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

International Nuclear Information System (INIS)

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

1980-01-01

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

Monitoring of ovarian activity by measurement of urinary excretion rates of estrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part II: reliability of home testing.

Science.gov (United States)

Blackwell, Leonard F; Vigil, Pilar; Gross, Barbara; d'Arcangues, Catherine; Cooke, Delwyn G; Brown, James B

2012-02-01

The UNDP/WHO/World Bank/Special Programme of Research, Development and Research Training in Human Reproduction (Geneva) set up a study to determine whether it is feasible for women to monitor their ovarian activity reliably by home testing. Daily self-monitoring of urinary hormone metabolites for menstrual cycle assessment was evaluated by comparison of results obtained with the Home Ovarian Monitor by untrained users both at home and in study centres. Women collected daily data for urinary estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) for two cycles, then the procedure was repeated in the women's local centre (in Chile, Australia or New Zealand) giving a total of 113 duplicate cycles. The tests were performed without the benefit of replicates or quality controls. The home and centre cycles were normalized and compared to identify assay errors, and the resulting home and centre menstrual cycle profiles were averaged. Reliable mean cycle profiles were obtained with the home and centre excretion rates agreeing to within 36 ± 21 nmol/24 h for E1G and 0.77 ± 0.28 µmol/24 h for baseline PdG values (1-5 µmol/24 h). The cycles had a mean length of 28.1 ± 3.1 days (n = 112; 5th and 95th percentiles: 24 and 35 days, respectively), a mean follicular phase of 14.8 ± 3.1 days (n = 107; 5th and 95th percentiles: 11 and 21 days) and a mean luteal phase length of 13.3 ± 1.5 days (n = 106; 5th and 95th percentiles: 11 and 17 days), calculated from the day of the LH peak. The study confirmed that the Ovarian Monitor pre-coated assay tubes worked well even in the hands of lay users, without standard curves, quality controls or replicates. Point-of-care monitoring to give reliable fertility data is feasible.

In vitro characterization of glucuronidation of vanillin: identification of human UDP-glucuronosyltransferases and species differences.

Science.gov (United States)

Yu, Jian; Han, Jing-Chun; Hua, Li-Min; Gao, Ya-Jie

2013-09-01

Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP-glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a hydrolysis reaction catalyzed by β-glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis-Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 μM and 81.3 ± 11.3 μM for K(m) of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP-glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V(max)/K(m) values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K(m)  = 25.6 ± 3.2 μM) and the lowest affinity for the mice liver microsomes enzyme (K(m)  = 149.1 ± 18.4 μM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin. Copyright © 2012 John Wiley & Sons, Ltd.

Identification and characterization of human UDP-glucuronosyltransferases responsible for the in-vitro glucuronidation of arctigenin.

Science.gov (United States)

Xin, Hong; Xia, Yang-Liu; Hou, Jie; Wang, Ping; He, Wei; Yang, Ling; Ge, Guang-Bo; Xu, Wei

2015-12-01

This study aimed to characterize the glucuronidation pathway of arctigenin (AR) in human liver microsomes (HLM) and human intestine microsomes (HIM). HLM and HIM incubation systems were employed to catalyse the formation of AR glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards AR was screened. A combination of chemical inhibition assay and kinetic analysis was used to determine the UGT isoforms involved in the glucuronidation of AR in HLM and HIM. AR could be extensively metabolized to one mono-glucuronide in HLM and HIM. The mono-glucuronide was biosynthesized and characterized as 4'-O-glucuronide. UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7 and 2B17 participated in the formation of 4'-O-G, while UGT2B17 demonstrated the highest catalytic activity in this biotransformation. Both kinetic analysis and chemical inhibition assays demonstrated that UGT1A9, UGT2B7 and UGT2B17 played important roles in AR-4'-O-glucuronidation in HLM. Furthermore, HIM demonstrated moderate efficiency for AR-4'-O-glucuronidation, implying that AR may undergo a first-pass metabolism during the absorption process. UGT1A9, UGT2B7 and UGT2B17 were the major isoforms responsible for the 4'-O-glucuronidation of AR in HLM, while UGT2B7 and UGT2B17 were the major contributors to this biotransformation in HIM. © 2015 Royal Pharmaceutical Society.

Autism and Phthalate Metabolite Glucuronidation

Science.gov (United States)

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

2013-01-01

Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured…

Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism.

Science.gov (United States)

Gan, Jinping; Chen, Weiqi; Shen, Hong; Gao, Ling; Hong, Yang; Tian, Yuan; Li, Wenying; Zhang, Yueping; Tang, Yuwei; Zhang, Hongjian; Humphreys, William Griffith; Rodrigues, A David

2010-12-01

To further explore the mechanism underlying the interaction between repaglinide and gemfibrozil, alone or in combination with itraconazole. Repaglinide metabolism was assessed in vitro (human liver subcellular fractions, fresh human hepatocytes, and recombinant enzymes) and the resulting incubates were analyzed, by liquid chromatography-mass spectrometry (LC-MS) and radioactivity counting, to identify and quantify the different metabolites therein. Chemical inhibitors, in addition to a trapping agent, were also employed to elucidate the importance of each metabolic pathway. Finally, a panel of human liver microsomes (genotyped for UGT1A1*28 allele status) was used to determine the importance of UGT1A1 in the direct glucuronidation of repaglinide. The results of the present study demonstrate that repaglinide can undergo direct glucuronidation, a pathway that can possibly contribute to the interaction with gemfibrozil. For example, [³H]-repaglinide formed glucuronide and oxidative metabolites (M2 and M4) when incubated with primary human hepatocytes. Gemfibrozil effectively inhibited (∼78%) both glucuronide and M4 formation, but had a minor effect on M2 formation. Concomitantly, the overall turnover of repaglinide was also inhibited (∼80%), and was completely abolished when gemfibrozil was co-incubated with itraconazole. These observations are in qualitative agreement with the in vivo findings. UGT1A1 plays a significant role in the glucuronidation of repaglinide. In addition, gemfibrozil and its glucuronide inhibit repaglinide glucuronidation and the inhibition by gemfibrozil glucuronide is time-dependent. Inhibition of UGT enzymes, especially UGT1A1, by gemfibrozil and its glucuronide is an additional mechanism to consider when rationalizing the interaction between repaglinide and gemfibrozil. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

Energy Technology Data Exchange (ETDEWEB)

Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

1994-07-01

Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

Radioimmunoassay of estriol-16-glucuronide using tritiated and radioiodinated radioligands: direct radioimmunoassay of urinary estriol-16-glucuronide during the menstrual cycle

International Nuclear Information System (INIS)

Stanczyk, F.Z.; Miyakawa, I.; Soares, J.R.; Goebelsmann, U.

1979-01-01

Estriol-16-glucuronide-[ 125 I]-iodohistamine (E 3 -16G-[ 125 ]) was prepared and utilized in a radioimmunoassay (RIA) in conjunction with anti-estriol-16-glucuronide-bovine serum albumin (E 3 -16G-BSA) serum (RIA No.1). This RIA was then compared with two other RIA methods employing [ 3 H]-labeled estriol-16-glucuronide (E 3 -16G) together with either anti-E 3 -16G-BAS serum (RIA No.2) or anti-estriol-16-glucuronide-2-azobenzoic acid-bovine serum albumin (E 3 -16G-2-BSA) serum (RIA No. 3). All three RIA's were accurate and precise, however, they differed in assay sensitivity and specificity. Most sensitive was RIA No.1 and least sensitive was RIA No.3. Both RIA's No.1 and 2 were less specific than RIA No.3. since unconjugated estriol and estrone 3-sulfate exhibited large and comparable cross-reactions in RIA's No.1 and 2, averaging 50% and 41% respectively. Furthermore, measurement of E 3 -16G in 10 different urine aliquots collected from non-pregnant women employing RIA's No. 1-3 showed that RIA's No. 1 and 2 yielded comparable results, however, the results obtained by RIA No.3 were, on the average, 26% lower than the mean of the values measured with RIA's No. 1 and 2. Consequently, RIA Bo.3 was used to measure daily 24-hour urinary E 3 -16G excretion in 7 women throughout an entire menstrual cycle. These data are in agreement with colorimetric and fluorimetric estimates of 24-h urinary estriol values throughout the menstrual cycle. The perovulatory rise of urinary E 3 -16G excretion, as quantitated by this RIA, is comparable to that of serum estradiol measured in the same 7 women, but peaks 1 to 2 days later than the serum estradiol surge. (author)

The Uptake by Plants of Diethylstilboestrol and of Its Glucuronide

DEFF Research Database (Denmark)

Gregers Hansen, B.

1964-01-01

The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments. It is con......The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments...

False-positive ethyl glucuronide immunoassay screening caused by a propyl alcohol-based hand sanitizer.

Science.gov (United States)

Arndt, Torsten; Grüner, Joachim; Schröfel, Stefanie; Stemmerich, Karsten

2012-11-30

Urine ethyl glucuronide (EtG) is considered as a specific marker of recent ethanol consumption. We describe false-positive DRI(®) EIA EtG enzyme immunoassay results caused by propyl glucuronides in urine after using a propanol-based hand sanitizer. EtG screening was done with the DRI(®) EIA EtG assay (Microgenics), using a cut-off of 0.5 mg/L as recommended by the manufacturer and of 0.1 mg/L as demanded by the German Regulations for Reissuing Drivers Licenses. Confirmatory EtG analysis was done with the ClinMass(®) EtG LC-MS/MS testkit (Recipe), extended by the mass transitions 235.1→75.1, 235.1→85.1, and 235.1→113.1 for the detection of the 1- and 2-propyl glucuronides. Self-experiments were done by staff members of our lab (n=7), using 3 mL Sterillium(®) Classic Pure (30 g/100 g 1-propanol and 45 g/100 g 2-propanol) for hand sanitation every quarter of an hour for 8 h according to DIN EN 1500:2011-05 with and without an exhauster and by passive inhalation of the sanitizer vapor. Spot urine samples were taken immediately before and up to 24 h after the first sanitizer use. False-positive immunoassay results of up to 4 mg/L or 2.3 mg/g creatinine were obtained after normal use of the sanitizer and also after passive inhalation of the sanitizer vapor (up to 0.89 mg/L or 0.61 mg/g). Immunoassay results were positive even after 4-fold use of the sanitizer (up to 0.14 mg/L or 0.38 mg/g) and up to 6 h after the last sanitizer contact (maximum 0.63 mg/L and 0.33 mg/g for sanitizer users and 0.25 mg/g after passive inhalation). Spiking of EtG-free urine with 1-propyl glucuronide (Athena Environmental Sciences) between 0.05 and 10 mg/L clearly demonstrated a cross reaction of the immunoassay of approx. 10% as compared to EtG. LC-MS/MS of urines with a positive immunoassay EtG result did not show EtG signals, but distinct signals of 1-propyl glucuronide (n-propyl glucuronide) and 2-propyl glucuronide (iso-propyl glucuronide). An exhauster effectively prevented

Studies to further investigate the inhibition of human liver microsomal CYP2C8 by the acyl-β-glucuronide of gemfibrozil.

Science.gov (United States)

Jenkins, S M; Zvyaga, T; Johnson, S R; Hurley, J; Wagner, A; Burrell, R; Turley, W; Leet, J E; Philip, T; Rodrigues, A D

2011-12-01

In previous studies, gemfibrozil acyl-β-glucuronide, but not gemfibrozil, was found to be a mechanism-based inhibitor of cytochrome P450 2C8. To better understand whether this inhibition is specific for gemfibrozil acyl-β-glucuronide or whether other glucuronide conjugates are potential substrates for inhibition of this enzyme, we evaluated several pharmaceutical compounds (as their acyl glucuronides) as direct-acting and metabolism-dependent inhibitors of CYP2C8 in human liver microsomes. Of 11 compounds that were evaluated as their acyl glucuronide conjugates, only gemfibrozil acyl-β-glucuronide exhibited mechanism-based inhibition, indicating that CYP2C8 mechanism-based inhibition is very specific to certain glucuronide conjugates. Structural analogs of gemfibrozil were synthesized, and their glucuronide conjugates were prepared to further examine the mechanism of inhibition. When the aromatic methyl groups on the gemfibrozil moiety were substituted with trifluoromethyls, the resulting glucuronide conjugate was a weaker inhibitor of CYP2C8 and mechanism-based inhibition was abolished. However, the glucuronide conjugates of monomethyl gemfibrozil analogs were mechanism-based inhibitors of CYP2C8, although not as potent as gemfibrozil acyl-β-glucuronide itself. The ortho-monomethyl analog was a more potent inhibitor than the meta-monomethyl analog, indicating that CYP2C8 favors the ortho position for oxidation and potential inhibition. Molecular modeling of gemfibrozil acyl-β-glucuronide in the CYP2C8 active site is consistent with the ortho-methyl position being the favored site of covalent attachment to the heme. Moreover, hydrogen bonding to four residues (Ser100, Ser103, Gln214, and Asn217) is implicated.

Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

DEFF Research Database (Denmark)

Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

2007-01-01

After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

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

Science.gov (United States)

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

2013-01-01

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 μM 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

Synthesis of a radioiodinated antiestrogen glucuronide compound (TAM-G)

International Nuclear Information System (INIS)

Fazilet Zumrut Biber Muftuler; Perihan Unak; Cigdem Ichedef; Ilknur Demir

2011-01-01

Tamoxifen [TAM; ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine) has been used as an antiestrogen drug for treatment and prevention of human breast cancer. The aim of this study is conjugation of hydrophilic glucuronic acid to the starting substance TAM and labeling with 131 I using iodogen as oxidizing agent. The reactions are completed in three steps, including enzymatic reaction, with the following sub-steps; preparation of microsomal fraction from rat liver and subsequent purification of UDP-glucuronyl transferase (UDPGT), estimation of protein amount in microsomal samples and glucuronidation reaction. Synthesized glucuronide derivative (TAM-G) was purified using high performance liquid chromatography (HPLC). Mass spectroscopy of cold standard showed that the labeling most probably occurs in ortho position to the aromatic ring containing the ether group of TAM-G as expected. Radiochemical yield of the 131 I labeled TAM-G ([ 131 I]TAM-G) is determined by using Thin Layer Radio Chromatography (TLRC). The radiopharmaceutical potential of [ 131 I]TAM-G is examined by biodistribution studies that is run on normal female Albino Wistar rats. According to biodistribution results 131 I labeled TAM-G may be proposed as a new antiestrogen glucuronide imaging agent for breast and uterus. Electronic supplementary material. The online version of this article (doi:10.1007/s10967-010-0932-7) contains supplementary material, which is available to authorized users. (author)

Analysis and interpretation of specific ethanol metabolites, ethyl sulfate, and ethyl glucuronide in sewage effluent for the quantitative measurement of regional alcohol consumption.

Science.gov (United States)

Reid, Malcolm J; Langford, Katherine H; Mørland, Jørg; Thomas, Kevin V

2011-09-01

The quantitative measurement of urinary metabolites in sewage streams and the subsequent estimation of consumption rates of the parent compounds have previously been demonstrated for pharmaceuticals and narcotics. Ethyl sulfate and ethyl glucuronide are excreted in urine following the ingestion of alcohol, and are useful biomarkers for the identification of acute alcohol consumption. This study reports a novel ion-exchange-mediated chromatographic method for the quantitative measurement of ethyl sulfate and ethyl glucuronide in sewage effluent, and presents a novel calculation method for the purposes of relating the resulting sewage concentrations with rates of alcohol consumption in the region. A total of 100 sewage samples covering a 25-day period were collected from a treatment plant servicing approximately 500,000 people, and analyzed for levels of ethyl sulfate and ethyl glucuronide. The resulting data were then used to estimate combined alcohol consumption rates for the region, and the results were compared with alcohol related sales statistics for the same region. Ethyl glucuronide was found to be unstable in sewage effluent. Ethyl sulfate was stable and measurable in all samples at concentrations ranging from 16 to 246 nM. The highest concentrations of the alcohol biomarker were observed during weekend periods. Sixty one percent of the total mass of ethyl sulfate in sewage effluent corresponds to alcohol consumption on Friday and Saturday. Sales statistics for alcohol show that consumption in the region is approximately 6,750 kg/d. The quantity of ethyl sulfate passing through the sewage system is consistent with consumption of 4,900 to 7,800 kg/d.   Sewage epidemiology assessments of ethyl sulfate can provide accurate estimates of community alcohol consumption, and detailed examination of the kinetics of this biomarker in sewage streams can also identify time-dependent trends in alcohol consumption patterns. 2011 by the Research Society on Alcoholism.

PRACTICAL PREPARATION OF RESVERATROL 3-O-β-D-GLUCURONIDE

OpenAIRE

Jungong, Christian S.; Novikov, Alexei V.

2012-01-01

A practical synthesis of resveratrol 3-O-β-D-glucuronide, suitable for preparation of large quantities, was developed using selective deacetylation of resveratrol triacetate with ammonium acetate. A simplified procedure for large scale preparation of resveratrol is also reported.

Synthesis, physicochemical properties, and biological activity of bile acids 3-glucuronides: Novel insights into bile acid signalling and detoxification.

Science.gov (United States)

Mostarda, Serena; Passeri, Daniela; Carotti, Andrea; Cerra, Bruno; Colliva, Carolina; Benicchi, Tiziana; Macchiarulo, Antonio; Pellicciari, Roberto; Gioiello, Antimo

2018-01-20

Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine. However, the pathophysiological significance of bile acid glucuronidation is still controversial and debated among the scientific community. Progress in this field has been strongly limited by the lack of appropriate methods for the preparation of pure glucuronides in the amount needed for biological and pharmacological studies. In this work, we have developed a new synthesis of bile acid C3-glucuronides enabling the convenient preparation of gram-scale quantities. The synthesized compounds have been characterized in terms of physicochemical properties and abilities to modulate key nuclear receptors including the farnesoid X receptor (FXR). In particular, we found that C3-glucuronides of chenodeoxycholic acid and lithocholic acid, respectively the most abundant and potentially cytotoxic species formed in patients affected by cholestasis, behave as FXR agonists and positively regulate the gene expression of transporter proteins, the function of which is critical in human conditions related to imbalances of bile acid homeostasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of pregnancy and estradiol-17 beta treatment on the biliary transport maximum of dibromosulfophthalein, and the glucuronide conjugates of 5-phenyl-5-p-hydroxyphenyl[14C]hydantoin and [14C]morphine in the isolated perfused rat liver

International Nuclear Information System (INIS)

Auansakul, A.C.; Vore, M.

1982-01-01

The biliary transport maximum (Tm) of three organic axions was determined in the isolated perfused livers of untreated female (control), estradiol-17 beta (E2)-treated female (1 mg/kg/day, s.c. for 14 days), and pregnant (19-21 days of gestation) rats. Dibromosulfophthalein (DBSP), 5-phenyl-5-p-hydroxyphenyl[ 14 C]hydantoin (HPPH) and [ 14 C]morphine were infused continuously into the perfusate for a total dose of 41.2, 18, or 40.5 mumol, respectively. The concentration of [ 14 C]HPPH and [ 14 C]morphine declined in the perfusate, whereas the concentrations of [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide increased during the 90-min experiment, indicating that the rate of formation of the glucuronide exceeded its rate of excretion in bile. E2 treatment decreased the Tm (nmol/min/g liver) for [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide but not for DBSP, whereas pregnancy decreased the Tm for all three organic anions. Pregnancy, and to a lesser extent E2 treatment, increased liver weight. When expressed per whole liver, the Tm was not altered by pregnancy for any of three organic anions. E2 treatment increased the Tm for DBSP, had no effect on the Tm for HPPH glucuronide and decreased the Tm for [ 14 C]morphine glucuronide. These data suggest the presence of multiple carriers for organic anions which are differentially affected by estrogen treatment and pregnancy

Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-β-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat.

Science.gov (United States)

Cai, Yu; Li, Sai; Li, Ting; Zhou, Ruina; Wai, Alfred Tai-Seng; Yan, Ru

2016-07-15

Scutellariae Radix (SR) has been extensively prescribed in folk medicines due to its notable beneficial activities. The flavonoid glucuronides baicalin (BG), wogonoside (WG), oroxylin A 7-O-β-d-glucuronide (OG) and their aglycones baicalein, wogonin and oroxylin A, are the main components of the herb. So far, majority of previous studies failed to report the pharmacokinetics and none offered an explanation for the systemic exposures of these six flavonoids when the herbal extract was orally administered. In this study, when a SR extract was orally dosed to rats (800mg/kg, equivalent to BG 324.80, WG 124.00, OG 43.04, baicalein 25.36, wogonin 24.40, and oroxylin A 5.79mg/kg), all six flavonoids were detectable throughout the experimental period (48h) using an LC-MS/MS method with the Cmax and AUC0-48h of the glucuronides 10-130 times that of respective aglycones. As the lowest among the three glucuronides in the herb, OG was the most abundant in vivo, while the systemic exposure of wogonin was the highest amongst the three aglycones. The dose-normalized AUC0-48h descended in orders of OG/oroxylin A, WG/wogonin and BG/baicalein. Two di-conjugates of baicalein (BG glucuronide and BG glucoside), two BG isomers (minor BM1 and major BM2), and one WG isomer (wogonin 5-O-glucuronide) were detected in rat plasma. Semi-quantitation of the isomers with peak area data revealed that the AUPs (area under peak area ratio-time curves) of BG isomers were ∼3 times that of BG, yet the AUP of wogonin 5-O-glucuronide was only one seventh of WG. BM2, tentatively assigned as baicalein 6-O-glucuronide, was formed from both microbial isomerization of BG and hepatic glucuronidation of baicalein. Wogonin 5-O-glucuronide was only formed in hepatic glucuronidation of wogonin. Demethylated wogonin was observed in gut bacteria, offering an optional origin of BM1 apart from baicalein glucuronidation. Microbial isomerization of BG and extensive hepatic glucuronidation of baicalein to form BM2as

Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction.

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Martin Perreault

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

Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2)

NARCIS (Netherlands)

Seitz, S.; Kretz-Rommel, A.; Oude Elferink, R. P.; Boelsterli, U. A.

1998-01-01

Previous work demonstrates that the reactive acyl glucuronide of the nonsteroidal antiinflammatory drug diclofenac forms selective protein adducts in the liver, which may play a causal role in the pathogenesis of diclofenac-associated liver toxicity. Because glucuronide conjugates can be exported

In vitro Inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea, and Curcuma xanthorrhiza Extracts and Constituents on Human Liver Glucuronidation Activity.

Science.gov (United States)

Husni, Zulhilmi; Ismail, Sabariah; Zulkiffli, Mohd Halimhilmi; Afandi, Atiqah; Haron, Munirah

2017-07-01

Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated. In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity. Herbal extracts (aqueous, methanolic and ethanolic extracts) and their constituents were incubated with human liver microsomes with the addition of UDPGA to initiate the reaction. Working concentrations of herbal extracts and their constituents ranged from 10 μg/mL to 1000 μg/mL and 10 μM to 300 μM respectively. IC50 was determined by monitoring the decrement of glucuronidation activity with the increment of herbal extracts or phytochemical constituent's concentrations. All herbal extracts inhibited human liver glucuronidation activity in range of 34.69 μg/mL to 398.10 μg/mL whereas for the constituents, only xanthorrhizol and curcumin (constituents of Curcuma xanthorrhiza ) inhibited human liver glucuronidation activity with IC50 of 538.50 and 32.26 μM respectively. In the present study, we have proved the capabilities of Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza to interfere with in vitro glucuronidation process in human liver microsomes. This study documented the capabilities of Andrographis paniculata , Gynura procumbens , Ficus deltoidea and Curcuma xanthorrhiza to inhibit human liver glucuronidation activity which may affect the metabolism of therapeutic drugs or hazardous toxicants that follow the same glucuronidation pathway. Abbreviations used: UGT: Uridine 5'-diphospho-glucuronosyltransferase; 4-MU: 4-methylumbelliferone; IC50: Half Maximal Inhibitory Concentration; Km: Michaelis constant; Vmax: Maximum velocity.

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

International Nuclear Information System (INIS)

Richardson, Terrilyn A.; Klaassen, Curtis D.

2010-01-01

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

Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.

OpenAIRE

Takikawa, H; Beppu, T; Seyama, Y

1985-01-01

Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acid...

Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

Science.gov (United States)

Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

2016-10-01

Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

Urinary Excretion of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant Women Receiving Buprenorphine Maintenance Treatment

Science.gov (United States)

Kacinko, Sherri L.; Jones, Hendree E.; Johnson, Rolley E.; Choo, Robin E.; Concheiro-Guisan, Marta; Huestis, Marilyn A.

2011-01-01

BACKGROUND Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 µg/L for BUP and BUP-Gluc and 25 µg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation. PMID:19325013

Identification of glucuronides as in vivo liver conjugates of seven cannabinoids and some of their hydroxy and acid metabolites.

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Harvey, D J; Martin, B R; Paton, W D

1977-02-01

Glucuronide conjugates of cannabidiol (CBD), 7-hydroxy-CBD, propyl-CBD, cannabinol (CBN), 7-hydroxy-CBN, CBN-7-oic acid, propyl CBN and cannabichromene have been identified as major metabolites of CBD, CBN and their propyl homologues and of cannabichromene in mouse liver. Trace amounts of the glucuronide conjugates of delta1- and delta1(6)-tetrahydrocannabinol (THC) were also detected. Identification was made by combined gas-liquid chromatographic and mass spectrometric studies of the trimethylsilyl (TMS), d9-TMS and methyl ester-TMS derivatives of the glucuronides and the TMS derivatives of the product of the reduction of the metabolites with lithium aluminium deuteride.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs do not influence the urinary testosterone/epitestosterone glucuronide ratio

Directory of Open Access Journals (Sweden)

Jonas eLundmark

2013-05-01

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

High-Throughput LC-MS/MS Method for Direct Quantification of Glucuronidated, Sulfated and Free Enterolactone in Human Plasma

DEFF Research Database (Denmark)

Nørskov, Natalja; Kyrø, Cecilie; Olsen, Anja

2016-01-01

Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized that ente......Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized......−MS/MS and a fluoroimmunoassay; however, most of these methods measure the total concentration of enterolactone, without any specification of its conjugation pattern. Here for the first time we present a high-throughput LC−MS/MS method to quantify enterolactone in its intact form as glucuronide, sulfate, and free enterolactone....... The method has shown good accuracy and precision at low concentration and very high sensitivity, with LLOQ for enterolactone sulfate at 16 pM, enterolactone glucuronide at 26 pM, and free enterolactone at 86 pM. The short run time of 2.6 min combined with simple sample clean up and high sensitivity make...

Bisphenol A glucuronidation in patients with Parkinson's disease.

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Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

2017-12-01

Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (pBisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.

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Pilar Galindo

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Determination of salbutamol and salbutamol glucuronide in human urine by means of liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Mareck, Ute; Guddat, Sven; Schwenke, Anne

2012-01-01

The determination of salbutamol and its glucuronide in human urine following the inhalative and oral administration of therapeutic doses of salbutamol preparations was performed by means of direct urine injection utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employing d(3...... glucuronide values between 8 and 15 ng/ml. The approach enabled the rapid determination of salbutamol and its glucuronic acid conjugate in human urine and represents an alternative to existing procedures since time-consuming hydrolysis or derivatization steps were omitted. Moreover, the excretion...

Use of positive ion fast atom bombardment mass spectrometry for rapid identification of a bile alcohol glucuronide isolated from cerebrotendinous xanthomatosis patients

International Nuclear Information System (INIS)

Dayal, B.; Salen, G.; Tint, G.S.; Shefer, S.; Benz, S.W.

1990-01-01

The identification of a major biliary and plasma bile alcohol glucuronide, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol-3-0-beta-D-glucuronide, present in cerebrotendinous xanthomatosis (CTX) patients, was investigated by positive ion fast atom bombardment mass spectrometry (FAB-MS). The spectrum was characterized by abundant ions formed by attachment of a proton, [M + H]+, or of alkali ions, [M + Na]+ and [M + 39K]+, to the glucuronide salt. These ions allowed an unambiguous deduction of the molecular weight of the sample. It is suggested that FAB-MS could be used in the rapid diagnosis of CTX

UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation.

Science.gov (United States)

Krishnaswamy, Soundararajan; Hao, Qin; Al-Rohaimi, Abdul; Hesse, Leah M; von Moltke, Lisa L; Greenblatt, David J; Court, Michael H

2005-06-01

UDP glucuronosyltransferase (UGT) 1A6 is a major isoform in human liver that glucuronidates numerous drugs, toxins, and endogenous substrates with high interindividual variability. The molecular basis for this variability remains unknown, although it likely involves genetic and environmental factors. Phenotype-genotype studies were conducted using a well characterized human liver bank (n = 54) and serotonin glucuronidation as a UGT1A6-specific phenotype marker. A positive moderate-to-heavy alcohol use history (>14 drinks per week) was the only demographic factor examined that correlated with phenotype and was associated with 2-fold higher serotonin glucuronidation (p g, -1310del5, and -652g-->a). Initial univariate analyses did not identify any significant phenotype-genotype associations. However, in livers without substantial alcohol exposure, 50% lower UGT1A6 mRNA levels (p = 0.026) were found in carriers of the linked S7A-enhancer polymorphisms compared with noncarriers but without significant effect on UGT1A6 protein content or glucuronidation activities. Three major haplotypes, including (*)1A (reference), (*)1B (-1535g-->a and -427g-->c), and (*)2 (-1710c-->g, -1310del5, -652g-->a, S7A, T181A, and R184S), were identified, accounting for 90% of alleles. No association of haplotype with any of the phenotype measures could be discerned. In conclusion, although the identified UGT1A6 polymorphisms did not explain the observed glucuronidation variability, there does seem to be a significant role for environmental factors associated with alcohol consumption.

Preparation and separation of the glucuronide and sulfate conjugates of thyroxine and triiodothyronine

International Nuclear Information System (INIS)

Hays, M.T.; Hsu, L.

1987-01-01

An enzymatic method for synthesis of labelled thyroxine glucuronide (T4G) and triiodothyronine glucuronide (T3G) from labelled thyroxine (T4) and triiodothyronine (T3) is presented. The synthetic glucuronides are completely digested by beta-glucuronidase, with recovery of the parent T4 or T3. They have distinctive elution patterns on HPLC and on Sephadex G25 chromatography, and can be clearly separated from T4 and T3 as well as from synthetic T4 sulfate (T4S) and T3 sulfate (T3S). On LH 20 chromatography, elution of T4G and T3G is intermediate between that of T4 and T3 and that of T4S and T3S. T3G can be well separated from other thyronines by HPLC alone, but T4G coelutes with rT3 on HPLC; these are then separated by adding a Sephadex G25 chromatography step. Biosynthetic 131 I-T3G and 125 I-T4G from the bile of a cat given 131 I-T3 and 125 I-T4 had similar HPLC chromatographic patterns to those of synthetic T3G and T4G. That the identified peaks from analysis of the bile were indeed T3G and T4G was confirmed by recovery of the parent T3 and T4 after beta-glucuronidase digestion

Dose-dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposure to 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl

Energy Technology Data Exchange (ETDEWEB)

Boyer, P.M.; Ndayibagira, A.; Spear, P.A.

2000-03-01

Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with tetratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer. Sexually mature brook trout were injected imtraperitoneally with the coplanar PCB 3,3{prime}, 4,4{prime}-tetrachlorobiphenyl (TCBP) and again 4 weeks later. At 8 weeks, retinoic acid metabolism was measured in liver microsomes. To the authors' knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rate of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over the dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 {micro}g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly greater production of 4-hydroxyretinoic acid at the 10 {micro}g/g dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greatest at the 1 {micro}g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitate/oleate were significantly decreased at the 5 and 10 {micro}g/g dose levels.

Is THC-COOH-glucuronide a useful marker for Tetrahydrocannabinol (THC) in DUID cases?

DEFF Research Database (Denmark)

Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

Is THC-COOH-glucuronide a useful marker for Tetrahydrocannabinol (THC) in DUID cases? Retrospective data analysis on UPLC-HR-TOFMS data files from 2 years of DUID cases. Telving R.(rt@forens.au.dk)*, Hasselstrøm J.B., Andreasen M.F. Department of Forensic Medicine, Aarhus University (Denmark......). Introduction The physical and chemical nature of THC makes it difficult to include in traditional screening procedures along with other common legal and illegal drugs. Development of multi-component toxicological screening procedures that include THC is therefore a challenge but also highly desirable in high...... throughput laboratories. Aims The aim of the present study was to evaluate the detection of THC indirectly by detecting the presence of THC-COOH-glucuronide in whole blood from individuals suspected of driving under the influence of drugs (DUID). We will compare existing data from THC screening...

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

Science.gov (United States)

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

1985-01-01

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.

Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination.

Science.gov (United States)

Miners, J O; Robson, R A; Birkett, D J

1984-01-01

The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differences between the groups in clofibric acid free fraction. Along with previous data the results suggest that induction of drug glucuronidation by OCS may be of clinical importance, although any sex-related differences are unlikely to be of clinical significance. PMID:6487463

Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants

NARCIS (Netherlands)

E.H.J. Krekels (Elke); S. Van Ham (Saskia); K.M. Allegaert (Karel); J.N. de Hoon; D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

2015-01-01

textabstractPurpose: Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling

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

Energy Technology Data Exchange (ETDEWEB)

Biber, F.Z. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey)]. E-mail: fazilet.zumrut.biber@ege.edu.tr; Unak, P. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey); Ertay, T. [Department of Nuclear Medicine, Faculty of Medicine, Dokuz Eylul University, Inciralti Izmir (Turkey); Medine, E.I. [Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, 35100 Bornova Izmir (Turkey); Zihnioglu, F. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey); Tasci, C. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey); Durak, H. [Department of Biochemistry, Faculty of Sciences, Ege University, 35100 Bornova Izmir (Turkey)

2006-07-15

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

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

DEFF Research Database (Denmark)

Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

2015-01-01

Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

Use of urinary pregnanediol 3-glucuronide to confirm ovulation.

Science.gov (United States)

Ecochard, R; Leiva, R; Bouchard, T; Boehringer, H; Direito, A; Mariani, A; Fehring, R

2013-10-01

Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM. Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility. After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days. The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine. Copyright © 2013 Elsevier Inc. All rights reserved.

Androstanediol glucuronide isomers in normal men and women and in men infused with labeled dihydrotestosterone

International Nuclear Information System (INIS)

Rittmaster, R.S.; Thompson, D.L.; Listwak, S.; Loriaux, D.L.

1988-01-01

3 alpha-Androstanediol glucuronide (Adiol G) is a major metabolite of dihydrotestosterone (DHT). Adiol G actually represents 2 different compounds, since the glucuronide can be conjugated at the 3-carbon position (Adiol 3-G) or at the 17-carbon position (Adiol 17-G). To determine which glucuronide represents the predominant physiological DHT metabolite and which isomer is the major circulating form, we developed a RIA to directly measure Adiol 3-G in serum extracts. In 10 normal men, mean serum Adiol 3-G and total Adiol G levels were 4.44 +/- 0.49 (+/- SE) nmol/L (208 +/- 23 ng/dL) and 27.9 +/- 2.8 nmol/L (1310 +/- 129 ng/dL), respectively (13.9 +/- 3.0% of Adiol G was Adiol 3-G). In 10 normal women sampled during the early follicular phase, mean serum Adiol 3-G and total Adiol G levels were 2.64 +/- 0.64 nmol/L (124 +/- 30 ng/dL) and 14.9 +/- 1.5 nmol/L (697 +/- 69 ng/dL), respectively (17.4 +/- 3.6% of Adiol G was Adiol 3-G). In 4 normal men infused for 8 h with tritiated DHT, 17.4 +/- 3.4% of the resulting tritiated Adiol G was Adiol 3-G. These results indicate that Adiol 17-G is the predominant circulating form of Adiol G in normal men and women and that it is also the major Adiol G isomer derived from DHT

Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases

NARCIS (Netherlands)

Beekmann, Karsten; Haan, De Laura H.J.; Actis-Goretta, Lucas; Bladeren, Van Peter J.; Rietjens, Ivonne M.C.M.

2016-01-01

To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the

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

International Nuclear Information System (INIS)

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

1984-01-01

The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E 3 G) and pregnanediol-3-glucuronide (P 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 3 G and P 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 3 G and P 2 G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit

Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.

Science.gov (United States)

Cook, Sarah F; Stockmann, Chris; Samiee-Zafarghandy, Samira; King, Amber D; Deutsch, Nina; Williams, Elaine F; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-11-01

This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CL formation ) of oxidative pathway metabolites. Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CL formation for all metabolites increased with weight; CL formation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CL formation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CL formation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CL formation increased paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

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

Science.gov (United States)

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

2015-06-24

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

Development of a UPLC–MS/MS method for determining ɣ-hydroxybutyric acid (GHB) and GHB glucuronide concentrations in hair and application to forensic cases

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Linnet, Kristian

2016-01-01

We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5.3). The co......We present a series of forensic cases measuring concentrations in hair of γ-hydroxybutyric acid (GHB) and its glucuronide. The compounds were extracted from hair by incubation for 1.5 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8 % acetonitrile, pH 5...... to detection of exogenous exposure. To our knowledge, this is the first report to present GHB glucuronide in human hair....

S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

DEFF Research Database (Denmark)

Mortensen, R. W.; Corcoran, O.; Cornett, Claus

2001-01-01

Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first or...

In vivo biological evaluation of 131I radiolabeled-paclitaxel glucuronide (131I-PAC-G)

International Nuclear Information System (INIS)

Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P.

2012-01-01

Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high β-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with 131 I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with 131 I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of 131 I-PAC-G was 84.30 ± 7.40% (n=10). The biodistribution of 131 I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that 131 I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that 131 I-PAC-G bears a therapy potential because of the 131 I radionuclide and can be improved with further investigations. (orig.)

Identification of 2,5-dimethyl-4-hydroxy-3[2H]-furanone beta-D-glucuronide as the major metabolite of a strawberry flavour constituent in humans.

Science.gov (United States)

Roscher, R; Koch, H; Herderich, M; Schreier, P; Schwab, W

1997-08-01

2,5-Dimethyl-4-hydroxy-3[2H]furanone (Furaneol, DMHF) [3658-77-3], an important flavour constituent of strawberry fruit, was administered to four male and two female volunteers using fresh strawberries as a natural DMHF source. The amount excreted was determined by measuring urinary levels of DMHF and DMHF glucuronide. DMHF glucuronide was synthesized and the structure elucidated by mens of 1H, 13C and two dimensional nuclear magnetic resonance, as well as mass spectral data. Identification and quantification of DMHF glucuronide in human urine were achieved after solid phase extraction on XAD-2 using reverse-phase reverse-phase HPLC with either on-line UV/VIS or electrospray tandem mass spectrometry detection. Male and female volunteers excreted 59-69% and 81-94%, respectively, of the DMHF dose (total of free and glycosidically bound DMHF in strawberries) as DMHF glucuronide in urine within 24 hr. The amount of DMHF excretion was independent of the dose size and the ratio of free to glycosidically bound forms of DMHF in strawberry fruit. DMHF, DMHF glucoside and its 6'-O-malonyl derivative, naturally occurring in strawberries, were not detected in human urine.

Effects of lactate and acetate on the determination of serum ethyl glucuronide by CZE

Czech Academy of Sciences Publication Activity Database

Mrázková, Michaela; Caslavska, J.; Thormann, W.; Křivánková, Ludmila

2006-01-01

Roč. 27, č. 23 (2006), s. 4772-4778 ISSN 0173-0835 R&D Projects: GA ČR GA203/05/2106; GA AV ČR IAA4031401; GA AV ČR IAA400310609 Institutional research plan: CEZ:AV0Z40310501 Keywords : acetate * CZE * ethyl glucuronide Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.101, year: 2006

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

Energy Technology Data Exchange (ETDEWEB)

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

1984-11-01

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

Evaluation of bisphenol A glucuronidation according to UGT1A1*28 polymorphism by a new LC–MS/MS assay

International Nuclear Information System (INIS)

Trdan Lušin, Tina; Roškar, Robert; Mrhar, Aleš

2012-01-01

The endocrine disruptor bisphenol A (BPA) is a frequently used chemical in the manufacture of consumer products. In humans, BPA is extensively metabolized to BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms. The study has been performed with the intention to improve the accuracy of published physiologically based pharmacokinetic models and to improve regulatory risk assessments of BPA. In order to gain insight into intestine, kidney, liver, and lung glucuronidation of BPA, human microsomes of all tested organs were used. BPAG formation followed Michaelis–Menten kinetics in the intestine and kidney, but followed substrate inhibition kinetics in the liver. Human lung microsomes did not show glucuronidation activity towards BPA. While the liver intrinsic clearance was very high (857 mL min −1 kg body weight −1 ), the tissue intrinsic clearances for the kidney and intestine were less than 1% of liver intrinsic clearance. Since BPA is a UGT1A1 substrate, we postulated that the common UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min −1 kg body weight −1 , respectively. Prior to microsomal experiments, the bioproduction of BPAG and stable isotope-labeled BPAG (BPAG d16 ) was performed for the purpose of the reliable and accurate quantification of BPAG. In addition, a sensitive LC–MS/MS analytical method for the simultaneous determination of BPA and BPAG based on two stable isotope-labeled internal standards was developed and validated. In conclusion, our in vitro results show that the liver is the main site of BPA glucuronidation (K m 8.9 μM, V max 8.5 nmol min −1 mg −1 ) and BPA metabolism may be significantly influenced by a person's genotype (K m 10.0–13.1 μM, V max 3.4–16.2 nmol min −1 mg −1 ). This discovery may be an important fact for the

Influence of renal function on the elimination of morphine and morphine glucuronides

DEFF Research Database (Denmark)

Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

1988-01-01

plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...... = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function....

Endogenous morphine-6-glucuronide (M6G) is present in the plasma of patients: validation of a specific anti-M6G antibody for clinical and basic research.

Science.gov (United States)

Laux-Biehlmann, Alexis; Chung, Hélène; Mouheiche, Jinane; Vérièpe, Julie; Delalande, François; Lamshöft, Marc; Welters, Ingeborg D; Soldevila, Stéphanie; Bazin, Hervé; Lamarque, Laurent; Van Dorsselaer, Alain; Poisbeau, Pierrick; Schneider, Francis; Goumon, Yannick; Garnero, Patrick

2014-01-01

Endogenous morphine and its derivatives (morphine-6-glucuronide [M6G]; morphine-3-glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the concentrations of endogenous morphine have been demonstrated in several pathologies (sepsis, Parkinson's disease, etc.), and they might be relevant as pathological markers. While endogenous morphine levels are detectable using enzyme-linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was, so far, the only approach to detect and quantify M6G. This study describes the preparation of a specific anti-M6G rabbit polyclonal antibody and its validation. The specificity of this antibody was assessed against 30 morphine-related compounds. Then, a M6G-specific ELISA-assay was tested to quantify M6G in the plasma of healthy donors, morphine-treated, and critically ill patients. The antibody raised against M6G displays a strong affinity for M6G, codeine-6-glucuronide, and morphine-3-6-glucuronide, whereas only weak cross-reactivities were observed for the other compounds. Both M6G-ELISA and LC-MS/MS approaches revealed the absence of M6G in the plasma of healthy donors (controls, n = 8). In all positive donors treated with morphine-patch (n = 5), M6G was detected using both M6G-ELISA and LC-MS/MS analysis. Finally, in a study on critically ill patients with circulating endogenous morphine (n = 26), LC-MS/MS analysis revealed that 73% of the positive-patients (19 of 26), corresponding to high M6G-levels in M6G-ELISA, contained M6G. In conclusion, we show that endogenous M6G can be found at higher levels than morphine in the blood of morphine-naive patients. With respect to the interest of measuring endogenous M6G in pathologies, we provide evidences that our ELISA procedure represents a powerful tool as it can easily and specifically detect endogenous M6G levels. © 2013 International Union of Biochemistry and Molecular Biology.

Forensic relevance of glucuronidation in phase-II-metabolism of alcohols and drugs.

Science.gov (United States)

Kaeferstein, Herbert

2009-04-01

Forensic toxicology means detecting toxic or pharmacologically active substances in body fluids and organs and the evaluation and judgement of the respective results. In the legal judgement, not only the taken in active drugs, but also their metabolites are to be included. Regarding metabolism one distinguishes phase-I- and phase-II-metabolism. In the phase-I-metabolism, active substances are converted by oxidation, reduction or hydrolysis, but influencing the polarity of more lipophilic substances often not decisively. The pharmacological activity is often preserved or even increased. In phase-II-metabolism a highly hydrophilic substance--mostly glucuronic acid--is coupled to the active substances or the respective phase-I-metabolites. This reaction step decisively increases hydrophilicity of lipophilic substances, thus enhancing renal elimination and often also abolishing pharmacologically and/or toxicologically effects. Nevertheless the interaction of different drugs and alcohols in glucuronidation and the glucuronides of phase-II-metabolism still do not play a substantial role in the forensic-toxicological analysis and interpretation of results so far. However, in vitro investigations since 1999 in our lab show that such interactions are not unlikely. For valid interpretation of complex cases in the future it may become necessary not only to quantify drugs and the phase-I-metabolites but also the phase-II-metabolites and discuss possible interactions in the metabolism.

Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair.

Science.gov (United States)

Meier, Ulf; Briellmann, Thomas; Scheurer, Eva; Dussy, Franz

2018-04-01

Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS 3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N-methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy-N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of clofibric acid on the biliary excretion of benoxaprofen glucuronide and taurine conjugate in rats.

Science.gov (United States)

Okada, K; Kanoh, H; Mohri, K

2011-10-01

Benoxaprofen (BOP) is a 2-methyl propionic acid derivative with anti-inflammatory activity. BOP has an asymmetric carbon, and receives chiral inversion from R to S in vivo. BOP is metabolized to glucuronide (BOP-G) and taurine conjugate (BOP-T). The configuration of BOP-G is mainly S, and that of BOP-T is R. Chiral inversion of R to S of the propionic acid moiety and amino acid conjugation of carboxyl compounds proceed via an acyl CoA intermediate. It is known that fibrates, used in hyperlipidemia, induce acyl CoA synthetase and increase CoA concentration. We administered racemic BOP (10 mg/kg body weight) to rats (CFA+) pre-administered clofibric acid (CFA, 280 mg/kg/day), and studied BOP, BOP-G, and BOP-T enantiomer concentrations in plasma and bile up to 12 h after administration. The findings were compared with those in rats (CFA-) that had not received CFA. Furthermore, we studied the amounts of BOP-G enantiomer produced by glucuronidation in vitro using microsomes pretreated with CFA. The amounts of (S)-BOP-G in CFA+ rats were 2.7-fold larger than that in CFA- rats. Although (R)-BOP-T was excreted in CFA- rats, BOP-T could not be detected in CFA+ rats. Plasma clearance values of racemic BOP and (S)-BOP in CFA+ rats were 5-fold and 6-fold larger than those in CFA- rats, respectively. (S)-BOP-G formation activities were higher than (R)-BOP-G formation activities in both CFA+and CFA- microsomes. These findings suggest that CFA increases biliary excretion of (S)-BOP-G and facilitates plasma elimination of BOP, and further suggests that CFA predominantly induces chiral inversion to S rather than metabolic reaction to (R)-BOP-T, resulting in an increase of (S)-BOP-G.

