illing, H. P. A.

1972-01-01

85

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation.  

PubMed

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo. PMID:2863100

Griffeth, L K; Rosen, G M; Rauckman, E J

1985-01-01

86

Molecular Structure of Ethyl acetate  

NSDL National Science Digital Library

Ethyl acetate is a colorless, volatile liquid with a mild and fragrant odor. It is used as solvent in chemistry laboratories but can also be found in many household products such as paints, coatings, and adhesives. The compound is also used in some extraction processes such as decaffeination or purification of antibiotics. It is present in both nail polish and removers. Some synthetic fruit essences may contain this and other esters. Etymologists like to use this solvent for insect collecting as the vapor kill the insect quickly and keep it soft for mounting.

2006-03-08

87

Mechanism of peroxisome proliferator-activated receptor gamma (PPAR?) transactivation by hesperetin glucuronides is distinct from that by a thiazolidine-2,4-dione agent.  

PubMed

Hesperidin, a flavanone glycoside present abundantly in citrus fruits, is predominantly metabolized to hesperetin-7-O-?-D-glucuronide (H7-OG) and hesperetin-3'-O-?-D-glucuronide (H3'-OG), which exhibit partial agonistic activity towards peroxisome proliferator-activated receptor gamma (PPAR?). Here, in order to understand the mechanism(s) of action of PPAR? transactivation elicited by hesperetin glucuronides, we compared the transactivation activities of PPAR? (ligand-binding domain (LBD)) mutants by hesperetin glucuronides and troglitazone, a thiazolidine-2,4-dione class PPAR? full agonist. The assay results indicated that the mechanisms of activation of PPAR? by hesperetin glucuronides and by troglitazone are distinct, probably due to a difference in the binding sites of these compounds on the PPAR? LBD. Flavanone-class PPAR? partial agonists, luteolin and hesperetin glucuronides, showed similar activation profiles of the PPAR? LBD mutants, even though they have different side chain functionalities. PMID:24789933

Gamo, Kanae; Shiraki, Takuma; Matsuura, Nobuyasu; Miyachi, Hiroyuki

2014-01-01

88

Simultaneous Quantification of Free and Glucuronidated Cannabinoids in Human Urine by Liquid Chromatography-Tandem Mass Spectrometry  

PubMed Central

Background Cannabis is the most commonly abused drug of abuse and is commonly quantified during urine drug testing. We conducted a controlled drug administration studies investigating efficacy of urinary cannabinoid glucuronide metabolites for documenting recency of cannabis intake and for determining stability of urinary cannabinoids. Methods A liquid chromatography tandem mass spectrometry method was developed and validated quantifying ?9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide and THCCOOH-glucuronide in 0.5 ml human urine via supported-liquid extraction. Chromatography was performed on an Ultra Biphenyl column with a gradient of 10 mmol/l ammonium acetate, pH 6.15 and 15% methanol in acetonitrile at 0. 4ml/min. Analytes were monitored by positive and negative mode electrospray ionization and multiple reaction monitoring mass spectrometry. Results Linear ranges were 0.5–50 ng/ml for THC-glucuronide, 1–100 ng/ml for THCCOOH, 11-OH-THC and cannabidiol, 2–100 ng/ml for THC and cannabinol, and 5–500 ng/ml for THCCOOH-glucuronide (R2>0.99). Mean extraction efficiencies were 34–73% with analytical recovery (bias) 80.5–118.0% and total imprecision 3.0–10.2% coefficient of variation. Conclusion This method simultaneously quantifies urinary cannabinoids and phase II glucuronide metabolites, and enables evaluation of urinary cannabinoid glucuronides for documenting recency of cannabis intake and cannabinoid stability. The assay is applicable for routine urine cannabinoid testing. PMID:22771478

Scheidweiler, Karl B.; Desrosiers, Nathalie A.; Huestis, Marilyn A.

2012-01-01

89

Mechanism of biosynthesis of thio- -D-glucuronides and thio- -D-glucosides.  

PubMed

1. The thio-beta-d-glucosiduronic acids (thio-beta-glucuronides) of o-aminothiophenol, diethyldithiocarbamic acid, p-nitrothiophenol and thiophenol are formed biosynthetically in broken- and intact-cell preparations of mouse liver. 2. For this biosynthesis to occur in homogenates or microsomal fractions, UDP-glucuronic acid was required during incubation; glucose, glucuronic acid or UDP could not replace it. UDP was a product of the reaction. 3. The biosynthetic mechanism linking glucuronic acid to thiol and carbodithioic groups therefore requires UDP-glucuronyltransferase activity and resembles that forming the various types of O-glucuronides. 4. An analogous enzymic mechanism employing UDP-glucose synthesizes the thio-beta-d-glucosides of diethyldithiocarbamic acid and thiophenol in gut preparations of the mollusc Arion ater; this mechanism resembles that forming the O-glucosides. The thio-beta-d-glucosides are formed also in intact cells. 5. As expected from the distribution of O-glycosides, S-glucuronides of these aglycones were not detectable with the invertebrate, nor were the S-glucosides with the vertebrate. 6. Despite their similar biosyntheses, S- and O-beta-glycosides differ in susceptibility to hydrolysis by beta-glycosidases. Rat preputial-gland beta-glucuronidase hydrolysed thioglucuronides of o-aminothiophenol, diethyldithiocarbamic acid and p-nitrothiophenol, hydrolysis being inhibited by glucarolactone; the thioglucuronide of thiophenol was not hydrolysed by preputial-gland or liver beta-glucuronidase. The two S-glucosides resisted hydrolysis by beta-glucosidase from almond emulsin. PMID:4658987

Dutton, G J; Illing, H P

1972-09-01

90

In Vitro Glucuronidation of Fenofibric Acid by Human UDP-Glucuronosyltransferases and Liver Microsomes  

PubMed Central

Fenofibric acid (FA), the active moiety of fenofibrate, is an agonist of the peroxisome proliferator-activated nuclear receptor ? that modulates triglyceride and cholesterol profiles. Lipid response to fenofibrate and FA serum concentrations is highly variable. Although FA is reported to be almost exclusively inactivated by UDP-glucuronosyltransferases (UGTs) into FA-glucuronide (FA-G), the contribution of UGT isoenzymes has never been systematically assessed. Heterologously expressed human UGT1A and UGT2B and their coding variants were tested for FA glucuronidation using liquid chromatography/mass spectrometry. Recombinant UGT2B7 presented the highest Vmax/Km value (2.10 ?l/min/mg), 16-fold higher than the activity of other reactive UGTs, namely, UGT1A3, UGT1A6, and UGT1A9 (0.13, 0.09, and 0.02 ?l/min/mg, respectively). UGT2B7.1 (His268) and UGT2B7.2 (Tyr268) enzyme activity was similar, whereas UGT1A3.2 (R11A47), UGT1A3.3 (Trp11), and UGT1A9.3 (Thr33) showed 61 to 96% reduced Vmax/Km values compared with the respective (1) reference proteins. FA-G formation by a human liver bank (n = 48) varied by 10-fold, but the rate of formation was not associated with common genetic variations in UGT1A3, UGT1A6, UGT1A9, and UGT2B7. Correlation with activities for the probe substrates zidovudine (UGT2B7; r2 = 0.75), mycophenolic acid (UGT1A9; r2 = 0.42), fulvestrant (UGT1A3; r2 = 0.36), but not serotonin (UGT1A6; r2 = 0.06) indicated a primary role for UGT2B7 and lesser roles of UGT1A9 and UGT1A3 in hepatic FA glucuronidation. This was confirmed by a strong correlation of FA-G formation with UGT2B7 protein content and inhibition by fluconazole, a known UGT2B7 selective inhibitor. Additional studies are required to identify genetic factors contributing to the observed FA glucuronidation variability. PMID:19661212

Tojcic, Jelena; Benoit-Biancamano, Marie-Odile; Court, Michael H.; Straka, Robert J.; Caron, Patrick

2009-01-01

91

Characterisation and identification of the human N +-glucuronide metabolite of cediranib  

Microsoft Academic Search

Cediranib (4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline; RECENTIN™), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) of all three VEGF receptors, is currently in Phase III clinical trials for the first-line treatment of colorectal cancer and the treatment of recurrent glioblastoma.During its clinical development a unique human metabolite, an N+-glucuronide, was identified as a major circulating metabolite and one of the major metabolites

Eva M. Lenz; Michael Spear; C. Drake; Christopher R. J. Pollard; Michelle Ward; Timothy Schulz-Utermoehl; Mike Harrison

2010-01-01

92

Glucuronidation of tobacco-specific nitrosamines by UGT2B10.  

PubMed

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important tobacco-specific nitrosamine (TSNA) in the etiology of tobacco-related cancers, and N-glucuronidation is an important mechanism of NNAL detoxification. In the present study, an analysis of the UDP-glucuronosyltransferases (UGTs) responsible for the N-glucuronidation of the TSNAs N'-nitrosonornicotine, N'-nitrosoanabasine, and N'-nitrosoanatabine was performed. Using human embryonic kidney 293 cells overexpressing UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, and UGT2B17, only UGT1A4 and UGT2B10 exhibited N-glucuronidating activity against these TSNAs. The K(M)s for UGT2B10 were 15 to 22-fold lower than those of UGT1A4 against the three TSNAs and were similar to those observed for microsomes prepared from human liver specimens. The overall activity of UGT2B10 was 3.6 to 27-fold higher than UGT1A4 against the three TSNAs as determined by V(max)/K(M) after normalization by levels of UGT2B10 versus UGT1A4 mRNA. Similarly high levels of activity were also observed for UGT2B10 against a fourth TSNA, NNAL, exhibiting a 6.3-fold lower K(M) and 3-fold higher normalized V(max)/K(M) than that observed for UGT1A4. Real-time polymerase chain reaction analysis showed that UGT2B10 was expressed at a level that, on average, was 26% higher than that observed for UGT1A4 in a screening of normal liver tissue specimens from 20 individual subjects. These data suggest that UGT2B10 is likely the most active UGT isoform in human liver for the N-glucuronidation of TSNAs. PMID:18238858

Chen, Gang; Dellinger, Ryan W; Sun, Dongxiao; Spratt, Thomas E; Lazarus, Philip

2008-05-01

93

In vitro glucuronidation of Armillarisin A: UDP-glucuronosyltransferase 1A9 acts as a major contributor and significant species differences.  

PubMed

1. This study is performed to investigate liver microsomal glucuronidation of Armillarisin A (A.A), an effective cholagogue drug, aiming at characterizing the involved UDP-glucuronosyltranferases (UGT) and revealing potential species differences. 2. A.A glucuronidation in human liver microsomes (HLM) generates one metabolite (M2) glucuronidated at the phenol hydroxyl group, obeying Michaelis-Menten kinetic model. Multiple isoforms including UGT1A1, 1A7, 1A9 and 2B15 can catalyze A.A glucuronidation. Kinetic assays and chemical inhibition studies both demonstrate that UGT1A9 is responsible for A.A glucuronidation in HLM. A.A glucuronidation in Cynomolgus monkey microsomes (CyLM) also follows Michaelis-Menten model, but can additionally catalyze the traced glucuronosyl substitution at the alcohol hydroxyl group (M1). The reactions in liver microsomes from Sprague-Dawley rats (RLM), ICR/CD-1 mouse (MLM), Beagle dog (DLM) all display biphasic kinetics and only M2 is detected. HLM, RLM and CyLM exhibit very similar catalytic activities towards A.A glucuronidation, with the intrinsic clearance values of respective 38, 37 and 37??L/min/mg, which are much higher than MLM and DLM. 3. This in vitro study indicates that UGT1A9 acts as a major contributor to A.A glucuronidation in human liver, and the reaction displays large species differences. PMID:24916899

Sun, Dongxue; Zhu, Liangliang; Xiao, Ling; Xia, Yangliu; Ge, Guangbo; Cao, Yunfeng; Wu, Yan; Yin, Jun; Yang, Ling

2014-11-01

94

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

PubMed

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

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

2014-01-01

95

Determination of tapentadol and tapentadol-O-glucuronide in human serum samples by UPLC-MS/MS.  

PubMed

Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action, MOR agonism and noradrenaline (NA) reuptake inhibition in a single molecule. It is the first member of a new therapeutic class, MOR-NRI. A high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantitative analysis of tapentadol and its O-glucuronide metabolite in human serum. Simultaneous quantification was deemed to be challenging because of the large difference in concentrations between tapentadol and its O-glucuronide metabolite in clinical samples. Therefore, a method was established using a common processed sample, but with different injection volumes and chromatographic conditions for each analyte. Tapentadol and tapentadol-O-glucuronide were determined by protein precipitation of 0.100ml of the samples with acetonitrile. The internal standards used are D6-tapentadol and D6-tapentadol-O-glucuronide. The validated concentration range was 0.200-200ng/ml (tapentadol) and 10.0-10,000ng/ml (tapentadol-O-glucuronide). Chromatographic separation was achieved by gradient elution on a Waters Acquity UPLC BEH C18 (1.7?m, 2.1×50mm) column, with mobile phase consisting of 0.01M ammonium formate (adjusted to pH 4 using formic acid) (A) and methanol (B). A separate injection was done for measurement of each analyte, with a different gradient and run time. The analytes were detected by using an electrospray ion source on a triple quadrupole mass spectrometer operating in positive ionization mode. The run time was 1.6min for tapentadol and 1.5min for tapentadol-O-glucuronide. The high sensitivity and acceptable performance of the assay allowed its application to the analysis of serum samples in clinical trials. The validated method was used for analysis of tapentadol in over 17,000 samples. PMID:25600054

Hillewaert, Vera; Pusecker, Klaus; Sips, Luc; Verhaeghe, Tom; de Vries, Ronald; Langhans, Manfred; Terlinden, Rolf; Timmerman, Philip

2015-02-15

96

Quantitative prediction of intestinal glucuronidation of drugs in rats using in vitro metabolic clearance data.  

PubMed

UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of nine UGT substrates (ketoprofen, tolcapone, telmisartan, raloxifene, entacapone, resveratrol, buprenorphine, quercetin, and ezetimibe) via UGT in intestinal microsomes (CL(int, UGT)) in rats. F(a)F(g) was calculated from pharmacokinetic parameters after intravenous and oral administration or using the portal-systemic concentration difference method, with values ranging from 0.027 (ezetimibe) to 1 (tolcapone). Glucuronides of model compounds were observed in the portal plasma after oral administration, with CL(int, UGT) values ranging from 57.8 (tolcapone) to 19,200 µL/min/mg (resveratrol). An inverse correlation between F(a)F(g) and CL(int, UGT) was observed for most compounds and was described using a simplified intestinal availability model reported previously. This model gave accurate predictions of F(a)F(g) values for three in-house compounds. Our results show that F(a)F(g) in rats is affected by UGT and can be predicted using CL(int, UGT). This work should hasten the development of a method to predict F(a)F(g) in humans. PMID:21970858

Furukawa, Takako; Nakamori, Fumihiro; Tetsuka, Kazuhiro; Naritomi, Yoichi; Moriguchi, Hiroyuki; Yamano, Katsuhiro; Terashita, Shigeyuki; Teramura, Toshio

2012-01-01

97

Process for the preparation of ethyl benzene  

DOEpatents

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.

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

1995-01-01

98

27 CFR 21.108 - Ethyl ether.  

Code of Federal Regulations, 2010 CFR

...FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific gravity at 15.56 °/15.56 °C. Not more than 0.728. [T.D. ATF-133,...

2010-04-01

99

Process for the preparation of ethyl benzene  

DOEpatents

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.

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

1995-12-19

100

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...

101

Discovery of dopamine glucuronide in rat and mouse brain microdialysis samples using liquid chromatography tandem mass spectrometry.  

PubMed

A liquid chromatographic-electrospray/tandem mass spectrometric (LC-ESI-MS/MS) method was developed for the analysis of dopamine and its phase I and phase II metabolites from brain microdialysis samples. The method provides for the first time the analysis of intact dopamine glucuronide and sulfate without hydrolysis. The paper describes also an enzymatic synthesis method using rat liver microsomes as biocatalysts and characterization of dopamine glucuronide as a reference compound. The method was validated for quantitative analysis by determining limits of detection and quantitation, linearity,repeatability, and specificity. Dopamine glucuronide was found for the first time in rat and mouse brain microdialysis samples. The concentrations of dopamine and its glucuronide in the microdialysates collected from the striatum of rat brains were approximately equal (2 nM).Dopamine sulfate was not detected in the microdialysates(limit of detection 0.8 nM). The main metabolites of dopamine were dihydroxyphenylacetic acid (DOPAC,1200 nM) and homovanillic acid (HVA, 700 nM). PMID:19125450

Uutela, Päivi; Karhu, Laura; Piepponen, Petteri; Käenmäki, Mikko; Ketola, Raimo A; Kostiainen, Risto

2009-01-01

102

Multiple UDP-glucuronosyltransferases in human liver microsomes glucuronidate both R- and S-7-hydroxywarfarin into two metabolites.  

PubMed

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

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

2014-12-15

103

Release of mutagenic metabolites of benzo[a]pyrene from the perfused rat liver after inhibition of glucuronidation and sulfation by salicylamide.  

PubMed

The role of glucuronide and sulfate conjugation in presystemic inactivation of benzo[a]pyrene (BP) metabolites was investigated with rat livers perfused with BP (12 mumol). Comparisons were made between metabolite profiles and mutagenicity of medium from perfusions with and without salicylamide, a selective inhibitor of glucuronide and sulfate conjugation. After 4 h perfusion in the presence of salicylamide, certain BP metabolites (diols, quinones, phenols, and metabolites more polar than BP-9,10-diol) were significantly increased at the expense of quinones and phenols in the glucuronide fraction. Mutagenicity of medium (detected by the Ames test, using tester strains TA98 and TA100) was low in perfusion without salicylamide. Mutagenicity detected with tester strain TA98 was significantly increased in perfusions with salicylamide. Involvement of glucuronidation in BP inactivation was also observed at the subcellular level; when cofactors of glucuronidation were added to liver homogenates along with the NADPH regenerating system in the Ames test, BP mutagenicity was markedly decreased. Both the activation of BP to mutagenic metabolites and the inactivation of BP metabolites by glucuronidation was much more pronounced with liver homogenates from 3-methylcholanthrene-treated rats than with those from phenobarbital-treated animals or untreated controls. The results suggest an important role for glucuronidation and sulfation in the inactivation and elimination of polycyclic aromatic hydrocarbons. PMID:6268312

Bock, K W; Bock-Hennig, B S; Lilienblum, W; Volp, R F

1981-08-01

104

Capillary electrophoresis-mass spectrometry determination of morphine and its isobaric glucuronide metabolites.  

PubMed

The determination of morphine and its isobaric metabolites morphine-3-beta-d-glucuronide (M3G) and morphine-6-beta-d-glucuronide (M6G) is useful for therapeutic drug monitoring and forensic identification of drug use. In particular, capillary electrophoresis with mass spectrometry (CE-MS) represents an attractive tool for opioid analysis. Whereas volatile background electrolytes in CE often improve electrospray ionization for coupled MS detection, such electrolytes may reduce CE separation efficiency and resolution. To better understand the effects of background electrolyte (BGE) composition on separation efficiency and detection sensitivity, this work compares and contrasts method development for both volatile (ammonium formate and acetate) and nonvolatile (ammonium phosphate and borate) buffers. Peak efficiencies and migration times for morphine and morphine metabolites were optimal with a 25mM ammonium borate buffer (pH=9.5) although greater sensitivities were achieved in the ammonium formate buffer. Optimized CE methods allowed for the resolution of the isobaric morphine metabolites prior to high mass accuracy, electrospray ionization quadrupole time-of-flight (ESI-QTOF) MS detection applicable to the analysis of urine samples in under seven minutes. Urine sample preparation required only a 10-fold dilution with BGE prior to analysis. Limits of detection (LOD) in normal human urine were found to be 1.0?g/mL for morphine and 2.5?g/mL for each of M3G and M6G by CE-ESI-QTOF-MS. These LODs were comparable to those for CE-UV analysis of opioid standards in buffer, whereas CE-ESI-QTOF-MS analysis of opioid standards in buffer yielded LODs an order of magnitude lower. Patient urine samples (N=12) were analyzed by this new CE-ESI-QTOF-MS method and no significant difference in total morphine content relative to prior liquid chromatography-mass spectrometry (LC-MS) results was found as per a paired-t test at the 99% confidence level. Whereas the LC-MS method applied to these samples determined only total morphine content, this new CE-ESI-QTOF-MS method allowed for species differentiation in addition to total morphine determination. By this method, it was found that M3G and M6G metabolites were present in a 5:1 concentration ratio, on average, in patient samples. Therefore, the CE-ESI-QTOF-MS method not only allows for total morphine concentration determination comparable to established LC-MS methods, but also allows for differentiation between morphine and its trace glucuronides, yielding additional biochemical information about drug metabolism. PMID:25589256

Isbell, Theresa A; Strickland, Erin C; Hitchcock, Jennifer; McIntire, Gregory; Colyer, Christa L

2015-02-01

105

Determination and study on residue and dissipation of benazolin-ethyl and quizalofop-p-ethyl in rape and soil  

Microsoft Academic Search

A QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for the determination of benazolin-ethyl and quizalofop-p-ethyl in rape and soil by high-performance liquid chromatography-tandem mass spectrometry has been developed in this study. The residue and dissipation of benazolin-ethyl and quizalofop-p-ethyl in rape and soil were determined with the developed method. The half-lives of benazolin-ethyl in rape straw and soil

Wenbi Guan; Hongyan Zhang

2012-01-01

106

Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta.  

PubMed

Epidemiological studies have reported an inverse association between dietary flavonoid intake and mortality for ischemic heart disease. Quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, but it is rapidly metabolized during absorption by methylation, glucuronidation and sulfation. We have analyzed the vasorelaxant effects and the role on NO bioavailability and endothelial function of quercetin and its conjugated metabolites (quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin-3'-sulfate) in rat aorta. Thoracic aortic rings isolated from Wistar rats were mounted for isometric force recording and endothelial function was tested by measuring the vasorelaxant response to acetylcholine. NADPH-enhanced O(2)(-) release was quantified in homogenates from cultured aortic smooth muscle cells using lucigenin chemiluminescence. Unlike quercetin, the conjugated metabolites had no direct vasorelaxant effect, and did not modify endothelial function or the biological activity of NO. However, all metabolites (at 10 micromol/L) prevented, at least partially, the impairment of endothelial-derived NO response under conditions of high oxidative stress induced by the SOD inhibitor DETCA. Furthermore, they protected the biological activity of exogenous NO when impaired by DETCA. Quercetin and quercetin-3'-sulfate (>or=10 micromol/L) or quercetin-3-glucuronide (100 micromol/L) inhibited NADPH oxidase-derived O(2)(-) release. Quercetin and quercetin-3-glucuronide (1 micromol/L) prevented the endothelial dysfunction induced by incubation with ET-1. These data indicate, for the first time, that the conjugated metabolites could be responsible for the in vivo protective activity of quercetin on endothelial dysfunction. PMID:18801486

Lodi, Federica; Jimenez, Rosario; Moreno, Laura; Kroon, Paul A; Needs, Paul W; Hughes, David A; Santos-Buelga, Celestino; Gonzalez-Paramas, Ana; Cogolludo, Angel; Lopez-Sepulveda, Rocío; Duarte, Juan; Perez-Vizcaino, Francisco

2009-05-01

107

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

Microsoft Academic Search

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

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

2010-01-01

108

Sex-dependent disposition of acetaminophen sulfate and glucuronide in the in situ perfused mouse liver.  

PubMed

Breast cancer resistance protein (BCRP, ABCG2) is expressed in the hepatic canalicular membrane and mediates biliary excretion of xenobiotics including sulfate and glucuronide metabolites of some compounds. Hepatic Bcrp expression is sex-dependent, with higher expression in male mice. The hypothesis that sex-dependent Bcrp expression influences the hepatobiliary disposition of phase II metabolites was tested in the present study using acetaminophen (APAP) and the generated APAP glucuronide (AG) and sulfate (AS) metabolites in single-pass in situ perfused livers from male and female wild-type and Abcg(-/-) (Bcrp-deficient) mice. Pharmacokinetic modeling was used to estimate parameters governing the hepatobiliary disposition of APAP, AG, and AS. In wild-type mice, the biliary excretion rate constant was 2.5- and 7-fold higher in males than in females for AS and AG, respectively, reflecting male-predominant Bcrp expression. Sex-dependent differences in AG biliary excretion were not observed in Bcrp-deficient mice, and AS biliary excretion was negligible. Interestingly, sex-dependent basolateral excretion of AG (higher in males) and AS (higher in females) was noted in wild-type mice with a similar trend in Bcrp-deficient mouse livers, reflecting an increased rate constant for AG formation in male and AS formation in female mouse livers. In addition, the rate constant for AS basolateral excretion was increased significantly in female mouse livers compared with that in male mouse livers. It is interesting to note that multidrug resistance-associated protein 4 was higher in female than in male mouse livers. In conclusion, sex-dependent differences in conjugation and transporter expression result in profound differences in the hepatobiliary disposition of AG and AS in male and female mouse livers. PMID:19487254

Lee, Jin Kyung; Abe, Koji; Bridges, Arlene S; Patel, Nita J; Raub, Thomas J; Pollack, Gary M; Brouwer, Kim L R

2009-09-01

109

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

SciTech Connect

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.

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

1987-06-01

110

Photoinduced covalent binding of frusemide and frusemide glucuronide to human serum albumin  

PubMed Central

Aims To study reaction of photoactivated frusemide (F) and F glucuronide (Fgnd metabolite) with human serum albumin in order to find a clue to clarify a mechanism of phototoxic blisters from high frusemide dosage. Methods F was exposed to light in the presence of human serum albumin (HSA). HSA treated with this method (TR-HSA) was characterized by fluorescence spectroscopic experiment, alkali treatment and reversible binding experiment. Results Less 4-hydroxyl-N-furfuryl-5-sulphamoylanthranilic acid (4HFSA, a photodegradation product of F) was formed in the presence of HSA than in the absence of HSA. A new fluorescence spectrum excited at 320 nm was observed for TR-HSA. Alkali treatment of TR-HSA released 4HFSA. Quenching of the fluorescence due to the lone tryptophan near the warfarin-binding site of HSA was observed in TR-HSA. The reversible binding of F or naproxen to the warfarin-binding site of TR-HSA was less than to that of native HSA. These results indicate the photoactivated F was covalently bound to the warfarin-binding site of HSA. The covalent binding of Fgnd, which is also reversibly bound to the wafarin-binding site of HSA, was also induced by exposure to sunlight. Fgnd was more photoactive than F, indicating that F could be activated by glucuronidation to become a more photoactive compound. Conclusions The reactivity of photoactivated F and Fgnd to HSA and/or to other endogenous compounds may cause the phototoxic blisters that result at high F dosage. PMID:10383564

Mizuma, Takashi; McDonagh, Antony F; Lin, Emil T; Benet, Leslie Z

1999-01-01

111

Quantitation of the flavonoid wogonin and its major metabolite wogonin-7?- d-glucuronide in rat plasma by liquid chromatography–tandem mass spectrometry  

Microsoft Academic Search

This study described the application of liquid chromatography–tandem mass spectrometry for the quantitation of wogonin and its major metabolite in rat plasma. Only one conjugated metabolite with glucuronic acid was identified by chromatographic and electrospray multi-stage mass spectrometric assay. A derivatization reaction with 2-chlorethanol further demonstrated that the metabolite was wogonin-7?-d-glucuronide (W-7-G), not wogonin-5?-d-glucuronide. Other conjugated metabolites, e.g., sulfates and

Xiaoyan Chen; Hongyan Wang; Yue Du; Dafang Zhong

2002-01-01

112

40 CFR 180.429 - Chlorimuron ethyl; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...measuring only chlorimuron ethyl, ethyl 2-[[[[(4-chloro-6-methoxypyrimidin-2yl)amino]carbonyl]sulfonyl]benzoate] in or on the following commodities: Commodity Parts per million Berry, low growing, except strawberry,...

2010-07-01

113

40 CFR 180.429 - Chlorimuron ethyl; tolerances for residues.  

Code of Federal Regulations, 2014 CFR

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

2014-07-01

114

PUMMERER REARRANGEMENTS OF ETHYL ETHYLTHIOMETHYL SULPHOXIDE  

Microsoft Academic Search

Some Pummerer rearrangements, in which ethyl ethylthiomethyl sulphoxide (I) is supposed to react initially as a nucleophile, were investigated in connection with the observed decrease of basicity in this compound, due to electronic interaction between ?-sulphur atom and sulphinyl group. In fact, it proved to be quite resistant to the acetic anhydride induced rearrangement, being totally recovered under conditions in

B. Wladislaw; L. Marzorati; F. A. C. Andrade; M. A. Andrade

1979-01-01

115

Ethyl pyruvate improves survival in awake hemorrhage  

PubMed Central

Classical experimental models of hemorrhage are characterized by the use of anesthetics that may interfere with the typical immune responses and pathology of hemorrhage/resuscitation. Thus, therapeutic strategies successful in anesthetized animals might not be beneficial in clinical trials. In this study, we analyzed whether ethyl pyruvate could provide therapeutic benefits during resuscitation in awake (unanesthetized) hemorrhage. Our results indicate that hemorrhage in unanesthetized animals required approximately 25% higher blood withdrawal than anesthetized animals to achieve the same targeted mean arterial blood pressure. Resuscitation with Hextend reestablished circulatory volume and improved survival during resuscitation of awake rodents. Yet, over 75% of the animals resuscitated with Hextend died within the first hours after hemorrhage. Resuscitation with Hextend containing 50 mM ethyl pyruvate protected over 87% of the animals. This survival benefit did not correlate with significant changes in the metabolic markers but with an anti-inflammatory potential during resuscitation. Unlike classical hemorrhage in anesthetized animals, ethyl pyruvate reestablished mean arterial blood pressure significantly earlier than Hextend in unanesthetized rodents. Unanesthetized animals showed twofold higher serum tumor necrosis factor (TNF)-? than anesthetized animals subjected to the same blood pressure. This process was not due to the response of a single organ, but affected all the analyzed organs including the lung, heart, spleen, and liver. Although resuscitation with Hextend failed to attenuate systemic TNF-? levels, it inhibited TNF-? levels in the lung, heart, and liver but not in the spleen. Unlike Hextend, resuscitation with ethyl pyruvate prevented high serum TNF-? levels and blunted TNF-? responses in all the organs including the spleen. These studies indicate that the inflammatory responses in anesthetized animals differ from that in unanesthetized animals and that awake hemorrhage can provide advantages in the study of anti-inflammatory strategies during resuscitation. Ethyl pyruvate may attenuate systemic inflammatory responses during resuscitation and improve survival in experimental models of awake hemorrhage. PMID:19172241

Cai, Bolin; Brunner, Michael; Wang, Haichao; Wang, Ping; Deitch, Edwin A.

2011-01-01

116

Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice.  

PubMed

A series of crocetin glycosides (crocins) are the main pigment of the stigmas of saffron (Crocussativus L.) and the fruits of gardenia (Gardenia jasminoides Ellis). Although numerous studies have demonstrated that crocetin and crocins have a variety of biological functions, the metabolism of dietary crocetin and crocins remains unknown. In the present study, we investigated the intestinal absorption of orally administered crocetin and crocins in mice. Orally administered crocetin was rapidly absorbed into the blood circulation and was present in plasma as an intact free form and as glucuronide conjugates (crocetin-monoglucuronide and -diglucuronide). Crocetin and its glucuronide conjugates were also found in crocins-administered mouse plasma, whereas intact crocins (glycoside forms) were not detected. These results indicate that orally administered crocins are hydrolyzed to crocetin before or during intestinal absorption, and absorbed crocetin is partly metabolized to mono- and diglucuronide conjugates. PMID:16131146

Asai, Akira; Nakano, Takahisa; Takahashi, Masahiro; Nagao, Akihiko

2005-09-01

117

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

Code of Federal Regulations, 2010 CFR

...Tolerances are established for the combined residues of the herbicide fenoxaprop-ethyl [(±)-ethyl 2-[4-[(6-chloro-2-benzoxazolyl...Time-limited tolerances are established for combined residues of the herbicide fenoxaprop-ethyl, [(±)-ethyl...

2010-07-01

118

Determination of Coumarin, 7HydroxyCoumarin, 7Hydroxycoumarin-Glucuronide, and 3Hydroxycoumarin by High-Performance Liquid Chromatography  

Microsoft Academic Search

A selective and sensitive method for the determination of coumarin and its main metabolites 7-hydroxycoumarin, 7-hydroxycoumarin-glucuronide and 3-hydroxycoumarin in human plasma and\\/or urine is described. Coumarin and 7-hydroxycoumarin were extracted from plasma with n-hexane\\/chloroform and with chloroform. After evaporation under vacuum, the residue was redissolved in methanol\\/water and injected onto the HPLC column (LiChroCART 250-4, RP 8e 5 ?m; Merck,

Sheida Sharifi; Hans Christoph Michaelis; Erich Lotterer; Johannes Bircher

1993-01-01

119

Stability of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in the presence of human serum albumin  

Microsoft Academic Search

9-Aminocamptothecin glucuronide (9ACG) is a new water-soluble prodrug of 9-aminocamptothecin (9AC) that is a substrate for ?-glucuronidase and displays potent antitumor activity against human tumor xenografts. The lactone ring of camptothecins (CPTs) is required for antitumor activity but spontaneously opens under physiological conditions to an inactive carboxy form. The carboxy form of many CPTs, including 9AC, preferentially binds to human

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

2003-01-01

120

Glucuronidation of the red clover isoflavone irilone by liver microsomes from different species and human UDP-glucuronosyltransferases.  

