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1

[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

2

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

3

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

4

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

5

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

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

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

8

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

9

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

10

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

11

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

12

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

13

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

14

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

15

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

16

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

17

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

18

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

19

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

20

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

21

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

22

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

23

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

24

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

25

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

26

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

27

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

28

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

29

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

30

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

31

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

32

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

33

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

34

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

35

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

36

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

37

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

38

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

39

Determination of ethyl carbamate in wine by high performance liquid chromatography.  

PubMed

Kinetics of pre-column derivatization with 9-xanthydrol for the determination of ethyl carbamate (EC) in wine by a previous high performance liquid chromatographic method with fluorescence detection was studied and further developed. The life-time of the derivatized product and its excitation/absorption spectra were systematically investigated. Using low acidity (pH=2.5 set by phosphate buffers) only 3% of 9-xanthyl ethyl carbamate (XEC) decomposes in ?48h, allowing a prolonged storage time of the derivatized EC conferring more accurate determination for large sample batches. Detection limit of this method is 3?gL(-1), while its average recovery is 98.5±4.9%. Calibration is linear up to 400?gL(-1). The EC content in 33 Hungarian wine samples ranges from 4.9 to 39.9?gL(-1) (average: 17.7?gL(-1), median: 16.7?gL(-1)), while only three of them was slightly over 30?gL(-1) EC, it being the maximum allowed concentration in countries already having legislation. PMID:23790917

Ajtony, Zsolt; Szoboszlai, Norbert; Bencs, László; Viszket, Erna; Mihucz, Victor G

2013-11-15

40

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

41

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

42

Determination of butyl- and phenyltin compounds in sediments by GC-FPD after NaBEt 4 ethylation  

Microsoft Academic Search

A reliable and rapid speciation method for the simultaneous determination of butyl- and phenyltin species in sediment samples has been developed. Two extraction procedures are compared: methanolic hydrochloric acid (at four different concentrations) and ethanoic acid leaching. Derivatization is carried out by the one-step ethylation\\/extraction procedure using the sodium tetraethylborate reagent directly in aqueous phase in the presence of an

C. Carlier-Pinasseau; G. Lespes; M. Astruc

1997-01-01

43

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

44

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

45

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

46

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

47

Determinations of morin, quercetin and their conjugate metabolites in serum.  

PubMed

Morin and quercetin are isomeric antioxidant flavonols. High-performance liquid chromatographic methods were developed for the quantitation of morin and quercetin in serum. The method employed a Cosmosil RP-18 column, using acetonitrile/0.2% o-phosphoric acid 28/72 and 27/73 (v/v) as mobile phases, with ethyl paraben and 6,7-dimethoxycoumarin used as internal standards for morin and quercetin, respectively. Moreover, a strategy to stabilize morin/quercetin released from their glucuronides/sulfates in serum during hydrolysis was established. The present methods are applicable for determining morin, quercetin, and their glucuronides/sulfates in serum. PMID:11510497

Hsiu, S L; Tsao, C W; Tsai, Y C; Ho, H J; Chao, P D

2001-08-01

48

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

49

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

50

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

51

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

52

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

53

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

54

Determination of enthalpy of formation of methyl and ethyl esters of fatty acids.  

PubMed

Biofuels composed by fatty acid methyl esters are widely used as partly substituting fuels for diesel fossil fuels. Additionally, it is expected that the diesel biofuel norms will be extended to ethyl esters produced from bioethanol in the upcoming years. A precise knowledge of the standard enthalpy of formation is necessary for the calculation of some parameters useful for the analysis of the combustion process and emissions of a diesel engine operating with different fuels, such as the heating value, the adiabatic flame temperature or the kinetic mechanisms. However, experimental data for this property are scarce, and only available for short-chain, saturated methyl esters. In this work, four estimation methods for the calculation of the enthalpy of formation are examined and compared. Three of them are simple methods based on groups or bonds contribution, and another one is a computational method (with Gaussian 03 software). After presenting the implementation rules for each of them, conclusions are stated based on the results attained. Gaussian and Benson-Groups methods seem to be more accurate in predicting the actual values of the enthalpy of formation, both methods considering the separation between double bonds and the edge effects in the molecule. However, only the Gaussian method considers the effect of the position of the double bond in the molecule for all the unsaturated esters. PMID:19917272

Lapuerta, Magín; Rodríguez-Fernández, José; Oliva, Fermín

2010-02-01

55

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.

56

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

57

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

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

58

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

59

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

60

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

61

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

62

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

PubMed

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

Liu, Xiaolu; Yang, Tao; Hu, Jiye

2013-01-01

63

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

64

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

65

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

66

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

67

Migrants determination and bioaccessibility study of ethyl lauroyl arginate (LAE) from a LAE based antimicrobial food packaging material.  

PubMed

Ethyl lauroyl arginate (LAE, ethyl-N-dodecanoyl-L-arginate hydrochloride) is a strong antimicrobial agent that was included as an active compound in an antimicrobial food packaging material. The potential existence of non-intentionally added substances (NIASs) such as impurities must therefore be checked before launching any food contact material onto the market. For this reason, an untargeted analysis of the migration was performed in both food simulants and fresh chicken breast fillets wrapped with the active material. The analysis was performed by liquid chromatography coupled to mass spectrometry detection with a quadrupole-time-of-flight analyzer, LC-MS(QTOF), for the identification of nonvolatile substances. The migration values found for LAE were 0.94±0.14 and 1.62±0.70 ?g/g in ethanol 10% v/v (simulant A) and in ethanol 95% v/v (simulant D), respectively, and 0.93±0.17 ?g/g in chicken. Other migrants such as dipropylene glycol methyl ether or tributyl-o-acetylcitrate, both coming from the coating were also found, but none of them have potential adverse effects. Bioaccessibility studies showed that after a simulated gastrointestinal digestion, LAE was not available anymore for subsequent intestinal absorption and new toxic compounds were not formed. PMID:23485618

Aznar, M; Gómez-Estaca, J; Vélez, D; Devesa, V; Nerín, C

2013-06-01

68

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

69

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

70

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

71

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

72

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

PubMed

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

Hamasaki, Tetsuo

2013-10-15

73

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

74

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

75

An HPLC Method for the Quantitative Determination of 1,4-Dihydroxy-5,8 Bis [[2-[(2-Hydroxyethyl) Amino] Ethyl] Amino] 9,10 - Anthracenedione (DHAQ, Lederle Labs CL232 315, NCS 301739) in Serum  

Microsoft Academic Search

An HPLC method using reverse phase chromatography is presented for the quantitative determination of 1,4-Dihydroxy-5,8 Bis [[2-[(2-Hydroxyethyl) amino] ethyl] amino] 9,10 - anthracenedione in serum and urine at levels which are expected to be found in clinical trials of this drug.

Fred Ostroy; Richard A. Gams

1980-01-01

76

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

77

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

78

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

PubMed

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

Zhao, Xirong; Jiang, Changxing

2015-06-15

79

[Determination of the optimal ROI setting position of the input function for the ??mTc-ethyl cysteinate dimmer brain uptake ratio method].  

PubMed

Determination of the input function for the (99m)Tc-ethyl cysteinate dimmer brain uptake ratio ((99m)Tc-ECD BUR) method as a non-invasive quantitative measurement of cerebral blood flow measurement is of critical importance in order to improve the accuracy of this method. The input functions were experimentally obtained by setting the regions of interest (ROIs) in the ascending aorta, aortic arch, and descending aorta on the 49 chest RI-angio images. rCBFs by the BUR method with 3 input functions of the 6 cases were compared with those by the (123)I-iodoamphetamine (IMP) continuous arterial blood sampling method in order to determine the best location for the ROI of the input function. The input function of the ascending aorta was higher than those of the aortic arch and the descending aorta. The input functions of the aortic arch and the descending aorta decreased due to the origin of the three branches of the right brachiocephalic artery, left subclavian artery, and left common carotid artery. A good correlation was found in the regional cerebral blood flow (rCBF) values between the (123)I-IMP continuous arterial blood sampling method and the (99m)Tc-ECD BUR method with the input function of the ascending aorta. Therefore, the ascending aorta is the best location for the ROI of the input function for the (99m)Tc-ECD BUR method. PMID:22449903

Inoue, Shinya; Kabuto, Takuma; Masunaga, Shinichiro; Souma, Tsutomu; Takaki, Akihiro; Hosoya, Tetsuo; Yoshioka, Katsunori; Ito, Shigeki

2012-01-01

80

Novel ethyl-derivatization approach for the determination of fluoride by headspace gas chromatography/mass spectrometry.  