Analysis of ethyl glucuronide in human serum by capillary electrophoresis with sample self-stacking and indirect detection

Czech Academy of Sciences Publication Activity Database

Křivánková, Ludmila; Caslavska, J.; Malášková, Hana; Gebauer, Petr; Thormann, W.

2005-01-01

Roč. 1081, č. 1 (2005), s. 2-8 ISSN 0021-9673 R&D Projects: GA AV ČR IAA4031401 Institutional research plan: CEZ:AV0Z40310501 Keywords : ethyl glucuronide * capillary electrophoresis * serum Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.096, year: 2005

In vivo biological evaluation of {sup 131}I radiolabeled-paclitaxel glucuronide ({sup 131}I-PAC-G)

Energy Technology Data Exchange (ETDEWEB)

Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

2012-07-01

Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high {beta}-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with {sup 131}I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with {sup 131}I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of {sup 131}I-PAC-G was 84.30 {+-} 7.40% (n=10). The biodistribution of {sup 131}I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that {sup 131}I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that {sup 131}I-PAC-G bears a therapy potential because of the {sup 131}I radionuclide and can be improved with further investigations. (orig.)

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

Science.gov (United States)

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

2015-11-02

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

Identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-COOH-glu) in hair by ultra-performance liquid chromatography tandem mass spectrometry as a potential hair biomarker of cannabis use.

Science.gov (United States)

Pichini, Simona; Marchei, Emilia; Martello, Simona; Gottardi, Massimo; Pellegrini, Manuela; Svaizer, Fiorenza; Lotti, Andrea; Chiarotti, Marcello; Pacifici, Roberta

2015-04-01

We developed and validated an ultra-high-pressure liquid chromatography-tandem mass spectrometry method to identify and quantify 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in hair of cannabis consumers. After hair washing with methyl alcohol and diethyl ether and subsequent addition of amiodarone as internal standard hair samples were treated with 500 μl VMA-T M3 buffer reagent for 1 h at 100 °C. After cooling, 10 μl VMA-T M3 extract were injected into chromatographic system. Chromatographic separation was carried out on a reversed phase column using a linear gradient elution with two solvents: 5 mM ammonium formate pH 3.0 (solvent A) and 0.1% formic acid in acetonitrile (solvent B). The flow rate was kept constant at 0.4 ml/min during the analysis. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode via positive electrospray ionization. Linear calibration curves were obtained for 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide with correlation coefficients (r(2)) of 0.99 and a limit of quantification of 0.25 pg/mg hair. Analytical recovery was between 79.6% and 100.7% and intra- and inter-assay imprecision and inaccuracy were always lower than 15%. Ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of 20 different hair samples of cannabis consumers disclosed the presence of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in the range of 0.5-8.6 pg/mg hair. These data provided a good start to consider 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide as alternative hair biomarker of cannabis consumption. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Synthesis, isolation and identification of glucuronides and mercapturic acids of a novel antiparasitic agent, licochalcone A

DEFF Research Database (Denmark)

Nadelmann, L.; Tjornelund, J.; Hansen, S. H.

1997-01-01

-glucuronide conjugate of a beta-hydroxylated Lica metabolite. The metabolites were identified by hplc-nmr (one and two-dimensional nmr) as well as hplc-ms. 3. At pH 8.5 Lica reacted with N-acetyl-L-cysteine giving the two epimeric conjugates, which were then isolated by preparative hplc and identified by one and two...

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

Science.gov (United States)

Zonja, Bozo; Pérez, Sandra; Barceló, Damià

2016-01-05

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

Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

OpenAIRE

Choudhury, Ambar K.; Raja, Suganya; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

2015-01-01

Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated co...

Inhalation but not transdermal resorption of hand sanitizer ethanol causes positive ethyl glucuronide findings in urine.

Science.gov (United States)

Arndt, Torsten; Schröfel, Stefanie; Güssregen, Brunhilde; Stemmerich, Karsten

2014-04-01

Ethyl glucuronide (EtG) in urine is considered a specific marker of recent ethanol consumption. There is an ongoing debate about whether inhalation or transdermal resorption of sanitizer ethanol is the underlying cause for positive EtG findings after hand disinfection. Desderman(®) pure (Schülke & Mayr GmbH, Norderstedt) with 78.2g 96% (v/v) ethanol/100g and approx. 10% 2-propanol was used for multiple hand disinfection without and under an exhauster. Simulating a common working day in a clinic, 5 co-workers of our lab used the sanitizer 32 fold within 8h and 2 persons were merely exposed to the sanitizer vapor but without any dermal sanitizer contact. Any additional ethanol intake or exposition was reliably excluded. Spot urine was collected at baseline, after 1, 2, 4, 6 … 14, and finally 24h after the first sanitizer use. A validated LC-MS/MS was used for MRM and MS(3) of EtG and qualitative analyses of ethyl sulfate and 2-propyl glucuronide. Multiple hand disinfection caused positive EtG findings of up to 2.1mg/L or 1.7mg/g creatinine in 4 out of 5 test persons and even of 0.6mg/L or 0.8mg/g for 2 controls which were merely exposed to the sanitizer vapor but without any sanitizer contact. EtG results between the clinical (0.5mg/g) and the forensic (0.1mg/g) cut-off were obtained even 6h after the last sanitizer exposition. An exhauster prevented the sanitizer vapor inhalation and reduced the EtG excretion to mostly below the detection limit of 0.02mg/g. The maximum value was 0.09mg/g. Ethyl sulfate and 2-propyl glucuronide (2-PpG) were detectable only in the EtG positive samples. 2-PpG is a metabolite of 2-propanol, which is quite frequently used in disinfectants. Thus, the detection of this substance can be used in cases of odd EtG results as an indicator of (unintended) sanitizer exposition. Ethanol from hand sanitizers is predominantly incorporated by the respiratory tract but not via the skin. It can cause a distinct ethyl glucuronide excretion and thus

Quantification of Cannabinoids and their Free and Glucuronide Metabolites in Whole Blood by Disposable Pipette Extraction and Liquid Chromatography Tandem Mass Spectrometry

Science.gov (United States)

Scheidweiler, Karl B.; Newmeyer, Matthew N.; Barnes, Allan J.; Huestis, Marilyn A.

2016-01-01

Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1 h for cannabidiol (CBD) and cannabinol (CBN) and THC-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4 h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8 h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200 μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100 μg/L for THC and THCCOOH; 0.5-50 μg/L for 11-OH-THC, CBD, CBN, and THC-glucuronide; 1-50 μg/L for CBG, THCV, and THCVCOOH; and 5-500 μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and −25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. PMID:27236483

A MONOCLONAL ANTIBODY-BETA-GLUCURONIDASE CONJUGATE AS ACTIVATOR OF THE PRODRUG EPIRUBICIN-GLUCURONIDE FOR SPECIFIC TREATMENT OF CANCER

NARCIS (Netherlands)

Haisma, Hidde; BOVEN, E; VANMUIJEN, M; DEJONG, J; VANDERVIJGH, WJF; PINEDO, HM

The anti-pan carcinoma monoclonal antibody (MAb) 323/A3, linked to E. coli-derived beta-glucuronidase (GUS) was used to study the tumour-site-selective activation of the prodrug Epirubicin-glucuronide (Epi-glu). Epi-glu was isolated from the urine of patients treated with Epirubicin (Epi) by

Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination.

OpenAIRE

Miners, J O; Robson, R A; Birkett, D J

1984-01-01

The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differ...

Enzymatic synthesis of {sup 125/131}I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence

Energy Technology Data Exchange (ETDEWEB)

Yesilagac, Reyhan [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Unak, Perihan, E-mail: perihan.unak@ege.edu.t [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Medine, E. Ilker; Ichedef, Cigdem A. [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey); Ertay, Turkan [Dokuz Eyluel University, Medical School, Department of Nuclear Medicine, Inciralti, Izmir (Turkey); Mueftueler, F.Z. Biber [Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir (Turkey)

2011-02-15

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

Antioxidative Flavonol Glucuronides and Anti-HBsAg Flavonol from Rotala rotundifolia

Directory of Open Access Journals (Sweden)

Li-Jie Zhang

2011-10-01

Full Text Available Two new flavonol glucuronides, quercetin 3-O-β-d-2″-acetylglucuronide (1 and quercetin 3-O-β-d-2″-acetylglucuronide methyl ester (2, along with four known flavonoids (3-6 were isolated from the whole parts of Rotala rotundifolia. The structures of 1 and 2 were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques. Biological evaluation showed that all of isolated flavonoid compounds have potent anti-oxidative activities by DPPH and superoxide anion methods, and kaempferol (3 and quercetin (4 exhibited significant anti-HBV activity assayed by anti-HBsAg production. The HPLC fingerprint with photodiode array detection (HPLC-DAD for quality control of R. rotundifolia partitioned EtOAc layer was also established.

A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction to simultaneously determine trans-resveratrol and its glucuronide and sulfate conjugates in rat plasma and its application to pharmacokinetic assay.

Science.gov (United States)

Qiu, Zhixia; Yu, Jiaojiao; Dai, Yu; Yang, Yue; Lu, Xiaoyu; Xu, Jiaqiu; Qin, Zhiying; Huang, Fang; Li, Ning

2017-11-01

A simple LC-MS/MS method facilitated by salting-out assisted liquid-liquid extraction (SALLE) was applied to simultaneously investigate the pharmacokinetics of trans-resveratrol (Res) and its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile-methanol (80:20, v/v) and ammonium acetate (10 mol L -1 ) were used as extractant and salting-out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC-MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (>85%) and low variation of precision (extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg kg -1 ; intravenous, 10 mg kg -1 ). The systemic exposures to Res conjugates were much higher than those to Res (AUC 0-t , i.v., 7.43 μm h; p.o., 8.31 μm h); Res-3-O-β-d-glucuronide was the major metabolite (AUC 0-t , i.v., 66.1 μm h; p.o., 333.4 μm h). The bioavailability of Res was estimated to be ~22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio-samples. Copyright © 2017 John Wiley & Sons, Ltd.

An evaluation of the DRI-ETG EIA method for the determination of ethyl glucuronide concentrations in clinical and post-mortem urine.

Science.gov (United States)

Turfus, Sophie C; Vo, Tu; Niehaus, Nadia; Gerostamoulos, Dimitri; Beyer, Jochen

2013-06-01

A commercial enzyme immunoassay for the qualitative and semi-quantitative measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902 analyzer. The determined concentrations were compared with those obtained using a previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5 µg/ml and LC-MS/MS limit of reporting of 0.1 µg/ml, there was a sensitivity of 60.8% and a specificity of 100% for clinical samples. For post-mortem samples, sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the cut-off to 0.1 µg/ml, the sensitivity and specificity were 83.3% and 100% for clinical samples whereas for post-mortem samples the sensitivity and specificity were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 µg/ml were achieved when using immunoassay cut-offs of 0.3 and 0.092 µg/ml, respectively. There was good correlation between quantitative results obtained by both methods but analysis of samples by LC-MS/MS gave higher concentrations than by enzyme immunoassay (EIA), with a statistically significant proportional bias (P<0.0001, Deming regression) for both sample types. The immunoassay is reliable for the qualitative and semi-quantitative presumptive detection of ethyl glucuronide in urine. Copyright © 2012 John Wiley & Sons, Ltd.

Species differences in the biotransformation of an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist: the effects of distinct glucuronide metabolites on overall compound disposition.

Science.gov (United States)

Shaffer, Christopher L; Gunduz, Mithat; Ryder, Tim F; O'Connell, Thomas N

2010-02-01

The metabolism and disposition of (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-3-benzazepine (1), an alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist, was investigated in Sprague-Dawley rats and cynomolgus monkeys receiving (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-4[(14)C]-3- benzazepine hydrochloride ([(14)C]1) orally. Although both species chiefly (>or=62%) cleared 1 metabolically, species-specific dispositional profiles were observed for both 1 and total radioactivity. Radioactivity was excreted equally in the urine and feces of intact rats but largely (72%) in bile in bile duct-cannulated animals. In monkeys, radioactivity recoveries were 50-fold greater in urine than feces and minimal (<5%) in bile. Both species metabolized 1 similarly: four-electron oxidation to one of four amino acids or two lactams (minor) and glucuronide formation (major). In rats, the latter pathway predominantly formed an N-carbamoyl glucuronide (M6), exclusively present in bile (69% of dose), whereas in monkeys it afforded an N-O-glucuronide (M5), a minor biliary component (4%) but the major plasma (62%) and urinary (42%) entity. In rats, first-pass hepatic conversion of 1 to M6, which was confirmed in rat hepatocytes, and its biliary secretion resulted in the indirect enterohepatic cycling of 1 via M6 and manifested in double-humped plasma concentration-time curves and long t(1/2) for both 1 and total radioactivity. In monkeys, in which only M5 was formed, double-humped plasma concentration-time curves were absent, and moderate t(1/2) for both 1 and total radioactivity were observed. A seemingly subtle, yet critical, difference in the chemical structures of these two glucuronide metabolites considerably affected the overall disposition of 1 in rats versus monkeys.

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-01-01

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

Social motivation in prospective memory: higher importance ratings and reported performance rates for social tasks.

Science.gov (United States)

Penningroth, Suzanna L; Scott, Walter D; Freuen, Margaret

2011-03-01

Few studies have addressed social motivation in prospective memory (PM). In a pilot study and two main studies, we examined whether social PM tasks possess a motivational advantage over nonsocial PM tasks. In the pilot study and Study 1, participants listed their real-life important and less important PM tasks. Independent raters categorized the PM tasks as social or nonsocial. Results from both studies showed a higher proportion of tasks rated as social when important tasks were requested than when less important tasks were requested. In Study 1, participants also reported whether they had remembered to perform each PM task. Reported performance rates were higher for tasks rated as social than for those rated as nonsocial. Finally, in Study 2, participants rated the importance of two hypothetical PM tasks, one social and one nonsocial. The social PM task was rated higher in importance. Overall, these findings suggest that social PM tasks are viewed as more important than nonsocial PM tasks and they are more likely to be performed. We propose that consideration of the social relevance of PM will lead to a more complete and ecologically valid theoretical description of PM performance. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Rich or poor: Who should pay higher tax rates?

Science.gov (United States)

Murilo Castro de Oliveira, Paulo

2017-08-01

A dynamic agent model is introduced with an annual random wealth multiplicative process followed by taxes paid according to a linear wealth-dependent tax rate. If poor agents pay higher tax rates than rich agents, eventually all wealth becomes concentrated in the hands of a single agent. By contrast, if poor agents are subject to lower tax rates, the economic collective process continues forever.

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

NARCIS (Netherlands)

Sesink, A.L.A.; Arts, I.C.W.; Boer, de V.C.J.; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

NARCIS (Netherlands)

Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Doping test results dependent on genotype of uridine diphospho-glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation.

Science.gov (United States)

Schulze, Jenny Jakobsson; Lundmark, Jonas; Garle, Mats; Skilving, Ilona; Ekström, Lena; Rane, Anders

2008-07-01

Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. The large variation in testosterone glucuronide (TG) excretion and its strong association with a deletion polymorphism in the uridine diphospho-glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio test. Our objective was to investigate whether genotype-based cutoff values will improve the sensitivity and specificity of the test. This was an open three-armed comparative study. A total of 55 healthy male volunteers with either two, one, or no allele [insertion/insertion, insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was included in the study. A single im dose of 500 mg testosterone enanthate was administered. Urinary excretion of TG after dose and the T/E ratio during 15 d were calculated. The degree and rate of increase in the TG excretion rate were highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the insertion/insertion group compared with the del/del group. Of the del/del subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the dose. When differentiated cutoff levels for the del/del (1.0) and the other genotypes (6.0) were applied, the sensitivity increased substantially for the del/del group, and false positives in the other genotypes were eliminated. Consideration of the genetic variation in disposition of androgens will improve the sensitivity and specificity of the testosterone doping test. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society.

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

DEFF Research Database (Denmark)

Syed, Muzeeb; Srinivas, Nuggehally R

2016-01-01

Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

beta-Glucuronidase-resistant bilirubin glucuronide isomers in cholestatic liver disease--determination of bilirubin metabolites in serum by means of high-pressure liquid chromatography

NARCIS (Netherlands)

Jansen, P. L.

1981-01-01

"Direct reacting bilirubin" in serum of patients with cholestatic liver disease and in serum of bile duct-ligated rats consists of a complex mixture of bilirubin metabolites. These metabolites were studied by means of high-pressure liquid chromatography. Bilirubin glucuronides in normal bile are

LC-H-1 NMR used for determination of the elution order of S-naproxen glucuronide isomers in two isocratic reversed-phase LC-systems

DEFF Research Database (Denmark)

Mortensen, R. W.; Corcoran, O.; Cornett, Claus

2001-01-01

. In both systems the elution order for the 2-, 3- and 4-O-acyl isomers corresponded with previously published results for 2-, 3-, and 4-fluorobenzoic acid glucuronide isomers determined by reversed phase HPLC-H-1 NMR [U.G. Sidelmann, S.H. Hansen, C. Gavaghan, A.W. Nicholls, H.A.J. Carless, J.C. Lindon, I...

Introduction of sample tubes with sodium azide as a preservative for ethyl glucuronide in urine.

Science.gov (United States)

Luginbühl, Marc; Weinmann, Wolfgang; Al-Ahmad, Ali

2017-09-01

Ethyl glucuronide (EtG) is a direct alcohol marker, which is widely used for clinical and forensic applications, mainly for abstinence control. However, the instability of EtG in urine against bacterial degradation or the post-collectional synthesis of EtG in contaminated samples may cause false interpretation of EtG results in urine samples. This study evaluates the potential of sodium azide in tubes used for urine collection to hinder degradation of ethyl glucuronide by bacterial metabolism taking place during growth of bacterial colonies. The tubes are part of a commercial oral fluid collection device. The sampling system was tested with different gram-positive and gram-negative bacterial species previously observed in urinary tract infections, such as Escherichia coli, Staphylococcus aureus, Enterecoccus faecalis, Staphylococcus epidermidis, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Inhibition of bacterial growth by sodium azide, resulting in lower numbers of colony forming units compared to control samples, was observed for all tested bacterial species. To test the prevention of EtG degradation by the predominant pathogen in urinary tract infection, sterile-filtered urine and deficient medium were spiked with EtG, and inoculated with E. coli prior to incubation for 4 days at 37 °C in tubes with and without sodium azide. Samples were collected every 24 hours, during four consecutive days, whereby the colony forming units (CFU) were counted on Columbia blood agar plates, and EtG was analyzed by LC-MS/MS. As expected, EtG degradation was observed when standard polypropylene tubes were used for the storage of contaminated samples. However, urine specimens collected in sodium azide tubes showed no or very limited bacterial growth and no EtG degradation. As a conclusion, sodium azide is useful to reduce bacterial growth of gram-negative and gram-positive bacteria. It inhibits the degradation of EtG by E. coli and can be used for

Higher rates of sex evolve in spatially heterogeneous environments.

Science.gov (United States)

Becks, Lutz; Agrawal, Aneil F

2010-11-04

The evolution and maintenance of sexual reproduction has puzzled biologists for decades. Although this field is rich in hypotheses, experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations; other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination and selfing. However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high- or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs. Counter to some alternative theories for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations.

Bioavailability of {sup 99m}Tc-paclitaxel-glucuronide ({sup 99m}Tc-PAC-G)

Energy Technology Data Exchange (ETDEWEB)

Biber Muftuler, F.Z.; Demir, I.; Uenack, P.; Ichedef, C.; Yurt Kilcar, A. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

2011-07-01

An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound (paclitaxel-glucuronide (PAC-G)) was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with {sup 99m}Tc and the radiochemical yield of radiolabeled compound ({sup 99m}Tc-PAC-G) was 98.0 {+-} 02.74% (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240 min. All these experimental studies indicate that {sup 99m}Tc-PAC-G may potentially be used in breast tissue as an imaging agent. (orig.)

Enabling Higher Data Rates for Planetary Science Missions

Science.gov (United States)

Deutsch, L. J.; Townes, S. A.; Lazio, J.; Bell, D. J.; Chahat, N. E.; Kovalik, J. M.; Kuperman, I.; Sauder, J.; Liebrecht, P. E.

2017-12-01

The data rate from deep space spacecraft has increased by more than 10 orders of magnitude since the first lunar missions in the 1960s. The demand for increased data rates has stemmed from the increasing sophistication of the science questions being addressed and the concomitant increase in the complexity of the missions themselves (from fly-by to orbit to land and rove). Projections for the next few decades suggest the demand for data rates for deep space missions will continue to increase by approximately one order of magnitude every decade, driven by these same factors. Achieving higher data rates requires a partnership between the spacecraft and the ground system. We describe a series of technology developments for flight telecommunications systems, both at radio frequency (RF) and optical, to enable spacecraft to transmit and receive larger data volumes. These technology developments include deployable high gain antennas for small spacecraft, re-programmable software-defined radios, and optical communication packages designed for CubeSat form factors. The intent is that these developments would provide enhancements in capability for both spacecraft-Earth and spacecraft-spacecraft telecommunications. We also describe the future planning for NASA's Deep Space Network (DSN), which remains the prime conduit for data from all planetary science missions. Through a combination of new antennas and backends being installed over the next five years and incorporation of optical communications, the DSN aims to ensure that the historical improvements in data rates and volumes will continue for many decades. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.

Deposition of ethyl glucuronide in WHP rat hair after chronic ethanol intake.

Science.gov (United States)

Małkowska, Anna; Szutowski, Mirosław; Dyr, Wanda

2012-01-01

This study investigated the relationship between ethanol intake in rats and the resulting level of ethyl glucuronide (EtG) in rat hair. Rats (n = 50) consumed a 10% ethanol solution for 4 weeks, then EtG was extracted from samples of their hair using a novel extraction procedure involving freezing and thawing. The EtG concentration was measured using gas chromatography and mass spectrometry. The animals voluntarily drank ethanol, with daily consumption in most rats exceeding 5 g/kg b.w. The silylated EtG was stable for at least 28 h. The limit of detection was 0.03 ng/mg, and the limit of quantification was 0.1 ng/mg. Hair samples from rats that consumed ethanol had EtG levels ranging from 0.17-20.72 ng/mg in female rats and 0.15-13.72 ng/mg in males. There was a correlation between the amount of alcohol consumed and the EtG levels in hair from female (p < 0.01), but not male, rats. The method presented allows detection and quantification of EtG in rat hair. We also observed differences in EtG deposition in male and female rats.

United States private schools have higher rates of exemptions to school immunization requirements than public schools.

Science.gov (United States)

Shaw, Jana; Tserenpuntsag, Boldtsetseg; McNutt, Louise-Anne; Halsey, Neal

2014-07-01

To compare medical, religious, and personal belief immunization exemption rates between private and public schools in US. Exemption rates were calculated using the Centers for Disease Control and Prevention School Immunization Assessment Surveys for the 2009-2010 school year excluding states with incomplete survey data. Standardized exemption rates weighted on enrollments in public and private schools were calculated. Differences in exemption rates between public and private schools were tested using Wilcoxon signed rank test. The overall state exemption rate was higher in US private than public schools, 4.25% (SD 4.27) vs 1.91% (1.67), P = .0001 and private schools had higher exemption rates for all types of exemptions; medical 0.58% (0.71) vs 0.34% (0.34) respectively (P = .0004), religious 2.09% (3.14) vs 0.83% (1.05) respectively (P = .0001), and personal belief 6.10% (4.12) vs 2.79% (1.57), respectively (P = .006). Overall exemption rates were significantly higher in states that allowed personal belief exemptions. Exemption rates were significantly higher in US private than in public schools. Children attending private schools may be at higher risk of vaccine-preventable diseases than public school children. Copyright © 2014 Elsevier Inc. All rights reserved.

Vastus Lateralis Motor Unit Firing Rate Is Higher in Women With Patellofemoral Pain.

Science.gov (United States)

Gallina, Alessio; Hunt, Michael A; Hodges, Paul W; Garland, S Jayne

2018-05-01

To compare neural drive, determined from motor unit firing rate, in the vastus medialis and lateralis in women with and without patellofemoral pain. Cross-sectional study. University research laboratory. Women (N=56) 19 to 35 years of age, including 36 with patellofemoral pain and 20 controls. Not applicable. Participants sustained an isometric knee extension contraction at 10% of their maximal voluntary effort for 70 seconds. Motor units (N=414) were identified using high-density surface electromyography. Average firing rate was calculated between 5 and 35 seconds after recruitment for each motor unit. Initial firing rate was the inverse of the first 3 motor unit interspike intervals. In control participants, vastus medialis motor units discharged at higher rates than vastus lateralis motor units (P=.001). This was not observed in women with patellofemoral pain (P=.78) because of a higher discharge rate of vastus lateralis compared with control participants (P=.002). No between-group differences were observed for vastus medialis (P=.93). Similar results were obtained for the initial motor unit firing rate. These findings suggest that women with patellofemoral pain have a higher neural drive to vastus lateralis but not vastus medialis, which may be a contributor of the altered patellar kinematics observed in some studies. The different neural drive may be an adaptation to patellofemoral pain, possibly to compensate for decreased quadriceps force production, or a precursor of patellofemoral pain. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.

Science.gov (United States)

Sell, David R; Nemet, Ina; Liang, Zhili; Monnier, Vincent M

2018-04-01

LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes. The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs). We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid. LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC). Advanced NMR techniques ( 1 H-NMR, 13 C-NMR, 1 H- 13 C HSQC, 1 H- 1 H TOCSY, 1 H- 13 C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1. To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS. Only glucuronidase could cleave the sugar from the parent molecule. These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications". Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.

A higher chest compression rate may be necessary for metronome-guided cardiopulmonary resuscitation.

Science.gov (United States)

Chung, Tae Nyoung; Kim, Sun Wook; You, Je Sung; Cho, Young Soon; Chung, Sung Phil; Park, Incheol

2012-01-01

Metronome guidance is a simple and economical feedback system for guiding cardiopulmonary resuscitation (CPR). However, a recent study showed that metronome guidance reduced the depth of chest compression. The results of previous studies suggest that a higher chest compression rate is associated with a better CPR outcome as compared with a lower chest compression rate, irrespective of metronome use. Based on this finding, we hypothesized that a lower chest compression rate promotes a reduction in chest compression depth in the recent study rather than metronome use itself. One minute of chest compression-only CPR was performed following the metronome sound played at 1 of 4 different rates: 80, 100, 120, and 140 ticks/min. Average compression depths (ACDs) and duty cycles were compared using repeated measures analysis of variance, and the values in the absence and presence of metronome guidance were compared. Both the ACD and duty cycle increased when the metronome rate increased (P = .017, metronome rates of 80 and 100 ticks/min were significantly lower than those for the procedures without metronome guidance. The ACD and duty cyle for chest compression increase as the metronome rate increases during metronome-guided CPR. A higher rate of chest compression is necessary for metronome-guided CPR to prevent suboptimal quality of chest compression. Copyright © 2012 Elsevier Inc. All rights reserved.

Aldosterone glucuronidation inhibition as a potential mechanism for arterial dysfunction associated with chronic celecoxib and diclofenac use in patients with rheumatoid arthritis.

Science.gov (United States)

Crilly, Michael A; Mangoni, Arduino A; Knights, Kathleen M

2013-01-01

Adverse cardiovascular (CV) effects of non-steroidal anti-inflammatory drugs (NSAIDs) are largely independent of their cyclooxygenase (COX) enzyme selectivity, but could be a consequence of aldosterone 18ß-glucuronidation inhibition (AGI), which varies between NSAIDS. This study assesses the chronic effects of celecoxib (selective COX-2 inhibitor) versus diclofenac (non-selective NSAID) therapy on arterial dysfunction in patients with rheumatoid arthritis (RA). AGI was assessed in vitro using human kidney cortical microsomes. Arterial function was measured clinically as the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWTT, msec) of arterial wave reflection using radial applanation pulse wave analysis (SphygmoCor PWA device) in 39 RA patients without overt CV disease aged 40-65. A higher AIX% (and lower RWTT) indicates arterial dysfunction. Clinical assessment on a single occasion included a fasting blood sample, patient questionnaire and medical record review. Multivariable analysis was used to adjust for sex, mean blood pressure, arthritis duration, cumulative ESR-years and current DMARD therapy. The inhibition constant (Ki) for celecoxib was lower than that of diclofenac (Ki, 3.5 vs. 8.4 μM). Chronic celecoxib use was associated with a higher AIX% (34.8 vs. 32.3) and lower RWTT (130.1 vs. 132.7 msec) compared with diclofenac. Adjusted mean differences were AIX% 4.7 (95%CI 0.6 to 8.9; p=0.03) and RWTT -3.6 (95%CI -10.0 to 2.7; p=0.26). Celecoxib has a greater potency for AGI than diclofenac and its use is associated with a significantly higher AIX%. Our findings support AGI as a plausible mechanism for the CV toxicity of NSAIDs.

In vitro inhibitory effects of major bioactive constituents of Andrographis paniculata, Curcuma longa and Silybum marianum on human liver microsomal morphine glucuronidation: A prediction of potential herb-drug interactions arising from andrographolide, curcumin and silybin inhibition in humans.

Science.gov (United States)

Uchaipichat, Verawan

2018-02-01

This study aimed to investigate the liver microsomal inhibitory effects of silybin, silychristin, andrographolide, and curcumin by using morphine as an in vitro UGT2B7 probe substrate, and predict the magnitude of the herb-drug interaction arising from these herbal constituents' inhibition in vivo. Studies were performed in the incubation with and without bovine serum albumin (BSA). Andrographolide and curcumin showed a marked inhibition on morphine 3- and 6-glucuronidation with IC 50 of 50&87 and 96&111 μM, respectively. In the presence of 2%BSA, andrographolide also showed a strong inhibition on morphine 3- and 6-glucuronidation (IC 50 4.4&21.6 μM) whereas curcumin showed moderate inhibition (IC 50 338&333 μM). In the absence and presence of 2%BSA, morphine 3- and 6-glucuronidation was moderately inhibited by silybin (IC 50 583&862 and 1252&1421 μM, respectively), however was weakly inhibited by silychristin (IC 50 3527&3504 and 1124&1530 μM, respectively). The K i of andrographolide, curcumin and silybin on morphine 3- and 6-glucuronidation were 7.1&9.5, 72.7&65.2, and 224.5&159.7 μM, respectively, while the respective values generated from the system containing 2%BSA were 2.4&3.1, 96.4&108.8, and 366.3&394.5 μM. Using the in vitro and in vivo extrapolation approach, andrographolide was herbal component that may have had a potential interaction in vivo when it was co-administered with morphine. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

Science.gov (United States)

Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

2016-07-01

Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

Science.gov (United States)

Watts, Eleanor L; Appleby, Paul N; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A; Holly, Jeff M P; Hoover, Robert N; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S; Ziegler, Regina G; Allen, Naomi E; Key, Timothy J; Travis, Ruth C

2017-01-01

Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a

Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

KAUST Repository

Zia, Asif I.; Mukhopadhyay, Subhas Chandra; Yu, Paklam; Al-Bahadly, Ibrahim H.; Yudhana, Anton; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

2013-01-01

A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle's equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

Ovarian Hormone Estrone Glucuronide (E1G) quantification-impedimetric electrochemical spectroscopy approach

KAUST Repository

Zia, Asif I.

2013-12-01

A study was conducted on detection and concentration measurement of estrone glucuronide (E1G), an important metabolite of the ovarian hormone estradiol, by using Electrochemical Impedance Spectroscopy (EIS) technique. A miniature planar Inter-digital (ID) capacitive sensor fabricated on single crystal silicon substrate with sputtered gold electrodes coupled with EIS was used to measure conductivity, permeability and dielectric properties of the said hormone metabolite. A thin film of Silicon Nitride (50 um) was coated on the sensor as passivation layer to avoid Faradic currents through the sensor. Impedance spectrums were obtained with various concentrations of E1G in buffer solution by exposing the samples to electrical perturbations at certain frequency range. Relationship of sample conductance with E1G concentration was studied on basis Randle\\'s equivalent circuit model and results were analyzed to deduce Constant Phase Equivalent (CPE) Circuit model in order to evaluate the double layer capacitance produced at the solution-electrode interface due to kinetic processes taking place in the electrochemical cell. The sensitivity of the sensor was evaluated against concentration. The result analysis confirmed that fabricated ID sensor together with EIS can provide a rapid and successful low cost sensing system which can help a lay user to determine peak time for feminine reproductive fertility at home without submitting samples for an expensive and time consuming laboratory test. © 2013 IEEE.

Strain rate effects in nuclear steels at room and higher temperatures

Energy Technology Data Exchange (ETDEWEB)

Solomos, G. E-mail: george.solomos@jrc.it; Albertini, C.; Labibes, K.; Pizzinato, V.; Viaccoz, B

2004-04-01

An investigation of strain rate, temperature and size effects in three nuclear steels has been conducted. The materials are: ferritic steel 20MnMoNi55 (vessel head), austenitic steel X6CrNiNb1810 (upper internal structure), and ferritic steel 26NiCrMo146 (bolting). Smooth cylindrical tensile specimens of three sizes have been tested at strain rates from 0.001 to 300 s{sup -1}, at room and elevated temperatures (400-600 deg. C). Full stress-strain diagrams have been obtained, and additional parameters have been calculated based on them. The results demonstrate a clear influence of temperature, which amounts into reducing substantially mechanical strengths with respect to RT conditions. The effect of strain rate is also shown. It is observed that at RT the strain rate effect causes up shifting of the flow stress curves, whereas at the higher temperatures a mild downshifting of the flow curves is manifested. Size effect tendencies have also been observed. Some implications when assessing the pressure vessel structural integrity under severe accident conditions are considered.

Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

Energy Technology Data Exchange (ETDEWEB)

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

2013-11-29

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

Why do younger women have higher breast cancer recurrence rates after breast-conserving surgery?

International Nuclear Information System (INIS)

Nishimura, Reiki; Matsuda, Masakazu; Miyayama, Haruhiko; Okazaki, Shinji; Kai, Chiharu; Ozaki, N.

2003-01-01

Preventing breast cancer recurrence after breast-conserving surgery is an important issue. The main factors contributing to such recurrence are positive margins, absence of radiotherapy and young age. To investigate the clinical significance of age in breast-conserving surgery, we examined the relationship between clinicopathological findings or outcome and age, especially young age. The cases were divided into three groups by age; 35 years old or less, 36-50y.o. and 51y.o. or higher. Between April 1989 and March 2003, 743 patients were treated with breast-conserving surgery. There were 49 patients aged 35 years old or less (6.6%). Younger age significantly correlated with positive surgical margin, lymph node metastases, higher proliferative activity, negative estrogen receptor (ER) or progesterone receptor (PgR), larger tumor size, and shorter nipple-tumor distances. Although younger patients had a higher recurrence rate irrespective of radiotherapy, margin status had an impact on recurrence rate. Thus, the reason young age was a significant factor for breast recurrence after breast-conserving surgery was that young patients frequently had numerous risk factors such as positive margin, higher proliferative activity, positive nodes, negative ER/PgR and larger tumor. However, negative surgical margins could reduce recurrence rates even in young women. These results suggest that more suitable criteria and strategies may be needed for young patients with breast cancer. (author)

Will ageing lead to a higher real exchange rate for the Netherlands?

NARCIS (Netherlands)

van Ewijk, C.; Volkerink, M.

2012-01-01

Long term projections for the Netherlands indicate that demand for nontradables—e.g. health care services—will increase relative to supply due to population ageing. If this leads to higher future real exchanges rates this will erode the return of the savings currently made to prepare for ageing.

Will ageing lead to a higher real exchange rate for the Netherlands?

NARCIS (Netherlands)

van Ewijk, C.; Volkerink, M.

2011-01-01

Long-term projections for the Netherlands indicate that demand for nontradables - e.g. health care services - will increase relative to supply due to population ageing. If this leads to higher future real exchanges rates this will erode the return of the savings currently made to prepare for ageing.

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

Science.gov (United States)

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

2009-07-01

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

Determination of Ethyl Glucuronide in Hair for Detection of Alcohol Consumption in Patients After Liver Transplantation.

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Andresen-Streichert, Hilke; von Rothkirch, Gregor; Vettorazzi, Eik; Mueller, Alexander; Lohse, Ansgar W; Frederking, Dorothea; Seegers, Barbara; Nashan, Bjoern; Sterneck, Martina

2015-08-01

Early detection of alcohol misuse in orthotopic liver transplantation recipients is essential to offer patients support and prevent organ damage. Here, ethyl glucuronide, a metabolite of ethanol found in hair (hEtG), was evaluated for detection of alcohol consumption. In 104 transplant recipients, 31 with underlying alcoholic liver disease (ALD) and 73 with non-ALD, hEtG was determined in addition to the alcohol markers urine EtG, blood ethanol, methanol, and carbohydrate-deficient transferrin. Results were compared with patients' self-reports in a questionnaire and with physicians' assessments. By physicians' assessments, 22% of the patients were suspected of consuming alcohol regularly, although only 6% of the patients acknowledged consumption of a moderate or high amount of alcohol. By testing all markers except for hEtG, alcohol consumption was detected in 7% of the patients. When hEtG testing was added to the assessment, consumption was detected in 17% of the patients. Hair-EtG determination alone revealed chronic alcohol consumption of >10 g/d in 15% of the patients. ALD patients had a positive hEtG result significantly more often than non-ALD patients did (32% versus 8%; P = 0.003). Also, the concentration of hEtG was higher in ALD patients (P = 0.049) and revealed alcohol abuse with consumption of >60 g ethanol per day in 23% of ALD and 3% of non-ALD patients. Patients' self-reports and physicians' assessments had a low sensitivity of 27% and 67%, respectively, for detecting regular alcohol intake as indicated by hEtG. Hair-EtG determination improved the detection of liver transplant patients who used alcohol, and revealed regular alcohol consumption in 32% of ALD and 8% of non-ALD patients.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

Directory of Open Access Journals (Sweden)

Eleanor L Watts

Full Text Available Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.Circulating sex hormones in men are strongly associated with age and body mass

UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes.

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Ghaoui, Roula; Sallustio, Benedetta C; Burcham, Philip C; Fontaine, Frank R

2003-05-06

Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide metabolites. These electrophilic species alkylate cell proteins and may be implicated in the pathogenesis of a number of toxic syndromes seen in patients receiving the parent aglycones. Whether acyl glucuronides also attack nuclear DNA is unknown, although the acyl glucuronide formed from clofibric acid was recently found to decrease the transfection efficiency of phage DNA and generate strand breaks in plasmid DNA in vitro. To determine if such a DNA damage occurs within a cellular environment, the comet assay (i.e. single-cell gel electrophoresis) was used to detect DNA lesions in the nuclear genome of isolated mouse hepatocytes cultured with clofibric acid. Overnight exposure to 50 microM and higher concentrations of clofibric acid produced concentration-dependent increases in the comet areas of hepatocyte nuclei, with 1 mM clofibrate producing a 3.6-fold elevation over controls. These effects closely coincided with culture medium concentrations of the glucuronide metabolite formed from clofibric acid, 1-O-beta-clofibryl glucuronide. Consistent with a role for glucuronidation in the DNA damage observed, the glucuronidation inhibitor borneol diminished glucuronide formation from 100 microM clofibrate by 98% and returned comet areas to baseline levels. Collectively, these results suggest that the acyl glucuronide formed from clofibric acid is capable of migrating from its site of formation within the endoplasmic reticulum to generate strand nicks in nuclear DNA.

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

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

2010-04-01

The application of the design of experiments to optimize method development in the field of forensic toxicology using the urinary morphine 3-glucuronide acid hydrolysis as an example is described. Morphine and its trideuterated analogue (used as an internal standard) were extracted from urine samples by liquid-liquid extraction (ToxiTubes A) and derivatized by silylation. Chromatographic analysis was done by gas chromatography-mass spectrometry in the selected ion monitoring mode. Using the peak area ratio (morphine-to-internal standard) as the response, we investigated the independent variables that could influence the acid hydrolysis, including temperature (range 70-130 degrees C), acid volume (range 500-1,000 microL) and time (range 15-90 min). A 2(3) full factorial design for the screening and a response surface methodology, including a central composite design for optimization, were applied. The factors which influenced the response to a greater extent were temperature and its interaction both with time and acid volume. By application of a multiple regression analysis to the experimental data, a second-order polynomial equation was obtained. The optimal predicted conditions for morphine 3-glucuronide acid hydrolysis were 115 degrees C, 38 min and 500 microL for temperature, time and acid volume, respectively. Using design of experiments, instead of the one factor at a time approach, we achieved the optimum combination of all factor values, and this allowed the best results to be obtained, simultaneously optimizing resources. In addition, time and money can be saved, since other approaches are in general more time-consuming and laborious, and do not take into account the interactions between factors.

Inhibitory Effects of Diclofenac on Steroid Glucuronidation In Vivo Do Not Affect Hair-Based Doping Tests for Stanozolol.

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Zachár, Gergely; Deshmukh, Naved I K; Petróczi, Andrea; Székely, Andrea D; Shah, Iltaf; Barker, James; Naughton, Declan P

2017-06-12

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3'-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair, which holds considerable advantages over urinalysis for anti-doping tests.

Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-β-Glucuronide.

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Varma, Manthena V S; Lin, Jian; Bi, Yi-an; Kimoto, Emi; Rodrigues, A David

2015-07-01

Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-O-β-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-O-β-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Development of an on-line solid phase extraction ultra-high-performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations.

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Grandin, Flore; Picard-Hagen, Nicole; Gayrard, Véronique; Puel, Sylvie; Viguié, Catherine; Toutain, Pierre-Louis; Debrauwer, Laurent; Lacroix, Marlène Z

2017-12-01

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL -1 for BPS and 10ngmL -1 for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids.

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Syed, Muzeeb; Srinivas, Nuggehally R

2016-05-01

Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings. Copyright © 2016 John Wiley & Sons, Ltd.

Does the Economic Crisis Have an Influence on the Higher Education Dropout Rate?

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Leão Fernandes, Graça; Chagas Lopes, Margarida

2016-01-01

This research aims to identify the effects of the economic crisis on higher education (HE) dropout rates at Lisbon School of Economics and Management (ISEG)--Universidade de Lisboa, after having controlled for individual characteristics, family background, High School and HE trajectories. Our main hypothesis is that the economic crisis induces…

Calm Merino ewes have a higher ovulation rate and more multiple pregnancies than nervous ewes.

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van Lier, E; Hart, K W; Viñoles, C; Paganoni, B; Blache, D

2017-07-01

In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; Pewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; Pewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

Energy Technology Data Exchange (ETDEWEB)

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree; Crowell, Susan R.; Corley, Richard A.

2017-03-01

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 µM), and higher intrinsic clearance at lower substrate concentrations (<0.07 µM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.

Continuous fermentation and in-situ reed separation of butyric acid for higher sugar consumption rate and productivity

DEFF Research Database (Denmark)

Baroi, George Nabin; Skiadas, Ioannis; Westermann, Peter

that disconnection of the REED system resulted to much lower (48 and 83% for glucose and xylose, respectively) sugars consumption rates and consequently lower butyric acid production rates. It was also noticeable that continuous operation, even without the REED system, resulted to higher glucose consumption rates...

Estimating diversification rates for higher taxa: BAMM can give problematic estimates of rates and rate shifts.

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Meyer, Andreas L S; Wiens, John J

2018-01-01

Estimates of diversification rates are invaluable for many macroevolutionary studies. Recently, an approach called BAMM (Bayesian Analysis of Macro-evolutionary Mixtures) has become widely used for estimating diversification rates and rate shifts. At the same time, several articles have concluded that estimates of net diversification rates from the method-of-moments (MS) estimators are inaccurate. Yet, no studies have compared the ability of these two methods to accurately estimate clade diversification rates. Here, we use simulations to compare their performance. We found that BAMM yielded relatively weak relationships between true and estimated diversification rates. This occurred because BAMM underestimated the number of rates shifts across each tree, and assigned high rates to small clades with low rates. Errors in both speciation and extinction rates contributed to these errors, showing that using BAMM to estimate only speciation rates is also problematic. In contrast, the MS estimators (particularly using stem group ages), yielded stronger relationships between true and estimated diversification rates, by roughly twofold. Furthermore, the MS approach remained relatively accurate when diversification rates were heterogeneous within clades, despite the widespread assumption that it requires constant rates within clades. Overall, we caution that BAMM may be problematic for estimating diversification rates and rate shifts. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Splenectomy is associated with higher infection and pneumonia rates among trauma laparotomy patients.

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Fair, Kelly A; Connelly, Christopher R; Hart, Kyle D; Schreiber, Martin A; Watters, Jennifer M

2017-05-01

Splenectomy increases lifetime risk of thromboembolism (VTE) and is associated with long-term infectious complications, primarily, overwhelming post-splenectomy infection (OPSI). Our objective was to evaluate risk of VTE and infection at index hospitalization post-splenectomy. Retrospective review of all patients who received a laparotomy in the NTDB. Propensity score matching for splenectomy was performed, based on ISS, abdominal abbreviated injury score >3, GCS, sex and mechanism. Major complications, VTE, and infection rates were compared. Multiple logistic regression models were utilized to evaluate splenectomy-associated complications. 93,221 laparotomies were performed and 17% underwent splenectomy. Multiple logistic regression models did not demonstrate an association between splenectomy and major complications (OR 0.96, 95% CI 0.91-1.03, p = 0.25) or VTE (OR 1.05, 95% CI 0.96-1.14, p = 0.33). Splenectomy was independently associated with infection (OR 1.07, 95% CI 1.00-1.14, p = 0.045). Subgroup analysis of patients with infection demonstrated that splenectomy was most strongly associated with pneumonia (OR 1.41, 95% CI 1.26-1.57, p Splenectomy is not associated with higher overall complication or VTE rates during index hospitalization. However, splenectomy is associated with a higher rate of pneumonia. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

Science.gov (United States)

Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

2016-10-01

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L-1 or 24625.1 ± 1563.8 mg·h·L-1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L-1 or 1394.6 ± 868.1 mg·h·L-1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

Higher Magnitude Cash Payments Improve Research Follow-up Rates Without Increasing Drug Use or Perceived Coercion

Science.gov (United States)

Festinger, David S.; Marlowe, Douglas B.; Dugosh, Karen L.; Croft, Jason R.; Arabia, Patricia L.