PubMed

Red clover (Trifolium pratense L.) is used as a source for isoflavone (IF) dietary supplements. In this study, we focused on the red clover IF irilone (IRI), because of its reported comparatively high bioavailability. Because the conjugative metabolism plays a key role in the elimination of IF, we investigated the species-specific differences and glucuronidation kinetics of IRI using different liver microsomes as well as the recombinant UDP-glucuronosyltransferases (UGTs) 1A1, 1A7, 1A8, 1A9, 1A10, and 2B15. Both possible monoglucuronides, the IRI-O-4'-monoglucuronide (IRI-G4') and the IRI-O-5-monoglucuronide (IRI-G5), were detected. Human liver microsomes (HLM) as well as rat liver microsomes predominantly formed IRI-G5, whereas for porcine liver microsomes, IRI-G4' prevailed. HLM showed an apparent V(max) value of 0.43 nmol/min · mg and an apparent K(m) value of 9.8 ?M for the formation of IRI-G5 and a V(max) of 0.35 nmol/min · mg and a K(m) of 64.7 ?M in the case of IRI-G4'. Formation of both glucuronides was best fit using the substrate inhibition equation. The glucuronidation of IRI by UGTs led to values for the intrinsic clearance varying between 4 and 100 ml/min · mg, with UGT1A7 showing the lowest and UGT1A10 the highest IRI conversion rate. The results indicate that IRI undergoes an efficient glucuronidation, presumably in the intestine and liver, following atypical kinetic profiles. PMID:21177485

Maul, Ronald; Siegl, Diana; Kulling, Sabine E

2011-04-01

121

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

PubMed

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

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

2014-03-28

122

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

PubMed Central

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

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

123

Evidence of in vitro glucuronidation and enzymatic transformation of paralytic shellfish toxins by healthy human liver microsomes fraction.  

PubMed

Paralytic Shellfish Toxins (PST) are endemic components found in filter bivalves in Southern Chile. Post-mortems analysis of fluid and tissue samples has shown biotransformation of PST in humans. The Gonyautoxin 3 (GTX3) and Gonyautoxin 2 (GTX2) are the major PST components in the toxin profile found in Chilean shellfish extracts, being as much as 65% of the total content of PST in filter bivalves. Therefore, they are the major accountable components of the human intoxication by shellfish consumption. The aim of this study is to show in vitro glucuronidation and biotransformation of GTX3 and GTX2 when they are incubated with microsomal fraction isolated from healthy human livers. Microsomes fractions isolated from human livers were incubated with GTX3 and GTX2 purified from contaminated mussels. After different incubation times, incubated samples were extracted and analyzed by HPLC with fluorescent on line detection and HPLC-MS analysis. The results revealed that GTX3 and GTX2, only when they were incubated with microsomal fraction and appropriated cofactors, showed to be enzymatic transformed in vitro. The glucuronidation of GTX3 and GTX2 followed typical Michaelis-Menten kinetics, resulting in apparent kinetic parameters of Km=39.4+/-0.24 microM and Vmax=6.0x10(-3) pmol/min/mg protein. In addition, the microsomes fraction also oxidized GTX3 and GTX2 into Gonyautoxin 4 (GTX 4) and Gonyautoxin 1 (GTX 1) resulting in 0.339x10(-3) pmol/min/mg protein. In conclusion, this study reports oxidation and glucuronidation of GTX3 and GTX2 when they are incubated with human liver microsomal fraction. The metabolism occurs via a glucuronidation reaction, the basis first step of biotransformation in human liver. Also it is showed that GTX4 and GTX1 came by biotransformation from GTX3 and GTX2 in humans. This data confirm human biotransformation found in human post-mortem fluid and tissue samples described previously. This data is the first evidence of in vitro glucuronidation of PST, given a metabolic pathway of detoxification and excretion of PST in human. PMID:19041885

García, Carlos; Rodriguez-Navarro, Alberto; Díaz, Juan Carlos; Torres, Rafael; Lagos, Néstor

2009-02-01

124

Selective release of a cyclopamine glucuronide prodrug toward stem-like cancer cell inhibition in glioblastoma.  

PubMed

Recent data suggest that inhibition of the Hedgehog pathway could be a therapeutic target for glioblastoma. Alkaloid cyclopamine inhibits Hedgehog signaling, depleting stem-like cancer cells derived from glioblastoma. However, this compound is toxic for somatic stem cells, preventing its use for clinical applications. In this study, we tested a derivatization product of cyclopamine in the form of cyclopamine glucuronide prodrug (CGP-2). This compound was used in vitro and in vivo toward glioblastoma-initiating cells (GIC). Results obtained in vitro indicate that CGP-2 is active only in the presence of ?-glucuronidase, an enzyme detected in high levels in necrotic areas of glioblastomas. CGP-2 decreased proliferation and inhibited the self-renewal of all GIC lines tested. Hedgehog pathway blockade by 10 ?mol/L of CGP-2 induced a 99% inhibition of clonogenicity on GICs, similar to cyclopamine treatment. Combination of CGP-2 with radiation decreased clonogenic survival in all GIC lines compared with CGP-2 alone. In a subcutaneous glioblastoma xenograft model, a two-week CGP-2 treatment prevented tumor growth with 75% inhibition at 8 weeks, and this inhibition was still significant after 14 weeks. Unlike cyclopamine, CGP-2 had no detectable toxic effects in intestinal crypts. Our study suggests that inhibition of the Hedgehog pathway with CGP-2 is more effective than conventional temozolomide adjuvant, with much lower concentrations, and seems to be an effective therapeutic strategy for targeting GICs. PMID:25053823

Balbous, Anaïs; Renoux, Brigitte; Cortes, Ulrich; Milin, Serge; Guilloteau, Karline; Legigan, Thibaut; Rivet, Pierre; Boissonnade, Odile; Martin, Sébastien; Tripiana, Caroline; Wager, Michel; Bensadoun, René Jean; Papot, Sébastien; Karayan-Tapon, Lucie

2014-09-01

125

Chemical and Enzyme-Assisted Syntheses of Norbuprenorphine-3-?-D-Glucuronide  

PubMed Central

Norbuprenorphine-3-?-D-glucuronide (nBPN-3-?-D-G, 1) is a major phase II metabolite of buprenorphine, a pharmaceutical used for the treatment of opioid addiction. The pharmacological activity of compound 1 is not clear because investigations have been limited by the lack of chemically pure, well characterized 1 in sufficient quantities for in vitro and in vivo experiments. This work describes two concise, new methods of synthesis of 1, a chemical and an enzyme-assisted synthesis. The chemical synthesis used a strategy based on a combination of Koenig-Knorr coupling and amino-silyl protection. The enzyme-assisted synthesis used dog liver to convert substrate norbuprenorphine (nBPN, 2) to 1. Both methods provided 1, characterized by 1H NMR and tandem mass spectrometry, with purity >96%. The fractional yield of the enzyme-assisted synthesis was greater than that of the chemical synthesis (67% vs 5.3%), but due to larger reaction volumes, the chemical synthesis afforded greater amounts of total 1. PMID:21434652

Fan, Jinda; Brown, Sarah M.; Tu, Zhude; Kharasch, Evan D.

2011-01-01

126

Bis(tri­ethyl­ammonium) chloranilate  

PubMed Central

In the crystal structure of the title compound [systematic name: bis­(tri­ethyl­ammonium) 2,5-di­chloro-3,6-dioxo­cyclo­hexa-1,4-diene-1,4-diolate], 2C6H16N+·C6Cl2O4 2?, the chloranilate anion lies on an inversion center. The tri­ethyl­ammonium cations are linked on both sides of the anion via bifurcated N—H?(O,O) and weak C—H?O hydrogen bonds to give a centrosymmetric 2:1 aggregate. The 2:1 aggregates are further linked by C—H?O hydrogen bonds into a zigzag chain running along [01-1]. PMID:24427039

Gotoh, Kazuma; Maruyama, Shinpei; Ishida, Hiroyuki

2013-01-01

127

Production of ethyl alcohol from bananas  

SciTech Connect

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.

Jones, R.L.; Towns, T.

1983-12-01

128

Analysis of intact glucuronides and sulfates of serotonin, dopamine, and their phase I metabolites in rat brain microdialysates by liquid chromatography-tandem mass spectrometry.  

PubMed

A method for the analysis of intact glucuronides and sulfates of common neurotransmitters serotonin (5-HT) and dopamine (DA) as well as of 5-hydroxy-3-indoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat brain microdialysates by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Enzyme-assisted synthesis using rat liver microsomes as a biocatalyst was employed for the production of 5-HT-, 5-HIAA-, DOPAC-, and HVA-glucuronides for reference compounds. The sulfate conjugates were synthesized either chemically or enzymatically using a rat liver S9 fraction. The LC-MS/MS method was validated by determining the limits of detection and quantitation, linearity, and repeatability for the quantitative analysis of 5-HT and DA and their glucuronides, as well as of 5-HIAA, DOPAC, and HVA and their sulfate-conjugates. In this study, 5-HT-glucuronide was for the first time detected in rat brain. The concentration of 5-HT-glucuronide (1.0-1.7 nM) was up to 2.5 times higher than that of free 5-HT (0.4-2.1 nM) in rat brain microdialysates, whereas the concentration of DA-glucuronide (1.0-1.4 nM) was at the same level or lower than the free DA (1.2-2.4 nM). The acidic metabolites of neurotransmitters, 5-HIAA, HVA, and DOPAC, were found in free and sulfated form, whereas their glucuronidation was not observed. PMID:19772284

Uutela, Päivi; Reinilä, Ruut; Harju, Kirsi; Piepponen, Petteri; Ketola, Raimo A; Kostiainen, Risto

2009-10-15

129

Phase II Metabolism in Human Skin: Skin Explants Show Full Coverage for Glucuronidation, Sulfation, N-Acetylation, Catechol Methylation, and Glutathione Conjugation.  

PubMed

Although skin is the largest organ of the human body, cutaneous drug metabolism is often overlooked, and existing experimental models are insufficiently validated. This proof-of-concept study investigated phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model containing all skin cell types. Results show that skin explants have significant capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17?-estradiol, N-acetylprocainamide, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 ?M substrate incubations spanned a 1000-fold: from the highest 4.758 pmol·mg skin(-1)·h(-1) for p-toluidine N-acetylation to the lowest 0.006 pmol·mg skin(-1)·h(-1) for 17?-estradiol 17-glucuronidation. Interindividual variability was 1.4- to 13.0-fold, the highest being 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 hours, although 24-hour incubations enabled detection of metabolites in trace amounts. All reactions were unaffected by the inclusion of cosubstrates, and freezing of the fresh skin led to loss of glucuronidation activity. The predicted whole-skin intrinsic metabolic clearances were significantly lower compared with corresponding whole-liver intrinsic clearances, suggesting a relatively limited contribution of the skin to the body's total systemic phase II enzyme-mediated metabolic clearance. Nevertheless, the fresh full-thickness skin explants represent a suitable model to study cutaneous phase II metabolism not only in drug elimination but also in toxicity, as formation of acyl glucuronides and sulfate conjugates could play a role in skin adverse reactions. PMID:25339109

Manevski, Nenad; Swart, Piet; Balavenkatraman, Kamal Kumar; Bertschi, Barbara; Camenisch, Gian; Kretz, Olivier; Schiller, Hilmar; Walles, Markus; Ling, Barbara; Wettstein, Reto; Schaefer, Dirk J; Itin, Peter; Ashton-Chess, Joanna; Pognan, Francois; Wolf, Armin; Litherland, Karine

2015-01-01

130

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

PubMed

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

Cataldo, Franco

2013-01-01

131

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

SciTech Connect

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.

Richardson, Terrilyn A.; Klaassen, Curtis D., E-mail: cklaasse@kumc.ed

2010-10-01

132

Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as a perpetrator of drug-drug interactions.  

PubMed

Cerivastatin and repaglinide are substrates of cytochrome P450 (CYP)2C8, CYP3A4, and organic anion-transporting polypeptide (OATP)1B1. A recent study revealed an increased risk of rhabdomyolysis in patients using cerivastatin with clopidogrel, warranting further studies on clopidogrel interactions. In healthy volunteers, repaglinide area under the concentration-time curve (AUC(0-?)) was increased 5.1-fold by a 300-mg loading dose of clopidogrel and 3.9-fold by continued administration of 75?mg clopidogrel daily. In vitro, we identified clopidogrel acyl-?-D-glucuronide as a potent time-dependent inhibitor of CYP2C8. A physiologically based pharmacokinetic model indicated that inactivation of CYP2C8 by clopidogrel acyl-?-D-glucuronide leads to uninterrupted 60-85% inhibition of CYP2C8 during daily clopidogrel treatment. Computational modeling resulted in docking of clopidogrel acyl-?-D-glucuronide at the CYP2C8 active site with its thiophene moiety close to heme. The results indicate that clopidogrel is a strong CYP2C8 inhibitor via its acyl-?-D-glucuronide and imply that glucuronide metabolites should be considered potential inhibitors of CYP enzymes. PMID:24971633

Tornio, A; Filppula, A M; Kailari, O; Neuvonen, M; Nyrönen, T H; Tapaninen, T; Neuvonen, P J; Niemi, M; Backman, J T

2014-10-01

133

The association of serum androsterone glucuronide with inflammatory lesions in women with adult acne.  

PubMed

Serum androsterone glucuronide (AoG) is a metabolite of circulating androgens under the influence of 5alpha-reductase activity and has been shown to be particularly elevated in women with acne. In this study, we wanted to evaluate changes in AoG before and after treatment with an oral contraceptive or placebo, and to assess whether changes correlated with the number and type of acne lesions. In order to accomplish these aims, we obtained sera from a completed prospective randomized trial, which was designed to assess the effectiveness of an oral contraceptive compared to placebo. Assessments were carried out in 56 women with moderate acne who were treated with Ortho Tri-Cyclen (norgestimate and ethinylestradiol) (30 patients) or placebo (26 patients) for 6 months. Before and after treatment, the number and type of skin lesions, serum levels of total T, free-T, DHEAS and AoG were determined. Serum AoG increased significantly in women with moderate acne, although T, free-T and DHEAS were normal. 75% of acne patients had elevated levels of serum AoG. Ratios of serum AoG to androgen precursors were also elevated. Oral contraceptive (OC) treatment significantly reduced levels of free-T and AoG, both of which were unaffected by placebo. While both OC and placebo treatment resulted in improvement of comedones and inflammatory lesions, OC treatment decreased inflammatory lesions to a greater extent (p<0.05). After treatment, serum AoG correlated with the number of inflammatory lesions. Results showed that serum AoG is a sensitive marker of acne in women, even in those with normal circulating precursor androgens; and is lowered by OC treatment, correlating with the reduction of inflammatory lesions. We hypothesize that the increase of serum AoG in normoandrogenic acne may be related to inflammation, and serum AoG may serve as a marker of this process. PMID:12398233

Carmina, E; Godwin, A J; Stanczyk, F Z; Lippman, J S; Lobo, R A

2002-10-01

134

The hydroxylation, dechlorination, and glucuronidation of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes.  

PubMed

Since chlorine placement and the degree of chlorination of the biphenyl nucleus play an important role in the metabolism and ultimate elimination of polychlorinated biphenyls (PCBs), we have studied the metabolism of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes. This low molecular weight PCB congener is substituted at the preferred site of metabolism (para-position). 4-DCB was metabolized by human microsomes with a Km of 0.43 microM and a Vmax of 1.2 pmoles/mg microsomal protein/min. Six metabolites were identified: 4,4'-dichloro-3,3'-biphenyldiol, 4'-chloro-3-biphenylol, 4'-chloro-4-biphenylol, 4,4'-dichloro-2-biphenylol, 4,4'-dichloro-3-biphenylol (most abundant), and 3,4'-dichloro-4-biphenylol. [14C]-4-DCB equivalents were found to covalently bind to microsomal protein. Addition of a 1 mM concentration of reduced glutathione decreased the degree of covalent binding. These data suggest that human microsomes metabolize this PCB through an arene oxide and that an "NIH shift" occurs. When UDPGA was added to the incubation, human microsomal glucuronosyltransferase catalyzed the formation of the glucuronide of the major metabolite, 4,4'-dichloro-3-biphenylol. These and previous in vitro results show that the biotransformation of PCBs by humans is governed by the same principles established for the in vivo biotransformation of PCBs by the rat, mouse and monkey. That is, PCBs without two adjacent unsubstituted carbon atoms are poorly metabolized and that an unsubstituted para-position facilitates metabolism. PMID:6437410

Schnellmann, R G; Volp, R F; Putnam, C W; Sipes, I G

1984-11-01

135

Efflux transport is an important determinant of ethinylestradiol glucuronide and ethinylestradiol sulfate pharmacokinetics.  

PubMed

17?-ethinylestradiol (EE) undergoes extensive conjugation to 17?-ethinylestradiol-3-O-glucuronide (EEG) and 17?-ethinylestradiol-3-O-sulfate (EES). Thus, oral contraceptive drug-drug interaction (DDI) studies usually characterize metabolite pharmacokinetics, with changes typically attributed to modulation of metabolism. EE passively diffuses through plasma membranes, but its conjugates are hydrophilic and require active transport. Unlike EE metabolism, EEG and EES transport has not been explored in vivo as a potential mechanism of DDIs. Recent in vitro studies demonstrated that EEG is transported by multidrug resistance-associated protein (MRP) 2 and MRP3 and EES is a breast cancer resistance protein (BCRP) substrate. In the study presented here, pharmacokinetics of EE and conjugates were studied in TR? rats, which lack Mrp2, have marginal hepatic Bcrp expression, and overexpress hepatic Mrp3. EE pharmacokinetics in TR? rats were comparable to wild type; however, EEG and EES systemic exposures were altered markedly. EEG exposure was greatly increased: 20-fold and >100-fold after intravenous and oral EE administration, respectively. In contrast, EES exposure was lower in TR? rats: 65% decreased (intravenously) and 83% decreased (orally). In intestinal and liver perfusions, EE intestinal permeability and metabolism and hepatic clearance were unchanged in TR? rats; however, secretion of EEG into intestinal lumen was halved, EEG was not detected in TR? bile, and EES biliary excretion was 98% decreased. After oral EE administration to Mrp2- and Bcrp-knockout mice, EEG exposure increased 46- and 2-fold, respectively, whereas EES concentrations were decreased modestly. In conclusion, altered efflux transport resulted in major alterations of EEG and EES pharmacokinetics, highlighting transport as a potential site of DDIs with EE conjugates. PMID:21708882

Zamek-Gliszczynski, Maciej J; Day, Jeffrey S; Hillgren, Kathleen M; Phillips, Diane L

2011-10-01

136

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

SciTech Connect

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.

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

1988-01-01

137

Optimization of ethyl ester production assisted by ultrasonic irradiation.  

PubMed

This study presents the optimization of the continuous flow potassium hydroxide-catalyzed synthesis of ethyl ester from palm oil with ultrasonic assistance. The process was optimized by application of factorial design and response surface methodology. The independent variables considered were ethanol to oil molar ratio, catalyst concentration, reaction temperature and ultrasonic amplitude; and the response was ethyl ester yield. The results show that ethanol to oil molar ratio, catalyst concentration, and ultrasonic amplitude have positive effect on ethyl ester yield, whereas reaction temperature has negative influence on ethyl ester yield. Second-order models were developed to predict the responses analyzed as a function of these three variables, and the developed models predicts the results in the experimental ranges studied adequately. This study shows that ultrasonic irradiation improved the ethyl ester production process to achieve ethyl ester yields above 92%. PMID:25116594

Noipin, K; Kumar, S

2015-01-01

138

Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem mass spectrometry  

Microsoft Academic Search

The first method for quantifying cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem\\u000a mass spectrometry (LC–MS\\/MS) was developed and validated. Solid-phase extraction followed protein precipitation with acetonitrile.\\u000a High-performance liquid chromatography separation was achieved in 16 min via gradient elution. Electrospray ionization was\\u000a utilized for cannabinoid detection; both positive (?9-tetrahydrocannabinol [THC] and cannabinol [CBN]) and negative (11-hydroxy-THC [11-OH-THC], 11-nor-9-carboxy-THC [THCCOOH],

David M. Schwope; Karl B. Scheidweiler; Marilyn A. Huestis

139

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

SciTech Connect

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.

Malfatti, M A; Felton, J S

2004-04-06

140

Evaluation of pharmaceutical excipients as cosolvents in 4-methyl umbelliferone glucuronidation in human liver microsomes: applications for compounds with low solubility.  

PubMed

Standard incubation procedures for carrying out microsomal assays involve the use of less than 1% w/v organic solvents to minimize the potential inhibitory effects of organic solvents on metabolic activity. This presents a practical limitation for poorly soluble xenobiotics, which cannot be incubated at concentrations high enough to obtain a V(max), and therefore subsequent values for K(m) and Cl(int) cannot be calculated. Our goal was to study the application of a variety of pharmaceutical excipients to aid the solubilization of compounds in vitro in glucuronidation incubations, without affecting the reaction kinetics. In vitro glucuronidation incubations were carried out in human liver microsomes with 4-methylumbelliferone (4-MU) and the kinetics of 4-MU glucuronidation in the presence of excipients were compared to that in control incubations without any excipients. In addition, IC(75) values were calculated for each excipient. We observed that HPBCD (Hydroxypropyl-?-cyclodextrin) may be employed in in vitro glucuronidation incubations up to 0.5% w/v without affecting the Cl(int) of 4-MU. Although NMP (N-methyl-2-pyrrolidone) and DMA (N,N-dimethylacetamide); showed low IC(75) values approximately 0.1% w/v each, neither excipients altered the Cl(int) of 4-MUG (4-methylumbelliferyl-?-D-glucuronide) formation. Our studies point toward possible applications of pharmaceutical excipients to carry out in vitro glucuronidation of substrates with poor aqueous solubility, in order to estimate Cl(int) and subsequently scaled organ clearance values. PMID:21084760

Argikar, Upendra A; Liang, Guiqing; Bushee, Jennifer L; Hosagrahara, Vinayak P; Lee, Wendy

2011-01-01

141

Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine  

Microsoft Academic Search

Objective: To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the\\u000a relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients.\\u000a \\u000a \\u000a \\u000a Methods: Forty patients with malignant disease and intolerable pain on weak opioids (codeine\\/dextropropoxyphen) were included. After\\u000a a wash-out period, titration with immediate-release (IR) morphine was started. When a stable

P. Klepstad; S. Kaasa; P. C. Borchgrevink

2000-01-01

142

High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol A and nonylphenol in rats.  

PubMed

4-n-Nonylphenol and bisphenol A are endocrine disrupting chemicals that are mainly detoxified through glucuronidation. A factor that may modulate their glucuronidation rates is co-exposure to pharmaceuticals. This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors. Nonylphenol and bisphenol A were co-incubated in freshly isolated rat hepatocytes with, drugs at a high concentration. Statistically significant metabolic inhibition of bisphenol A and nonylphenol biotransformation was observed with nine drugs (>50% inhibition by naproxen, salicylic acid, carbamazepine and mefenamic acid). Inhibition assays of UGT activity in rat liver microsomes revealed: 1) competitive inhibition by naproxen (K(i)(app) = 848.3 microM) and carbamazepine (K(i)(app) = 1023.1 microM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition. Detoxification of nonylphenol and bisphenol A was shown to be impaired by excessive concentrations of many drugs and health risk assessment should therefore address this issue. PMID:19916736

Verner, M-A; Magher, T; Haddad, S

2010-02-01

143

Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites.  

PubMed

The liver is the primary site of drug metabolism in the body. Typically, metabolic conversion of a drug results in inactivation, detoxification, and enhanced likelihood for excretion in urine or feces. Sulfation, glucuronidation, and glutathione conjugation represent the three most prevalent classes of phase II metabolism, which may occur directly on the parent compounds that contain appropriate structural motifs, or, as is usually the case, on functional groups added or exposed by phase I oxidation. These three conjugation reactions increase the molecular weight and water solubility of the compound, in addition to adding a negative charge to the molecule. As a result of these changes in the physicochemical properties, phase II conjugates tend to have very poor membrane permeability, and necessitate carrier-mediated transport for biliary or hepatic basolateral excretion into sinusoidal blood for eventual excretion into urine. This review summarizes sulfation, glucuronidation, and glutathione conjugation reactions, as well as recent progress in elucidating the hepatic transport mechanisms responsible for the excretion of these conjugates from the liver. The discussion focuses on alterations of metabolism and transport by chemical modulators, and disease states, as well as pharmacodynamic and toxicological implications of hepatic metabolism and/or transport modulation for certain active phase II conjugates. A brief discussion of issues that must be considered in the design and interpretation of phase II metabolite transport studies follows. PMID:16472997

Zamek-Gliszczynski, Maciej J; Hoffmaster, Keith A; Nezasa, Ken-ichi; Tallman, Melanie N; Brouwer, Kim L R

2006-04-01

144

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

PubMed

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

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

2008-05-01

145

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

Code of Federal Regulations, 2010 CFR

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

2010-04-01

146

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

Code of Federal Regulations, 2011 CFR

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

2011-04-01

147

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

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Importation of ethyl alcohol for nonbeverage purposes. 10.99 Section...REDUCED RATE, ETC. General Provisions Ethyl Alcohol § 10.99 Importation of ethyl alcohol for nonbeverage purposes. (a)...

2013-04-01

148

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

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Importation of ethyl alcohol for nonbeverage purposes. 10.99 Section...REDUCED RATE, ETC. General Provisions Ethyl Alcohol § 10.99 Importation of ethyl alcohol for nonbeverage purposes. (a)...

2012-04-01

149

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

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Importation of ethyl alcohol for nonbeverage purposes. 10.99 Section...REDUCED RATE, ETC. General Provisions Ethyl Alcohol § 10.99 Importation of ethyl alcohol for nonbeverage purposes. (a)...

2014-04-01

150

4-Chloro-3-ethyl­phenol  

PubMed Central

The title compound, C8H9ClO, packs with two independent mol­ecules in the asymmetric unit, without significant differences in corresponding bond lengths and angles, with the ethyl group in each oriented nearly perpendicular to the aromatic ring having ring-to-side chain torsion angles of 81.14?(18) and ?81.06?(19)°. In the crystal, mol­ecules form an O—H?O hydrogen-bonded chain extending along the b-axis direction, through the phenol groups in which the H atoms are disordered. These chains pack together in the solid state, giving a sheet lying parallel to (001), via an offset face-to-face ?-stacking inter­action characterized by a centroid–centroid distance of 3.580?(1)?Å, together with a short inter­molecular Cl?Cl contact [3.412?(1)?Å]. PMID:25161582

Majer, Sean H.; Tanski, Joseph M.

2014-01-01

151

The gelation of oil using ethyl cellulose.  

PubMed

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

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

2015-03-01

152

Simultaneous spectrophotometric determination of maltol, ethyl maltol, vanillin and ethyl vanillin in foods by multivariate calibration and artificial neural networks  

Microsoft Academic Search

Maltol (MAL), ethyl maltol (EMA), vanillin (VAN) and ethyl vanillin (EVA) are food additives, and they have well defined UV spectra. However, these overlapped seriously, and it is difficult to determine them individually from their mixtures without a pre-separation. In this paper, chemometric approaches were applied to resolve the overlapping spectra and to determine these compounds simultaneously. The analysis of

Yongnian Ni; Guowen Zhang; Serge Kokot

2005-01-01

153

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

PubMed

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

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

2013-12-01

154

Antioxidant activity of phenolic acids and their metabolites: synthesis and antioxidant properties of the sulfate derivatives of ferulic and caffeic acids and of the acyl glucuronide of ferulic acid.  

PubMed

The main metabolites of caffeic and ferulic acids (ferulic acid-4'-O-sulfate, caffeic acid-4'-O-sulfate, and caffeic acid-3'-O-sulfate), the most representative phenolic acids in fruits and vegetables, and the acyl glucuronide of ferulic acid were synthesized, purified, and tested for their antioxidant activity in comparison with those of their parent compounds and other related phenolics. Both the ferric reducing antioxidant power (FRAP) assay and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging method were used. Ferulic acid-4'-O-sulfate and ferulic acid-4'-O-glucuronide exhibited very low antioxidant activity, while the monosulfate derivatives of caffeic acid were 4-fold less efficient as the antioxidant than caffeic acid. The acyl glucuronide of ferulic acid showed strong antioxidant action. The antioxidant activity of caffeic acid-3'-O-glucuronide and caffeic acid-4'-O-glucuronide was also studied. Our results demonstrate that some of the products of phenolic acid metabolism still retain strong antioxidant properties. Moreover, we first demonstrate the ex vivo synthesis of the acyl glucuronide of ferulic acid by mouse liver microsomes, in addition to the phenyl glucuronide. PMID:23157164

Piazzon, A; Vrhovsek, U; Masuero, D; Mattivi, F; Mandoj, F; Nardini, M

2012-12-19

155

Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.  

PubMed

Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk. PMID:25233931

Murphy, Sharon E; Park, Sung-Shim L; Thompson, Elizabeth F; Wilkens, Lynne R; Patel, Yesha; Stram, Daniel O; Le Marchand, Loic

2014-11-01

156

The glucuronidation of R- and S-lorazepam: human liver microsomal kinetics, UDP-glucuronosyltransferase enzyme selectivity, and inhibition by drugs.  

PubMed

The widely used hypnosedative-anxiolytic agent R,S-lorazepam is cleared predominantly by conjugation with glucuronic acid in humans, but the enantioselective glucuronidation of lorazepam has received little attention. The present study characterized the kinetics of the separate R and S enantiomers of lorazepam by human liver microsomes (HLMs) and by a panel of recombinant human UDP-glucuronosyltransferase (UGT) enzymes. Respective mean K(m) and V(max) values for R- and S-lorazepam glucuronidation by HLM were 29 ± 8.9 and 36 ± 10 µM, and 7.4 ± 1.9 and 10 ± 3.8 pmol/min ? mg. Microsomal intrinsic clearances were not significantly different, suggesting the in vivo clearances of R- and S-lorazepam are likely to be similar. Both R- and S-lorazepam were glucuronidated by UGT2B4, 2B7, and 2B15, whereas R-lorazepam was additionally metabolized by the extrahepatic enzymes UGT1A7 and 1A10. Based on in vitro clearances and consideration of available in vivo and in vitro data, UGT2B15 is likely to play an important role in the glucuronidation of R- and S-lorazepam. However, the possible contribution of other enzymes and the low activities observed in vitro indicate that the lorazepam enantiomers are of limited use as substrate probes for UGT2B15. To identify potential drug-drug interactions, codeine, fluconazole, ketamine, ketoconazole, methadone, morphine, valproic acid, and zidovudine were screened as inhibitors of R- and S-lorazepam glucuronidation by HLM. In vitro-in vivo extrapolation suggested that, of these drugs, only ketoconazole had the potential to inhibit lorazepam clearance to a clinically significant extent. PMID:23554428

Uchaipichat, Verawan; Suthisisang, Chuthamanee; Miners, John O

2013-06-01

157

Orbital floor reconstruction with ethyl-2-cyanoacrylate.  

PubMed

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

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

2015-02-01

158

40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.  

Code of Federal Regulations, 2014 CFR

... Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2014-07-01

159

40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.  

Code of Federal Regulations, 2013 CFR

... Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2013-07-01

160

40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.  

Code of Federal Regulations, 2012 CFR

... Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2012-07-01

161

40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.  

Code of Federal Regulations, 2011 CFR

... Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2011-07-01

162

Experimental Pathology Laboratories, Inc. Ethyl-Tertiary-Butyl Ether  

E-print Network

Experimental Pathology Laboratories, Inc. Ethyl-Tertiary-Butyl Ether C00117/00117-64 AMENDED PATHOLOGY QUALITY ASSESSMENT REVIEW AND PWG COORDINATOR'S REPORT Park, NC 27709 Submitted by: Experimental Pathology Laboratories, Inc. Street Address: Mailing Address

Baker, Chris I.

163

40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

... Quizalofop ethyl; tolerances for residues. 180.441 Section 180.441...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2010-07-01

164

77 FR 26456 - Carfentrazone-ethyl; Pesticide Tolerances  

Federal Register 2010, 2011, 2012, 2013, 2014

...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...

2012-05-04

165

Ethyl Butanoate Formation by Dairy Lactic Acid Bacteria  

Microsoft Academic Search

The formation of ethyl butanoate by non-growing cells of 22 starter and 49 non-starter dairy lactic acid bacteria (LAB) varied widely (0.4–310units 100mg-1 dry weight cells) and was both species and strain dependent. Strains of the thermophilic starter Streptococcus salivarius subsp. thermophilus produced the highest levels of ethyl butanoate (an average of 156 units 100mg-1 dry weight cells), while strains

S.-Q Liu; R Holland; V. L Crow

1998-01-01

166

Ethyl alcohol: experimental agent for interventional therapy of neurovascular lesions.  

PubMed

Perfusion of absolute ethyl alcohol into the middle cerebral artery of six rhesus monkeys was performed using the Pevsner miniballoon catheter system. The animals were sacrificed by thoracotomy and intracardiac perfusion of a mixed aldehyde solution for fixation. Preliminary angiography and electron microscopy suggest absolute ethyl alcohol is a good neurovascular occlusive agent, and a possible replacement for isobutyl 2-cyanoacrylate in the treatment of angiomas and tumors. PMID:6410752

Pevsner, P H; Klara, P; Doppman, J; George, E; Girton, M

1983-01-01

167

(2-Ethyl-2-oxazoline-?N)bis(N-ethyl-N-phenyl­dithio­carbamato-?2 S,S?)cadmium  

PubMed Central

In the title compound, [Cd(C9H10NS2)2(C5H9NO)], the CdII atom is five-coordinated in a distorted square-pyramidal geometry by four S atoms from two chelating N-ethyl-N-phenyl dithio­carbamate ligands and one N atom from a 2-ethyl-2-oxazoline ligand. Inter­molecular C—H?? inter­actions are observed in the crystal structure. PMID:23125621

Onwudiwe, Damian C.; Strydom, Christien A.; Hosten, Eric C.

2012-01-01

168

Three-Dimensional Quantitative Structure-Activity Relationship Studies on UGT1A9-Mediated 3-O-Glucuronidation of Natural Flavonols Using a Pharmacophore-Based Comparative Molecular Field Analysis ModelS?  