PubMed

We report a novel derivatization chemistry for determination of fluoride based on the batch reaction of fluoride ions with triethyloxonium tetrachloroferrate(III) in a closed vessel to yield fluoroethane. Gaseous fluoroethane was readily separated from the matrix, sampled from the headspace, and determined by gas chromatography/mass spectrometry. The method was validated using rainwater certified reference material (IRMM CA408) and subsequently applied to the determination of fluoride in various matrixes, including tap water, seawater, and urine. An instrumental limit of detection of 3.2 ?g/L with a linear range up to 50 mg/L was achieved. The proposed derivatization is a one-step reaction, requires no organic solvents, and is safe, as the derivatizing agent is nonvolatile. Determination of fluoride is affected by common fluoride-complexing agents, such as Al(III) and Fe(III). The effect of large amounts of these interferences was studied, and the adverse effect of these ions was eliminated by use of the method of standard additions. PMID:23215254

Pagliano, Enea; Meija, Juris; Ding, Jianfu; Sturgeon, Ralph E; D'Ulivo, Alessandro; Mester, Zoltán

2013-01-15

81

Determination of methyltin compounds in urine of occupationally exposed and general population by in situ ethylation and headspace SPME coupled with GC-FPD.  

PubMed

A method for the determination of methyltin compounds in human urine samples was developed using headspace solid-phase microextration (HS-SPME) coupled with gas chromatographic separation and flame photometric detection. Three methyltin compounds, monomethyltin (MMT), dimethyltin (DMT), and trimethyltin (TMT) were in situ ethylated by sodium tetraethylborate (NaBEt(4)) for SPME and GC-FPD analysis. Under the optimized condition, the detection limits of MMT, DMT, and TMT were 8.1, 2.5 and 5.6 ng Sn L(-1), and the relative standard deviations were 11.0%, 7.3% and 4.0%, respectively. Methyltin compounds in thirteen urine samples from occupationally exposed population and two from general population were analyzed by the proposed method. The concentrations of total methyltin in the tested urine samples of occupationally exposed population ranged from 26.0 to 7892 ng Sn L(-1), and the average level is higher than those of the two non-occupationally exposed individuals. The methyltins in urine were adjusted by osmolality in order to enhance the comparability of different urine samples and the feasibility of this correction method was validated. PMID:21726734

Cui, Zongyan; Zhang, Kegang; Zhou, Qunfang; Liu, Jiyan; Jiang, Guibin

2011-08-15

82

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...

83

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

84

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

85

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

86

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

87

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

88

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

89

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

90

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

91

Determination of the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl) piperazine (IP/66) in rat and human plasma by high-performance liquid chromatography and isotope dilution mass spectrometry.  

PubMed

In connection with pharmacokinetic studies on the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine (IP/66) (I), appropriate high-performance liquid chromatographic (HPLC) and gas chromatographic-mass spectrometric isotope dilution (GC-MS-ID) methods for its determination in rat and human plasma, respectively, were developed. In both techniques, deproteinized and basified plasma samples were extracted and purified by adsorption on an Extrelut-1 column, then the drug was eluted with dichloromethane. Quantitative HPLC analysis was performed on a C8 reversed-phase column. The mobile phase was phosphate buffer (0.02 M, pH 2.8)-acetonitrile (65:35), with UV detection at 208 nm. The internal standard was 1-[2-butoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine, a homologue of I. The inter-assay coefficient of variation (C.V.) was 9.9% for a drug level of 2 micrograms/ml. Quantitative GC-MS-ID analysis was performed with a DB-17 fused-silica capillary column using the selected-ion monitoring technique. The deuterated form of I, 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-2'-trideuteromethoxyphenyl)pipe razine, utilized as internal standard, was synthesized. The inter-assay C.V. was 7.36% for a drug level of 1 ng/ml. PMID:2723000

Agostini, O; Moneti, G; Bonacchi, G; Fedi, M; Manzini, S

1989-02-24

92

New spectrofluorimetric methods for determination of melatonin in the presence of N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]- ethyl}acetamide: a contaminant in commercial melatonin preparations  

PubMed Central

Background Melatonin (MLT) has many health implications, therefore it is of valuable importance to develop specific analytical methods for determination of MLT in the presence of its main contaminant, N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl}acetamide (10). For development of these analytical methods, compound 10 had to be prepared in an adequate amount. Results Compound 10 was synthesized in six steps starting from 5-methoxyindole-2-carboxylic acid (1). Analytical performance of the proposed spectrofluorimetric methods was statistically validated with respect to linearity, accuracy, precision and specificity. The proposed methods were successfully applied for the assay of MLT in laboratory prepared mixtures containing up to 60 % of compound 10 and in commercial MLT tablets with recoveries not less than 99.00 %. No interference was observed from common pharmaceutical additives and the results were favorably compared with those obtained by a reference method. Conclusions This work describes simple, sensitive, and reliable second derivative spectrofluorimetric method in addition to two multivariate calibration methods, principal component regression (PCR) and partial least square (PLS), for the determination of MLT in the presence of compound 10. PMID:22551394

2012-01-01

93

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

94

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 ...

95

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

96

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

97

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

98

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

99

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

100

Determination of peptides and amino acids from wool and beer with sensitive fluorescent reagent 2-(9-carbazole)-ethyl chloroformate by reverse phase high-performance liquid chromotography and liquid chromotography mass spectrometry.  

PubMed

A new method for the sensitive determination of amino acids and peptides using the tagging reagent 2-(9-carbazole)-ethyl chloroformate (CEOC) with fluorescence (FL) detection has been developed. Identification of derivatives was carried out by liquid chromotography mass spectrometry. The chromophore in the 2-(9-fluorenyl)-ethyl chloroformate (FMOC) reagent was replaced by carbazole, which resulted in a sensitive fluorescence lerivatizing agent CEOC. CEOC can easily and quickly label peptides and amino acids. Derivatives are stable enough to be efficiently analyzed by high-performance liquid chromatography. Studies on derivatization demonstrate excellent derivative yields over the pH range 8.8-10.0. Maximal yields close to 100% are observed with three- to fourfold molar reagent excess. Derivatives exhibit strong fluorescence and allow direct injection of the reaction mixture with no significant disturbance from the major fluorescent reagent degradation by-products, such as 2-(9-carbazole)-ethanol and bis-(2-(9-carbazole)-ethyl) carbonate. In addition, the detection responses for CEOC derivatives are compared to those obtained with FMOC. The ratios AC(CEOC)/AC(FMOC) = 1.00-1.82 for fluorescence (FL) response and AC'(CEOC)/AC'(FMOC) = 1.00-1.21 for ultraviolet (UV) response are observed (here, AC and AC' are, respectively, FL and UV response). Separation of the derivatized peptides and amino acids has been optimized on a Hypersil BDS C18 column. Excellent linear responses are observed. This method was used successfully to analyze protein hydrolysates from wool and from direct-derivatized beer. PMID:12576053

You, Jinmao; Shan, Yichu; Zhen, Liang; Zhang, Lin; Zhang, Yukui

2003-02-01

101

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

102

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

103

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.

104

Determination of conformational and spectroscopic features of ethyl trans-alfa-cyano-3-indole-acrylate compound: An experimental and quantum chemical study  

NASA Astrophysics Data System (ADS)

The optimized geometrical structure, vibrational and electronic transitions, chemical shifts and non-linear optical properties of ethyl trans-alfa-cyano-3-indole-acrylate (C14H12N2O2) compound were presented in this study. The ground state geometrical structure and vibrational wavenumbers were carried out by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational spectra of title compound were recorded in solid state with FT-IR and FT-Raman in the range of 4000-400 cm-1 and 4000-10 cm-1, respectively. The fundamental assignments were done on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The 1H, 13C and DEPT NMR spectra were recorded in DMSO solution, and gauge-invariant atomic orbitals (GIAO) method was used to predict the isotropic chemical shifts. The UV-Vis absorption spectra of the compound were recorded in the range of 200-800 nm in various solvents of different polarity (acetone, benzene, chlorobenzene, chloroform, DMSO, ethanol, methanol and toluene). Solvent effects were calculated using TD-DFT and CIS method. To investigate the non-linear optical properties, the polarizability, anisotropy of polarizability and molecular first hyperpolarizability were computed. A detailed description of spectroscopic behaviors of compound was given based on the comparison of experimental measurements and theoretical computations.

Cinar, Mehmet; Karabacak, Mehmet

2013-03-01

105

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

106

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 ...

107

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

108

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

109

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

110

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

111

Rapid and simultaneous determination of twenty amino acids in complex biological and food samples by solid-phase microextraction and gas chromatography-mass spectrometry with the aid of experimental design after ethyl chloroformate derivatization.  