2008-01-01

In a prior study (Festinger et al., 2005) we found that neither the mode (cash vs. gift card) nor magnitude ($10, $40, or $70) of research follow-up payments increased rates of new drug use or perceptions of coercion. However, higher payments and payments in cash were associated with better follow-up attendance, reduced tracking efforts, and improved participant satisfaction with the study. The present study extended those findings to higher payment magnitudes. Participants from an urban outpatient substance abuse treatment program were randomly assigned to receive $70, $100, $130, or $160 in either cash or a gift card for completing a follow-up assessment at 6 months post-admission (n ≅ 50 per cell). Apart from the payment incentives, all participants received a standardized, minimal platform of follow-up efforts. Findings revealed that neither the magnitude nor mode of payment had a significant effect on new drug use or perceived coercion. Consistent with our previous findings, higher payments and cash payments resulted in significantly higher follow-up rates and fewer tracking calls. In addition participants receiving cash vs. gift cards were more likely to use their payments for essential, non-luxury purchases. Follow-up rates for participants receiving cash payments of $100, $130, and $160 approached or exceeded the FDA required minimum of 70% for studies to be considered in evaluations of new medications. This suggests that the use of higher magnitude payments and cash payments may be effective strategies for obtaining more representative follow-up samples without increasing new drug use or perceptions of coercion. PMID:18395365

Higher resting heart rate variability predicts skill in expressing some emotions.

Science.gov (United States)

Tuck, Natalie L; Grant, Rosemary C I; Sollers, John J; Booth, Roger J; Consedine, Nathan S

2016-12-01

Vagally mediated heart rate variability (vmHRV) is a measure of cardiac vagal tone, and is widely viewed as a physiological index of the capacity to regulate emotions. However, studies have not directly tested whether vmHRV is associated with the ability to facially express emotions. In extending prior work, the current report tested links between resting vmHRV and the objectively assessed ability to facially express emotions, hypothesizing that higher vmHRV would predict greater expressive skill. Eighty healthy women completed self-reported measures, before attending a laboratory session in which vmHRV and the ability to express six emotions in the face were assessed. A repeated measures analysis of variance revealed a marginal main effect for vmHRV on skill overall; individuals with higher resting vmHRV were only better able to deliberately facially express anger and interest. Findings suggest that differences in resting vmHRV are associated with the objectively assessed ability to facially express some, but not all, emotions, with potential implications for health and well-being. © 2016 Society for Psychophysiological Research.

Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies.

Science.gov (United States)

Xu, Beibei; Yang, Guanyi; Ge, Shufan; Yin, Taijun; Hu, Ming; Gao, Song

2013-11-01

The purpose of this study is to develop an UPLC-MS/MS method to quantify 3-hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG) from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1% formic acid in water as mobile phases. The mass analysis was performed in an API 5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive scan mood. The one-step protein precipitation by acetonitrile was used to extract the analytes from blood. The results showed that the linear response range was 0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than 15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than 20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%, accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10 μl of blood is needed due to the high sensitivity of this method. The validated method was successfully used to pharmacokinetic study in A/J mouse, transport study in the Caco-2 cell culture model, and glucuronidation study using mice liver and intestine microsomes. The applications revealed that this method can be used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers such HBSS and KPI. Copyright © 2013 Elsevier B.V. All rights reserved.

Monitoring people at risk of drinking by a rapid urinary ethyl glucuronide test

Directory of Open Access Journals (Sweden)

Fucci Nadia

2017-12-01

Full Text Available Alcohol and illicit drug abuse are major public health problems worldwide. Since alcohol is the predominant substance of choice in polydrug abusers, monitoring its use, along with urinary drug screening in patients in rehabilitation programs, appeared to be crucial in identifying patients at risk of alcohol disorders leading to impaired quality of life. Ethyl β-D-6-glucuronide, a non-oxidative, non-volatile, stable and minor direct ethanol metabolite, has a 6h to 4 day window of detection in urine after the last alcohol intake. Each of the 119 subjects (85 males, 34 females registered with the Public Health Service for Drug Dependence Treatment provided a urine sample for ethylglucoronide (EtG determination in an immunochemical test with a 500 ng/ml cutoff. All results were evaluated with confirmation criteria of a fully validated gas chromatography/mass spectrometry assay. The diagnostic performance of the EtG immunochemical test was assessed using Receiver Operating Characteristic Curve analysis. The immunochemical test specificity was 100% for EtG urinary values above 500 ng/ml. No false positive results were found. With levels below 500 ng/ml, 12% of the samples were classified as negative. The average consumption of the incorrectly classified subjects was 171 ng/ml, with a misclassification error of 6.5% to 18.5%. High agreement between EtG as determined in an immunochemical test and gas chromatography/mass spectrometry, suggests that the rapid EtG test is a reliable, cost-effective alcohol monitoring assay for patient management in many non-forensic settings, such as drug rehabilitation programs.

Concerns and perceptions immediately following Superstorm Sandy: ratings for property damage were higher than for health issues.

Science.gov (United States)

Burger, Joanna; Gochfeld, Michael

Governmental officials, health and safety professionals, early responders, and the public are interested in the perceptions and concerns of people faced with a crisis, especially during and immediately after a disaster strikes. Reliable information can lead to increased individual and community preparedness for upcoming crises. The objective of this research was to evaluate concerns of coastal and central New Jersey residents within the first 100 days of Superstorm Sandy's landfall. Respondents living in central New Jersey and Jersey shore communities were differentially impacted by the storm, with shore residents having higher evacuation rates (47% vs. 13%), more flood waters in their homes, longer power outages (average 23 vs. 6 days), and longer periods without Internet (29 vs. 6 days). Ratings of concerns varied both among and within categories as a function of location (central vs. coastal New Jersey), stressor level (ranging from 1 to 3 for combinations of power outages, high winds, and flooding), and demographics. Respondents were most concerned about property damage, health, inconveniences, ecological services, and nuclear power plants in that order. Respondents from the shore gave higher ratings to the concerns within each major category, compared to those from central Jersey. Four findings have implications for understanding future risk, recovery, and resiliency: (1) respondents with the highest stressor level (level 3) were more concerned about water damage than others, (2) respondents with flood damage were more concerned about water drainage and mold than others, (3) respondents with the highest stressor levels rated all ecological services higher than others, and (4) shore respondents rated all ecological services higher than central Jersey residents. These data provide information to design future preparedness plans, improve resiliency for future severe weather events, and reduce public health risk.

Reduction Rates for Higher Americium Oxidation States in Nitric Acid

Energy Technology Data Exchange (ETDEWEB)

Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-09-30

The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair.

Science.gov (United States)

Martins Ferreira, Liliane; Binz, Tina; Yegles, Michel

2012-05-10

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE), non-volatile, direct metabolites of ethanol have been shown to be suitable markers for the evaluation of social and chronic excessive alcohol consumption. Previous investigations have shown that the regular use of hair-care products with high alcohol content lead to an increase of FAEE concentration and consequently gave false-positive results for the determination of FAEE in hair. In this study we investigated the influence of a long-term hair treatment with EtOH containing lotion, on the EtG concentrations in hair. In this study 7 volunteer subjects (classified as either rare, social or heavy drinkers) treated the right side of their scalp every day during a one or two month period with a commercial hair tonic (Seborin), which contains 44.0% ethanol (vol%). Collection of hair specimens from both sides of the scalp was done one day before hair treatment, one week and one month after treatment (for 5 subjects also after two months of treatment). A hair segment of 3 centimeters (cm) was cut and then washed with water and acetone, and then pulverized. EtG was quantified by GC/MS after pulverization and 2h of ultrasonication in water, extraction by solid phase extraction using Oasis MAX columns and derivatization with HFBA. Measurements were done in negative chemical ionization mode using EtG-D5 as internal standard. Comparison of EtG concentration in the treated and in the non-treated hair specimens did not show any increase at the different dates of collection for the 7 subjects. In conclusion, these results show that there is no indication for an increase of EtG after use of ethanol containing hair cosmetics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

With age a lower individual breathing reserve is associated with a higher maximal heart rate.

Science.gov (United States)

Burtscher, Martin; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Johannes

2018-01-01

Maximal heart rate (HRmax) is linearly declining with increasing age. Regular exercise training is supposed to partly prevent this decline, whereas sex and habitual physical activity do not. High exercise capacity is associated with a high cardiac output (HR x stroke volume) and high ventilatory requirements. Due to the close cardiorespiratory coupling, we hypothesized that the individual ventilatory response to maximal exercise might be associated with the age-related HRmax. Retrospective analyses have been conducted on the results of 129 consecutively performed routine cardiopulmonary exercise tests. The study sample comprised healthy subjects of both sexes of a broad range of age (20-86 years). Maximal values of power output, minute ventilation, oxygen uptake and heart rate were assessed by the use of incremental cycle spiroergometry. Linear multivariate regression analysis revealed that in addition to age the individual breathing reserve at maximal exercise was independently predictive for HRmax. A lower breathing reserve due to a high ventilatory demand and/or a low ventilatory capacity, which is more pronounced at a higher age, was associated with higher HRmax. Age explained the observed variance in HRmax by 72% and was improved to 83% when the variable "breathing reserve" was entered. The presented findings indicate an independent association between the breathing reserve at maximal exercise and maximal heart rate, i.e. a low individual breathing reserve is associated with a higher age-related HRmax. A deeper understanding of this association has to be investigated in a more physiological scenario. Copyright © 2017 Elsevier B.V. All rights reserved.

Steady-state kinetics and dynamics of morphine in cancer patients

DEFF Research Database (Denmark)

Christrup, Lona Louring; Sjøgren, P; Jensen, N H

1999-01-01

Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after...... samples for analysis of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were obtained. Pain intensity, sedation, and continuous reaction time (CRT) were assessed. No significant differences could be demonstrated in AUC/dose, Cmin, Cmax or fluctuation index values between the two treatments...... and the variability in the data, the statistical power of the test was only 0.074. The risk of a type II error is 0.926. These data demonstrate the PK and PD similarities and differences between CR and IR morphine. They suggest that there may be a relationship between Tmax (determined by absorption rate) and sedation...

Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

Science.gov (United States)

Chen, Z R; Somogyi, A A; Reynolds, G; Bochner, F

1991-04-01

1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in

Graduation Rates and the Higher Education Demographic Evolution

Science.gov (United States)

Hunsaker, B. Tom; Thomas, Douglas E.

2013-01-01

In his 1918 orienting work, The Higher Learning in America, Veblen highlights two primary aims of the higher education institution: (a) scientific and scholarly inquiry, and (b) the instruction of students (Veblen, 1918). As of 2006, this overarching mission remained intact. In contemporary literature, a common measure of the efficacy of the…

Comparison of higher order spectra in heart rate signals during two techniques of meditation: Chi and Kundalini meditation.

Science.gov (United States)

Goshvarpour, Ateke; Goshvarpour, Atefeh

2013-02-01

The human heartbeat is one of the important examples of complex physiologic fluctuations. For the first time in this study higher order spectra of heart rate signals during meditation have explored. Specifically, the aim of this study was to analysis and compares the contribution of quadratic phase coupling of human heart rate variability during two forms of meditation: (1) Chinese Chi (or Qigong) meditation and (2) Kundalini Yoga meditation. For this purpose, Bispectrum was estimated by using biased, parametric and the direct (FFT) method. The results show that the mean Bispectrum magnitude of heart rate signals increased during Kundalini Yoga meditation, but it decreased significantly during Chi meditation. However, in both meditation techniques phase-coupled harmonics are shifted to the higher frequencies during meditation. In addition, it has shown that not only there are significant differences between rest and meditation states, but also heart rate patterns appear to be influenced by different types of meditation.

Higher dosage nicotine patches increase one-year smoking cessation rates : results from the European CEASE trial

NARCIS (Netherlands)

Tonnesen, P; Paoletti, P; Gustavsson, G; Russell, MA; Saracci, R; Gulsvik, A; Rijcken, B

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study, The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six

New system for higher recovery rate of water borne Cryptosporidium oocysts and Giardia cysts

DEFF Research Database (Denmark)

Al-Sabi, Mohammad Nafi Solaiman; Gad, Jens; Klinting, Mette

2012-01-01

Background: The two most common water borne pathogenic protozoa, Cryptosporidium and Giardia, cause diarrhea worldwide. Detecting these parasites in water samples depends on effective parasite recovery from the water matrix. The reported low recovery rates of the currently used filter methods...... motivate the development of systems with higher recovery rates. Materials and methods: Five replicates of IMS purified Cryptosporidium oocysts and Giardia cysts (N=2x103) were injected into a specially coated filter unit with a carefully chosen pore size. Following filtration, sonication was performed...... were 85% were recorded when the filter was sonicated. Sonication usually affects parasite viability but could be tuned into a useful tool for enhanced backwash collection of parasites using a specially constructed filter unit and a sonication protocol. The filtration...

Why the EU-15 Maintains Higher CIT Rates than the New Member States?

Directory of Open Access Journals (Sweden)

Karpowicz Andrzej

2014-11-01

Full Text Available The European Union is not a homogenous area. This lack of homogeneity extends to taxes, which vary across jurisdictions. On average, Western Europe imposes significantly higher taxes on capital than New Member States, which joined the Community in 2004 and 2007. Often this fact is simply taken for granted. However, there are several arguments that can explain this variance. Although several of these arguments are well known and have been researched, they have not been assessed in combination, or used in a comparative analysis of corporate income tax (CIT rates between EU member states. Because of interest in harmonizing CIT throughout the EU, the roots of divergent CIT is of particular and timely value. Therefore, this article we attempts to demonstrate the differences in CIT rates in the EU-15 and New Member States. In so doing the general characteristics of these country grouping is identified, and then discussed in the context of the taxation theory.

Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy.

Science.gov (United States)

Rota Nodari, E; Alonso, S; Mancin, M; De Nardi, M; Hudson-Cooke, S; Veggiato, C; Cattoli, G; De Benedictis, P

2017-03-01

The current European Union (EU) legislation decrees that pets entering the EU from a rabies-infected third country have to obtain a satisfactory virus-neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006-2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non-EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross-breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease-free area. �

Influence of bleaching and coloring on ethyl glucuronide content in human hair.

Science.gov (United States)

Petzel-Witt, Silvana; Pogoda, Werner; Wunder, Cora; Paulke, Alexander; Schubert-Zsilavecz, Manfred; Toennes, Stefan W

2018-01-01

Ethyl glucuronide (EtG) is increasingly used in forensic toxicology as a marker for alcohol use in analyses of hair samples, especially in abstinence control. Some cosmetic treatments are considered to markedly reduce the EtG content. In view of especially many women with coloured hair the present study was performed to further investigate the effect of a variety of colouring procedures (bleaching, tinting, permanent and semi-permanent dyeing, henna) on the EtG content. Untreated hair samples (n = 12, EtG 13.9-64.7 pg/mg) were re-analyzed (gas chromatography- negative chemical ionization mass spectrometry, 0.8 pg/mg quantification limit) after different treatment procedures. A decrease of the EtG content of at least 10% occurred in every case. The reduction in comparison to the untreated hair was expectedly high for permanent dyeing and bleaching with 18.1% of the initial content (median, range 0.0-50.9%) and 18.4% (0.0-46.7%), respectively. For henna this was 38.3% (0.0-83.0%), for tinting 70.4% (29.0-90.8%), for semi-permanent dyeing 41.9% (0.0-77.4%). With permanent hair dye the EtG content was decreased to below 7 pg/mg in 10 of 12 cases, in 3 cases even below the LOD (0.2 pg/mg). Surprisingly henna treatment without oxidative component had a marked influence, EtG was below 2 pg/mg in 2 of 12 samples. The study showed that all tested coloration procedures markedly affected the deposited EtG content. Even temporary or henna coloration may have a marked effect. The present data support the recommendation to exclude hair samples with colour manipulations for analysis on the EtG content as a precaution in alcohol abstinence programs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Higher order constraints on the Higgs production rate from fixed-target DIS data

International Nuclear Information System (INIS)

Alekhin, S.; Bluemlein, J.; Moch, S.

2011-01-01

The constraints of fixed-target DIS data in fits of parton distributions including QCD corrections to next-to-next-to leading order are studied. We point out a potential problem in the analysis of the NMC data which can lead to inconsistencies in the extracted value for α s (M Z ) and the gluon distribution at higher orders in QCD. The implications for predictions of rates for Standard Model Higgs boson production at hadron colliders are investigated. We conclude that the current range of excluded Higgs boson masses at the Tevatron appears to be much too large. (orig.)

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

Science.gov (United States)

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

2012-05-10

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

A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat.

Science.gov (United States)

Selvam, Anjan Panneer; Muthukumar, Sriram; Kamakoti, Vikramshankar; Prasad, Shalini

2016-03-21

We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 μg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 μg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 μg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours.

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

Science.gov (United States)

Davidson, B J

1986-10-01

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

Invasive acacias experience higher ant seed removal rates at the invasion edges

Directory of Open Access Journals (Sweden)

D. Montesinos

2012-06-01

Full Text Available Seed dispersal is a key process for the invasion of new areas by exotic species. Introduced plants often take advantage of native generalist dispersers. Australian acacias are primarily dispersed by ants in their native range and produce seeds bearing a protein and lipid rich reward for ant mutualists (elaiosome. Nevertheless, the role of myrmecochory in the expansion of Australian acacias in European invaded areas is still not clear. We selected one European population of Acacia dealbata and another of A. longifolia and offered elaiosome-bearing and elaiosome-removed seeds to local ant communities. For each species, seeds were offered both in high-density acacia stands and in low-density invasion edges. For both acacia species, seed removal was significantly higher at the low-density edges. For A. longifolia, manual elimination of elaiosomes reduced the chance of seed removal by 80% in the low-density edges, whereas it made no difference on the high-density stands. For A. dealbata, the absence of elaiosome reduced seed removal rate by 52%, independently of the acacia density. Our data suggests that invasive acacias have found effective ant seed dispersers in Europe and that the importance of such dispersers is higher at the invasion edges.

Higher dose rate Gamma Knife radiosurgery may provide earlier and longer-lasting pain relief for patients with trigeminal neuralgia.

Science.gov (United States)

Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle

2015-10-01

Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease

Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

Science.gov (United States)

Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

2012-01-01

AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

ESTIMATING RETURN RATE OF HIGHER EDUCATION FUND IN RUSSIA

Directory of Open Access Journals (Sweden)

Semenikhina V. A.

2014-06-01

Full Text Available Currently, the Russian government pays great attention to the field of higher and postgraduate education. But in the Russian scientific literature there are gaps related to the effectiveness of the overall evaluation of the higher education sector. The article dwells upon the problem of interregional income spread of the Russian population. Empirical estimator of difference influence accounting for human capital accumulated in Russian regions on wage levels and maximum increase of total wage levels and population income for 2001-2011 is carried out. Higher education, exceeding the influence of accumulated volume of the main funds, has a great influence on income spread in Russian regions. Besides, increase of higher education fund in Russian regions contributes to the population’s wage increase and growth in income, but at the same time it decreases legal wages. Results of the study extend knowledge of the economics of education of the Russian Federation.

Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?

OpenAIRE

Moll, E.; Korevaar, J.C.; Bossuyt, P.M.M.; van der Veen, F.

2008-01-01

BACKGROUND An RCT among newly diagnosed, therapy naive women with polycystic ovary syndrome (PCOS) showed no significant differences in ovulation rate, ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate. We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates. METHODS Subgroup analysis based on clinical and biochemical para...

The Active Management of Risk in Multiparous Pregnancy at Term: association between a higher preventive labor induction rate and improved birth outcomes

Science.gov (United States)

Nicholson, James M.; Caughey, Aaron; Stenson, Ms. Morghan H.; Cronholm, Peter; Kellar, Lisa; Bennett, Ian; Margo, Katie; Stratton, Joseph

2009-01-01

Objective To determine if exposure of multiparous women to a high rate of preventive labor induction was associated with a significantly lower cesarean delivery rate. Study Design Retrospective cohort study involving 123 multiparas, who were exposed to the frequent use of preventive labor induction, and 304 multiparas, who received standard management. Rates of cesarean delivery and other adverse birth outcomes were compared in the two groups. Logistic regression controlled for confounding covariates. Results The exposed group had a lower cesarean delivery rate (aOR 0.09, 0.8% vs. 9.9%, p = 0.02) and a higher uncomplicated vaginal delivery rate (OR 0.53, 78.9% vs. 66.4%, p=0.01). Exposure was not associated with higher rates of other adverse birth outcomes. Conclusion Exposure of multiparas to a high rate of preventive labor induction was significantly associated with improved birth outcomes including a very low cesarean delivery rate. A prospective randomized trial is needed to determine causality. PMID:19254584

Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

Directory of Open Access Journals (Sweden)

S.J. Borghoff

Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

Higher Rates of DZ Twinning in a Twenty-First Century Birth Cohort.

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Rhea, Sally Ann; Corley, Robin P; Heath, Andrew C; Iacono, William G; Neale, Michael C; Hewitt, John K

2017-09-01

The Colorado Twin Registry is a population based registry initiated in 1984 with the involvement of the Colorado Department of Health, Division of Vital Statistics. Recruitment includes birth cohorts several years prior to 1984 and all subsequent years. As part of a recent evaluation of Colorado birth records for the years 2006 through 2008 we became aware of a shifting trend in the proportion of MZ and DZ twins in the Colorado population. Historically (Bulmer 1970 The biology of twinning in man, Clarendon, Oxford) we have expected a 1/3, 1/3, 1/3 ratio of MZ, same-sex DZ and opposite sex DZ twins in Caucasian populations. An excess of MZ pairs in most studies was assumed to be due to selection bias. Somewhat more recently, Hur et al.(1995 Behav Genet 25, 337-340) provided evidence that the DZ twinning rate was falling and that therefore selection bias was not the reason for higher MZ enrollment in most twin studies. They suggested that twin researchers might consider strategies to over-enroll DZ pairs to maximize statistical power. In contrast, we now find that of the 3217 twin births in Colorado from 2006 to 2008 with identified sex information the MZ rate is estimated at only 22%, and we have corroborating reports from other states of similar estimates. These were calculated applying Weinberg's rule which assumes an equal birth rate for same sex and opposite sex DZ pairs so that the proportion of MZ in a sample is the proportion of same sex (MM + FF) minus the proportion of opposite-sex (MF, FM). We explore factors, such as an increase in the proportion of non-Caucasian parents and an increase in average maternal age, which may contribute to this shift.

A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat

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Panneer Selvam, Anjan; Muthukumar, Sriram; Kamakoti, Vikramshankar; Prasad, Shalini

2016-03-01

We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 μg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 μg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 μg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours.

Ethyl glucuronide in vitreous humor and blood postmortem specimens: analysis by liquid chromatography-electrospray tandem mass spectrometry and interpreting results of neo-formation of ethanol

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Sara Vezzoli

2015-03-01

Full Text Available Introduction. The determination of ethyl glucuronide (EtG, a stable and sensitive marker that is specific to alcohol intake, finds many applications both in the forensic toxicology and clinical fields. Aim. The aim of the study is to examine the possibility of using a cadaveric biological matrix, vitreous humor (VH, to determine EtG as a marker of recent ethanol use. Methods. The blood, taken from the femoral vein, and the VH were obtained from 63 autopsy cases. Analysis of the EtG was performed using an LC/MS/MS system. Analyses of the ethanol and putrefaction biomarkers, such as acetaldehyde and n-propanol, were performed using the HS-GC/FID technique in both the matrices. Results. In 17 cases, both ethanol and EtG were absent in both matrices.Nineteen cases presented ethanol in blood from 0.05 to 0.30 g/L, EtG-Blood concentration from 0.02 to 3.27 mg/L, and EtG-VH concentration from 0.01 mg/L to 2.88 mg/L. Thirteen cases presented ethanol in blood > 0.05 g/L but EtG concentration in blood and VH lower than 0.01 mg/L, are part of these 8 samples presented acetic aldehyde and n- propanol in blood or VH, means identification of putrefaction indicators. Fourteen cases presented ethanol in blood > 0.46 and EtG concentration in blood and VH higher than 0.01 mg/L. Conclusions. The determination of EtG in biological material is important in those cases where the intake of ethanol appears doubtful, as it allows us to exclude the possibility of any post-mortem formation of ethanol.

Effect of additives for higher removal rate in lithium niobate chemical mechanical planarization

International Nuclear Information System (INIS)

Jeong, Sukhoon; Lee, Hyunseop; Cho, Hanchul; Lee, Sangjik; Kim, Hyoungjae; Kim, Sungryul; Park, Jaehong; Jeong, Haedo

2010-01-01

High roughness and a greater number of defects were created by lithium niobate (LN; LiNbO 3 ) processes such as traditional grinding and mechanical polishing (MP), should be decreased for manufacturing LN device. Therefore, an alternative process for gaining defect-free and smooth surface is needed. Chemical mechanical planarization (CMP) is suitable method in the LN process because it uses a combination approach consisting of chemical and mechanical effects. First of all, we investigated the LN CMP process using commercial slurry by changing various process conditions such as down pressure and relative velocity. However, the LN CMP process time using commercial slurry was long to gain a smooth surface because of lower material removal rate (MRR). So, to improve the material removal rate (MRR), the effects of additives such as oxidizer (hydrogen peroxide; H 2 O 2 ) and complexing agent (citric acid; C 6 H 8 O 7 ) in a potassium hydroxide (KOH) based slurry, were investigated. The manufactured slurry consisting of H 2 O 2 -citric acid in the KOH based slurry shows that the MRR of the H 2 O 2 at 2 wt% and the citric acid at 0.06 M was higher than the MRR for other conditions.

Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls.

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Kirby, Kris N; Petry, Nancy M

2004-04-01

To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction. The delay-discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases. We estimated participants' discount rates on the basis of their pattern of choices between smaller immediate rewards ($11-80) and larger, delayed rewards ($25-85; at delays from 1 week to 6 months) in a questionnaire format. Participants had a one-in-six chance of winning a reward that they chose on one randomly selected trial. Heroin (n = 27), cocaine (n = 41) and alcohol (n = 33) abusers and non-drug-using controls (n = 44) were recruited from advertisements. They were tested in a drug abuse research clinic at a medical school. On average, the cocaine and heroin groups had higher rates than controls (both P rates for heroin abusers (P = 0.03), but not for cocaine or alcohol abusers (both P > 0.50). These data suggest that discount rates vary with the preferred drug of abuse, and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts.

Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features.

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Kolb, Jennifer M; Argiriadi, Pamela; Lee, Karen; Liu, Xiaoyu; Bagiella, Emilia; Lucas, Aimee L; Kim, Michelle Kang; Kumta, Nikhil A; Nagula, Satish; Sarpel, Umut; DiMaio, Christopher J

2018-03-11

or invasive cancers. BD-IPMNs that developed worrisome features were associated with a significantly higher rate of growth than lesions with low-risk features. Low risk BD-IPMNs that grow more than 2.5 mm/year might require surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Student Ratings of Instruction in Turkish Higher Education

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Nehir Sert

2013-05-01

Full Text Available The end-of-term student evaluations have a twofold purpose: to provide information for administrators to make personnel decisions, and to help instructors to improve the quality of their teaching. The aim of this study is to investigate the ‘utility’ of the Student Ratings of Instruction (SRI. To that end, the concerns of the administrators, instructors and students regarding the use of the SRI in formative and summative evaluations are questioned. This study also investigates possible variables associated with the SRI: 1 what are the differences in ratings among the below-average, average and the above-average students? and 2 what is the correlation between the students’ grades and ratings? The participants of the study consisted of 5 administrators, 17 instructors and 292 students from the faculty of education of a foundation university in Ankara. A triangulation of quantitative and qualitative methods was adopted. In the first phase, causal comparative and correlation research methods were implemented. In the second phase, qualitative data were collected through semi-structured interviews. The results revealed that there was no significant difference in the SRI among the below-average, average and above-average students. The correlation between the student grades and the SRI was significant at a low level. The SRI were reportedly utilised to make teaching more effective and to make decisions when employing part-time personnel only. The permanent personnel were not affected by the SRI. Suggestions have been put forward to verify the usefulness of SRI.

Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer

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Fan Yun

2014-01-01

Full Text Available Objective: The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1 gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC. Materials and Methods: A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy. Results: A total of 25 cases (80.6% were UGT1A1FNx0128 wild-type (TA 6 /(TA 6 ; 6 cases (19.4% were heterozygous mutant (TA 6 /(TA 7 , no homozygous mutant genotype (TA 7 /(TA 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA 6 /(TA 6 and heterozygous (TA 6 /(TA 7 had no statistical difference (P > 0.05 for all. The overall response rate (ORR was 32.3%. Median progression free survival (PFS and overall survival (OS were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA 6 /(TA 6 patients and heterozygous (TA 6 /(TA 7 patients. Conclusion: Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.

Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period.

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Blackwell, Leonard F; Vigil, Pilar; Alliende, María Elena; Brown, Simon; Festin, Mario; Cooke, Delwyn G

2016-02-01

Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning

Lack of genetic association between OCT1, ABCB1, and UGT2B7 variants and morphine pharmacokinetics

DEFF Research Database (Denmark)

Nielsen, L M; Sverrisdóttir, E; Stage, T B

2017-01-01

from a double-blinded, randomized, crossover trial in 37 healthy subjects. Pharmacokinetic data were analyzed in NONMEM®, and the time-concentration relationship of morphine, morphine-3-glucuronide, and morphine-6-glucuronide was parameterized as the transit compartment rate constant (ktr), clearance...... (CL), and volume of distribution (VD). The area under the plasma concentration-time curve (AUC0-150min) and the maximum plasma concentration (Cmax) were also calculated. Pharmacodynamic data were measured as pain tolerance thresholds to mechanical stimulation of the rectum and muscle, as well as tonic...

Hydraulic conductance as well as nitrogen accumulation plays a role in the higher rate of leaf photosynthesis of the most productive variety of rice in Japan.

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Taylaran, Renante D; Adachi, Shunsuke; Ookawa, Taiichiro; Usuda, Hideaki; Hirasawa, Tadashi

2011-07-01

An indica variety Takanari is known as one of the most productive rice varieties in Japan and consistently produces 20-30% heavier dry matter during ripening than Japanese commercial varieties in the field. The higher rate of photosynthesis of individual leaves during ripening has been recognized in Takanari. By using pot-grown plants under conditions of minimal mutual shading, it was confirmed that the higher rate of leaf photosynthesis is responsible for the higher dry matter production after heading in Takanari as compared with a japonica variety, Koshihikari. The rate of leaf photosynthesis and shoot dry weight became larger in Takanari after the panicle formation and heading stages, respectively, than in Koshihikari. Roots grew rapidly in the panicle formation stage until heading in Takanari compared with Koshihikari. The higher rate of leaf photosynthesis in Takanari resulted not only from the higher content of leaf nitrogen, which was caused by its elevated capacity for nitrogen accumulation, but also from higher stomatal conductance. When measured under light-saturated conditions, stomatal conductance was already decreased due to the reduction in leaf water potential in Koshihikari even under conditions of a relatively small difference in leaf-air vapour pressure difference. In contrast, the higher stomatal conductance was supported by the maintenance of higher leaf water potential through the higher hydraulic conductance in Takanari with the larger area of root surface. However, no increase in root hydraulic conductivity was expected in Takanari. The larger root surface area of Takanari might be a target trait in future rice breeding for increasing dry matter production.

Biodegradation testing of chemicals with high Henry’s constants – separating mass and effective concentration reveals higher rate constants

DEFF Research Database (Denmark)

Birch, Heidi; Andersen, Henrik Rasmus; Comber, Mike

Microextraction (HS-SPME) was applied directly on the test systems to measure substrate depletion by biodegradation relative to abiotic controls. HS-SPME was also applied to determine air to water partitioning ratios. Water phase biodegradation rate constants, kwater, were up to 72 times higher than test system...

Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity.

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Sallustio, Benedetta C; Degraaf, Yvette C; Weekley, Josephine S; Burcham, Philip C

2006-05-01

Nonenzymatic modification of proteins by acyl glucuronides is well documented; however, little is known about their potential to damage DNA. We have previously reported that clofibric acid undergoes glucuronidation-dependent bioactivation to DNA-damaging species in cultured mouse hepatocytes. The aim of this study was to investigate the mechanisms underlying such DNA damage, and to screen chemically diverse carboxylic acid drugs for their DNA-damaging potential in glucuronidation proficient murine hepatocytes. Cells were incubated with each aglycone for 18 h, followed by assessment of compound cytotoxicity using the MTT assay and evaluation of DNA damage using the Comet assay. Relative cytotoxic potencies were ketoprofen > diclofenac, benoxaprofen, nafenopin > gemfibrozil, probenecid > bezafibrate > clofibric acid. At a noncytotoxic (0.1 mM) concentration, only benoxaprofen, nafenopin, clofibric acid, and probenecid significantly increased Comet moments (P Clofibric acid and probenecid exhibited the greatest DNA-damaging potency, producing significant DNA damage at 0.01 mM concentrations. The two drugs produced maximal increases in Comet moment of 4.51 x and 2.57 x control, respectively. The glucuronidation inhibitor borneol (1 mM) abolished the induction of DNA damage by 0.5 mM concentrations of clofibric acid and probenecid. In an in vitro cell-free system, clofibric acid glucuronide was 10 x more potent than glucuronic acid in causing DNA strand-nicking, although both compounds showed similar rates of autoxidation to generate hydroxyl radicals. In cultured hepatocytes, the glycation inhibitor, aminoguanidine, and the iron chelator, desferrioxamine mesylate, inhibited DNA damage by clofibric acid, whereas the free radical scavengers Trolox and butylated hydroxytoluene, and the superoxide dismutase mimetic bis-3,5-diisopropylsalicylate had no effect. In conclusion, clinically relevant concentrations of two structurally unrelated carboxylic acids, probenecid and

Red wine and component flavonoids inhibit UGT2B17 in vitro

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Jenkinson Carl

2012-09-01

Full Text Available Abstract Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analyzed using HPLC; and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8%, the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HPLC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%, caffeic acid (22% and gallic acid (9%; using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 μM despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common

Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients.

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Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Dom, Geert; Cappelle, Delphine; Maudens, Kristof E; van Nuijs, Alexander L N; Covaci, Adrian; Neels, Hugo

2015-02-01

Ethyl glucuronide (EtG), a minor metabolite of alcohol, is used as a sensitive marker in hair to detect the retrospective consumption of alcohol. The proximal 0-3 cm hair segment is often used for analysis, providing information on alcohol consumption over the past 3 months. Using more distal segments would allow the detection of alcohol consumption over longer time periods, thereby addressing the chronicity of the consumption. In view of this, permanent coloring and bleaching were shown in vitro to alter EtG concentrations in hair, but no in vivo studies are available to prove or disprove this. To investigate the influence of repeated bleaching and permanent coloring on EtG concentrations in vivo and to assess the stability of EtG concentrations in distal compared to proximal hair segments. Hair samples from alcohol-dependent patients with uncolored/unbleached (N=4), permanent coloration (N=5) and bleached hair (N=5) were analyzed in two to six 3 cm long segments for EtG concentrations, and alcohol consumption and hair cosmetic treatments were assessed. We observed that hair bleaching and permanent coloring reduces EtG concentrations by 82±11% and 65±24%, respectively, with correlations between the number of cosmetic treatments and the decrease in EtG concentrations. EtG remained stable in untreated hair samples up to 18 cm. EtG is a sensitive marker to assess chronic alcohol consumption up to 18 months in alcohol-dependent patients with no cosmetic hair treatments. However, in alcohol-dependent patients who color or bleach their hair, care should be taken when interpreting EtG measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin in the Blood.

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Ozawa, Hitomi; Imaizumi, Atsushi; Sumi, Yoshihiko; Hashimoto, Tadashi; Kanai, Masashi; Makino, Yuji; Tsuda, Takanori; Takahashi, Nobuaki; Kakeya, Hideaki

2017-01-01

Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

Obese Japanese adults with type 2 diabetes have higher basal metabolic rates than non-diabetic adults.

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Miyake, Rieko; Ohkawara, Kazunori; Ishikawa-Takata, Kazuko; Morita, Akemi; Watanabe, Shaw; Tanaka, Shigeho

2011-01-01

Several cross-sectional studies in Pima Indians and Caucasians have indicated that obese individuals with type 2 diabetes have a higher basal metabolic rate (BMR) than healthy, obese individuals. However, no study has investigated this comparison in Japanese subjects, who are known to be susceptible to type 2 diabetes due to genetic characteristics. Thirty obese Japanese adults with pre-type 2 diabetes (n=7) or type 2 diabetes (n=13) or without diabetes (n=10) participated in this study. BMR was measured using indirect calorimetry. The relationships between residual BMR (calculated as measured BMR minus BMR adjusted for fat-free mass, fat mass, age, and sex) and biomarkers including fasting glucose, glycosylated hemoglobin (HbA(1c)), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-R), triglycerides, and free fatty acids were examined using Pearson's correlation. BMR in diabetic subjects adjusted for fat-free mass, fat mass, age, and sex was 7.1% higher than in non-diabetic subjects. BMR in diabetic subjects was also significantly (pBMR and fasting glucose (r=0.391, p=0.032). These results indicate that in the Japanese population, obese subjects with type 2 diabetes have higher BMR compared with obese non-diabetic subjects. The fasting glucose level may contribute to these differences.

Understanding the Effect of Response Rate and Class Size Interaction on Students Evaluation of Teaching in a Higher Education

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Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

2016-01-01

Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design: A retrospective study design was chosen. Methods: One thousand four hundred and forty four different courses…

Modified Mitchell osteotomy alone does not have higher rate of residual metatarsalgia than combined first and lesser metatarsal osteotomy

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Shu-Jung Chen

2015-04-01

Full Text Available Transfer metatarsalgia (TM is a common forefoot disorder secondary to hallux valgus (HV. Some authors suggest that a combined lesser metatarsal osteotomy while undergoing HV surgery improves metatarsalgia, whereas others concluded that isolated HV corrective osteotomy can improve symptomatic metatarsalgia. The main purpose of this retrospective study was to compare clinical outcomes in patients with and without combined lesser metatarsal osteotomy while receiving HV correction surgery. We retrospectively reviewed the patients who underwent osteotomy for HV correction between January 2000 and December 2010. All patients underwent HV correction with modified Mitchell osteotomy. Clinical evaluations including the American Orthopaedic Foot and Ankle Society score and residual metatarsalgia were assessed, and radiographic measurements were carried out. Sixty-five patients (83 feet meeting the selection criteria were enrolled. Thirty feet receiving a combined lesser metatarsal osteotomy were classified as the combined surgery (CS group, and the others were classified as the control (CN group (53 feet. The overall rate of persistent symptomatic metatarsalgia was 19.28% after operative treatment. There were six feet with residual metatarsalgia in the CS group, and 10 feet in the CN group. There was no significant difference in the rate of persistent symptoms between the two groups (p = 0.9. According to this result, modified Mitchell osteotomy alone did not have a higher rate of residual metatarsalgia than CS. We also found that the average recovery rate of TM was about 80.7% and those patients whose preoperative HV angle was > 30° had the higher risk of residual metatarsalgia after surgery.

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

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Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

2004-06-01

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Effects of kale ingestion on pharmacokinetics of acetaminophen in rats.

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Yamasaki, Izumi; Uotsu, Nobuo; Yamaguchi, Kohji; Takayanagi, Risa; Yamada, Yasuhiko

2011-12-01

Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.

Clinical Pharmacology of Paracetamol in Neonates: A Review

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Gian Maria Pacifici, MD, PhD

2015-12-01

Paracetamol clearance is lower in neonates than in children and adults. After metabolic conversion, paracetamol is subsequently eliminated by the renal route. The main metabolic conversions are conjugation with glucuronic acid and with sulphate. In the urine of neonates sulphated paracetamol concentration is higher than the glucuronidated paracetamol level, suggesting that sulfation prevails over glucuronidation in neonates. A loading dose of 20 mg/kg followed by 10 mg/kg every 6 hours of intravenous paracetamol is suggested to achieve a compartment concentration of 11 mg/L in late preterm and term neonates. Aiming for the same target concentration, oral doses are similar with rectal administration of 25 to 30 mg/kg/d in preterm neonates of 30 weeks’ gestation, 45 mg/kg/d in preterm infants of 34 weeks’ gestation, and 60 mg/kg/d in term neonates are suggested. The above-mentioned paracetamol doses for these indications (pain, fever are well tolerated in neonates, but do not result in a significant increase in liver enzymes, and do not affect blood pressure and have limited effects on heart rate. In contrast, the higher doses suggested in extreme preterm neonates to induce closure of the patent ductus arteriosus have not yet been sufficiently evaluated regarding efficacy or safety. Moreover, focussed pharmacovigilance to explore the potential causal association between paracetamol exposure during perinatal life and infancy and subsequent atopy is warranted.

Endometrial Scratch Injury Induces Higher Pregnancy Rate for Women With Unexplained Infertility Undergoing IUI With Ovarian Stimulation: A Randomized Controlled Trial.

Science.gov (United States)

Maged, Ahmed M; Al-Inany, Hesham; Salama, Khaled M; Souidan, Ibrahim I; Abo Ragab, Hesham M; Elnassery, Noura

2016-02-01

To explore the impact of endometrial scratch injury (ESI) on intrauterine insemination (IUI) success. One hundred and fifty four infertile women received 100 mg of oral clomiphene citrate for 5 days starting on day 3 of the menstrual cycle. Patients were randomized to 2 equal groups: Group C received IUI without ESI and group S had ESI. Successful pregnancy was confirmed by ultrasound. 13, 21, and 10 women got pregnant after the first, second, and third IUI trials, respectively, with 28.6% cumulative pregnancy rate (PR). The cumulative PR was significantly higher in group S (39%) compared to group C (18.2%). The PR in group S was significantly higher compared to that in group C at the second and third trials. The PR was significantly higher in group S at the second trial compared to that reported in the same group at the first trial but nonsignificantly higher compared to that reported during the third trial, while in group C, the difference was nonsignificant. Eight pregnant women had first trimester abortion with 18.2% total abortion rate with nonsignificant difference between studied groups. The ESI significantly improves the outcome of IUI in women with unexplained infertility especially when conducted 1 month prior to IUI. © The Author(s) 2015.

APPRAISAL OF STUDENT RATING AS A MEASURE TO MANAGE THE QUALITY OF HIGHER EDUCATION IN INDIA: AN INSTITUTIONAL STUDY USING SIX SIGMA MODEL APPROACH

Directory of Open Access Journals (Sweden)

Arun Vijay

2013-12-01

Full Text Available Students' rating of teaching is one of the most widely accepted methods of measuring the quality in Higher Education worldwide. The overall experience gained by the students during their academic journey in their respective college is a key factor to determine the Institutional Quality. This study was conducted among the Physical Therapy students with an objective to capture the overall experience related to various aspects of their Academic environment including teaching and learning process adopted in their college. To facilitate that, a unique questionnaire called,"Academic Environment Evaluation Questionnaire (AEEQ was developed covering all the important teaching elements of the Higher Education Institutions. The students' opinion was captured and analyzed through six sigma analytical tool using Poisson distribution model. From the non-conformance level captured through the responses from the students about the various categories of teaching and learning elements, the corresponding Sigma rating for each teaching element was measured. Accordingly, a six point Quality rating system was developed customizing to each sigma values. This study brings a new, innovative student driven Quality rating system for the Higher Education Institutions in India.

Predicting higher education graduation rates from institutional characteristics and resource allocation

Directory of Open Access Journals (Sweden)

Florence A. Hamrick

2004-05-01

Full Text Available This study incorporated institutional characteristics (e.g., Carnegie type, selectivity and resource allocations (e.g., instructional expenditures, student affairs expenditures into a statistical model to predict undergraduate graduation rates. Instructional expenditures, library expenditures, and a number of institutional classification variables were significant predictors of graduation rates. Based on these results, recommendations as well as warranted cautions are included about allocating academic financial resources to optimize graduation rates

Higher Education Support Services and Graduation Rates of Structured Education Program Students

Science.gov (United States)

Hepner, Seth

2017-01-01

The 1st-year retention rate of the Structured Education Program (SEP) is 90%, yet the 6-year graduation rate of SEP students is 29%. The gap between SEP 1st-year retention and graduation rates is the problem that this study addressed. The low graduation rate of SEP students is an important issue because graduation rates are used to measure the…

Effect of temperature during ion sputtering on the surface segregation rate of antimony in an iron-antimony alloy at higher temperatures

International Nuclear Information System (INIS)

Oku, M.; Hirokawa, K.; Kimura, H.; Suzuki, S.

1986-01-01

The surface segregation of antimony in an iron-0.23 at% antimony alloy was studied by XPS. The segregation rate in the temperature range between 800 and 900 K depends on the temperature during sputtering with argon ion of kinetic energy of 1 keV. The sputtering at room temperature or 473 K gives higher values of the segregation rate than those at 673 K. Both cases give the activation energy of 170 kJmol -1 for the surface segregation rate. The segregation of antimony is not observed after the sample is heated at 1000 K. (author)

Retinyl β-glucoronide: its occurrence in human serum, chemical synthesis and biological activity

International Nuclear Information System (INIS)

Barua, A.B.; Batres, R.O.; Olson, J.A.

1986-01-01

When retinol is administered to rats, retinyl and retinoyl β-glucuronides appear in the bile. Retinyl or retinoyl β-glucuronide is also synthesized in vitro when rat liver microsomes are incubated with uridinediphosphoglucuronic acid and either retinol or retinoic acid. Retinoyl β-glucuronide, a major metabolite of retinoic acid in a number of tissues, is highly active biologically, has been chemically synthesized, and is found in human blood. The physiological significance of the glucuronides of vitamin A are not known yet. To investigate further its metabolism and possible physiological role, retinyl β-glucuronide was chemically synthesized from retinol and characterized by study of its ultra-violet spectrum (γ/sub max/ 325 nm in methanol, 329 nm in water), 1 H-NMR and mass spectra. Retinyl β-glucuronide was extensively hydrolyzed by bacterial β-glucuronidase to retinol. Retinyl β-glucuronide is soluble in water and was detected in significant amounts in the serum of healthy human adults. The biological activity of synthetic retinyl β-glucuronide was determined in rats by the rat growth bioassay method

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

Science.gov (United States)

Ruderman, Michael A; Wilson, Deirdra F; Reid, Savanna

2015-01-01

This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17), drug violations (HR 2.44 95% CI: 2.00-2.98), non-violent violations (HR 2.14 95% CI: 1.73-2.64), violent and serious violations (HR 1.88 95% CI: 1.45-2.43), and technical violations (HR 1.86 95% CI: 1.37-2.53). Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

Ethyl glucuronide, ethyl sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer.