PubMed Central

Glucuronidation is often recognized as one of the rate-determining factors that limit the bioavailability of flavonols. Hence, design and synthesis of more bioavailable flavonols would benefit from the establishment of predictive models of glucuronidation using kinetic parameters [e.g., Km, Vmax, intrinsic clearance (CLint) = Vmax/Km] derived for flavonols. This article aims to construct position (3-OH)-specific comparative molecular field analysis (CoMFA) models to describe UDP-glucuronosyltransferase (UGT) 1A9-mediated glucuronidation of flavonols, which can be used to design poor UGT1A9 substrates. The kinetics of recombinant UGT1A9-mediated 3-O-glucuronidation of 30 flavonols was characterized, and kinetic parameters (Km, Vmax, CLint) were obtained. The observed Km, Vmax, and CLint values of 3-O-glucuronidation ranged from 0.04 to 0.68 ?M, 0.04 to 12.95 nmol/mg/min, and 0.06 to 109.60 ml/mg/min, respectively. To model UGT1A9-mediated glucuronidation, 30 flavonols were split into the training (23 compounds) and test (7 compounds) sets. These flavonols were then aligned by mapping the flavonols to specific common feature pharmacophores, which were used to construct CoMFA models of Vmax and CLint, respectively. The derived CoMFA models possessed good internal and external consistency and showed statistical significance and substantive predictive abilities (Vmax model: q2 = 0.738, r2 = 0.976, rpred2 = 0.735; CLint model: q2 = 0.561, r2 = 0.938, rpred2 = 0.630). The contour maps derived from CoMFA modeling clearly indicate structural characteristics associated with rapid or slow 3-O-glucuronidation. In conclusion, the approach of coupling CoMFA analysis with a pharmacophore-based structural alignment is viable for constructing a predictive model for regiospecific glucuronidation rates of flavonols by UGT1A9. PMID:21068207

Wu, Baojian; Morrow, John Kenneth; Singh, Rashim; Zhang, Shuxing

2011-01-01

169

Enantiomer selective glucuronidation of the non-steroidal pure anti-androgen bicalutamide by human liver and kidney: role of the human UDP-glucuronosyltransferase (UGT)1A9 enzyme.  

PubMed

Bicalutamide (Casodex(®) ) is a non-steroidal pure anti-androgen used in the treatment of localized prostate cancer. It is a racemate drug, and its activity resides in the (R)-enantiomer, with little in the (S)-enantiomer. A major metabolic pathway for bicalutamide is glucuronidation catalysed by UDP-glucuronosyltransferase (UGT) enzymes. While (S)bicalutamide is directly glucuronidated, (R)bicalutamide requires hydroxylation prior to glucuronidation. The contribution of human tissues and UGT isoforms in the metabolism of these enantiomers has not been extensively investigated. In this study, both (R) and/or (S)bicalutamide were converted into glucuronide (-G) derivatives after incubation of pure and racemic solutions with microsomal extracts from human liver and kidney. Intestinal microsomes exhibited only low reactivity with these substrates. Km values of liver and kidney samples for (S)bicalutamide glucuronidation were similar, and lower than values obtained with the (R)-enantiomer. Among the 16 human UGTs tested, UGT1A8 and UGT1A9 were able to form both (S) and (R)bicalutamide-G from pure or racemic substrates. UGT2B7 was also able to form (R)bicalutamide-G. Kinetic parameters of the recombinant UGT2B7, UGT1A8 and UGT1A9 enzymes support a predominant role of the UGT1A9 isoform in bicalutamide metabolism. Accordingly, (S)bicalutamide inhibited the ability of human liver and kidney microsomes to glucuronidate the UGT1A9 probe substrate, propofol. In conclusion, the present study provides the first comprehensive analysis of in vitro bicalutamide glucuronidation by human tissues and UGTs and identifies UGT1A9 as a major contributor for (R) and (S) glucuronidation in the human liver and kidney. PMID:23527766

Grosse, Laurent; Campeau, Anne-Sophie; Caron, Sarah; Morin, Frédéric-Alexandre; Meunier, Kim; Trottier, Jocelyn; Caron, Patrick; Verreault, Mélanie; Barbier, Olivier

2013-08-01

170

Modulation of Strawberry/Cranberry Phenolic Compounds Glucuronidation by Co-Supplementation with Onion: Characterization of Phenolic Metabolites in Rat Plasma Using an Optimized ?SPE-UHPLC-MS/MS Method.  

PubMed

Plant phenolic compounds are suggested to exert pharmacological activities in regards to obesity and type-2 diabetes, but their mode of action is poorly understood due to a lack of information about their bioavailability. This work aimed to study the bioavailability of GlucoPhenol phenolic compounds, a strawberry-cranberry extracts blend, by characterizing plasma phenolic profile in obese rats. A comparison was performed by co-supplementation with an onion extract. Using an optimized ?SPE-UHPLC-MS/MS method, 21 phenolic metabolites were characterized, mostly conjugated metabolites and microbial degradation products of the native phenolic compounds. Their kinetic profiles revealed either an intestinal or hepatic formation. Among identified metabolites, isorhamnetin glucuronide sulfate was found in greater amount in plasma. Three glucuronidated conjugates of strawberry-cranberry phenolic compounds, p-hydroxybenzoic acid glucuronide, catechins glucuronide, and methyl catechins glucuronide were found in higher quantities when GlucoPhenol was ingested together with onion extract (+252%, +279%, and +118% respectively), suggesting a possible induction of glucuronidation processes by quercetin. This work allowed the characterization of actual phenolic metabolites generated in vivo following a phenolic intake, the analysis of their kinetics and suggested a possible synergistic activity of phenolic compounds for improving bioavailability. PMID:24628392

Dudonné, Stéphanie; Dubé, Pascal; Pilon, Geneviève; Marette, André; Jacques, Hélène; Weisnagel, John; Desjardins, Yves

2014-03-26

171

An in vitro experiment on the interaction of charcoal or wheat bran with 11-nor-9-carboxy-?(9)-tetrahydrocannabinol and its glucuronide.  

PubMed

The rather long yet variable terminal half-lives and detection times since last use of urinary cannabinoids may partly be attributed to their enterohepatic circulation which generally can be interrupted or restricted by chemical adsorbents. Therefore, an in vitro experiment was performed to study the adsorption/binding of 11-nor-9-carboxy-?9-tetrahydrocannabinol (THC-COOH) and its glucuronide to activated charcoal and wheat bran; remaining concentrations were determined by liquid chromatography/tandem mass spectrometry. Adsorption/binding of 1,000 ng/mL of free or conjugated THC-COOH was complete using as little as 5 mg of charcoal whereas adsorption/binding to wheat bran increased with increasing amounts. Taking of remedies affecting enterohepatic recycling of THC-COOH and its glucuronide may challenge interpretation of cannabinoid concentrations used to detect or assess frequency of drug use or the time since last drug consumption. PMID:24077855

Skopp, Gisela; Mikus, Gerd

2013-11-01

172

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, 2014 CFR

...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...processed, or used in the employer's workplace, the employer...

2014-07-01

173

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, 2012 CFR

...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...processed, or used in the employer's workplace, the employer...

2012-07-01

174

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

...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12- 18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...processed, or used in the employer's workplace, the employer...

2010-07-01

175

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, 2011 CFR

...diester with C12-18 fatty acids, ethyl sulfates (salts...diester with C12- 18 fatty acids, ethyl sulfates (salts...diester with C12-18 fatty acids, ethyl sulfates (salts...processed, or used in the employer's workplace, the employer...

2011-07-01

176

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

...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...

2013-07-01

177

Evaluation of in situ generated valproyl 1-O-?-acyl glucuronide in valproic acid toxicity in sandwich-cultured rat hepatocytes.  

PubMed

Acyl glucuronides are reactive electrophilic metabolites implicated in the toxicity of carboxylic acid drugs. Valproyl 1-O-?-acyl glucuronide (VPA-G), which is a major metabolite of valproic acid (VPA), has been linked to the development of oxidative stress in VPA-treated rats. However, relatively little is known about the toxicity of in situ generated VPA-G and its contribution to VPA hepatotoxicity. Therefore, we investigated the effects of modulating the in situ formation of VPA-G on lactate dehydrogenase (LDH) release (a marker of necrosis), BODIPY 558/568 C12 accumulation (a marker of steatosis), and cellular glutathione (GSH) content in VPA-treated sandwich-cultured rat hepatocytes. VPA increased LDH release and BODIPY 558/568 C12 accumulation, whereas it had little or no effect on total GSH content. Among the various uridine 5'-diphospho-glucuronosyltransferase inducers evaluated, ?-naphthoflavone produced the greatest increase in VPA-G formation. This was accompanied by an attenuation of the increase in BODIPY 558/568 C12 accumulation, but did not affect the change in LDH release or total GSH content in VPA-treated hepatocytes. Inhibition of in situ formation of VPA-G by borneol was not accompanied by substantive changes in the effects of VPA on any of the toxicity markers. In a comparative study, in situ generated diclofenac glucuronide was not toxic to rat hepatocytes, as assessed using the same chemical modulators, thereby demonstrating the utility of the sandwich-cultured rat hepatocyte model. Overall, in situ generated VPA-G was not toxic to sandwich-cultured rat hepatocytes, suggesting that VPA glucuronidation per se is not expected to be a contributing mechanism for VPA hepatotoxicity. PMID:25147275

Surendradoss, Jayakumar; Chang, Thomas K H; Abbott, Frank S

2014-11-01

178

Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [ 13 C 3] isoflavone internal standards  

Microsoft Academic Search

A method has been developed for the analysis of phytoestrogens and their conjugates in human urine using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS\\/MS). Stable isotopically labeled [13C3]daidzein and [13C3]genistein were synthesized and used as internal standards for isotope dilution mass spectrometry. Free aglycons and intact glucuronide, sulfate, diglucuronide, disulfate, and mixed sulfoglucuronide conjugates of isoflavones and lignans were

Don B Clarke; Antony S Lloyd; Nigel P Botting; Mark F Oldfield; Paul W Needs; Helen Wiseman

2002-01-01

179

Hydrolysis of the soluble fluorescent molecule carboxyumbelliferyl-beta-D-glucuronide by E. coli beta-glucuronidase as applied in a rugged, in situ optical sensor.  

PubMed

Techniques utilizing ?-glucuronidase (GUS) activity as an indicator of Escherichia coli (E. coli) presence use labeled glucuronides to produce optical signals. Carboxyumbelliferyl-?-d-glucuronide (CUGlcU) is a fluorescent labeled glucuronide that is soluble and highly fluorescent at natural water pHs and temperatures and, therefore, may be an ideal reagent for use in an in situ optical sensor. This paper reports for the first time the Michaelis-Menten kinetic parameters for the binding of E. coli GUS with CUGlcU as K(m)=910 ?M, V(max)=41.0 ?M min(-1), V(max)/K(m) 45.0 ?mol L(-1)min(-1), the optimal pH as 6.5 ± 1.0, optimal temperature as 38°C, and the Gibb's free energy of activation as 61.40 kJ mol(-1). Additionally, it was found CUGlcU hydrolysis is not significantly affected by heavy solvents suggesting proton transfer and solvent addition that occur during hydrolysis are not limiting steps. Comparison studies were made with the more common fluorescent molecule methylumbelliferyl-?-d-glucuronide (MUGlcU). Experiments showed GUS preferentially binds to MUGlcU in comparison to CUGlcU. CUGlcU was also demonstrated in a prototype optical sensor for the detection of E. coli. Initial bench testing of the sensor produced detection of low concentrations of E. coli (1.00 × 10(3)CFU/100mL) in 230 ± 15.1 min and high concentrations (1.05×10(5)CFU/100mL) in 8.00 ± 1.01 min. PMID:22112264

Geary, Joseph R; Nijak, Gary M; Larson, Steven L; Talley, Jeffrey W

2011-06-10

180

Design of experiments, a powerful tool for method development in forensic toxicology: application to the optimization of urinary morphine 3-glucuronide acid hydrolysis  

Microsoft Academic Search

The application of the design of experiments to optimize method development in the field of forensic toxicology using the\\u000a urinary morphine 3-glucuronide acid hydrolysis as an example is described. Morphine and its trideuterated analogue (used as\\u000a an internal standard) were extracted from urine samples by liquid–liquid extraction (ToxiTubes® A) and derivatized by silylation.\\u000a Chromatographic analysis was done by gas chromatography–mass

S. Costa; M. Barroso; A. Castañera; M. Dias

2010-01-01

181

Accurate Prediction of Glucuronidation of Structurally Diverse Phenolics by Human UGT1A9 Using Combined Experimental and In Silico Approaches  

PubMed Central

Purpose The catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics were determined experimentally using 145 phenolics, and analyzed by 3D-QSAR methods. Methods The catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using the CoMFA and CoMSIA techniques. Molecular alignment of the substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered as a separate substrate. Results The 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2= 0.949, r2pred = 0.775; CoMSIA: q2 = 0.579, r2= 0.876, r2pred = 0.700). The contour coefficient maps were applied to elucidate structural features among substrates that are responsible for the selectivity differences. Furthermore, the contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9; this enabled us to identify the UGT1A9 catalytic pocket with a high degree of confidence. Conclusion The CoMFA/CoMSIA models can predict the substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and its substrate selectivity. PMID:22302521

Wu, Baojian; Wang, Xiaoqiang; Zhang, Shuxing; Hu, Ming

2012-01-01

182

Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee.  

PubMed

Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols. PMID:24216280

Marmet, Cynthia; Actis-Goretta, Lucas; Renouf, Mathieu; Giuffrida, Francesca

2014-01-01

183

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

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

Suominen, Tina; Uutela, Päivi; Ketola, Raimo A.; Bergquist, Jonas; Hillered, Lars; Finel, Moshe; Zhang, Hongbo; Laakso, Aki; Kostiainen, Risto

2013-01-01

184

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

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

Suominen, Tina; Uutela, Päivi; Ketola, Raimo A; Bergquist, Jonas; Hillered, Lars; Finel, Moshe; Zhang, Hongbo; Laakso, Aki; Kostiainen, Risto

2013-01-01

185

[Formation of ethyl carbamate in umeshu (plum liqueur)].  

PubMed

Samples of umeshu, a Japanese plum liqueur made from unripe plums, shochu and crystal sugar, were stored under fluorescent light, in the dark and in the refrigerator. The amount of ethyl carbamate formed in umeshu exposed to light or room temperature was larger than that in the dark or at low temperature. The amount of ethyl carbamate formed in umeshu to which cyanide had been added was larger than that in the absence of added cyanide. Thus, the amount of ethyl carbamate formed in the umeshu was increased by not only light and higher temperature, but also cyanide. Samples of model alcoholic beverages were stored under various conditions using red, yellow and blue cellophanes. The amount of ethyl carbamate formed in the model alcoholic beverage with blue cellophane was larger than in the cases of red and yellow cellophanes. It was found that the amount of ethyl carbamate formed in the model alcoholic beverage was increased by light in the wavelength range of 375-475 nm. PMID:11875819

Suzuki, K; Kamimura, H; Ibe, A; Tabata, S; Yasuda, K; Nishijima, M

2001-12-01

186

Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering  

PubMed Central

A previously unknown chemical structure, 6-desmethyl-6-ethylerythromycin A (6-ethylErA), was produced through directed genetic manipulation of the erythromycin (Er)-producing organism Saccharopolyspora erythraea. In an attempt to replace the methyl side chain at the C-6 position of the Er polyketide backbone with an ethyl moiety, the methylmalonate-specific acyltransferase (AT) domain of the Er polyketide synthase was replaced with an ethylmalonate-specific AT domain from the polyketide synthase involved in the synthesis of the 16-member macrolide niddamycin. The genetically altered strain was found to produce ErA, however, and not the ethyl-substituted derivative. When the strain was provided with precursors of ethylmalonate, a small quantity of a macrolide with the mass of 6-ethylErA was produced in addition to ErA. Because substrate for the heterologous AT seemed to be limiting, crotonyl-CoA reductase, a primary metabolic enzyme involved in butyryl-CoA production in streptomycetes, was expressed in the strain. The primary macrolide produced by the reengineered strain was 6-ethylErA. PMID:9636144

Stassi, D. L.; Kakavas, S. J.; Reynolds, K. A.; Gunawardana, G.; Swanson, S.; Zeidner, D.; Jackson, M.; Liu, H.; Buko, A.; Katz, L.

1998-01-01

187

Bidirectional placental transfer of Bisphenol A and its main metabolite, Bisphenol A-Glucuronide, in the isolated perfused human placenta.  

PubMed

The widespread human exposure to Bisphenol A (BPA), an endocrine disruptor interfering with developmental processes, raises the question of the risk for human health of BPA fetal exposure. In humans, highly variable BPA concentrations have been reported in the feto-placental compartment. However the human fetal exposure to BPA still remains unclear. The aim of the study was to characterize placental exchanges of BPA and its main metabolite, Bisphenol A-Glucuronide (BPA-G) using the non-recirculating dual human placental perfusion. This high placental bidirectional permeability to the lipid soluble BPA strongly suggests a transport by passive diffusion in both materno-to-fetal and feto-to-maternal direction, leading to a calculated ratio between fetal and maternal free BPA concentrations of about 1. In contrast, BPA-G has limited placental permeability, particularly in the materno-to-fetal direction. Thus the fetal exposure to BPA conjugates could be explained mainly by its limited capacity to extrude BPA-G. PMID:24933518

Corbel, T; Gayrard, V; Puel, S; Lacroix, M Z; Berrebi, A; Gil, S; Viguié, C; Toutain, P-L; Picard-Hagen, N

2014-08-01

188

A Nonlinear Mixed Effects Pharmacokinetic Model for Dapagliflozin and Dapagliflozin 3-O-glucuronide in Renal or Hepatic Impairment.  

PubMed

Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor in development for the treatment of type 2 diabetes mellitus. A semi-mechanistic population pharmacokinetic (PK) model was developed for dapagliflozin and its inactive metabolite dapagliflozin 3-O-glucuronide (D3OG) with emphasis on renal and hepatic contribution to dapagliflozin metabolism. Renal and hepatic impairment decreased the clearance of dapagliflozin to D3OG and the clearance of D3OG. The fraction of D3OG formed via the renal route decreased from 40-55% in subjects with normal renal function (creatinine clearance (CLcr) > 80?ml/min) to 10% in subjects with severe renal insufficiency (CLcr = 13?ml/min). The model-based simulations suggested that the increase of systemic exposure (AUCss) of dapagliflozin and D3OG was less than twofold in subjects with mild or moderate renal impairment. This population modeling analysis presents a useful approach to evaluate the impact of renal and hepatic function on the PK of dapagliflozin.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e42; doi:10.1038/psp.2013.20; advance online publication 8 May 2013. PMID:23887724

van der Walt, J-S; Hong, Y; Zhang, L; Pfister, M; Boulton, D W; Karlsson, M O

2013-01-01

189

Trichloridobis(ethyl­diphenyl­phosphine)(tetra­hydro­furan)­molybdenum(III)  

PubMed Central

In the mononuclear title compound, [MoCl3(C4H8O)(C14H15P)2], obtained by the reaction of trichloro­tris­(tetra­hydro­furan)­molybdenum(III) and ethyl­diphenyl­phosphine in tetra­hydro­furan (THF) solution, the MoIII atom is six-coordinated by one O atom of a THF mol­ecule, two P atoms from two ethyl­diphenyl­phosphine ligands and three Cl atoms in a distorted octa­hedral geometry. The C atoms of the THF molecule are disordered over two positions in a 0.55?(2):0.45?(2) ratio. PMID:21587711

Kruczy?ski, Tomasz; Pikies, Jerzy; Ponikiewski, ?ukasz

2010-01-01

190

Spectroscopic characterization and detection of Ethyl Mercaptan in Orion  

E-print Network

New laboratory data of ethyl mercaptan, CH$_{3}$CH$_{2}$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$_3$CH$_2$SH towards Orion KL. 77 unblended or slightly blended lines plus no missing transitions in the range 80-280 GHz support this identification. A detection of methyl mercaptan, CH$_{3}$SH, in the spectral survey of Orion KL is reported as well. Our column density results indicate that methyl mercaptan is $\\simeq$ 5 times more abundant than ethyl mercaptan in the hot core of Orion KL.

Kolesniková, L; Cernicharo, J; Alonso, J L; Daly, A M; Gordon, B P; Shipman, S T

2014-01-01

191

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

PubMed Central

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

Zahmatkesh, Saeed; Vakili, Mohammad Reza

2010-01-01

192

40 CFR 180.221 - O-Ethyl S-phenyl ethylphos-phonodithioate; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false O-Ethyl S-phenyl ethylphos-phonodithioate...FOOD Specific Tolerances § 180.221 O -Ethyl S -phenyl ethylphos-phonodithioate...established for residues of the insecticide O -Ethyl S...

2010-07-01

193

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

Code of Federal Regulations, 2012 CFR

...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]-,...

2012-07-01

194

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

Code of Federal Regulations, 2014 CFR

...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]-,...

2014-07-01

195

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

Code of Federal Regulations, 2013 CFR

...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]-,...

2013-07-01

196

The effects of pH on the enzymatic formation of ?-glucuronides of various retinoids by induced and noninduced microsomal UDPGA-glucuronosyltransferases of several rat tissues in vitro 1 1 Abbreviations used: acitretin, 9-(2?,3?,6? trimethyl, 4?methoxybenzyl1?) 3,7 dimethyl, nona-2,4,6,8 tetraenoic acid; acitretin-G, acitretin-glucuronide; BHT, butylated hydroxytoluene; CD367, tetramethyl, tetrahydro-anthracenyl-benzoic acid; CD367-G, CD367 glucuronide; HPLC, high-performance liquid chromatography; 3MC, 3-methylcholanthrene; MES, 2-[N-morpholino]ethanesulfonic acid; NEM, N-ethylmaleimide; 4-oxo-RA, 4-oxoretinoic acid; 4-oxo-RAG, 4-oxoretinoyl ?-glucuronide; RA, retinoic acid; RAG, retinoyl ?-glucuronide; RAR, retinoic acid receptor; ROL, retinol; RXR, retinoid X receptor; Tris, tris [hydroxymethyl] aminomethane; TTNPB, tetramethyl, tetrahydronaphthenyl-propenyl-benzoic acid; TTNPB-G, TTNPB glucuronide; UDPGA, UDP-glucuronic acid; UGT, UDPGA-glucuronosyl transferase  

Microsoft Academic Search

All-trans retinoyl-?-glucuronide, a prominent water-soluble metabolite of all-trans retinoic acid (RA) in animals, is formed by the enzymic transfer of the glucuronyl moiety of uridine diphosphoglucuronic acid to RA. Uridine diphosphoglucuronic acid glucuronosyl transferases (UGTs) of microsomal preparations catalyze this reaction. In noninduced rat liver microsomes, maximal activity was observed in the physiologic range (pH 6.9–7.5) for all-trans-RA, 9-cis-RA, all-trans-4-oxo-RA,

Giuseppe Genchi; Arun B Barua; Wei Wang; Wayne R Bidlack; James A Olson

1998-01-01

197

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 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...

2011-07-01

198

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 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...

2010-07-01

199

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 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...

2014-07-01

200

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 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...

2012-07-01

201

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 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...

2013-07-01

202

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

Code of Federal Regulations, 2010 CFR

... Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether... Additional requirements for carbon disulfide (carbon bisulfide) and ethyl ether...requirements of § 151.50-41 for carbon disulfide (carbon bisulfide ) and §...

2010-10-01

203

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

Code of Federal Regulations, 2012 CFR

...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...

2012-07-01

204

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

Code of Federal Regulations, 2013 CFR

...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...

2013-07-01

205

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

Code of Federal Regulations, 2012 CFR

...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...

2012-07-01

206

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

Code of Federal Regulations, 2011 CFR

...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...

2011-07-01

207

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

Code of Federal Regulations, 2010 CFR

...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,...

2010-07-01

208

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

Code of Federal Regulations, 2011 CFR

...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,...

2011-07-01

209

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

Code of Federal Regulations, 2013 CFR

...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,...

2013-07-01

210

Synthesis of Ethyl Nalidixate: A Medicinal Chemistry Experiment  

ERIC Educational Resources Information Center

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…

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

2012-01-01

211

MATERIAL SAFETY DATA SHEET ETHYL ALCOHOL USP -200 PROOF  

E-print Network

MATERIAL SAFETY DATA SHEET ETHYL ALCOHOL USP - 200 PROOF AAPER MSDS NUMBER: E200 EFFECTIVE DATE receiving this Material Safety Data Sheet (MSDS) to study it carefully to become aware of hazards, if any, of the product involved. In the interest of safety, you should: (1) notify your employees, agents

Choi, Kyu Yong

212

The antiestrogen [2-(4-benzyl-phenoxy)ethyl]diethylammonium  

E-print Network

)ethyl]diethylammonium chloride, (I), is a diphenylmethane analogue of the antiestrogen tamoxifen which antagonizes the binding hydrochloride (Ernst & Hite, 1976), and tamoxifen (Precigoux et al., 1979), the angles are 78 and 87 overlap. The same situation holds for (I) and tamoxifen, as tamoxifen and clomiphene have been shown

213

Reactions of 2- and 4-methylpyrylium salts with ethyl orthoformate  

Microsoft Academic Search

Under mild conditions 2- and 4-methylpyrylium salts react with ethyl orthoformate to give their ?-ethoxyvinyl derivatives. Symmetrical and unsymmetrical cyanine dyes were synthesized by heating the latter with 2- and 4-methylpyrylium salts or N-methylquinaldinium perchlorate. The pyrylocyanines react with perchloric acid to give bispyrylium salts, and they are converted to the corresponding pyridine bases by the action of ammonium acetate.

A. L. Vasserman; V. V. Mezheritskii; G. N. Dorofeenko

1974-01-01

214

Enantioselective Metabolism of Quizalofop-Ethyl in Rat  

PubMed Central

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

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

2014-01-01

215

Glucuronidation does not suppress the estrogenic activity of quercetin in yeast and human breast cancer cell model systems.  

PubMed

Several plant-derived molecules, referred to as phytoestrogens, are thought to mimic the actions of endogenous estrogens. Among these, quercetin, one of the most widespread flavonoids in the plant kingdom, has been reported as estrogenic in some occasions. However, quercetin occurs in substantial amounts as glycosides such as quercetin-3-O-glucoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) in dietary sources. It is now well established that quercetin undergoes substantial phase II metabolism after ingestion by humans, with plasma metabolites after a normal dietary intake rarely exceeding nmol/L concentrations. Therefore, attributing phytoestrogenic activity to flavonoids without taking into account the fact that it is their phase II metabolites that enter the circulatory system, will almost certainly lead to misleading conclusions. With the aim of clarifying the above issue, the goal of the present study was to determine if plant-associated quercetin glycosides and human phase II quercetin metabolites, actually found in human biological fluids after intake of quercetin containing foods, are capable of interacting with the estrogen receptors (ER). To this end, we used a yeast-based two-hybrid system and an estrogen response element-luciferase reporter assay in an ER-positive human cell line (MCF-7) to probe the ER interaction capacities of quercetin and its derivatives. Our results show that quercetin-3-O-glucuronide, one of the main human phase II metabolites produced after intake of dietary quercetin, displays ER?- and ER?-dependent estrogenic activity, the functional consequences of which might be related to the protective activity of diets rich in quercetin glycosides. PMID:24657077

Ruotolo, Roberta; Calani, Luca; Brighenti, Furio; Crozier, Alan; Ottonello, Simone; Del Rio, Daniele

2014-10-01

216

Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene.  

PubMed Central

Polychlorinated biphenyls (PCBs) can be metabolized by cytochromes P450 to hydroxylated biotransformation products. In mammalian studies, some of the hydroxylated products have been shown to be strong inhibitors of steroid sulfotransferases. As a part of ongoing research into the bioavailability of environmental pollutants in catfish intestine, we investigated the effects of a series of hydroxylated PCBs (OH-PCBs) on two conjugating enzymes, phenol-type sulfotransferase and glucuronosyltransferase. We incubated cytosolic and microsomal samples prepared from intestinal mucosa with 3-hydroxy-benzo[a]pyrene and appropriate cosubstrates and measured the effect of OH-PCBs on the formation of BaP-3-glucuronide and BaP-3-sulfate. We used PCBs with 4, 5, and 6 chlorine substitutions and the phenolic group in the ortho, meta, and para positions. OH-PCBs with the phenolic group in the ortho position were weak inhibitors of sulfotransferase; the median inhibitory concentration (IC50) ranged from 330 to 526 microM. When the phenol group was in the meta or para position, the IC50 was much lower (17.8-44.3 microM). The OH-PCBs were more potent inhibitors of glucuronosyltransferase, with IC50s ranging from 1.2 to 36.4 microM. The position of the phenolic group was not related to the inhibitory potency: the two weakest inhibitors of sulfotransferase, with the phenolic group in the ortho position, were 100 times more potent as inhibitors of glucuronosyltransferase. Inhibition of glucuronosyltransferase by low concentrations of OH-PCBs has not been reported before and may have important consequences for the bioavailability, bioaccumulation, and toxicity of other phenolic environmental contaminants. PMID:11940451

van den Hurk, Peter; Kubiczak, Gerhard A; Lehmler, Hans-Joachim; James, Margaret O

2002-01-01

217

Evaluation and mechanistic analysis of the cytotoxicity of the acyl glucuronide of nonsteroidal anti-inflammatory drugs.  

PubMed

The chemical reactivity of acyl glucuronide (AG) has been thought to be associated with the toxic properties of drugs containing carboxylic acid moieties, but there has been no direct evidence showing that AG formation is related to the observed toxicity. In the present study, the cytotoxicity of AGs, especially that associated with the inflammatory response, was investigated. The changes in the mRNA and protein expression levels of interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP)-1 induced by the treatment of human peripheral blood mononuclear cells (PBMCs) with diclofenac (Dic), probenecid (Pro), tolmetin (Tol), ibuprofen (Ibu), naproxen (Nap), and their AGs were investigated by real-time reverse transcription polymerase chain reaction, and the viabilities of CD3+, CD14+, and CD19+ cells were measured by flow cytometry. Treatment with Dic-AG, Pro-AG, and Tol-AG significantly increased the expression levels of IL-8 and MCP-1. In addition, Dic-AG, Pro-AG, and Tol-AG significantly decreased the viability of CD14+ cells. Of these three AGs, Dic-AG showed the most potent changes, followed by Tol-AG and Pro-AG. Treatment with Ibu-AG and Nap-AG affected neither the expression levels of IL-8 and MCP-1 nor the viability of CD14+ cells. None of the drugs affected the CD3+ and CD19+ cell populations. Dic-AG increased the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2. The pretreatment of peripheral blood mononuclear cells (PBMCs) with SB203580 (p38 inhibitor) significantly suppressed the Dic-AG-induced expression of inflammatory factors and cytotoxicity of CD14+ cells. In conclusion, AGs induce inflammatory responses and cytotoxicity against CD14+ cells via the p38 MAPK pathway. These factors may be useful biomarkers for evaluating the toxicity of AGs. PMID:24104198

Miyashita, Taishi; Kimura, Kento; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

2014-01-01

218

Quantitative determination of free and total bisphenol A in human urine using labeled BPA glucuronide and isotope dilution mass spectrometry.  

PubMed

Bisphenol A (BPA) is a widely used industrial chemical in the manufacturing of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt normal hormonal function and hence, potentially, have negative effects on the human health. While total BPA is frequently reported, it is recognized that free BPA is the biologically active form and is rarely reported in the literature. The objective of this study was to develop a sensitive and improved method for the measurement of free and total BPA in human urine. Use of a labeled conjugated BPA (bisphenol A-d6 ?-D-glucuronide) allowed for the optimization of the enzymatic reaction and permitted an accurate determination of the conjugated BPA concentration in urine samples. In addition, a (13)C12-BPA internal standard was used to account for the analytical recoveries and performance of the isotope dilution method. Solid-phase extraction (SPE) combined with derivatization and analysis using a triple quadrupole GC-EI/MS/MS system achieved very low method detection limit of 0.027 ng/mL. BPA concentrations were measured in urine samples collected during the second and third trimesters of pregnancy in 36 Canadian women. Total maternal BPA concentrations in urine samples ranged from not detected to 9.40 ng/mL (median, 1.21 ng/mL), and free BPA concentrations ranged from not detected to 0.950 ng/mL (median, 0.185 ng/mL). Eighty-six percent of the women had detectable levels of conjugated BPA, whereas only 22 % had detectable levels of free BPA in their urine. BPA levels measured in this study agreed well with data reported internationally. PMID:24817354

Kubwabo, Cariton; Kosarac, Ivana; Lalonde, Kaela; Foster, Warren G

2014-07-01

219

Natural prenylated resveratrol analogs arachidin-1 and -3 demonstrate improved glucuronidation profiles and have affinity for cannabinoid receptors  

PubMed Central

1. Rationale The therapeutic promise of trans-resveratrol (tRes) is limited by poor bioavailability following rapid metabolism. We hypothesise that trans-arachidin-1 (tA1) and trans-arachidin-3 (tA3), peanut hairy root-derived isoprenylated analogs of tRes, will exhibit slower metabolism/enhanced bioavailability and retain biological activity via cannabinoid receptor (CBR) binding relative to their non-prenylated parent compounds trans-piceatannol (tPice) and tRes, respectively. 2. Results The activities of eight human UDP-glucuronosyltransferases (UGTs) toward these compounds were evaluated. The greatest activity was observed for extrahepatic UGTs 1A10 and 1A7, followed by hepatic UGTs 1A1 and 1A9. Importantly, an additional isoprenyl and/or hydroxyl group in tA1 and tA3 slowed overall glucuronidation. CBR binding studies demonstrated that all analogs bound to CB1Rs with similar affinities (5–18 µM); however, only tA1 and tA3 bound appreciably to CB2Rs. Molecular modelling studies confirmed that the isoprenyl moiety of tA1 and tA3 improved binding affinity to CB2Rs. Finally, although tA3 acted as a competitive CB1R antagonist, tA1 antagonised CB1R agonists by both competitive and non-competitive mechanisms. 3. Conclusions Prenylated stilbenoids may be preferable alternatives to tRes due to increased bioavailability via slowed metabolism. Similar structural analogs might be developed as novel CB therapeutics for obesity and/or drug dependency. PMID:21970716

Brents, Lisa K.; Medina-Bolivar, Fabricio; Seely, Kathryn A.; Nair, Vipin; Bratton, Stacie M.; Ñopo-Olazabal, Luis; Patel, Ronak Y.; Liu, Haining; Doerksen, Robert J.; Prather, Paul L.; Radominska-Pandya, Anna

2013-01-01

220

40 CFR 721.4250 - Hexanoic acid, 2-ethyl-, ethenyl ester.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 false Hexanoic acid, 2-ethyl-, ethenyl ester...Substances § 721.4250 Hexanoic acid, 2-ethyl-, ethenyl ester...substance identified as hexanoic acid, 2-ethyl-, ethenyl...worker in the following state(s): Open liquid...