PubMed

Amino acids play a vital role as intermediates in many important metabolic pathways such as the biosynthesis of nucleotides, vitamins and secondary metabolites. A sensitive and rapid analytical method has been proposed for the first time for the simultaneous determination of twenty amino acids using solid-phase microextraction (SPME). The protein samples were hydrolyzed by 6M HCl under microwave radiation for 120 min. Then the amino acids were derivatized by ethyl chloroformate (ECF) and the ethoxy carbonyl ethyl esters of amino acids formed were extracted using SPME by direct immersion. Finally the extracted analytes on the SPME fiber were desorbed at 260°C and analyzed by gas chromatography-mass spectrometer (GC-MS) in electron ionization mode. Factors which affect the SPME efficiency were screened by Plackett-Burmann design; most significant factors were optimized with response surface methodology. The optimum conditions for SPME are as follows: pH of 1.7, ionic strength of 733 mg, extraction time of 30 min and fiber of divinyl benzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS). The recovery of all the amino acids was found to be in the range of 89.17-100.98%. The limit of detection (LOD) of all derivatized amino acids in urine, hair and soybean was found to be in the range of 0.20-7.52 ?g L(-1), 0.21-8.40 ?g L(-1) and 0.18-5.62 ?g L(-1), respectively. Finally, the proposed technique was successfully applied for the determination of amino acids in complex biological (hair, urine) and food samples (soybean). The method can find wide applications in the routine analysis of amino acids in any biological as well as food samples. PMID:22998980

Mudiam, Mohana Krishna Reddy; Ratnasekhar, Ch; Jain, Rajeev; Saxena, Prem Narain; Chauhan, Abhishek; Murthy, R C

2012-10-15

112

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

113

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

114

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

115

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

116

Separate determination of human urinary conjugated and unconjugated 3-methoxy-4-hydroxyphenylethyleneglycol.  

PubMed

A new determination procedure for human urinary 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was established. In addition to the previously established solid-phase extraction method for unconjugated MHPG, another solid-phase extraction method for conjugated MHPG was developed. Unconjugated MHPG was adsorbed on a Sep-Pak Diol cartridge and selectively recovered by elution with ethyl acetate. The eluate was evaporated and the residue was redissolved and analyzed by reversed-phase high-performance liquid chromatography with fluorimetric detection. Conjugated (sulfate plus glucuronide) MHPG was adsorbed on a Sep-Pak Accell QMA cartridge and quantitatively eluted with 0.2 M NaCl. After enzymatic hydrolysis, deconjugated MHPG was extracted using a Sep-Pak Diol cartridge and analyzed in the same manner as unconjugated MHPG. The new method is simple and rapid and can quantitate conjugated and unconjugated MHPG discriminatively. PMID:9613928

Inagaki, H; Hirata, K; Minami, M

1998-04-10

117

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

118

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

119

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

120

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

121

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

122

Potentialities of two solventless extraction approaches--stir bar sorptive extraction and headspace solid-phase microextraction for determination of higher alcohol acetates, isoamyl esters and ethyl esters in wines.  

PubMed

A stir bar sorptive extraction with liquid desorption followed by large volume injection coupled to gas chromatography-quadrupole mass spectrometry (SBSE-LD/LVI-GC-qMS) was evaluated for the simultaneous determination of higher alcohol acetates (HAA), isoamyl esters (IsoE) and ethyl esters (EE) of fatty acids. The method performance was assessed and compared with other solventless technique, the solid-phase microextraction (SPME) in headspace mode (HS). For both techniques, influential experimental parameters were optimised to provide sensitive and robust methods. The SBSE-LD/LVI methodology was previously optimised in terms of extraction time, influence of ethanol in the matrix, liquid desorption (LD) conditions and instrumental settings. Higher extraction efficiency was obtained using 60 min of extraction time, 10% ethanol content, n-pentane as desorption solvent, 15 min for the back-extraction period, 10 mL min(-1) for the solvent vent flow rate and 10 degrees C for the inlet temperature. For HS-SPME, the fibre coated with 50/30 microm divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) afforded highest extraction efficiency, providing the best sensitivity for the target volatiles, particularly when the samples were extracted at 25 degrees C for 60 min under continuous stirring in the presence of sodium chloride (10% (w/v)). Both methodologies showed good linearity over the concentration range tested, with correlation coefficients higher than 0.984 for HS-SPME and 0.982 for SBES-LD approach, for all analytes. A good reproducibility was attained and low detection limits were achieved using both SBSE-LD (0.03-28.96 microg L(-1)) and HS-SPME (0.02-20.29 microg L(-1)) methodologies. The quantification limits for SBSE-LD approach ranging from 0.11 to 96.56 microg L(-)and from 0.06 to 67.63 microg L(-1) for HS-SPME. Using the HS-SPME approach an average recovery of about 70% was obtained whilst by using SBSE-LD obtained average recovery were close to 80%. The analytical and procedural advantages and disadvantages of these two methods have been compared. Both analytical methods were used to determine the HAA, IsoE and EE fatty acids content in "Terras Madeirenses" table wines. A total of 16 esters were identified and quantified from the wine extracts by HS-SPME whereas by SBSE-LD technique were found 25 esters which include 2 higher alcohol acetates, 4 isoamyl esters and 19 ethyl esters of fatty acids. Generally SBSE-LD provided higher sensitivity with decreased analysis time. PMID:19836529

Perestrelo, R; Nogueira, J M F; Câmara, J S

2009-12-15

123

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

124

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

125

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

126

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

127

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

128

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

129

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...

130

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

131

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

132

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

133

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

134

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

135

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

136

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

137

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

138

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

139

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

140

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

141

?-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

142

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

143

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

144

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

145

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

146

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...

147

Crystal structures of frozen room temperature ionic liquids, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF 4), hexafluoroniobate (EMImNbF 6) and hexafluorotantalate (EMImTaF 6), determined by low-temperature X-ray diffraction  

NASA Astrophysics Data System (ADS)

The crystal structures of three salts, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF 4), hexafluoroniobate (EMImNbF 6) and hexafluorotantalate (EMImTaF 6), all of which form room-temperature ionic liquids (RTILs), have been determined by low-temperature X-ray diffraction studies of their single crystals. EMImBF 4 crystallizes in the monoclinic space group P2/c with a=8.653(5) Å, b=9.285(18) Å, c=13.217(7) Å, ?=121.358(15) Å, V=906.8(19) Å, Z=4 at 100 K. EMImBF 4 exhibits a unique structure wherein EMIm cations form one-dimensional pillars facing the imidazolium ring to the next ring linked by H(methylene)⋯ ? electron interaction. The BF 4 anion also forms one-dimensional pillars along the same direction with the nearest F⋯F contact distance of 3.368(3) Å. EMImNbF 6 and EMImTaF 6 are isostructural to each other and crystallize in the orthorhombic space group P222: EMImNbF 6, a=9.204(4) Å, b=9.770(15) Å, c=12.499(13) Å, V=1124(2) Å, Z=4 at 200 K; EMImTaF 6, a=9.216(5) Å, b=9.763(2) Å, c=12.502(17) Å, V=1124.9(17) Å, Z=4 at 200 K. In EMImNbF 6 and EMImTaF 6, EMIm cations also form a one-dimensional pillar structure and the hexafluorocomplex anions are located in a zig-zag arrangement along the same direction with the nearest F⋯F distance of 3.441(12) Å. This structure (Type-B(MF 6)) is different from the Type-A(MF 6) structure previously reported for EMImPF 6, EMImAsF 6 and EMImSbF 6. Hydrogen bonds in the Type-A(MF 6) (EMImPF 6 (333 K), EMImAsF 6 (326 K) and EMImSbF 6 (283 K)) crystal lattice are weaker than those in the Type-B(MF 6) (EMImNbF 6 (272 K) and EMImTaF 6 (275 K)) crystal lattice. This suggests that the strength of the hydrogen bond is not always a decisive and determining factor for the melting points of RTILs. The measurement of cell parameters for EMImBF 4 between 100 K and its melting point revealed that EMImBF 4 essentially preserves the same structure in this temperature range and increases its volume by only 4% due to the melting.

Matsumoto, Kazuhiko; Hagiwara, Rika; Mazej, Zoran; Benki?, Primož; Žemva, Boris

2006-10-01

148

IN VIVO RATE OF PHENOL GLUCURONIDATION BY RAINBOW TROUT  

EPA Science Inventory

Induction of vitellogenin (VTG) in male fish has become an accepted biomarker for xenoestrogenicity. This study utilized the male rainbow trout liver slice model to determine the estrogenicity of parent compound, methoxychlor (MXC) and metabolites, di-hydroxy methoxychlor (HPTE) ...

149

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

150

Determination of L-(5-(3,4-Dimethoxyphenyl)-Pyrazol-3-Yl-Oxypropyl)-3-[N-methyl-N- 2-(3,4-dimethoxyphenyl)ethyl-amino] Propane Hydrochloride and Its Two Metabolites in Dog Plasma by High Performance Liquid Chromatography with Fluorescence Detection  

Microsoft Academic Search

A simple, specific and sensitive high-performance liquid chromatographic (HPLC) method was developed for the determination of l-(5-(3,4-dimetoxyphenyl)-pyrazol-3-yl-oxypropyl)-3-[n-methyl-n-[2-(3,4-dimethoxyphenyl)ethyl]amino] propane hydrochloride (KC11346) and two of its metabolites (KC12795, KC12816) in dog plasma. KC11346, KC12795, KC12816 and KC11294 (internal standard) are extracted from dog plasma by methyl t-butyl ether (MTBE) following an alkalization of plasma. MTBE is removed from the extract with a

Yi Lau Lau; Colette A. Wagner; Glenn D. Hanson; J. Borlak

1996-01-01

151

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

152

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

153

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

154

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

155

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

156

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

157

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

158

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

159

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

160

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

161

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...