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

2011-03-01

To assess the degree of ethanol absorption and subsequent formation of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) following sustained application of hand sanitizer, 11 volunteers cleansed their hands with Purell(™) hand sanitizer (62% ethanol) every 5 min for 10 h on three consecutive days. Urine specimens were obtained at the beginning and end of each day of the study, and on the morning of the fourth day. Urinary creatinine, ethanol, EtG, and EtS concentrations were measured. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (73 and 37 ng/mL). None of the pre-study specimens had detectable ethanol. The maximum EtG and EtS concentrations over the course of the study were 2001 and 84 ng/mL, respectively, and nearly all EtG- and EtS-positive urine specimens were collected at the conclusion of the individual study days. Only two specimens had detectable EtG at the beginning of any study day (96 and 139 ng/mL), and only one specimen had detectable EtS at the beginning of a study day (64 ng/mL), in addition to the two with detectable EtS prior to the study. Creatinine-adjusted maximum EtG and EtS concentrations were 1998 and 94 μg/g creatinine, respectively. In patients being monitored for ethanol use by urinary EtG concentrations, currently accepted EtG cutoffs do not distinguish between ethanol consumption and incidental exposures, particularly when urine specimens are obtained shortly after sustained use of ethanolcontaining hand sanitizer. Our data suggest that EtS may be an important complementary biomarker in distinguishing ethanol consumption from dermal exposure.

Ethanol and ethyl glucuronide urine concentrations after ethanol-based hand antisepsis with and without permitted alcohol consumption.

Science.gov (United States)

Gessner, Stephan; Below, Elke; Diedrich, Stephan; Wegner, Christian; Gessner, Wiebke; Kohlmann, Thomas; Heidecke, Claus-Dieter; Bockholdt, Britta; Kramer, Axel; Assadian, Ojan; Below, Harald

2016-09-01

During hand antisepsis, health care workers (HCWs) are exposed to alcohol by dermal contact and by inhalation. Concerns have been raised that high alcohol absorptions may adversely affect HCWs, particularly certain vulnerable individuals such as pregnant women or individuals with genetic deficiencies of aldehyde dehydrogenase. We investigated the kinetics of HCWs' urinary concentrations of ethanol and its metabolite ethyl glucuronide (EtG) during clinical work with and without previous consumption of alcoholic beverages by HCWs. The median ethanol concentration was 0.7 mg/L (interquartile range [IQR], 0.5-1.9 mg/L; maximum, 9.2 mg/L) during abstinence and 12.2 mg/L (IQR, 1.5-139.6 mg/L; maximum, 1,020.1 mg/L) during alcohol consumption. During abstinence, EtG reached concentrations of up to 958 ng/mL. When alcohol consumption was permitted, the median EtG concentration of all samples was 2,593 ng/mL (IQR, 890.8-3,576 ng/mL; maximum, 5,043 ng/mL). Although alcohol consumption was strongly correlated with both EtG and ethanol in urine, no significant correlation for the frequency of alcoholic hand antisepsis was observed in the linear mixed models. The use of ethanol-based handrub induces measurable ethanol and EtG concentrations in urine. Compared with consumption of alcoholic beverages or use of consumer products containing ethanol, the amount of ethanol absorption resulting from handrub applications is negligible. In practice, there is no evidence of any harmful effect of using ethanol-based handrubs as much as it is clinically necessary. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Bioavailability of trans-resveratrol from red wine in humans.

Science.gov (United States)

Vitaglione, Paola; Sforza, Stefano; Galaverna, Gianni; Ghidini, Cristiana; Caporaso, Nicola; Vescovi, Pier Paolo; Fogliano, Vincenzo; Marchelli, Rosangela

2005-05-01

Many in vitro studies demonstrated significant biological effects of trans-resveratrol. Thus, understanding the rate of intestinal absorption and metabolization in vivo of trans-resveratrol is the prerequisite to evaluate its potential health impact. Bioavailability studies mainly in animals or in humans using the pure compound at very high doses were performed. In this work, trans-resveratrol bioavailability from a moderate consumption of red wine in 25 healthy humans has been studied by three different experiments. The wine ingestion was associated to three different dietary approaches: fasting, a standard meal, a meal with high and low amount of lipids. Trans-resveratrol 3- and 4'-glucuronides were synthesized, purified, and characterized as pure standards. Bioavailability data were obtained by measuring the concentration of free, 3-glucuronide and 4'-glucuronide trans-resveratrol by high-performance liquid chromatography (HPLC), both with ultraviolet (UV) and mass spectrometry (MS) detection, in serum samples taken at different times after red wine administration. Free trans-resveratrol was found, in trace amounts, only in some serum samples collected 30 min after red wine ingestion while after longer times resveratrol glucuronides predominated. Trans-resveratrol bioavailability was shown to be independent from the meal or its lipid content. The finding in human serum of trans-resveratrol glucuronides, rather than the free form of the compound, with a high interindividual variability, raises some doubts about the health effects of dietary resveratrol consumption and suggests that the benefits associated to red wine consumption could be probably due to the whole antioxidant pool present in red wine.

Binding of bilirubin and its structural analogues to hepatic microsomal bilirubin UDP glucuronyltransferase

International Nuclear Information System (INIS)

Vanstapel, F.; Blanckaert, N.

1987-01-01

Hepatic glucuronidation of the asymmetrical natural bilirubin molecule results in formation of two different positional isomers, bilirubin C-8 monoglucuronide and bilirubin C-12 monoglucuronide. In view of the existence of multiple isoforms of UDPglucuronyltransferase, which is the microsomal enzyme system responsible for bilirubin esterification, the authors performed kinetic analysis of microsomal glucuronidation of bilirubin and a number of its structural congeners to determine whether synthesis of the two monoglucuronide isomers involved two distinct substrate-binding sites or reflected two different modes of binding to a single catalytic site. Both isomers were found in all tested species (man, rat, guinea pig, sheep), but there were marked species differences in the C-8/C-12 ratio of monoglucuronide found in bile or formed by liver microsomes. Correspondence between in vivo and in vitro results for such regioselectivity of glucuronidation was excellent in each species. On the basis of these results of kinetic analysis of bilirubin esterification at variable pigment substrate concentrations and inhibition studies with alternative substrates, the authors postulate that both natural monoglucuronide isomers are synthesized at a single binding site. Possible mechanisms responsible for the markedly regioselective esterification of bilirubin by rat and sheep liver were investigated by study of glucuronidation of selected structural analgoues of the pigment. Collectively, their findings suggest that the molecular from(s) of bilirubin able to engage in catalytically effective binding to UDPglucuronyltransferase does (do) not correspond with intramolecularly hydrogen-bonded conformers and that the nature of the β-substituents of the outer pyrromethenone rings is a key determinant of glucuronidation rate

Metabolism and pharmacokinetics of morphine in neonates: A review

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Gian Maria Pacifici

Full Text Available Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is glucuronidated and sulfated at positions 3 and 6; the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight. Moreover, morphine clearance correlates positively with gestational age and birth weight. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Ordinary doses cause constipation, urinary retention and respiratory depression. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml seem adequate for children. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. The initial and final cutoff points were January 1990 and September 2015, respectively. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based.

Faster eating rates are associated with higher energy intakes during an ad libitum meal, higher BMI and greater adiposity among 4·5-year-old children: results from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort.

Science.gov (United States)

Fogel, Anna; Goh, Ai Ting; Fries, Lisa R; Sadananthan, Suresh A; Velan, S Sendhil; Michael, Navin; Tint, Mya-Thway; Fortier, Marielle V; Chan, Mei Jun; Toh, Jia Ying; Chong, Yap-Seng; Tan, Kok Hian; Yap, Fabian; Shek, Lynette P; Meaney, Michael J; Broekman, Birit F P; Lee, Yung Seng; Godfrey, Keith M; Chong, Mary F F; Forde, Ciarán G

2017-04-01

Faster eating rates are associated with increased energy intake, but little is known about the relationship between children's eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children's BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

Directory of Open Access Journals (Sweden)

Michael A Ruderman

Full Text Available This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004.Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees.Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs with 95% confidence intervals (CIs were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis.Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17, drug violations (HR 2.44 95% CI: 2.00-2.98, non-violent violations (HR 2.14 95% CI: 1.73-2.64, violent and serious violations (HR 1.88 95% CI: 1.45-2.43, and technical violations (HR 1.86 95% CI: 1.37-2.53.Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis

Science.gov (United States)

Ruderman, Michael A.; Wilson, Deirdra F.; Reid, Savanna

2015-01-01

Objective This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Background Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Methods Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Results Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05–4.17), drug violations (HR 2.44 95% CI: 2.00–2.98), non-violent violations (HR 2.14 95% CI: 1.73–2.64), violent and serious violations (HR 1.88 95% CI: 1.45–2.43), and technical violations (HR 1.86 95% CI: 1.37–2.53). Conclusions Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted. PMID:26492490

Higher Rate of Tuberculosis in Second Generation Migrants Compared to Native Residents in a Metropolitan Setting in Western Europe

Science.gov (United States)

Marx, Florian M.; Fiebig, Lena; Hauer, Barbara; Brodhun, Bonita; Glaser-Paschke, Gisela; Haas, Walter

2015-01-01

Background In Western Europe, migrants constitute an important risk group for tuberculosis, but little is known about successive generations of migrants. We aimed to characterize migration among tuberculosis cases in Berlin and to estimate annual rates of tuberculosis in two subsequent migrant generations. We hypothesized that second generation migrants born in Germany are at higher risk of tuberculosis compared to native (non-migrant) residents. Methods A prospective cross-sectional study was conducted. All tuberculosis cases reported to health authorities in Berlin between 11/2010 and 10/2011 were eligible. Interviews were conducted using a structured questionnaire including demographic data, migration history of patients and their parents, and language use. Tuberculosis rates were estimated using 2011 census data. Results Of 314 tuberculosis cases reported, 154 (49.0%) participated. Of these, 81 (52.6%) were first-, 14 (9.1%) were second generation migrants, and 59 (38.3%) were native residents. The tuberculosis rate per 100,000 individuals was 28.3 (95CI: 24.0–32.6) in first-, 10.2 (95%CI: 6.1–16.6) in second generation migrants, and 4.6 (95%CI: 3.7–5.6) in native residents. When combining information from the standard notification variables country of birth and citizenship, the sensitivity to detect second generation migration was 28.6%. Conclusions There is a higher rate of tuberculosis among second generation migrants compared to native residents in Berlin. This may be explained by presumably frequent contact and transmission within migrant populations. Second generation migration is insufficiently captured by the surveillance variables country of birth and citizenship. Surveillance systems in Western Europe should allow for quantifying the tuberculosis burden in this important risk group. PMID:26061733

Theoretical and computational study of the energy dependence of the muon transfer rate from hydrogen to higher-Z gases

Energy Technology Data Exchange (ETDEWEB)

Bakalov, Dimitar, E-mail: dbakalov@inrne.bas.bg [Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, Tsarigradsko chaussée 72, Sofia 1784 (Bulgaria); Adamczak, Andrzej [Institute of Nuclear Physics, Polish Academy of Sciences, ul. Radzikowskiego 152, 31-342 Krakow (Poland); Stoilov, Mihail [Institute for Nuclear Research and Nuclear Energy, Bulgarian Academy of Sciences, Tsarigradsko chaussée 72, Sofia 1784 (Bulgaria); Vacchi, Andrea [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, Via A. Valerio 2, 34127 Trieste (Italy)

2015-01-23

The recent PSI Lamb shift experiment and the controversy about proton size revived the interest in measuring the hyperfine splitting in muonic hydrogen as an alternative possibility for comparing ordinary and muonic hydrogen spectroscopy data on proton electromagnetic structure. This measurement critically depends on the energy dependence of the muon transfer rate to heavier gases in the epithermal range. The available data provide only qualitative information, and the theoretical predictions have not been verified. We propose a new method by measurements of the transfer rate in thermalized target at different temperatures, estimate its accuracy and investigate the optimal experimental conditions. - Highlights: • Method for measuring the energy dependence of muon transfer rate to higher-Z gases. • Thermalization and depolarization of muonic hydrogen studied by Monte Carlo method. • Optimal experimental conditions determined by Monte Carlo simulations. • Mathematical model and for estimating the uncertainty of the experimental results.

Emotional Competence and Drop-Out Rates in Higher Education

Science.gov (United States)

Kingston, Emma

2008-01-01

Purpose: The purpose of this paper is to compare the emotional competence of first year undergraduates enrolled on a high or low drop-out rate (HDR and LDR, respectively) course, at a newly established university within the UK. Design/methodology/approach: A mixed methods approach using both quantitative and qualitative data collection methods was…

Higher USA State Resident Neuroticism Is Associated With Lower State Volunteering Rates.

Science.gov (United States)

McCann, Stewart J H

2017-12-01

Highly neurotic persons have dispositional characteristics that tend to precipitate social anxiety that discourages formal volunteering. With the 50 American states as analytical units, Study 1 found that state resident neuroticism correlated highly ( r = -.55) with state volunteering rates and accounted for another 26.8% of the volunteering rate variance with selected state demographics controlled. Study 2 replicated Study 1 during another period and extended the association to college student, senior, secular, and religious volunteering rates. Study 3 showed state resident percentages engaged in other social behaviors involving more familiarity and fewer demands than formal volunteering related to state volunteering rates but not to neuroticism. In Study 4, state resident neuroticism largely accounted statistically for relations between state volunteering rates and state population density, collectivism, social capital, Republican preference, and well-being. This research is the first to show that state resident neuroticism is a potent predictor of state volunteering rates.

Does higher income inequality adversely influence infant mortality rates? Reconciling descriptive patterns and recent research findings.

Science.gov (United States)

Siddiqi, Arjumand; Jones, Marcella K; Erwin, Paul Campbell

2015-04-01

As the struggle continues to explain the relatively high rates of infant mortality (IMR) exhibited in the United States, a renewed emphasis is being placed on the role of possible 'contextual' determinants. Cross-sectional and short time-series studies have found that higher income inequality is associated with higher IMR at the state level. Yet, descriptively, the longer-term trends in income inequality and in IMR seem to call such results into question. To assess whether, over the period 1990-2007, state-level income inequality is associated with state-level IMR; to examine whether the overall effect of income inequality on IMR over this period varies by state; to test whether the association between income inequality and IMR varies across this time period. IMR data--number of deaths per 1000 live births in a given state and year--were obtained from the U.S. Centers for Disease Control Wonder database. Income inequality was measured using the Gini coefficient, which varies from zero (complete equality) to 100 (complete inequality). Covariates included state-level poverty rate, median income, and proportion of high school graduates. Fixed and random effects regressions were conducted to test hypotheses. Fixed effects models suggested that, overall, during the period 1990-2007, income inequality was inversely associated with IMR (β = -0.07, SE (0.01)). Random effects models suggested that when the relationship was allowed to vary at the state-level, it remained inverse (β = -0.05, SE (0.01)). However, an interaction between income inequality and time suggested that, as time increased, the effect of income inequality had an increasingly positive association with total IMR (β = 0.009, SE (0.002)). The influence of state income inequality on IMR is dependent on time, which may proxy for time-dependent aspects of societal context. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predicting higher education graduation rates from institutional characteristics and resource allocation

OpenAIRE

Florence A. Hamrick; John H. Schuh; Mack C. Shelley

2004-01-01

This study incorporated institutional characteristics (e.g., Carnegie type, selectivity) and resource allocations (e.g., instructional expenditures, student affairs expenditures) into a statistical model to predict undergraduate graduation rates. Instructional expenditures, library expenditures, and a number of institutional classification variables were significant predictors of graduation rates. Based on these results, recommendations as well as warranted cautions are included about allocat...

Vigorous physical activity predicts higher heart rate variability among younger adults.

Science.gov (United States)

May, Richard; McBerty, Victoria; Zaky, Adam; Gianotti, Melino

2017-06-14

Baseline heart rate variability (HRV) is linked to prospective cardiovascular health. We tested intensity and duration of weekly physical activity as predictors of heart rate variability in young adults. Time and frequency domain indices of HRV were calculated based on 5-min resting electrocardiograms collected from 82 undergraduate students. Hours per week of both moderate and vigorous activity were estimated using the International Physical Activity Questionnaire. In regression analyses, hours of vigorous physical activity, but not moderate activity, significantly predicted greater time domain and frequency domain indices of heart rate variability. Adjusted for weekly frequency, greater daily duration of vigorous activity failed to predict HRV indices. Future studies should test direct measurements of vigorous activity patterns as predictors of autonomic function in young adulthood.

Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms.

Science.gov (United States)

Ismail, Sabariah; Hanapi, Nur Aziah; Ab Halim, Mohd Rohaimi; Uchaipichat, Verawan; Mackenzie, Peter I

2010-05-14

The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor, MgCl(2), cell lysate of respective isoform, and 4MU at the approximate apparent K(m) or S(50) value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 microg/mL and 0.01, 0.10, 1.0, 10 and 50 microg/mL respectively. Both extracts variably inhibited the activity of most of the isoforms in a concentration dependent manner. Andrographis paniculata extract was the better inhibitor of all the isoforms studied (IC(50) 1.70 microg/mL for UGT1A3, 2.57 microg/mL for UGT1A8, 2.82 microg/mL for UGT2B7, 5.00 micorg/mL for UGT1A1, 5.66 microg/mL for UGT1A6, 9.88 microg/mL for UGT1A7 and 15.66 microg/mL for UGT1A10). Both extracts showed less than 70% inhibition of UGT2B15, so the IC(50) values were >50 microg/mL. The inhibition of human UGTs by Andrographis paniculata and Orthosiphon stamineus extracts in vitro suggests a potential for drug-herbal extract interactions in the therapeutic setting.

In vivo metabolism of cannabinol by the mouse and rat and a comparison with a metabolism of delta 1-tetrahydrocannabinol and cannabidiol.

Science.gov (United States)

Harvey, D J; Martin, B R; Paton, W D

1977-12-01

The in vivo liver metabolism of cannabinol has been studied in the mouse and rat by combined gas chromatography and mass spectrometry. Cannabinol glucuronide was the major metabolite of cannabinol in the mouse and was accompanied by relatively large amounts of 7-hydroxycannabinol, cannabinol-7-oic acid and their corresponding glucuronide conjugates. Lower concentrations of glucuronides were found in the rat. Two series of disubstituted metabolites were found containing either a 7-hydroxyl or a 7-carboxylic acid group and a second hydroxyl group in the 1 inch-4 inch positions of the sidechain. These were of low concentration in the mouse but higher in the rat; 1 inch-hydroxy metabolites were particularly abundant in the latter species. Also found in the rat livers were small amounts of sidechain monohydroxy metabolites and larger quantities of 4 inches, 5 inches-bisnorcannabinol-3 inches-oic acid; these were absent in the mouse. The metabolites were identified using the trimethylsilyl (TMS), [2H9] TMS and methyl ester-TMS derivatives, and by reduction of acid metabolites with lithium aluminium deuteride to the corresponding alcohols.

Is the higher rate of parental child homicide in stepfamilies an effect of non-genetic relatedness?

Institute of Scientific and Technical Information of China (English)

Hans TEMRIN; Johanna NORDLUND; Mikael RYING; Birgitta S. TULLBERG

2011-01-01

In an evolutionary perspective individuals are expected to vary the degree of parental love and care in relation to the fitness value that a child represents. Hence, stepparents are expected to show less solicitude than genetically related parents, and this lack of genetic relatedness has been used to explain the higher frequencies of child abuse and homicide found in stepfamilies.However, other factors than non-genetic relatedness may cause this over-representation in stepfamilies. Here we use a 45-year data set of parental child homicides in Sweden to test two hypotheses related to the higher incidence in stepfamilies: 1) adults in different types of family differ in their general disposition to use violence, and 2) parents are more likely to kill stepchildren than genetically related children. Of the 152 perpetrators in biparental families there was an overrepresentation of perpetrators in stepfamilies (n=27) compared with the general population. We found support for the first hypothesis in that both general and violent crime rates were higher in stepfamilies, both in the general population and among perpetrators of child homicide. However, we found no support for the second hypothesis because of the 27 perpetrators in stepfamilies the perpetrator killed a genetically related child in 13 cases, a stepchild in 13 cases and both types of children in one case. Moreover, out of the 12 families where the perpetrator lived with both stepchildren and genetic children, there was no bias towards killing stepchildren. Thus, we found no evidence for an effect of non-genetic relatedness per se [Current Zoology 57 (3): 253-59, 2011].

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

Science.gov (United States)

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

2014-11-01

The assessment of quantification results of the alcohol abuse marker ethyl glucuronide (EtG) in hair in comparison to the cut-off values for the drinking behavior may be complicated by cosmetic hair bleaching. Thus, the impact of increasing exposure to hydrogen peroxide on the EtG content of hair was investigated. Simultaneously, the change of absorbance in the range of 1000-1100 cm(-1) indicative for the oxidation of cystine was investigated non-destructively by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) using pulverized portions of the respective hair samples. Hair samples treated with hydrogen peroxide consistently displayed a significantly increased absorbance at 1040 cm(-1) associated with the formation of cysteic acid. The EtG content decreased significantly if the hair was treated with alkaline hydrogen peroxide as during cosmetic bleaching. It could be shown that ATR-FTIR is capable of detecting an exposure to hydrogen peroxide when still no brightening was visible and already before the EtG content deteriorated significantly. Thus, hair samples suspected of having been exposed to oxidative treatment may be checked non-destructively by a readily available technique. This assay is also possible retrospectively after EtG extraction and using archived samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In Vivo Exposure of Kaempferol Is Driven by Phase II Metabolic Enzymes and Efflux Transporters.

Science.gov (United States)

Zheng, Liang; Zhu, Lijun; Zhao, Min; Shi, Jian; Li, Yuhuan; Yu, Jia; Jiang, Huangyu; Wu, Jinjun; Tong, Yunli; Liu, Yuting; Hu, Ming; Lu, Linlin; Liu, Zhongqiu

2016-09-01

Kaempferol is a well-known flavonoid; however, it lacks extensive pharmacokinetic studies. Phase II metabolic enzymes and efflux transporters play an important role in the disposition of flavonoids. This study aimed to investigate the mechanism by which phase II metabolic enzymes and efflux transporters determine the in vivo exposure of kaempferol. Pharmacokinetic analysis in Sprague-Dawley rats revealed that kaempferol was mostly biotransformed to conjugates, namely, kaempferol-3-glucuronide (K-3-G), kaempferol-7-glucuronide (K-7-G), and kaempferol-7-sulfate, in plasma. K-3-G represented the major metabolite. Compared with that in wild-type mice, pharmacokinetics in knockout FVB mice demonstrated that the absence of multidrug resistance protein 2 (MRP2) and breast cancer resistance protein (BCRP) significantly increased the area under the curve (AUC) of the conjugates. The lack of MRP1 resulted in a much lower AUC of the conjugates. Intestinal perfusion in rats revealed that the glucuronide conjugates were mainly excreted in the small intestine, but 7-sulfate was mainly excreted in the colon. In Caco-2 monolayers, K-7-G efflux toward the apical (AP) side was significantly higher than K-3-G efflux. In contrast, K-3-G efflux toward the basolateral (BL) side was significantly higher than K-7-G efflux. The BL-to-AP efflux was significantly reduced in the presence of the MRP2 inhibitor LTC4. The AP-to-BL efflux was significantly decreased in the presence of the BL-side MRPs inhibitor MK571. The BCRP inhibitor Ko143 decreased the glucuronide conjugate efflux. Therefore, kaempferol is mainly exposed as K-3-G in vivo, which is driven by phase II metabolic enzymes and efflux transporters (i.e., BCRP and MRPs).

Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium for detection of alcohol abuse during pregnancy: Correlation study between both biomarkers.

Science.gov (United States)

Cabarcos, Pamela; Tabernero, María Jesús; Otero, José Luís; Míguez, Martha; Bermejo, Ana María; Martello, Simona; De Giovanni, Nadia; Chiarotti, Marcello

2014-11-01

This article presents results from 47 meconium samples, which were analyzed for fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for detection of gestational alcohol consumption. A validated microwave assisted extraction (MAE) method in combination with GC-MS developed in the Institute of Forensic Science (Santiago de Compostela) was used for FAEE and the cumulative concentration of ethyl myristate, ethyl palmitate and ethyl stearate with a cut-off of 600ng/g was applied for interpretation. A simple method for identification and quantification of EtG has been evaluated by ultrasonication followed solid phase extraction (SPE). Successful validation parameters were obtained for both biochemical markers of alcohol intake. FAEE and EtG concentrations in meconium ranged between values lower than LOD and 32,892ng/g or 218ng/g respectively. We have analyzed FAEE and EtG in the same meconium aliquot, enabling comparison of the efficiency of gestational ethanol exposure detection. Certain agreement between the two biomarkers was found as they are both a very specific alcohol markers, making it a useful analysis for confirmation. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of gamma irradiation and steam explosion pretreatment for ethanol production from agricultural residues

International Nuclear Information System (INIS)

Wang, Ke-qin; Xiong, Xing-yao; Chen, Jing-ping; Chen, Liang; Su, Xiaojun; Liu, Yun

2012-01-01

It was evaluated the influence of gamma irradiation and steam explosion pretreatment on the components and the water-soluble sugars of rice straw. Compared with the steam explosion pretreated rice straw, cellucose, hemicellucose and lignin for irradiation pretreated rice sample were much more greatly degraded and the relative content of glucose was significantly enhanced from 6.58% to 47.44%. Interestingly, no glucuronide acid was detected in irradiation pretreated rice straw, while glucuronide acid with the content from 8.5 mg/g to 9.2 mg/g was obtained in steam explosion pretreated sample. Followed by enzymatic hydrolysis, higher concentration of reducing sugars (including glucose and xylose) of irradiation pretreated rice sample (90.3 mg/g) was obtained, which was approximately 2.4- and 1.1- fold higher of the unpretreated (37.2 mg/g) and of steam explosion pretreated sample (85.4 mg/g). To further verify the effectiveness of irradiation pretreatment, characterizations of rice straw, corn stalk and bagasse by an integrated process of dilute acid/enzymatic hydrolysis and irradiation pretreatment were also investigated. -- Highlights: ► We compare irradiation and steam explosion pretreatments for bioethanol production. ► We examine changes in compositions of the components and the water-soluble sugars. ► No glucuronide acid was detected in gamma irradiation pretreated rice straw. ► We evaluate an integrated method of acid/enzyme-hydrolyzed irradiation pretreatment.

Removal of boron(III) by N-methylglucamine-type cellulose derivatives with higher adsorption rate

International Nuclear Information System (INIS)

Inukai, Yoshinari; Tanaka, Yoshiharu; Matsuda, Toshio; Mihara, Nobutake; Yamada, Kouji; Nambu, Nobuyoshi; Itoh, Osamu; Doi, Takao; Kaida, Yasuhiko; Yasuda, Seiji

2004-01-01

To obtain adsorbents for boron(III) derived from a natural polymer, two forms (powder and fiber) of N-methylglucamine-type cellulose derivatives were newly synthesized. After the graft polymerization of two forms of cellulose with vinyl monomer having epoxy groups, the N-methylglucamine-type cellulose derivatives were obtained by the reaction of the grafted cellulose with N-methylglucamine. The adsorption capacities of the cellulose derivatives for boron(III) were the same levels as that of a commercially available N-methylglucamine-type polystyrene resin. However, the cellulose derivatives adsorbed boron(III) more quickly than the polystyrene resin. The adsorption and desorption of boron(III) with a column method using the cellulose fiber were achieved at a higher flow rate than that using the polystyrene resin. In addition, the boron(III), adsorbed on the cellulose fiber column, was quantitatively recovered with dilute hydrochloric acid in 20- and 200-fold increased concentrations. Consequently, it was found that the cellulose derivatives were superior to the polystyrene resin as adsorbents for boron(III) for treatment of a large quantity of wastewater

Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction.

Science.gov (United States)

Serra, Aida; Rubió, Laura; Macià, Alba; Valls, Rosa-M; Catalán, Úrsula; de la Torre, Rafael; Motilva, Maria-José

2013-11-01

Two different rapid sample pretreatment strategies, dried spot cards, and microelution solid-phase extraction plates (μSPE), with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been developed and validated for the determination of hydroxytyrosol and its metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3'-O-glucuronide, hydroxytyrosol-4'-O-glucuronide, hydroxytyrosol-3-O-sulphate, and homovanillic alcohol-4'-O-glucuronide were used as the target compounds. Using the FTA DMPK-A dried urine spot card under optimum conditions, with 5 μL of preconcentrated urine volume and 100 μL of methanol/water (50/50, v/v) as the elution solvent, the extraction recovery (%R) of the compounds studied was higher than 80%, and the matrix effect (%ME) was less than 8%. The stability of these cards and punching at the centre or side of the card were also studied, obtaining an excellent stability after 7 days of storage and complete homogeneity across the surface of the dried drop. The different μSPE parameters that affect the efficiency were also studied, and under optimum conditions, the %R and the %ME were higher than 70% and lower than 17%, respectively. The linearity range in dried urine spot cards was 2.5-20 μM for all the metabolites, with the exception of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 μM and 2.5-50 μM respectively. With regards to μSPE, the linearity range was 0.5-5 μM for all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08-5 μM. The quantification limits (LOQs) were 0.3-2.5 μM and 0.08-0.5 μM in dried spot cards and in μSPE, respectively. The two developed methods were then applied and compared for determining hydroxytyrosol and its metabolites in human 24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched virgin olive oil. The metabolites identified were hydroxytyrosol in its glucuronide and sulphate

Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

Science.gov (United States)

Berger, Jean-Luc; Nguyen, Yohan; Lebrun, Delphine; Migault, Caroline; Hentzien, Maxime; Marty, Hélène; Bani-Sadr, Firouzé

2017-01-01

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin

International Nuclear Information System (INIS)

Liu, Wei; Feng, Qian; Li, Ye; Ye, Ling; Hu, Ming; Liu, Zhongqiu

2012-01-01

Emodin is a poorly bioavailable but promising plant-derived anticancer drug candidate. The low oral bioavailability of emodin is due to its extensive glucuronidation in the intestine and liver. Caco-2 cell culture model was used to investigate the interplay between UDP-glucuronosyltransferases (UGTs) and efflux transporters in the intestinal disposition of emodin. Bidirectional transport assays of emodin at different concentrations were performed in the Caco-2 monolayers with or without multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP) efflux transporter chemical inhibitors. The bidirectional permeability of emodin and its glucuronide in the Caco-2 monolayers was determined. Emodin was rapidly metabolized to emodin glucuronide in Caco-2 cells. LTC4, a potent inhibitor of MRP2, decreased the efflux of emodin glucuronide and also substantially increased the intracellular glucuronide level in the basolateral-to-apical (B–A) direction. MK-571, chemical inhibitor of MRP2, MRP3, and MRP4, significantly reduced the efflux of glucuronide in the apical-to-basolateral (A–B) and B–A directions in a dose-dependent manner. However, dipyridamole, a BCRP chemical inhibitor demonstrated no effect on formation and efflux of emodin glucuronide in Caco-2 cells. In conclusion, UGT is a main metabolic pathway for emodin in the intestine, and the MRP family is composed of major efflux transporters responsible for the excretion of emodin glucuronide in the intestine. The coupling of UGTs and MRP efflux transporters causes the extensive metabolism, excretion, and low bioavailability of emodin. -- Highlights: ► Glucuronidation is the main reason for the poor oral bioavailability of emodin. ► Efflux transporters are involved in the excretion of emodin glucuronide. ► The intestine is the main organ for metabolism of emodin.

Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin

Energy Technology Data Exchange (ETDEWEB)

Liu, Wei; Feng, Qian; Li, Ye; Ye, Ling [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China); Hu, Ming, E-mail: mhu@uh.edu [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China); Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX 77030 (United States); Liu, Zhongqiu, E-mail: liuzq@smu.edu.cn [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China)

2012-12-15

Emodin is a poorly bioavailable but promising plant-derived anticancer drug candidate. The low oral bioavailability of emodin is due to its extensive glucuronidation in the intestine and liver. Caco-2 cell culture model was used to investigate the interplay between UDP-glucuronosyltransferases (UGTs) and efflux transporters in the intestinal disposition of emodin. Bidirectional transport assays of emodin at different concentrations were performed in the Caco-2 monolayers with or without multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP) efflux transporter chemical inhibitors. The bidirectional permeability of emodin and its glucuronide in the Caco-2 monolayers was determined. Emodin was rapidly metabolized to emodin glucuronide in Caco-2 cells. LTC4, a potent inhibitor of MRP2, decreased the efflux of emodin glucuronide and also substantially increased the intracellular glucuronide level in the basolateral-to-apical (B–A) direction. MK-571, chemical inhibitor of MRP2, MRP3, and MRP4, significantly reduced the efflux of glucuronide in the apical-to-basolateral (A–B) and B–A directions in a dose-dependent manner. However, dipyridamole, a BCRP chemical inhibitor demonstrated no effect on formation and efflux of emodin glucuronide in Caco-2 cells. In conclusion, UGT is a main metabolic pathway for emodin in the intestine, and the MRP family is composed of major efflux transporters responsible for the excretion of emodin glucuronide in the intestine. The coupling of UGTs and MRP efflux transporters causes the extensive metabolism, excretion, and low bioavailability of emodin. -- Highlights: ► Glucuronidation is the main reason for the poor oral bioavailability of emodin. ► Efflux transporters are involved in the excretion of emodin glucuronide. ► The intestine is the main organ for metabolism of emodin.

In Vitro and in Vivo Metabolism of Verproside in Rats

Directory of Open Access Journals (Sweden)

Dae Hee Shin

2012-10-01

Full Text Available Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to verproside glucuronides (M1 and M2, verproside sulfates (M3 and M4, picroside II (M5, M5 glucuronide (M7, M5 sulfate (M9, isovanilloylcatalpol (M6, M6 glucuronide (M8, M6 sulfate (M10, 3,4-dihydroxybenzoic acid (M11, M11 glucuronide (M12, M11 sulfates (M13 and M14, 3-methyoxy-4-hydroxybenzoic acid (M15, M15 glucuronides (M17 and M18, M15 sulfate (M20, 3-hydroxy-4-methoxybenzoic acid (M16, M16 glucuronide (M19, and M16 sulfate (M21. Incubation of verproside with rat hepatocytes resulted in thirteen metabolites (M1–M11, M13, and M14. Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of verproside, the drug was recovered in bile (0.77% of dose and urine (4.48% of dose, and O-methylation of verproside to picroside II (M5 and isovanilloylcatalpol (M6 followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of verproside in rats.

Is the higher rate of parental child homicide in stepfamilies an effect of non-genetic relatedness?

Directory of Open Access Journals (Sweden)

Hans TEMRIN, Johanna NORDLUND, Mikael RYING, Birgitta S. TULLBERG

2011-06-01

Full Text Available In an evolutionary perspective individuals are expected to vary the degree of parental love and care in relation to the fitness value that a child represents. Hence, stepparents are expected to show less solicitude than genetically related parents, and this lack of genetic relatedness has been used to explain the higher frequencies of child abuse and homicide found in stepfamilies. However, other factors than non-genetic relatedness may cause this over-representation in stepfamilies. Here we use a 45-year data set of parental child homicides in Sweden to test two hypotheses related to the higher incidence in stepfamilies: 1 adults in different types of family differ in their general disposition to use violence, and 2 parents are more likely to kill stepchildren than genetically related children. Of the 152 perpetrators in biparental families there was an overrepresentation of perpetrators in stepfamilies (n=27 compared with the general population. We found support for the first hypothesis in that both general and violent crime rates were higher in stepfamilies, both in the general population and among perpetrators of child homicide. However, we found no support for the second hypothesis because of the 27 perpetrators in stepfamilies the perpetrator killed a genetically related child in 13 cases, a stepchild in 13 cases and both types of children in one case. Moreover, out of the 12 families where the perpetrator lived with both stepchildren and genetic children, there was no bias towards killing stepchildren. Thus, we found no evidence for an effect of non-genetic relatedness per se [Current Zoology 57 (3: 253–259, 2011].

Competing pathways in drug metabolism. I. Effect of input concentration on the conjugation of gentisamide in the once-through in situ perfused rat liver preparation

International Nuclear Information System (INIS)

Morris, M.E.; Yuen, V.; Tang, B.K.; Pang, K.S.

1988-01-01

Sulfation and glucuronidation are two parallel pathways for the metabolism of phenolic substrates. Gentisamide (GAM) was used as a model compound to examine the effects of parallel competing pathways on drug disappearance and metabolite formation in the once-through perfused rat liver preparation. GAM was found to form one glucuronide (GAM-5G) and two sulfate (GAM-2S and GAM-5S) conjugates. These GAM conjugates were biosynthesized in recirculating rat liver preparations, and were isolated by preparative high-performance liquid chromatography. Specific incorporation of 35S-sodium sulfate and [14C]glucose into GAM sulfate and glucuronide conjugates revealed corresponding elution patterns as labeled GAM metabolites. Their identities were characterized by enzymatic and acid hydrolyses and by NMR spectroscopy. Gentisamide-5-sulfate (GAM-5S) and gentisamide-5-glucuronide (GAM-5G) are major metabolites, and gentisamide-2-sulfate (GAM-2S) is a minor metabolite. Single-pass rat liver perfusions were used to examine the effect of stepwise increases/decreases of input GAM concentration (CIn) on the extraction ratio (E) of GAM and formation of metabolites. The E of GAM remained constant (about 0.89) at input concentrations from 0.9 to 120 microM and decreased at CIn greater than 120 microM. Metabolite patterns, however, changed with GAM CIn, even when E was constant at CIn up to 120 microM. GAM-5S was present as the major metabolite of GAM at all GAM CInS in most liver preparations but the proportions of GAM-5S and GAM-2S decreased at increasing CIn; the proportion of GAM-5G, a minor metabolite at low CIn, increased with increasing CIn. Biliary excretion rates at steady state accounted for 5.3 +/- 2.7% (mean +/- S.D.) of the input rate: GAM-5G was the predominant metabolite found

Improving the ablation efficiency of excimer laser systems with higher repetition rates through enhanced debris removal and optimized spot pattern.

Science.gov (United States)

Arba-Mosquera, Samuel; Klinner, Thomas

2014-03-01

To evaluate the reasons for the required increased radiant exposure for higher-repetition-rate excimer lasers and determine experimentally possible compensations to achieve equivalent ablation profiles maintaining the same single-pulse energies and radiant exposures for laser repetition rates ranging from 430 to 1000 Hz. Schwind eye-tech-solutions GmbH and Co. KG, Kleinostheim, Germany. Experimental study. Poly(methyl methacrylate) (PMMA) plates were photoablated. The pulse laser energy was maintained during all experiments; the effects of the flow of the debris removal, the shot pattern for the correction, and precooling the PMMA plates were evaluated in terms of achieved ablation versus repetition rate. The mean ablation performance ranged from 88% to 100%; the variability between the profile measurements ranged from 1.4% to 6.2%. Increasing the laser repetition rate from 430 Hz to 1000 Hz reduced the mean ablation performance from 98% to 91% and worsened the variability from 1.9% to 4.3%. Increasing the flow of the debris removal, precooling the PMMA plates to -18°C, and adapting the shot pattern for the thermal response of PMMA to excimer ablation helped stabilize the variability. Only adapting the shot pattern for the thermal response of PMMA to excimer ablation helped stabilize the mean ablation performance. The ablation performance of higher-repetition-rate excimer lasers on PMMA improved with improvements in the debris removal systems and shot pattern. More powerful debris removal systems and smart shot patterns in terms of thermal response improved the performance of these excimer lasers. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Morphine metabolites

DEFF Research Database (Denmark)

Christrup, Lona Louring

1997-01-01

, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

The Effects of Gun Ownership Rates and Gun Control Laws on Suicide Rates

OpenAIRE

Mark Gius

2011-01-01

The purpose of the present study is to determine the effects of gun control laws and gun ownership rates on state-level suicide rates. Using the most recent data on suicide rates, gun control measures, and gun ownership rates, the results of the present study suggest that states that require handgun permits have lower gun-related suicide rates, and states that have higher gun ownership rates have higher gun-related suicide rates. Regarding non-gun suicides, results suggest that stricter gun c...

Absorption of N-phenylpropenoyl-L-amino acids in healthy humans by oral administration of cocoa (Theobroma cacao).

Science.gov (United States)

Stark, Timo; Lang, Roman; Keller, Daniela; Hensel, Andreas; Hofmann, Thomas

2008-10-01

Besides flavan-3-ols, a family of N-phenylpropenoyl-L-amino acids (NPAs) has been recently identified as polyphenol/amino acid conjugates in the seeds of Theobroma cacao as well as in a variety of herbal drugs. Stimulated by reports on their biological activity, the purpose of this study was to investigate if these amides are absorbed by healthy volunteers after administration of a cocoa drink. For the first time, 12 NPAs were quantified in human urine by means of a stable isotope dilution analysis with LC-MS/MS (MRM) detection. A maximum amount was found in the urine taken 2 h after the cocoa consumption. The highest absolute amount of NPAs excreted with the urine was found for N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid (5), but the highest recovery rate (57.3 and 22.8%), that means the percentage amount of ingested amides excreted with the urine, were determined for N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid (6) and N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-tyrosine (13). In order to gain first insights into the NPA metabolism in vivo, urine samples were analyzed by LC-MS/MS before and after beta-glucuronidase/sulfatase treatment. As independent of the enzyme treatment the same NPA amounts were found in urine, there is strong evidence that these amides are metabolized neither via their O-glucuronides nor their O-sulfates. In order to screen for caffeic acid O-glucuronides as potential NPA metabolites, urine samples were screened by means of LC-MS/MS for caffeic acid 3-O-beta-D-glucuronide and 4-O-beta-D-glucuronide. But not even trace amounts of one of these glucuronides were detectable, thus excluding them as major NPA metabolites and underlining the importance of future investigations on a potential O-methylation or reduction of the N-phenylpropenoyl moiety in NPAs.

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

Science.gov (United States)

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

2014-01-01

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

Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

International Nuclear Information System (INIS)

Sabourin, P.J.; Sun, J.D.; MacGregor, J.T.; Wehr, C.M.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

1990-01-01

Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased

Higher speciation and lower extinction rates influence mammal diversity gradients in Asia.

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Tamma, Krishnapriya; Ramakrishnan, Uma

2015-02-04

Little is known about the patterns and correlates of mammal diversity gradients in Asia. In this study, we examine patterns of species distributions and phylogenetic diversity in Asia and investigate if the observed diversity patterns are associated with differences in diversification rates between the tropical and non-tropical regions. We used species distribution maps and phylogenetic trees to generate species and phylogenetic diversity measures for 1° × 1° cells across mainland Asia. We constructed lineage-through-time plots and estimated diversification shift-times to examine the temporal patterns of diversifications across orders. Finally, we tested if the observed gradients in Asia could be associated with geographical differences in diversification rates across the tropical and non-tropical biomes. We estimated speciation, extinction and dispersal rates across these two regions for mammals, both globally and for Asian mammals. Our results demonstrate strong latitudinal and longitudinal gradients of species and phylogenetic diversity with Southeast Asia and the Himalayas showing highest diversity. Importantly, our results demonstrate that differences in diversification (speciation, extinction and dispersal) rates between the tropical and the non-tropical biomes influence the observed diversity gradients globally and in Asia. For the first time, we demonstrate that Asian tropics act as both cradles and museums of mammalian diversity. Temporal and spatial variation in diversification rates across different lineages of mammals is an important correlate of species diversity gradients observed in Asia.

Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

LENUS (Irish Health Repository)

O'Seaghdha, C M

2011-04-06

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?

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Moll, E; Korevaar, J C; Bossuyt, P M M; van der Veen, F

2008-08-01

An RCT among newly diagnosed, therapy naive women with polycystic ovary syndrome (PCOS) showed no significant differences in ovulation rate, ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate. We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates. Subgroup analysis based on clinical and biochemical parameters of 111 women randomized to clomifene citrate plus metformin compared with 114 women randomized to clomifene citrate plus placebo. The data for age, BMI, waist-hip ratio (WHR) and plasma testosterone were available in all women, 2 h glucose in 80% of women and homeostatic model assessment for assessing insulin sensitivity (HOMA) in 50% of women. Of the women who were allocated to the metformin group, 44 women (40%) reached an ongoing pregnancy. In the placebo group, 52 women (46%) reached an ongoing pregnancy. There was a significantly different chance of an ongoing pregnancy for metformin versus placebo between subgroups based on age and WHR (P = 0.014). There was a positive effect of metformin versus placebo on pregnancy rate in older women (>or=28 years) with a high WHR, a negative effect of metformin versus placebo in young women (Metformin may be an effective addition to clomifene citrate in infertile women with PCOS, especially in older and viscerally obese patients.

Results of a pilot scale melter test to attain higher production rates

International Nuclear Information System (INIS)

Elliott, M.L.; Perez, J.M. Jr.; Chapman, C.C.

1991-01-01

A pilot-scale melter test was completed as part of the effort to enhance glass production rates. The experiment was designed to evaluate the effects of bulk glass temperature and feed oxide loading. The maximum glass production rate obtained, 86 kg/hr-m 2 , was over 200% better than the previous record for the melter used

Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

Science.gov (United States)

Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

2018-02-28

A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

3D versus 2D Systematic Transrectal Ultrasound-Guided Prostate Biopsy: Higher Cancer Detection Rate in Clinical Practice

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Alexandre Peltier

2013-01-01

Full Text Available Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P<0.05. There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.

International comparisons of preterm birth: higher rates of late preterm birth are associated with lower rates of stillbirth and neonatal death.