2012-07-01

221

40 CFR 721.4250 - Hexanoic acid, 2-ethyl-, ethenyl ester.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Hexanoic acid, 2-ethyl-, ethenyl ester...Substances § 721.4250 Hexanoic acid, 2-ethyl-, ethenyl ester...substance identified as hexanoic acid, 2-ethyl-, ethenyl...worker in the following state(s): Open liquid...

2013-07-01

222

40 CFR 721.4250 - Hexanoic acid, 2-ethyl-, ethenyl ester.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 false Hexanoic acid, 2-ethyl-, ethenyl ester...Substances § 721.4250 Hexanoic acid, 2-ethyl-, ethenyl ester...substance identified as hexanoic acid, 2-ethyl-, ethenyl...worker in the following state(s): Open liquid...

2014-07-01

223

40 CFR 721.4250 - Hexanoic acid, 2-ethyl-, ethenyl ester.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 false Hexanoic acid, 2-ethyl-, ethenyl ester...Substances § 721.4250 Hexanoic acid, 2-ethyl-, ethenyl ester...substance identified as hexanoic acid, 2-ethyl-, ethenyl...worker in the following state(s): Open liquid...

2011-07-01

224

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2010-12-29

225

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2013-02-12

226

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-12-30

227

Use of a sensitive and robust UPLC-MS/MS method to determine the gender-dependent pharmacokinetics in rats of emodin and its glucuronide  

PubMed Central

The purpose of this research was to set up a sensitive and consistent UPLC-UV and UPLCMS/MS method to analyze emodin and its glucuronidated metabolite, and to determine how gender differences affect its pharmacokinetic behaviors. In addition, a breast cancer resistance protein inhibitor dipyridamole was used to test how significant the absolute oral biovailabilty of emodin or its glucuronide is increased. A sensitive and fast UPLC-MS/MS method was successfully applied to determine emodin and its metabolite in male and female SD rat plasma. The absolute oral bioavailability of emodin was extremely low whether in male rats (7.5%) and female rats (5%). Following a single intravenous injection of 4 mg/kg emodin, the emodin plasma concentration-time data fit for a good two-compartment model either in male or female SD rats. The t1/2? were 13.26±6.28min (male rats) and 13.52±7.28min (female rats). The t1/2? were 187.38±0.16min (male rats) and 118.50±83.09min (female rats). Emodin showed significant gender differences in i.v. PK profiles with higher AUC values in male (422.71 ± 163.40 mg*?g/ml) than female (282.52 ± 98.42 mg*?g/ml) SD rats (n=6). Emodin glucuronide was suggested a good fit for single compartmental model for the plasma emodin metabolite concentrations. The t1/2Ke were 167.40±50.91min(male rats) and 251.31±114.20min (female rats), the area under the curve (AUC0-?, i.v.) were 2210.02 ± 950.09 mg*?g/ml and 1054.42 ± 290.31 mg*?g/ml (female rats)(n=6). There was no good fit for any PK compartmental model for the plasma concentration-time data for single dose oral administration of emodin (8mg/kg) and its metabolite. Analyzing the oral PK data using non-compartmental model, Cmax, Tmax and AUC0-?, p.o. of emodin in male rats were: 0.31±0.094 were ?g/ml, 18.00±6.71min and 65.76±34.77 mg*?g/ml respectively; whereas Cmax, Tmax and AUC0-?, p.o. of emodin in female rats were: 0.039±0.011 ?g/ml, 18.75±7.51min and 33.82±4.09 mg*?g/ml respectively. The parameters of emodin glucuronide were significant different with emodin, the Cmax, Tmax and AUC0-?, p.o of emodin glucuronide in male rats were 6.69±1.06 ?g/ml, 240min and 2261.89±655.87 mg*?g/ml respectively, in female rats, the Cmax, Tmax and AUC0-?, p.o. were 1.81±0.58 ?g/ml, 60min and 458.50±373.29 mg*?g/ml respectively. The absolute bioavailability of emodin glucuronide was 60% (male rats) and 15% (female rats). The absolute bioavailability of emodin was no significant changed (7.3%) in male rats by using dipyridamole, the bioavailability of metabolite of emodin was significant declined to 14.6%. PMID:21195574

Liu, Wei; Gao, Song; Zheng, Zhijie; Liu, Xi; Ye, Ling; Yang, Zhen; Hu, Ming; Liu, Zhongqiu

2014-01-01

228

Effects of P-glycoprotein and Mrp2 inhibitors on the hepatobiliary disposition of Rhodamine 123 and its glucuronidated metabolite in isolated perfused rat livers.  

PubMed

The hepatobiliary disposition of rhodamine 123 (RH-123) and its glucuronidated (RH-Glu) and deacylated (RH-110) metabolites were studied in an isolated perfused rat liver (IPRL) model in the presence and absence of P-glycoprotein (P-gp) and Mrp2 inhibitors. A single dose (180 microg) of RH-123 was added to a recirculating perfusate in the absence (Control) or presence of cyclosporine A (CyA) or dibromosulfophthalein (DBSP) in the perfusate. Serial (0-90 min) perfusate and bile and terminal liver samples were collected for analysis by HPLC. In the Control livers, 25.4 +/- 2.2% (mean +/- SD) of the dose was recovered as RH-123 (11.7 +/- 2.0%) and RH-Glu (13.2 +/- 0.9%) in the bile. Whereas CyA substantially (90%) reduced (p < 0.001) the biliary excretion of RH-123 without affecting the excretion of RH-Glu, DBSP reduced the biliary excretion of RH-Glu by >80% (p < 0.001) with no effect on the biliary excretion of RH-123. Mass balance studies showed that DBSP, in addition to reducing the biliary clearance of RH-Glu, also strongly inhibited the glucuronidation of RH-123, an effect that was confirmed in vitro using the glucuronidation marker umbelliferone. It is concluded that the use of RH-123 in an IPRL model may serve as a dual marker for the determination of the altered functions of P-gp and/or Mrp2. PMID:19499568

Parasrampuria, Ridhi; Mehvar, Reza

2010-01-01

229

Coal liquefaction process with controlled recycle of ethyl acetate-insolubles  

SciTech Connect

A process for increasing the conversion of coal to ethyl acetate-soluble products comprising: (a) heating a slurry comprising a solvent and particulate coal in a dissolution zone to produce a first effluent slurry comprising ethyl acetate-soluble liquid components and ethyl acetate-insolubles; (b) contacting at least a portion of said first effluent slurry with hydrogen in a reaction zone in the presence of an externally-supplied hydrogenation catalyst under hydrogenation conditions to produce a second effluent slurry which comprises ethyl acetate-soluble liquid components and ethyl acetate-insolubles, said ethyl acetate insolubles comprising organic components and inorganic components; (c) partitioning said ethyl acetate-insolubles in at least a portion of said second effluent slurry to provide a solids-rich fraction containing ethyl acetate-insolubles enriched in inorganic components and a solids-lean fraction containing ethyl acetate insolubles enriched in organic components; and (d) recycling at least a portion of said solids-lean fraction to said dissolution zone, said recycle stream containing ethyl acetate-insolubles in an amount (1) sufficient to increase substantially the conversion of said coal to ethyl acetate-soluble components and (2) insufficient to cause the hydrogenation fouling rate of said catalyst to exceed 0.3/sup 0/ C. per hour.

Kuehler, C.W.; Samil, B.

1984-01-31

230

Preparation of ethyl magnesium bromide for regiospecific analysis of triacylglycerols.  

PubMed

This paper presents a procedure for preparation of a Grignard reagent, ethyl magnesium bromide, used for partial deacylation of triacylglycerols (TAG) in their regiospecific analysis. Magnesium turnings were reacted with ethereal solution of bromoethane in a screw-capped test tube to synthesize 2 mL of 1 M ethyl magnesium bromide. Continuously stirred with a vortex mixer, the reaction smoothly proceeded at room temperature. Regiospecific analysis of 1,3-distearoyl-2-oleoylglycerol using this product showed that fatty acid compositions of the sn-1(3) and sn-2 positions were contaminated by less than 2 mol% of fatty acids migrated from isomeric positions. The analyses of lard and cod liver/mackerel oil TAG showed typical distribution patterns of 16:0, 22:5n-3 and 22:6n-3 in pig and fish depot TAG. These results confirmed the view that the freshly prepared reagent is usable for regiospecific analysis of TAG. PMID:18622130

Ando, Yasuhiro; Tomita, Yuki; Haba, Yusuke

2008-01-01

231

Identification of an antioxidant, ethyl protocatechuate, in peanut seed testa.  

PubMed

The antioxidant activity and identification of the antioxidant component of peanut seed testa were investigated. The antioxidant activity of peanut seed testa was studied in the linoleic acid model system by using the ferric thiocyanate method. Among the five organic solvent extracts, the ethanolic extracts of peanut seed testa (EEPST) produced higher yields and stronger antioxidant activity than other organic solvent extracts. EEPST was separated into 17 fractions on silica gel column chromatography. Fraction 17, which showed the largest yield and significant antioxidant activity, was separated by thin-layer chromatography. Four major antioxidative subfractions were present. Subfraction 17-2 was found to be effective in preventing oxidation of linoleic acid. This subfraction was further fractionated and isolated and characterized by UV, MS, IR, and (1)H NMR techniques. The active compound was identified as ethyl protocatechuate (3,4-dihydroxybenzoic acid ethyl ester). PMID:12670184

Huang, Shiow Chyn; Yen, Gow-Chin; Chang, Lee-Wen; Yen, Wen-Jye; Duh, Pin-Der

2003-04-01

232

Solubility behavior of ethyl cellulose in supercritical fluid solvents  

Microsoft Academic Search

Solubility data to 180°C and 1200 bar are reported for ?1.0 wt.% ethyl cellulose (50% ethoxyl content, 2.5 average degree of substitution) (EC) in neat supercritical fluid (SCF) chlorodifluoromethane (F22); difluoromethane; 1-chloro-1,1-difluoroethane; 1,1-difluoroethane; and dimethyl ether (DME). The pressures needed to dissolve EC in the polar fluorocarbons decreases with increasing solvent size. The exception in this trend is F22 which

Dan Li; Mark A. McHugh

2004-01-01

233

Ethyl 2-acetyl­hydrazono-2-phenyl­acetate  

PubMed Central

The title compound, C12H14N2O3, was synthesized as an inter­mediate for the synthesis of metamitron. The benzene ring forms dihedral angles of 86.3?(2) and 10.0?(3)° with the ethyl group and the acetyl­imino plane, respectively. The crystal structure involves inter­molecular C—H?O and N—H?O hydrogen bonds. PMID:21200890

Xu, Liang-Zhong; Yi, Xu; An, Guang-Wei; Zhang, Gong-Sheng; Li, Chun-Fang

2008-01-01

234

Sensory reception of the primer pheromone ethyl oleate  

NASA Astrophysics Data System (ADS)

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.

Muenz, Thomas S.; Maisonnasse, Alban; Plettner, Erika; Le Conte, Yves; Rössler, Wolfgang

2012-05-01

235

Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.  

PubMed

Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications. PMID:22690908

Demiro?lu, Hasan; Avciba?i, Ugur; Ünak, Perihan; Müftüler, Fazilet Zümrüt Biber; ?çhedef, Ç A; Gümü?er, Fikriye Gül; Sakarya, Serhan

2012-08-01

236

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

E-print Network

between Tautomers and Its Effects on Enthalpies of Formation Patamaporn Umnahanant and James S. Chickos The enthalpies of formation of pure liquid and gas-phase ethyl 3-oxobutanoate and ethyl Z-3-hydroxy- 2-butenoate of formation of the equilibrium mixture, new enthalpies of formation for ethyl 3-oxobutanoate and ethyl Z-3

Chickos, James S.

237

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...

238

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...

239

Estimating Driver Risk Using Alcohol Biomarkers, Interlock BAC Tests and Psychometric Assessments: Initial Descriptives  

PubMed Central

Aim To identify alcohol biomarker and psychometric measures that relate to drivers’ blood alcohol concentration (BAC) patterns from ignition interlock devices (IIDs). Design, Setting, Participants, Measurements In Alberta, Canada, 534 drivers, convicted of driving under the influence of alcohol (DUI), installed IIDs and agreed to participate in a research study. IID BAC tests are an established proxy for predicting future DUI convictions. Three risk groups were defined by rates of failed BAC tests. Program entry and followup blood samples (n=302, 171) were used to measure phosphatidyl ethanol (PETH), carbohydrate deficient transferrin (%CDT), gamma glutamyltransferase (GGT) and other biomarkers. Program entry urine (n=130) was analyzed for ethyl glucuronide (ETG) and ethyl sulfate (ETS). Entry hair samples were tested for fatty acid ethyl esters (FAEE) (n=92) and ETG (n=146). Psychometric measures included the DSM-4 Diagnostic Interview Schedule Alcohol Module, Alcohol Use Disorders Identification Test (AUDIT), the Timeline Followback (TLFB), the Drinker Inventory of Consequences (DRINC), and the Temptation and Restraint Inventory (TRI). Findings Except for FAEE, all alcohol biomarkers were significantly related to the interlock BAC test profiles; higher marker levels predicted higher rates of interlock BAC test failures. PETH, the strongest with an overall ANOVA F ratio of 35.5, had significant correlations with all nine of the other alcohol biomarkers and with 16 of 19 psychometric variables. Urine ETG and ETS were strongly correlated with the IID BAC tests. Conclusions The findings suggest several alcohol biomarkers and assessments could play an important role in the prediction and control of driver alcohol risk when relicensing. PMID:19922520

Marques, Paul; Tippetts, Scott; Allen, John; Javors, Martin; Alling, Christer; Yegles, Michel; Pragst, Fritz; Wurst, Friedrich

2009-01-01

240

Morphine-3-glucuronide: evidence to support its putative role in the development of tolerance to the antinociceptive effects of morphine in the rat.  

PubMed

Antinociceptive tolerance to morphine (MOR) was induced in groups of Sprague-Dawley rats receiving continuous intravenous infusions of morphine sulphate administered by 3 different MOR dosing regimes. At appropriate intervals throughout each infusion period, antinociceptive testing was performed using the tail-flick latency test and blood samples were collected. Groups of saline (SAL)-infused control rats also underwent antinociceptive testing and blood sample collection. Complete antinociceptive tolerance developed during each MOR infusion period and was characterized by a marked decline in the degree of antinociception from values greater than 90% of the maximum possible effect (%MPE) to pre-dosing baseline values. By contrast, %MPE values in SAL-infused control animals and in sham-operated rats were not significantly different from pre-dosing values throughout the infusion period, indicating that the experimental procedures themselves did not contribute to the development of antinociceptive tolerance to MOR. In addition, the rate of MOR tolerance development was inversely proportional to the MOR infusion rate. A very significant inverse relationship was observed between the mean degree of antinociception (%MPE) and the mean plasma molar concentration ratio, [morphine-3-glucuronide]/[MOR], for each of the 3 MOR dosing regimes and for the cumulated data. This relationship showed that near-maximum antinociception was attainable at ratio values less than approximately 0.50, whilst at ratio values above approximately 1.5, little or no antinociception was observed. Although %MPE was highly inversely correlated with the mean plasma morphine-3-glucuronide (M3G) concentrations for rats receiving regimes A and B, this was not the case for rats receiving regime C where antinociceptive tolerance was partially reversed by an increase in the morphine infusion rate part-way through the infusion period. In addition, a poor relationship was observed between %MPE and the mean plasma MOR concentration, possibly due to the confounding presence of M3G in all samples. Thus, we may conclude from this study in Sprague-Dawley rats that irrespective of the rate of antinociceptive tolerance development, the level of antinociception achievable appears to be highly inversely correlated with the mean [M3G]/[MOR] plasma molar concentration ratio and poorly correlated with the plasma MOR concentration, consistent with the notion that it is perhaps the balance between the excitatory effects of M3G and the inhibitory effects of MOR at the functional level which is the important determinant. Further research is required in carefully conducted studies in cancer patients to evaluate the possible contribution of the MOR metabolites, M3G and morphine-6-glucuronide (MbG), to increasing dosing requirements of MOR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7478708

Smith, G D; Smith, M T

1995-07-01

241

Bis(ethyl­enediammonium) tetra­deca­borate  

PubMed Central

The title compound, 2C2H10N2 2+·B14O20(OH)6 4?, consists of a centrosymmetric tetra­deca­borate anion and two ethyl­enediammonium cations. The anions are inter­connected through strong O—H?O hydrogen bonds into a three-dimensional supra­molecular network with channels along [100], [010], [001] and [111]. The diprotonated cations reside in the channels and inter­act with the inorganic framework by extensive N—H?O hydrogen bonds. PMID:21580636

Wang, Guo-Ming; Wang, Pei; Li, Zeng-Xin; Li, Hui; Liu, Hui-Luan

2010-01-01

242

Effect of Aging on Glucuronidation of Valproic Acid in Human Liver Microsomes and the Role of UDP-Glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10  

PubMed Central

Valproic acid (VPA) is a widely used anticonvulsant that is also approved for mood disorders, bipolar depression, and migraine. In vivo, valproate is metabolized oxidatively by cytochromes P450 and ?-oxidation, as well as conjugatively via glucuronidation. The acyl glucuronide conjugate (valproate-glucuronide or VPAG) is the major urinary metabolite (30–50% of the dose). It has been hypothesized that glucuronidation of antiepileptic drugs is spared over age, despite a known decrease in liver mass. The formation rates of VPAG in a bank of elderly (65 years onward) human liver microsomes (HLMs) were measured by liquid chromatography/tandem mass spectrometry and compared with those in a younger (2–56 years) HLM bank. In vitro kinetic studies with recombinant UDP-glucuronosyltransferases (UGTs) were completed. A 5- to 8-fold variation for the formation of VPAG was observed within the microsomal bank obtained from elderly and younger donors. VPAG formation ranged from 6.0 to 53.4 nmol/min/mg protein at 1 mM substrate concentration (n = 36). The average velocities at 0.25, 0.5, and 1 mM VPA were 7.0, 13.4, and 25.4 nmol/min/mg protein, respectively, in the elderly HLM bank. Rates of VPAG formation were not significantly different in the HLM bank obtained from younger subjects. Intrinsic clearances (Vmax/Km) for several cloned, expressed UGTs were determined. UGT1A4, UGT1A8, and UGT1A10 also were found to catalyze the formation of VPAG in vitro. This is the first reported activity of these UGTs toward VPA glucuronidation. UGT2B7 had the highest intrinsic clearance, whereas UGT1A1 demonstrated no activity. In conclusion, our investigation revealed no differences in VPAG formation in younger versus elderly HMLs and revealed three other UGTs that form VPAG in vitro. PMID:18838507

Argikar, Upendra A.; Remmel, Rory P.

2009-01-01

243

Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N(+)-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry.  

PubMed

Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To investigate the pharmacokinetic profiles of morinidazole and its major metabolites in humans, a liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of morinidazole, its N-oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N(+)-glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced protein precipitation was employed to extract five analytes and internal standard metronidazole from 50?L human plasma. To avoid the interference from the in-source dissociation of the sulfate and achieve the baseline-separation of diastereoisomeric N(+)-glucuronides, all the analytes were separated from each other with the mobile phase consisting of 10mM ammonium formate and acetonitrile using gradient elution on a Hydro-RP C(18) column (50mm×2mm, 4?m) with a total run time of 5min. The API 4000 triple quadrupole mass spectrometer was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. The developed method was linear in the concentration ranges of 10.0-12,000ng/mL for morinidazole, 1.00-200ng/mL for M4-1, 2.50-500ng/mL for M7, 3.00-600ng/mL for M8-1, and 10.0-3000ng/mL for M8-2. The intra- and inter-day precisions for each analyte met the accepted value. Results of the stability of morinidazole and its metabolites in human plasma were also presented. The method was successfully applied to the clinical pharmacokinetic studies of morinidazole injection in healthy subjects, patients with moderate hepatic insufficiency, and patients with severe renal insufficiency, respectively. PMID:23122401

Gao, Ruina; Zhong, Dafang; Liu, Ke; Xia, Yu; Shi, Rongwei; Li, Hua; Chen, Xiaoyan

2012-11-01

244

Discovery of Methyl Acetate and Gauche Ethyl Formate in Orion  

NASA Astrophysics Data System (ADS)

We report on the discovery of methyl acetate, CH3COOCH3, through the detection of a large number of rotational lines from each one of the spin states of the molecule: AA species (A1 or A2), EA species (E1), AE species (E2), and EE species (E3 or E4). We also report, for the first time in space, the detection of the gauche conformer of ethyl formate, CH3CH2OCOH, 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) × 1015 cm-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) × 1014 cm-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. This work was based on observations carried out with the IRAM 30 m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).

Tercero, B.; Kleiner, I.; Cernicharo, J.; Nguyen, H. V. L.; López, A.; Muñoz Caro, G. M.

2013-06-01

245

Evolution of toxicity upon hydrolysis of fenoxaprop-p-ethyl.  

PubMed

Hydrolysis of fenoxaprop-p-ethyl (FE), a widely used herbicide, was studied in aqueous buffer solutions at pH ranging from 4.0 to 10.0. The degradation kinetics, strongly dependent on pH values, followed first-order kinetics. FE was relatively stable in neutral media, whereas it degraded rapidly with decreasing or increasing pH. In acidic conditions (pH = 4, 5), the benzoxazolyl-oxy-phenyl ether linkage of FE was cleaved to form ethyl 2-(4-hydroxyphenoxy)propanoate (EHPP) and 6-chloro-2,3-dihydrobenzoxazol-2-one (CDHB). While in basic conditions (pH = 8, 9, 10), herbicidal activity fenoxaprop-p (FA) was formed via breakdown of the ester bond of the herbicide. Both the two pathways were concurrent in neutral conditions (pH = 6, 7). Toxicity studies on Daphnia magna showed that FE was most toxic to D. magna with 48 h EC(50) of 14.3 micromol/L, followed by FA (43.8 micromol/L), CDHB (49.8 micromol/L), and EHPP (333.1 micromol/L). Mode of toxic action analysis indicated that EHPP exhibited toxicity via polar narcosis, whereas CDHB belonged to reactive acing compound. The mixture toxicity of CDHB and EHPP was nonadditive and can be predicted by a response addition model. Therefore, the evaluation of overall FE toxicity to D. magna in the aquatic systems needs to consider the degradation of FE. PMID:17685541

Lin, Jing; Chen, Jingwen; Cai, Xiyun; Qiao, Xianliang; Huang, Liping; Wang, Degao; Wang, Zhuang

2007-09-01

246

Transesterification process to manufacture ethyl ester of rape oil  

SciTech Connect

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].

Korus, R.A.; Hoffman, D.S.; Bam, N.; Peterson, C.L.; Drown, D.C. [Univ. of Idaho, Moscow, ID (United States)

1993-12-31

247

DISCOVERY OF METHYL ACETATE AND GAUCHE ETHYL FORMATE IN ORION  

SciTech Connect

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.

Tercero, B.; Cernicharo, J.; Lopez, A.; Caro, G. M. Munoz [Department of Astrophysics, CAB, INTA-CSIC, Crta Torrejon-Ajalvir, km. 4, E-28850 Torrejon de Ardoz, Madrid (Spain); Kleiner, I.; Nguyen, H. V. L., E-mail: terceromb@cab.inta-csic.es, E-mail: jcernicharo@cab.inta-csic.es, E-mail: lopezja@cab.inta-csic.es, E-mail: munozcg@cab.inta-csic.es, E-mail: isabelle.kleiner@lisa.u-pec.fr, E-mail: nguyen@pc.rwth-aachen.de [Laboratoire Interuniversitaire des Systemes Atmospheriques, CNRS/IPSL UMR7583 et Universites Paris Diderot et Paris Est, 61 av. General de Gaulle, F-94010 Creteil (France)

2013-06-10

248

Clinical (Non-forensic) Application Of Ethylglucuronide Measurement: Are We Ready?  

PubMed Central

Ethyl glucuronide (Etg) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary drug abuse screening, has largely been restricted to forensic and law enforcement situations. Despite a real need for an objective and possibly quantitative marker of ethanol exposure for use in conjunction with outpatient clinical trials and treatment programs, measurement of these metabolites has seen only limited clinical application. The barriers to more extensive clinical use of EtG/EtS testing, particularly misleading assay results that can occur as a consequence of inadvertent exposure to non-beverage ethanol containing substances, are reviewed and put into perspective. Additional information needed to develop guidelines for optimal clinical utilization of EtG/EtS measurements is discussed. PMID:20374218

Jatlow, Peter; O'Malley, Stephanie S.

2013-01-01

249

Biodegradation of benazolin-ethyl by strain Methyloversatilis sp. cd-1 isolated from activated sludge.  

PubMed

Benazolin-ethyl has been used on a wide range of weeds present in various crops since 1964. Because benazolin-ethyl is a potential hazard to the environment and human health, it is important to remove this herbicide from the environment. However, to the best of our knowledge, no report is available in the literature regarding the microbial degradation of benazolin-ethyl by bacteria. In this study, one strain named cd-1, which is capable of degrading benazolin-ethyl, was isolated from benazolin-ethyl wastewater treatment pool. The isolate was identified as Methyloversatilis sp. according to its morphological, physiological, biochemical properties, and 16S rRNA gene sequences analysis. This strain utilizes benazolin-ethyl as the sole carbon source. and degrades 100 mg l?¹ benazolin-ethyl to non-detectable level within 48 h. Three metabolites were identified as benazolin, 7-chloro-3-methylbenzo[d]thiazol-2(3H)-one, and 2-chloro-6-(methyleneamino)benzenethiol based on the MS/MS and GC/MS analyses. The first step involved in the degradation of benazolin-ethyl was the cleavage of the ester bond to form benazolin. Benazolin was subsequently subjected to demethylation for decomposition into 7-chloro-3-methylbenzo[d]thiazol-2(3H)-one and methanol. The last step was to form 2-chloro-6-(methyleneamino)benzenethiol. PMID:20848105

Cai, Tianming; Qian, Lihua; Cai, Shu; Chen, Liwei

2011-02-01

250

Orientational dynamics of the ionic organic liquid 1-ethyl-3-methylimidazolium nitrate  

E-print Network

on ionic organic liquids as supercooled liquids, and a wide range of fragilities have been observed.15Orientational dynamics of the ionic organic liquid 1-ethyl-3-methylimidazolium nitrate Hu Cang, Jie-OKE experiments are used to study the orientational dynamics of the ionic organic liquid 1-ethyl-3

Fayer, Michael D.

251

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...

252

The effect of benzoic acid or its ethyl ester on rumen fermentation parameters  

E-print Network

The effect of benzoic acid or its ethyl ester on rumen fermentation parameters J Nousiainen Valio response of BA or its ethyl ester (EB) on the rumen fermentation parameters in the continuous culture to represent the maximum amount in vivo. The fermentation apparatus and the design of trials as well

Paris-Sud XI, Université de

253

Lipase-mediated conversion of vegetable oils into biodiesel using ethyl acetate as acyl acceptor.  

PubMed

Ethyl acetate was explored as an acyl acceptor for immobilized lipase-catalyzed preparation of biodiesel from the crude oils of Jatropha curcas (jatropha), Pongamia pinnata (karanj) and Helianthus annuus (sunflower). The optimum reaction conditions for interesterification of the oils with ethyl acetate were 10% of Novozym-435 (immobilized Candida antarctica lipase B) based on oil weight, ethyl acetate to oil molar ratio of 11:1 and the reaction period of 12h at 50 degrees C. The maximum yield of ethyl esters was 91.3%, 90% and 92.7% with crude jatropha, karanj and sunflower oils, respectively under the above optimum conditions. Reusability of the lipase over repeated cycles in interesterification and ethanolysis was also investigated under standard reaction conditions. The relative activity of lipase could be well maintained over twelve repeated cycles with ethyl acetate while it reached to zero by 6th cycle when ethanol was used as an acyl acceptor. PMID:16822671

Modi, Mukesh Kumar; Reddy, J R C; Rao, B V S K; Prasad, R B N

2007-04-01

254

Interaction of Ethyl Alcohol Vapor with Sulfuric Acid Solutions  

NASA Technical Reports Server (NTRS)

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.

Leu, Ming-Taun

2006-01-01

255

Effects of acetone on methyl ethyl ketone peroxide runaway reaction.  

PubMed

Runaway reactions by methyl ethyl ketone peroxide (MEKPO) are an important issue in Asia, due to its unstable structure and extensive heat release during upset situations. This study employed differential scanning calorimetry (DSC) to draw the experimental data for MEKPO 31 mass% and with acetone 99 mass% on three types of heating rate of 2, 4, and 10 degrees C/min; the kinetic and safety parameters were then evaluated via curve fitting. Through the reproducible tests in each condition, the results show that acetone is not a contaminant, because it could increase the activation energy (Ea) and onset temperature (To) when combined with MEKPO, which differs from the hazard information of the material safety data sheet (MSDS). PMID:17988795

Lin, Yan-Fu; Tseng, Jo-Ming; Wu, Tsung-Chih; Shu, Chi-Min

2008-05-30

256

Biomonitoring of N-ethyl-2-pyrrolidone in automobile varnishers.  

PubMed

N-alkyl-2-pyrrolidones are important organic solvents for varnishes in industry. This study investigates exposure to N-ethyl-2-pyrrolidone (NEP) in varnishing of hard plastic components in an automobile plant. Two specific biomarkers of exposure, 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), were analyzed in urine samples of 14 workers. For this purpose, pre-shift, post-shift and next day pre-shift urine samples were collected midweek. Twelve workers performed regular work tasks (loading, wiping and packing), whereas two workers performed special work tasks including cleaning the sprayer system with organic solvents containing N-alkyl-2-pyrrolidones. Spot urine samples of nine non-exposed persons of the same plant served as controls. Median post-shift urinary levels of workers with regular work tasks (5-HNEP: 0.15 mg/L; 2-HESI: 0.19 mg/L) were ?5-fold higher compared to the controls (0.03 mg/L each). Continuously increasing metabolite levels, from pre-shift via post-shift to pre-shift samples of the following day, were observed in particular for the two workers with the special working tasks. Maximum levels were 31.01 mg/L (5-HNEP) and 8.45 mg/L (2-HESI). No clear trend was evident for workers with regular working tasks. In summary, we were able to show that workers can be exposed to NEP during varnishing tasks in the automobile industry. PMID:25455446

Koslitz, Stephan; Meier, Swetlana; Schindler, Birgit Karin; Weiss, Tobias; Koch, Holger Martin; Brüning, Thomas; Käfferlein, Heiko Udo

2014-12-01

257

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 FailureS?  

PubMed Central

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

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

2013-01-01

258

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

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

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

259

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 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...

2010-07-01

260

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 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...

2011-07-01

261

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 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...

2012-07-01

262

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 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...

2012-07-01

263

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 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...

2011-07-01

264

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 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...

2013-07-01

265

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 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...

2010-07-01

266

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 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...

2014-07-01

267

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 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...

2014-07-01

268

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 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...

2013-07-01

269

Distribution of uidA gene sequences in Escherichia coli isolates in water sources and comparison with the expression of beta-glucuronidase activity in 4-methylumbelliferyl-beta-D-glucuronide media.  

PubMed

The uidA gene, which encodes the beta-glucuronidase enzyme, was detected in 97.7% of 435 Escherichia coli isolates from treated and raw water sources by DNA-DNA hybridization; 92.4% of the strains expressed the translational product in 4-methylumbelliferyl-beta-D-glucuronide-containing media after reinoculation. Upon initial isolation from water samples, the minimal medium o-nitrophenyl-beta-D-galactopyranoside-4-methylum-belliferyl -beta-D-glucuronide preparations failed to detect more than 50% of the E. coli isolates that possessed uidA gene. Treated water gave the lowest recovery, with Colilert producing 26% positive samples and Coliquik producing 48% positive samples. There appears to be no relationship between the intensity of the autoradiographic signals of the uidA gene and the expression of beta-glucuronidase activity. Therefore, another variable such as physiological condition of the bacteria could be responsible for the nonexpression of the enzyme activity. PMID:8357258

Martins, M T; Rivera, I G; Clark, D L; Stewart, M H; Wolfe, R L; Olson, B H

1993-07-01

270

Immunotoxicity of ethyl carbamate in female BALB/c mice: role of esterase and cytochrome P450.  