162

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

163

Determination of low level methyl tert-butyl ether, ethyl tert-butyl ether and methyl tert-amyl ether in human urine by HS-SPME gas chromatography/mass spectrometry.  

PubMed

Methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are oxygenated compounds added to gasoline to enhance octane rating and to improve combustion. They may be found as pollutants of living and working environments. In this work a robotized method for the quantification of low level MTBE, ETBE and TAME in human urine was developed and validated. The analytes were sampled in the headspace of urine by SPME in the presence of MTBE-d12 as internal standard. Different fibers were compared for their linearity and extraction efficiency: carboxen/polydimethylsiloxane, polydimethylsiloxane/divinylbenzene, and polydimethylsiloxane. The first, although highly efficient, was discarded due to deviation of linearity for competitive displacement, and the polydimethylsiloxane/divinylbenzene fiber was chosen instead. The analysis was performed by GC/MS operating in the electron impact mode. The method is very specific, with range of linearity 30-4600 ng L(-1), within- and between-run precision, as coefficient of variation, <22 and <16%, accuracy within 20% the theoretical level, and limit of detection of 6 ng L(-1) for all the analytes. The influence of the matrix on the quantification of these ethers was evaluated analysing the specimens of seven traffic policemen exposed to autovehicular emissions: using the calibration curve and the method of standard additions comparable levels of MTBE (68-528 ng L(-1)), ETBE (<6 ng L(-1)), and TAME (<6 ng L(-1)) were obtained. PMID:17386425

Scibetta, Licia; Campo, Laura; Mercadante, Rosa; Foà, Vito; Fustinoni, Silvia

2007-01-01

164

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

165

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

166

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

167

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

168

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

169

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

170

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

171

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

172

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

173

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

174

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

175

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

176

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

177

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

178

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

179

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

180

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

181

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

182

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

183

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

184

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

185

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

186

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

187

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

188

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

189

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

190

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

191

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

192

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

193

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

194

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

195

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

196

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

197

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

198

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

199

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

200

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

201

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

202

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

203

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

204

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

205

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

206

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

207

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

208

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

209

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

210

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

211

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate.  

PubMed

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and (13)C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-(13)C]-ethyl pyruvate relative to hyperpolarized [1-(13)C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-(13)C]-ethyl pyruvate and [1-(13)C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study. PMID:20432284

Hurd, Ralph E; Yen, Yi-Fen; Mayer, Dirk; Chen, Albert; Wilson, David; Kohler, Susan; Bok, Robert; Vigneron, Daniel; Kurhanewicz, John; Tropp, James; Spielman, Daniel; Pfefferbaum, Adolf

2010-05-01

212

Metabolic Imaging in the Anesthetized Rat Brain Using Hyperpolarized [1-13C] Pyruvate and [1-13C] Ethyl Pyruvate  

PubMed Central

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-13C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and 13C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-13C]-ethyl pyruvate relative to hyperpolarized [1-13C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-13C]-ethyl pyruvate and [1-13C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study. PMID:20432284

Hurd, Ralph E.; Yen, Yi-Fen; Mayer, Dirk; Chen, Albert; Wilson, David; Kohler, Susan; Bok, Robert; Vigneron, Daniel; Kurhanewicz, John; Tropp, James; Spielman, Daniel; Pfefferbaum, Adolf

2010-01-01

213

Phosphate-Solubilizing and Plant-Growth-Promoting Pseudomonas aeruginosa PS1 Improves Greengram Performance in Quizalafop- p -ethyl and Clodinafop Amended Soil  

Microsoft Academic Search

The quizalafop-p-ethyl- and clodinafop-tolerant phosphate-solubilizing and plant-growth-promoting Pseudomonas\\u000a aeruginosa PS1 isolated from the rhizospheric soils of mustard was used to determine its phosphate-solubilizing activity and other plant-growth-promoting\\u000a traits both in the presence and absence of technical grade quizalafop-p-ethyl and clodinafop under in vitro conditions. Quizalafop-p-ethyl (at 40, 80, and 120 ppb) and clodinafop (at 400, 800, and 1200 ppb) reduced the P-solubilizing

Munees Ahemad; Mohammad Saghir Khan

2010-01-01

214

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

215

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

216

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

217

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

218

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

219

Amphiphilic networks XII: synthesis and characterization of quaternized amphiphilic networks derived from polyisobutylene-l-poly(2-(dimethylamino)ethyl methacrylate)  

Microsoft Academic Search

Polyisobutylene-l-poly(2-(dimethylamino)ethyl methacrylate) amphiphilic networks were quaternized by reaction with methyl iodide. Quaternization of the tertiary amine groups in the poly(2-(dimethylamino)ethyl methacrylate) (DMEAMA) segments was close to quantitative as determined by gravimetry and nitrogen and iodine analysis. The glass transition temperature of the DMEAMA phase strongly increased upon quaternization. The swelling behavior of the quaternized networks did not much vary with

Anthony J. Allen; Joseph P. Kennedy

1999-01-01

220

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

221

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

222

N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: effects of acute feeding in the rat.  

PubMed

The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7657297

Angelico, M; Mangiameli, A; Nistri, A; Baiocchi, L; Sofia, M; Maina, M; Di Martino, M; Blasi, A

1995-09-01

223

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

224

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

225

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

226

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

227

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.

228

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

229

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

230

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

231

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

232

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

233

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

PubMed Central

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

2014-01-01

234

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

235

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

236

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

237

(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

238

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

239

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

240

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

241

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

242

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

243

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

244

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

245

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

246

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

247

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

248

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

249

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

250

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

251

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

252

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

253

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

254

[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

255

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

256

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

257

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

258

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

259

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

260

Salt-enhanced removal of 2-ethyl-1-hexanol from aqueous solutions by adsorption on activated carbon.  

PubMed

2-Ethyl-1-hexanol has extensive industrial applications in solvent extraction, however, in view of its potential pollution to environment, the removal and recovery of 2-ethyl-1-hexanol is considered an essential step toward its sustainable use in the future. In this work, we report the removal of 2-ethyl-1-hexanol from aqueous solutions containing salts in high concentrations by adsorption on a coal-based activated carbon. Adsorption thermodynamics showed that the experimental isotherms were conformed well to the Langmuir equation. Also it was found that inorganic salts, i.e. MgCl2 and CaCl2 in high concentration significantly enhanced the adsorption capacity from 223 mg/g in the deionized water to 277 mg/g in a saline water. This phenomenon of adsorption enhancement could be ascribed to the salt-out effect. Kinetic analysis indicated that adsorption kinetics follows the pseudo-second-order equation and the adsorption rate constants increase with the salt concentration. The dynamic breakthrough volume and adsorbed amount of 2-ethyl-1-hexanol were significantly elevated when the salt is present in the water. The dynamic saturated adsorption amount increased from 218.3mg/g in the deionized water to 309.5mg/g in a salt lake brine. The Tomas model was well applied to predict the breakthrough curves and determine the characteristics parameters of the adsorption column. PMID:24144367

Chang, Ganggang; Bao, Zongbi; Zhang, Zhiguo; Xing, Huabin; Su, Baogen; Yang, Yiwen; Ren, Qilong

2013-12-15

261

Rotational spectrum of ethyl cyanoacetylene (C2H5C?C-C?N), a compound of potential astrochemical interest  

NASA Astrophysics Data System (ADS)

Context. New radiotelescopes, such as the very sensitive ALMA, will enable the detection of interstellar molecules in much lower concentrations than previously possible. A successful identification of an interstellar molecule requires that laboratory microwave and millimeter-wave spectra are investigated. Several cyanopolyynes and alkynylcarbonitriles have already been detected in the interstellar medium (ISM). Cyanoacetylene (HC?C-C?N) is abundant in the ISM and its methyl derivative, 2-butynenitrile (CH3C?C-C?N), is also present. The next derivative, ethyl cyanoacetylene, (2-pentynenitrile C2H5C?C-C?N) may also be present in interstellar space. Aims: We report the rotational spectrum of the ethyl cyanoacetylene (C2H5C?C-C?N). This is hoped to facilitate identifying gaseous ethyl cyanoacetylene in the ISM. Methods: We studied the rotational spectrum of C2H5C?C-C?N between 13 and 116 GHz with the microwave spectrometer of the University of Oslo. The spectroscopic study was augmented by high-level quantum-chemical calculations at B3LYP/cc-pVTZ and CCSD/cc-pVTZ levels of theory. Results: We present for the first time the rotational spectrum of the ethyl cyanoacetylene (C2H5C?C-C?N). We assigned 342 transitions of the vibrational ground state, accurate values were obtained for rotational and centrifugal distortion constants, and the dipole moment was determined as well.