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Lisonkova, S; Sabr, Y; Butler, B; Joseph, K S

2012-12-01

To examine international rates of preterm birth and potential associations with stillbirths and neonatal deaths at late preterm and term gestation. Ecological study. Canada, USA and 26 countries in Europe. All deliveries in 2004. Information on preterm birth (Statistics Canada, the EURO-PERISTAT project and the National Center for Health Statistics. Pearson correlation coefficients and random-intercept Poisson regression were used to examine the association between preterm birth rates and gestational age-specific stillbirth and neonatal death rates. Rate ratios with 95% confidence intervals were estimated after adjustment for maternal age, parity and multiple births. Stillbirths and neonatal deaths ≥ 32 and ≥ 37 weeks of gestation. International rates of preterm birth (births. Preterm birth rates at 32-36 weeks were inversely associated with stillbirths at ≥ 32 weeks (adjusted rate ratio 0.94, 95% CI 0.92-0.96) and ≥ 37 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) of gestation and inversely associated with neonatal deaths at ≥ 32 weeks (adjusted rate ratio 0.88, 95% CI 0.85-0.91) and ≥ 37 weeks (adjusted rate ratio 0.82, 95% CI 0.78-0.86) of gestation. Countries with high rates of preterm birth at 32-36 weeks of gestation have lower stillbirth and neonatal death rates at and beyond 32 weeks of gestation. Contemporary rates of preterm birth are indicators of both perinatal health and obstetric care services. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Role of UDP-Glucuronosyltransferase (UGT) 2B2 in Metabolism of Triiodothyronine: Effect of Microsomal Enzyme Inducers in Sprague Dawley and UGT2B2-Deficient Fischer 344 Rats

Science.gov (United States)

Richardson, Terrilyn A.; Klaassen, Curtis D.

2010-01-01

Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) can impact thyroid hormone homeostasis in rodents. Increased glucuronidation can result in reduction of serum thyroid hormone and a concomitant increase in thyroid-stimulating hormone (TSH). UGT2B2 is thought to glucuronidate triiodothyronine (T3). The purposes of this study were to determine the role of UGT2B2 in T3 glucuronidation and whether increased T3 glucuronidation mediates the increased TSH observed after MEI treatment. Sprague Dawley (SD) and UGT2B2-deficient Fischer 344 (F344) rats were fed a control diet or diet containing pregnenolone-16α-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum thyroxine (T4), T3, and TSH concentrations, hepatic androsterone/T4/T3 glucuronidation, and thyroid follicular cell proliferation were determined. In both SD and F344 rats, MEI treatments decreased serum T4, whereas serum T3 was maintained (except with PCB treatment). Hepatic T4 glucuronidation increased significantly after MEI in both rat strains. Compared with the other MEI, only PCN treatment significantly increased T3 glucuronidation (281 and 497%) in both SD and UGT2B2-deficient F344 rats, respectively, and increased both serum TSH and thyroid follicular cell proliferation. These data demonstrate an association among increases in T3 glucuronidation, TSH, and follicular cell proliferation after PCN treatment, suggesting that T3 is glucuronidated by other PCN-inducible UGTs in addition to UGT2B2. These data also suggest that PCN (rather than 3-MC or PCB) promotes thyroid tumors through excessive TSH stimulation of the thyroid gland. PMID:20421340

[Effect of high magnesium ion concentration on the electron transport rate and proton exchange in thylakoid membranes in higher plants].

Science.gov (United States)

Ignat'ev, A R; Khorobrykh, S A; Ivanov, B N

2001-01-01

The effects of magnesium ion concentration on the rate of electron transport in isolated pea thylakoids were investigated in the pH range from 4.0 up to 8.0. In the absence of magnesium ions in the medium and in the presence of 5 mM MgCl2 in the experiments not only without added artificial acceptors but also with ferricyanide or methylviologen as an acceptor, this rate had a well-expressed maximum at pH 5.0. It was shown that, after depression to minimal values at pH 5.5-6.5, it gradually rose with increasing pH. An increase in magnesium ion concentration up to 20 mM essentially affected the electron transfer rate: it decreased somewhat at pH 4.0-5.0 but increased at higher pH values. At this magnesium ion concentration, the maximum rate was at pH 6.0-6.5 and the minimum, at pH 7.0. Subsequent rise upon increasing pH to 8.0 was expressed more sharply. The influence of high magnesium ion concentration on the rate of electron transport was not observed in the presence of gramicidin D. It was found that without uncoupler, the changes in the electron transfer rate under the influence of magnesium ions correlated to the changes in the first-order rate constant of the proton efflux from thylakoids. It is supposed that the change in the ability of thylakoids to keep protons by the action of magnesium ions is the result of electrostatic interactions of these ions with the charges on the external surface of membranes. A possible role of regulation of the electron transport rate by magnesium ions in vivo is discussed.

Hatching rate and growth rate of Nothobranchius guentheri fertilized eggs after space flight

International Nuclear Information System (INIS)

Guo Mingzhong; Zheng Leyun; Lin Guangji; Zhong Jianxing; Yang Huosheng; Zheng Yangfu

2012-01-01

Hatching, abnormal, growth and survival rate of the fertilized eggs of Nothobranchius guentheri were carried by Shenzhou 7 spacecraft were studied. The results indicated that the hatching and abnormal rate were no significant difference between the spaceflight group (99.3% and 16.8%) and ground group (97.2% and 10.4%); but the growth rate of male fish from spaceflight group was significant higher (0.094 g/d) than that of ground group (0.059 g/d), leading to the significant bigger of the male fish from spaceflight group. The survival rate of spaceflight group (66.7%) was higher than the ground group (47.9%). It was concluded that there was a higher growth and survival rate of Nothobranchius guentheri fertilized eggs after space flight. (authors)

Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms

Directory of Open Access Journals (Sweden)

Sabariah Ismail

2010-05-01

Full Text Available The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA as the cofactor, MgCl2, cell lysate of respective isoform, and 4MU at the approximate apparent Km or S50 value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 μg/mL and 0.01, 0.10, 1.0, 10 and 50 μg/mL respectively. Both extracts variably inhibited the activity of most of the isoforms in a concentration dependent manner. Andrographis paniculata extract was the better inhibitor of all the isoforms studied (IC50 1.70 μg/mL for UGT1A3, 2.57 μg/mL for UGT1A8, 2.82 μg/mL for UGT2B7, 5.00 μg/mL for UGT1A1, 5.66 μg/mL for UGT1A6, 9.88 μg/mL for UGT1A7 and 15.66 μg/mL for UGT1A10. Both extracts showed less than 70% inhibition of UGT2B15, so the IC50 values were >50μg/mL. The inhibition of human UGTs by Andrographis paniculata and Orthosiphon stamineus extracts in vitro suggests a potential for drug-herbal extract interactions in the therapeutic setting.

Higher Education, Poverty and Development

Science.gov (United States)

Tilak, Jandhyala B. G.

2010-01-01

There is a presumption among many policy makers that higher education is not necessary for economic growth and development; it is literacy and basic education and at best secondary education that are argued to be important. Estimates of internal rate of return contributed to strengthening of such a presumption. Accordingly, higher education has…

The Offer of Advanced Imaging Techniques Leads to Higher Acceptance Rates for Screening Colonoscopy - a Prospective Study.

Science.gov (United States)

Albrecht, Heinz; Gallitz, Julia; Hable, Robert; Vieth, Michael; Tontini, Gian Eugenio; Neurath, Markus Friedrich; Riemann, Jurgen Ferdinand; Neumann, Helmut

2016-01-01

Colonoscopy plays a fundamental role in early diagnosis and management of colorectal cancer and requires public and professional acceptance to ensure the ongoing success of screening programs. The aim of the study was to prospectively assess whether patient acceptance rates to undergo screening colonoscopy could be improved by the offer of advanced imaging techniques. Overall, 372 randomly selected patients were prospectively included. A standardized questionnaire was developed that inquired of the patients their knowledge regarding advanced imaging techniques. Second, several media campaigns and information events were organized reporting about advanced imaging techniques, followed by repeated evaluation. After one year the evaluation ended. At baseline, 64% of the patients declared that they had no knowledge about new endoscopic methods. After twelve months the overall grade of information increased significantly from 14% at baseline to 34%. The percentage of patients who decided to undergo colonoscopy because of the offer of new imaging methods also increased significantly from 12% at baseline to 42% after 12 months. Patients were highly interested in the offer of advanced imaging techniques. Knowledge about these techniques could relatively easy be provided using local media campaigns. The offer of advanced imaging techniques leads to higher acceptance rates for screening colonoscopies.

Reducing Error Rates for Iris Image using higher Contrast in Normalization process

Science.gov (United States)

Aminu Ghali, Abdulrahman; Jamel, Sapiee; Abubakar Pindar, Zahraddeen; Hasssan Disina, Abdulkadir; Mat Daris, Mustafa

2017-08-01

Iris recognition system is the most secured, and faster means of identification and authentication. However, iris recognition system suffers a setback from blurring, low contrast and illumination due to low quality image which compromises the accuracy of the system. The acceptance or rejection rates of verified user depend solely on the quality of the image. In many cases, iris recognition system with low image contrast could falsely accept or reject user. Therefore this paper adopts Histogram Equalization Technique to address the problem of False Rejection Rate (FRR) and False Acceptance Rate (FAR) by enhancing the contrast of the iris image. A histogram equalization technique enhances the image quality and neutralizes the low contrast of the image at normalization stage. The experimental result shows that Histogram Equalization Technique has reduced FRR and FAR compared to the existing techniques.

How to Pay for Higher Education.

Science.gov (United States)

Killingsworth, Charles C.

The financial crisis for institutions of higher education is deepening. Higher tuition rates may be one of the answers, but this would exclude even more young people from attending college because of inability to pay, at a time when greater equality of opportunity in higher education has become an important goal. Federal support has helped but not…

Optimizing rate of nitrogen application for higher growth and yield of wheat (triticum aestivum l.) cultivars

International Nuclear Information System (INIS)

Maqsood, M.; Shehzad, M.A.; Asim, A.; Ahmad, W.

2012-01-01

In order to optimize the nitrogen rates in three wheat (Triticum aestivum L.) cultivars for obtaining higher grain yield, a split plot experiment based on Randomized Complete Block Design with three replicates was conducted in the research field of University of Agriculture, Faisalabad during Rabi season 2006-07. Among treatments nitrogen levels (N0= 0, N/sub 1/= 50, N2= 100, N3= 150 kg ha/sup -1/) in main while wheat cultivars (V1= Punjnad-I, V/sub 2/= Fareed-2006, V3=Uqab-2000) were allocated in sub plots during the course of growing season. Traits as plant height, fertile tillers, spike length, spikelets spike-1, grains spike-1, 1000-grain weight, straw yield, grain yield and harvest index (HI) were significantly (P=0.05) affected by treatment combinations. Maximum grain yield was obtained by V3 (Uqab-2000) cultivar when treated with N3 (150 kg ha/sup -1/) fertilizer level. Also, results showed that with increasing nitrogen rates, wheat yield increases significantly up to a level of significance (P=0.05). Increasing nitrogen levels led to significantly increase in plant height (101.81 cm), spike bearing tillers (495.77), grains spike/sup -1/ (61.45), straw yield (8.60 t ha/sup -1/) and harvest index (36.17%) of V3 (Uqab-2000). In all traits except germination count, V3 (Uqab-2000) was found to be superior. (author)

Authors attain comparable or slightly higher rates of citation publishing in an open access journal (CytoJournal compared to traditional cytopathology journals - A five year (2007-2011 experience

Directory of Open Access Journals (Sweden)

Nora K Frisch

2014-01-01

Full Text Available Background: The era of Open Access (OA publication, a platform which serves to better disseminate scientific knowledge, is upon us, as more OA journals are in existence than ever before. The idea that peer-reviewed OA publication leads to higher rates of citation has been put forth and shown to be true in several publications. This is a significant benefit to authors and is in addition to another relatively less obvious but highly critical component of the OA charter, i.e. retention of the copyright by the authors in the public domain. In this study, we analyzed the citation rates of OA and traditional non-OA publications specifically for authors in the field of cytopathology. Design: We compared the citation patterns for authors who had published in both OA and traditional non-OA peer-reviewed, scientific, cytopathology journals. Citations in an OA publication (CytoJournal were analyzed comparatively with traditional non-OA cytopathology journals (Acta Cytologica, Cancer Cytopathology, Cytopathology, and Diagnostic Cytopathology using the data from web of science citation analysis site (based on which the impact factors (IF are calculated. After comparing citations per publication, as well as a time adjusted citation quotient (which takes into account the time since publication, we also analyzed the statistics after excluding the data for meeting abstracts. Results: Total 28 authors published 314 publications as articles and meeting abstracts (25 authors after excluding the abstracts. The rate of citation and time adjusted citation quotient were higher for OA in the group where abstracts were included (P < 0.05 for both. The rates were also slightly higher for OA than non-OA when the meeting abstracts were excluded, but the difference was statistically insignificant (P = 0.57 and P = 0.45. Conclusion : We observed that for the same author, the publications in the OA journal attained a higher rate of citation than the publications in the

Does basal metabolic rate drive eating rate?

Science.gov (United States)

Henry, Christiani Jeyakumar; Ponnalagu, Shalini; Bi, Xinyan; Forde, Ciaran

2018-05-15

There have been recent advances in our understanding of the drivers of energy intake (EI). However, the biological drivers of differences in eating rate (ER) remain less clear. Studies have reported that the fat-free mass (FFM) and basal metabolic rate (BMR) are both major components that contribute to daily energy expenditure (EE) and drive EI. More recently, a number of observations report that higher ER can lead to greater EI. The current study proposed that adults with a higher BMR and higher energy requirements would also exhibit higher ERs. Data on BMR, FFM, and ER were collected from 272 Chinese adults (91 males and 181 females) in a cross-sectional study. Analysis showed significant positive associations between BMR and ER (r s  = 0.405, p BMR explained about 15% of the variation in ER which was taken to be metabolically significant. This association provides metabolic explanation that the differences in an individual's BMR (hence energy requirements) may be correlated with ERs. This merits further research. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacokinetics and Biliary Excretion of Fisetin in Rats.

Science.gov (United States)

Huang, Miao-Chan; Hsueh, Thomas Y; Cheng, Yung-Yi; Lin, Lie-Chwen; Tsai, Tung-Hu

2018-06-14

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague-Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios ( k (%) = AUC conjugate /AUC free-form ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate ( k BE (%) = AUC bile /AUC plasma ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

Neuroexcitatory effects of morphine-3-glucuronide are dependent on Toll-like receptor 4 signaling

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Due Michael R

2012-08-01

Full Text Available Abstract Background Multiple adverse events are associated with the use of morphine for the treatment of chronic non-cancer pain, including opioid-induced hyperalgesia (OIH. Mechanisms of OIH are independent of opioid tolerance and may involve the morphine metabolite morphine-3-glucuronide (M3G. M3G exhibits limited affinity for opioid receptors and no analgesic effect. Previous reports suggest that M3G can act via the Toll-like receptor 4 (TLR4/myeloid differentiation protein-2 (MD-2 heterodimer in the central nervous system to elicit pain. Methods Immunoblot and immunocytochemistry methods were used to characterize the protein expression of TLR4 present in lumbar dorsal root ganglion (DRG. Using in vitro intracellular calcium and current clamp techniques, we determined whether TLR4 activation as elicited by the prototypical agonists of TLR4, lipopolysaccharide (LPS and M3G, contributed to changes in intracellular calcium and increased excitation. Rodents were also injected with M3G to determine the degree to which M3G-induced tactile hyperalgesia could be diminished using either a small molecule inhibitor of the MD-2/TLR4 complex in rats or TLR4 knockout mice. Whole cell voltage-clamp recordings were made from small- and medium-diameter DRG neurons (25 μm  Results We observed that TLR4 immunoreactivity was present in peptidergic and non-peptidergic sensory neurons in the DRG. Non-neuronal cells in the DRG lacked evidence of TLR4 expression. Approximately 15% of assayed small- and medium-diameter sensory neurons exhibited a change in intracellular calcium following LPS administration. Both nociceptive and non-nociceptive neurons were observed to respond, and approximately 40% of these cells were capsaicin-insensitive. Increased excitability observed in sensory neurons following LPS or M3G could be eliminated using Compound 15, a small molecule inhibitor of the TLR4/MD-2 complex. Likewise, systemic injection of M3G induced rapid tactile, but

Increased Total Anesthetic Time Leads to Higher Rates of Surgical Site Infections in Spinal Fusions.

Science.gov (United States)

Puffer, Ross C; Murphy, Meghan; Maloney, Patrick; Kor, Daryl; Nassr, Ahmad; Freedman, Brett; Fogelson, Jeremy; Bydon, Mohamad

2017-06-01

A retrospective review of a consecutive series of spinal fusions comparing patient and procedural characteristics of patients who developed surgical site infections (SSIs) after spinal fusion. It is known that increased surgical time (incision to closure) is associated with a higher rate of postoperative SSIs. We sought to determine whether increased total anesthetic time (intubation to extubation) is a factor in the development of SSIs as well. In spine surgery for deformity and degenerative disease, SSI has been associated with operative time, revealing a nearly 10-fold increase in SSI rates in prolonged surgery. Surgical time is associated with infections in other surgical disciplines as well. No studies have reported whether total anesthetic time (intubation to extubation) has an association with SSIs. Surgical records were searched in a retrospective fashion to identify all spine fusion procedures performed between January 2010 and July 2012. All SSIs during that timeframe were recorded and compared with the list of cases performed between 2010 and 2012 in a case-control design. There were 20 (1.7%) SSIs in this fusion cohort. On univariate analyses of operative factors, there was a significant association between total anesthetic time (Infection 7.6 ± 0.5 hrs vs. no infection -6.0 ± 0.1 hrs, P operative time (infection 5.5 ± 0.4 hrs vs. no infection - 4.4 ± 0.06 hrs, P infections, whereas level of pathology and emergent surgery were not significant. On multivariate logistic analysis, BMI and total anesthetic time remained independent predictors of SSI whereas ASA status and operative time did not. Increasing BMI and total anesthetic time were independent predictors of SSIs in this cohort of over 1000 consecutive spinal fusions. 3.

Mechanisms promoting higher growth rate in arctic than in temperate shorebirds

NARCIS (Netherlands)

Schekkerman, H.; Tulp, I.Y.M.; Piersma, T.; Visser, G.H.

2003-01-01

We compared prefledging growth, energy expenditure, and time budgets in the arctic-breeding red knot (Calidris canutus) to those in temperate shorebirds, to investigate how arctic chicks achieve a high growth rate despite energetic difficulties associated with precocial development in a cold

Mechanisms promoting higher growth rate in arctic than in temperate shorebirds

NARCIS (Netherlands)

Schekkerman, H; Tulp, Ingrid; Piersma, T.; Visser, G.H.

We compared prefledging growth, energy expenditure, and time budgets in the arctic-breeding red knot (Calidris canutus) to those in temperate shorebirds, to investigate how arctic chicks achieve a high growth rate despite energetic difficulties associated with precocial development in a cold

Ways to be different: Foraging adaptations that facilitate higher intake rates in a northerly wintering shorebird compared with a low-latitude conspecific

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Ruthrauff, Daniel R.; Dekinga, Anne; Gill, Robert E.; van Gils, Jan A.; Piersma, Theunis

2015-01-01

At what phenotypic level do closely related subspecies that live in different environments differ with respect to food detection, ingestion and processing? This question motivated an experimental study on rock sandpipers (Calidris ptilocnemis). The species' nonbreeding range spans 20 deg of latitude, the extremes of which are inhabited by two subspecies: C. p. ptilocnemis that winters primarily in upper Cook Inlet, Alaska (61°N) and C. p. tschuktschorum that overlaps slightly with C. p. ptilocnemis but whose range extends much farther south (∼40°N). In view of the strongly contrasting energetic demands of their distinct nonbreeding distributions, we conducted experiments to assess the behavioral, physiological and sensory aspects of foraging and we used the bivalve Macoma balthica for all trials. C. p. ptilocnemis consumed a wider range of prey sizes, had higher maximum rates of energy intake, processed shell waste at higher maximum rates and handled prey more quickly. Notably, however, the two subspecies did not differ in their abilities to find buried prey. The subspecies were similar in size and had equally sized gizzards, but the more northern ptilocnemis individuals were 10–14% heavier than their same-sex tschuktschorum counterparts. The higher body mass in ptilocnemis probably resulted from hypertrophy of digestive organs (e.g. intestine, liver) related to digestion and nutrient assimilation. Given the previously established equality of the metabolic capacities of the two subspecies, we propose that the high-latitude nonbreeding range of ptilocnemis rock sandpipers is primarily facilitated by digestive (i.e. physiological) aspects of their foraging ecology rather than behavioral or sensory aspects.

Mechanistic dissimilarities between environmentally-influenced fatigue-crack propagation at near-threshold and higher growth rates in lower-strength steels

Energy Technology Data Exchange (ETDEWEB)

Suresh, S.; Ritchie, R. O.

1981-11-01

The role of hydrogen gas in influencing fatigue crack propagation is examined for several classes of lower strength pressure vessel and piping steels. Based on measurements over a wide range of growth rates from 10/sup -8/ to 10/sup -2/ mm/cycle, crack propagation rates are found to be significantly higher in dehumidified gaseous hydrogen compared to moist air in two distinct regimes of crack growth, namely (i) at the intermediate range of growth typically above approx. 10/sup -5/ mm/cycle, and (ii) at the near-threshold region below approx. 10/sup -6/ mm/cycle approaching lattice dimensions per cycle. Both effects are seen at maximum stress intensities (K/sub max/) far below the sustained-load threshold stress intensity for hydrogen-assisted cracking (K/sub Iscc/). Characteristics of environmentally influenced fatigue crack growth in each regime are shown to be markedly different with regard to fractography and the effect of such variables as load ratio and frequency. It is concluded that the primary mechanisms responsible for the influence of the environment in each regime are distinctly different. Whereas corrosion fatigue behavior at intermediate growth rates can be attributed to hydrogen embrittlement processes, the primary role of moist environments at near-threshold levels is shown to involve a contribution from enhanced crack closure due to the formation of crack surface corrosion deposits at low load ratios.

Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls.

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Kirby, K N; Petry, N M; Bickel, W K

1999-03-01

Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ($11-$80) available immediately and larger rewards ($25-$85) available after delays ranging from 1 week to 6 months. Participants had a 1-in-6 chance of winning a reward that they chose on one randomly selected trial. Delay-discounting rates were estimated from the pattern of participants' choices. The discounting model of impulsiveness (Ainslie, 1975) implies that delay-discounting rates are positively correlated with impulsiveness. On average, heroin addicts' discount rates were twice those of controls (p = .004), and discount rates were positively correlated with impulsivity as measured by self-report questionnaires (p discounting rate as a measure of impulsiveness, a characteristic associated with substance abuse.

Education Pays, 2010: The Benefits of Higher Education for Individuals and Society. Trends in Higher Education Series

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Baum, Sandy; Ma, Jennifer; Payea, Kathleen

2010-01-01

Students who attend institutions of higher education obtain a wide range of personal, financial, and other lifelong benefits; likewise, taxpayers and society as a whole derive a multitude of direct and indirect benefits when citizens have access to postsecondary education. Accordingly, uneven rates of participation in higher education across…

Fast-Rate Capable Electrode Material with Higher Energy Density than LiFePO4: 4.2V LiVPO4F Synthesized by Scalable Single-Step Solid-State Reaction.

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Kim, Minkyung; Lee, Seongsu; Kang, Byoungwoo

2016-03-01

Use of compounds that contain fluorine (F) as electrode materials in lithium ion batteries has been considered, but synthesizing single-phase samples of these compounds is a difficult task. Here, it is demonstrated that a simple scalable single-step solid-state process with additional fluorine source can obtain highly pure LiVPO 4 F. The resulting material with submicron particles achieves very high rate capability ≈100 mAh g -1 at 60 C-rate (1-min discharge) and even at 200 C-rate (18 s discharge). It retains superior capacity, ≈120 mAh g -1 at 10 C charge/10 C discharge rate (6-min) for 500 cycles with >95% retention efficiency. Furthermore, LiVPO 4 F shows low polarization even at high rates leading to higher operating potential >3.45 V (≈3.6 V at 60 C-rate), so it achieves high energy density. It is demonstrated for the first time that highly pure LiVPO 4 F can achieve high power capability comparable to LiFePO 4 and much higher energy density (≈521 Wh g -1 at 20 C-rate) than LiFePO 4 even without nanostructured particles. LiVPO 4 F can be a real substitute of LiFePO 4.

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

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Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

2017-10-01

During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017

Evaluation of abalone β-glucuronidase substitution in current urine hydrolysis procedures.

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Malik-Wolf, Brittany; Vorce, Shawn; Holler, Justin; Bosy, Thomas

2014-04-01

This study examined the potential of abalone β-glucuronidase as a viable and cost effective alternative to current hydrolysis procedures using acid, Helix pomatia β-glucuronidase and Escherichia coli β-glucuronidase. Abalone β-glucuronidase successfully hydrolyzed oxazepam-glucuronide and lorazepam-glucuronide within 5% of the spiked control concentration. Benzodiazepines present in authentic urine specimens were within 20% of the concentrations obtained with the current hydrolysis procedure using H. pomatia β-glucuronidase. JWH 018 N-(5-hydroxypentyl) β-d-glucuronide was hydrolyzed within 10% of the control concentration. Authentic urine specimens showed improved glucuronide cleavage using abalone β-glucuronidase with up to an 85% increase of drug concentration, compared with the results obtained using E. coli β-glucuronidase. The JWH 018 and JWH 073 carboxylic acid metabolites also showed increased drug concentrations of up to 24%. Abalone β-glucuronidase was able to completely hydrolyze a morphine-3-glucuronide control, but only 82% of total morphine was hydrolyzed in authentic urine specimens compared with acid hydrolysis results. Hydrolysis of codeine and hydromorphone varied between specimens, suggesting that abalone β-glucuronidase may not be as efficient in hydrolyzing the glucuronide linkages in opioid compounds compared with acid hydrolysis. Abalone β-glucuronidase demonstrates effectiveness as a low cost option for enzyme hydrolysis of benzodiazepines and synthetic cannabinoids.

Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.

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Lawrence Soon-U Lee

Full Text Available Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods.Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5.SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01. Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01. SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC (r = -0.397 p<0.05. Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005, but not UGT1A1 genotype.Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy.Clinicaltrials.gov NCT00808184.

Substrate mediated enzyme prodrug therapy.

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Betina Fejerskov

Full Text Available In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol, β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose - dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.

CpG Oligonucleotide and Interleukin 2 stimulation enables higher cytogenetic abnormality detection rates than 12-o-tetradecanolyphorbol-13-acetate in Asian patients with B-cell chronic lymphocytic leukemia (B-CLL).

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Liaw, Fiona Pui San; Lau, Lai Ching; Lim, Alvin Soon Tiong; Lim, Tse Hui; Lee, Geok Yee; Tien, Sim Leng

2014-12-01

The present study was designed to compare abnormality detection rates using DSP30 + IL2 and 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Asian patients with B-CLL. Hematological specimens from 47 patients (29 newly diagnosed, 18 relapsed) were established as 72 h-DSP30 + IL2 and TPA cultures. Standard methods were employed to identify clonal aberrations by conventional cytogenetics (CC). The B-CLL fluorescence in situ hybridization (FISH) panel comprised ATM, CEP12, D13S25, and TP53 probes. DSP30 + IL2 cultures had a higher chromosomal abnormality detection rate (67 %) compared to TPA (44 %, p 0.05). Thirteen cases with abnormalities were found exclusively in DSP30 + IL2 cultures compared to one found solely in TPA cultures. DSP30 + IL2 cultures were comparable to the FISH panel in detecting 11q-, +12 and 17p- but not 13q-. It also has a predilection for 11q- bearing leukemic cells compared to TPA. FISH had a higher abnormality detection rate (84.1 %) compared to CC (66.0 %) with borderline significance (p = 0.051), albeit limited by its coverage. In conclusion, DSP30 + IL2 showed a higher abnormality detection rate. However, FISH is indispensable to circumvent low mitotic indices and detect subtle abnormalities.

Flavonoids extraction from Alpinia zerumbet (Pers.) Burtt et Smith leaves using different procedures

International Nuclear Information System (INIS)

Victorio, Cristiane P.; Lage, Celso Luiz S.; Kuster, Ricardo M.

2010-01-01

The current study aims to verify the best method for a rapid and efficient extraction of flavonoids from Alpinia zerumbet. Dried leaves were extracted using distillated water and ethanol 70% by extraction methods of shaking maceration, ultrasonic, microwave and stirring. By the application of TLC and reversed-phase HPLC techniques the rutin and kaempferol-3-O-glucuronide were detected. Ethanol 70% was more efficient for flavonoids extraction than water. No significant yielding variation was verified for ultrasonic, microwave and stirring methods using ethanol 70% (11 to 14%). Relative concentration of rutin and kaempferol-3-O-glucuronide, respectively, was higher by ultrasonic (1.5 and 5.62 mg g -1 dried leaves) and by microwave (1.0 and 6.64 mg g -1 dried leaves) methods using 70% ethanol. Rapid and simplified extraction proceeding optimize phytochemical work and acquisition of secondary metabolites. (author)

Deposition of diazepam and its metabolites in hair following a single dose of diazepam

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong

2017-01-01

Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy...... volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide...... no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were...

High Heating Rates Affect Greatly the Inactivation Rate of Escherichia coli

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Huertas, Juan-Pablo; Aznar, Arantxa; Esnoz, Arturo; Fernández, Pablo S.; Iguaz, Asunción; Periago, Paula M.; Palop, Alfredo

2016-01-01

Heat resistance of microorganisms can be affected by different influencing factors. Although, the effect of heating rates has been scarcely explored by the scientific community, recent researches have unraveled its important effect on the thermal resistance of different species of vegetative bacteria. Typically heating rates described in the literature ranged from 1 to 20°C/min but the impact of much higher heating rates is unclear. The aim of this research was to explore the effect of different heating rates, such as those currently achieved in the heat exchangers used in the food industry, on the heat resistance of Escherichia coli. A pilot plant tubular heat exchanger and a thermoresistometer Mastia were used for this purpose. Results showed that fast heating rates had a deep impact on the thermal resistance of E. coli. Heating rates between 20 and 50°C/min were achieved in the heat exchanger, which were much slower than those around 20°C/s achieved in the thermoresistometer. In all cases, these high heating rates led to higher inactivation than expected: in the heat exchanger, for all the experiments performed, when the observed inactivation had reached about seven log cycles, the predictions estimated about 1 log cycle of inactivation; in the thermoresistometer these differences between observed and predicted values were even more than 10 times higher, from 4.07 log cycles observed to 0.34 predicted at a flow rate of 70 mL/min and a maximum heating rate of 14.7°C/s. A quantification of the impact of the heating rates on the level of inactivation achieved was established. These results point out the important effect that the heating rate has on the thermal resistance of E. coli, with high heating rates resulting in an additional sensitization to heat and therefore an effective food safety strategy in terms of food processing. PMID:27563300

Training in Using Earplugs or Using Earplugs with a Higher than Necessary Noise Reduction Rating? A Randomized Clinical Trial

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M Salmani Nodoushan

2014-09-01

Full Text Available Background: Noise-induced hearing loss (NIHL is one of the most common occupational diseases and the second most common cause of workers' claims for occupational injuries. Objective: Due to high prevalence of NIHL and several reports of improper use of hearing protective devices (HPDs, we conducted this study to compare the effect of face-to-face training in effective use of earplugs with appropriate NRR to overprotection of workers by using earplugs with higher than necessary noise reduction rating (NRR. Methods: In a randomized clinical trial, 150 workers referred to occupational medicine clinic were randomly allocated to three arms—a group wearing earplugs with an NRR of 25 with no training in appropriate use of the device; a group wearing earplugs with an NRR of 25 with training; another group wearing earplugs with an NRR of 30, with no training. Hearing threshold was measured in the study groups by real ear attenuation at threshold (REAT method. This trial is registered with Australian New Zealand clinical trials Registry, number ACTRN00363175. Results: The mean±SD age of the participants was 28±5 (range: 19–39 years. 42% of participants were female. The mean noise attenuation in the group with training was 13.88 dB, significantly higher than those observed in other groups. The highest attenuation was observed in high frequencies (4, 6, and 8 kHz in the group with training. Conclusion: Training in appropriate use of earplugs significantly affects the efficacy of earplugs—even more than using an earplug with higher NRR.

Older Adults With a Combination of Vision and Hearing Impairment Experience Higher Rates of Cognitive Impairment, Functional Dependence, and Worse Outcomes Across a Set of Quality Indicators.

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Davidson, Jacob G S; Guthrie, Dawn M

2017-08-01

Hearing and vision impairment were examined across several health-related outcomes and across a set of quality indicators (QIs) in home care clients with both vision and hearing loss (or dual sensory impairment [DSI]). Data collected using the Resident Assessment Instrument for Home Care (RAI-HC) were analyzed in a sample of older home care clients. The QIs represent the proportion of clients experiencing negative outcomes (e.g., falls, social isolation). The average age of clients was 82.8 years ( SD = 7.9), 20.5% had DSI and 8.5% had a diagnosis of Alzheimer's disease (AD). Clients with DSI were more likely to have a diagnosis of dementia (not AD), have functional impairments, report loneliness, and have higher rates across 20 of the 22 QIs, including communication difficulty and cognitive decline. Clients with highly impaired hearing, and any visual impairment, had the highest QI rates. Individuals with DSI experience higher rates of adverse events across many health-related outcomes and QIs. Understanding the unique contribution of hearing and vision in this group can promote optimal quality of care.

"Terrain Paper" on Demography and Higher Education.

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Hodgkinson, Harold L.

Major demographic trends and consequences for higher education are examined. The Baby Boom sharply increased birth rates from 1946 to 1964 and was followed by a decline in births that lasted from 1964 to 1978. Currently there is an increased birth rate, but of much smaller size than the Baby Boom rates, due largely to the smaller size of the…

Non-English speakers attend gastroenterology clinic appointments at higher rates than English speakers in a vulnerable patient population

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Sewell, Justin L.; Kushel, Margot B.; Inadomi, John M.; Yee, Hal F.

2009-01-01

Goals We sought to identify factors associated with gastroenterology clinic attendance in an urban safety net healthcare system. Background Missed clinic appointments reduce the efficiency and availability of healthcare, but subspecialty clinic attendance among patients with established healthcare access has not been studied. Study We performed an observational study using secondary data from administrative sources to study patients referred to, and scheduled for an appointment in, the adult gastroenterology clinic serving the safety net healthcare system of San Francisco, California. Our dependent variable was whether subjects attended or missed a scheduled appointment. Analysis included multivariable logistic regression and classification tree analysis. 1,833 patients were referred and scheduled for an appointment between 05/2005 and 08/2006. Prisoners were excluded. All patients had a primary care provider. Results 683 patients (37.3%) missed their appointment; 1,150 (62.7%) attended. Language was highly associated with attendance in the logistic regression; non-English speakers were less likely than English speakers to miss an appointment (adjusted odds ratio 0.42 [0.28,0.63] for Spanish, 0.56 [0.38,0.82] for Asian language, p gastroenterology clinic appointment, not speaking English was most strongly associated with higher attendance rates. Patient related factors associated with not speaking English likely influence subspecialty clinic attendance rates, and these factors may differ from those affecting general healthcare access. PMID:19169147

Metabolism of androstenone, 17β-estradiol and dihydrotestosterone in primary cultured pig hepatocytes and the role of 3β-hydroxysteroid dehydrogenase in this process.

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Gang Chen

Full Text Available Steroids metabolism plays an important role in mammals and contributes to quality of pig meat. The main objective of this study was to identify metabolites of androstenone, 17β-estradiol and dihydrotestosterone using primary cultured pig hepatocytes as a model system. The role of 3β-hydroxysteroid dehydrogenase (3βHSD in regulation of steroid metabolism was also validated using trilostane, a specific 3βHSD inhibitor. Steroid glucuronide conjugated metabolites were detected by liquid chromatography time of flight mass spectrometry (LC-TOF-MS. 3βHSD enzyme was essential for metabolism of androstenone to 5α-androst-16-en-3β-ol, which then formed androstenone glucuronide conjugate. Metabolism of 17β-estradiol was accompanied by formation of glucuronide-conjugated estrone and glucuronide-conjugated estradiol. The ratio of the two metabolites was around 5:1. 3βHSD enzyme was not involved in 17β-estradiol metabolism. 5α-Dihydrotestosterone-17β-glucuronide was identified as a dihydrotestosterone metabolite, and this metabolism was related to 3βHSD enzyme activity as demonstrated by inhibition study.

Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes.

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Jeong, Hyeon-Uk; Kim, Ju-Hyun; Kong, Tae Yeon; Choi, Won Gu; Lee, Hye Suk

2016-04-01

Honokiol has antitumor, antioxidative, anti-inflammatory, and antithrombotic effects. Here we aimed to identify the metabolic profile of honokiol in mouse, rat, dog, monkey, and human hepatocytes and to characterize the enzymes responsible for the glucuronidation and sulfation of honokiol. Honokiol had a high hepatic extraction ratio in all five species, indicating that it was extensively metabolized. A total of 32 metabolites, including 17 common and 15 different metabolites, produced via glucuronidation, sulfation, and oxidation of honokiol allyl groups were tentatively identified using liquid chromatography-high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-2'-glucuronide) was the predominant metabolic pathway in hepatocytes of all five species; however, interspecies differences between 4- and 2'-glucuronidation of honokiol were observed. UGT1A1, 1A8, 1A9, 2B15, and 2B17 played major roles in M8 formation, whereas UGT1A7 and 1A9 played major roles in M9 formation. Human cDNA-expressed SULT1C4 played a major role in M10 formation (honokiol-2'-sulfate), whereas SULT1A1*1, 1A1*2, and 1A2 played major roles in M11 formation (honokiol-4-sulfate). In conclusion, honokiol metabolism showed interspecies differences.

Species-related exposure of phase II metabolite gemfibrozil 1-O-β-glucuronide between human and mice: A net induction of mouse P450 activity was revealed.

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Luo, Min; Dai, Manyun; Lin, Hante; Xie, Minzhu; Lin, Jiao; Liu, Aiming; Yang, Julin

2017-12-01

Gemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, six volunteers were recruited and took a therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0.75%) for 7 days, following which a cocktail-based inhibitory DDI experiment was performed. Plasma samples and liver tissues from mice were collected for determination of gemfibrozil, gem-glu concentration and cytochrome p450 enzyme (P450) induction analysis. In human, the molar ratio of gem-glu/gemfibrozil was 15% and 10% at the trough concentration and the concentration at 1.5 h after the 6th dose. In contrast, this molar ratio at steady state in mice was 91%, demonstrating a 6- to 9-fold difference compared with that in human. Interestingly, a net induction of P450 activity and in vivo inductive DDI potential in mice was revealed. The P450 activity was not inhibited although the gem-glu concentration was high. These data suggested species difference of relative gem-glu exposure between human and mice, as well as a net inductive DDI potential of gemfibrozil in mouse model. Copyright © 2017 John Wiley & Sons, Ltd.

Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis.

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Bichler, J; Benseler, S M; Krumrey-Langkammerer, M; Haas, J-P; Hügle, B

2015-01-01

Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution. A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008). Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

Treatment of moderate acute malnutrition with ready-to-use supplementary food results in higher overall recovery rates compared with a corn-soya blend in children in southern Ethiopia: an operations research trial.

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Karakochuk, Crystal; van den Briel, Tina; Stephens, Derek; Zlotkin, Stanley

2012-10-01

Moderate and severe acute malnutrition affects 13% of children malnutrition affects fewer children but is associated with higher rates of mortality and morbidity. Supplementary feeding programs aim to treat moderate acute malnutrition and prevent the deterioration to severe acute malnutrition. The aim was to compare recovery rates of children with moderate acute malnutrition in supplementary feeding programs by using the newly recommended ration of ready-to-use supplementary food (RUSF) and the more conventional ration of corn-soya blend (CSB) in Ethiopia. A total of 1125 children aged 6-60 mo with moderate acute malnutrition received 16 wk of CSB or RUSF. Children were randomly assigned to receive one or the other food. The daily rations were purposely based on the conventional treatment rations distributed at the time of the study in Ethiopia: 300 g CSB and 32 g vegetable oil in the control group (1413 kcal) and 92 g RUSF in the intervention group (500 kcal). The higher ration size of CSB was provided because of expected food sharing. The HR for children in the CSB group was 0.85 (95% CI: 0.73, 0.99), which indicated that they had 15% lower recovery (P = 0.039). Recovery rates of children at the end of the 16-wk treatment period trended higher in the RUSF group (73%) than in the CSB group (67%) (P = 0.056). In comparison with CSB, the treatment of moderate acute malnutrition with RUSF resulted in higher recovery rates in children, despite the large ration size and higher energy content of the conventional CSB ration.

Metabolic patterns of JWH-210, RCS-4, and THC in pig urine elucidated using LC-HR-MS/MS: Do they reflect patterns in humans?

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Schaefer, Nadine; Helfer, Andreas G; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Ewald, Andreas H; Meyer, Markus R; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

2017-04-01

The knowledge of pharmacokinetic (PK) properties of synthetic cannabinoids (SCs) is important for interpretation of analytical results found for example in intoxicated individuals. In the absence of human data from controlled studies, animal models elucidating SC PK have to be established. Pigs providing large biofluid sample volumes were tested for prediction of human PK data. In this context, the metabolic fate of two model SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4), was elucidated in addition to Δ 9 -tetrahydrocannabinol (THC). After intravenous administration of the compounds, hourly collected pig urine was analyzed by liquid chromatography-high resolution mass spectrometry. The following pathways were observed: for JWH-210, hydroxylation at the ethyl side chain or pentyl chain and combinations of them followed by glucuronidation; for RCS-4, hydroxylation at the methoxyphenyl moiety or pentyl chain followed by glucuronidation as well as O-demethylation followed by glucuronidation or sulfation; for THC, THC glucuronidation, 11-hydroxylation, followed by carboxylation and glucuronidation. For both SCs, parent compounds could not be detected in urine in contrast to THC. These results were consistent with those obtained from human hepatocyte and/or human case studies. Urinary markers for the consumption of JWH-210 were the glucuronide of the N-hydroxypentyl metabolite (detectable for 3-4 h) and of RCS-4 the glucuronides of the N-hydroxypentyl, hydroxy-methoxyphenyl (detectable for at least 6 h), and the O-demethyl-hydroxy metabolites (detectable for 4 h). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma

DEFF Research Database (Denmark)

Bergmann, Troels K; Filppula, Anne M; Launiainen, Terhi

2015-01-01

% of the cohort geometric mean (385 L/h; range 176-726). She was hospitalised thrice, developed severe neuropathy and paclitaxel treatment was subsequently discontinued. In vitro, 30 min preincubation with 100 μM clopidogrel acyl-β-D-glucuronide inhibited the depletion rate of 0.5 μM paclitaxel by 51......AIM: The aim of this case report is to describe a novel pharmacokinetic drug-drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel. METHODS: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated...... with paclitaxel. The effect of clopidogrel acyl-β-D-glucuronide on the metabolism of paclitaxel was assessed in human liver microsomes. The analysis of clopidogrel in plasma and the quantification of paclitaxel and 6α-hydroxypaclitaxel in in vitro samples were performed by liquid chromatography tandem mass...

Antiinflammatory and Antioxidant Flavonoids and Phenols from Cardiospermum halicacabum (倒地鈴 Dào Dì Líng)

OpenAIRE

Cheng, Hui-Ling; Zhang, Li-Jie; Liang, Yu-Han; Hsu, Ya-Wen; Lee, I-Jung; Liaw, Chia-Ching; Hwang, Syh-Yuan; Kuo, Yao-Haur

2013-01-01

Seventeen compounds, quercetin-3-O-α-l-rhamnoside (1), kaempferol-3-O-α-L-rhamnoside (2), apigenin-7-O-β-D-glucuronide (3), apigenin 7-O-β-D-glucuronide methyl ester (4), apigenin 7-O-β-D-glucuronide ethyl ester (5), chrysoeriol (6), apigenin (7), kaempferol (8), luteolin (9), quercetin (10), methyl 3,4-dihydroxybenzoate (11), p-coumaric acid (12), 4-hydroxybenzoic acid (13), hydroquinone (14), protocathehuic acid (15), gallic acid (16), and indole-3-carboxylic acid (17), were isolated from t...

Antiinflammatory and Antioxidant Flavonoids and Phenols from Cardiospermum halicacabum (倒地鈴 Dào Dì Líng)

OpenAIRE

Hui-Ling Cheng; Li-Jie Zhang; Yu-Han Liang; Ya-Wen Hsu; I-Jung Lee; Chia-Ching Liaw; Syh-Yuan Hwang; Yao-Haur Kuo

2013-01-01

Seventeen compounds, quercetin-3-O-α-l-rhamnoside (1), kaempferol-3-O-α-l-rhamnoside (2), apigenin-7-O-β-d-glucuronide (3), apigenin 7-O-β-d-glucuronide methyl ester (4), apigenin 7-O-β-d-glucuronide ethyl ester (5), chrysoeriol (6), apigenin (7), kaempferol (8), luteolin (9), quercetin (10), methyl 3,4-dihydroxybenzoate (11), p-coumaric acid (12), 4-hydroxybenzoic acid (13), hydroquinone (14), protocathehuic acid (15), gallic acid (16), and indole-3-carboxylic acid (17), were isolated from t...

Effectiveness of high interest rate policy on exchange rates: A reexamination of the Asian financial crisis

Directory of Open Access Journals (Sweden)

Chin Diew Lai

2006-09-01

Full Text Available One of the most controversial issues in the aftermath of the Asian financial crisis has been the appropriate response of monetary policy to a sharp decline in the value of some currencies. In this paper, we empirically examine the effects on Asian exchange rates of sharply higher interest rates during the Asian financial crisis. Taking account of the currency contagion effect, our results indicate that sharply higher interest rates helped to support the exchange rates of South Korea, the Philippines, and Thailand. For Malaysia, no significant causal relation is found from the rate of interest to exchange rates, as the authorities in Malaysia did not actively adopt a high interest rate policy to defend the currency.

Enhancing Brain Lesions during Acute Optic Neuritis and/or Longitudinally Extensive Transverse Myelitis May Portend a Higher Relapse Rate in Neuromyelitis Optica Spectrum Disorders.