PubMed

Ethyl carbamate, a potent carcinogen, has been characterized to be metabolized by cytochrome P450 (P450) and esterase. It has recently been demonstrated that P450 may activate ethyl carbamate to immunotoxic metabolites. To investigate the role of esterase in ethyl carbamate-induced immunosuppression, mice were pretreated intraperitoneally with an esterase inhibitor, diazinon, at 20 mg/kg 30 min prior to the administration of ethyl carbamate intraperitoneally at 100 and 400 mg/kg for 7 consecutive days. Pretreatment with diazinon completely blocked the serum esterase activity. Histopathologically splenic and thymic atrophy was observed when mice were treated with ethyl carbamate, which was potentiated by the pretreatment with diazinon. In spleen, lymphocytes in the periarteriolar lymphoid sheath and the marginal zone appeared to be depleted in the white pulps. In thymus, ethyl carbamate caused a marked depletion of cells in cortex. The antibody response to sheep red blood cells (SRBCs) was more suppressed by ethyl carbamate in diazinon-pretreated groups than in corn oil-pretreated groups. These results suggest that the metabolism of ethyl carbamate by esterase may be an inactivation pathway in ethyl carbamate-induced immunosuppression. In addition, ethyl N-hydroxycarbamate, a P450 metabolite, suppressed the lymphoproliferative response induced by lipopolysaccharide and concanavalin A in splenocyte cultures. These results indicate that the metabolism of ethyl carbamate by P450 may be an activation pathway in immunosuppression by ethyl carbamate. PMID:10814887

Cha, S W; Gu, H K; Lee, K P; Lee, M H; Han, S S; Jeong, T C

2000-06-01

271

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 2014-04-01 false Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane...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 -...

2014-04-01

272

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 2013-04-01 false Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane...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 -...

2013-04-01

273

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 2012-04-01 false Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane...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 -...

2012-04-01

274

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 2011-04-01 false Chromium (Cr III) complex of N-ethyl-N-heptadecylfluoro-octane...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 -...

2011-04-01

275

Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model.  

PubMed

Pharmacokinetics of trans-resveratrol in its aglycone (RES(AGL)) and glucuronide (RES(GLU)) forms were studied following intravenous (15 mg/kg i.v.) and oral (50 mg/kg p.o.) administration of trans-resveratrol in a solution of beta-cyclodextrin to intact rats. In addition, the enterohepatic recirculation of RES(AGL) and RES(GLU) was assessed in a linked-rat model. Multiple plasma and urine samples were collected and concentrations of RES(AGL) and RES(GLU) were determined using an electrospray ionization-liquid chromatography/tandem mass spectrometry method. After i.v. administration, plasma concentrations of RES(AGL) declined with a rapid elimination half-life (T(1/2), 0.13 h), followed by sudden increases in plasma concentrations 4 to 8 h after drug administration. These plasma concentrations resulted in a significant prolongation of the terminal elimination half-life of RES(AGL) (T(1/2TER), 1.31 h). RES(AGL) and RES(GLU) also displayed sudden increases in plasma concentrations 4 to 8 h after oral administration, with T(1/2TER) of 1.48 and 1.58 h, respectively. RES(AGL) bioavailability was 38% and its exposure was approximately 46-fold lower than that of RES(GLU) (AUC(inf), 7.1 versus 324.7 micromol.h/l). Enterohepatic recirculation was confirmed in the linked-rat model since significant plasma concentrations of RES(AGL) and RES(GLU) were observed in bile-recipient rats at 4 to 8 h. The percentages of the exposures of RES(AGL) and RES(GLU) that were due to enterohepatic recirculation were 24.7 and 24.0%, respectively. The fraction of drug excreted in the urine over a period of 12 h was negligible. These results confirm that RES(AGL) is bioavailable and undergoes extensive first-pass glucuronidation, and that enterohepatic recirculation contributes significantly to the exposure of RES(AGL) and RES(GLU) in rats. PMID:12065739

Marier, Jean-Francois; Vachon, Pascal; Gritsas, Ari; Zhang, Jie; Moreau, Jean-Pierre; Ducharme, Murray P

2002-07-01

276

ECHINACEA SANGUINEA AND ECHINACEA PALLIDA EXTRACTS STIMULATE GLUCURONIDATION AND BASOLATERAL TRANSFER OF BAUER ALKAMIDES 8 AND 10 AND KETONE 24 AND INHIBIT P-GLYCOPROTEIN TRANSPORTER IN CACO-2 CELLS  

PubMed Central

The use of Echinacea as a medicinal herb is prominent in the United States, and many studies have assessed the effectiveness of Echinacea as an immunomodulator. We hypothesized that Bauer alkamides 8, 10 and 11 and ketone 24 were absorbed similarly either as pure compounds or from Echinacea sanguinea and Echinacea pallida ethanol extracts, and that these Echinacea extracts could inhibit P-glycoprotein transporter (P-gp) in Caco-2 human intestinal epithelial cells. Using HPLC analysis, the permeation rate of Bauer alkamides by passive diffusion across Caco-2 cells corresponded with compound hydrophilicity (alkamide 8 > 10 > 11), independent of the plant extract matrix. Both Echinacea ethanol extracts stimulated apparent glucuronidation and basolateral efflux of glucuronides of alkamides 8 and 10 but not alkamide 11. Bauer ketone 24 was totally metabolized to more hydrophilic metabolites when administered as a single compound, but was also glucuronidated when present in Echinacea extracts. Bauer alkamides 8, 10 and 11 (175–230 ?M) and ethanol extracts of E. sanguinea (1 mg/mL, containing ~90 ?M total alkamides) and E. pallida (5 mg/mL, containing 285 ?M total alkamides) decreased the efflux of the P-gp probe calcein-AM from Caco-2 cells. These results suggest that other constituents in these Echinacea extracts facilitated the metabolism and efflux of alkamides and ketones, which might improve therapeutic benefits. Alkamides and Echinacea extracts might be useful in potentiating some chemotherapeutics which are substrates for P-gp. PMID:23408271

Qiang, Zhiyi; Hauck, Cathy; McCoy, Joe-Ann; Widrlechner, Mark P.; Reddy, Manju B.; Murphy, Patricia A.; Hendrich, Suzanne

2013-01-01

277

Ethyl benzene should be considered ototoxic at occupationally relevant exposure concentrations.  

PubMed

Organic solvents can produce ototoxic effects in both man and experimental animals. The objective of this study was to review the literature on the effects of low-level exposure to ethyl benzene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible exposure limits. In Quebec, the Time-Weighed Average Exposure Value for 8A h (TWAEV) is 100A ppm (434A mg/m(3)) and the Short-Term Exposure Value for 15A min (STEV) is 125A ppm (543A mg/m(3)). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. In workers, there is no evidence of either ethyl benzene-induced hearing losses or ototoxic interaction after combined exposure to ethyl benzene and noise. In rats, ethyl benzene affects the auditory function mainly in the cochlear mid-frequency range and ototoxic interaction was observed after combined exposure to noise and ethyl benzene. Further studies with sufficient data on the ethyl benzene exposure of workers are necessary to make a definitive conclusion. Given the current evidence from animal studies, we recommend considering ethyl benzene as an ototoxic agent. PMID:19022877

Vyskocil, A; Leroux, T; Truchon, G; Lemay, F; Gendron, M; Gagnon, F; El Majidi, N; Viau, C

2008-05-01

278

Mechanism of quizalofop-ethyl selectivity in monocotyledonous and dicotyledonous species  

SciTech Connect

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.

Ruizzo, M.A.

1986-01-01

279

Reactions of Ethyl Groups on a Model Chromia Surface: Ethyl Chloride on Stoichiometric Alpha-Cr2O3(1012)  

SciTech Connect

The reaction of CH3CH2Cl over the nearly-stoichiometric ?-Cr2O3 (1 0 View the MathML source 2) surface yields gas phase CH2double bond; length as m-dashCH2, CH3CH3, H2 and surface chlorine adatoms. The decomposition reaction is initiated via C-Cl bond cleavage to give a surface ethyl (CH3CH2-) intermediate. A rate-limiting ?-hydride elimination from the surface ethyl species produces gas phase CH2double bond; length as m-dashCH2 and surface hydrogen atoms. Two parallel competing reactions form CH3CH3, via ?-hydride addition to remaining surface ethyl species (reductive elimination), and H2, via the combination of two surface hydrogen atoms. The chlorine freed from the dissociation of CH3CH2Cl binds at the five-coordinate surface Cr3+ sites on the stoichiometric surface and inhibits the surface chemistry via simple site blocking. No surface carbon deposition is observed from the thermal reaction of ethyl chloride, suggesting that ethyl intermediates are not primary coke forming intermediates in the dehydrogenation of ethane over (1 0 View the MathML source 2) facets of ?-Cr2O3.

Brooks, J.; Ma, Q; Cox, D

2009-01-01

280

The synthesis and purification of aromatic hydrocarbons V : 1-ethyl-3-methylbenzene  

NASA Technical Reports Server (NTRS)

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.

Ebersole, Earl R

1946-01-01

281

[Study on vibrational spectra of ethyl hexanoate molecule].  

PubMed

The vibrational spectra of ethyl hexanoate were calculated by the density functional theory (DFT) with B3LYP complex function, diffuse function and polarization function added to heavy atoms and light atoms. On the base of this, the normal Raman spectrum (NRS) and the infrared spectrum (IR) were assigned in detail in the present paper. Comparing the calculated results with the experimental data, the calculated results are in good agreement with the experimental results. The comparison of the experimental Raman and infrared spectra shows that in the experimental Raman spectrum, the strongest bands appear at the frequencies of 2600-3100 cm(-1), while the strongest band is not 1734 cm(-1) but 1444 cm(-1) at the frequencies of 400-2000 cm(-1). The band 1734 cm(-1) attributed to the C=O stretch vibration is the distinctive mark of organic ester compounds, and the band 1444 cm(-1) is related to the symmetric and anti-symmetric scissors vibration of C-H. In the experimental infrared spectrum, the strongest vibrational band is 1739 cm(-1), which is related to C=O stretch vibration; At the frequencies of 400-2000 cm(-1), the relative intensity of the infrared spectrum is distinctively stronger than that of the Raman spectrum, but the relative intensity of infrared spectrum is weaker than that of the Raman spectrum at the frequencies of 2600-3100 cm(-1). In the frequencies of 2600-2800 cm(-1), the vibrational bands 2762 and 2732 cm(-1) do not appear in the experimental spectra, which may originate from two reasons: (1) the weak interaction of molecules. Also, the relative intensity of these vibrational bands is very weak in the experimental spectra, and this may testify that the interaction of molecules is rather weak; (2) the vibrational bands may belong to second order vibrational mode at the frequencies of 2600-2800 cm(-1). The relative intensity of infrared bands is weaker than that of the Raman bands at the frequencies of 2600-2800 cm(-1). At the end, the stronger bands appearing in Raman and infrared experimental spectra are assigned as characteristic marks, respectively. The study on vibrational spectra of ethyl hexanoate molecule may have great application value in detection of liquor flavor, chemical industry and biology fields, providing important reference value for the related basic research field. PMID:19093572

Cai, Zhi-peng; Du, Ya-bing; Zhang, Ling; Li, Peng-wei; Jia, Ting-jian; Mo, Yu-jun

2008-09-01

282

Replication across Regioisomeric Ethylated Thymidine Lesions by Purified DNA Polymerases  

PubMed Central

Causal links exist between smoking cigarettes and cancer development. Some genotoxic agents in cigarette smoke are capable of alkylating nucleobases in DNA and higher levels of ethylated DNA lesions were observed in smokers than non-smokers. In this study, we examined comprehensively how the regioisomeric O2-, N3- and O4-ethylthymidine (O2-, N3- and O4-EtdT) perturb DNA replication mediated by purified human DNA polymerases (hPol) ?, ?, and ?, yeast DNA polymerase ? (yPol ?), and the exonuclease-free Klenow fragment (Kf?) of Escherichia coli DNA polymerase I. Our results showed that hPol ? and Kf? could bypass all three lesions and generate full-length replication products, whereas hPol ? stalled after inserting a single nucleotide opposite the lesions. Bypass carried out by hPol ? and yPol ? differed markedly amongst the three lesions: Consistent with its known capability in bypassing efficiently the minor-groove N2-substituted 2?-deoxyguanosine lesions, hPol ? was able to bypass O2-EtdT, though it experienced great difficulty in bypassing N3-EtdT and O4-EtdT; yPol ? was only modestly blocked by O4-EtdT, but the polymerase was highly hindered by O2-EtdT and N3-EtdT. LC-MS/MS analysis of the replication products revealed that DNA synthesis opposite O4-EtdT was highly error-prone, with dGMP being preferentially inserted, while the presence of O2-EtdT and N3-EtdT in template DNA directed substantial frequencies of misincorporation of dGMP and, for hPol ? and Kf?, dTMP. Thus, our results suggested that O2-EtdT and N3-EtdT may also contribute to the AT?TA and AT?GC mutations observed in cells and tissues of animals exposed to ethylating agents. PMID:24134187

Andersen, Nisana; Wang, Pengcheng; Wang, Yinsheng

2013-01-01

283

Simultaneous RP-HPLC determination of sotalol, metoprolol, alpha-hydroxymetoprolol, paracetamol and its glucuronide and sulfate metabolites in human urine.  

PubMed

The HPLC method for the determination of sotalol (SOT), metoprolol (MET) and alpha-hydroxymetoprolol metabolite (MET-H), paracetamol (PAR), paracetamol glucuronide (PAR-G) and paracetamol sulfate (PAR-S) in human urine is described. Analyses were carried out on a reversed-phase LiChroCART Purospher C18e column (125 mm x 3 mm, 5 microm particles) (Merck) with gradient elution as well as spectrophotometric and fluorometric detection. Good resolution of the analyzed substances was obtained within a time range of no longer than 15 min. The linearity ranges of the callibration curves in human urine (as matrix) were: 3.25-45 microg ml(-1) (SOT), 0.75-40 microg ml(-1) (MET), 0.6-40 microg ml(-1) (MET-H), 4.6-60 microg ml(-1) (PAR-G), 4.95-50 microg ml(-1) (PAR-S), 1.95-45 microg ml(-1) (PAR). An application to human urine samples was performed. PMID:19531885

Baranowska, Irena; Wilczek, Andrzej

2009-06-01

284

High-performance thin-layer chromatography method for quantitative determination of oenothein B and quercetin glucuronide in aqueous extract of Epilobii angustifolii herba.  

PubMed

A method was developed for separation and quantitative determination of oenothein B (OeB) and quercetin glucuronide (QG) in aqueous extract of Epilobii angustifolii herba by HPTLC-densitometry. The analyses were performed on HPTLC RP-18 WF(254) plates with 25% MeCN in water (+50mM H(3)PO(4)) as the mobile phase (distance of 8 cm) for OeB quantification and then with acetonitrile (distance of 4 cm) for QG quantification. OeB and QG were determined by densitometry at 270 and 350 nm, respectively. Their amounts were calculated using the regression equations of the calibration curves which were linear in a range of 1.14-2.28 microg spot(-1) for OeB and of 0.0768-0.6912 microg spot(-1) for QG. The amounts of OeB and QG in aqueous extract of Epilobii angustifolii herba measured by the method developed were 152.46+/-4.92 and 22.07+/-1.38 mg g(-1), respectively. The method was found to be relatively simple, specific, precise and accurate for the quality control of Epilobium angustifolium extracts. PMID:17980376

Bazylko, Agnieszka; Kiss, Anna K; Kowalski, Józef

2007-11-30

285

Changes in pharmacokinetic profiles of acetaminophen and its glucuronide after pretreatment with combinations of N-acetylcysteine and either glycyrrhizin, silibinin or spironolactone in rat.  

PubMed

1. The present study was to investigate the effects of giving N-acetylcysteine (NAC) alone and in combination with either glycyrrhizin (GL), silibinin (SIB) or spironolactone (SL) on the plasma pharmacokinetic (PK) profiles, hepatic exposure, biliary excretion and urinary excretion of acetaminophen (APAP) and its major metabolite, acetaminophen glucuronide (AG). 2. Groups of rats (n?=?5) were pretreated with oral doses of either NAC, NAC?+?GL, NAC?+?SIB or NAC?+?SL on five occasions every 12?h. At 1?h, after the last dose, they received APAP (200?mg/kg) by intraperitoneal injection. Blood, bile, liver and urine samples were collected at various times after APAP injection and analyzed for APAP and AG by HPLC. NAC alone and NAC?+?SIB did not significantly change the PK profiles of APAP and AG. In contrast, NAC?+?GL decreased the biliary excretion of APAP and AG leading to accumulation of APAP in the liver and systemic circulation whereas NAC?+?SL [multidrug resistance associated 2 (Mrp2) inducer] increased the biliary excretion of AG and decreased the hepatic exposure to APAP and AG. 3. Our results suggest that Mrp2 inhibitor GL should be discouraged with NAC to treat APAP hepatotoxicity. Such PK drug-drug interactions should be considered in the treatment of APAP-induced liver injury. PMID:24251357

Xu, Ruijuan; Wang, Qian; Zhang, Jing; Zang, Min; Liu, Xiaoquan; Yang, Jin

2014-06-01

286

Application of a physiologically based pharmacokinetic model to assess propofol hepatic and renal glucuronidation in isolation: utility of in vitro and in vivo data.  

PubMed

A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro-in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

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

2013-04-01

287

Gauche Ethyl Alcohol: Laboratory Assignments and Interstellar Identification  

NASA Technical Reports Server (NTRS)

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.

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

1997-01-01

288

Gauche Ethyl Alcohol: Laboratory Assignments and Interstellar Identification  

NASA Astrophysics Data System (ADS)

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 (?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 × 1015 cm-2. The column density is in reasonable agreement with the recent value of 2-3 × 1015 cm-2 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.

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

1997-05-01

289

The pharmacological actions of pempidine and its ethyl homologue  

PubMed Central

Pempidine, and other highly active ganglion blocking agents of the polyalkylpiperidine series, were developed from tertiary alkylamines, themselves weakly active, on the hypothesis that high activity was conferred by the presence in the molecule of a sterically hindered secondary or tertiary nitrogen atom. Pempidine and its N-ethyl homologue (26539) resembled mecamylamine qualitatively. All three drugs blocked sympathetic and parasympathetic ganglia; this action was slow in onset and protracted. They blocked neuromuscular transmission, but only about one hundredth as powerfully as ganglionic transmission. They caused a fall in amplitude and rate of the isolated heart, and reduced coronary flow. They had local anaesthetic properties in one of four tests used. They caused tremor. All were well absorbed when administered orally. Pempidine was about twice as active as mecamylamine on ganglia, but only about one half to one quarter as toxic as judged by death, growth, induction of tremor, or cardiotoxicity. Compound 26539 was also quantitatively superior to mecamylamine in respect of these safety margins, but unlike pempidine or mecamylamine damaged the pituitary gland and testis when administered daily for several months. The mode of action of the three drugs is discussed: the results give tentative support for the hypothesis that their action is intracellular. PMID:13618559

Spinks, A.; Young, E. H. P.; Farrington, J. A.; Dunlop, D.

1958-01-01

290

Determination of acetone and methyl ethyl ketone in water  

USGS Publications Warehouse

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)

Tai, D.Y.

1978-01-01

291

Decontamination of 2-Chloroethyl Ethyl Sulfide by Pulsed Corona Plasma  

NASA Astrophysics Data System (ADS)

Decontamination of 2-chloroethyl ethyl sulfide (2-CEES, CH3CH2SCH2CH2Cl) by pulsed corona plasma was investigated. The results show that 212.6 mg/m3 of 2-CEES, with the gas flow rate of 2 m3/h, can be decontaminated to 0.09 mg/m3. According to the variation of the inlet and outlet concentration of 2-CEES vapor with retention time, it is found that the reaction of 2-CEES in a pulsed corona plasma system follows the first order reaction, with the reaction rate constant of 0.463 s?1. The decontamination mechanism is discussed based on an analysis of the dissociation energy of chemical bonds and decontamination products. The C–S bond adjacent to the Cl atom will be destroyed firstly to form CH3CH2S· and ·CH2CH2Cl radicals. CH3CH2S· can be decomposed to ·C2H5 and ·S. ·S can be oxidized to SO2, while ·C2H5 can be finally oxidized to CO2 and H2O. The C–Cl bond in the ·CH2CH2Cl radical can be destroyed to form ·CH2CH2. and ·Cl, which can be mineralized to CO2, H2O and HCl. The H atom in the ·CH2CH2Cl radical can also be substituted by ·Cl to form CHCl2–CHCl2.

Li, Zhanguo; Hu, Zhen; Cao, Peng; Zhao, Hongjie

2014-11-01

292

Enhanced photochemistry of ethyl chloride on ag nanoparticles.  

PubMed

Enhanced photodecomposition of ethyl chloride (EC) adsorbed on SiO2/Si (100) supported silver nanoparticles (Ag NPs) under ultrahigh vacuum (UHV) conditions has been studied in order to assess the potential contribution of plasmonic effects. The cross section for photodecomposition of EC and overall photoyield were found to increase with increasing photon energy regardless of the plasmon resonant wavelength and with Ag coverage without any noticeable particle size effect. The influence of EC-Ag NPs separation distance on the rate of EC decomposition was studied in order to examine potential local electric field influence on the photodissociation process. Long (?5 nm) photoactivity decay distance has been observed which excludes local surface plasmon dominance in the photodecomposition event. These findings suggest that the alignment of excited electron energy and adsorbate affinity levels is central for efficient photochemical reactions, whereas short-range electric field enhancement by plasmon excitation on top and at the immediate vicinity of silver nanoparticles does not have any measurable effect. PMID:25555201

Toker, Gil; Bespaly, Alexander; Zilberberg, Liat; Asscher, Micha

2015-02-11

293

Theoretical Study of the Vibrational Spectroscopy of the Ethyl Radical  

NASA Astrophysics Data System (ADS)

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).

Tabor, Daniel P.; Sibert, Edwin. L. Sibert, Iii

2013-06-01

294

Production of ethyl levulinate by direct conversion of wheat straw in ethanol media.  

PubMed

The production of ethyl levulinate from wheat straw by direct conversion in ethanol media was investigated. Response surface methodology (RSM) was applied to optimize the effects of processing parameters, and the regression analysis was performed on the data obtained. A close agreement between the experimental results and the model predictions was achieved. The optimal conditions for ethyl levulinate production from wheat straw were acid concentration 2.5%, reaction temperature 183°C, mass ratio of liquid to solid 19.8 and reaction time 36 min. Under the optimum conditions, the yield of ethyl levulinate 17.91% was obtained, representing a theoretical yield of 51.0%. The results suggest that wheat straw can be used as potential raw materials for the production of ethyl levulinate by direct conversion in ethanol media. PMID:22858471

Chang, Chun; Xu, Guizhuan; Jiang, Xiaoxian

2012-10-01

295

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

Code of Federal Regulations, 2014 CFR

...Fenoxaprop-ethyl; tolerances for residues. 180.430 Section 180.430...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances §...

2014-07-01

296

PERSISTENCE OF METHYL AND ETHYL PARATHION FOLLOWING SPILLAGE ON CONCRETE SURFACES  

EPA Science Inventory

Tests were carried out to determine the potential hazard of spillage of the pesticides, methyl parathion and ethyl parathion, on concrete surfaces. Results indicated that although a toxic hazard exists, especially for potential contamination of foodstuff, when liquid concentrates...

297

Combustion chemical kinetics of biodiesel and related compounds (methyl and ethyl esters): Experiments and  

E-print Network

toward clean and efficient combustion in diesel engines. After briefly outlining the synergy between and ethyl biodiesels; Combustion; Diesel engine; Performance and emission; Chemical kinetics of oxidation energy and renewable materials. According to the International Energy Outlook of 2011, which

Paris-Sud XI, Université de

298

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

SciTech Connect

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.

NONE

1996-12-31

299

Hepatic studies of intraperitoneally administered tris(2-ethyl hexyl)trimellitate (TOTM) and di(2-ethyl hexyl)phthalate in rats.  

PubMed

Adult male rats receiving tris(2-ethyl hexyl)trimellitate (TOTM) intraperitoneally for seven days exhibited no significant changes in the activities of hepatic aminopyrine-N-demethylase, aryl hydrocarbon hydroxylase or glutathione-S-transferase, or in the glutathione contents. However, except for the glutathione level, the di(2-ethyl hexyl)phthalate (DEHP)-treated group showed significant increases in the activities of these enzymes. Changes in the body weight and the absolute and relative liver weights were also observed among the DHEP-treated group. PMID:2335710

Rathinam, K; Srivastava, S P; Seth, P K

1990-02-01

300

Spectrophotometric determination of uranium(VI) using a synergic mixture of ethyl acetoacetate and pyridine  

Microsoft Academic Search

A method is proposed for the extractive spectrophotometric determination of uranium(VI) using the synergic combination of ethyl acetoacetate (EAA) and pyridine (Py) as extractants. The optimum conditions have been evaluated by varying pH and ethyl acetoacetate and pyridine concentration. The nature of the extracted species has been determined by 1g D-1g C plots and the extracted species was found to

Veena D. Pillai; V. M. Shinde

1996-01-01

301

Biodegradation of Chlorimuron-ethyl by the Bacterium Klebsiella jilinsis 2N3  

Microsoft Academic Search

Enrichment culturing of sludge taken from an industrial wastewater treatment pond led to the identification of a bacterium (Klebsiella jilinsis H. Zhang) that degrades chlorimuron-ethyl with high efficiency. Klebsiella jilinsis strain 2N3 grows with chlorimuron-ethyl as the sole nitrogen source at the optimal temperature range of 30–35°C and pH values between 6.0–7.0. In liquid medium, the degradation activity was further

Hao Zhang; Xianghui Zhang; Wenhui Mu; Jiaxiu Wang; Hongyu Pan; Yu Li

2010-01-01

302

Simultaneous removal of ethyl acetate and toluene in air streams using compost-based biofilters  

Microsoft Academic Search

Biofitration was successfully applied to treat air streams containing a mixture of ethyl acetate and toluene. The experiment was performed by two identical bench-scale biofilters, which were acclimated by ethyl acetate and toluene, respectively. During a 3 month steady-state performance, the two biofilters showed equivalent elimination capacity (EC) for toluene (50g\\/m3 bed\\/h of pure toluene). However, the biofilter acclimated with

Yonghui Liu; Xie Quan; Yumei Sun; Jingwen Chen; Daming Xue; Jong Shik Chung

2002-01-01

303

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

PubMed Central

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

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

1994-01-01

304

Chlorimuron ethyl sorption and desorption kinetics in soils and herbicide-desiccated cover crop residues  

Microsoft Academic Search

Interaction between a herbicide and plant residue on the soil surface in plant residue management systems such as no-tillage or cover crop is of interest in terms of environmental fate of the herbicide. This study was designed to evaluate sorption and desorption of chlorimuron ethyl {ethyl 2-(((((4- chloro-6-methoxy-2-pyrimidinyl)aminolc~bonyll~olsulfonyllbenzoic acid} in herbicide-desiccated rye (Secale cereale L.) and hairy vetch (Vicia villosa

Krishna N. Reddy; Martin A. Locke; Stephen C. Wagner; Robert M. Zablotowicz; Lewis A. Gaston; Reid J. Smeda

1995-01-01

305

Extraction of compactin (ML236B): equilibrium distribution in water–ethyl acetate system  

Microsoft Academic Search

Equilibrium partitioning of compactin in water–ethyl acetate system was measured at 298K. The extraction pH showed strong influence on the partitioning ratio: the partitioning ratio decreased with pH. The dissociation constant and distribution coefficients of compactin were determined by treating equilibrium data with numerical approach. Distribution coefficient of compactin in water–ethyl acetate system was treated as a variable and a

Tippabust Eksangsri; Hiroaki Habaki; Junjiro Kawasaki

2004-01-01

306

40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...  

Code of Federal Regulations, 2010 CFR

...hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. ...hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate....

2010-07-01

307

Effect of ethyl alcohol on growth and intracellular alanine racemase of psychrotrophs.  

PubMed

The psychrotrophic alanine racemase from Pseudomonas fluorescens, a typical psychrotroph, is less resistant to organic solvents than the enzymes from thermophilic and mesophilic bacteria (Okubo et al., J. Home Econ. Jpn., 46: 1135-1140, 1995). To further elucidate this difference, we examined the effect of ethyl alcohol on the growth and intracellular alanine racemase activity of three typical psychrotrophs-P. fluorescens, Bacillus psychrosaccharolyticus and B. psychrophilus-in comparison with two mesophiles, Escherichia coli and B. subtilis. Although all the bacteria grew to the early stationary phase when cultivated at 22 degrees C for 36 h in the absence of ethyl alcohol, the growth of the psychrotrophs was more effectively suppressed by the addition of 3 and 5% ethyl alcohol to the medium than that of the mesophiles. The intracellular alanine racemase activity of the psychrotrophs was also more markedly reduced in the presence of ethyl alcohol than that of the mesophiles. When bacterial cells of each strain grown at 22 degrees C for 36 h in the absence of alcohol were suspended in 0-5 % ethyl alcohol solution and incubated at 30 degrees C for 1 h, both the survival ratio and intracellular alanine racemase activity of the psychrotrophs were lower than those of the mesophiles. Thus, ethyl alcohol effectively reduced both the growth of the psychrotrophs and their intracellular alanine racemase activity. Low concentrations of various other alcohols also repressed the growth of the psychrotrophs at 10 degrees C. PMID:16232459

Okubo, Y; Yokoigawa, K; Kawai, H

1999-01-01

308

Formation of ethyl acetate by Kluyveromyces marxianus on whey: studies of the ester stripping.  

PubMed

Kluyveromyces marxianus is capable of converting lactose into ethyl acetate offering a chance for an economical reuse of whey. The microbial formation of ethyl acetate as a bulk product calls for an aerobic process and, thus, the highly volatile ethyl acetate is discharged from the aerated bioreactor. This stripping process was modeled and investigated experimentally. The stripping rate was proportional to the gas flow and nearly independent of the stirring rate since the stripping was governed by the absorption capacity of the exhaust gas rather than the phase transfer. Cooling the exhaust gas did not noticeably influence the stripping. One batch experiment is presented in detail to demonstrate the formation of ethyl acetate by K. maxianus DSM 5422 on whey. Further batch experiments showed that a substantial formation of ethyl acetate only occurred when the yeast growth was limited by a lack of trace elements. The highest product yield observed was 0.25 g ethyl acetate per g lactose which is nearly 50% of the theoretical maximum. PMID:21191616

Urit, Thanet; Löser, Christian; Wunderlich, Martin; Bley, Thomas

2011-06-01

309

Elevated ethyl methanesulfonate (EMS) in nelfinavir mesylate (Viracept, Roche): overview.  

PubMed

Roche's protease inhibitor nelfinavir mesylate (Viracept) produced between March 2007-June 2007 was found to contain elevated levels of ethyl methanesulfonate (EMS), a known mutagen (alkylator) - leading to a global recall of the drug. EMS levels in a daily dose (2,500 mg Viracept/day) were predicted not to exceed a dose of approximately 2.75 mg/day (approximately 0.055 mg/kg/day based on 50 kg patient). As existing toxicology data on EMS did not permit an adequate patient risk assessment, a comprehensive animal toxicology evaluation of EMS was conducted. General toxicity of EMS was investigated in rats over 28 days. Two studies for DNA damage were performed in mice; chromosomal damage was assessed using a micronucleus assay and gene mutations were detected using the MutaMouse transgenic model. In addition, experiments designed to extrapolate animal exposure to humans were undertaken. A general toxicity study showed that the toxicity of EMS occurred only at doses >or= 60 mg/kg/day, which is far above that received by patients. Studies for chromosomal damage and mutations in mice demonstrated a clear threshold effect with EMS at 25 mg/kg/day, under chronic dosing conditions. Exposure analysis (Cmax) demonstrated that approximately 370-fold higher levels of EMS than that ingested by patients, are needed to saturate known, highly conserved, error-free, mammalian DNA repair mechanisms for alkylation. In summary, animal studies suggested that patients who took nelfinavir mesylate with elevated levels of EMS are at no increased risk for carcinogenicity or teratogenicity over their background risk, since mutations are prerequisites for such downstream events. These findings are potentially relevant to >40 marketed drugs that are mesylate salts. PMID:19660105

Pozniak, Anton; Müller, Lutz; Salgo, Miklos; Jones, Judith K; Larson, Peter; Tweats, David

2009-01-01

310

Ethyl Pyruvate Ameliorates Endotoxin-Induced Corneal Inflammation  

PubMed Central

Purpose. The purpose of this study was to evaluate the anti-inflammatory effect of ethyl pyruvate (EP) in a mouse model of lipopolysaccharide (LPS)-induced corneal inflammation. Methods. LPS was injected intrastromally into the corneas of C57BL/6 mice followed by treatment with a solution of 2.5% EP in 0.2% hydroxypropyl methylcellulose (HPMC) every 90 minutes during the course of 12 hours. Prednisolone acetate 1% solution (PRED FORTE) was used as a positive control. Mice were sacrificed after 3 days, and corneas were examined by in vivo confocal microscopy and analyzed for infiltrated cells by flow cytometry. Gr-1, TNF-?, and pNF-?B-p65 were detected immunohistochemically, and TNF-?, IL-6, and IL-1? levels were quantified by ELISA. Results. LPS-induced haze in mice corneas was decreased by 2-fold upon EP treatment; however, it was not changed upon PRED FORTE treatment. Flow cytometry and immunohistochemistry showed infiltration of leukocytes in the LPS-treated corneas; among the infiltrated cells, neutrophils (Gr-1+ and CD11b+) and macrophages (F4/80+ and CD11b+) were 3403.4- and 4.5-fold higher in number, respectively, than in vehicle-treated control corneas. EP or PRED FORTE treatment of LPS-injected corneas decreased the number of neutrophils 7.5- and 7.2-fold and macrophages by 5.6- and 3.5-fold, respectively. Both EP and PRED FORTE decreased TNF-? and IL-6 expression considerably, and to a lesser extent IL-1? expression, in the LPS-treated corneas. Conclusions. The present study demonstrated that EP reduces LPS-induced inflammation in the cornea and thus may have a potential therapeutic application in the inhibition of corneal inflammation. PMID:22918642

Gupta, Divya; Du, Yiqin; Piluek, Jordan; Jakub, Adam M.; Buela, Kristine Ann; Abbott, Akshar; Schuman, Joel S.; SundarRaj, Nirmala

2012-01-01

311

Lignin biodegradation and the production of ethyl alcohol from cellulose  

SciTech Connect

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.