Carles, S.; Møllendal, H.; Guillemin, J.-C.

2013-10-01

262

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

263

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

264

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

265

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

266

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

267

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

268

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

269

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

270

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

271

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

272

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

273

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

274

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

275

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

276

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

277

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

278

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

279

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

280

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

281

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

282

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

283

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

284

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

285

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

286

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

287

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

288

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

289

Development of a SPE-LC/MS/MS method for simultaneous quantification of baicalein, wogonin, oroxylin A and their glucuronides baicalin, wogonoside and oroxyloside in rats and its application to brain uptake and plasma pharmacokinetic studies.  

PubMed

This study aims to identify and quantify the six major bioactive flavones of the traditional Chinese medicine Scutellariae Radix (RS), including baicalein, baicalin, wogonin, wogonoside, oroxylin A and oroxyloside in rat after oral administration of a standardized RS extract. A novel, sensitive and selective method for simultaneous determination of these six analytes in rat brain and plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC/MS/MS) was developed and fully validated. The lower limits of quantification (LLOQs) for the six RS flavones in brain tissue were 0.02nmol/g. The LLOQs in plasma were 0.005nmol/ml for B, W and OA, 0.025nmol/ml for WG and OAG, and 0.1875nmol/ml for BG. The current study provides novel evidence of the presence of all the tested RS flavones and an isoform of BG (BG', probably baicalein-6-O-glucuronide) in the rat brain after oral administration of RS extract, suggesting their ability to permeate through the blood-brain barrier. The method was also successfully applied to the pharmacokinetic study of all these analytes in plasma after oral administration of RS extract (300mg/kg) to Sprague-Dawley rats. The developed assay method provides a useful tool for both preclinical and clinical investigations on the disposition of RS flavones in brain and plasma. PMID:24803030

Fong, Sophia Yui Kau; Wong, Yin Cheong; Zuo, Zhong

2014-08-01

290

Species and Gender Differences Affect the Metabolism of Emodin via Glucuronidation  

Microsoft Academic Search

The aim of the present study was to define the mechanisms responsible for poor bioavailability of emodin by determining its\\u000a metabolism using in vitro and in situ disposition models of the intestine and liver. Liver microsomes of mice, rats, guinea pigs, dogs, and humans were used along\\u000a with the rat intestinal perfusion model and the rat intestinal microsomes. In the

Wei Liu; Lan Tang; Ling Ye; Zheng Cai; Bijun Xia; Jiajie Zhang; Ming Hu; Zhongqiu Liu

2010-01-01

291

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

292

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

293

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

294

Determining \\  

Microsoft Academic Search

A loss of passivity in the face of certain frequency dynamics (eg: high frequency dynamics) given an otherwise passive system leads to the notion of a “mixed” system. A “mixed” system is one that has a concept of small gain associated with it over those frequency intervals where passivity is lost. In this paper, a test for determining “mixedness” for

Wynita M. Griggs; Brian D. O. Anderson; Robert N. Shorten

2010-01-01

295

Determinants  

NSDL National Science Digital Library

Created by Lewis Blake and Stephanie Fitchett of the Connected Curriculum Project, the purposes of this module are to explore the properties of determinants of matrices and to develop an important theoretical formula. This is part of a larger collection of material hosted by Duke University.

Blake, Lewis; Fitchett, Stephanie

2010-05-19

296

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

297

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

298

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

299

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

300

Derivatization followed by gas chromatography-mass spectrometry for quantification of ethyl carbamate in alcoholic beverages.  

PubMed

A sensitive and rapid analytical methodology based on derivatization followed by gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC, urethane, C(2)H(5)OCONH(2)) in alcoholic samples. EC was extracted using liquid-liquid extraction technique, and then silylated with bis-(trimethylsilyl)trifluoroacetamide, analysed finally by GC-MS. The isopropyl carbamate was used as the internal standard for quantitative analysis of EC in alcoholic samples. In this work, the sample extraction and derivatization reaction conditions were investigated, and the optimal extraction conditions obtained were: pH 9 and solvent of ethyl acetate, and the derivatization conditions were: derivatization reaction temperature of 80°C and time duration of 30 min. With the optimal conditions, the method validations were also studied. In the validation studies, EC exhibited good linearity with a regression coefficient of 0.9999. The limit of detection and limit of quantification were 0.30 and 5.0 ?g/kg, respectively. The precision was less than 8.4%. Finally, the proposed technique was successfully applied to the analysis of EC in 35 kinds of alcoholic samples. The experimental results have demonstrated that the proposed technique is a fast, reliable and low-cost method for determination of EC in alcoholic samples. PMID:22383421

Xu, Xuejiao; Gao, Yihan; Cao, Xiujun; Wang, Xiang; Song, Guoxin; Zhao, Jianfeng; Hu, Yaoming

2012-04-01

301

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

302

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

303

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

304

Development of a hybrid fermentation-enzymatic bioprocess for the production of ethyl lactate from dairy waste.  

PubMed

This work explores the potential for the development of a hybrid fermentation-enzymatic process for the production of ethyl lactate from dairy waste. Cheese whey was used in Kluyveromyces marxianus and Lactobacillus bulgaricus batch cultures to produce ethanol and lactic acid respectively. Subsequently, the fermentation products were transferred into an organic phase through liquid-liquid extraction and ethyl lactate was formed in an esterification reaction catalyzed by lipases. The production of ethanol and lactic acid achieved under different conditions was 23gL(-1) and 29gL(-1), respectively. Furthermore, the efficiency of various organic solvents for the esterification reaction was evaluated and toluene was chosen for application in the process. The effect of water content was determined aiming to maximize the product yield and 40mgml(-1) was the optimal enzyme concentration. The bioprocess achieved maximum conversion of 33% constituting a valuable alternative to the application of energy demanding chemically derived methods. PMID:24785788

Koutinas, Michalis; Menelaou, Maria; Nicolaou, Evrydiki N

2014-08-01

305

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

PubMed

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

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

2006-08-01

306

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

307

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

308

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

309

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

310

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

311

Effects of wildlife of ethyl and methyl parathion applied to California USA 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

312

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

PubMed

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

Bae, Su Y; Winemiller, Mark D

2013-07-01

313

Rheological behaviors of cellulose in 1-ethyl-3-methylimidazolium chloride/dimethylsulfoxide.  

PubMed

Dynamic rheological behaviors of ?-cellulose 1-ethyl-3-methylimidazolium chloride ([Emim]Cl)/dimethylsulfoxide (DMSO) solutions were investigated in a large range of cellulose concentrations (0.1-10 wt%) at 25°C. The overlap concentration c* and the entanglement concentration ce for cellulose in [Emim]Cl/DMSO were determined to be 0.5 wt% and 2.0 wt% respectively, and the exponents of the specific viscosity ?sp versus cellulose concentration c were determined as 1.1, 2.1 and 4.7 for dilute, semidilute unentangled and entangled regimes respectively, which were in accordance with the scaling prediction for neutral polymer in ? solvent. Under the same cellulose concentration, the complex viscosity ?*, the reptation time ?rep and the relaxation time of a segment between entanglements ?e all decreased with increasing DMSO content in the solvent, while the number of entanglements of cellulose chains and the molar mass of an entanglement strand Me both remained unchanged. PMID:24906758

Wang, Lejun; Gao, Lei; Cheng, Bowen; Ji, Xiujie; Song, Jun; Lu, Fei

2014-09-22

314

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.

315

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...

316

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...

317

Heat capacity, saturation vapor pressure, and thermodynamic functions of ethyl esters of C3-C5 and C18 carboxylic acids  

NASA Astrophysics Data System (ADS)

The heat capacities of ethyl propanoate (EPr), ethyl n-pentanoate (EPen), and ethyl n-octadecanoate (ethyl stearate, ESt) were measured by vacuum adiabatic calorimetry in the temperature range of 6 to 373 K. Triple point temperatures, fusion enthalpies and entropies, and purity of the samples of the sub-stances under study were determined. The saturation vapor pressures for EPr and EPen were determined by comparative ebulliometry in an atmospheric pressure range of 4.0 to 101.7 kPa. The normal boiling points and vaporization enthalpies vs. temperature were obtained. The standard thermodynamic functions ( S, H, and G) were calculated for the condensed and ideal gas states on the basis of the experimental data. The vapor pressures of the atmospheric range were extrapolated to entire ranges of the liquid phases of EPr and EPen using the principle of corresponding states and the combined processing of pT parameters and low-temperature differences in the heat capacities of an ideal gas and liquid.

Agafonova, L. E.; Varushchenko, R. M.; Druzhinina, A. I.; Polyakova, O. V.; Kolesov, Yu. S.

2011-09-01

318

Atmospheric chemistry of two biodiesel model compounds: methyl propionate and ethyl acetate.  