Science.gov (United States)

Orman, G; Wang, K Y; Pekcevik, Y; Thompson, C B; Mealy, M; Levy, M; Izbudak, I

2017-05-01

Neuromyelitis optica spectrum disorders are inflammatory demyelinating disorders with optic neuritis and/or longitudinally extensive transverse myelitis episodes. We now know that neuromyelitis optica spectrum disorders are associated with antibodies to aquaporin-4, which are highly concentrated on astrocytic end-feet at the blood-brain barrier. Immune-mediated disruption of the blood-brain barrier may manifest as contrast enhancement on brain MR imaging. We aimed to delineate the extent and frequency of contrast enhancement on brain MR imaging within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and to correlate contrast enhancement with outcome measures. Brain MRIs of patients with neuromyelitis optica spectrum disorders were evaluated for patterns of contrast enhancement (periependymal, cloudlike, leptomeningeal, and so forth). The Fisher exact test was used to evaluate differences between the proportion of contrast enhancement in patients who were seropositive and seronegative for aquaporin-4 antibodies. The Mann-Whitney test was used to compare the annualized relapse rate and disease duration between patients with and without contrast enhancement and with and without seropositivity. Brain MRIs of 77 patients were evaluated; 59 patients (10 males, 49 females) were scanned within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and were included in the analysis. Forty-eight patients were seropositive, 9 were seronegative, and 2 were not tested for aquaporin-4 antibodies. Having brain contrast enhancement of any type during an acute attack was significantly associated with higher annualized relapse rates ( P = .03) and marginally associated with shorter disease duration ( P = .05). Having periependymal contrast enhancement was significantly associated with higher annualized relapse rates ( P = .03). Brain MRIs of patients with neuromyelitis optica spectrum disorders with contrast

Testing Optimum Seeding Rates for five Bread Wheat Cultivars

International Nuclear Information System (INIS)

Wekesa, S.J.; Kiriswa, F.; Owuoche, J.

1999-01-01

A cultivar by seed rate trial was conducted in 1994-1995 crop seasons at Njoro, Kenya. Yield results were found to be significant (P > 0.01) for year, variety, seed rate and year by seed rate interaction. Test weight was highly significant (P -1 were grouped together for significantly higher yields (A) whereas seed rates 85 and 50 kg ha -1 had lower significant yields (B and C respectively). The same grouping was repeated for test weight. There was no significant cultivar by seed rate interaction and no cultivar, specific seed rate. However, since seed rates 245, 205, 165 and 125 kg ha -1 were grouped together, the lowest seed rate, 125 kg ha -1 can be recommended as the optimum seed rate for the above cultivars, as higher seed rates do not give significantly higher yields or higher test weights

Is patriarchy the source of men's higher mortality?

Science.gov (United States)

Stanistreet, D; Bambra, C; Scott-Samuel, A

2005-01-01

Objective: To examine the relation between levels of patriarchy and male health by comparing female homicide rates with male mortality within countries. Hypothesis: High levels of patriarchy in a society are associated with increased mortality among men. Design: Cross sectional ecological study design. Setting: 51 countries from four continents were represented in the data—America, Europe, Australasia, and Asia. No data were available for Africa. Results: A multivariate stepwise linear regression model was used. Main outcome measure was age standardised male mortality rates for 51 countries for the year 1995. Age standardised female homicide rates and GDP per capita ranking were the explanatory variables in the model. Results were also adjusted for the effects of general rates of homicide. Age standardised female homicide rates and ranking of GDP were strongly correlated with age standardised male mortality rates (Pearson's r = 0.699 and Spearman's 0.744 respectively) and both correlations achieved significance (ppatriarchy, the higher is the rate of mortality among men. Conclusion: These data suggest that oppression and exploitation harm the oppressors as well as those they oppress, and that men's higher mortality is a preventable social condition, which could be tackled through global social policy measures. PMID:16166362

Strain Rate Effect on Tensile Behavior for a High Specific Strength Steel: From Quasi-Static to Intermediate Strain Rates

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Wei Wang

2017-12-01

Full Text Available The strain rate effect on the tensile behaviors of a high specific strength steel (HSSS with dual-phase microstructure has been investigated. The yield strength, the ultimate strength and the tensile toughness were all observed to increase with increasing strain rates at the range of 0.0006 to 56/s, rendering this HSSS as an excellent candidate for an energy absorber in the automobile industry, since vehicle crushing often happens at intermediate strain rates. Back stress hardening has been found to play an important role for this HSSS due to load transfer and strain partitioning between two phases, and a higher strain rate could cause even higher strain partitioning in the softer austenite grains, delaying the deformation instability. Deformation twins are observed in the austenite grains at all strain rates to facilitate the uniform tensile deformation. The B2 phase (FeAl intermetallic compound is less deformable at higher strain rates, resulting in easier brittle fracture in B2 particles, smaller dimple size and a higher density of phase interfaces in final fracture surfaces. Thus, more energy need be consumed during the final fracture for the experiments conducted at higher strain rates, resulting in better tensile toughness.

HIV positivity but not HPV/p16 status is associated with higher recurrence rate in anal cancer.

Science.gov (United States)

Meyer, Joshua E; Panico, Vinicius J A; Marconato, Heloisa M F; Sherr, David L; Christos, Paul; Pirog, Edyta C

2013-12-01

.06). The regional and distant failure rate was not related to HPV/p16 positivity or histologic differentiation of ACA; however, HIV positivity appeared to be associated with a higher recurrence rate and worse recurrence-free survival.

Flavonoid extraction from Alpinia zerumbet (Pers.) Burtt et Smith leaves using different techniques and solvents

International Nuclear Information System (INIS)

Victorio, Cristiane P.; Lage, Celso Luiz S.; Kuster, Ricardo M.

2009-01-01

The current study aims to verify the best method for a rapid and efficient extraction of flavonoids from Alpinia zerumbet. Dried leaves were extracted using distillated water and ethanol 70% by extraction methods of shaking maceration, ultrasonic, microwave and stirring. By the application of TLC and reversed phase HPLC techniques the rutin and kempferol-3-O-glucuronide were detected. Ethanol 70% was more efficient for flavonoids extraction than water. No significant yielding variation was verified for ultrasonic, microwave and stirring methods using ethanol 70% (11 to 14%). The relative concentration of rutin and kempferol-3-O-glucuronide, respectively, was higher by ultrasonic (1.5 and 5.62 mg g -1 dried leaves, respectively) and by microwave (1.0 and 6.64 mg g -1 dried leaves) methods using ethanol. Rapid and simplified extraction proceeding optimize phyto chemical work and acquisition of secondary metabolites. (author)

Flavonoids extraction from Alpinia zerumbet (Pers.) Burtt et Smith leaves using different procedures

Energy Technology Data Exchange (ETDEWEB)

Victorio, Cristiane P.; Lage, Celso Luiz S., E-mail: cris.pvictor@gmail.co [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Fisiologia Vegetal; Kuster, Ricardo M. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nucleo de Pesquisas de Produtos Naturais (NPPN). Lab. de Fitoquimica

2010-07-01

The current study aims to verify the best method for a rapid and efficient extraction of flavonoids from Alpinia zerumbet. Dried leaves were extracted using distillated water and ethanol 70% by extraction methods of shaking maceration, ultrasonic, microwave and stirring. By the application of TLC and reversed-phase HPLC techniques the rutin and kaempferol-3-O-glucuronide were detected. Ethanol 70% was more efficient for flavonoids extraction than water. No significant yielding variation was verified for ultrasonic, microwave and stirring methods using ethanol 70% (11 to 14%). Relative concentration of rutin and kaempferol-3-O-glucuronide, respectively, was higher by ultrasonic (1.5 and 5.62 mg g{sup -1} dried leaves) and by microwave (1.0 and 6.64 mg g{sup -1} dried leaves) methods using 70% ethanol. Rapid and simplified extraction proceeding optimize phytochemical work and acquisition of secondary metabolites. (author)

Flavonoid extraction from Alpinia zerumbet (Pers.) Burtt et Smith leaves using different techniques and solvents

Energy Technology Data Exchange (ETDEWEB)

Victorio, Cristiane P.; Lage, Celso Luiz S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Fisiologia Vegetal], e-mail: cris.pvictor@gmail.com; Kuster, Ricardo M. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nucleo de Pesquisas de Produtos Naturais. Lab. de Fitoquimica

2009-01-15

The current study aims to verify the best method for a rapid and efficient extraction of flavonoids from Alpinia zerumbet. Dried leaves were extracted using distillated water and ethanol 70% by extraction methods of shaking maceration, ultrasonic, microwave and stirring. By the application of TLC and reversed phase HPLC techniques the rutin and kempferol-3-O-glucuronide were detected. Ethanol 70% was more efficient for flavonoids extraction than water. No significant yielding variation was verified for ultrasonic, microwave and stirring methods using ethanol 70% (11 to 14%). The relative concentration of rutin and kempferol-3-O-glucuronide, respectively, was higher by ultrasonic (1.5 and 5.62 mg g{sup -1} dried leaves, respectively) and by microwave (1.0 and 6.64 mg g{sup -1} dried leaves) methods using ethanol. Rapid and simplified extraction proceeding optimize phyto chemical work and acquisition of secondary metabolites. (author)

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats.

Science.gov (United States)

Nagao, Hidenori; Sasaki, Makoto; Imazu, Tetsuya; Takahashi, Kenjo; Aoki, Hironori; Minato, Kouichi

2014-10-29

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T4). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T4 turnover. We compared serum T4 turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T3). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T3 infusion. After the T3 infusion, the turnover rate of serum T4 in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T3 infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T3 infusion. This study suggests that repression of the disappearance of serum T4 in rats after Tx is a homeostatic response to decreased serum T3 concentrations. Additionally, T4 glucuronide is a storage form of T4, but may also have biological significance. These results suggest strongly that repression of deiodination of T4 by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimal Admission to Higher Education

DEFF Research Database (Denmark)

Albæk, Karsten

This paper constructs higher education admission rules that maximise graduation rates and thus increase the skill level of the work force. An application shows that students with a low level in mathematics in secondary school ought to find it easier to be admitted to an economics programme than...... to law or psychology programmes, even though economics is the most difficult programme from which to graduate without a strong background in mathematics. Indirect gains from optimal admission include the potential of making whole cohorts of students more able to graduate with a higher education degree....

Chemical communication in tilapia: a comparison of Oreochromis mossambicus with O. niloticus.

Science.gov (United States)

Hubbard, Peter C; Mota, Vasco C; Keller-Costa, Tina; da Silva, José Paulo; Canário, Adelino V M

2014-10-01

In allopatric speciation species differentiation generally results from different selective pressures in different environments, and identifying the traits responsible helps to understand the isolation mechanism(s) involved. Male Mozambique tilapia (Oreochromis mossambicus) use urine to signal dominance; furthermore, 5β-pregnane-3α,17,20β-triol-3α-glucuronide (and its α-epimer, 5β-pregnane-3α,17,20α-triol-3α-glucuronide), in their urine is a potent pheromone, the concentration of which is correlated with social status. The Nile tilapia (Oreochromisniloticus) is a close relative; species divergence probably resulted from geographical separation around 6 million years ago. This raises the question of whether the two species use similar urinary chemical cues during reproduction. The olfactory potency of urine, and crude extracts, from either species was assessed by the electro-olfactogram and the presence of the steroid glucuronides in urine from the Nile tilapia by liquid-chromatography/mass-spectrometry. Both species showed similar olfactory sensitivity to urine and respective extracts from either species, and similar sensitivity to the steroid glucuronides. 5β-Pregnan-3α,17α,20β-triol-3α-glucuronide was present at high concentrations (approaching 0.5mM) in urine from Nile tilapia, with 5β-pregnan-3α,17α,20α-triol-3α-glucuronide present at lower concentrations, similar to the Mozambique tilapia. Both species also had similar olfactory sensitivity to estradiol-3-glucuronide, a putative urinary cue from females. Together, these results support the idea that reproductive chemical cues have not been subjected to differing selective pressure. Whether these chemical cues have the same physiological and behavioural roles in O. niloticus as O. mossambicus remains to be investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibition of P-glycoprotein and multidrug resistance-associated protein 2 regulates the hepatobiliary excretion and plasma exposure of thienorphine and its glucuronide conjugate

Directory of Open Access Journals (Sweden)

Ling-Lei Kong

2016-08-01

Full Text Available Thienorphine (TNP is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic.

Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

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Ling Ye

Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of cannabinoids and phase I and II metabolites in meconium.

Science.gov (United States)

Prego-Meleiro, Pablo; Lendoiro, Elena; Concheiro, Marta; Cruz, Angelines; López-Rivadulla, Manuel; de Castro, Ana

2017-05-12

A liquid chromatography-tandem mass spectrometry (LC-MSMS) method was developed and fully validated for the determination of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxyTHC (OHTHC), 11-nor-9-carboxyTHC (THCCOOH), 8-β-11-dihydroxyTHC (diOHTHC), cannabinol, cannabidiol, and THC and THCCOOH glucuronides in 0.25±0.02g meconium. Samples were homogenized in methanol and subjected to cation exchange solid-phase extraction. Chromatographic separation was performed on a Kinetex C18 column (50 mm×2.1mm, 2.6μm) at 35°C, with a gradient of 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min; total run time was 10min. Two transitions per analyte were monitored in MRM mode. The method was specific and sensitive; LOD was from 1 to 2ng/g, and LOQ from 4 to 10ng/g; linearity ranged from 4 to 400 ng/g for all the analytes, except for THC glucuronide (10-400ng/g); intra-assay, inter-assay and total imprecision were <11.2%, <13.45% and <15.6%, respectively; accuracy ranged from 93.9% to 109.0% of the target concentration; matrix effect, extraction and process efficiency ranged from -26.4% to -71.4%, 49.9% to 69.5% and 14.3% to 45.0%, respectively. The inclusion of THC and THCCOOH glucuronides avoided the need for the hydrolysis process, thus facilitating sample pretreatment. Application of the method to 19 authentic meconium specimens from uncontrolled pregnancies or women suspicious of drug consumption revealed fetal cannabis exposure in 4 newborns. THCCOOH (24.1-288.8ng/g), diOHTHC (53.2-332.4ng/g), THC (4.2-7.7ng/g), CBN (30.7-93.3ng/g) and CBD (7.1-251.5ng/g) were detected in all cases; THCCOOH glucuronide (190.2-306.8ng/g) in 3 cases; and OHTHC (11.9ng/g) in the remaining one; however, THC glucuronide was not identified in any specimen. Copyright © 2017 Elsevier B.V. All rights reserved.

Factors Impacting Online Ratings for Otolaryngologists.

Science.gov (United States)

Calixto, Nathaniel E; Chiao, Whitney; Durr, Megan L; Jiang, Nancy

2018-06-01

To identify factors associated with online patient ratings and comments for a nationwide sample of otolaryngologists. Ratings, demographic information, and written comments were obtained for a random sample of otolaryngologists from HealthGrades.com and Vitals.com . Online Presence Score (OPS) was based on 10 criteria, including professional website and social media profiles. Regression analyses identified factors associated with increased rating. We evaluated for correlations between OPS and other attributes with star rating and used chi-square tests to evaluate content differences between positive and negative comments. On linear regression, increased OPS was associated with higher ratings on HealthGrades and Vitals; higher ratings were also associated with younger age on Vitals and less experience on HealthGrades. However, detailed correlation studies showed weak correlation between OPS and rating; age and graduation year also showed low correlation with ratings. Negative comments more likely focused on surgeon-independent factors or poor bedside manner. Though younger otolaryngologists with greater online presence tend to have higher ratings, weak correlations suggest that age and online presence have only a small impact on the content found on ratings websites. While most written comments are positive, deficiencies in bedside manner or other physician-independent factors tend to elicit negative comments.

Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine

Directory of Open Access Journals (Sweden)

Bård Helge Hoff

2012-01-01

Full Text Available A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri-O-benzoyl-α-D-glycopyranosyl bromideuronate proceeded to give the N2-conjugate. However, lamotrigine-N2-glucuronide was most efficiently synthesised from methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromideuronate. Employing nitromethane as solvent with CdCO3 as a base lamotrigine-N2 glucuronide was prepared in a high yield (41%. Also methyl (2,3-di-O-benzoyl-4-deoxy-4-fluoro-α-D-glucosyl bromideuronate underwent N-glucuronidation, but the product was unstable, eliminating hydrogen fluoride to give the corresponding enoate conjugate.

Quantitative Developments in Turkish Higher Education since 1933

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Aslı GÜNAY

2011-01-01

Full Text Available In this study, quantitative developments in Turkish higher education during the Republic period from 1933, when the first university was established, to date are tried to be demonstrated. In parallel with this purpose, first, establishment dates of universities, number of universities by years as well as number of universities established during the periods of each presidents of Turkish Council of Higher Education are listed. Also, spread to all provinces as of 2008, the distribution of the number of universities with regard to provinces is given. On the other hand, development of Turkish higher education by years is examined by using several quantitative indicators about higher education. Thus, number of students in higher education, total number of academic staffs as well as those with PhD, improvement in the number of students per academic staff and higher education gross enrollment rates by years are shown. Furthermore, especially for big provinces in Turkey (Ankara, İstanbul and İzmir number of universities, number of students in higher education and higher education gross enrollment rates are provided. Distribution of higher education students according to higher education institutions, higher education programs and education types in 2011 is presented as well as distribution of academic staffs according to higher education institutions and information about their academic positions. In addition, quantitative data about higher education bachelor and associate degrees (numbers of programs types, programs, quotas and placed students in 2010 is given. Finally, the position of Turkish higher education in the world with respect to the number of academic publications and the change in the number of academic publications per staff by years are analyzed.

Authors attain comparable or slightly higher rates of citation publishing in an open access journal (CytoJournal) compared to traditional cytopathology journals - A five year (2007-2011) experience.

Science.gov (United States)

Frisch, Nora K; Nathan, Romil; Ahmed, Yasin K; Shidham, Vinod B

2014-01-01

The era of Open Access (OA) publication, a platform which serves to better disseminate scientific knowledge, is upon us, as more OA journals are in existence than ever before. The idea that peer-reviewed OA publication leads to higher rates of citation has been put forth and shown to be true in several publications. This is a significant benefit to authors and is in addition to another relatively less obvious but highly critical component of the OA charter, i.e. retention of the copyright by the authors in the public domain. In this study, we analyzed the citation rates of OA and traditional non-OA publications specifically for authors in the field of cytopathology. We compared the citation patterns for authors who had published in both OA and traditional non-OA peer-reviewed, scientific, cytopathology journals. Citations in an OA publication (CytoJournal) were analyzed comparatively with traditional non-OA cytopathology journals (Acta Cytologica, Cancer Cytopathology, Cytopathology, and Diagnostic Cytopathology) using the data from web of science citation analysis site (based on which the impact factors (IF) are calculated). After comparing citations per publication, as well as a time adjusted citation quotient (which takes into account the time since publication), we also analyzed the statistics after excluding the data for meeting abstracts. Total 28 authors published 314 publications as articles and meeting abstracts (25 authors after excluding the abstracts). The rate of citation and time adjusted citation quotient were higher for OA in the group where abstracts were included (P citation than the publications in the traditional non-OA journals in the field of cytopathology over a 5 year period (2007-2011). However, this increase was statistically insignificant if the meeting abstracts were excluded from the analysis. Overall, the rates of citation for OA and non-OA were slightly higher to comparable.

The uridine diphosphate glucuronosyltransferases: quantitative structure-activity relationships for hydroxyl polychlorinated biphenyl substrates

Energy Technology Data Exchange (ETDEWEB)

Wang, Degao [Dalian University of Technology, Department of Environmental Science and Technology, Dalian (China)

2005-10-01

Quantitative structure-activity relationships (QSARs), which relate the glucuronidation of hydroxyl polychlorinated biphenyls (OH-PCBs) - catalyzed by the uridine diphosphate glucuronosyltransferases (UGTs) - to their physicochemical properties and molecular structural parameters, can be used to predict the rate constants and interpret the mechanism of glucuronidation. In this study, QSARs have been developed that use 23 semi-empirical calculated quantum chemical descriptors to predict the logarithms of the constants 1/K{sub m} and V{sub max}, related to enzyme kinetics. A partial least squares regression method was used to select the optimal set of descriptors to minimize the multicollinearity between the descriptors, as well as to maximize the cross-validated coefficient (Q{sup 2} {sub cum}) values. The key descriptors affecting log(1/K{sub m}) were E{sub lumo}- E{sub homo} (the energy gap between the lowest unoccupied molecular orbital and the highest occupied molecular orbital) and q{sub C}{sup -} (the largest negative net atomic charge on a carbon atom), while the key descriptors affecting log V{sub max} were the polarizability {alpha}, the Connolly solvent-excluded volume (CSEV), and logP (the logarithm of the partition coefficient for octanol/water). From the results obtained it can be concluded that hydrophobic and electronic aspects of OH-PCBs are important in the glucuronidation of OH-PCBs. (orig.)

Higher Prevalence and Awareness, but Lower Control Rate of Hypertension in Patients with Diabetes than General Population: The Fifth Korean National Health and Nutrition Examination Survey in 2011

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Seung-Hyun Ko

2014-02-01

Full Text Available BackgroundWe investigated the prevalence, awareness, treatment, and control rate of hypertension in Korean adults with diabetes using nationally representative data.MethodsUsing data of 5,105 adults from the fifth Korea National Health and Nutrition Examination Survey in 2011 (4,389 nondiabetes mellitus [non-DM], 242 newly diagnosed with DM (new-DM, and 474 previously diagnosed with DM (known-DM, we analyzed the prevalence of hypertension (mean systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medication and control rate of hypertension (blood pressure [BP] <130/80 mm Hg.ResultsThe prevalence of hypertension in diabetic adults was 54.6% (44.4% in new-DM and 62.6% in known-DM, P<0.0001 and P<0.0001, respectively compared with non-DM adults (26.2%. Compared to non-DM, awareness (85.7%, P<0.001 and treatment (97.0%, P=0.020 rates were higher in known-DM, whereas no differences were found between new-DM and non-DM. Control rate among all hypertensive subjects was lower in new-DM (14.9%, compared to non-DM (35.1%, P<0.001 and known-DM (33.3%, P=0.004. Control rate among treated subjects was also lower in new-DM (25.2%, compared to non-DM (68.4%, P<0.0001 and known-DM (39.9%, P<0.0001.ConclusionHigher prevalence and low control rate of hypertension in adults with diabetes suggest that stringent efforts are needed to control BP in patients with diabetes, particularly in newly diagnosed diabetic patients.

Higher Education Leadership: Servant Leadership and the Effects on Student Satisfaction

Science.gov (United States)

Padron, Joshua

2012-01-01

The enormous challenge confronting higher education today in relation to its revenue shortfall, lack of student persistence and low graduation rates are problematic. The literature proposes that if an institution of higher education increases student satisfaction rates, they will increase student persistence. Also, the literature suggests that an…

Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy.

Science.gov (United States)

Sennerstam, Roland B; Franzén, Bo S H; Wiksell, Hans O T; Auer, Gert U

2017-10-01

The literature offers discordant results regarding whether diagnostic biopsy is associated with the dissemination of cancer cells, resulting in local and/or distant metastasis. The long-term outcomes of patients with breast cancer were compared between those who were diagnosed using either fine-needle aspiration biopsy (FNAB) or core-needle biopsy (CNB) during 2 decades: the 1970s and 1990s. In the 1970s, the only diagnostic needle biopsy method used for breast cancer in Sweden was FNAB. CNB was introduced 1989 and became established in Stockholm Gotland County in the early 1990s. The authors compared the clinical outcomes of patients diagnosed using FNAB from 1971 to 1976 (n = 354) versus those of patients diagnosed using CNB from 1991 to 1995 (n = 1729). Adjusting for differences in various treatment modalities, mammography screening, tumor size, DNA ploidy, and patient age between the 2 decades, 2 strictly matched samples representing FNAB (n = 181) and CNB (n = 203) were selected for a 15-year follow-up study. In a comparison of the rates of distant metastasis in the strictly matched patient groups from the FNAB and CNB cohorts, significantly higher rates of late-appearing (5-15 years after diagnosis) distant metastasis were observed among the patients who were diagnosed on CNB compared with those who were diagnosed on FNAB. No significant difference in local metastasis was observed between the 2 groups. At 5 to 15 years after diagnosis of the primary tumor, CNB-diagnosed patients had significantly higher rates of distant metastases than FNAB-diagnosed patients. Cancer Cytopathol 2017;125:748-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

Expensive Brains: “Brainy” Rodents have Higher Metabolic Rate

Science.gov (United States)

Sobrero, Raúl; May-Collado, Laura J.; Agnarsson, Ingi; Hernández, Cristián E.

2011-01-01

Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution of traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass (BM) varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006). Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR) correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species BM is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of BM for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of BM) and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur. PMID:21811456

Mortality rates in people with intellectual disabilities

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Rachael Williams

2017-04-01

National English data confirm that patients with ID have higher mortality rates than those without. Mortality rates for patients with ID were higher across all age/sex groups and causes, with almost half of deaths classified as avoidable.

The Roles of Public Higher Education Expenditure and the Privatization of the Higher Education on U.S. States Economic Growth

Science.gov (United States)

Curs, Bradley R.; Bhandari, Bornali; Steiger, Christina

2011-01-01

Previous empirical literature finds that government expenditure on higher education has a negative, or null, effect on U.S. economic growth rates. This empirical result may be driven by omission of an important variable--the privatization of higher education. Using state-level panel data from 1970 to 2005, this analysis investigates whether the…

Countries with women inequalities have higher stroke mortality.

Science.gov (United States)

Kim, Young Dae; Jung, Yo Han; Caso, Valeria; Bushnell, Cheryl D; Saposnik, Gustavo

2017-10-01

Background Stroke outcomes can differ by women's legal or socioeconomic status. Aim We investigated whether differences in women's rights or gender inequalities were associated with stroke mortality at the country-level. Methods We used age-standardized stroke mortality data from 2008 obtained from the World Health Organization. We compared female-to-male stroke mortality ratio and stroke mortality rates in women and men between countries according to 50 indices of women's rights from Women, Business and the Law 2016 and Gender Inequality Index from the Human Development Report by the United Nations Development Programme. We also compared stroke mortality rate and income at the country-level. Results In our study, 176 countries with data available on stroke mortality rate in 2008 and indices of women's rights were included. There were 46 (26.1%) countries where stroke mortality in women was higher than stroke mortality in men. Among them, 29 (63%) countries were located in Sub-Saharan African region. After adjusting by country income level, higher female-to-male stroke mortality ratio was associated with 14 indices of women's rights, including differences in getting a job or opening a bank account, existence of domestic violence legislation, and inequalities in ownership right to property. Moreover, there was a higher female-to-male stroke mortality ratio among countries with higher Gender Inequality Index (r = 0.397, p Gender Inequality Index was more likely to be associated with stroke mortality rate in women than that in men (p gender inequality status is associated with women's stroke outcomes.

Seasonal changes in steroid metabolism in the male reproductive organ-system of the African catfish, Clarias gariepinus

NARCIS (Netherlands)

Resink, J.W.; Schoonen, W.G.E.J.; Hurk, R. van den; Viveen, W.J.A.R.; Lambert, J.G.D.

1987-01-01

Steroid and steroid glucuronide synthesis in feral male African catfish was investigated in vitro by incubating testes with [3H]-pregnenolone and seminal vesicles with [3H]-androstenedione. In testes, the capacity to form progestins, androgens, especially 11-oxygenated ones, and steroid glucuronides

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

Directory of Open Access Journals (Sweden)

Ida Nymann Petersen

2013-04-01

Full Text Available γ-Hydroxybutanoic acid (GHB is used as a date-rape drug, which renders the victims unconscious and defenceless. Intoxications are very difficult to detect for forensic scientists due to rapid metabolism to endogenous levels of GHB. We recently discovered a new major metabolite, 2, of GHB (1 that could potentially extend the analytical detection window for GHB intoxications. Herein we disclose synthetic procedures based on a Koenigs–Knorr glucuronidation approach that provides GHB glucuronide 2 and a deuterium-labelled analogue d4-2 of high purity suitable for analytical chemistry. In addition, we have assessed the stability of GHB glucuronide 2 by mimicking the natural pH range for urine, which is of importance in the development of new analytical methods. Using NMR we show that GHB glucuronide 2 is highly stable towards aqueous hydrolysis within the pH range normally observed for urine even at elevated temperature.

Analysis of 162 colon injuries in patients with penetrating abdominal trauma: concomitant stomach injury results in a higher rate of infection.

Science.gov (United States)

O'Neill, Patricia A; Kirton, Orlando C; Dresner, Lisa S; Tortella, Bartholomew; Kestner, Mark M

2004-02-01

Fecal contamination from colon injury has been thought to be the most significant factor for the development of surgical site infection (SSI) after trauma. However, there are increasing data to suggest that other factors may play a role in the development of postinjury infection in patients after colon injury. The purpose of this study was to determine the impact of gastric wounding on the development of SSI and nonsurgical site infection (NSSI) in patients with colon injury. Post hoc analysis was performed on data prospectively collected for 317 patients presenting with penetrating hollow viscus injury. One hundred sixty-two patients with colon injury were subdivided into one of three groups: patients with isolated colon wounds (C), patients with colon and stomach wounds with or without other organ injury (C+S), and patients with colon and other organ injury but no stomach injury (C-S) and assessed for the development of SSI and NSSI. Infection rates were also determined for patients who sustained isolated gastric injury (S) and gastric injury in combination with other injuries other than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel-Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by multivariate logistic regression. C+S patients had a higher rate of SSI infection (31%) than C patients (3.6%) (p=0.008) and C-S patients (13%) (p=0.021). Similarly, the incidence of NSSI was also significantly greater in the C+S group (37%) compared with the C patients (7.5%) (p=0.07) and the C-S patients (17%) (p=0.019). There was no difference in the rate of SSI or NSSI between the C and C-S groups (p=0.3 and p=0.24, respectively). The rate of SSI was significantly greater in the C+S patients when compared with the S-C patients (31% vs. 10%, p=0.008), but there was no statistical difference in the rate of NSSI in the C+S group and the S-C group (37

Evaluating Competitiveness of Faculties of Higher Educational Establishments in Slovakia

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Rayevnyeva Olena V.

2016-02-01

Full Text Available The problem of competitiveness of higher education, efficiency of its functioning and training graduates of higher educational establishments according to the current and future needs of the market are among the key issues of socio-economic development strategy in EU countries. The aim of the study is to determine the competitiveness of faculties of major higher educational establishments based on the use of the cluster analysis and rating evaluations provided by national experts. The paper describes the methodology of rating evaluation of faculties of higher educational establishments in Slovakia on the basis of such components as: educational process; attractiveness of the program; science and research activities; doctoral studies; attracted grants. Shortcomings of the approach to faculty rating evaluations based on the averaged value have been determined. In order to improve analysis of the competitive positions of individual faculties of higher educational establishments in Slovakia, the cluster analysis was used and the results of breaking the faculties into five groups were presented. To forecast changes in the competitive positions of faculties of higher educational establishments in Slovakia, discriminant functions enabling to determine possible qualitative changes in the state of the faculties’ competitiveness due to external or internal factors have been built.

Do Astronauts have a Higher Rate of Orthopedic Shoulder Conditions than a Cohort of Working Professionals?

Science.gov (United States)

Laughlin, Mitzi S.; Murray, Jocelyn D.; Young, Millenia; Wear, Mary L.; Tarver, W. J.; Van Baalen, Mary

2016-01-01

Occupational surveillance of astronaut shoulder injuries began with operational concerns at the Neutral Buoyancy Laboratory (NBL) during Extra Vehicular Activity (EVA) training. NASA has implemented several occupational health initiatives during the past 20 years to decrease the number and severity of injuries, but the individual success rate is unknown. Orthopedic shoulder injury and surgery rates were calculated, but classifying the rates as normal, high or low was highly dependent on the comparison group. The purpose of this study was to identify a population of working professionals and compare orthopedic shoulder consultation and surgery rates.

Infusions of artichoke and milk thistle represent a good source of phenolic acids and flavonoids.

Science.gov (United States)

Pereira, Carla; Barros, Lillian; Carvalho, Ana Maria; Santos-Buelga, Celestino; Ferreira, Isabel C F R

2015-01-01

Cynara scolymus L. (artichoke) and Silybum marianum (L.) Gaertn (milk thistle) are two herbs well-known for their efficiency in the prevention/treatment of liver injuries, among other chronic diseases. Therefore, the aim of this work was to characterize specific bioactive components, phenolic compounds, in hydromethanolic extracts but also in infusions (the most commonly used preparations) obtained from the whole plant of milk thistle and artichoke. The phenolic profiles were accessed using HPLC-DAD-MS/ESI. Infusions of both species presented higher phenolic contents than the hydromethanolic extracts. Milk thistle presented a similar phenolic composition between the two preparations, revealing only differences in the quantities obtained. Nevertheless, artichoke revealed a slightly different profile considering infusion and hydromethanolic extracts. Apigenin-7-O-glucuronide was the major flavonoid found in milk thistle, while luteolin-7-O-glucuronide was the most abundant in artichoke. Therefore, infusions of both artichoke and milk thistle represent a good source of bioactive compounds, especially phenolic acids and flavonoids.

Flower color changes in three Japanese hibiscus species: further quantitative variation of anthocyanin and flavonols.

Science.gov (United States)

Shimokawa, Satoshi; Iwashina, Tsukasa; Murakami, Noriaki

2015-03-01

One anthocyanin and four flavonols were detected from the petals of Hibiscus hamabo, H. tiliaceus and H. glaber. They were identified as cyanidin 3-0- sambubioside, gossypetin 3-O-glucuronide-8-O-glucoside, quercetin 7-O-rutinoside, gossypetin 3-O-glucoside and gossypetin 8-O-glucuronide by UV spectra, LC-MS, acid hydrolysis and HPLC. The flavonoid composition was essentially the same among the petals ofH. hamabo, H. tiliaceus and H. glaber, and there was little quantitative variation, except for cyanidin 3-O-sambubioside, the content of which in the petals ofH. tiliaceus and H. glaber was much higher than in that of H. hamabo. Flower colors of H. tiliaceus and H. glaber change from yellow to red, and that of H. hamabo changes from yellow to orange. These changes were caused by contents of anthocyanin and flavonols, which increased after flowering of H. hamabo, H. tiliaceus and H. glaber.

The Successful Educational Journeys of American Indian Women: Forming Aspirations for Higher Education

Science.gov (United States)

Andrade, Maureen Snow

2014-01-01

American Indians (AIs) have lower higher education enrollment and completion rates than Whites and most minority groups. AI women, however, participate at higher rates than AI men, White women, and White men. Research has not examined what contributes to their higher education aspirations. This study explored the middle and high school experiences…

Outlook on Student Retention in Higher Education University Reforms in Morocco

OpenAIRE

Zoulal Mansouri; Mohamed El Amine Moumine

2017-01-01

High student attrition rates at university have become one of the most challenging issues in higher education worldwide in the last five decades. Moroccan universities are no exception. At-risk students drop out of studies for a plethora of reasons, and the attrition rate is increasing despite the efforts made in education reforms carried out since 1999. This article reviews the most important components of the higher education reforms that have been adopted in Moroccan higher education in th...

Self-Rated Competences Questionnaires from a Design Perspective

Science.gov (United States)

Braun, Edith; Woodley, Alan; Richardson, John T. E.; Leidner, Bernhard

2012-01-01

This paper provides a theoretical review of self-rated competences questionnaires. This topic is influenced by the ongoing world-wide reform of higher education, which has led to a focus on the learner outcomes of higher education. Consequently, questionnaires on self-rated competences have increasingly been employed. However, self-ratings are…

Central nervous system tumours among adolescents and young adults (15-39 years) in Southern and Eastern Europe: Registration improvements reveal higher incidence rates compared to the US.

Science.gov (United States)

Georgakis, Marios K; Panagopoulou, Paraskevi; Papathoma, Paraskevi; Tragiannidis, Athanasios; Ryzhov, Anton; Zivkovic-Perisic, Snezana; Eser, Sultan; Taraszkiewicz, Łukasz; Sekerija, Mario; Žagar, Tina; Antunes, Luis; Zborovskaya, Anna; Bastos, Joana; Florea, Margareta; Coza, Daniela; Demetriou, Anna; Agius, Domenic; Strahinja, Rajko M; Sfakianos, Georgios; Nikas, Ioannis; Kosmidis, Sofia; Razis, Evangelia; Pourtsidis, Apostolos; Kantzanou, Maria; Dessypris, Nick; Petridou, Eleni Th

2017-11-01

To present incidence of central nervous system (CNS) tumours among adolescents and young adults (AYAs; 15-39 years) derived from registries of Southern and Eastern Europe (SEE) in comparison to the Surveillance, Epidemiology and End Results (SEER), US and explore changes due to etiological parameters or registration improvement via evaluating time trends. Diagnoses of 11,438 incident malignant CNS tumours in AYAs (1990-2014) were retrieved from 14 collaborating SEE cancer registries and 13,573 from the publicly available SEER database (1990-2012). Age-adjusted incidence rates (AIRs) were calculated; Poisson and joinpoint regression analyses were performed for temporal trends. The overall AIR of malignant CNS tumours among AYAs was higher in SEE (28.1/million) compared to SEER (24.7/million). Astrocytomas comprised almost half of the cases in both regions, albeit the higher proportion of unspecified cases in SEE registries (30% versus 2.5% in SEER). Similar were the age and gender distributions across SEE and SEER with a male-to-female ratio of 1.3 and an overall increase of incidence by age. Increasing temporal trends in incidence were documented in four SEE registries (Greater Poland, Portugal North, Turkey-Izmir and Ukraine) versus an annual decrease in Croatia (-2.5%) and a rather stable rate in SEER (-0.3%). This first report on descriptive epidemiology of AYAs malignant CNS tumours in the SEE area shows higher incidence rates as compared to the United States of America and variable temporal trends that may be linked to registration improvements. Hence, it emphasises the need for optimisation of cancer registration processes, as to enable the in-depth evaluation of the observed patterns by disease subtype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Student Drop-Out from German Higher Education Institutions

Science.gov (United States)

Heublein, Ulrich

2014-01-01

28% of students of any one year currently give up their studies in bachelor degree programmes at German higher education institutions. Drop-out is to be understood as the definite termination in the higher education system without obtaining an academic degree. The drop-out rate is thereby calculated with the help of statistical estimation…

Being born under adverse economic conditions leads to a higher cardiovascular mortality rate later in life: evidence based on individuals born at different stages of the business cycle

DEFF Research Database (Denmark)

van den Berg, Gerard J; Doblhammer-Reiter, Gabriele; Christensen, Kaare

2011-01-01

since the 1870s and including the cause of death. To capture exogenous variation of conditions early in life, we use the state of the business cycle around birth. We find significant negative effects of economic conditions around birth on the individual CV mortality rate at higher ages...

Attaining the rate-independent limit of a rate-dependent strain gradient plasticity theory

DEFF Research Database (Denmark)

El-Naaman, Salim Abdallah; Nielsen, Kim Lau; Niordson, Christian Frithiof

2016-01-01

The existence of characteristic strain rates in rate-dependent material models, corresponding to rate-independent model behavior, is studied within a back stress based rate-dependent higher order strain gradient crystal plasticity model. Such characteristic rates have recently been observed...... for steady-state processes, and the present study aims to demonstrate that the observations in fact unearth a more widespread phenomenon. In this work, two newly proposed back stress formulations are adopted to account for the strain gradient effects in the single slip simple shear case, and characteristic...... rates for a selected quantity are identified through numerical analysis. Evidently, the concept of a characteristic rate, within the rate-dependent material models, may help unlock an otherwise inaccessible parameter space....

Does Accelerating Access to Higher Education Lower Its Quality? The Australian Experience

Science.gov (United States)

Pitman, Tim; Koshy, Paul; Phillimore, John

2015-01-01

In the pursuit of mass higher education, fears are often expressed that the quality of higher education suffers as access is increased. This quantitative study considers three proxies of educational quality: (1) prior academic achievement of the student, (2) attrition and retention rates and (3) progression rates, to establish whether educational…

Interferon-free treatment for patients with chronic hepatitis C and autoimmune liver disease: higher SVR rates with special precautions for deterioration of autoimmune hepatitis.

Science.gov (United States)

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Imazeki, Fumio; Moriyama, Mitsuhiko; Kato, Naoya

2018-02-20

Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR. Three patients took prednisolone (PSL) at baseline, and 3 did not take PSL during interferon-free treatment. In one HCV patient with AIH and cirrhosis, PSL were not administered at baseline, but she needed to take 40 mg/day PSL at week 8 for liver dysfunction. She also complained back pain and was diagnosed with vasospastic angina by coronary angiography at week 11. However, she completed interferon-free treatment. All 5 HCV patients with primary biliary cholangitis (PBC) completed treatment and achieved SVR. Three of these HCV patients with PBC were treated with UDCA during interferon-free treatment. Interferon-free regimens could result in higher SVR rates in HCV patients with autoimmune liver diseases. As interferon-free treatment for HCV may have an effect on hepatic immunity and activity of the autoimmune liver diseases, careful attention should be paid to unexpected adverse events in their treatments. Total 12 patients with HCV and autoimmune liver diseases [7 AIH and PBC], who were treated with interferon-free regimens, were retrospectively analyzed.

Effects of Rating Purpose and Rater Self-Esteem on Performance Ratings.

Science.gov (United States)

1983-03-01

examined in a laboratory study, using a 2x2 analysis of variance design. Results indicate that low self - esteem raters assign significantly higher...design. Results indicate that low self - esteem raters assign significantly higher performance ratings when performance appraisal information will be used...studies indicated that individuals low in self - esteem have less self -confidence, feel less competent, and rely more on others’ opinions than do individuals

Effect of 60Co γ-irradiation on germination rate of corms and selection of a higher temperature-tolerance mutant 'zf893' of Crocus sativus L

International Nuclear Information System (INIS)

Zhang Qiaosheng; Wang Zhiping; Pan Jianyong; Li Xuebing; Xu Bujin; Zou Fenglian; Lu Gang

2009-01-01

The effects of 60 Co γ-rays irradiation on germination rate of corms of saffron (Crocus sativus L.) were studied and the results were as follows: (1) The corm germination rate raised with the corm fresh weight M (g) increasing, and the corms of 3 60 Co γ-rays, the typical radiation effect of dose on germination rate were obtained, and the semi-lethal dose (D 50 ) for the corms of 3 60 Co γ-rays and the stigma productivity of ZF893 was 1.3 times as that of the parent, for the field growing period, total weight of daughter corms and flower numbers of ZF893 were 22%, 27% and 30% higher than that of the parent, respectively. (4) The soluble protein SDS-PAGE patterns between ZF893 and it's parent were very similar, but the 54.8kD bands were much stronger in ZF893 and the 20.9 kD bands which were clear in ZF893, but were nearly absent in it's parent. (authors)

Nonlocal higher order evolution equations

KAUST Repository

Rossi, Julio D.

2010-06-01

In this article, we study the asymptotic behaviour of solutions to the nonlocal operator ut(x, t)1/4(-1)n-1 (J*Id -1)n (u(x, t)), x ∈ ℝN, which is the nonlocal analogous to the higher order local evolution equation vt(-1)n-1(Δ)nv. We prove that the solutions of the nonlocal problem converge to the solution of the higher order problem with the right-hand side given by powers of the Laplacian when the kernel J is rescaled in an appropriate way. Moreover, we prove that solutions to both equations have the same asymptotic decay rate as t goes to infinity. © 2010 Taylor & Francis.

Vitreous flow rates through dual pneumatic cutters: effects of duty cycle and cut rate

Directory of Open Access Journals (Sweden)

Abulon DJK

2015-02-01

Full Text Available Dina Joy K Abulon Medical Affairs, Alcon Research, Ltd, Lake Forest, CA, USA Purpose: We aimed to investigate effects of instrument settings on porcine vitreous flow rates through dual pneumatic high-speed vitrectomy probes. Methods: The CONSTELLATION® Vision System was tested with 250, 450, and 650 mmHg of vacuum using six ULTRAVIT® vitrectomy probes of each diameter (25+®, 25, 23, and 20 gauge operated from 500 cuts per minute (cpm up to 5,000 cpm. Duty cycle modes tested included biased open, 50/50, and biased closed. Flow rates were calculated by assessing the change in weight of porcine eyes during vitreous aspiration. Volumetric flow rate was measured with a computer-connected electronic scale. Results: At lower cut rates, the biased open mode produced higher flow than did the 50/50 mode, which produced higher flow than did the biased closed mode. In the biased closed and 50/50 modes, vitreous flow rates tended to increase with increasing cut rate. Vitreous flow rates in the biased open duty cycle mode remained relatively constant across cut rates. Conclusion: Vitreous flow rates through dual pneumatic vitrectomy probes could be manipulated by changing the duty cycle modes on the vitrectomy system. Differences in duty cycle behavior suggest that high-speed cut rates of 5,000 cpm may optimize vitreous aspiration. Keywords: enhanced 25-gauge vitrectomy, 25-gauge vitrectomy, 20-gauge vitrectomy, 23-gauge vitrectomy, aspiration, Constellation Vision System

Heart rate effects of intraosseous injections using slow and fast rates of anesthetic solution deposition.

Science.gov (United States)

Susi, Louis; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel; Drum, Melissa

2008-01-01

The authors, using a crossover design, randomly administered, in a single-blind manner, 3 primary intraosseous injections to 61 subjects using: the Wand local anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow injection); a conventional syringe injection at a deposition rate of 4 minutes and 45 seconds (slow injection), in 3 separate appointments spaced at least 3 weeks apart. A pulse oximeter measured heart rate (pulse). The results demonstrated the mean maximum heart rate was statistically higher with the fast intraosseous injection (average 21 to 28 beats/min increase) than either of the 2 slow intraosseous injections (average 10 to 12 beats/min increase). There was no statistically significant difference between the 2 slow injections. We concluded that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000 epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted in a significantly higher heart rate when compared with a 4-minute and 45-second anesthetic solution deposition using either the Wand or traditional syringe.

Steroid hormone excretion is enhanced by sucrose feeding to rats

International Nuclear Information System (INIS)

Kruger, T.C.; Hsu, H.; Saunders, J.P.; Kim, S.S.; Given-Proctor, J.; Ahrens, R.A.

1986-01-01

The hypothesis tested was that feeding rats sucrose rather than invert sugar (50:50 mixture of glucose and fructose) or cornstarch would result in a more rapid excretion of intravenously injected 1,2- 3 H aldosterone or 1,2,6,7- 3 H cortisol. The three carbohydrate sources provided 45% of dietary energy when fed, respectively, to one of three groups of 10 male, Sprague Dawley rats. After 4 or 8 weeks of ad lib feeding of the three diets 5 μCI of 3 H-labeled hormones were injected intravenously and % recovery in urine and feces was measured for 4 days by liquid scintillation counting. Nearly 90% of the 3 H injected as 1,2- 3 H aldosterone was recovered over 4 days in the excreta of the sucrose fed rats. This recovery of 3 H from aldosterone was significantly greater (P 3 H from intravenously injected 1,2,6,7- 3 H cortisol followed a similar pattern. The authors anticipate that the excretion of all metabolic end products and xenobiotics excreted as glucuronides would be enhanced by sucrose feeding. Oxocarbonium ions from the glucose portion of sucrose digestion in the mammalian small intestine are thought to compete with oxocarbonium ions from the glucuronic acid portion of glucuronide hydrolysis. Such competition may slow glucuronide hydrolysis and promote glucuronide excretion, including the glucuronides derived from aldosterone and cortisol

23 CFR 650.707 - Rating factor.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Rating factor. 650.707 Section 650.707 Highways FEDERAL..., STRUCTURES, AND HYDRAULICS Discretionary Bridge Candidate Rating Factor § 650.707 Rating factor. (a) The.... ER15OC02.010 The lower the rating factor, the higher the priority for selection and funding. (b) The terms...