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

1981-02-01

312

Laboratory and Observational Studies of Methyl Ethyl Ketone  

NASA Astrophysics Data System (ADS)

A large fraction of the detected interstellar molecules are complex organic molecules (COMs) containing five or more atoms. Despite the prominence of these species in many types of astrophysical environments, the formation processes for these molecules are not well-understood. We have therefore undertaken a combined laboratory, modeling, and observational program in an attempt to more fully understand the effects that physical environment have on the chemical composition of astronomical sources. As part of this effort, we have conducted deep submillimeter spectral line surveys of multiple interstellar sources with varying physical conditions including hot cores, shocked regions, low-mass star forming regions, and stellar outflows. These surveys were conducted using a broadband receiver at the Caltech Submillimeter Observatory (CSO), and are forerunner observations to our upcoming Herschel OT1 program to continue these surveys at higher frequencies. In order to fully analyze these spectral line surveys, we have also collected laboratory spectra of several suspected interstellar organic molecules. One such molecular target is methyl ethyl ketone (CH_3COCH_2CH_3, MEK), which is a likely candidate for interstellar detection. The spectra for MEK were collected from 8.7 to 18.3 GHz using the chirped-pulse waveguide Fourier Transform microwave (FTMW) spectrometer at New College Florida. We have also collected spectra of MEK in selected frequency ranges from 32 to 125 GHz using the direct absorption flow cell spectrometer at Emory University. We will report on the laboratory characterization of MEK and compare these results to our observational spectral line surveys.

Kroll, J. A.; Shipman, S.; Widicus Weaver, S. L.

2011-05-01

313

Divergent effects of eicosapentaenoic and docosahexaenoic acid ethyl esters, and fish oil on hepatic fatty acid oxidation in the rat.  

PubMed

The physiological activity of fish oil, and ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affecting hepatic fatty acid oxidation was compared in rats. Five groups of rats were fed various experimental diets for 15 days. A group fed a diet containing 9.4% palm oil almost devoid of n-3 fatty acids served as a control. The test diets contained 4% n-3 fatty acids mainly as EPA and DHA in the form of triacylglycerol (9.4% fish oil) or ethyl esters (diets containing 4% EPA ethyl ester, 4% DHA ethyl ester, and 1% EPA plus 3% DHA ethyl esters). The lipid content of diets containing EPA and DHA ethyl esters was adjusted to 9.4% by adding palm oil. The fish oil diet and ethyl ester diets, compared to the control diet containing 9.4% palm oil, increased activity and mRNA levels of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes, though not 3-hydroxyacyl-CoA dehydrogenase activity. The extent of the increase was, however, much greater with the fish oil than with EPA and DHA ethyl esters. EPA and DHA ethyl esters, compared to the control diet, increased 3-hydroxyacyl-CoA dehydrogenase activity, but fish oil strongly reduced it. It is apparent that EPA and DHA in the form of ethyl esters cannot mimic the physiological activity of fish oil at least in affecting hepatic fatty acid oxidation in rat. PMID:14642774

Hong, Dang Diem; Takahashi, Yoko; Kushiro, Masay; Ide, Takashi

2003-11-30

314

Mass spectrometric characterization of circulating covalent protein adducts derived from a drug acyl glucuronide metabolite: multiple albumin adductions in diclofenac patients.  

PubMed

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

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; Williams, Dominic P

2014-08-01

315

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

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

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

2015-01-01

316

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

PubMed Central

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

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

317

Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms.  

PubMed

The domestic cat has a significantly lower capacity to glucuronidate planar phenolic xenobiotics compared with most other mammalian species. The aim of this study was to determine the mechanistic basis for this anomaly. Current knowledge of the substrate specificity of UDP-glucuronosyltransferase (UGT) isoforms indicates that the cat may either lack or poorly express UGT1A6. Initially, a novel cloning technique was used to identify UGT1A genes expressed in cat liver. Only two unique UGT1A isoforms could be discriminated. The first (28%, of clones) was most homologous to UGT1A1 (the bilirubin-UGT), while the second (72% of clones) showed homology to several isoforms, but could not be unambiguously identified, and was designated cat UGT1A02. Southern blot analysis confirmed the presence of a single UGT1A6-homologous region in the cat genome. Subsequent cloning and sequencing of the entire UGT1A6 exon 1 coding region revealed five deleterious genetic mutations. Identical mutations were found by sequencing of UGT1A6 exon 1 from five other unrelated cats. Four of these five genetic lesions were also identified in the UGT1A6 exon 1 region of a margay (Leopardus wiedii). Finally, RT-PCR of liver mRNA from four different cats confirmed the presence of UGT1A1 and UGT1A02, but not UGT1A6. In conclusion, UGT1A6 is a pseudogene in the domestic cat and in at least one other phylogenetically related species. Furthermore, cats appear to have a less diverse pattern of UGT1A isoform expression compared with other species. Such differences most likely reflect the highly carnivorous diet of Feliform species and resultant minimal exposure to phytoalexins. PMID:10862526

Court, M H; Greenblatt, D J

2000-06-01

318

Ethyl tertiary-butyl ether: a toxicological review.  

PubMed

A number of oxygenated compounds (oxygenates) are available for use in gasoline to reduce vehicle exhaust emissions, reduce the aromatic compound content, and avoid the use of organo-lead compounds, while maintaining high octane numbers. Ethyl tertiary-butyl ether (ETBE) is one such compound. The current use of ETBE in gasoline or petrol is modest but increasing, with consequently similar trends in the potential for human exposure. Inhalation is the most likely mode of exposure, with about 30% of inhaled ETBE being retained by the lungs and distributed around the body. Following cessation of exposure, the blood concentration of ETBE falls rapidly, largely as a result of its metabolism to tertiary-butyl alcohol (TBA) and acetaldehyde. TBA may be further metabolized, first to 2-methyl-1,2-propanediol and then to 2-hydroxyisobutyrate, the two dominant metabolites found in urine of volunteers and rats. The rapid oxidation of acetaldehyde suggests that its blood concentration is unlikely to rise above normal as a result of human exposure to sources of ETBE. Single-dose toxicity tests show that ETBE has low toxicity and is essentially nonirritant to eyes and skin; it did not cause sensitization in a maximization test in guinea pigs. Neurological effects have been observed only at very high exposure concentrations. There is evidence for an effect of ETBE on the kidney of rats. Increases in kidney weight were seen in both sexes, but protein droplet accumulation (with alpha(2u)-globulin involvement) and sustained increases in cell proliferation occurred only in males. In liver, centrilobular necrosis was induced in mice, but not rats, after exposure by inhalation, although this lesion was reported in some rats exposed to very high oral doses of ETBE. The proportion of liver cells engaged in S-phase DNA synthesis was increased in mice of both sexes exposed by inhalation. ETBE has no specific effects on reproduction, development, or genetic material. Carcinogenicity studies have been conducted with ETBE, TBA, and ethanol (included in this review as an endogenous precursor of acetaldehyde in the absence of TBA). A single experiment with ETBE in rats and several experiments with ethanol in rats and mice were not considered adequate for an evaluation of ETBE carcinogenicity. In male rats only, TBA induced alpha(2u)-globulin nephropathy-related renal tubule adenomas. These are generally considered to have no human relevance. In addition, increases in thyroid follicular cell adenoma incidence were associated with TBA treatment in female mice. This result lacks independent confirmation and is not supported by experiments in which similar or higher internal doses of TBA were delivered. PMID:17453936

McGregor, Douglas

2007-05-01

319

Fumigation of wheat using liquid ethyl formate plus methyl isothiocyanate in 50-tonne farm bins.  

PubMed

Australian Standard White wheat, Triticum aestivum L. (a marketing grade with mixed grain hardness),with a moisture content of 12.5% was fumigated with a new ethyl formate formulation (95% ethyl formate plus 5% methyl isothiocyanate) identified and developed by Commonwealth Scientific and Industrial Research Organization Entomology, Canberra, Australia. Wheat was fumigated with the formulation at a calculated application rate of 80 g/m3 in two 50-tonne sealed metal vertical silos located at Fisherman Islands, Queensland, Australia. Access was gained through the top of the silo where the application of the formulation was completed within a few minutes by pouring it onto the top of the wheat. After 2 h of recirculation, using a 0.5-kW fan, the in-bin concentrations of ethyl formate achieved equilibrium with a concentration variation < 7%. The ethyl formate concentration, in both silos 1 and 2, during the first day's exposure period remained above 10 g/m3. The concentration of ethyl formate by time product achieved was 790 and 650 g h/m3 in silos 1 and 2, respectively. In silo 1, the formulation was sufficient to kill all life stages of mixed age cultures of Sitophilus oryzae (L.), Rhyzopertha dominica (F.), and Tribolium castaneum (Herbst). In silo 2, control was 100% for R. dominica and T. castaneum and 99.4% for S. oryzae. After 5 d fumigation, the silo top-hatch was opened but no forced aeration was initiated. The in-bin concentration of ethyl formate was lower than the Australian experimental threshold limit value of 100 ppm. The ethyl formate and methyl isothiocyanate residues in the grain had declined to below the Australian experimental maximum residue limit of 0.2 and 0.1 mg/kg, respectively. The workspace and environmental levels of ethyl formate and methyl isothiocyanate were less than the detection limit of 0.1 ppm. The treatment with ethyl formate formulation had no affect on the wheat germination and seed color compared with untreated controls. PMID:18459432

Ren, Yonglin; Lee, Byungho; Mahon, Daphne; Xin, Ni; Head, Matthew; Reid, Robin

2008-04-01

320

Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats  

PubMed Central

Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum (H. perforatum) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats. PMID:23569798

Arokiyaraj, S; Balamurugan, R; Augustian, P

2011-01-01

321

Experimental and computational investigation on the gas phase reaction of ethyl formate with Cl atoms.  

PubMed

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

Balaganesh, M; Dash, Manas Ranjan; Rajakumar, B

2014-07-17

322

Effect of Potent Ethyl Acetate Fraction of Stereospermum suaveolens Extract in Streptozotocin-Induced Diabetic Rats  

PubMed Central

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

Balasubramanian, T.; Chatterjee, Tapan Kumar; Senthilkumar, G. P.; Mani, Tamizh

2012-01-01

323

Formation of ethyl acetate from whey by Kluyveromyces marxianus on a pilot scale.  

PubMed

Whey arising in huge amounts during milk processing is a valuable renewable resource in the field of White Biotechnology. Kluyveromyces marxianus is able to convert whey-borne lactose into ethyl acetate, an environmentally friendly solvent. Formation of ethyl acetate as a bulk product is triggered by iron (Fe). K. marxianus DSM 5422 was cultivated aerobically in whey-borne medium originally containing 40 ?g/L Fe, supplemented with 1, 3 or 10 mg/L Fe in the pre-culture, using an 1 L or 70 L stirred reactor. The highest Fe content in the pre-culture promoted yeast growth in the main culture causing a high sugar consumption for growth and dissatisfactory formation of ethyl acetate, while the lowest Fe content limited yeast growth and promoted ester synthesis but slowed down the process. An intermediate Fe dose (ca. 0.5 ?g Fe/g sugar) lastly represented a compromise between some yeast growth, a quite high yield of ethyl acetate and an acceptable duration of the process. The mass of ethyl acetate related to the sugar consumed amounted to 0.113, 0.265 and 0.239 g/g in the three processes corresponding to 21.9%, 51.4% and 46.3% of the theoretically maximum yield. The performance on a pilot scale was somewhat higher than on lab scale. PMID:23089728

Löser, Christian; Urit, Thanet; Stukert, Anton; Bley, Thomas

2013-01-10

324

Ethyl Radical Ejection During Photodecomposition of Butanone on TiO2(110)  

SciTech Connect

The photodecomposition of acetone and butanone were examined on the (110) surface of rutile TiO2 using temperature programmed desorption (TPD) and photon stimulated desorption (PSD). In both cases, photodecomposition was proceeded by a required thermal reaction between the adsorbed ketone and coadsorbed oxygen resulting in a diolate species. The diolate photodecomposed by ejection of an organic radical from the surface leaving behind a carboxylate species. In the acetone case, only methyl radical PSD was detected and acetate was left on the surface. In the butanone case there was a possibility of either methyl or ethyl radical ejection, with propionate or acetate left behind, respectively. However, only ethyl radical PSD was detected and the species left on the surface (acetate) was the same as in the acetone case. The preference for ethyl radical ejection is linked to the greater thermal stability of the ethyl radical over that of the methyl radical. Unlike in the acetone case, where the ejected methyl radicals did not participate in thermal chemistry on the TiO2(110) surface after photoactivation of the acetone diolate, ethyl radicals photodesorbing at 100 K from butanone diolate showed a preference for dehydrogenation to ethene through the influence of coadsorbed oxygen. These results reemphasize the mechanistic importance of organic radical production during photooxidation reactions on TiO2 surface.

Henderson, Michael A.

2008-10-15

325

Ethyl Radical Ejection During Photodecomposition of Butanone on TiO2(110)  

SciTech Connect

The photodecomposition of acetone and butanone were examined on the (110) surface of rutile TiO2 using temperature programmed desorption (TPD) and photon stimulated desorption (PSD). In both cases, photodecomposition was proceeded by a required thermal reaction between the adsorbed ketone and coadsorbed oxygen resulting in a diolate species. The diolate photodecomposed by ejection of an organic radical from the surface leaving behind a carboxylate species. In the acetone case, only methyl radical PSD was detected and acetate was left on the surface. In the butanone case there was a possibility of either methyl or ethyl radical ejection, with propionate or acetate left behind, respectively. However, only ethyl radical PSD was detected and the species left on the surface (acetate) was the same as in the acetone case. The preference for ethyl radical ejection is linked to the greater thermal stability of the ethyl radical over that of the methyl radical. Unlike in the acetone case, where the ejected methyl radicals did not participate in thermal chemistry on the TiO2(110) surface after photoactivation of the acetone diolate, ethyl radicals photodesorbing at 100 K from butanone diolate showed a preference for dehydrogenation to ethene through the influence of coadsorbed oxygen. These results reemphasize the mechanistic importance of organic radical production during photooxidation reactions on TiO2 surface. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.

Henderson, Michael A.

2008-10-15

326

Lignin is linked to ethyl-carbamate formation in ume (Prunus mume) liqueur.  

PubMed

Ethyl carbamate concentrations in oak barrel-aged ume (Prunus mume) liqueurs were measured, and possible explanations for elevated levels were examined. The average concentration was 0.30 mg/L, significantly higher than in ume liqueurs not aged in oak (0.08 mg/L). Oak powder extracts were prepared from both untoasted and toasted oak powder by extraction with aqueous ethanol, and these were used to make ume liqueurs. Relative to a no-oak control, the ethyl carbamate concentrations were 3.8 and 11 times higher in the ume liqueur made with the untoasted and toasted oak powder extracts respectively. The extracts were loaded onto a C18 column, washed with water, and eluted with methanol. The (13)C-NMR spectra for the main constituents of the methanol elution fractions were consistent with those for lignin or fragments thereof. The methanol fractions were added to ume liqueur which was stored for 3 months. Relative to a control, the ethyl carbamate concentrations in the 3-month old liqueurs were found to be 1.2 and 4.6 higher for the untoasted oak-powder and the toasted oak-powder respectively. Ethyl carbamate was formed when lignin was added to a 40% aqueous ethanol solution that contained potassium cyanide. These observations suggest that lignin or fragments thereof promote the formation of ethyl carbamate. PMID:22232267

Hashiguchi, Tomokazu; Izu, Hanae; Sudo, Shigetoshi

2012-01-01

327

Determination of fatty acid ethyl esters in hair by GC-MS and application in a population of cocaine users.  

PubMed

A gas chromatography-mass spectrometry method for the determination of ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate in hair samples was developed, validated and applied to real samples. Ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate are fatty acid ethyl esters (FAEE) which are known to be direct biotransformation products of ethanol. Their presence in the body fluids and tissue is therefore indicative of alcohol intake and, in particular, FAEE concentration in hair higher than 0.5 ng/mg is indicative of excessive chronic alcohol consumption. The method was applied to 80 hair samples formerly found positive for cocaine and FAEE analytical results were compared with the presence of cocaethylene, a cocaine metabolite formed only when alcohol and cocaine are used together. According to our data the two biomarkers (FAEE and cocaethylene in hair) are tools of great value in the assessment of the diagnosis of use of cocaine and ethanol. In fact, discrepancies were noted and might be related to various factors including differences in consumption habits and thus permitting to distinguish the use of both substances non-concurrently or concurrently. Also, the determination of both markers may, in some cases, discriminate the use of moderate or heavy alcohol amounts when associated with cocaine. Finally, in a population of non-cocaine-users our results support FAEE as valuable means in the assessment of excessive alcohol chronic use. PMID:21159458

Politi, Lucia; Mari, Francesco; Furlanetto, Sandra; Del Bravo, Ester; Bertol, Elisabetta

2011-04-01

328

Quantitative determination of 4-ethylphenol and 4-ethyl-2-methoxyphenol in wines by a stable isotope dilution assay  

Microsoft Academic Search

The deuterium-labelled standards 4-ethylphenol-d3 and 4-ethyl-2-methoxyphenol-d3 were synthesized and utilized in a rapid, sensitive, and accurate stable isotope dilution assay for 4-ethylphenol and 4-ethyl-2-methoxyphenol in wine. For a 5-mL sample of a Merlot wine, quantitation was reliable down to 500ng\\/L for 4-ethylphenol and 100ng\\/L for 4-ethyl-2-methoxyphenol at estimated signal-to-noise ratio of 3:1, respectively. The concentrations of 4-ethylphenol and 4-ethyl-2-methoxyphenol were

Sierra Rayne; Nigel J. Eggers

2007-01-01

329

Chromatographic purification and identification of polar metabolites of benazolin-ethyl from soybean.  

PubMed

The metabolism of benazolin-ethyl (4-chloro-2-oxobenzothiazolin-3-ylacetic acid ethyl ester), a post emergence herbicide, has been studied in soybean using (14C)-phenyl labelled compound. Preliminary studies were performed on excised soybean leaves. Following hydrolysis of the ethyl ester to benazolin acid (4-chloro-2-oxobenzothiazolin-3-ylacetic acid), extensive metabolism to polar conjugates was observed. The polar fraction from a Bligh-Dyer extraction was purified by solvent partitioning, preparative TLC and reverse phase HPLC with ion suppression. The two major metabolites were characterised by fast atom bombardment mass spectrometry with accurate mass determination as an aspartate conjugate and a malonyl-beta-glucose ester of benazolin acid. Subsequent experiments were performed by spraying intact plants at growth stage V4. The major polar metabolite isolated one month after treatment was identified as the aspartate conjugate by mass spectrometry and high resolution nuclear magnetic resonance spectroscopy. PMID:3744655

Kelly, I D; Smith, S

1986-01-01

330

Organosolv pretreatment of Sitka spruce wood: conversion of hemicelluloses to ethyl glycosides.  

PubMed

A range of Organosolv pretreatments, using ethanol:water mixtures with dilute sulphuric acid, were applied to Sitka spruce sawdust with the aim of generating useful co-products as well as improving saccharification yield. The most efficient of the pretreatment conditions, resulting in subsequent saccharification yields of up to 86%, converted a large part of the hemicellulose sugars to their ethyl glycosides as identified by GC/MS. These conditions also reduced conversion of pentoses to furfural, the ethyl glycosides being more stable to dehydration than the parent pentoses. Through comparison with the behaviour of model compounds under the same reaction conditions it was shown that the anomeric composition of the products was consistent with a predominant transglycosylation reaction mechanism, rather than hydrolysis followed by glycosylation. The ethyl glycosides have potential as intermediates in the sustainable production of high-value chemicals. PMID:24269088

Bouxin, Florent P; David Jackson, S; Jarvis, Michael C

2014-01-01

331

Characterization and Antioxidant Properties of Six Algerian Propolis Extracts: Ethyl Acetate Extracts Inhibit Myeloperoxidase Activity  

PubMed Central

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

Boufadi, Yasmina Mokhtaria; Soubhye, Jalal; Riazi, Ali; Rousseau, Alexandre; Vanhaeverbeek, Michel; Nève, Jean; Boudjeltia, Karim Zouaoui; Van Antwerpen, Pierre

2014-01-01

332

Potential options and manufacturing changes for ethyl ether in support of pollution prevention  

SciTech Connect

This project addresses the elimination or reduction of a hazardous substance/toxic chemical, ethyl ether, as listed by the US Environmental Protection Agency in the Toxic Release Inventory. The study focuses on replacing or eliminating the need for the substance in Department of Defense systems (e.g., weapon systems, ammunition manufacturing, propellant manufacturing and processing). An analysis of the processes using ethyl ether, a search for substitutions, and a review of modern techniques are central to this project. The results and procedures form the basis for broader application and chemical change. Ethyl ether is the first of two chemical candidates for replacement and the primary subject of this paper. All conclusions and recommendations require laboratory verification.

Watts, D.J.; Zimmer, I.B. [New Jersey Inst. of Tech., Newark, NJ (United States). Emission Reduction Research Center

1996-12-31

333

Photo-catalyzed oxidation of ethyl chloride and chlorobenzene adsorbed on titania catalysts  

SciTech Connect

The use of titania as a catalyst in photooxidation reactions for the destruction of hazardous hydrocarbon waste material has been the subject of much investigation. Titania has been shown to be a stable and effective catalysts for mineralization of chlorinated hydrocarbons. The reaction intermediates and the mechanism by which these reactions take place, however, are still controversial. In this work, we have investigated the photo-oxidation of gas phase ethyl chloride and chlorobenzene adsorbed on titania by infrared spectroscopy. For ethyl chloride we have identified ethoxide as an intermediate species. The addition of metal particles to the titania catalyst has also been studied and will be presented.

McGee, K.C.; Scigliano, E.P.; Grassian, V.H. [Univ. of Iowa, Iowa City, IA (United States)

1996-10-01

334

Photostability of Isovaline and its Precursor 5-Ethyl-5- methylhydantoin Exposed to Simulated Space Radiations  

PubMed Central

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

Sarker, Palash K.; Takahashi, Jun-ichi; Kawamoto, Yukinori; Obayashi, Yumiko; Kaneko, Takeo; Kobayashi, Kensei

2012-01-01

335

Investigating the performance of CoxOy/activated carbon catalysts for ethyl acetate catalytic combustion  

NASA Astrophysics Data System (ADS)

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).

Xie, Hongmei; Zhao, Xiaoping; Zhou, Guilin; He, Xiaoling; Lan, Hai; Jiang, Zongxuan

2015-01-01

336

Storage effects on desorption efficiencies of methyl ethyl ketone and styrene collected on activated charcoal  

E-print Network

STORAGE EFf ECTS ON DESORP'TIC'N EFFICIENCIES OF METHYL ETHYL KF10NE AND STYRENE COLLECTED ON ACTIVATED CHARCOAL A Thesis by RICHARD ALVIN DONiNiER Approved as to style and content by: ( ha1ris a of Coll'Jn1 t tee Nay l978 QQZSGH ABSTRACT... Storage Effects on Desorption Efficiercies of i&lethyl Ethyl Ketone and Styrene Colleci-. ed on Activated Charcoal (liay 1978) Richard A. Dommer, B. S. , Central !'iichigan D&nivers ity Directed by: Dr, Ralph J. Vernon The effects on the desorption...

Dommer, Richard Alvin

1978-01-01

337

Molecular Model of trans-3-(9-Anthryl)-2-Propenoic Acid Ethyl Ester  

NSDL National Science Digital Library

The Featured Molecules this month come from the paper by Nguyen and Weisman on solvent-free Wittig reactions and the stereochemical consequences of crowding in the transition state. The molecules include those pictured in the paper as well as the cis-isomer of 3-(9-anthryl)-2-propenoic acid ethyl ester. All structures were optimized at the B3LPY/6-31G* level. In the case of ethyl cinnamate, the cis-isomer is slightly more stable thermodynamically than the trans isomer, lending further support for the argument that the observed product distribution arises from the energetics of the transition state.

338

Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ??-adrenergic signaling.  

PubMed

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

Yamazaki, Shunsuke; Miyoshi, Noriyuki; Kawabata, Kyuichi; Yasuda, Michiko; Shimoi, Kayoko

2014-09-01

339

Evaluation of UGT protein interactions in human hepatocytes: Effect of siRNA down regulation of UGT1A9 and UGT2B7 on propofol glucuronidation in human hepatocytes?  

PubMed Central

Previous experiments performed in recombinant systems have suggested that protein–protein interactions occur between the UGTs and may play a significant role in modulating enzyme activity. However, evidence of UGT protein–protein interactions either in vivo or in more physiologically relevant in vitro systems has yet to be demonstrated. In this study, we examined oligomerization and its ability to affect glucuronidation in plated human hepatocytes. siRNA down regulation experiments and activity studies were used to examine changes in metabolite formation of one UGT isoform due to down regulation of a second UGT isoform. Selective siRNA directed towards UGT1A9 or UGT2B7 resulted in significant and selective decreases in their respective mRNA levels. As expected, the metabolism of the UGT1A9 substrate propofol decreased with UGT1A9 down regulation. Interestingly, UGT1A9 activity, but not UGT1A9 mRNA expression, was also diminished when UGT2B7 expression was selectively inhibited, implying potential interactions between the two isoforms. Minor changes to UGT1A4, UGT2B4 and UGT2B7 activity were also observed when UGT1A9 expression was selectively down regulated. To our knowledge, this represents the first piece of evidence that UGT protein–protein interactions occur in human hepatocytes and suggests that expression levels of UGT2B7 may directly impact the glucuronidation activity of selective UGT1A9 substrates. PMID:23562620

Konopnicki, Camille M.; Dickmann, Leslie J.; Tracy, Jeffrey M.; Tukey, Robert H.; Wienkers, Larry C.; Foti, Robert S.

2014-01-01

340

Species difference in the inhibitory potentials of non-steroidal anti-inflammatory drugs on the hepatic sulfation and glucuronidation of bioactive flavonoids: differential observations among common inhibition parameters.  

PubMed

1. This study elucidated the species differences between rats and humans in the inhibitory potential of drugs against sulfation and glucuronidation, and whether such differences depend on the inhibition parameter adopted. 2. With 14 non-steroidal anti-inflammatory drugs (NSAIDs) as model inhibitors and three flavanoids baicalein, wogonin and oroxylin A as model substrates, three common inhibition parameters percentage of control, IC50 and Ki were determined in rat liver cytosols (RLCs), human liver cytosols (HLCs), rat liver microsomes (RLMs) and human liver microsomes (HLMs). The closeness of the inhibition parameters from rat liver preparations to that from human liver preparations was analyzed by geometric mean fold error (GMFE) and statistical comparisons. 3. The percentage of control in RLC/RLM was not significantly different from that in HLC/HLM, with a GMFE of 0.85 (RLC-HLC) and 1.03 (RLM-HLM); whereas the IC50 and Ki in RLC/RLM were significantly different from that in HLC/HLM. The trend of difference was consistent between IC50 and Ki, where these parameters in RLC and RLM underestimated (GMFE <0.5) and overestimated (GMFE >2) that in HLC and HLM, respectively. 4. In conclusion, the inhibitory potentials of NSAIDs against sulfation and glucuronidation in rats and humans were different and depended on the adopted inhibition parameters. PMID:24168065

Fong, Sophia Yui Kau; Zuo, Zhong

2014-05-01

341

Determination of a novel nonfluorinated quinolone, nemonoxacin, in human feces and its glucuronide conjugate in human urine and feces by high-performance liquid chromatography-triple quadrupole mass spectrometry.  

PubMed

Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-?-d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-?-d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12?µg/g and the calibration curve was linear in the concentration range of 0.12-48.00?µg/g. The LLOQ of the metabolite was 0.0010?µg/mL and 0.03?µg/g in urine and feces matrices, while the linear range was 0.0010-0.2000?µg/mL and 0.03-3.00?µg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25322721

He, Gaoli; Guo, Beining; Yu, Jicheng; Zhang, Jing; Wu, Xiaojie; Cao, Guoying; Shi, Yaoguo; Tsai, Cheng-Yuan

2014-10-17

342

Disappearance of Chlorpyrifos Ethyl Pesticide Residues on Tomatoes, Citrus Fruits and Sugar Beet Grown in the Open Field  

Microsoft Academic Search

In this study, the prevalence of chlorpyrifos ethyl in tomatoes, citrus fruit and sugar beet produced in an area of Northern Morocco (Berkane) was investigated. Samples were taken from the major production areas during 2005-2006. Another objective of this work was to evaluate the degradation behaviour and residue levels of chlorpyrifos ethyl in tomatoes, citrus fruits, and sugar beet grown

R. Salghi; H. Zerouali; M. Zougagh; A. Hormatallah; L. Bazzi; A. Chakir; A. Rios

343

Small angle neutron scattering study of deuterated sodium dodecylsulfate micellization in dilute poly((2edimethylamino)ethyl methacrylate) solutions  

E-print Network

Small angle neutron scattering study of deuterated sodium dodecylsulfate micellization in dilute 2010 Keywords: Poly((2edimethylamino)ethyl methacrylate) Micelle Small angle neutron scattering a b angle neutron scattering. We found three transitions of the poly ((2edimethylamino)ethyl methacrylate

Kofinas, Peter

344

Practical preparation of potentially anesthetic uorinated ethyl methyl ethers by means of bromine triuoride and other methods  

E-print Network

Practical preparation of potentially anesthetic ¯uorinated ethyl methyl ethers by means of bromine of his 85th birthday Abstract Synthetic methods, especially those that use bromine tri Elsevier Science S.A. All rights reserved. Keywords: Fluorinated ethyl methyl ethers; Bromine tri

Hudlicky, Tomas

345

On using film boiling to thermally decompose liquid organic chemicals: Application to ethyl acetate as a model compound  

E-print Network

On using film boiling to thermally decompose liquid organic chemicals: Application to ethyl acetate 21 August 2013 Keywords: Film boiling Thermal decomposition Pyrolysis Ethyl acetate Critical heat flux (CHF) Leidenfrost point a b s t r a c t Film boiling on a horizontal tube is used to study

Walter, M.Todd

346

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

...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...

2014-07-01

347

Detection of chlorpyrifos-ethyl (Dursban) and its metabolites in urine samples using immunoassays with confirmation by gas chromatography/mass spectrometry  

E-print Network

Chlorpyrifos-ethyl (Dursban) belongs to the organophosphate class of pesticides. Many organophosphates, such as parathion and chlordane, are highly toxic and have restricted usage. Others, including chlorpyrifos-ethyl, are widely used for domestic...

Clewis, Suenda Beth

2012-06-07

348

Antiplasmodial Properties and Bioassay-Guided Fractionation of Ethyl Acetate Extracts from Carica papaya Leaves  

PubMed Central

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

Melariri, Paula; Campbell, William; Etusim, Paschal; Smith, Peter

2011-01-01

349

Plant Physiol. (1995) 108: 399-409 Alteration of Seed Fatty Acid Composition by an Ethyl  

E-print Network

Plant Physiol. (1995) 108: 399-409 Alteration of Seed Fatty Acid Composition by an Ethyl in the formation of very long-chain fatty acids (VLCFAs) in the Brassicaceae, we have gen- erated a series and accumulates 18:3 as the major fatty acid in triacylglycerols. Proportions of 18:2 remain similar to WT. Ce

Kunst, Ljerka

350

IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) (2009 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. Please refer...

351

Patterning and hardening of Gold Black infrared absorber by shadow mask deposition with Ethyl Cyanoacrylate  

E-print Network

Patterning and hardening of Gold Black infrared absorber by shadow mask deposition with Ethyl is reported. Gold black nano-structured films are deposited through a thin metal shadow mask in a thermalTM "). 2. EXPERIMENT Gold black is deposited by the method of Harris.[1] Thick, porous films of gold black

Peale, Robert E.

352

Development of an Enzyme-Linked Immunosorbent Assay for the Organophosphorus Insecticide Bromophos-ethyl  

E-print Network

-ethyl KWANG-OK KIM, YOO JUNG KIM, YONG TAE LEE, BRUCE D. HAMMOCK,§ AND HYE-SUNG LEE*, Department of Food of pesticides, there is increasing concern over food and environmental contamination caused by their use. The current methods such as gas chromatography (GC) and high-performance liquid chromatography (HPLC) have

Hammock, Bruce D.

353

Transformation Kinetics and Mechanism of the Sulfonylurea Herbicides Pyrazosulfuron Ethyl and Halosulfuron Methyl in Aqueous Solutions  

Microsoft Academic Search

Pyrazosulfuron ethyl (PE) and halosulfuron methyl (HM) are two new highly active sulfonylurea herbicides that have been widely used for weed control in a variety of vegetables and other crops. These two herbicides have similar molecular structures, differing only in the substitutions on the pyrazole ring. Chemical hydrolysis is a primary process affecting the environmental fate of sulfonylurea pesticides. The

Wei Zheng; Scott R. Yates; Sharon K. Papiernik

2008-01-01

354

Amino acids and glycine ethyl ester as new crystallization reagents for lysozyme  

PubMed Central

Several amino acids and their derivatives are prominent additives in the field of protein chemistry. This study reports the use of charged amino acids and glycine ethyl ester as precipitants in protein crystallization, using hen egg-white lysozyme (HEWL) as a model. A discussion of the crystallization of HEWL using these reagents as precipitating agents is given. PMID:20516616

Ito, Len; Shiraki, Kentaro; Yamaguchi, Hiroshi

2010-01-01

355

Antiangiogenic effects and mechanisms of trans-ethyl p-methoxycinnamate from Kaempferia galanga L.  