PubMed

The atmospheric chemistry of two C(4)H(8)O(2) isomers (methyl propionate and ethyl acetate) was investigated. With relative rate techniques in 980 mbar of air at 293 K the following rate constants were determined: k(C(2)H(5)C(O)OCH(3) + Cl) = (1.57 ± 0.23) × 10(-11), k(C(2)H(5)C(O)OCH(3) + OH) = (9.25 ± 1.27) × 10(-13), k(CH(3)C(O)OC(2)H(5) + Cl) = (1.76 ± 0.22) × 10(-11), and k(CH(3)C(O)OC(2)H(5) + OH) = (1.54 ± 0.22) × 10(-12) cm(3) molecule(-1) s(-1). The chlorine atom initiated oxidation of methyl propionate in 930 mbar of N(2)/O(2) diluent (with, and without, NO(x)) gave methyl pyruvate, propionic acid, acetaldehyde, formic acid, and formaldehyde as products. In experiments conducted in N(2) diluent the formation of CH(3)CHClC(O)OCH(3) and CH(3)CCl(2)C(O)OCH(3) was observed. From the observed product yields we conclude that the branching ratios for reaction of chlorine atoms with the CH(3)-, -CH(2)-, and -OCH(3) groups are <49 ± 9%, 42 ± 7%, and >9 ± 2%, respectively. The chlorine atom initiated oxidation of ethyl acetate in N(2)/O(2) diluent gave acetic acid, acetic acid anhydride, acetic formic anhydride, formaldehyde, and, in the presence of NO(x), PAN. From the yield of these products we conclude that at least 41 ± 6% of the reaction of chlorine atoms with ethyl acetate occurs at the -CH(2)- group. The rate constants and branching ratios for reactions of OH radicals with methyl propionate and ethyl acetate were investigated theoretically using transition state theory. The stationary points along the oxidation pathways were optimized at the CCSD(T)/cc-pVTZ//BHandHLYP/aug-cc-pVTZ level of theory. The reaction of OH radicals with ethyl acetate was computed to occur essentially exclusively (?99%) at the -CH(2)- group. In contrast, both methyl groups and the -CH(2)- group contribute appreciably in the reaction of OH with methyl propionate. Decomposition via the ?-ester rearrangement (to give C(2)H(5)C(O)OH and a HCO radical) and reaction with O(2) (to give CH(3)CH(2)C(O)OC(O)H) are competing atmospheric fates of the alkoxy radical CH(3)CH(2)C(O)OCH(2)O. Chemical activation of CH(3)CH(2)C(O)OCH(2)O radicals formed in the reaction of the corresponding peroxy radical with NO favors the ?-ester rearrangement. PMID:21797203

Andersen, Vibeke F; Berhanu, Tesfaye A; Nilsson, Elna J K; Jørgensen, Solvejg; Nielsen, Ole John; Wallington, Timothy J; Johnson, Matthew S

2011-08-18

319

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

320

Removal of 1-ethyl-3-methylimidazolium cations with bacterial biosorbents from aqueous media.  

PubMed

This study aims to determine whether biosorption can be used for the removal of ionic liquids (ILs), especially their cationic parts, from aqueous media. As a model IL, 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc) was used. Five types of bacterial biosorbents were prepared from fermentation wastes through chemical modification of the bacterial surface. Screening study was performed to compare the cationic [EMIM] biosorption capacity among the bacterial biosorbents, indicating that the succinated Escherichia coli biomass (SB-E) was the best biosorbent for removing [EMIM] cations. The [EMIM] biosorption performance of SB-E was evaluated in detail through various experiments. The optimal pH range for [EMIM] biosorption was from 7 to 10, and biosorption equilibrium was reached within 10 min. The maximum uptake of SB-E was also estimated to be 72.6 mg/g. Moreover, [EMIM] cations were easily desorbed from [EMIM]-sorbed SB-E by adding acetic acid. PMID:23246948

Won, Sung Wook; Choi, Sun Beom; Mao, Juan; Yun, Yeoung-Sang

2013-01-15

321

Mixed monolayers of dipalmitoyl phosphatidylcholine and ethyl palmitate at the air/water interface  

NASA Astrophysics Data System (ADS)

The behaviour of monolayers containing dipalmitoyl phosphatidylcholine and ethyl palmitate and their mixtures at different molar fraction, using surface pressure-molecular area results, was investigated. The negative deviation from additivity of the mean molecular areas as a function of the mixture composition indicates the miscibility. The miscibility was confirmed by applying the two-dimensional phase rule, since the collapse pressure values vary with the composition of the mixtures. Also the free energy of mixing ? Gmix and the excess free energy of mixing ?GmixE were determined. The negative values of ? Gmix and ?GmixE indicate that the mixed monolayers are thermodynamically more stable compared to the pure ones and that the compounds in the two dimensional state experience mainly attractive interactions.

Gzyl, Barbara; Paluch, Maria

2005-06-01

322

Microwave Spectrum, Structural Parameters and Quadrupole Coupling for Azaborine and 1-ETHYL-AZABORINE  

NASA Astrophysics Data System (ADS)

The first microwave spectra for the unusual and elusive aromatic molecules, 1,2-dihydro-1,2-azaborine (azaborine) and 1-ethyl-azaborine have been measured, in the 7-18 GHz range, providing accurate rotational constants, nitrogen and boron quadrupole coupling strengths, important bond lengths and other structural parameters. Azaborine (BNC_4H_6)is an aromatic, B-N substituted analog of benzene, the quintessential aromatic molecule. The experimental bond lengths determined for azaborine are: R(B-N) = 1.45(3) Å, R(B-C) = 1.51(1) Å, and R(N-C) = 1.37(3) Å. Accurate measurements of 14N, 11B, and 10B nuclear quadrupole coupling were obtained. The inertial defect ? = 0.02 amu Å^2 indicating a planar structure. A Townes-Dailey population analysis of the B and N quadrupole coupling constants provided the valence p-electron occupancy

Daly, Adam; Kukolich, Stephen G.; Tanjaroon, Chakree; Marwitz, Adam J. V.; Liu, Shih-Yuan

2010-06-01

323

Synthesis and anticonvulsant activity of ethyl 2,2-dimethyl-1-(2-substitutedhydrazinecarboxamido) cyclopropanecarboxylate derivatives.  

PubMed

In this study on the development of new anticonvulsants, fourteen ethyl 2,2-dimethyl-1-(2-substitutedhydrazinecarboxamido) cyclopropanecarboxylate derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Two compounds 6f and 6k showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 6k showed the maximal electroshock-induced seizures with ED50 value of 9.2 mg/kg and TD50 value of 387.5 mg/kg after intraperitoneally injection to mice, which provided compound 6k with a protective index (TD50/ED50 ) of 42.1 in the maximal electroshock test. PMID:24571574

Zhong, Min; Zhang, Yongmin; He, Xianran

2014-08-01

324

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

325

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

326

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

327

Determination of Five Phthalate Monoesters in Human Urine Using Gas Chromatography-Mass Spectrometry  

Microsoft Academic Search

We have developed a gas chromatography-mass spectrometry (GC–MS) method to determine five phthalate monoesters (monoethyl\\u000a phthalate (MEP), mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), monoisononyl phthalate (MINP) and monobenzyl phthalate (MBz))\\u000a in human urine. Human urine samples were subjected to enzymatic deconjugation of the glucuronides followed by extraction with\\u000a hexane. The extracted phthalate monoesters were methylated with diazomethane, purified on a

Fumio Kondo; Yoshitomo Ikai; Rumiko Hayashi; Masanao Okumura; Satoshi Takatori; Hiroyuki Nakazawa; Shun-ichiro Izumi; Tsunehisa Makino

2010-01-01

328

Ethyl side-chain modifications in novel flexible antiestrogens--design, synthesis and biological efficacy in assay against the MCF-7 breast tumor cell line.  

PubMed

To examine the efficacy of ethyl side-chain modifications in a family of flexible non-steroidal modulators of the estrogen receptor, a series of novel compounds was prepared and their antiproliferative effects on human MCF-7 breast tumor cells evaluated. These flexible antiestrogens consisted of members wherein the ethyl portion of the parent compound, a flexible analogue of tamoxifen, had been modified so as to introduce halogens or a nitro group, or to extend the side-chain length from ethyl to propyl or butyl. The compounds demonstrated potency at low micromolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low associated cytotoxicity. Tested compounds exhibited nanomolar binding affinity (Ki) for the estrogen receptor (ER) as determined through displacement of radiolabelled estradiol. Semiempirical calculations predict an inherent lower oxidative potential at the allylic position, similar to that calculated for the established analogue toremifene, indicating a lesser propensity of such compounds towards metabolic oxidative carbocation generation and consequent DNA adduct formation. Computational studies predict these compounds to bind in a typical estrogen antagonist mode within the ER-ligand binding domain (LBD). Ethyl side-chain modification in this compound class is well tolerated within the ER and is not detrimental to compound efficacy, with additional potential anti-carcinogenic properties imbued to the molecule. PMID:11762645

Meegan, M J; Hughes, R B; Lloyd, D G; Williams, D C; Zisterer, D M

2001-02-01

329

Ion kinetic energy distributions and cross sections for the electron impact ionization of ethyl tert-butyl ether  

NASA Astrophysics Data System (ADS)

The kinetic energy distributions and the cross sections of the ions produced in the electron impact of ethyl tert-butyl ether (ETBE) have been studied by time of flight (TOF) mass spectrometry. The kinetic energy distributions have been deduced from the TOF peak shape analysis and a Montecarlo simulation method of the ion trajectories has been used to evaluate the collection efficiency of the spectrometer as a function of the ion initial kinetic energy. The measured ion yields have been corrected for the collection efficiency and the partial and total ionization cross sections of ETBE determined in the range 20-150 eV.