Pharmacokinetics and metabolism of (R,R)-methoxyfenoterol in rat.

Science.gov (United States)

Siluk, D; Mager, D E; Kim, H S; Wang, Y; Furimsky, A M; Ta, A; Iyer, L V; Green, C E; Wainer, I W

2010-03-01

(R,R)-fenoterol (Fen), a beta(2)-adrenoceptor agonist, is under clinical investigation in the treatment of congestive heart disease. The pharmacokinetics and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have been determined following intravenous and oral administration to the rat and compared with corresponding results obtained with (R,R)-Fen. Results from the study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages in comparison to an earlier (R,R)-Fen. The oral administration revealed that the net exposure of (R,R)-MFen was about three-fold higher than that of (R,R)-Fen (7.2 versus 2.3 min x nmol ml(-1)), while intravenous administration proved that the clearance was significantly reduced, 48 versus 146 ml min(-1) kg(-1), the T(1/2) was significantly longer, 152.9 versus 108.9 min, and the area under the curve (AUC) was significantly increased, 300 versus 119 min x nmol ml(-1). (R,R)-MFen was primarily cleared by glucuronidation associated with significant presystemic glucuronidation of the compound. After intravenous and oral administration of (R,R)-MFen, (R,R)-Fen and (R,R)-Fen-G were detected in the urine samples indicating that (R,R)-MFen was O-demethylated and subsequently conjugated to (R,R)-Fen-G. The total (R,R)-Fen and (R,R)-Fen-G as a percentage of the dose after intravenous administration was 3.6%, while after oral administration was 0.3%, indicating that only a small fraction of the drug escaped presystemic glucuronidation and was available for O-demethylation. The glucuronidation pattern was confirmed by the results from in vitro studies where incubation of (R,R)-MFen with rat hepatocytes produced (R,R)-MFen-G, (R,R)-Fen and (R,R)-Fen-G, while incubation with rat intestinal microsomes only resulted in the formation of (R,R)-MFen-G.

Content and ratings of mature-rated video games.

Science.gov (United States)

Thompson, Kimberly M; Tepichin, Karen; Haninger, Kevin

2006-04-01

To quantify the depiction of violence, blood, sexual themes, profanity, substances, and gambling in video games rated M (for "mature") and to measure agreement between the content observed and the rating information provided to consumers on the game box by the Entertainment Software Rating Board. We created a database of M-rated video game titles, selected a random sample, recorded at least 1 hour of game play, quantitatively assessed the content, performed statistical analyses to describe the content, and compared our observations with the Entertainment Software Rating Board content descriptors and results of our prior studies. Harvard University, Boston, Mass. Authors and 1 hired game player. M-rated video games. Percentages of game play depicting violence, blood, sexual themes, gambling, alcohol, tobacco, or other drugs; use of profanity in dialogue, song lyrics, or gestures. Although the Entertainment Software Rating Board content descriptors for violence and blood provide a good indication of such content in the game, we identified 45 observations of content that could warrant a content descriptor in 29 games (81%) that lacked these content descriptors. M-rated video games are significantly more likely to contain blood, profanity, and substances; depict more severe injuries to human and nonhuman characters; and have a higher rate of human deaths than video games rated T (for "teen"). Parents and physicians should recognize that popular M-rated video games contain a wide range of unlabeled content and may expose children and adolescents to messages that may negatively influence their perceptions, attitudes, and behaviors.

Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

DEFF Research Database (Denmark)

Bochner, F.; Somogyi, A.A.; Danz, C.

1999-01-01

, its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting...

Camptothecin resistance

DEFF Research Database (Denmark)

Brangi, M; Litman, Thomas; Ciotti, M

1999-01-01

. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A...

Satellite telemetry reveals higher fishing mortality rates than previously estimated, suggesting overfishing of an apex marine predator.

Science.gov (United States)

Byrne, Michael E; Cortés, Enric; Vaudo, Jeremy J; Harvey, Guy C McN; Sampson, Mark; Wetherbee, Bradley M; Shivji, Mahmood

2017-08-16

Overfishing is a primary cause of population declines for many shark species of conservation concern. However, means of obtaining information on fishery interactions and mortality, necessary for the development of successful conservation strategies, are often fisheries-dependent and of questionable quality for many species of commercially exploited pelagic sharks. We used satellite telemetry as a fisheries-independent tool to document fisheries interactions, and quantify fishing mortality of the highly migratory shortfin mako shark ( Isurus oxyrinchus ) in the western North Atlantic Ocean. Forty satellite-tagged shortfin mako sharks tracked over 3 years entered the Exclusive Economic Zones of 19 countries and were harvested in fisheries of five countries, with 30% of tagged sharks harvested. Our tagging-derived estimates of instantaneous fishing mortality rates ( F = 0.19-0.56) were 10-fold higher than previous estimates from fisheries-dependent data (approx. 0.015-0.024), suggesting data used in stock assessments may considerably underestimate fishing mortality. Additionally, our estimates of F were greater than those associated with maximum sustainable yield, suggesting a state of overfishing. This information has direct application to evaluations of stock status and for effective management of populations, and thus satellite tagging studies have potential to provide more accurate estimates of fishing mortality and survival than traditional fisheries-dependent methodology. © 2017 The Author(s).

XY model with higher-order exchange.

Science.gov (United States)

Žukovič, Milan; Kalagov, Georgii

2017-08-01

An XY model, generalized by inclusion of up to an infinite number of higher-order pairwise interactions with an exponentially decreasing strength, is studied by spin-wave theory and Monte Carlo simulations. At low temperatures the model displays a quasi-long-range-order phase characterized by an algebraically decaying correlation function with the exponent η=T/[2πJ(p,α)], nonlinearly dependent on the parameters p and α that control the number of the higher-order terms and the decay rate of their intensity, respectively. At higher temperatures the system shows a crossover from the continuous Berezinskii-Kosterlitz-Thouless to the first-order transition for the parameter values corresponding to a highly nonlinear shape of the potential well. The role of topological excitations (vortices) in changing the nature of the transition is discussed.

Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages.

Science.gov (United States)

Pragst, F; Rothe, M; Moench, B; Hastedt, M; Herre, S; Simmert, D

2010-03-20

In this study the combined use of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for diagnoses of chronically excessive alcohol abuse is investigated at 174 hair samples from driving ability examination, workplace testing and child custody cases for family courts and evaluated with respect to the basics of interpretation. Using the cut-off values of 0.50 ng/mg for FAEE and 25 pg/mg for EtG, both markers were in agreement in 75% of the cases with 103 negative and 28 positive results and there were 30 cases with FAEE positive and EtG negative and 13 cases with FAEE negative and EtG positive. As the theoretical basis of interpretation, the pharmacokinetics of FAEE and EtG is reviewed for all steps between drinking of ethanol to incorporation in hair with particular attention to relationships between alcohol dose and concentrations in hair. It is shown that the concentrations of both markers are essentially determined by the area under the ethanol concentration in blood vs. time curve AUC(EtOH), despite large inter-individual variations. It is demonstrated by calculation of AUC(EtOH) on monthly basis for moderate, risky and heavy drinking that AUC(EtOH) increases very strongly in the range between 60 and 120 g ethanol per day. This specific feature which is caused by the zero-order elimination of ethanol is a favorable prerequisite for a high discrimination power of the hair testing for alcohol abuse. From the consideration of the different profiles of FAEE and EtG along the hair and in agreement with the literature survey, a standardized hair segment 0-3 cm is proposed with cut-off values of 0.5 ng/mg for FAEE and 30 pg/mg for EtG. This improves also the agreement between FAEE and EtG results in the cases of the present study. A scheme for combined interpretation of FAEE and EtG is proposed which uses the levels of abstinence and the double of the cut-off values as criteria in addition to the cut-off's. Considering the large variations in the relationship

Fermion tunneling from higher-dimensional black holes

International Nuclear Information System (INIS)

Lin Kai; Yang Shuzheng

2009-01-01

Via the semiclassical approximation method, we study the 1/2-spin fermion tunneling from a higher-dimensional black hole. In our work, the Dirac equations are transformed into a simple form, and then we simplify the fermion tunneling research to the study of the Hamilton-Jacobi equation in curved space-time. Finally, we get the fermion tunneling rates and the Hawking temperatures at the event horizon of higher-dimensional black holes. We study fermion tunneling of a higher-dimensional Schwarzschild black hole and a higher-dimensional spherically symmetric quintessence black hole. In fact, this method is also applicable to the study of fermion tunneling from four-dimensional or lower-dimensional black holes, and we will take the rainbow-Finsler black hole as an example in order to make the fact explicit.

Preharvest application of oxalic acid improves quality and phytochemical content of artichoke (Cynara scolymus L.) at harvest and during storage.

Science.gov (United States)

Martínez-Esplá, Alejandra; García-Pastor, María Emma; Zapata, Pedro Javier; Guillén, Fabián; Serrano, María; Valero, Daniel; Gironés-Vilaplana, Amadeo

2017-09-01

In this study the effect of oxalic acid (OA) treatment of artichoke plants (Cynara scolymus L.) on head artichoke development and on artichokes quality parameters (weight loss, firmness, and color), respiration rate, antioxidant activity and phenolics (measured by Folin Ciocalteu and HPLC-DAD-ESI/MS n ) at harvest and during storage for 21days at 2°C was evaluated. OA treatment increased the percentage of the first class artichokes although no significant effect was found in artichoke developmental process. OA-treatment reduced the respiration rate of artichokes and led to higher total hydrosoluble antioxidant activity and total phenolics and hydroxycinnamics and luteolins concentration both at harvest and during cold storage. In addition, luteolin 7-O-glucuronide 3-O-glucoside was identified for the first time in artichoke. Thus, it can be concluded that OA preharvest treatment could be a natural and useful tool to delay the artichoke postharvest senescence and improve the reported health-beneficial properties of artichokes consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Higher Education Sustainability Staffing Survey, 2010

Science.gov (United States)

Association for the Advancement of Sustainability in Higher Education, 2011

2011-01-01

This paper shows that despite national unemployment rates that hovered near 10 percent in 2010, those with positions in the higher education sustainability workforce report a sense of job security and feel satisfied with the work they are doing. With 433 completed surveys, the results offer a comprehensive look at the demographics, roles, salaries…

Flavonoids of Calligonum polygonoides and their cytotoxicity.

Science.gov (United States)

Ahmed, Hayam; Moawad, Abeer; Owis, Asmaa; AbouZid, Sameh; Ahmed, Osama

2016-10-01

Context Calligonum polygonoides L. subsp. comosum L' Hér. (Polygonaceae), locally known as "arta", is a slow-growing small leafless desert shrub. Objective Isolation, structure elucidation and evaluation of cytotoxic activity of flavonoids from C. polygonoides aerial parts. Materials and methods Flavonoids in the hydroalcoholic extract of the of C. polygonoides were isolated and purified using column chromatography and preparative HPLC. The structures of the isolated flavonoids were elucidated on the basis of spectroscopic data including 2D NMR techniques. The cytotoxic activity of the isolated flavonoids (6.25, 25, 50 and 100 μg/mL) was evaluated against liver HepG2 and breast MCF-7 cancer cell lines using sulphorhodamine-B assay. Results A new flavonoid, kaempferol-3-O-β-D-(6″-n-butyl glucuronide) (1), and 13 known flavonoids, quercetin 3-O-β-D-(6″-n-butyl glucuronide) (2), kaempferol-3-O-β-D-(6″-methyl glucuronide) (3), quercetin-3-O-β-D-(6″-methyl glucuronide) (4), quercetin-3-O-glucuronide (5), kaempferol-3-O-glucuronide (6), quercetin-3-O-α-rhamnopyranoside (7), astragalin (8), quercetin-3-O-glucopyranoside (9), taxifolin (10), (+)-catechin (11), dehydrodicatechin A (12), quercetin (13), and kaempferol (14), were isolated from the aerial parts of C. polygonoides. Quercetin showed significant cytotoxic activity against HepG2 and MCF-7 cell lines with IC50 values of 4.88 and 0.87 μg/mL, respectively. Structure-activity relationships were analyzed by comparing IC50 values of several pairs of flavonoids differing in one structural element. Discussion and conclusion The activity against breast cancer cell lines decreased by glycosylation at C-3. The presence of 2,3-double bond in ring C, carbonyl group at C-4 and 3',4'-dihydroxy substituents in ring B are essential structural requirements for the cytotoxic activity against breast cancer cells.

Higher dropout rate in non-native patients than in native patients in rehabilitation in The Netherlands

NARCIS (Netherlands)

Sloots, Maurits; Scheppers, Emmanuel F.; van de Weg, Frans B.; Bartels, Edien A.; Geertzen, Jan H.; Dekker, Joost; Dekker, Jaap

Dropout from a rehabilitation programme often occurs in patients with chronic nonspecific low back pain of non-native origin. However, the exact dropout rate is not known. The objective of this study was to determine the difference in dropout rate between native and non-native patients with chronic

Urinary analysis reveals high deoxynivalenol exposure in pregnant women from Croatia.

Science.gov (United States)

Sarkanj, Bojan; Warth, Benedikt; Uhlig, Silvio; Abia, Wilfred A; Sulyok, Michael; Klapec, Tomislav; Krska, Rudolf; Banjari, Ines

2013-12-01

In this pilot survey the levels of various mycotoxin biomarkers were determined in third trimester pregnant women from eastern Croatia. First void urine samples were collected and analysed using a "dilute and shoot" LC-ESI-MS/MS multi biomarker method. Deoxynivalenol (DON) and its metabolites: deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were detected in 97.5% of the studied samples, partly at exceptionally high levels, while ochratoxin A was found in 10% of the samples. DON exposure was primarily reflected by the presence of deoxynivalenol-15-glucuronide with a mean concentration of 120 μg L(-1), while free DON was detected with a mean concentration of 18.3 μg L(-1). Several highly contaminated urine samples contained a third DON conjugate, tentatively identified as deoxynivalenol-7-glucuronide by MS/MS scans. The levels of urinary DON and its metabolites measured in this study are the highest ever reported, and 48% of subjects were estimated to exceed the provisional maximum tolerable daily intake (1 μg kg(-1) b.w.). Copyright © 2013 Elsevier Ltd. All rights reserved.

HPLC-DAD-ESI/MS(n) analysis of phenolic compounds for quality control of Grindelia robusta Nutt. and bioactivities.

Science.gov (United States)

Ferreres, Federico; Grosso, Clara; Gil-Izquierdo, Angel; Valentão, Patrícia; Azevedo, Carolina; Andrade, Paula B

2014-06-01

The phenolic composition of herbal tea (HT) and hydromethanolic extract (HME) obtained from Grindelia robusta Nutt. was studied by HPLC-DAD-ESI/MS(n). Thirty six flavonoids and hydroxycinnamic acids were detected, from which thirty are described for the first time in this species. Quantification by HPLC-DAD showed that diosmetin-7-O-glucuronide-3'-O-pentoside+apigenin-7-O-glucuronide-4'-O-pentoside, apigenin-7-O-glucuronide+diosmetin-7-O-glucuronide and 3,5-dicaffeoylquinic acid+3,4-dicaffeoylquinic acid were the major compounds. Since the health-promoting effects of natural phenolic compounds against brain disorders is of increasing interest, HT and HME were also tested against oxygen and nitrogen reactive species and against enzymes related with Alzheimer's disease and depression. Extracts displayed strong in vitro scavenging activity and monoamine oxidase-A (MAO-A) inhibitory activity. The anti-MAO-A capacity was observed at non-toxic concentrations for SH-SY5Y human neuroblastoma cell line, reinforcing the benefits of G. robusta HT. However, no protection against hydrogen peroxide treatment was observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil Renato B. Fagundes ... [et al.

OpenAIRE

Fagundes, Renato Borges; Abnet, Christian C.; Strickland, Paul T.; Kamangar, Farin; Roth, Mark J.; Taylor, Philip R.; Dawsey, Sanford M.

2006-01-01

Background: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern B...

Are Interpersonal Violence Rates Higher Among Young Women in College Compared With Those Never Attending College?

Science.gov (United States)

Coker, Ann L; Follingstad, Diane R; Bush, Heather M; Fisher, Bonnie S

2016-05-01

Estimates of sexual violence and partner violence rates among young women are generated primarily from college samples. Few studies have data to compare rates among similar-aged women attending college with those who never attended college. This study aims to estimate rates of partner violence by type (sexual, physical, and psychological) and severity (mild, moderate, severe), sexual harassment, and knowing or suspecting that someone put a drug in a drink (drugged drink) among a national sample of 959 young women aged 18 to 24 in an intimate relationship in the past 12 months who were either currently in college (college;n= 272) or never attended college (non-college;n= 687). After adjusting for demographic differences between these two groups, no significant differences were found in rates of sexual partner violence (28.4% non-college, 23.5% college), physical partner violence (27.9% non-college, 26.3% college), psychological partner violence (Mscore: 6.10 non-college, 5.59 college), sexual harassment (15.5% non-college, 14.1% college), or drugged drink (8.5% non-college, 7.8% college). Finding high rates of interpersonal violence among young women who are and are not currently attending college indicates the need to target all young adults with violence prevention interventions in educational, workplace, and other community-based settings. © The Author(s) 2015.

Exchange rate regimes and inflation: Evidence from India.

OpenAIRE

Mohanty, Biswajit; Bhanumurthy, N.R.

2014-01-01

Exchange rate stability is crucial for inflation management as a stable rate is expected to reduce domestic inflation pressures through a `policy discipline effect'- restricting money supply growth, and a `credibility effect'- inducing higher money demand and reduced velocity of money. Alternatively, the impossibility trillema predicts that in the presence of an open capital account, a stable exchange rate may lead to lack of control on monetary policy and, hence, higher inflation. Using a mo...

Studies on Rate Enhancement of Polymerization in NMRP

Institute of Scientific and Technical Information of China (English)

HUANG Jian-ying; XU Miao-qing; YAN Ming-fa; CHEN Yi-hong; CHU Jia-yan; ZHUANG Jia-ming; DAI Li-zong; ZOU You-si

2005-01-01

In NMRP, the polymerization of MMA, the polymerization of St and the copolymerization of MMA with St were distinctly accelerated by the addition of a small amount of MN. The polymerization proceeds in a living fashion as indicated by the increase in molecular weight with the increase of time and conversion and a relatively low polydispersity. It has been found that the addition of MN results in a nearly one hundred times higher rate of the polymerization of MMA, a nearly twenty times higher rate of the polymerization of St and a nearly fifteen times higher rate of the copolymerization of St and MMA.

Higher Precision of Heart Rate Compared with VO2 to Predict Exercise Intensity in Endurance-Trained Runners.

Science.gov (United States)

Reis, Victor M; den Tillaar, Roland Van; Marques, Mario C

2011-01-01

The aim of the present study was to assess the precision of oxygen uptake with heart rate regression during track running in highly-trained runners. Twelve national and international level male long-distance road runners (age 30.7 ± 5.5 yrs, height 1.71 ± 0.04 m and mass 61.2 ± 5.8 kg) with a personal best on the half marathon of 62 min 37 s ± 1 min 22 s participated in the study. Each participant performed, in an all-weather synthetic track five, six min bouts at constant velocity with each bout at an increased running velocity. The starting velocity was 3.33 m·s(-1) with a 0.56 m·s(-1) increase on each subsequent bout. VO2 and heart rate were measured during the runs and blood lactate was assessed immediately after each run. Mean peak VO2 and mean peak heart rate were, respectively, 76.2 ± 9.7 mL·kg(-1)·min(-1) and 181 ± 13 beats·min(-1). The linearity of the regressions between heart rate, running velocity and VO2 were all very high (r > 0.99) with small standard errors of regression (i.e. Sy.x at the velocity associated with the 2 and 4 mmol·L(-1) lactate thresholds). The strong relationships between heart rate, running velocity and VO2 found in this study show that, in highly trained runners, it is possible to have heart rate as an accurate indicator of energy demand and of the running speed. Therefore, in this subject cohort it may be unnecessary to use VO2 to track changes in the subjects' running economy during training periods. Key pointsHeart rate is used in the control of exercise intensity in endurance sports.However, few studies have quantified the precision of its relationship with oxygen uptake in highly trained runners.We evaluated twelve elite half-marathon runners during track running at various intensities and established three regressions: oxygen uptake / heart rate; heart rate / running velocity and oxygen uptake / running velocity.The three regressions presented, respectively, imprecision of 4,2%, 2,75% and 4,5% at the velocity

THE PRICE OF HIGHER EDUCATION AND INDIVIDUAL DEMAND

Directory of Open Access Journals (Sweden)

Filiz Golpek

2012-01-01

Full Text Available The rise in the living standards in most of the world, the rise in population and schooling rates have increased the demand for higher education. The attribution of semi public property becomes determinant to decide whom will provide the supply and the production in semi public properties is realized by means of a supply and demand mechanism. The supply of higher education is mostly secured in accordance with the public demand as well as the resources available.  In addition, the fact that higher education services have produced significant benefits has led to over demand. This situation relates to a simple economic rule that a commodity or service which costs almost nothing or little will increase until the mariginal benefit of its demand equals to 0 or almost 0. However, the educational supply and demand is difficult to identify in accordance to the supply and demand and balance of price as observed in the economic theory. The high profits that would be attracted in the future are significant factors influencing individual’s decisions for investment. The decision for investment depends on the possible return in the future, the cost of investment, and the current interest rates. Higher education with investment purposes is influenced by these three factors and higher education is demanded more and more by individuals on the expectation that they will gain high profits In theory, it is accepted that the basic factors identifying the demand for higher education are in harmony with empirical research results in several countries including Turkey.

Public Policies, Prices, and Productivity in American Higher Education. Stretching the Higher Education Dollar. Special Report 3

Science.gov (United States)

Hauptman, Arthur M.

2013-01-01

Rapid increases in what colleges charge and what they spend per student have been and remain one of the most controversial aspects of American higher education. Tuition, fees, and other college charges have increased in both the public and private sectors at more than twice the rate of inflation for over a quarter century. Trends over time in what…

Accounting for Risk of Non-Completion in Private and Social Rates of Return to Higher Education

Science.gov (United States)

Toutkoushian, Robert K.; Shafiq, M. Najeeb; Trivette, Michael J.

2013-01-01

Conventional studies of the private and social rates of return to a Bachelor's degree focus on the earnings difference between Bachelor degree holders and high school graduates, and find that there are large rates of return for degree recipients. The estimates in these studies, however, do not take into account the risk of not completing a degree.…

Do higher-priced generic medicines enjoy a competitive advantage under reference pricing?

Science.gov (United States)

Puig-Junoy, Jaume

2012-11-01

In many countries with generic reference pricing, generic producers and distributors compete by means of undisclosed discounts offered to pharmacies in order to reduce acquisition costs and to induce them to dispense their generic to patients in preference over others. The objective of this article is to test the hypothesis that under prevailing reference pricing systems for generic medicines, those medicines sold at a higher consumer price may enjoy a competitive advantage. Real transaction prices for 179 generic medicines acquired by pharmacies in Spain have been used to calculate the discount rate on acquisition versus reimbursed costs to pharmacies. Two empirical hypotheses are tested: the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical presentations for which there are more generic competitors; and, the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical forms for which the consumer price has declined less in relation to the consumer price of the brand drug before generic entry (higher-priced generic medicines). An average discount rate of 39.3% on acquisition versus reimbursed costs to pharmacies has been observed. The magnitude of the discount positively depends on the number of competitors in the market. The higher the ratio of the consumer price of the generic to that of the brand drug prior to generic entry (i.e. the smaller the price reduction of the generic in relation to the brand drug), the larger the discount rate. Under reference pricing there is intense price competition among generic firms in the form of unusually high discounts to pharmacies on official ex-factory prices reimbursed to pharmacies. However, this effect is highly distorting because it favours those medicines with a higher relative price in relation to the brand price before generic entry.

Evaluating the underlying factors behind variable rate debt.

Science.gov (United States)

McCue, Michael J; Kim, Tae Hyun Tanny

2007-01-01

Recent trends show a greater usage of variable rate debt among health care bond issues. In 2004, 63.4% of the total health care bonds issued were variable rate compared with 30.6% in 1995 (Fitch Ratings, 2005). The purpose of this study is to gain a better understanding of the underlying factors, credit spread, issue characteristics, and issuer factors behind why hospitals and health system borrowers select variable rate debt compared with fixed rate debt. From 2000 to 2004, this study sampled 230 newly issued tax-exempt bonds issued by acute care hospitals and health care systems that included both variable and fixed rate debt issues. Using a logistic regression model, hospitals with variable rate debt issues were assigned a value of 1, whereas hospitals with fixed rate debt issues were assigned a value of 0. This study found a positive association between bond insurance and variable rate debt and a negative association between callable feature and variable rate debt. Facilities located in certificate-of-need states that possessed higher case mix acuity, earned higher profit margins, generated higher debt service coverage, and held less debt were more likely to issue variable rate debt. Overall, hospital managers and board members of hospitals possessing a strong financial performance have an interest in utilizing variable rate debt to lower their cost of capital. In addition, this outcome may also reflect that investment bankers are doing a better job in educating senior hospital management about the interest rate savings benefit of variable rate compared with fixed rate debt.

Accuracy of rate coding: When shorter time window and higher spontaneous activity help

Czech Academy of Sciences Publication Activity Database

Leváková, Marie; Tamborrino, M.; Košťál, Lubomír; Lánský, Petr

2017-01-01

Roč. 95, č. 2 (2017), č. článku 022310. ISSN 2470-0045 R&D Projects: GA ČR(CZ) GA15-08066S; GA MŠk(CZ) 7AMB17AT048 Institutional support: RVO:67985823 Keywords : rate coding * observation window * spontaneous activity * Fisher information * perfect integrate- and -fire model * Wiener process Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 2.366, year: 2016

Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans.

Science.gov (United States)

Urpi-Sarda, Mireia; Garrido, Ignacio; Monagas, María; Gómez-Cordovés, Carmen; Medina-Remón, Alexander; Andres-Lacueva, Cristina; Bartolomé, Begoña

2009-11-11

Nut skins are considered to be a rich source of polyphenols and may be partially responsible for the numerous health effects associated with nut consumption. However, more bioavailability studies of nut skin polyphenols are needed to understand the health effects derived from nut consumption. The aim of the present study was to determine the profiles of both phase II and microbial-derived phenolic metabolites in plasma and urine samples before and after the intake of almond skin polyphenols by healthy human subjects (n = 2). Glucuronide, O-methyl glucuronide, sulfate, and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and glucuronide and sulfate conjugates of isorhamnetin, were detected in plasma and urine samples after consumption of almond skin polyphenols. The main microbial-derived metabolites of flavanols, such as 5-(dihydroxyphenyl)-gamma-valerolactone and 5-(hydroxymethoxyphenyl)-gamma-valerolactone, were also detected in their glucuronide and sulfate forms. In addition, numerous metabolites derived from further microbial degradation of hydroxyphenylvalerolactones, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and hydroxyhippuric acids, registered major changes in urine after the consumption of almond skin polyphenols. The urinary excretion of these microbial metabolites was estimated to account for a larger proportion of the total polyphenol ingested than phase II metabolites of (epi)catechin, indicating the important role of intestinal bacteria in the metabolism of highly polymerized almond skin polyphenols. To the authors' knowledge this study constitutes the most complete report of the absorption of almond skin polyphenols in humans.

UO2 dissolution rates: A review

International Nuclear Information System (INIS)

McKenzie, W.F.

1992-09-01

This report reviews literature data on UO 2 dissolution kinetics and provides a framework for guiding future experimental studies as well as theoretical modeling studies. Under oxidizing conditions, UO 2 dissolution involves formation of an oxidized surface layer which is then dissolved by formation of aqueous complexes. Higher oxygen pressures or other oxidants are required at higher temperatures to have dissolution rates independent of oxygen pressure. At high oxygen pressures (1-5 atm, 25-70 C), the dissolution rate has a one-half order dependence on oxygen pressure, whereas at oxygen pressures below 0.2 atm, Grandstaff (1976), but nobody else, observed a first-order dependence on dissolution rate. Most people found a first-order dependence on carbonate concentration; Posey-Dowty (1987) found independence of carbonate at pH 7 to 8.2. Dissolution rates increase with temperature except in experiments involving granitic groundwater. Dissolution rates were generally greater under acid or basic conditions than near neutral pH

38 CFR 21.9640 - Rates of payment of educational assistance.

Science.gov (United States)

2010-07-01

... semester by the public institution of higher learning having the highest rate of regularly-charged fees in... States dollars using the foreign exchange conversion rate as published by the Federal Reserve effective... by the public institution of higher learning having the highest rate of regularly-charged tuition per...

Urinary steroid hormone analysis of ovarian cycles and pregnancy in mandrills (Mandrillus sphinx) indicate that menses, copulatory behavior, sexual swellings and reproductive condition are associated with changing estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG).

Science.gov (United States)

Phillips, Rebecca Sellin; Wheaton, Catharine J

2008-07-01

The objective of this study was to determine if sexual swellings in mandrills (Mandrillus sphinx) are a reflection of reproductive endocrine state. Urine samples were assayed using an enzyme immunoassay measuring pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1)C). Hormone patterns of ovarian cycles, pregnancy and lactation were characterized and compared with sexual swellings and copulations relative to menses and peak E(1)C. Cycle lengths averaging 28.7 days and pregnancy length of 181 days determined by hormonal and sexual swelling measures were similar to those reported in other Old World primate species. First day of copulation was observed during rising E(1)C concentrations and preceded observations of peak swelling by 1-2 days. Observations of peak sexual swellings occurred at or on the day after peak E(1)C and decreased following the ovulatory increase in PdG. Observations of menses and sexual swellings are a useful method to track mandrill ovarian cycles and can assist zoos in determining the reproductive state of females in their collections. Zoo Biol 27:320-330, 2008. (c) 2008 Wiley-Liss, Inc.

29 CFR 1620.12 - Wage “rate.”

Science.gov (United States)

2010-07-01

... Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.12 Wage... gender than the other for the performance of equal work, the higher rate serves as a wage standard. When a violation of the Act is established, the higher rate paid for equal work is the standard to which...

Low dose rate and high dose rate intracavitary treatment for cervical cancer

International Nuclear Information System (INIS)

Hareyama, Masato; Oouchi, Atsushi; Shidou, Mitsuo

1997-01-01

From 1984 through 1993, 144 previous untreated patients with carcinoma of uterine cervix were treated with either low dose rate 137 Cs therapy (LDR) or high dose rate 60 Co therapy (HDR). The local failure rates for more than 2-years for the primary lesions were 11.8% (8 of 63 patients) for LDR and 18.0% (11 of 61 patients). Rectal complication rates were significantly lower for HDR versus LDR (14.3% VS. 32.8%. p<0.01). Also, bladder complication rates were significantly lower for HDR versus LDR (0% VS. 10.4%, p<0.005). Treatment results in term of local control were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the LDR group than for the HDR group. (author)

Pathways of hepatic glycogen formation in humans following ingestion of a glucose load in the fed state

International Nuclear Information System (INIS)

Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

1989-01-01

The relative contributions of the direct and the indirect pathways to hepatic glycogen formation following a glucose load given to humans four hours after a substantial breakfast have been examined. Glucose loads labeled with [6-( 14 )C]glucose were given to six healthy volunteers along with diflunisal (1 g) or acetaminophen (1.5 g), drugs excreted in urine as glucuronides. Distribution of 14 C in the glucose unit of the glucuronide was taken as a measure of the extent to which glucose was deposited directly in liver glycogen (ie, glucose----glucose-6-phosphate----glycogen) rather than indirectly (ie, glucose----C3-compound----glucose-6-phosphate----glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 77% +/- 4%, which is somewhat higher than previous estimates in humans fasted overnight (65% +/- 1%, P less than 0.05). Thus, the indirect pathway of liver glycogen formation following a glucose load is operative in both the overnight fasted and the fed state, although its contribution may be somewhat less in the fed state

Radiolysis of Aqueous Benzene Solutions at higher temperatures

Energy Technology Data Exchange (ETDEWEB)

Christensen, H

1964-07-15

Aqueous solutions of benzene have been irradiated with Co {gamma}-rays with doses of up to 2.3 Mrad in the temperature region 100 - 200 C. At 100 C a linear relationship between the phenol concentration and the absorbed dose was obtained, but at 150 C and at higher temperatures the rate of the phenol formation increased significantly after an initial constant period. With higher doses the rate decreased again, falling almost to zero at 200 C after a dose of 2.2 Mrad. The G value of phenol in the initial linear period increased from 2.8 at 100 C to 8.0 at 200 C. The reaction mechanism is discussed and reactions constituting a chain reaction are suggested. The result of the addition of iron ions and of a few inorganic oxides to the system is presented and briefly discussed.

Radiolysis of Aqueous Benzene Solutions at higher temperatures

International Nuclear Information System (INIS)

Christensen, H.

1964-07-01

Aqueous solutions of benzene have been irradiated with Co γ-rays with doses of up to 2.3 Mrad in the temperature region 100 - 200 C. At 100 C a linear relationship between the phenol concentration and the absorbed dose was obtained, but at 150 C and at higher temperatures the rate of the phenol formation increased significantly after an initial constant period. With higher doses the rate decreased again, falling almost to zero at 200 C after a dose of 2.2 Mrad. The G value of phenol in the initial linear period increased from 2.8 at 100 C to 8.0 at 200 C. The reaction mechanism is discussed and reactions constituting a chain reaction are suggested. The result of the addition of iron ions and of a few inorganic oxides to the system is presented and briefly discussed

IMPROVING MANAGEMENT INFORMATION SYSTEMS AT A HIGHER EDUCATIONAL INSTITUTION

Directory of Open Access Journals (Sweden)

Nataliya N. Fedyakova

2016-06-01

Full Text Available Introduction: this paper deals with the foreign and domestic experience of creation and use of educational institution management automation systems. The problems of higher educational institutions management are essential in conditions of growing competition between educational institutions. Their complexity and timeliness defines multifunctional activity of higher educational institutions, diversity of funding sources, the variety of forms and types of educational, scientific, industrial and economic activities, the need for monitoring of the market of educational services and the labor market (including the need for employment of graduates, the necessity for adaptation to continuously changing economic conditions. Materials and Methods: system approach and method of comparison were used in analysing the current state of development and organisation of the automated information systems of higher education. These methods were also used to compare the qualitative characteristics of different technologies and methods of creation of the automated information systems. Results: the foreign and domestic educational institution management automation systems SIMS. net, Capita Education, SPRUT, Galaxy of Higher Educational Institution Management”, and “GSVedomosty” were analysed. Disadvantages of the functional module AIS – AWP pertaining to the University Rector of the higher educational institution were found. The improvement of higher educational institution AIS by implementing decision support systems for the management, made on the basis of the model of SaaS (software as a service is discussed. The author developed a model of automated score-rating system to assess the individual performance of students. Discussion and Conclusions: the author tackles the problems of higher educational institution AIS taking into account the specifics of the use of higher educational institution management information systems. They have a practical

Extended inflation from higher-dimensional theories

International Nuclear Information System (INIS)

Holman, R.; Kolb, E.W.; Vadas, S.L.; Wang, Y.

1991-01-01

We consider the possibility that higher-dimensional theories may, upon reduction to four dimensions, allow extended inflation to occur. We analyze two separate models. One is a very simple toy model consisting of higher-dimensional gravity coupled to a scalar field whose potential allows for a first-order phase transition. The other is a more sophisticated model incorporating the effects of nontrivial field configurations (monopole, Casimir, and fermion bilinear condensate effects) that yield a nontrivial potential for the radius of the internal space. We find that extended inflation does not occur in these models. We also find that the bubble nucleation rate in these theories is time dependent unlike the case in the original version of extended inflation

Comparative rates of violence in chimpanzees and humans.

Science.gov (United States)

Wrangham, Richard W; Wilson, Michael L; Muller, Martin N

2006-01-01

This paper tests the proposal that chimpanzees (Pan troglodytes) and humans have similar rates of death from intraspecific aggression, whereas chimpanzees have higher rates of non-lethal physical attack (Boehm 1999, Hierarchy in the forest: the evolution of egalitarian behavior. Harvard University Press). First, we assembled data on lethal aggression from long-term studies of nine communities of chimpanzees living in five populations. We calculated rates of death from intraspecific aggression both within and between communities. Variation among communities in mortality rates from aggression was high, and rates of death from intercommunity and intracommunity aggression were not correlated. Estimates for average rates of lethal violence for chimpanzees proved to be similar to average rates for subsistence societies of hunter-gatherers and farmers. Second, we compared rates of non-lethal physical aggression for two populations of chimpanzees and one population of recently settled hunter-gatherers. Chimpanzees had rates of aggression between two and three orders of magnitude higher than humans. These preliminary data support Boehm's hypothesis.

Being born under adverse economic conditions leads to a higher cardiovascular mortality rate later in life: evidence based on individuals born at different stages of the business cycle.

Science.gov (United States)

van den Berg, Gerard J; Doblhammer-Reiter, Gabriele; Christensen, Kaare

2011-05-01

We connect the recent medical and economic literatures on the long-run effects of early-life conditions by analyzing the effects of economic conditions on the individual cardiovascular (CV) mortality rate later in life, using individual data records from the Danish Twin Registry covering births since the 1870s and including the cause of death. To capture exogenous variation of conditions early in life, we use the state of the business cycle around birth. We find significant negative effects of economic conditions around birth on the individual CV mortality rate at higher ages. There is no effect on the cancer-specific mortality rate. From variation within and between monozygotic and dizygotic twin pairs born under different conditions, we conclude that the fate of an individual is more strongly determined by genetic and household-environmental factors if early-life conditions are poor. Individual-specific qualities come more to fruition if the starting position in life is better.

Long-Term Results of Fixed High-Dose I-131 Treatment for Toxic Nodular Goiter: Higher Euthyroidism Rates in Geriatric Patients

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Gül Ege Aktaş

2015-10-01

Full Text Available Objective: Geriatric patient population has special importance due to particular challenges. In addition to the increase in incidence of toxic nodular goiter (TNG with age, it has a high incidence in the regions of low-medium iodine intake such as in our country. The aim of this study was to evaluate the overall outcome of high fixed dose radioiodine (RAI therapy, and investigate the particular differences in the geriatric patient population. Methods: One hundred and three TNG patients treated with high dose I-131 (370-740 MBq were retrospectively reviewed. The baseline characteristics; age, gender, scintigraphic patterns and thyroid function tests before and after treatment, as well as follow-up, duration of antithyroid drug (ATD medication and achievement of euthyroid or hypothyroid state were evaluated. The patient population was divided into two groups as those=>65 years and those who were younger, in order to assess the effect of age. Results: Treatment success was 90% with single dose RAI therapy. Hyperthyroidism was treated in 7±7, 2 months after RAI administration. At the end of the first year, overall hypothyroidism rate was 30% and euthyroid state was achieved in 70% of patients. Age was found to be the only statistically significant variable effecting outcome. A higher ratio of euthyroidism was achieved in the geriatric patient population. Conclusion: High fixed dose I-131 treatment should be preferred in geriatric TNG patients in order to treat persistent hyperthyroidism rapidly. The result of this study suggests that high fixed dose RAI therapy is a successful modality in treating TNG, and high rates of euthyroidism can be achieved in geriatric patients.

Higher contamination rate than usual. Treatment and disinfection of water in hot whirlpool systems

Energy Technology Data Exchange (ETDEWEB)

Herschman, W

1985-10-01

Hot whirlpools must meet the hygienic standards set in the Federal Law Concerning Prevention of Epidemics of 18 Dec 1979. The low water volume of whirlpool systems and the extraordinary contamination rate in uninterrupted operation require a specific water treatment and disinfestation technology to make up for the poor buffer capacity of the low water volume. (orig./BWI).

Unethical and Deadly Symbiosis in Higher Education

Science.gov (United States)

Crumbley, D. Larry; Flinn, Ronald; Reichelt, Kenneth J.

2012-01-01

As administrators are pressured to increase retention rates in accounting departments, and higher education in general, a deadly symbiosis is occurring. Most students and parents only wish for high grades, so year after year many educators engage in unethical grade inflation and course work deflation. Since administrators use the students to audit…

High pressure liquid chromatographic method for the separation and quantitation of water-soluble radiolabeled benzene metabolites

International Nuclear Information System (INIS)

Sabourin, P.J.; Bechtold, W.E.; Henderson, R.F.

1988-01-01

The glucuronide and sulfate conjugates of benzene metabolite as well as muconic acid and pre-phenyl- and phenylmercapturic acids were separated by ion-pairing HPLC. The HPLC method developed was suitable for automated analysis of a large number of tissue or excreta samples. p-Nitrophenyl [ 14 C]glucuronide was used as an internal standard for quantitation of these water-soluble metabolites. Quantitation was verified by spiking liver tissue with various amounts of phenylsulfate or glucuronides of phenol, catechol, or hydroquinone and analyzing by HPLC. Values determined by HPLC analysis were within 10% of the actual amount with which the liver was spiked. The amount of metabolite present in urine following exposure to [ 3 H]benzene was determined using p-nitrophenyl [ 14 C]glucuronide as an internal standard. Phenylsulfate was the major water-soluble metabolite in the urine of F344 rats exposed to 50 ppm [ 3 H]benzene for 6 h. Muconic acid and an unknown metabolite which decomposed in acidic media to phenylmercapturic acid were also present. Liver, however, contained a different metabolic profile. This indicates that urinary metabolite profiles may not be a true reflection of what is seen in individual tissues

Market Concentration Rate and Market Performance of China’s Swine Industry

Institute of Scientific and Technical Information of China (English)

Jia ZHANG; Yucheng HE

2016-01-01

Empirical study on market concentration rate and market performance of China’s Swine Industry indicates that higher market concentration rate brings higher overall performance of swine industry. There exists no obvious causal relation between market concentration rate and market performance,but market performance is highly correlated with market concentration rate. The improvement in performance of swine industry is dependent on further optimization of market concentration rate and other factors.

Millennials: Their Attitudes and Their Effects on Freshman Retention in Higher Education

Science.gov (United States)

Naples, Susan G.

2010-01-01

Some institutions of higher education have become aware of escalating student attrition rates. Student attrition rates cause many problems, including a decrease in student population, unfavorable completion and placement rates, and a reduced cash flow. Most importantly, students are not fulfilling their education goals. The goal for most students…

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

Science.gov (United States)

Mutlu, Mehmet Firat; Erdem, Mehmet; Mutlu, Ilknur; Bulut, Berk; Erdem, Ahmet

2017-09-01

To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, pcycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. Basal P levels were associated with increased incidence of PPR but not with CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive threshold control for auto-rate fallback algorithm in IEEE 802.11 multi-rate WLANs

Science.gov (United States)

Wu, Qilin; Lu, Yang; Zhu, Xiaolin; Ge, Fangzhen

2012-03-01

The IEEE 802.11 standard supports multiple rates for data transmission in the physical layer. Nowadays, to improve network performance, a rate adaptation scheme called auto-rate fallback (ARF) is widely adopted in practice. However, ARF scheme suffers performance degradation in multiple contending nodes environments. In this article, we propose a novel rate adaptation scheme called ARF with adaptive threshold control. In multiple contending nodes environment, the proposed scheme can effectively mitigate the frame collision effect on rate adaptation decision by adaptively adjusting rate-up and rate-down threshold according to the current collision level. Simulation results show that the proposed scheme can achieve significantly higher throughput than the other existing rate adaptation schemes. Furthermore, the simulation results also demonstrate that the proposed scheme can effectively respond to the varying channel condition.

Surgical site infection and transfusion rates are higher in underweight total knee arthroplasty patients

Directory of Open Access Journals (Sweden)

Jorge Manrique, MD

2017-03-01

Conclusions: Our study demonstrates that UW TKA patients have a higher likelihood of developing SSI and requiring blood transfusions. The specific reasons are unclear, but we conjecture that it may be related to decreased wound healing capabilities and low preoperative hemoglobin. Investigation of local tissue coverage and hematologic status may be beneficial in this patient population to prevent SSI. Based on the results of this study, a prospective evaluation of these factors should be undertaken.

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

Science.gov (United States)

Pragst, Fritz; Yegles, Michel

2008-04-01

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

Ultra-high-performance liquid chromatography tandem mass spectrometry determination of GHB, GHB-glucuronide in plasma and cerebrospinal fluid of narcoleptic patients under sodium oxybate treatment.

Science.gov (United States)

Tittarelli, Roberta; Pichini, Simona; Pedersen, Daniel S; Pacifici, Roberta; Moresco, Monica; Pizza, Fabio; Busardò, Francesco Paolo; Plazzi, Giuseppe

2017-05-01

Sodium oxybate (Xyrem ® ), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment. To characterize the plasma pharmacokinetics of GHB, three subjects with NT1 were administered at time 0 and 4h with 1.25, 1.5 and 3.55g Xyrem ® , respectively and had their blood samples collected at 7 time points throughout an 8-h session. CSF specimens, collected for orexin A measurement from the same three subjects 6h after their second administration, were also tested. The results obtained suggested that GHB plasma values increased disproportionally with the rising doses, (C max0-4 : 12.53, 32.95 and 69.62μg/mL; C max4-8 : 44.93, 75.03 and 111.93μg/mL for total Xyrem ® dose of 2.5, 3 and 7g respectively) indicating non-linear dose-response. GHB-Gluc was present only in traces in all plasma samples from treated patients, not changing with increasing Xyrem ® doses. GHB values of 5.62, 6.10 and 17.74μg/mL for 2, 3 and 7g Xyrem ® were found in CSF with a significant difference from control values. GHB-Gluc was found in negligible concentrations with no differences to those of control individuals. In conclusion this simple and fast UHPLC-MS/MS method proved useful for pharmacokinetic studies and therapeutic drug monitoring of GHB in narcoleptic patients treated with sodium oxybate. Copyright © 2017 Elsevier B.V. All rights reserved.

Physiological barriers to the oral delivery of curcumin.