PubMed

Kaempferia galanga L. (Zingiberaceae) is an aromatic herb and a popular spice used as a condiment in Asian cuisine. The ethanol extract of the dried plant and its successive four subfractions were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay. Both n-hexane and ethyl acetate fractions had antiangiogenic activity, and two major active components (trans-ethyl p-methoxycinnamate and kaempferol) showed potent antiangiogenic effects on wild-type zebrafish. Because of its much stronger effect and no antiangiogenic activity reported, trans-ethyl p-methoxycinnamate was further investigated for its action mechanism. It dose dependently inhibited vessel formation on both wild- and Tg(fli1a:EGFP)y1-type zebrafish embryos. The semiquantitative reverse transcription polymerase chain reaction assay suggested that trans-ethyl p-methoxycinnamate affects multiple molecular targets related to angiogenesis. In vitro, it specifically inhibited the migration and tube formation of human umbilical vein endothelial cells. In vivo, it could block bFGF-induced vessel formation on Matrigel plug assay. PMID:23106130

He, Zhi-Heng; Yue, Grace Gar-Lee; Lau, Clara Bik-San; Ge, Wei; But, Paul Pui-Hay

2012-11-14

356

Neurotoxicity Associated with Occupational Exposure to Acetone, Methyl Ethyl Ketone, and Cyclohexanone  

Microsoft Academic Search

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

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

1997-01-01

357

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

ERIC Educational Resources Information Center

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…

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

2005-01-01

358

nanodroplet water imbibed in poly(2-hydroxy-ethyl-methacrylate) (polyHEMA) near its glass  

E-print Network

hyperquenched metallic glasses, apparently remains in the glassy state until it crystallizes (at 150 to 160 Knanodroplet water imbibed in poly(2-hydroxy- ethyl-methacrylate) (polyHEMA) near its glass times are also Arrhenius in character and faster than the relaxation responsible for the glass

Kansas, University of

359

40 CFR 180.1323 - Ethyl-2E,4Z-decadienoate (Pear Ester); exemption from the requirement of a tolerance.  

Code of Federal Regulations, 2014 CFR

...false Ethyl-2E,4Z-decadienoate (Pear Ester); exemption from the requirement...1323 Ethyl-2E,4Z-decadienoate (Pear Ester); exemption from the requirement...pesticide, ethyl-2E,4Z-decadienoate (pear ester), in or on all food...

2014-07-01

360

40 CFR 721.10665 - 2-Propenoic acid, (2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl ester.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 false 2-Propenoic acid, (2-ethyl-2-methyl-1...721.10665 2-Propenoic acid, (2-ethyl-2-methyl-1...generically as 2-propenoic acid, (2-ethyl-2- methyl-1...and ink formulations) and (s) (50,000 kilograms)....

2014-07-01

361

40 CFR 721.10665 - 2-Propenoic acid, (2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl ester.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false 2-Propenoic acid, (2-ethyl-2-methyl-1...721.10665 2-Propenoic acid, (2-ethyl-2-methyl-1...generically as 2-propenoic acid, (2-ethyl-2-methyl-1...and ink formulations) and (s) (50,000 kilograms)....

2013-07-01

362

40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...  

Code of Federal Regulations, 2010 CFR

...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil,...

2010-07-01

363

40 CFR 721.5375 - Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter, bis-[[[[(sub-sti-tut-ed)] amino]-alkyl-phenyl...  

Code of Federal Regulations, 2011 CFR

...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...ni-tro-thio-phene-car-boxy-lic acid, ethyl ester,...

2011-07-01

364

40 CFR 721.5375 - Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter, bis-[[[[(sub-sti-tut-ed)] amino]-alkyl-phenyl...  

Code of Federal Regulations, 2010 CFR

...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...ni-tro-thio-phene-car-boxy-lic acid, ethyl ester,...

2010-07-01

365

40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...  

Code of Federal Regulations, 2014 CFR

...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil,...

2014-07-01

366

40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...  

Code of Federal Regulations, 2011 CFR

...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil,...

2011-07-01

367

40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...  

Code of Federal Regulations, 2013 CFR

...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil,...

2013-07-01

368

40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...  

Code of Federal Regulations, 2012 CFR

...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil, reaction...2-hydroxyethyl)amino]ethyl], reaction...sulfur dioxide; fatty acids, tall-oil,...

2012-07-01

369

40 CFR 721.5375 - Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter, bis-[[[[(sub-sti-tut-ed)] amino]-alkyl-phenyl...  

Code of Federal Regulations, 2012 CFR

...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...ni-tro-thio-phene-car-boxy-lic acid, ethyl ester,...

2012-07-01

370

40 CFR 721.5375 - Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter, bis-[[[[(sub-sti-tut-ed)] amino]-alkyl-phenyl...  

Code of Federal Regulations, 2013 CFR

...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...ni-tro-thio-phene-car-boxy-lic acid, ethyl ester,...

2013-07-01

371

40 CFR 721.5375 - Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter, bis-[[[[(sub-sti-tut-ed)] amino]-alkyl-phenyl...  

Code of Federal Regulations, 2014 CFR

...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...Ni-tro-thio-phene-car-boxy-lic acid, ethyl es-ter...sub-sti-tut-ed)] amino]-alkyl-phenyl...ni-tro-thio-phene-car-boxy-lic acid, ethyl ester,...

2014-07-01

372

40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...  

Code of Federal Regulations, 2012 CFR

...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100 Section 721...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium...

2012-07-01

373

40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...  

Code of Federal Regulations, 2011 CFR

...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100 Section 721...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium...

2011-07-01

374

40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...  

Code of Federal Regulations, 2013 CFR

...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100 Section 721...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium...

2013-07-01

375

40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...  

Code of Federal Regulations, 2014 CFR

...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100 Section 721...N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium...

2014-07-01

376

Sorption of chlorimuron-ethyl on montmorillonite clays: effects of exchangeable cations, pH, and ionic strength.  

PubMed

Sorption interaction of chlorimuron-ethyl with montmorillonite clays was investigated under varied types of exchangeable cation, pH, and ionic strength conditions. Chlorimuron-ethyl sorption on bentonites exhibited pronounced cation dependency, and the sorption ability increased as the sequence Ca(2+)- < Na(+)- < Al(3+)- < Fe(3+)-bentonite, due to different sorption mechanisms, whereas the cation dependency was influenced by the clay type and much weaker for montmorillonites. The decrease of pH at the range of 4.0-6.0 prominently increased sorption of chlorimuron-ethyl on all cation-exchanged montmorillonite clays, and nearly a neglected sorption (about 2 %) can be observed at pH over 7.0. In the presence of CaCl2, sorption of chlorimuron-ethyl on Fe(3+)-bentonite was promoted because of complexion of Ca(2+) and the surface of Fe(3+)-bentonite. However, as the concentration of CaCl2 increased, chlorimuron-ethyl sorption on Ca(2+)- and Fe(3+)-exchanged bentonite decreased, suggesting that Ca bridging was not the prevailing mechanism for sorption of chlorimuron-ethyl on these clays. Furthermore, chlorimuron-ethyl sorption was relatively sensitive to pH, and the change of pH may obscure effect of other factors on the sorption, so it was quite necessary to control pH at a constant value when the effect of other factor was being studied. PMID:25028319

Ren, Wenjie; Teng, Ying; Zhou, Qixing; Paschke, Albrecht; Schüürmann, Gerrit

2014-10-01

377

Nosocomial pseudoepidemic caused by Bacillus cereus traced to contaminated ethyl alcohol from a liquor factory.  

PubMed

From September 1990 to October 1990, 15 patients who were admitted to four different departments of the National Taiwan University Hospital, including nine patients in the emergency department, three in the hematology/oncology ward, two in the surgical intensive care unit, and one in a pediatric ward, were found to have positive blood (14 patients) or pleural effusion (1 patient) cultures for Bacillus cereus. After extensive surveillance cultures, 19 additional isolates of B. cereus were recovered from 70% ethyl alcohol that had been used as a skin disinfectant (14 isolates from different locations in the hospital) and from 95% ethyl alcohol (5 isolates from five alcohol tanks in the pharmacy department), and 10 isolates were recovered from 95% ethyl alcohol from the factory which supplied the alcohol to the hospital. In addition to these 44 isolates of B. cereus, 12 epidemiologically unrelated B. cereus isolates, one Bacillus sphaericus isolate from a blood specimen from a patient seen in May 1990, and two B. sphaericus isolates from 95% alcohol in the liquor factory were also studied for their microbiological relatedness. Among these isolates, antibiotypes were determined by using the disk diffusion method and the E test, biotypes were created with the results of the Vitek Bacillus Biochemical Card test, and random amplified polymorphic DNA (RAPD) patterns were generated by arbitrarily primed PCR. Two clones of the 15 B. cereus isolates recovered from patients were identified (clone A from 2 patients and clone B from 13 patients), and all 29 isolates of B. cereus recovered from 70 or 95% ethyl alcohol in the hospital or in the factory belonged to clone B. The antibiotype and RAPD pattern of the B. sphaericus isolate from the patient were different from those of isolates from the factory. Our data show that the pseudoepidemic was caused by a clone (clone B) of B. cereus from contaminated 70% ethyl alcohol used in the hospital, which we successfully traced to preexisting contaminated 95% ethyl alcohol from the supplier, and by another clone (clone A) without an identifiable source. PMID:10364598

Hsueh, P R; Teng, L J; Yang, P C; Pan, H L; Ho, S W; Luh, K T

1999-07-01

378

Effect of ionic liquid [BMIM][PF 6 ] on asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate by Saccharomyces cerevisiae  

Microsoft Academic Search

The effect of ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) on the asymmetric reduction of ethyl 2-oxo-4-phenylbutyrate (EOPB) to synthesize optical active ethyl 2-hydroxy-4-phenylbutyrate\\u000a (EHPB) catalyzed by Saccharomyces cerevisiae was investigated. (R)-EHPB [70.4%, e.e.(R)] is obtained using ethyl ether or benzene as the solvent. The main product is (S)-EHPB [27.7%, e.e.(S)] in [BMIM][PF6]. However, in ionic liquid-water (10:1, v\\/v) biphasic system, the

Yu-Gang Shi; Yun Fang; Yue-Ping Ren; Hong-Ping Wu; Hui-Lei Guan

2008-01-01

379

Absolute quantification of UGT1A1 in various tissues and cell lines using isotope label-free UPLC-MS/MS method determines its turnover number and correlates with its glucuronidation activities.  

PubMed

Uridine 5'-diphosphate-glucuronosyltransferase (UGT)1A1 is a major phase II metabolism enzyme responsible for glucuronidation of drugs and endogenous compounds. The purpose of this study was to determine the expression level of UGT1A1 in human liver microsomes and human cell lines by using an isotope label-free LC-MS/MS method. A Waters Ultra performance liquid chromatography (UPLC) system coupled with an API 5500Qtrap mass spectrometer was used for the analysis. Two signature peptides (Pep-1, and Pep-2) were employed to quantify UGT1A1 by multiple reaction monitoring (MRM) approach. Standard addition method was used to validate the assay to account for the matrix effect. 17?-Estradiol was used as the marker substrate to determine UGT1A1 activities. The validated method has a linear range of 200-0.0195nM for both signature peptides. The precision, accuracy, and matrix effect were in acceptable ranges. UGT1A1 expression levels were then determined using 8 individual human liver microsomes, a pooled human liver microsomes, three UGT1A1 genotyped human liver microsomes, and four cell lines (Caco-2, MCF-7, Hela, and HepG2). The correlations study showed that the UGT1A1 protein levels were strongly correlated with its glucuronidation activities in human liver microsomes (R(2)=0.85) and in microsomes prepared from cell lines (R(2)=0.95). Isotope-labeled peptides were not necessary for LC-MS/MS quantitation of proteins. The isotope label-free absolute quantification method used here had good accuracy, sensitivity, linear range, and reproducibility, and were used successfully for the accurate determination of UGT1A1 from tissues and cell lines. PMID:24055854

Xu, Beibei; Gao, Song; Wu, Baojian; Yin, Taijun; Hu, Ming

2014-01-01

380

Dynamics simulations and statistical modeling of thermal decomposition of 1-ethyl-3-methylimidazolium dicyanamide and 1-ethyl-2,3-dimethylimidazolium dicyanamide.  

PubMed

Quasi-classical, direct dynamics trajectories were calculated at the B3LYP/6-31G* level of theory, in an attempt to understand decomposition mechanisms of 1-ethyl-3-methylimidazolium dicyanamide (EMIM(+)DCA(-)) and 1-ethyl-2,3-dimethylimidazolium dicyanamide (EMMIM(+)DCA(-)). The trajectories showed many dissociation paths for these two ionic liquids. Using trajectory results as a guide, structures of transition states and products that might be important for decomposition of these two compounds were determined using density functional theory calculations. Rice-Ramsperger-Kassel-Marcus (RRKM) theory was then utilized to examine properties of energized ionic liquids and to determine unimolecular rates for crossing various transition states. On the basis of RRKM modeling, initial decomposition paths for energized EMIM(+)DCA(-) correspond to formation of an N-heterocyclic carbene and acid pair via transfer of the C2 proton of EMIM(+) to DCA(-), and evolution of methylimidazole and ethylimidazole via SN2 alkyl abstraction by DCA(-). Similar decomposition paths were identified for energized EMMIM(+)DCA(-), except that the reactivity of C2 of the imidazolium cation is significantly reduced upon substitution of a methyl group for a hydrogen atom at this position. The present work demonstrates that dynamics simulations, in conjunction with statistical modeling, are able to provide insight into decomposition mechanisms, kinetics, and dynamics for alkylimidazolium-based ionic liquids and to predict product branching ratios and how they vary with decomposition temperatures. PMID:25275818

Liu, Jianbo; Chambreau, Steven D; Vaghjiani, Ghanshyam L

2014-11-26

381

Reaction rate coefficients of OH radicals and Cl atoms with ethyl propanoate, n-propyl propanoate, methyl 2-methylpropanoate, and ethyl n-butanoate.  

PubMed

Kinetics of the reactions of OH radicals and Cl atoms with four saturated esters have been investigated. Rate coefficients for the gas-phase reactions of OH radicals with ethyl propanoate (k(1)), n-propyl propanoate (k(2)), methyl 2-methylpropanoate (k(3)), and ethyl n-butanoate (k(4)) were measured using a conventional relative rate method and the pulsed laser photolysis-laser induced fluorescence technique. At (296 +/- 2) K, the rate coefficients obtained by the two methods were in good agreement. Significant curvatures in the Arrhenius plots have been observed in the temperature range 243-372 K for k(1), k(3), and k(4). The rate coefficients for the reactions of the four esters with Cl atoms were determined using the relative rate method at (296 +/- 2) K and atmospheric pressure. The values obtained are presented, compared with the literature values when they exist, and discussed. Reactivity trends and atmospheric implications for these esters are also presented. PMID:19746921

Cometto, Pablo M; Daële, Véronique; Idir, Mahmoud; Lane, Silvia I; Mellouki, Abdelwahid

2009-10-01

382

Analysis of O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products by packed capillary liquid chromatography-electrospray mass spectrometry.  

PubMed

Packed capillary column liquid chromatography (LC)-electrospray mass spectrometry (ESI-MS) was used for the first time to detect and identify O-ethyl, S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products, including compounds containing a P-CH3 bond, bis(diisopropylamino)thioalkanes and ureas commonly employed as VX stabilizers. The reported ESI-MS data were generally acquired with a higher sampling cone voltage, a setting that promoted collisionally activated dissociation, and resulted in the acquisition in informative mass spectra containing both molecular and product ion information. The developed method appears to be an attractive alternative to GC-MS for the analysis of aqueous sample containing the degradation products of VX, since they may be analysed directly with little risk of thermal decomposition and without the need for additional sample handling or derivatization. Application of this method to a degraded VX sample resulted in the detection of a number of novel polar and higher-molecular-mass degradation products, not previously associated with VX during GC-MS analysis. PMID:10227178

D'Agostino, P A; Hancock, J R; Provost, L R

1999-04-01

383

Kinetics of gas-phase hydrolysis of ethyl acetate catalyzed by immobilized lipase.  

PubMed

Reactions catalyzed by supported enzymes present important advantages when compared with those in aqueous media or organic solvents: separation of enzymes from substrate is easily accomplished, enzyme stability may be improved, and control of the reaction products is more accurate. We present the experimental results of the kinetic study of ethyl acetate hydrolysis in gaseous phase catalyzed by a commercial immobilized lipase (Lipozyme IM; Novo Nordisk). The hydrolysis reaction was studied as a function of ethyl ester and water partial pressure at a constant temperature of 318 K. The amount of biocatalyst used was varied between 100 and 300 mg, and the reaction was studied in a flow-through glass microreactor. Under the conditions used, water was an important parameter in the gas-phase reaction. Activation energy was 24.8 kJ/mol and the overall order of reaction was one. Finally, a Bi-Bi reaction mechanism is proposed. PMID:17416975

Perez, Victor H; Miranda, Everson A; Valença, Gustavo P

2007-01-01

384

Effects of metadoxine on cellular formation of fatty acid ethyl esters in ethanol treated rats.  

PubMed

Free fatty acids (FFA) and fatty acid ethyl esters (FAEE) were extracted from different organs of rats administered ethanol, which was found to have induced FAEE formation, which reached its highest levels in the heart, followed by kidney, brain and liver; the ethanol administration resulted also in a marked increase of total FFA content, particularly in brain, kidney, heart and liver. Pretreatment of animals with Metadoxine one hour before ethanol administration inhibited significantly both FAEE and FFA accumulation in all organs examined. These effects were concomitant with the decreased levels of ethanol in blood found in alcohol-intoxicated rats pretreated with Metadoxine. Our results point to the role of fatty acid ethyl esters as possible mediators in the production of alcohol-dependent syndromes, especially in organs lacking oxidative pathways. Administration of Metadoxine, through an increment in alcohol metabolism and turnover, greatly reduces this metabolic abnormality, warranting its potential usefulness as a pharmacological tool in alcoholism management. PMID:8867649

Calabrese, V; Calderone, A; Ragusa, N; Rizza, V

1995-01-01

385

An Evaluation of Ethyl Silicate-Based Grouts for Weathered Silicate Stones  

NASA Astrophysics Data System (ADS)

Culturally significant monuments made of weathered siliceous stone often display sub-surface condition issues such as cracks and voids. These issues require grouts that are ideally compatible with the composition and properties of the substrate. Based on the successful application of ethyl silicates as consolidants in recent literature, this study examines possible formulation pathways for the development of a grout incorporating ethyl silicate. Tetraethylorthosilicate (TEOS), dibutyltin dilaurate (DBTL) as a catalyst, silicone oil (PDMS), various grades of ground quartz, sepiolite, and hollow glass spheres were used in differing concentrations to create samples. These were visually and physically assessed on workability, separation, shrinkage, cracking, strength, and flexibility. Quantitative analysis was performed on selected formulations using UV-Vis-NIR reflectance spectroscopy in coordination with a weight loss experiment to investigate kinetics, dynamic mechanical analysis (DMA), and scanning electron microscopy (SEM). Successful formulations tended to include oligomeric TEOS, crushed quartz of mixed grades, sepiolite powder, and PDMS, and show promise for future investigations.

Dolph, Brittany Helen

386

Continuous synthesis of methyl ethyl ketone peroxide in a microreaction system with concentrated hydrogen peroxide.  

PubMed

Methyl ethyl ketone peroxide (MEKPO) is widely used in polymer industry. It is highly sensitive to heat, friction, shock, flame or other sources of ignition, causing risks in production, storage and transportation. In this article, MEKPO is synthesized at a high throughput with concentrated hydrogen peroxide in a microreactor for on-site and on-demand production. The influences of acid concentration, residence time, feeding rate and ratio, and reaction temperature on the yield and the mass fractions of residual methyl ethyl ketone (MEK) and active oxygen of the product are systematically investigated. Under optimized condition, the reaction is completed in a few seconds, and the product contains less than 2 wt% residual MEK and has a mass active oxygen fraction higher than 22 wt%, which meets the standard for industrial application. PMID:20554382

Zhang, Jing; Wu, Wei; Qian, Gang; Zhou, Xing-Gui

2010-09-15

387

Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats.  

PubMed

The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes. PMID:23606892

Tan, Kok Keong; Kim, Kah Hwi

2013-01-01

388

Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats  

PubMed Central

The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes. PMID:23606892

Tan, Kok Keong; Kim, Kah Hwi

2013-01-01

389

Crystal structures of the solvates of diethylaminogossypol with ethyl acetate and pyridine  

Technology Transfer Automated Retrieval System (TEKTRAN)

The crystal structures of diethylaminogossypol with ethyl acetate (DEAG-EA) and pyridine (DEAG-P) were studied by room-temperature X-ray diffraction. The host-to-guest molecule ratio in these complexes is 2:1 for DEAG-EA and 2:5 for DEAG-P. The crystal and cell parameters for DEAG-EA are C34H40N2O6...

390

An experimental study of the combined effects of n-hexane and methyl ethyl ketone  

Microsoft Academic Search

This study was intended to determine whether or not methyl ethyl ketone (MEK) enhances the neurotoxicity of n-hexane at low concentration and after long term exposure. Separate groups of eight rats were exposed to 100 ppm n-hexane, 200 ppm MEK, 100 ppm n-hexane plus 200 ppm MEK, or fresh air in an exposure chamber for 12 hours a day for

Y Takeuchi; Y Ono; N Hisanaga; M Iwata; M Aoyama; J Kitoh; Y Sugiura

1983-01-01

391

Investigation of biological activities of dichloromethane and ethyl acetate fractions of Platonia insignis Mart. seed.  

PubMed

Platonia insignis Mart., a native species of the Brazilian Amazon more commonly known as bacuri, is a member of the Clusiaceae family. In this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from P. insignis seed ethanolic extract using different experimental models. Our results demonstrate in vitro antioxidant effects, by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1,1-diphenyl-2-picryl-hydrazyl assays, as well as in vivo effects in antioxidant-defective Saccharomyces cerevisiae strains to both fractions. Toxicity was evaluated against the micro-crustaceous Artemia salina Leach. and promastigote Leishmania amazonensis. The dichloromethane fraction was the most active fraction evaluated on A. salina and promastigote L. amazonensis (IC(50)  = 24.89 ?g/mL and 2.84 ?g/mL, respectively). In addition, a slight cytotoxicity was observed in mammalian V79 cells using ethyl acetate and dichloromethane fractions with MTT assays. Both fractions displayed genotoxicity up to 25 ?g/mL (dichloromethane) and 10 ?g/mL (ethyl acetate) in V79 cells, as evaluated by the alkaline comet assay. Thus, in this study, we demonstrate for the first time that ethyl acetate and dichloromethane fractions from P. insignis seeds display antioxidant effects, a toxic effect against A. salina and L. amazonensis and induce genotoxicity in V79 mammalian cells. The observed activities can be attributed to the phenolic compounds present in these fractions and to the presence of xanthones (alpha- and gamma-mangostin). PMID:22788872

Costa Júnior, Joaquim S; Ferraz, Alexandre B F; Sousa, Taciana O; Silva, Romézio A C; De Lima, Sidney G; Feitosa, Chistiane M; Citó, Antônia M G L; Melo Cavalcante, Ana A C; Freitas, Rivelilson M; Moura Sperotto, Angelo R; Péres, Valéria F; Moura, Dinara J; Saffi, Jenifer

2013-01-01

392

Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis  

Microsoft Academic Search

Compounds that cause peroxisome proliferation in rats and mice have been reported to interfere with mitochondrial (mt) bioenergetics and possibly biogenesis. The purpose of this investigation was to establish whether proliferation of peroxisomes and mitochondria are necessarily related. Perfluorooctanesulfonate (PFOS) and N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated as peroxisome proliferators in comparison to perfluorooctanoic acid (PFOA). Three parameters were chosen

Jessica Berthiaume; Kendall B Wallace

2002-01-01

393

Redox reaction in 1-ethyl-3-methylimidazolium–iron chlorides molten salt system for battery application  

Microsoft Academic Search

The redox reaction between divalent and trivalent iron species in binary and ternary molten salt systems consisting of 1-ethyl-3-methylimidazolium chloride (EMICl) with iron chlorides, FeCl2 and FeCl3, was investigated as a candidate of the half-cell reactions of novel rechargeable redox batteries based on low temperature molten salt systems. A reversible one-electron redox reaction between divalent and trivalent iron species was

Yasushi Katayama; Isamu Konishiike; Takashi Miura; Tomiya Kishi

2002-01-01

394

Surface attachment of nitrifying bacteria and their inhibition by potassium ethyl xanthate  

Microsoft Academic Search

Ion exchange resins and glass microscope slides were used to investigate factors affecting attachment of nitrifying bacteria to solid surfaces and the effect of attachment on inhibition ofNitrobacter by potassium ethyl xanthate. The ammonium oxidizerNitrosomonas attached preferentially to cation exchange resins while the nitrite oxidizerNitrobacter colonized anion exchange resins more extensively. Colonization was always associated with growth, and the site

S. E. Underhill; J. I. Prosser

1987-01-01

395

Effect of polybutadiene on the encapsulation efficiency of ethyl cellulose microcapsules of sulphadiazine.  

PubMed

The coacervation-inducing effect of polybutadiene (PBD), a liquid telomer of butadiene, in microencapsulation of sulphadiazine was investigated, using phase separation coacervation of ethyl cellulose, by solvent alteration, in heavy mineral oil medium. The effects of protective colloids and core-wall ratio on encapsulation efficiency were studied. Efficacy of PBD was studied compared to polyisobutylene (PIB). Experimental results revealed that PBD ensured better encapsulation efficiency compared to PIB. PMID:8263673

Das, S K

1993-01-01

396

Ethyl N-(2-acetyl-3-oxo-1-phenyl­but­yl)carbamate  

PubMed Central

In the title compound, C15H19NO4, all three carbonyl groups are syn-oriented with respect to the methine group attached to the phenyl ring. The mean planes of the phenyl ring and ethyl carbamate moiety form a dihedral angle of 65.2?(1)°. In the crystal, mol­ecules related by translation in [100] are linked into chains via N—H?O hydrogen bonds. PMID:24098217

Volov, Alexander N.; Zamilatskov, Ilia A.

2013-01-01

397

A Shock Tube and Chemical Kinetic Modeling Study of Methy Ethyl Ketone Oxidation  

Microsoft Academic Search

Shock-tube ignition delay times for methy ethyl ketone (MEK; or 2-butanone) were measured at a reflected shock pressure of 1 atm (±2%) in the temperature range of 1250–1850 K at equivalence ratios of 0.5–2.0 for dilute mixtures in argon with fuel concentrations of 1.0%, 1.5%, and 2.0%. Rate constants for unimolecular fuel decomposition reactions were treated for falloff in pressure and temperature,

Z. Serinyel; G. Black; H. J. Curran; J. M. Simmie

2010-01-01

398

Ethyl 2-[(2-oxo-2H-chromen-7-yl)­oxy]acetate  

PubMed Central

In the title compound, C13H12O5, the mean plane of the 2H-chromene ring system (r.m.s deviation = 0.026?Å) forms a dihedral angle of 81.71?(6)° with the mean plane of ethyl 2-hy­droxy­acetate moiety (r.m.s deviation = 0.034?Å). In the crystal, C—H?O hydrogen bonds result in the formation of zigzag layers parallel to the bc plane. PMID:23634050

Fun, Hoong-Kun; Quah, Ching Kheng; Aich, Krishnendu; Das, Sangita; Goswami, Shyamaprosad

2013-01-01

399

The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro)  

Microsoft Academic Search

Organophosphates are known primarily as neurotoxins. However, reactive oxygen species (ROS) caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study we aimed to examine how an organophosphate insecticide, chlorpyrifos-ethyl (CE) [0,0-diethyl 0 (3,5,6-trichloro-2-pyridyl) phosphorothioate], affects lipid peroxidation and the antioxidant defense system in vitro. For this purpose, four experiments were carried out. In

F. Gultekin; M. Ozturk; M. Akdogan

2000-01-01

400

Induction of HL60 apoptosis by ethyl acetate extract of Cordyceps sinensis fungal mycelium  

Microsoft Academic Search

The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially extracted by petroleum ether, ethyl acetate (EtOAc), ethanol and water. The EtOAc extract showed the most potent cytotoxic effect against the proliferation of human premyelocytic leukemia cell HL-60, with an ED50 ? 25 ?g\\/ml for 2-day treatment. The EtOAc extract induced the characteristic apoptotic symptoms in the HL-60 cells,

Qiaoxia Zhang; Jianyong Wu; Zongding Hu; Duan Li

2004-01-01

401

Utilization of ethyl ester of waste vegetable oils as fuel in diesel engines  

Microsoft Academic Search

Jordan relies heavily on expensive and unreliable imported oil. Therefore, this study was initiated to investigate the potential of ethyl ester used as vegetable oil (VO; biodiesel) to substitute oil-based diesel fuel. The fuels tested were several ester\\/diesel blends including 100% ester in addition to diesel fuel, which served as the baseline fuel. Variable-speed tests were run on all fuels

Mohamad I Al-Widyan; Ghassan Tashtoush; Moh'd Abu-Qudais

2002-01-01

402

Methyl and ethyl soybean esters as renewable fuels for diesel engines  

Microsoft Academic Search

The primary problems associated with using straight soybean oil as a fuel in a compression ignition internal combustion engine\\u000a are caused by high fuel viscosity. Transesterification of soybean oil with an alcohol provides a significant reduction in\\u000a viscosity, thereby enhancing the physical properties of the renewable fuel to improve engine performance. The ethyl and methyl\\u000a esters of soybean oil with

S. J. Clark; L. Wagner; M. D. Schrock; P. G. Piennaar

1984-01-01

403

Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone  

Microsoft Academic Search

A total of 137 volunteers were recruited and tested for neurobehavioural performance before, during, and after a short duration (4 h) exposure to acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a placebo. Ethanol (95%-0.84 ml\\/kg) was used as a positive control. Performance testing was computer controlled

R B Dick; J V Setzer; B J Taylor; R Shukla

1989-01-01

404

Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice  

Microsoft Academic Search

Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice.BackgroundSepsis is a common cause of acute renal failure (ARF). The incidence of sepsis increases dramatically after 50 years of age; however, most ARF studies are performed in young mice.MethodsWe performed two common sepsis models, lipopolysaccharide (LPS) administration and cecal ligation puncture (CLP) in aged mice. We

Takehiko Miyaji; Xuzhen Hu; Peter S. T. Yuen; Yasunari Muramatsu; Swarnalatha Iyer; Stephen M. Hewitt; Robert A. Star

2003-01-01

405

40 CFR 721.1950 - 2-Butenedioic acid (Z), mono(2-((1-oxopropenyloxy)ethyl) ester .  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false 2-Butenedioic acid (Z), mono(2-((1-oxopropenyloxy)ethyl...Substances § 721.1950 2-Butenedioic acid (Z ), mono(2-((1-oxopropenyloxy...substance identified as 2-butenedioic acid (Z ),...

2010-07-01

406

DFT NORMAL MODES FOR ETHYL-TRANSFER TRANSITION STATE IN THE TMS+ ADDUCT OF Et2CMeCH=O  

E-print Network

DFT NORMAL MODES FOR ETHYL-TRANSFER TRANSITION STATE IN THE TMS+ ADDUCT OF Et2CMeCH=O Copyright proprietary and confidential information, including trade secrets, belonging to Gaussian, Inc. This software

Morton, Thomas Hellman

407

Sensory nerve-mediated nasal vasodilatory response to inspired ethyl acrylate.  

PubMed

The irritants acrolein, acetaldehyde, and acetic acid induce a rapid sensory nerve-mediated nasal vasodilatory response in the rat. The aim of the current study was to examine acute nasal sensory nerve-mediated acute responses to an irritant ester vapor, ethyl acrylate. For this purpose, the upper respiratory tract of the urethane-anesthetized male F344 rat was isolated by insertion of an endotracheal cannula, and ethyl acrylate-laden air was drawn continuously through that site at a flow rate of 100 ml/min for 50 min. Vascular function was monitored by measuring inert vapor (acetone) uptake throughout the exposure. Nasal flow resistance was also monitored during exposure, and plasma protein extravasation was measured by Evans blue dye leakage. At exposure concentrations of 100 to 400 ppm, ethyl acrylate induced a rapid nasal vasodilatory response, as indicated by increased acetone uptake rates. This response was maintained throughout the exposure. Changes in nasal flow resistance or in Evans blue dye leakage were not observed at these exposure concentrations. The vasodilatory response was diminished in animals pretreated with the sensory nerve toxin capsaicin, providing strong evidence that this response was sensory nerve mediated. Pretreatment with the carboxylesterase inhibitor bis-para-nitro-phenolphospahte at a dose sufficient to inhibit nasal carboxylesterase did not alter the response, suggesting that the parent ester, not the carboxylesterase metabolites, is primarily responsible for the sensory-nerve-mediated vasodilatory responses to this ester. PMID:12119070

Morris, John B

2002-06-01

408

In vitro evaluation of transdermal patches of flurbiprofen with ethyl cellulose.  

PubMed

This study was aimed to determine effects of penetration enhancers and plasticizers on drug release from rationally designed formulations of flurbiprofen based transdermal drug delivery system. Matrix type transdermal patches were formulated with ethyl cellulose (EC) as a polymer by using plate casting method. The plasticizers such as propylene glycol (PG) and dibutyl phthalate (DBP), and enhancers such as Span 20, Tween 20, sodium lauryl sulfate (SLS), isopropyl myristate (IPM) and ethanol (EtOH) were formulated in different concentrations in the patches. Such different combinations of polymer with various enhancers and plasticizers in patches were evaluated for their effect on the physicochemical properties and drug release behavior of flurbiprofen. The drug release study was carried out by the paddle-over-disk method and permeation of drug was performed by Franz diffusion cell using rabbit skin. Patches having ethanol with ethyl cellulose showed more uniformity in the physical properties while the smoothness and clarity of patches containing sodium lauryl sulfate were not satisfactory. The drug release from patches followed Higuchi and Korsmeyer-Pappas model while maximum drug release was obtained by isopropyl myristate (903 microg). It was concluded that the patches having ethyl cellulose with isopropyl myristate and propylene glycol are more useful for transdermal patches of flurbiprofen. PMID:25272649

Idrees, Arfat; Rahman, Nisar Ur; Javaid, Zeeshan; Kashif, Muhammad; Aslam, Irfan; Abbas, Khizar; Hussain, Talib

2014-01-01

409

Rotational isomers of N-(?-phenylpropionyl)alanine ethyl dithioester: a Raman spectroscopic and MO study  

NASA Astrophysics Data System (ADS)

Raman spectra of N-(?-phenylpropionyl)alanine ethyl dithioester (C 6H 5CH 2CH 2C(?O)NHCH(CH 3)C(?S)SC 2H 5) in CCl 4 and CH 3CN solutions were measured as a function of temperature and the enthalpy differences (? H) between rotational isomers differing by internal rotation around the NH?CH(CH 3) and CH(CH 3)?C(?S) bonds (forms A, B and C 5) were evaluated from relative band intensities. The spectroscopic results are consistent with a greater thermodynamical stability of the B-type conformer, where the N and S (thiol) atoms are in close contact. In addition, a comparison of the measured ? H(A-B) for the present molecules with previously reported values for a series of similar glycine-based ethyl dithioesters shows that the presence of the extra CH 3 group at the ?-carbon atom leads to a stabilization of the B-type conformer relative to the A-type form in the alanine-based dithioester. Semiempirical AM1 molecular orbital calculations were also performed on the title molecule and on its glycine analogue, N(?-phenylpropionyl)glycine ethyl dithioester. In general terms, the results of these calculations agree with the experimental findings, thus providing good theoretical support for the experimental data.