Di Palma, T. M.; Apicella, B.; Armenante, M.; Velotta, R.; Wang, X.; Spinelli, N.

2005-11-01

330

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

331

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.

332

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...

333

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

334

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

335

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

336

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

337

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

338

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

339

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

340

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

341

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

342

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

343

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

344

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

345

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

346

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

347

Diffusion of 1-Ethyl-3-methyl-imidazolium Acetate in Glucose, Cellobiose, and Cellulose Solutions  

PubMed Central

Solutions of glucose, cellobiose and microcrystalline cellulose in the ionic liquid 1-ethyl-3-methyl-imidazolium ([C2mim][OAc]) have been examined using pulsed-field gradient 1H NMR. Diffusion coefficients of the cation and anion across the temperature range 20–70 °C have been determined for a range of concentrations (0–15% w/w) of each carbohydrate in [C2mim][OAc]. These systems behave as an “ideal mixture” of free ions and ions that are associated with the carbohydrate molecules. The molar ratio of carbohydrate OH groups to ionic liquid molecules, ?, is the key parameter in determining the diffusion coefficients of the ions. Master curves for the diffusion coefficients of cation, anion and their activation energies are generated upon which all our data collapses when plotted against ?. Diffusion coefficients are found to follow an Arrhenius type behavior and the difference in translational activation energy between free and associated ions is determined to be 9.3 ± 0.9 kJ/mol. PMID:24405090

2014-01-01

348

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

349

Molecular recognition as shown by the solvent extraction of ( R )- and ( S )-[ ? -(1-naphthyl)ethyl] ammonium picrate or orange 2 by chiral pyridino-crown ethers  

Microsoft Academic Search

A solvent extraction technique was used to determine equilibrium constants for the reactions occurring when an aqueous phase containing [a-(1-naphthyl)ethyl]ammonium ions [(R)- and (S-isomers] is equilibrated with a chloroform phase containing chiral substituted pyridino-18-crown-6 ligands. Selectivity coefficients and equilibrium constants for the interactions in chloroform solutions were calculated. The existence of two different types of ion pairs separated by the

Alexander Y. Nazarenko; Peter Huszthy; Jerald S. Bradshaw; John D. Lamb; Reed M. Izatt

1994-01-01

350

Investigation of 60Co ?-irradiated L-(-) malic acid, N-methyl- DL-valine and L-glutamic acid ?-ethyl ester by electron paramagnetic resonance technique  

NASA Astrophysics Data System (ADS)

The electron paramagnetic resonance spectra of ?-irradiated L-(-) malic acid, N-methyl- DL-valine and L-glutamic acid ?-ethyl ester powders have been investigation at room temperature. Radiation damage centres are attributed to HOOCCH 2?HCOOH, (CH 3) 2?CH(NHCH 3)COOH and C 2H 5OCOCH 2CH 2?(NH 2)COOH radicals, respectively. The spectra have been computer simulated. The EPR parameters of the observed radicals have been determined and discussed.

Ba?kan, M. Halim; Ayd?n, Murat; Osmano?lu, ?emsettin

351

Characterisation of DSSC-electrolytes based on 1-ethyl-3-methylimidazolium dicyanamide: Measurement of triiodide diffusion coefficient, viscosity, and photovoltaic performance  

Microsoft Academic Search

A comprehensive characterisation of an ionic liquid based electrolyte for dye-sensitised solar cells (DSSC) was performed by determination of triiodide diffusion coefficients, viscosities and photovoltaic performances. The electrolyte, consisting of 1-ethyl-3-methylimidazolium dicyanamide, 1-methyl-3-propylimidazolium iodide (MPII), and iodine, was examined at varying ionic liquid molar ratio and fixed iodine concentration, as well as at fixed ionic liquid molar ratio and varying

Philipp Wachter; Markus Zistler; Christian Schreiner; Marko Berginc; Urša Opara Krašovec; Dirk Gerhard; Peter Wasserscheid; Andreas Hinsch; Heiner J. Gores

2008-01-01

352

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

353

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

354

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

355

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

356

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

357

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

EPA Science Inventory

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

358

HPLC determination of 4-hydroxy-anethole trithione in plasma via enzymatic hydrolysis and its application to bioequivalence study  

Microsoft Academic Search

A simple, selective and reproducible high-performance liquid chromatographic (HPLC) method via enzymatic hydrolysis of glucuronide conjugates of 4-hydroxy-anethole trithione (ATX) was established for simultaneous determination of ATX. Human plasma samples were hydrolyzed by ?-glucuronidase and followed by subsequent extraction with cyclohexane–isopropanol (95:5, v\\/v) using mifepristone as the internal standard. Chromatography was carried out on a reverse phase C18 column (250mm×4.6mm,

Weiyong Li; Jungang Deng; Jian Qiao; Qian Li; Ying Zhang

2008-01-01

359

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

360

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

361

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

362

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

363

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

364

Predicted and experimental crystal structures of ethyl-tert-butyl ether.  

PubMed

Possible crystal structures of ethyl-tert-butyl ether (ETBE) were predicted by global lattice-energy minimizations using the force-field approach. 33 structures were found within an energy range of 2 kJmol(-1) above the global minimum. Low-temperature crystallization experiments were carried out at 80-160 K. The crystal structure was determined from X-ray powder data. ETBE crystallizes in C2/m, Z = 4, with molecules on mirror planes. The ETBE molecule adopts a trans conformation with a (CH(3))(3)C-O-C-C torsion angle of 180°. The experimental structure corresponds with high accuracy to the predicted structure with energy rank 2, which has an energy of 0.54 kJmol(-1) above the global minimum and is the most dense low-energy structure. In some crystallization experiments a second polymorph was observed, but the quality of the powder data did not allow the determination of the crystal structure. Possibilities and limitations are discussed for solving crystal structures from powder diffraction data by real-space methods and lattice-energy minimizations. PMID:21422614

Hammer, Sonja M; Alig, Edith; Fink, Lothar; Schmidt, Martin U

2011-04-01

365

Prenatal developmental toxicity study of ethyl tertiary-butyl ether in rabbits.  

PubMed

Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, the prenatal developmental toxicity of ETBE was determined in rabbits. New Zealand white rabbits were given ETBE by gavage at 100, 300, or 1,000 mg/kg/day on gestational days (GDs) 6-27, and the pregnancy outcome was determined on GD 28. Neither death nor abortion occurred in the pregnant rabbits at any dose. Slightly and significantly suppressed maternal body-weight gain and transiently decreased maternal food consumption were found at 1,000 mg/kg/day during the administration period. At this dose, no changes in clinical or macroscopic finding were noted in dams. No treatment-related changes were observed in any dam treated at 300 mg/kg/day or less. There was no significant effect of ETBE on the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, incidences of pre- and postimplantation loss, viability of fetuses, fetal body weight, sex ratio of fetuses, or weights of gravid uteri. No significant difference was detected in the incidences of fetuses with malformations or variations between the ETBE-treated and control groups. Also, no adverse effects on the progress of ossification were noted in fetuses of dams given ETBE. Based on these findings, it is concluded that the no observed adverse effect levels of ETBE were 300 mg/kg/day for dams and 1,000 mg/kg/day for fetuses in rabbits. PMID:21649486

Asano, Yuzo; Ishikura, Toshikazu; Kudoh, Kayoko; Haneda, Ryo; Endoh, Takako

2011-07-01

366

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

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

367

[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

368

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

369

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

PubMed

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

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

2014-09-14

370

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

371

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

372

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

373

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

374

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

375

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

PubMed

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

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

2010-07-29

376

Determination of water-soluble polyphenolic compounds in commercial herbal teas from Lamiaceae: peppermint, melissa, and sage.  

PubMed

Chromatographic techniques (HPLC and HPTLC) were used for qualitative and quantitative determination of eriocitrin, luteolin 7-O-rutinoside, luteolin 7-O-beta-glucuronide, lithospermic acid, rosmarinic acid, and methyl rosmarinate together with other known compounds in commercial herbal teas from the Lamiaceae family: peppermint leaf (Menthae piperitae folium), melissa leaf (Melissae folium), and sage leaf (Salviae officinalis folium). Contents of analyzed compounds in infusions, the most popular forms, were established using a C18 column with acetonitrile-water-formic acid as a mobile phase. The HPLC method was validated for linearity, precision, and accuracy. Luteolin 7-O-beta-glucuronide and lithospermic acid were identified as new Mentha x piperita compounds. The investigated herbal teas delivered polyphenols in high amounts, up to 182.2 mg for the infusion of one peppermint tea bag. PMID:18052102

Fecka, Izabela; Turek, Sebastian

2007-12-26

377

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

378

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

379

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

380

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

381

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

382

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

383

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

384

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

385

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

386

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

387

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

388

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

389

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

PubMed Central

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

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

2014-01-01

390

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

PubMed Central

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

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

2013-01-01

391

Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films.  

PubMed

Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the films after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films. PMID:23159668

Andersson, Helene; Hjärtstam, Johan; Stading, Mats; von Corswant, Christian; Larsson, Anette

2013-01-23

392

Responses of Cultured Human Keratocytes and Myofibroblasts to Ethyl Pyruvate: A Microarray Analysis of Gene Expression  

PubMed Central

Purpose. Ethyl pyruvate (EP) has pharmacologic effects that remediate cellular stress. In the organ-cultured murine lens, EP ameliorates oxidative stress, and in a rat cataract model, it attenuates cataract formation. However, corneal responses to EP have not been elucidated. In this study, the potential of EP as a therapeutic agent in corneal wound healing was determined by examining its effects on the transition of quiescent corneal stromal keratocytes into contractile myofibroblasts. Methods. Three independent preparations of cultured human keratocytes were treated with TGF-?1, to elicit a phenotypic transition to myofibroblasts in the presence or absence of 10 or 15 mM EP. Gene expression profiles of the 12 samples (keratocytes ± EP ± TGF-?1 for three preparations) were produced by using gene microarrays. Results. TGF-?1–driven twofold changes in at least two of three experiments defined a group of 1961 genes. Genes showing twofold modulation by EP in at least two experiments appeared exclusively in myofibroblasts (857 genes), exclusively in keratocytes (409 genes), or in both phenotypes (252 genes). Analysis of these three EP-modulated groups showed that EP (1) inhibited myofibroblast proliferation with concomitant modulation of some cell cycle genes, (2) augmented the NRF2-mediated antioxidant response in both keratocytes and myofibroblasts, and (3) modified the TGF-?1–driven transition of keratocytes to myofibroblasts by inhibiting the upregulation of a subset of profibrotic genes. Conclusions. These EP-induced phenotypic changes in myofibroblasts indicate the potential of EP as a therapeutic agent in corneal wound healing. PMID:20053976

Guerriero, Emily; Charukamnoetkanok, Nahthai; Piluek, Jordan; Schuman, Joel S.; SundarRaj, Nirmala

2010-01-01

393

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

PubMed Central

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

Burba, Christopher M.; Frech, Roger

2011-01-01

394

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

395

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

396

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

397

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

398

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

399

Analysis and occurrence of estrogenic hormones and their glucuronides in surface water and waste water in The Netherlands  

Microsoft Academic Search

An analytical procedure was developed that enables routine analysis of four estrogenic hormones in concentrations below 1 ng\\/l in surface water and waste water. The recovery was 88–98% with a limit of detection of 0.1–2.4 ng\\/l depending on the compound and the matrix measured. This method was used to determine the occurrence of 17?-estradiol, 17?-estradiol, estrone and 17?-ethinylestradiol in the

A. C. Belfroid; A Van der Horst; A. D. Vethaak; A. J. Schäfer; G. B. J. Rijs; J. W. M. Wegener; W. P. Cofino

1999-01-01

400

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

401

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

402

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

403

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

404

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

405

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

406

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

407

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

408

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

409

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

410

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

411

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

412

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

413

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

414

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

415

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

416

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

417

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.

418

Ethyl t-butyl ether: review of reproductive and developmental toxicity.  

PubMed

Ethyl t-butyl ether (ETBE) is a motor fuel oxygenate used in reformulated gasoline. Knowledge of developmental and reproductive toxicity potential of ETBE is critical for making informed decisions about acceptance and regulations. This review discusses toxicology studies providing information about effects on reproduction and the conceptus. Seven GLP-compliant studies following widely accepted protocols have focused specifically on developmental and reproductive toxicity (DART) in rats and rabbits exposed to ETBE by gavage with doses up to 1,000 mg/kg body weight/day, the limit specified in standardized test guidelines. Other repeat-dose general toxicology studies have administered ETBE to rodents for up to 180 days, and included reproductive organ weights, histology, or other indications of reproductive system structure or function. DART potential of the main ETBE metabolite t-butyl alcohol and class-related MTBE has also been studied. More GLP-compliant studies exist for evaluating ETBE using well-established, currently recommended protocols than are available for many other chemicals used today. The database for determining ETBE DART potential is adequate, although not all study details are currently easily accessible for peer-review. ETBE does not appear to be selectively toxic to reproduction or embryofetal development in the absence of other manifestations of general toxicity. Studies using recommended methods for sample preservation and analysis have shown no targeted effect on the reproductive system. No embryofetal effects were observed in rabbits. Early postnatal rat pup deaths show no clear dose-response and have largely been attributed to total litter losses with accompanying evidence of maternal neglect or frank maternal morbidity. PMID:20544807

de Peyster, Ann

2010-06-01

419

Decreased Inflammatory Responses of Human Lung Epithelial Cells after Ethanol Exposure Are Mimicked by Ethyl Pyruvate  

PubMed Central

Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10?mM), sodium pyruvate (NaP, 10?mM), or EtOH (85–170?mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.

Relja, B.; Omid, N.; Kontradowitz, K.; Jurida, K.; Oppermann, E.; Störmann, P.; Werner, I.; Juengel, E.; Seebach, C.; Marzi, I.

2014-01-01

420

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

421

Electron paramagnetic resonance studies of gamma-irradiated DL-alanine ethyl ester hydrochloride, L-theanine and L-glutamic acid dimethyl ester hydrochloride  

NASA Astrophysics Data System (ADS)

The electron paramagnetic resonance (EPR) of gamma irradiated powders of DL-alanine ethyl ester hydrochloride, L-theanine and L-glutamic acid dimethyl ester hydrochloride were investigated at room temperature. The observed paramagnetic species were attributed to the CH3?HCOOC2H5, -CH2?HCOOH and -CH2?HCOOCH3 radicals, respectively. Hyperfine structure constants and g-values were determined for these three radicals. Some spectroscopic properties and suggestions concerning the possible structure of the radicals were also discussed.

Ba?kan, M. Halim; Ayd?n, Murat

2013-08-01

422

Electron paramagnetic resonance studies of gamma-irradiated DL-alanine ethyl ester hydrochloride, L-theanine and L-glutamic acid dimethyl ester hydrochloride.  

PubMed

The electron paramagnetic resonance (EPR) of gamma irradiated powders of DL-alanine ethyl ester hydrochloride, L-theanine and L-glutamic acid dimethyl ester hydrochloride were investigated at room temperature. The observed paramagnetic species were attributed to the CH3?HCOOC2H5, -CH2?HCOOH and -CH2?HCOOCH3 radicals, respectively. Hyperfine structure constants and g-values were determined for these three radicals. Some spectroscopic properties and suggestions concerning the possible structure of the radicals were also discussed. PMID:23680512

Ba?kan, M Halim; Ayd?n, Murat

2013-08-01

423

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

424

Multiple headspace solid-phase microextraction of ethyl carbamate from different alcoholic beverages employing drying agent based matrix modification.  

PubMed

Multiple headspace solid-phase microextraction (MHS-SPME) combined with gas chromatography-nitrogen phosphorus detector is proposed to determine the toxic contaminant ethyl carbamate (EC) in various alcoholic beverages after matrix modification. The remarkable feature of this method is that matrix effect, which commonly appears in SPME-based analysis, is avoided by determining the total amount of the analyte in the sample. To increase the sensitivity of the method, a novel polyethylene glycol/hydroxy-terminated silicone oil fiber was developed by sol-gel technique and applied for the analysis. Owing to the high polarity and hydrophilia of EC, an important problem still remains because the adsorption by sample matrix causes low transport of EC to the headspace and thus invalidates MHS-SPME for quantification. Mixing with anhydrous sodium sulphate, the sensitivity of the method can be improved. A Taguchi's L(16) (4(5)) orthogonal array design was employed to evaluate potentially significant factors and screen the optimum conditions for MHS-SPME of EC. Under the optimized conditions, limit of detection of 0.034 mg L(-1) was obtained. Relative standard deviation of replicate samples (n=6) was 2.19%. The proposed method was linear in the range of 0.04-100 mg L(-1), and the coefficient of determination was 0.9997. The method was used to determine EC in various alcoholic beverages. The concentrations obtained were compared with those obtained by standard addition method and no statistically significant differences were observed. PMID:21726869

Ye, Chang-Wen; Zhang, Xue-Na; Huang, Jiang-Yan; Li, Shan-Shan; Pan, Si-Yi; Wang, Yi-Long; Li, Xiu-Juan

2011-08-01

425

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