Fausto, R.; Teixeira-Dias, J. J. C.; Tonge, P. J.; Carey, P. R.

1994-07-01

410

Biopharmaceutical evaluation of a tablet dosage form made from ethyl cellulose encapsulated aspirin particles.  

PubMed

Ethyl cellulose encapsulated aspirin particles, suitable for preparation of direct compression tablets were prepared by the solvent evaporation method. Ethyl acetate was used as a solvent for the polymer in combination with a saturated solution of aspirin as the dispersing medium to prevent partitioning and drug loss. This resulted in a high yield of free-flowing, non-aggregated particles. In vitro-in vivo evaluations of the experimental aspirin tablets (made by direct compression of ethyl cellulose encapsulated particles) and three different commercial aspirin products (a conventional tablet, a timed-release tablet, and a timed-release caplet) were undertaken. Comparison of the dissolution in acidic media at pH 1.2 showed different release profiles for these products. While the conventional tablet and the timed-release caplet showed the highest and the lowest rate of release, respectively; the timed-release tablet and the experimentally made tablet revealed an intermediate rate and very similar release profiles. The cumulative urinary excretion data collected in a complete crossover study, using five healthy subjects further indicated that the experimental tablet has an in vivo availability identical to that of the timed-release tablet. PMID:1880688

Zia, H; Falamarzian, M; Raisi, A; Montaseri, H; Needham, T E

1991-01-01

411

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

PubMed

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 180-370K. 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 298K, 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

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

2015-01-01

412

Yeast tolerance to the ionic liquid 1-ethyl-3-methylimidazolium acetate.  

PubMed

Lignocellulosic plant biomass is the target feedstock for production of second-generation biofuels. Ionic liquid (IL) pretreatment can enhance deconstruction of lignocellulosic biomass into sugars that can be fermented to ethanol. Although biomass is typically washed following IL pretreatment, small quantities of residual IL can inhibit fermentative microorganisms downstream, such as the widely used ethanologenic yeast, Saccharomyces cerevisiae. The aim of this study was to identify yeasts tolerant to the IL 1-ethyl-3-methylimidazolium acetate, one of the top performing ILs known for biomass pretreatment. One hundred and sixty eight strains spanning the Ascomycota and Basidiomycota phyla were selected for screening, with emphasis on yeasts within or closely related to the Saccharomyces genus and those tolerant to saline environments. Based on growth in media containing 1-ethyl-3-methylimidazolium acetate, tolerance to IL levels ranging 1-5% was observed for 80 strains. The effect of 1-ethyl-3-methylimidazolium acetate concentration on maximum cell density and growth rate was quantified to rank tolerance. The most tolerant yeasts included strains from the genera Clavispora, Debaryomyces, Galactomyces, Hyphopichia, Kazachstania, Meyerozyma, Naumovozyma, Wickerhamomyces, Yarrowia, and Zygoascus. These yeasts included species known to degrade plant cell wall polysaccharides and those capable of ethanol fermentation. These yeasts warrant further investigation for use in saccharification and fermentation of IL-pretreated lignocellulosic biomass to ethanol or other products. PMID:25348480

Sitepu, Irnayuli R; Shi, Shuang; Simmons, Blake A; Singer, Steven W; Boundy-Mills, Kyria; Simmons, Christopher W

2014-12-01

413

Fast excited-state deactivation in N(5)-ethyl-4a-hydroxyflavin pseudobase.  

PubMed

We present a study of the excited-state behavior of N(5)-ethyl-4a-hydroxyflavin (Et-FlOH), a model compound for bacterial bioluminescence. Using femtosecond pump-probe spectroscopy, we found that the Et-FlOH excited state exhibits multiexponential dynamics, with the dominant decay component having a 0.5 ps lifetime. Several possible mechanisms for fast excited-state decay in Et-FlOH were considered: (i) excited-state deprotonation of the -OH proton, (ii) thermal deactivation via (1)n,?* ? (1)?,?* conical intersection, and (iii) excited-state release of OH(-) ion. These mechanisms were excluded based on transient absorption studies of two model compounds (N(5)-ethyl-4a-methoxyflavin, Et-FlOMe, and N(5)-ethyl-flavinium ion, Et-Fl(+)) and based on the results of time-dependent density functional theory (TD-DFT) calculations of Et-FlOH excited-states. Instead, we propose that the fast decay in Et-FlOH is caused by S(1) ? S(0) internal conversion, initiated by the excited-state nitrogen planarization (sp(3) ? sp(2) hybridization change at the N(5)-atom of Et-FlOH S(1) state) coupled with out-of-plane distortion of the pyrimidine moiety of flavin. PMID:21553832

Zhou, Dapeng; Mirzakulova, Ekaterina; Khatmullin, Renat; Schapiro, Igor; Olivucci, Massimo; Glusac, Ksenija D

2011-06-01

414

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

PubMed Central

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

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

2014-01-01

415

Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals  

PubMed Central

Objective To investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetula braunii, a plant used in ethnomedicine for the treatment of epilepsy. Methods The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks, pentylenetetrazole and 4-aminopyridine-induced seizures in mice. Results The preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins, carbohydrates, flavonoids, tannins, anthraquinones and steroids. Similarly, tannins, flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction. In the pharmacological screening, 150 mg/kg of the fraction protected 83.33% of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100% protection. In the 4-aminopyridine-induced seizure model, the fraction produced a significant (P<0.05) increase in the mean onset of seizure in unprotected animals. The fraction did not exhibit a significant activity against maximal electroshock convulsion. The median lethal dose of the fraction was found to be 1?261.91 mg/kg. Conclusions These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy. PMID:25182552

Aliyu, Musa Mumammad; Musa, Abdullahi Isma'il; Kamal, Muhammad Ja'afar; Mohammed, Magaji Garba

2014-01-01

416

Synthesis of Mn-doped ZnO diluted magnetic semiconductors in the presence of ethyl acetoacetate under solvothermal conditions  

Microsoft Academic Search

Mn-doped ZnO samples with 5%, 20% and 40% nominal Mn concentrations were prepared in the presence of ethyl acetoacetate under solvothermal conditions. UV absorption spectroscopic analysis discloses that chemical modification was achieved by reaction of Zn or Mn precursor with ethyl acetoacetate in ethanol medium. XRD and HRTEM characterizations indicate that ZnMnO3 impurity phase was formed in the 20% and

Chengbin Jing; Yingjing Jiang; Wei Bai; Junhao Chu; Aiyun Liu

2010-01-01

417

Effect of ethyl acetate on carbohydrate components and crystalline structure of pulp produced in aqueous acetic acid pulping  

Microsoft Academic Search

The aim of this study was to investigate the changes in carbohydrate components and the crystalline structure in hemp bast\\u000a fibers by adding ethyl acetate to acetic acid\\/water pulping processes. It was found that ethyl acetate added to acetic acid\\/water\\u000a process had a positive effect on yield, viscosity and carbohydrate components in pulp. It was assumed that the delignification\\u000a ratio

Esat Gümü?kaya; Mustafa Usta; Mualla Balaban Uçar

2009-01-01

418

Oxidized Ethyl Linoleate Induces Mucosal Hypertrophy of the Large Intestine and Affects Cecal Fermentation of Dietary Fiber in Rats1  

Microsoft Academic Search

Oxidized ethyl linoleate (OEL) was pre pared by aeration at low temperature. Peroxide value (POV, mEq\\/kg lipid) of OEL was 1400; the major oxi dized compounds were 9-hydroperoxy-cf's,irans-and 13- hydroperoxy-irans.cis-octadecadienoate. Rats fed fiber- free or sugar-beet fiber (SBF, 100 g\\/kg diet) diets were divided into three groups for each diet, and administered OEL (high OELgroup), OELdiluted with ethyl linoleate (low

HIROSHI HARÃ; SATOSHI ITO; TAKAHORI KASAI

419

The effects of ethyl cellulose on PV performance of DSSC made of nanostructured ZnO pastes  

Microsoft Academic Search

Nanostructured ZnO aggregates are synthesized via a hydrolysis route using zinc acetate dehydrate and diethylene glycol as the starting materials under carefully controlled conditions. They are employed in making a series of pastes with various ratios of the ZnO to ethyl cellulose for dye-sensitized solar cells, where the ZnO films are formed by doctor blade technique. Use of ethyl cellulose

Hui Li; Zhibin Xie; Yu Zhang; John Wang

2010-01-01

420

Effects of repeated applications of chlorimuron-ethyl on the soil microbial biomass, activity and microbial community in the greenhouse.  

PubMed

The impacts of repeated chlorimuron-ethyl applications on soil microbial community structure and function were studied under greenhouse conditions. Chlorimuron-ethyl was applied to soil samples at three different doses [1-,10-,100-fold of recommended field rate (T1, T10, T100)] for 3 years. The half-lives of chlorimuron-ethyl were 37.1-54.6 days. The soil microbial biomass (microbial biomass carbon and total phospholipid fatty acid), the microbial activity (basal respiration and average well color development), the ratio of Gram-negative/Gram-positive bacteria and Shannon index were stimulated by chlorimuron-ethyl during the initial period. Except for T100, the other treatments recovered to the untreated level. The ratio of fungi/bacteria decreased during the initial period and then recovered in the end. Principal component analysis of phospholipid fatty acid showed that chlorimuron-ethyl altered the microbial community structure. Except got T100, T1 and T10 were not different from the control at the end of experiment. These results suggested a dosage effect of chlorimuron-ethyl on the living microbial biomass and the microbial community. PMID:24264144

Xu, Jun; Zhang, Ying; Dong, Fengshou; Liu, Xingang; Wu, Xiaohu; Zheng, Yongquan

2014-02-01

421

The concentration of ethyl carbamate in commercial ume (Prunus mume) liqueur products and a method of reducing it.  

PubMed

The ethyl carbamate concentration of commercial ume liqueur products was studied, and a method of reducing it was examined from the viewpoint of antioxidation. The average ethyl carbamate concentration across 38 ume liqueur products was 0.12 mg/l (0.02-0.33 mg/l). When potassium metabisulfite was added to a concentration of 0-1,000 ppm during production, the generation of ethyl carbamate was reduced in a concentration-dependent manner, but when the amount of potassium metabisulfite added was below the maximum level allowed under the Japanese Food Sanitation Act, the reduction was only 27%. When ume liqueurs were produced under deoxygenated conditions created using an oxygen absorber, the ethyl carbamate concentration was reduced by up to 47% as compared with the control group, probably due mainly to a reduction in free hydrogen cyanide. When ume liqueur was produced in an oxygen atmosphere, the ethyl carbamate concentration increased by up to 50% as compared with the control group. Thus, oxygen may be involved in the generation of ethyl carbamate in ume liqueur production. PMID:20944415

Hashiguchi, Tomokazu; Horii, Sachie; Izu, Hanae; Sudo, Shigetoshi

2010-01-01

422

Ethyl gallate suppresses proliferation and invasion in human breast cancer cells via Akt-NF-?B signaling.  

PubMed

Euphorbia fischeriana Steud is a traditional Chinese Medicine that is known to possess a variety of anticarcinogenic properties. However, the bioactive constituents in Euphorbia fischeriana Steud and molecular mechanisms underlying this action in cancer treatment remain poorly understood. The present study investigated the chemotherapy activity and molecular targets of Ethyl gallate, which is identified as the major constituent extracted from the roots of Euphorbia fischeriana Steud in breast cancer cell lines in vitro. The results showed Ethyl gallate obviously decreased cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner. Highly invasive MDA-MB-231 cells were found to be highly sensitive to treatment. Furthermore, significantly decreased metastatic potential of highly metastatic MDA-MB?231 cells by Ethyl gallate was identified via the inhibition of cell motility using invasion and migration through a polyethylene terephthalate membrane. Ethyl gallate treatment decreased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 by the downregulation of mRNA levels using RT-PCR, enzymes that are critical to tumor invasion. Treatment with Ethyl gallate decreased phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor-?B (NF-?B) activation in MDA-MB-231 cells. These results indicate that Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-?B p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells. Thus, the present study shed new light on Ethyl gallate, an important bioactive constituent of Euphorbia fischeriana Steud, in human breast cancer treatment. The findings may provide basal theories for wide therapeutic application in human breast cancer. PMID:25522911

Cui, Hongxia; Yuan, Jiaxin; Du, Xiaohui; Wang, Ming; Yue, Liling; Liu, Jicheng

2015-03-01

423

Omacor (prescription omega-3-acid ethyl esters 90): From severe rhythm disorders to hypertriglyceridemia.  

PubMed

Despite progress made in post-myocardial infarction (MI) revascularization and background therapy for the failing heart, the prevention of adverse cardiac remodeling associated with severe rhythm disorders remains an important drug target. Part of the remodeling can be counteracted by modulating the activity of ion channels and exchangers by omega-3 acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the GISSI-Prevenzione and GISSI-HF trials, omega-3 fatty acids were administered as ethyl esters (Omacor Solvay Pharmaceuticals) and not as triglycerides present in fish oil. Ethyl esters result in a sustained intestinal absorption of EPA and DHA and require various purification steps during production, thereby minimizing the content of environmental toxins. Also the rather high (38%) DHA content of Omacor should not be ignored since in rats with low dose intake of omega-3 acids, DHA but not EPA inhibited ischemia-induced arrhythmias. In patients on multiple tablets, 840 mg EPA+DHA in one capsule is preferred to increase compliance. It is not justified to refer to Omacor as "n-3 polyunsaturated fatty acid supplementation" or even "fish oil" and, based on controlled clinical trials, there is no evidence that fish oil could be a substitute of Omacor. To avoid further confusion, guidelines should be precise and refer to the medication, eg, as in NICE guideline CG48: "Omega-3-acid ethyl esters treatment licensed for secondary prevention post-MI." The anti-arrhythmogenic action of Omacor should be seen in the context of implantable cardioverter-defibrillator trials (DINAMIT, IRIS) where non-sudden death was increased and total mortality unaltered. However, Omacor administered in the GISSI-HF trial reduced the incidence of severe arrhythmic events and mortality. Also in the GISSI-Prevenzione trial, arrhythmic death and mortality were reduced. At higher dosages (daily, 3-4 g) Omacor exhibits more pronounced cardiovascular benefits and, as a licensed indication, improves hypertriglyceridemia and related lipid parameters. PMID:19629408

Rupp, Heinz

2009-07-01

424

Treating high loads of ethyl acetate and toluene in a biofilter  

SciTech Connect

In the past, biofilters have primarily controlled dilute, usually odorous, off-gases with VOC concentrations < 1 g/m{sup 3} and VOC loads < 50 g/m{sup 3}h. Yet, US industry has also shown an interest in the removal of higher concentrations of VOC and hazardous air pollutants (HAP). In two such instances, the treatment of high loads of ethanol from a foundry and a bakery, respectively, caused degradation limitation, the formation of odorous acetic acid, and problems maintaining the proper moisture content because of the exothermic nature of the biodegradation process. For a more detailed study of the behavior of biofilters at high loads of binary VOC mixtures, two bench-scale biofilters were operated using a commercially available media and a mixture of wood chips and compost. Both were exposed to various high loads of mixtures of ethyl acetate and toluene. Concentration profiles and the corresponding elimination vs. load curves were established through frequent grab-sampling and GC analysis. Biofilter response to two frequently encountered operating problems, i.e. media dry-out and temperatures exceeding 40 C, was also evaluated under controlled conditions. Resident microbial populations were characterized to assure the presence of organisms capable of degrading both major off-gas constituents. The results demonstrated several characteristics of high-load biofilters: maximum elimination capacities for ethyl acetate were typically limited to 200 g/m3h; despite the presence of toluene degraders, the removal of toluene was inhibited by high loads of ethyl acetate; several by-products, particularly ethanol, were formed; and short-term dry-out and temperature excursions resulted in reduced performance. The paper discusses these observations in more detail. Its findings provide a quantitative assessment of some of the limitations of biofilters used for the treatment of high VOC loads.

Deshusses, M.; Johnson, C.T. [Univ. of California, Riverside, CA (United States). Coll. of Engineering; Hohenstein, G.A. [3M Environmental Technology and Services, St. Paul, MN (United States); Leson, G. [Gero Leson Environmental Consulting, Berkeley, CA (United States)

1997-12-31

425

Effect of hydration on the structure of non aqueous ethyl cellulose/propylene glycol dicaprylate gels.  

PubMed

Changes in the structural properties of ethyl cellulose/propylene glycol dicaprylate systems (EC/PGD), intended for topical drug delivery, upon addition of water were investigated. Although designed to be a non-aqueous vehicle for moisture sensitive drugs, these systems are expected to experience an aqueous environment during production, storage and application on the skin. Hence, the interaction of water molecules with the non aqueous gel system and their distribution within the gel network is of interest and critical to its application. Experimental techniques of this study were small-deformation dynamic oscillation in shear, modulated differential scanning calorimetry (MDSC), (2)H NMR spectroscopy, ATR-infrared spectroscopy, wide-angle X-ray diffraction patterns and light microscopy. Rheological profiles of the gels containing moisture from 0.1 to 40.0% (w/w) deviated considerably from that of the non aqueous system at levels of water above 10.0% in preparations. Gradual replacement of the EC/PGD dipole interactions with stronger hydrogen bonding between ethyl cellulose chains, as the level of hydration increased, contributed to these observations. Formation of clusters of ethyl cellulose, observed under a light microscope, was thus ensued. X-ray diffraction patterns showed that the rearrangement of the polymer chains led to the loss of liquid crystal structures found in the anhydrous gel. MDSC and (2)H NMR were used to further shed light on the thermodynamic state of added water molecules in the gels. Plots of enthalpy obtained calorimetrically and a good correlation between MDSC and (2)H NMR data indicate that gels with less than two percent hydration contain water in a non-freezable bound state, whereas freezable moieties are obtained at levels of hydration above five percent in composite (EC/PGD/water) gels. PMID:22227266

Bruno, Lilia; Kasapis, Stefan; Heng, Paul W S

2012-03-01

426

Origins of threefold rotational barriers of molecule containing two methyl groups: Ethyl propionate as paradigm  

NASA Astrophysics Data System (ADS)

Origins of the rotational barriers of TG- form of ethyl propionate molecule have been investigated. The barrier heights, as determined from the Raman spectrum, are estimated to be 2.88 and 3.17 kcal/mol for the -CH3 (I) and -CH3 (II) methyl groups of the molecule respectively. The detail analyses suggest that the combined relaxations of the C2-C3, C2-C4 bond lengths and H10-C3-H11, C2-C4-H13 angles together play a significant role to control the barrier heights of methyl CH3 (I), CH3 (II) groups of the molecule.

Dutta, Bipan; Chowdhury, Joydeep

2014-09-01

427

7-Chloro-4-(2-hy­droxy­ethyl­amino)­quinolin-1-ium chloride  

PubMed Central

In the title salt, C11H12ClN2O+·Cl?, the ten non-H atoms comprising the quinolinium residue are coplanar (r.m.s. deviation = 0.041?Å) and the hy­droxy­ethyl group is approximately perpendicular to this plane [Cring—N—Cmethyl­ene—C torsion angle = ?74.61?(18)°]. A supra­molecular chain aligned along [101] mediated by charge-assisted O/N—H?Cl? hydrogen bonds features in the crystal packing. Chains are connected into a three-dimensional architecture by C—H?O(hy­droxy) inter­actions. PMID:24826110

Gama, Ivson L.; de Souza, Marcus V. N.; Wardell, James L.; Tiekink, Edward R. T.

2014-01-01

428

Carboxymethyl cellulose-g-poly(2-(dimethylamino) ethyl methacrylate) hydrogel as adsorbent for dye removal.  

PubMed

A novel adsorbent was prepared via crosslinking graft copolymerization of 2-(dimethylamino) ethyl methacrylate (DMAEMA) onto carboxymethyl cellulose (CMC) backbone. Ethylene glycol dimethacrylate and potassium persulphate were used as crosslinker and initiator, respectively. CMC-g-PDMAEMA hydrogel was used to remove methyl orange (MO) from aqueous solutions. The adsorption kinetics and isotherms were found to follow Pseudo-second-order kinetic model and Langmuir model, respectively. The high maximum adsorption capacity (1825mg/g) implied that CMC-g-PDMAEMA can be used as promising adsorbent for the synthetic dyes removal from wastewater. PMID:25450049

Salama, Ahmed; Shukry, Nadia; El-Sakhawy, Mohamed

2015-02-01

429

Communication: Substrate induced dehydrogenation: Transformation of octa-ethyl-porphyrin into tetra-benzo-porphyrin  

NASA Astrophysics Data System (ADS)

Individual molecules of octa-ethyl-porhphyrin-iron(III)-chloride adsorbed on a Cu(111) surface are studied by scanning tunneling microscopy. Upon moderate heating the molecules are found to transform into Fe-tetra-benzo-porphyrin at a surprisingly low temperature of 380 K. If the annealing is interrupted, the different steps of the transformation can be imaged. By evaluating the ratio of transformed molecules as function of annealing temperature, an approximate activation energy of 1.2 eV ± 0.1 eV could be determined.

van Vörden, D.; Lange, M.; Schmuck, M.; Schaffert, J.; Cottin, M. C.; Bobisch, C. A.; Möller, R.

2013-06-01

430

4-Hy­droxy-3-meth­oxy­benzaldehyde 4-ethyl­thio­semicarbazone  

PubMed Central

In the crystal structure of the title compound, C11H15N3O2S, the C—N—N—C and C—N—C—C torsion angles involving the benzene ring and ethyl group are 11.91?(15) and 99.4?(2)°, respectively. An intra­molecular N—H?N hydrogen bond is observed. In the crystal, mol­ecules are linked via N—H?O and N—H?S hydrogen bonds into a three-dimensional hydrogen bonded network. Finally, the molecules show a herringbone arrangement when viewed along the a axis. PMID:25249915

de Oliveira, Adriano Bof; Beck, Johannes; Daniels, Jörg; Feitosa, Bárbara Regina Santos

2014-01-01

431

Crystal structure of ethyl 4-[(1H-pyrazol-1-yl)meth-yl]benzoate.  

PubMed

In the title mol-ecule, C13H14N2O2, the dihedral angle between the pyrazole and benzene ring mean planes is 76.06?(11)°, and the conformation of the ethyl side chain is anti [C-O-C-C = -175.4?(3)°]. In the crystal, the only directional inter-actions are very weak C-H ?? inter-actions involving both the pyrazole and benzene rings, leading to the formation of a three-dimensional network. PMID:25553050

Wang, Ju-Xian; Feng, Chao

2014-12-01

432

Patterning and hardening of gold black infrared absorber by shadow mask deposition with ethyl cyanoacrylate  

NASA Astrophysics Data System (ADS)

Patterning of gold-black infrared absorbing films by stencil lithography and hardening by polymer infusion is reported. Gold black nano-structured films are deposited through a thin metal shadow mask in a thermal evaporator in ~400 mTorr pressure of inert gas, followed by ethyl cyanoacrylate fuming through the same mask to produce rugged IR absorptive patterns of ~100 micron scale dimensions. Infrared absorptivity is determined by transmission and reflectivity measurements using a Fourier spectrometer and infrared microscope. Results indicate that the optimized hardening process reduces the usual degradation of the absorptivity with age. This work has potential application to infrared array bolometers.

Panjwani, Deep; Nader-Esfahani, Nima; Maukonen, Doug; Rezadad, Imen; Boroumand, Javaneh; Smith, Evan; Nath, Janardan; Peale, R. E.

2013-06-01

433

Crystal structure of ethyl 4-[(1H-pyrazol-1-yl)meth­yl]benzoate  

PubMed Central

In the title mol­ecule, C13H14N2O2, the dihedral angle between the pyrazole and benzene ring mean planes is 76.06?(11)°, and the conformation of the ethyl side chain is anti [C—O—C—C = ?175.4?(3)°]. In the crystal, the only directional inter­actions are very weak C—H ?? inter­actions involving both the pyrazole and benzene rings, leading to the formation of a three-dimensional network. PMID:25553050

Wang, Ju-Xian; Feng, Chao

2014-01-01

434

Metabolic disposition of ethyl eicosapentaenoate and its metabolites in rats and dogs.  

PubMed

When orally administered to rats, 14C-labelled ethyl eicosapentaenoate (14C-EPA-E) was hydrolyzed and, in the lymph, incorporated mainly into triglycerides (TG) in chylomicrons. In plasma and other tissues, eicosapentaenoic acid (EPA) and its metabolites, such as docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), were detected in TG and phospholipid fractions. In plasma, EPA and its metabolites were found to be integrated into lipoproteins. Tissue distribution of these metabolites showed characteristic patterns from one tissue to another, as did their compositional distribution in lipids. EPA, DPA and DHA were found to be metabolized via beta-oxidation in in vitro experiments with mitochondrial fraction. PMID:2842487

Ishiguro, J; Tada, T; Ogihara, T; Ohzawa, N; Murakami, K; Kosuzume, H

1988-04-01

435

Ethyl 4,9-dimethyl-9H-carbazole-3-carboxyl-ate.  

PubMed

In the title compound, C17H17NO2, the carbazole skeleton includes an eth-oxy-carbonyl group at the 3-position. The indole three-ring system is almost planar [maximum deviation = 0.065?(2)?Å], and the ethyl ester group is inclined to its mean plane by 15.48?(2)°. In the crystal, there are ?-? stacking inter-actions between parallel benzene rings and between parallel benzene and pyrrole rings of adjacent mol-ecules [centroid-centroid distances = 3.9473?(8) and 3.7758?(8)?Å, respectively]. Weak C-H?? inter-actions are also present. PMID:24764961

Oncüo?lu, Serkan; Dilek, Nefise; Caylak Deliba?, Nagihan; Ergün, Yavuz; Hökelek, Tuncer

2014-03-01

436

Bis[2-(2-amino­ethyl­amino)­ethanol]copper(II) dinitrate  

PubMed Central

In the title compound, [Cu(C4H12N2O)2](NO3)2, the central CuII atom has a distorted octa­hedral coordination geometry and is surrounded by four N atoms and two O atoms from the two inversion-related 2-(2-amino­ethyl­amino)­ethanol ligands. In the crystal, mol­ecules are held together by inter­molecular O—H?O and N—H?O hydrogen bonds, leading to the formation of a three-dimensional network. PMID:22058846

Azadbakht, Reza; Amiri Rudbari, Hadi; Bruno, Giuseppe

2011-01-01

437

Ethyl 4,9-dimethyl-9H-carbazole-3-carboxyl­ate  

PubMed Central

In the title compound, C17H17NO2, the carbazole skeleton includes an eth­oxy­carbonyl group at the 3-position. The indole three-ring system is almost planar [maximum deviation = 0.065?(2)?Å], and the ethyl ester group is inclined to its mean plane by 15.48?(2)°. In the crystal, there are ?–? stacking inter­actions between parallel benzene rings and between parallel benzene and pyrrole rings of adjacent mol­ecules [centroid–centroid distances = 3.9473?(8) and 3.7758?(8)?Å, respectively]. Weak C—H?? inter­actions are also present. PMID:24764961

Öncüo?lu, Serkan; Dilek, Nefise; Çaylak Deliba?, Nagihan; Ergün, Yavuz; Hökelek, Tuncer

2014-01-01

438

Ethyl-branched aldehydes, ketones, and diketones from caimans (Caiman and Paleosuchus; Crocodylia, Reptilia).  

PubMed

Secretions from the paracloacal glands of alligators (Alligator spp.) and caimans (Caiman spp., Melanosuchus niger, and Paleosuchus spp.) were examined by GC-MS. The secretions of the common caiman (C. crocodilus), the broad-snouted caiman (C. latirostris), the yacare caiman (C. yacare), the dwarf caiman (P. palpebrosus), and the smooth-fronted caiman (P. trigonatus) yielded a new family of 43 aliphatic carbonyl compounds that includes aldehydes, ketones, and beta-diketones with an ethyl branch adjacent to the carbonyl group. The identification of these glandular components and the syntheses and stereochemical investigations of selected compounds are described. PMID:16792401

Krückert, Karsten; Flachsbarth, Birte; Schulz, Stefan; Hentschel, Ute; Weldon, Paul J

2006-06-01

439

Ethyl 2-cyanoacrylate as an embolic agent for cranial arteriovenous malformations. An experimental study.  

PubMed

Physical properties of ethyl 2-cyanoacrylate (Aron Alpha) were studied in comparison with isobutyl 2-cyanoacrylate (IBCA). Aron Alpha is characterized by high viscosity, a short polymerization time, low spreadability and low fragmentability. On the other hand, IBCA had low viscosity, a relatively long polymerization time, high spreadability and high fragmentability. Based on these findings, it is suggested that IBCA is suitable for transcatheter embolization, and Aron Alpha for intraoperative embolization. Mixture of IBCA with 5% Aron Alpha suppressed the spreadability and the fragmentability of IBCA, resulting in reduction of distal migration of IBCA into the venous system. PMID:2980576

Katada, K; Sano, H; Katoh, Y; Kanno, T; Jain, V K; Mashita, S; Takeuchi, A; Koga, S

1986-01-01

440

N-{3-[Bis(2-hydroxy­ethyl)amino­meth­yl]-5-nitro­phen­yl}benzamide  

PubMed Central

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitro­benzyl methane­sulfonate with diethano­lamine and is an inter­mediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent mol­ecules, which differ only in the orientations of the hydroxy­ethyl groups. In the crystal structure, inter­molecular N—H?O and O—H?O hydrogen bonds link mol­ecules into one-dimensional chains. PMID:21202707

Mai, Anna; Khan, Gul S.; Clark, George R.; Barker, David

2008-01-01

441

N,N,N?,N?-Tetra­kis(2-hydroxy­ethyl)terephthalamide  

PubMed Central

The mol­ecule of the title compound, C16H24N2O6, which lies on a crystallographic inversion centre in the centre of the benzene ring, adopts an anti conformation in terms of the relative orientation of two amide carbonyl groups. One pair of the 2-hydroxy­ethyl groups is partially disordered with site occupancy factors of 0.811?(2) and 0.189?(2). The dihedral angle between the amide group and central benzene ring is 67.0?(2)°. Two O—H?O and one bifurcated O—H?(O,O) hydrogen bonds are present, resulting in a three-dimensional network. PMID:21581622

Wang, Zhi-Qiang; Xu, Chen; Li, Ying-Fei; Cen, Fei-Fei; Zhang, Yu-Qing

2009-01-01

442

In vitro evaluation of antiproliferative effect of ethyl gallate against human oral squamous carcinoma cell line KB.  

PubMed

Although some polyphenols are known to possess anticancer activity against different cancer cell lines through induction of apoptosis, the mode of antiproliferative effect of ethyl gallate against human oral squamous carcinoma cell line KB was not studied until now. Therefore, the antiproliferative effect of ethyl gallate was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in comparison with the reference drug paclitaxel. Generation of reactive oxygen species, mitochondrial membrane potential loss, DNA damage and apoptosis were determined using 2,7-diacetyldichlorofluorescein fluorescence, uptake of rhodamine-123 by mitochondria, comet assay and acridine orange/ethidium bromide dual-dye staining method. Both ethyl gallate and paclitaxel exhibited cytotoxicity in a dose-dependent manner. The 50% inhibitory concentration for ethyl gallate was 30 and 20 ?g/mL for paclitaxel. A volume of 50 ?g/mL of ethyl gallate was found to be significantly effective (P < 0.05) in controlling the cancer cell proliferation leading to acute apoptosis. PMID:25104086

Mohan, Shalini; Thiagarajan, Kalaivani; Chandrasekaran, Rajasekaran

2015-02-01

443

Formation of ethyl ferulate by rice koji enzyme in sake and mirin mash conditions.  

PubMed

Formation mechanism of ethyl ferulate (EF) in sake and mirin mash conditions was investigated to understand EF level control in the manufacturing process. Rice koji formed EF from ferulic acid (FA) and ethanol and decomposed EF to FA. This did not occur in sake yeast and chemical esterification was rare. Esterification of FA and hydrolysis of EF by rice koji might be due to feruloyl esterase(s). The rice koji enzyme showed normal Michaelis-Menten kinetics for FA in ethyl esterification and for EF in hydrolysis, but not for ethanol in the esterification reaction. Substrate specificity of the rice koji enzyme for hydroxycinnamic acids suggested that the main enzyme involved might be similar to type A feruloyl esterase. We studied the rice koji enzyme properties, short-term digestion of steamed rice grains with exogenous ethanol and small scale mirin making with pH adjustment. Our results suggested differences in the esterification and hydrolysis properties of the enzyme, in particular, different pH dependencies and different behaviors under high ethanol conditions; these factors might cause the differing EF levels in sake and mirin mashes. PMID:23597918

Hashizume, Katsumi; Ito, Toshihiko; Ishizuka, Takahiro; Takeda, Naoki

2013-08-01

444

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

USGS Publications Warehouse

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.

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

1985-01-01

445