Science.gov (United States)

Berginc, K; Trontelj, J; Basnet, N Skalko; Kristl, A

2012-06-01

Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

Extended inflation from higher dimensional theories

International Nuclear Information System (INIS)

Holman, R.; Kolb, E.W.; Vadas, S.L.; Wang, Yun.

1990-04-01

The possibility is considered that higher dimensional theories may, upon reduction to four dimensions, allow extended inflation to occur. Two separate models are analayzed. One is a very simple toy model consisting of higher dimensional gravity coupled to a scalar field whose potential allows for a first-order phase transition. The other is a more sophisticated model incorporating the effects of non-trivial field configurations (monopole, Casimir, and fermion bilinear condensate effects) that yield a non-trivial potential for the radius of the internal space. It was found that extended inflation does not occur in these models. It was also found that the bubble nucleation rate in these theories is time dependent unlike the case in the original version of extended inflation

Regional analysis of big five personality factors and suicide rates in Russia.

Science.gov (United States)

Voracek, Martin

2013-08-01

Extending cross-national and intranational studies on possible aggregate-level associations between personality dimensions and suicide prevalence, this study examined the associations of the Big Five personality factors and suicide rates across 32 regions of the Russian Federation. Failing to replicate one key finding of similar geographic studies, namely, a correspondence of higher suicide rates with lower Agreeableness and Conscientiousness (i.e., higher Psychoticism) scores, higher suicide rates corresponded to higher Agreeableness scores. This effect was obtained with one available data source (regional-level Big Five ratings based on the National Character Survey), but not with another (based on the NEO-PI-R measure). All in all, regional suicide rates across Russia were dissociated from regional variation in personality dimensions.

Toward the development of an efficient transposon marker system for soil bacteria based on the gusA gene

International Nuclear Information System (INIS)

Corbo, Joseph C.

1991-01-01

On account of the numerous drawbacks of presently existing marker gene systems, we have decided to concentrate on the use of the gusA gene as a marker, since it avoids many of the problems encountered by these other systems. Before I discuss the goals of my work, I would like briefly to describe the beta-gtucuronidase enzyme, its structural gene gusA, and their normal function in E. coli. The gusA gene was originally isolated from E. coli, one of the major constituents of the microflora of the mammalian gastrointestinal tract. In its native host it forms an operon with two other genes, gusB and gusC, and is involved in the uptake and degradation of glucuronidated compounds. Since glucuronidation (the covalent attachment of a glucuronide group) is the principal means of detoxification of xenobiotic compounds in human beings, it is reasonable enough that E. co//should have evolved such an enzyme. By selectively taking up the glucuronated compounds which it encounters in the gut, E. co//acquires a food source, glucuronic acid, which it obtains by hydrolyzing the glucuronide from its aglycone by means of the beta-glucuronidase enzyme. When we assay beta-glucuronidase activity we employ a colorless substrate known as X-gluc which has the chemical formula 5-bromo-4-chloro-3-indolyl beta-D-glucuronide. Upon removal of the glucuronide group the aglycone quickly dimerizes via oxidation to produce an insoluble, deep blue precipitate, which is readily identifiable as the hallmark sign of beta-glucuronidase activity. In this work it was tried to accomplish two related goals: the first goal was to build a marker gene construct using the gusA gene that would meet the requirements for a marker system that I have outlined above; the second goal was to find the best possible marker delivery system that would allow maximal ease of transfer of the marker gene from a host strain to the soil bacterium which is to be marked

Ovulation rate and early embryonic survival rate in female rabbits of a synthetic line and a local Algerian population

Directory of Open Access Journals (Sweden)

R. Belabbas

2016-12-01

Full Text Available A higher litter size at birth has been reported in female rabbits from a Synthetic line than in those of the Local Algerian population. The aim of this work was to analyse whether this difference in litter size was due to a higher ovulation rate and/or embryonic survival rate in Synthetic line than in Local Algerian population. In total, 24 multiparous female rabbits from Synthetic line and 23 from Local population were used in this experiment. Litter size at birth was recorded up to the first 3 parities. Litter size was 20% higher in Synthetic line than Local population. At their 4th gestation, the females were euthanized at 72 h post coitum. Synthetic line females had 50% more ova and embryos than those of Local population (+4.42 ova and +3.92 embryos, respectively. Synthetic line displayed a lower percentage of normal embryos and a larger number of unfertilized oocytes than Local population (–2.81% and +0.64 oocytes, respectively, but differences were not relevant. Synthetic line showed a lesser embryonic stage of development at 72 h post coitum, showing a higher percentage of early morulae (31.50 vs. 8.50% and a lower percentage of compact morulae (51.45 vs. 78.65% than Local population. No relevant difference was found for early embryonic survival rate between Synthetic line and Local population. In conclusion, the difference in litter size was mainly due to a higher ovulation rate in the Synthetic line, allowing more embryos to develop in this line.

From apprenticeship to higher vocational education in Denmark

DEFF Research Database (Denmark)

Jørgensen, Christian Helms

2017-01-01

patterns from apprenticeships to higher education in recent decades and examines why the transition rate has declined. Explanations for the decline are identified at the structural, the institutional and the individual levels. It concludes by pointing at a dilemma behind the policies pursued: Trying...

Mortality Rates Among Arab Americans in Michigan

OpenAIRE

Dallo, Florence J.; Schwartz, Kendra; Ruterbusch, Julie J.; Booza, Jason; Williams, David R.

2012-01-01

The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, ...

Radioimmunological determination of tetrahydroaldosterone (TH-ALDO) in human urine

International Nuclear Information System (INIS)

Kohl, K.H.

1979-01-01

Two white New Zealand rabbits were immunised against TH-Aldo. A 3α. 5β-TH-Aldo-20 oxime BSA complex served as antigen. The titration values found were between 1:16.000 and 1:18.000. All steroids and steroid metabolites with the exception of tetra-hydro-18-hydroxy-11-dehydrocorticosterone (18-OH-THA) exhibited insignifcant slight cross-reactions. The specifity of the antisera was also investigated with immunograms using paper chromatography which was developed from the n-butanol extract of the urine samples as well as after β-glucuronida treatment and dichloromethane extraction. The immunogram showed that the antibodies crossreacted with aldosterone-18-glucuronide and with tetrahydroaldosterone-glucuronide fraction (possibly with the TH-Aldo-21-glucuronide) as well as with a non-identified weakly polar material. (orig./AJ) [de

HIGHER PRECISION OF HEART RATE COMPARED WITH VO2 TO PREDICT EXERCISE INTENSITY IN ENDURANCE-TRAINED RUNNERS

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Victor M. Reis

2011-03-01

Full Text Available The aim of the present study was to assess the precision of oxygen uptake with heart rate regression during track running in highly-trained runners. Twelve national and international level male long-distance road runners (age 30.7 ± 5.5 yrs, height 1.71 ± 0.04 m and mass 61.2 ± 5.8 kg with a personal best on the half marathon of 62 min 37 s ± 1 min 22 s participated in the study. Each participant performed, in an all-weather synthetic track five, six min bouts at constant velocity with each bout at an increased running velocity. The starting velocity was 3.33 m·s-1 with a 0.56 m·s-1 increase on each subsequent bout. VO2 and heart rate were measured during the runs and blood lactate was assessed immediately after each run. Mean peak VO2 and mean peak heart rate were, respectively, 76.2 ± 9.7 mL·kg-1·min-1 and 181 ± 13 beats·min-1. The linearity of the regressions between heart rate, running velocity and VO2 were all very high (r > 0.99 with small standard errors of regression (i.e. Sy.x < 5% at the velocity associated with the 2 and 4 mmol·L-1 lactate thresholds. The strong relationships between heart rate, running velocity and VO2 found in this study show that, in highly trained runners, it is possible to have heart rate as an accurate indicator of energy demand and of the running speed. Therefore, in this subject cohort it may be unnecessary to use VO2 to track changes in the subjects' running economy during training periods.

Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

Science.gov (United States)

Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

2014-01-01

The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents. PMID:24618639

Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.

Science.gov (United States)

Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

2014-03-12

The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents.

Geometrical Sparing Factors for the Rectum and Bladder in the Prediction of Grade 2 and Higher Complications After High-Dose-Rate Brachytherapy for Cervical Cancer

International Nuclear Information System (INIS)

Chen, S.-W.; Liang, J.-A.; Hung, Y.-C.; Yeh, L.-S.; Chang, W.-C.; Yang, S.-N.; Lin, F.-J.

2009-01-01

Purpose: This study aimed to assess the predictive values of geometrical sparing factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer. Methods: A total of 392 patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using Ir-192 remote after-loading at 1-week intervals for three or four sessions. The geometrical sparing factor (GSF) was defined as the average of the ratios between the reference doses and the Point A dose. Results: A total of 46 patients (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3, and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis demonstrated a high risk of rectal sequelae in patients who developed bladder complications (p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than 0.7 (p = 0.01, hazard ratio 1.99). The high risk factors for bladder complications were development of rectal complications (p = 0.0004, hazard ratio 3.74), concurrent chemotherapy (p = 0.0001, relative risk 3.94), and a bladder GSF greater than 0.9 (p = 0.01, hazard ratio, 2.53). Conclusion: This study demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk for Grade 2 and higher late sequelae.

Geometrical sparing factors for the rectum and bladder in the prediction of grade 2 and higher complications after high-dose-rate brachytherapy for cervical cancer.

Science.gov (United States)

Chen, Shang-Wen; Liang, Ji-An; Hung, Yao-Ching; Yeh, Lian-Shung; Chang, Wei-Chun; Yang, Shih-Neng; Lin, Fang-Jen

2009-12-01

This study aimed to assess the predictive values of geometrical sparing factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer. A total of 392 patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using Ir-192 remote after-loading at 1-week intervals for three or four sessions. The geometrical sparing factor (GSF) was defined as the average of the ratios between the reference doses and the Point A dose. A total of 46 patients (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3, and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis demonstrated a high risk of rectal sequelae in patients who developed bladder complications (p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than 0.7 (p = 0.01, hazard ratio 1.99). The high risk factors for bladder complications were development of rectal complications (p = 0.0004, hazard ratio 3.74), concurrent chemotherapy (p = 0.0001, relative risk 3.94), and a bladder GSF greater than 0.9 (p = 0.01, hazard ratio, 2.53). This study demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk for Grade 2 and higher late sequelae.

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

Science.gov (United States)

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

2009-08-01

Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair. EtG was extracted from about 30 mg of hair by aqueous incubation and purified by solid-phase extraction (SPE) using mixed mode extraction cartridges followed by derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed in the selected reaction monitoring (SRM) mode using the transitions m/z 347-->163 (for the quantification) and m/z 347-->119 (for the identification) for EtG, and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we prepared quality controls (QC) using hair samples taken post mortem from 2 subjects with a known history of alcoholism. These samples were confirmed by a proficiency test with 7 participating laboratories. The assay linearity of EtG was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with 3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at 8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation, RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was applied to several hair samples obtained from autopsy cases with a history of alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged from 60 to 820 pg/mg hair.

Supernova rates from the SUDARE VST-Omegacam search II. Rates in a galaxy sample

Science.gov (United States)

Botticella, M. T.; Cappellaro, E.; Greggio, L.; Pignata, G.; Della Valle, M.; Grado, A.; Limatola, L.; Baruffolo, A.; Benetti, S.; Bufano, F.; Capaccioli, M.; Cascone, E.; Covone, G.; De Cicco, D.; Falocco, S.; Haeussler, B.; Harutyunyan, V.; Jarvis, M.; Marchetti, L.; Napolitano, N. R.; Paolillo, M.; Pastorello, A.; Radovich, M.; Schipani, P.; Tomasella, L.; Turatto, M.; Vaccari, M.

2017-02-01

Aims: This is the second paper of a series in which we present measurements of the supernova (SN) rates from the SUDARE survey. The aim of this survey is to constrain the core collapse (CC) and Type Ia SN progenitors by analysing the dependence of their explosion rate on the properties of the parent stellar population averaging over a population of galaxies with different ages in a cosmic volume and in a galaxy sample. In this paper, we study the trend of the SN rates with the intrinsic colours, the star formation activity and the masses of the parent galaxies. To constrain the SN progenitors we compare the observed rates with model predictions assuming four progenitor models for SNe Ia with different distribution functions of the time intervals between the formation of the progenitor and the explosion, and a mass range of 8-40 M⊙ for CC SN progenitors. Methods: We considered a galaxy sample of approximately 130 000 galaxies and a SN sample of approximately 50 events. The wealth of photometric information for our galaxy sample allows us to apply the spectral energy distribution (SED) fitting technique to estimate the intrinsic rest frame colours, the stellar mass and star formation rate (SFR) for each galaxy in the sample. The galaxies have been separated into star-forming and quiescent galaxies, exploiting both the rest frame U-V vs. V-J colour-colour diagram and the best fit values of the specific star formation rate (sSFR) from the SED fitting. Results: We found that the SN Ia rate per unit mass is higher by a factor of six in the star-forming galaxies with respect to the passive galaxies, identified as such both on the U-V vs. V-J colour-colour diagram and for their sSFR. The SN Ia rate per unit mass is also higher in the less massive galaxies that are also younger. These results suggest a distribution of the delay times (DTD) less populated at long delay times than at short delays. The CC SN rate per unit mass is proportional to both the sSFR and the galaxy

7 CFR 1780.13 - Rates and terms.

Science.gov (United States)

2010-01-01

...; and (2) The median household income of the service area is below the higher of the poverty line, or 80... poverty rate and for which the median household income of the service area is not more than 100 percent of... the market rate will be used to determine the poverty and intermediate interest rates. (b) Poverty...

Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats.

Science.gov (United States)

Bangphumi, Kunan; Kittiviriyakul, Chuleeporn; Towiwat, Pasarapa; Rojsitthisak, Pornchai; Khemawoot, Phisit

2016-12-01

Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach.

The Influence of CYP2D6 Phenotype on the Pharmacokinetic Profile of Atomoxetine in Caucasian Healthy Subjects

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Todor Ioana

2017-06-01

Full Text Available Objective: To analyze a potential phenotypic variation within the studied group based on the pharmacokinetic profile of atomoxetine and its active metabolite, and to further investigate the impact of CYP2D6 phenotype on atomoxetine pharmacokinetics. Methods: The study was conducted as an open-label, non-randomized clinical trial which included 43 Caucasian healthy volunteers. Each subject received a single oral dose of atomoxetine 25 mg. Subsequently, atomoxetine and 4-hydroxyatomoxetine-O-glucuronide (glucuronidated active metabolite plasma concentrations were determined and a noncompartmental method was used to calculate the pharmacokinetic parameters of both compounds. Further on, the CYP2D6 metabolic phenotype was assessed using the area under the curve (AUC metabolic ratio (atomoxetine/ 4-hydroxyatomoxetine-O-glucuronide and specific statistical tests (Lilliefors (Kolgomorov-Smirnov and Anderson-Darling test. The phenotypic differences in atomoxetine disposition were identified based on the pharmacokinetic profile of the parent drug and its metabolite. Results: The statistical analysis revealed that the AUC metabolic ratio data set did not follow a normal distribution. As a result, two different phenotypes were identified, respectively the poor metabolizer (PM group which included 3 individuals and the extensive metabolizer (EM group which comprised the remaining 40 subjects. Also, it was demonstrated that the metabolic phenotype significantly influenced atomoxetine pharmacokinetics, as PMs presented a 4.5-fold higher exposure to the parent drug and a 3.2-fold lower exposure to its metabolite in comparison to EMs. Conclusions: The pharmacokinetic and statistical analysis emphasized the existence of 2 metabolic phenotypes: EMs and PMs. Furthermore, it was proved that the interphenotype variability had a marked influence on atomoxetine pharmacokinetic profile.

Comparative Phenolic Fingerprint and LC-ESI+QTOF-MS Composition of Oregano and Rosemary Hydrophilic Extracts in Relation to their Antibacterial Effect

Directory of Open Access Journals (Sweden)

Florina Bunghez

2015-05-01

Full Text Available Rosemary (Rosmarinus officinalis and oregano (Origanum vulgare are known aromatic plants used as spice, with good flavoring, preservative, antioxidant and antibacterial activity. Beside their known terpenoid content responsible for the antibacterial activity, the water-soluble compounds (phenolic derivatives are of high interest not only for their antioxidant activity but as a good alternative or as a hydrophilic new antibacterial solution. Two hydrophilic extracts from each plant were obtained (15% plant in hot water and the phytochemicals were fingerprinted by UV-Vis and FTIR spectrometry and quantified. The total phenolic content was higher in case of oregano (54.2 mg GAE/g DW comparing to rosemary (54.25 vs 15.35 mg GAE/g dry matter. By LC-ESI+QTOF-MS analysis there were identified mainly, in both extracts, flavonoid and diterpene derivatives, mainly carnosol, carnosic acid, rosmarinic acid, kaempferol 3-O-glucuronide. Other flavonoid glucuronides were more specific to one or the other plant, e.g. Luteolin 3'-(4''-acetylglucuronide for rosemary and Apigenin 7-O-glucuronide for oregano. Water favorized increased extraction of flavonoid derivatives and soluble diterpenes, but not non-soluble  terpenes. The antibacterial activity of both extracts was tested against B.cereus, L. monocytogenes, Salmonella, S. aureus and E.coli. Both oregano and rosemary extracts showed a slight antibacterial activity, which can be related to the low concentration of terpenoids, known to have the most important antibacterial activity in these plants. Nevertheless, the antibacterial activity seems to be strain dependent, Bacillus cereus being the most sensitive bacterial strain comparing with the other four bacteria, the oregano extract having a slightly superior activity comparing to the rosemary extract.

Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans

International Nuclear Information System (INIS)

Shulman, G.I.; Cline, G.; Schumann, W.C.; Chandramouli, V.; Kumaran, K.; Landau, B.R.

1990-01-01

The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway

Equity in Higher Education and Graduate Labour Market Outcomes in Australia

Science.gov (United States)

Li, Ian W.; Mahuteau, Stephane; Dockery, Alfred M.; Junankar, P. N.

2017-01-01

The rate of higher education participation in Australia has increased over the past decade for individuals from disadvantaged backgrounds. This study contributes to the knowledge on the outcomes of disadvantaged individuals who complete higher education by looking at the labour market outcomes of university graduates from equity groups. The number…

Comparison of Biomarkers of Tobacco Exposure between Premium and Discount Brand Cigarette Smokers in the NHANES 2011-2012 Special Sample.

Science.gov (United States)

Wasserman, Emily J; Reilly, Samantha M; Goel, Reema; Foulds, Jonathan; Richie, John P; Muscat, Joshua E

2018-05-01

Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products. Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011-2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders. Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers. Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs. Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Citation Rate Predictors in the Plastic Surgery Literature.

Science.gov (United States)

Lopez, Joseph; Calotta, Nicholas; Doshi, Ankur; Soni, Ashwin; Milton, Jacqueline; May, James W; Tufaro, Anthony P

The purpose of this study is to determine and characterize the scientific and nonscientific factors that influence the rate of article citation in the field of plastic surgery. Cross-sectional study. We reviewed all entries in Annals of Plastic Surgery and Journal of Plastic, Reconstructive, and Aesthetic Surgery from January 1, 2007 to December 31, 2007; and Plastic and Reconstructive Surgery from January 1, 2007 to December 31, 2008. All scientific articles were analyzed and several article characteristics were extracted. The number of citations at 5 years was collected as the outcome variable. A multivariable analysis was performed to determine which variables were associated with higher citations rates. A total of 2456 articles were identified of which only 908 fulfilled the inclusion criteria. Most studies were publications in the fields of reconstructive (26.3%) or pediatric/craniofacial (17.6%) surgery. The median number of citations 5 years from publication was 8. In the multivariable analysis, factors associated with higher citations rates were subspecialty field (p = 0.0003), disclosed conflict of interest (p = 0.04), number of authors (p = 0.04), and journal (p = 0.02). We have found that higher level of evidence (or other study methodology factors) is not associated with higher citation rates. Instead, conflict of interest, subspecialty topic, journal, and number of authors are strong predictors of high citation rates in plastic surgery. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

[Photosynthetic rate, transpiration rate, and water use efficiency of cotton canopy in oasis edge of Linze].

Science.gov (United States)

Xie, Ting-Ting; Su, Pei-Xi; Gao, Song

2010-06-01

The measurement system of Li-8100 carbon flux and the modified assimilation chamber were used to study the photosynthetic characteristics of cotton (Gossypium hirsutum L.) canopy in the oasis edge region in middle reach of Heihe River Basin, mid Hexi Corridor of Gansu. At the experimental site, soil respiration and evaporation rates were significantly higher in late June than in early August, and the diurnal variation of canopy photosynthetic rate showed single-peak type. The photosynthetic rate was significantly higher (P transpiration rate also presented single-peak type, with the daily average value in late June and early August being (3.10 +/- 0.34) mmol H2O x m(-2) x s(-1) and (1.60 +/- 0.26) mmol H2O x m(-2) x s(-1), respectively, and differed significantly (P efficiency in late June and early August was (15.67 +/- 1.77) mmol CO2 x mol(-1) H2O and (23.08 +/- 5.54) mmol CO2 x mol(-1) H2O, respectively, but the difference was not significant (P > 0.05). Both in late June and in early August, the canopy photosynthetic rate was positively correlated with air temperature, PAR, and soil moisture content, suggesting that there was no midday depression of photosynthesis in the two periods. In August, the canopy photosynthetic rate and transpiration rate decreased significantly, because of the lower soil moisture content and leaf senescence, but the canopy water use efficiency had no significant decrease.

Religious affiliation and psychiatric morbidity in Brazil: higher rates among evangelicals and spiritists.

Science.gov (United States)

Dalgalarrondo, Paulo; Marín-León, Leticia; Botega, Neury José; Berti De Azevedo Barros, Marilisa; Bosco De Oliveira, Helenice

2008-11-01

To verify the association between the prevalence of mental symptoms and excessive alcohol intake with religious affiliation, church attendance and personal religiosity. A household survey of 515 adults randomly sampled included the WHO SUPRE-MISS questionnaire, SRQ-20 and AUDIT. Weighted prevalences were estimated and logistic analyses were performed. Minor psychiatric morbidity was greater among Spiritists and Protestants/ Evangelicals than in Catholics and in the ;no-religion' group. The latter had a greater frequency of abusive alcohol drinking pattern and Protestants/Evangelicals showed lower drinking patterns. Although belonging to Protestant/Evangelical churches in Brazil may inhibit alcohol involvement it seems to be associated to a higher frequency of depressive symptoms. Processes of seeking relief in new religious affiliations among sub-groups with previous minor psychiatric symptoms may probably occur in the Brazilian society.

HEART RATE RECOVERY AFTER EXERCISE AND NEURAL REGULATION OF HEART RATE VARIABILITY IN 30-40 YEAR OLD FEMALE MARATHON RUNNERS

Directory of Open Access Journals (Sweden)

Toshio Matsuoka

2005-03-01

Full Text Available The aim of the present study was to examine the effects of endurance training on heart rate (HR recovery after exercise and cardiac autonomic nervous system (ANS modulation in female marathon runners by comparing with untrained controls. Six female marathon runners (M group aged 32-40 years and eight age-matched untrained females (C group performed a maximum-effort treadmill running exercise. Maximal oxygen uptake (VO2max was measured during the exercise with a gas analyzer connected to subjects through a face mask. Heart rate, blood pressure and blood lactate were measured before and after the exercise. Rating of perceived exertion (RPE to the exercise was obtained immediately after the exercise. Holter ECG was recorded and analyzed with power spectral analysis of heart rate variability (HRV to investigate the cardiac ANS modulation. The M group had significantly higher VO2max, faster HR recovery after exercise, higher Mean RR, SDRR, HF power and lower LF/HF ratio at rest compared with the C group. The M group also presented greater percent decrease of blood pressure after exercise, although their blood pressure after exercise was higher than the C group. It is suggested that endurance training induced significant alterations in cardiac ANS modulation at rest and significant acceleration of HR recovery after exercise in female marathon runners. Faster HR recovery after exercise in the female marathon runners should result from their higher levels of HRV, higher aerobic capacity and exaggerated blood pressure response to exercise compared with untrained controls.

Ratings uplifts and bank characteristics in the Eurozone 2002-2011

NARCIS (Netherlands)

Dijkstra, M.A.

2013-01-01

This paper explores which characteristics define banks that are too-big-to-fail in the Eurozone over the period 2002-2011. These banks are identified through ratings uplift data from Moody’s. Higher ratings uplifts are associated with higher degrees of interest income and lower degrees of commission

Outdoor γ-ray dose rate in Shariki Village and environmental factors affecting outdoor γ-ray dose rate in IES

International Nuclear Information System (INIS)

Iyogi, Takashi; Hisamatsu, Shun'ichi; Inaba, Jiro

2000-01-01

Previously, we surveyed the outdoor γ-ray dose rate throughout Aomori Prefecture from 1992 to 1995, and found an annual mean dose rate of 51 nGy h -1 . Relatively high dose rates were also observed in several areas (municipalities) of the survey locations. In this study, we examined the detailed distribution of the γ-ray dose rate in one such high dose rate area, Shariki Village. Glass dosemeters were used for the monitoring of cumulative γ-ray dose rate at 10 locations in the village. The dose rate from each radioactive nuclide in the ground at the monitoring locations was measured by using an in situ γ-ray spectrometer with a Ge detector. The results obtained with the glass dosemeters showed that the γ-ray dose rates in Shariki Village varied from 49 to 55 nGy h -1 . Although the dose rates were generally higher than the mean dose in Aomori Prefecture (1992-1995), the rates were lower than other high dose rate areas which had already been measured. The in situ γ-ray spectrometry revealed that these relatively high dose rates were mainly caused by 40 K and Th series radionuclides in the village. The effect of meteorological conditions on the γ-ray dose rate was studied at a monitoring station in the IES site. The dose rate was continuously recorded by a DBM NaI(Tl) scintillation detector system. The mean dose rate obtained when precipitation was sensed was 27 nGy h -1 and higher than when no precipitation was sensed (25 nGy h -1 ). (author)

Metabolic rate and gross efficiency at high work rates in world class and national level sprint skiers.

Science.gov (United States)

Sandbakk, Øyvind; Holmberg, Hans-Christer; Leirdal, Stig; Ettema, Gertjan

2010-06-01

The present study investigated metabolic rate (MR) and gross efficiency (GE) at moderate and high work rates, and the relationships to gross kinematics and physical characteristics in elite cross-country skiers. Eight world class (WC) and eight national level (NL) male sprint cross-country skiers performed three 5-min stages using the skating G3 technique, whilst roller skiing on a treadmill. GE was calculated by dividing work rate by MR. Work rate was calculated as the sum of power against gravity and frictional rolling forces. MR was calculated using gas exchange and blood lactate values. Gross kinematics, i.e. cycle length (CL) and cycle rate (CR) were measured by video analysis. Furthermore, the skiers were tested for time to exhaustion (TTE), peak oxygen uptake (VO(2peak)), and maximal speed (V(max)) on the treadmill, and maximal strength in the laboratory. Individual performance level in sprint skating was determined by FIS points. WC skiers did not differ in aerobic MR, but showed lower anaerobic MR and higher GE than NL skiers at a given speed (all P higher V(max) and TTE (all P better technique and to technique-specific power.

Toward 100 GHz direct modulation rate of antenna coupled nanoLED

DEFF Research Database (Denmark)

Fortuna, Seth A.; Taghizadeh, Alireza; Yablonovitch, Eli

2016-01-01

We show that > 100 GHz direct modulation rate while maintaining a quantum efficiency higher than 25% is possible by using an optical antenna to enhance the spontaneous emission rate of an electrically injected III-V nanoLED.......We show that > 100 GHz direct modulation rate while maintaining a quantum efficiency higher than 25% is possible by using an optical antenna to enhance the spontaneous emission rate of an electrically injected III-V nanoLED....

Relationships between Medicare Advantage contract characteristics and quality-of-care ratings: an observational analysis of Medicare Advantage star ratings.

Science.gov (United States)

Xu, Peng; Burgess, James F; Cabral, Howard; Soria-Saucedo, Rene; Kazis, Lewis E

2015-03-03

The Centers for Medicare & Medicaid Services (CMS) publishes star ratings on Medicare Advantage (MA) contracts to measure plan quality of care with implications for reimbursement and bonuses. To investigate whether MA contract characteristics are associated with quality of care through the Medicare plan star ratings. Retrospective study of MA star ratings in 2010. Unadjusted and adjusted multivariable linear regression models assessed the relationship between 5-star rating summary scores and plan characteristics. CMS MA contracts nationally. 409 (71%) of a total of 575 MA contracts, covering 10.56 million Medicare beneficiaries (90% of the MA population) in the United States in 2010. The MA quality ratings summary score (stars range from 1 to 5) is a quality measure based on 36 indicators related to processes of care, health outcomes, access to care, and beneficiary satisfaction. Nonprofit, larger, and older MA contracts were more likely to receive higher star ratings. Star ratings ranged from 2 to 5. Nonprofit contracts received an average 0.55 (95% CI, 0.42 to 0.67) higher star ratings than for-profit contracts (P  star ratings than for-profit contracts. When comparing health plans in the future, the CMS should give increasing attention to for-profit plans with lower quality ratings and consider developing programs to assist newer and smaller plans in improving their care for Medicare beneficiaries. None.

An integrated approach for a higher success rate in mergers and acquisitions

Directory of Open Access Journals (Sweden)

Andrej Bertoncelj

2007-05-01

Full Text Available The paper outlines the importance of balanced management of hard and soft key success factors, combining the economic logic of corporate performance and human capital through an integrated approach to mergers and acquisitions. The study, based on a questionnaire and interviews, suggests that the achievement level ofmergers and acquisitions’ objectives of acquiring companies in Slovenia should be comparable to findings of similar studies; namely, the objectives that drove the deal were met only half the time. The results indicate that five hard success factors – a professional target search and due diligence, a realistic assessment of synergies, theright mix of financial sources, a detailed post-acquisition integration plan already prepared in the pre-deal phase and its speedy implementation – and five soft success factors – a new “combined” organizational culture, a competent management team, innovative employees, efficient and consistent communication and a creative business environment – are becoming increasingly relevant. Even though they differ in their importance for individual companies in the sample, they are all considered essential to increasing the success rate of corporate combinations

RATES OF PHOTOSPHERIC MAGNETIC FLUX CANCELLATION MEASURED WITH HINODE

International Nuclear Information System (INIS)

Park, Soyoung; Chae, Jongchul; Litvinenko, Yuri E.

2009-01-01

Photospheric magnetic flux cancellation on the Sun is generally believed to be caused by magnetic reconnection occurring in the low solar atmosphere. Individual canceling magnetic features are observationally characterized by the rate of flux cancellation. The specific cancellation rate, defined as the rate of flux cancellation divided by the interface length, gives an accurate estimate of the electric field in the reconnecting current sheet. We have determined the specific cancellation rate using the magnetograms taken by the Solar Optical Telescope (SOT) aboard the Hinode satellite. The specific rates determined with SOT turned out to be systematically higher than those based on the data taken by the Michelson Doppler Imager (MDI) aboard the Solar and Heliospheric Observatory. The median value of the specific cancellation rate was found to be 8 x 10 6 G cm s -1 -a value four times that obtained from the MDI data. This big difference is mainly due to a higher angular resolution and better sensitivity of the SOT, resulting in magnetic fluxes up to five times larger than those obtained from the MDI. The higher rates of flux cancellation correspond to either faster inflows or stronger magnetic fields of the reconnection inflow region, which may have important consequences for the physics of photospheric magnetic reconnection.

Heart Rate Fragmentation: A Symbolic Dynamical Approach

Directory of Open Access Journals (Sweden)

Madalena D. Costa

2017-11-01

Full Text Available Background: We recently introduced the concept of heart rate fragmentation along with a set of metrics for its quantification. The term was coined to refer to an increase in the percentage of changes in heart rate acceleration sign, a dynamical marker of a type of anomalous variability. The effort was motivated by the observation that fragmentation, which is consistent with the breakdown of the neuroautonomic-electrophysiologic control system of the sino-atrial node, could confound traditional short-term analysis of heart rate variability.Objective: The objectives of this study were to: (1 introduce a symbolic dynamical approach to the problem of quantifying heart rate fragmentation; (2 evaluate how the distribution of the different dynamical patterns (“words” varied with the participants' age in a group of healthy subjects and patients with coronary artery disease (CAD; and (3 quantify the differences in the fragmentation patterns between the two sample populations.Methods: The symbolic dynamical method employed here was based on a ternary map of the increment NN interval time series and on the analysis of the relative frequency of symbolic sequences (words with a pre-defined set of features. We analyzed annotated, open-access Holter databases of healthy subjects and patients with CAD, provided by the University of Rochester Telemetric and Holter ECG Warehouse (THEW.Results: The degree of fragmentation was significantly higher in older individuals than in their younger counterparts. However, the fragmentation patterns were different in the two sample populations. In healthy subjects, older age was significantly associated with a higher percentage of transitions from acceleration/deceleration to zero acceleration and vice versa (termed “soft” inflection points. In patients with CAD, older age was also significantly associated with higher percentages of frank reversals in heart rate acceleration (transitions from acceleration to

What is the empirical evidence that hospitals with higher-risk adjusted mortality rates provide poorer quality care? A systematic review of the literature

Directory of Open Access Journals (Sweden)

Mohammed Mohammed A

2007-06-01

Full Text Available Abstract Background Despite increasing interest and publication of risk-adjusted hospital mortality rates, the relationship with underlying quality of care remains unclear. We undertook a systematic review to ascertain the extent to which variations in risk-adjusted mortality rates were associated with differences in quality of care. Methods We identified studies in which risk-adjusted mortality and quality of care had been reported in more than one hospital. We adopted an iterative search strategy using three databases – Medline, HealthSTAR and CINAHL from 1966, 1975 and 1982 respectively. We identified potentially relevant studies on the basis of the title or abstract. We obtained these papers and included those which met our inclusion criteria. Results From an initial yield of 6,456 papers, 36 studies met the inclusion criteria. Several of these studies considered more than one process-versus-risk-adjusted mortality relationship. In total we found 51 such relationships in a widen range of clinical conditions using a variety of methods. A positive correlation between better quality of care and risk-adjusted mortality was found in under half the relationships (26/51 51% but the remainder showed no correlation (16/51 31% or a paradoxical correlation (9/51 18%. Conclusion The general notion that hospitals with higher risk-adjusted mortality have poorer quality of care is neither consistent nor reliable.

Evaluation of IOM personal sampler at different flow rates.

Science.gov (United States)

Zhou, Yue; Cheng, Yung-Sung

2010-02-01

The Institute of Occupational Medicine (IOM) personal sampler is usually operated at a flow rate of 2.0 L/min, the rate at which it was designed and calibrated, for sampling the inhalable mass fraction of airborne particles in occupational environments. In an environment of low aerosol concentrations only small amounts of material are collected, and that may not be sufficient for analysis. Recently, a new sampling pump with a flow rate up to 15 L/min became available for personal samplers, with the potential of operating at higher flow rates. The flow rate of a Leland Legacy sampling pump, which operates at high flow rates, was evaluated and calibrated, and its maximum flow was found to be 10.6 L/min. IOM samplers were placed on a mannequin, and sampling was conducted in a large aerosol wind tunnel at wind speeds of 0.56 and 2.22 m/s. Monodisperse aerosols of oleic acid tagged with sodium fluorescein in the size range of 2 to 100 microm were used in the test. The IOM samplers were operated at flow rates of 2.0 and 10.6 L/min. Results showed that the IOM samplers mounted in the front of the mannequin had a higher sampling efficiency than those mounted at the side and back, regardless of the wind speed and flow rate. For the wind speed of 0.56 m/s, the direction-averaged (the average value of all orientations facing the wind direction) sampling efficiency of the samplers operated at 2.0 L/min was slightly higher than that of 10.6 L/min. For the wind speed of 2.22 m/s, the sampling efficiencies at both flow rates were similar for particles < 60 microm. The results also show that the IOM's sampling efficiency at these two different flow rates follows the inhalable mass curve for particles in the size range of 2 to 20 microm. The test results indicate that the IOM sampler can be used at higher flow rates.

Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes

Science.gov (United States)

Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Shakleya, Diaa M.; Huestis, Marilyn A.

2010-01-01

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

Metabolism of methylphenidate in dog and rat

International Nuclear Information System (INIS)

Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

1981-01-01

The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Eckart, K; Röhrich, J; Breitmeier, D; Ferner, M; Laufenberg-Feldmann, R; Urban, R

2015-09-15

A liquid chromatography-tandem mass spectrometry method using electrospray ionization in positive ionization mode was developed for the simultaneous detection of multiple opioid-type drugs in plasma. The presented assay allows the quantitative determination of alfentanil, buprenorphine, codeine, desomorphine, dextromethorphan, dextrorphan, dihydrocodeine, dihydromorphine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, pholcodine, piritramide, remifentanil, sufentanil, and tramadol as well as the metabolites 6-monoacetylmorphine, bisnortilidine, morphine-3-glucuronide, morphine-6-glucuronide, naltrexol, norbuprenorphine, norfentanyl, norpethidine, nortilidine, and O-desmethyltramadol. Serum and blood samples were purified by solid-phase extraction. The analytes were separated on a phenyl-hexyl (100mm) column by formic acid/acetonitrile gradient elution using an UPLC 1290 Infinity coupled with a 6490 Triple Quadrupole mass spectrometer. The limits of detection ranged from 0.02 to 0.6ng/mL and the lower limits of quantification ranged from 0.1 to 2.0ng/mL. The calibration curves were linear between Calibration Levels 1-6 for all 35 substances. Recovery rates ranged between 51 and 88% for all compounds except alfentanil, bisnortilidine, pethidine, and morphine-3-glucuronide. The matrix effect ranged from 86% for ethylmorphine to 105% for desomorphine. Using the validation procedure proposed by the German Society of Toxicological and Forensic Chemistry, acceptable precision and accuracy data for almost all analytes were obtained. The method was successfully applied to 206 authentic serum samples provided by the palliative and intensive care units of the University Medical Center and the police authorities. Furthermore, a suspected fatal intoxication is demonstrated by an analysis of the sufentanil in post mortem body fluids and tissues. Copyright © 2015 Elsevier B.V. All

Influence of heavy cigarette smoking on heart rate variability and heart rate turbulence parameters

DEFF Research Database (Denmark)

Cagirci, Goksel; Cay, Serkan; Karakurt, Ozlem

2009-01-01

BACKGROUND: Cigarette smoking increases the risk of cardiovascular events related with several mechanisms. The most suggested mechanism is increased activity of sympathetic nervous system. Heart rate variability (HRV) and heart rate turbulence (HRT) has been shown to be independent and powerful......, 69 subjects and nonsmokers 74 subjects (control group) were enrolled in this study. HRV and HRT analyses [turbulence onset (TO) and turbulence slope (TS)] were assessed from 24-hour Holter recordings. RESULTS: The values of TO were significantly higher in heavy cigarette smokers than control group...... (-1.150 +/- 4.007 vs -2.454 +/- 2.796, P = 0.025, respectively), but values of TS were not statistically different between two groups (10.352 +/- 7.670 vs 9.613 +/- 7.245, P = 0.555, respectively). Also, the number of patients who had abnormal TO was significantly higher in heavy cigarette smokers...

Higher education, Graduate unemployment, Poverty and Economic growth in Tunisia, 1990-2013

Directory of Open Access Journals (Sweden)

Haifa Mefteh

2016-07-01

Full Text Available This paper examines the relationship between economic growth, higher education, unemployment and poverty using properties of time series variables while applying the Ordinary Least Squares (OLS method. Our study thus contributes to the existing literature by giving the first integrated approach to examine the four way linkages in the Tunisian background over the period 1990-2013. This paper holds that higher education can impact unemployment and graduate unemployment causes poverty which would affect economic growth. Our empirical results show that there is bi-directional causal relationship between per capita gross domestic product (GDP and poverty rate (POV and also between Number of graduate students (GRA and School enrollment tertiary education (ENR besides unidirectional causal relationship which running from Number of graduate students to Unemployment with tertiary education (UNP, from Higher education expenditure (EXP to poverty rate and from Unemployment with tertiary education to poverty rate. Our empirical results also verified the existence of positive effect of ENR, GRA and POV on economic growth, while, UNP and EXP have negative determining influence on economic growth with only GRA statistically significant. These empirical insights are of particular interest for the policy makers as they help build sound economic policies to sustain economic development and improve the higher educational quality.

Outlook on Student Retention in Higher Education University Reforms in Morocco

Science.gov (United States)

Mansouri, Zoulal; Moumine, Mohamed El Amine

2017-01-01

High student attrition rates at university have become one of the most challenging issues in higher education worldwide in the last five decades. Moroccan universities are no exception. At-risk students drop out of studies for a plethora of reasons, and the attrition rate is increasing despite the efforts made in education reforms carried out…

World Bank Okays Public Interest in Higher Education

Science.gov (United States)

Post, David; Clipper, Lutitia; Enkhbaatar, D.; Manning, Anitra; Riley, Thomas; Zaman, Husam

2004-01-01

This essay review discusses the report of The Task Force on Higher Education and Society (TFHES), convened in 1998 by the World Bank but independently financed and staffed in collaboration with UNESCO and several foundations. "Peril and Promise" marks an historic turning point in the framework for postsecondary educational planning. Rate-of-return…

Hand hygiene compliance rates: Fact or fiction?

Science.gov (United States)

McLaws, Mary-Louise; Kwok, Yen Lee Angela

2018-05-16

The mandatory national hand hygiene program requires Australian public hospitals to use direct human auditing to establish compliance rates. To establish the magnitude of the Hawthorne effect, we compared direct human audit rates with concurrent automated surveillance rates. A large tertiary Australian teaching hospital previously trialed automated surveillance while simultaneously performing mandatory human audits for 20 minutes daily on a medical and a surgical ward. Subtracting automated surveillance rates from human audit rates provided differences in percentage points (PPs) for each of the 3 quarterly reporting periods for 2014 and 2015. Direct human audit rates for the medical ward were inflated by an average of 55 PPs in 2014 and 64 PPs in 2015, 2.8-3.1 times higher than automated surveillance rates. The rates for the surgical ward were inflated by an average of 32 PPs in 2014 and 31 PPs in 2015, 1.6 times higher than automated surveillance rates. Over the 6 mandatory reporting quarters, human audits collected an average of 255 opportunities, whereas automation collected 578 times more data, averaging 147,308 opportunities per quarter. The magnitude of the Hawthorne effect on direct human auditing was not trivial and produced highly inflated compliance rates. Mandatory compliance necessitates accuracy that only automated surveillance can achieve, whereas daily hand hygiene ambassadors or reminder technology could harness clinicians' ability to hyperrespond to produce habitual compliance. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Explaining Cross-State Differences in Elderly Suicide Rates and Identifying State-Level Public Policy Responses that Reduce Rates

Science.gov (United States)

Giles-Sims, Jean; Lockhart, Charles

2006-01-01

Elderly Americans commit suicide at higher rates than other age groups. We contend that macro- and micro-social variables contribute distinct aspects to explanations of this tragic loss: the former focus on circumstances that affect overall rates, the latter reveal why certain individuals succumb to suicide. Our analysis focuses on the…

Mass spectrometric characterization of the hypoxia-inducible factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implementation into routine doping controls.

Science.gov (United States)

Dib, Josef; Mongongu, Cynthia; Buisson, Corinne; Molina, Adeline; Schänzer, Wilhelm; Thuss, Uwe; Thevis, Mario

2017-01-01

The development of new therapeutics potentially exhibiting performance-enhancing properties implicates the risk of their misuse by athletes in amateur and elite sports. Such drugs necessitate preventive anti-doping research for consideration in sports drug testing programmes. Hypoxia-inducible factor (HIF) stabilizers represent an emerging class of therapeutics that allows for increasing erythropoiesis in patients. BAY 85-3934 is a novel HIF stabilizer, which is currently undergoing phase-2 clinical trials. Consequently, the comprehensive characterization of BAY 85-3934 and human urinary metabolites as well as the implementation of these analytes into routine doping controls is of great importance. The mass spectrometric behaviour of the HIF stabilizer drug candidate BAY 85-3934 and a glucuronidated metabolite (BAY-348) were characterized by electrospray ionization-(tandem) mass spectrometry (ESI-MS(/MS)) and multiple-stage mass spectrometry (MS n ). Subsequently, two different laboratories established different analytical approaches (one each) enabling urine sample analyses by employing either direct urine injection or solid-phase extraction. The methods were cross-validated for the metabolite BAY-348 that is expected to represent an appropriate target analyte for human urine analysis. Two test methods allowing for the detection of BAY-348 in human urine were applied and cross-validated concerning the validation parameters specificity, linearity, lower limit of detection (LLOD; 1-5 ng/mL), ion suppression/enhancement (up to 78%), intra- and inter-day precision (3-21%), recovery (29-48%), and carryover. By means of ten spiked test urine samples sent blinded to one of the participating laboratories, the fitness-for-purpose of both assays was provided as all specimens were correctly identified applying both testing methods. As no post-administration study samples were available, analyses of authentic urine specimens remain desirable. Copyright © 2016 John Wiley

Extracting factors for interest rate scenarios

Science.gov (United States)

Molgedey, L.; Galic, E.

2001-04-01

Factor based interest rate models are widely used for risk managing purposes, for option pricing and for identifying and capturing yield curve anomalies. The movements of a term structure of interest rates are commonly assumed to be driven by a small number of orthogonal factors such as SHIFT, TWIST and BUTTERFLY (BOW). These factors are usually obtained by a Principal Component Analysis (PCA) of historical bond prices (interest rates). Although PCA diagonalizes the covariance matrix of either the interest rates or the interest rate changes, it does not use both covariance matrices simultaneously. Furthermore higher linear and nonlinear correlations are neglected. These correlations as well as the mean reverting properties of the interest rates become crucial, if one is interested in a longer time horizon (infrequent hedging or trading). We will show that Independent Component Analysis (ICA) is a more appropriate tool than PCA, since ICA uses the covariance matrix of the interest rates as well as the covariance matrix of the interest rate changes simultaneously. Additionally higher linear and nonlinear correlations may be easily incorporated. The resulting factors are uncorrelated for various time delays, approximately independent but nonorthogonal. This is in contrast to the factors obtained from the PCA, which are orthogonal and uncorrelated for identical times only. Although factors from the ICA are nonorthogonal, it is sufficient to consider only a few factors in order to explain most of the variation in the original data. Finally we will present examples that ICA based hedges outperforms PCA based hedges specifically if the portfolio is sensitive to structural changes of the yield curve.

Vodka and violence: alcohol consumption and homicide rates in Russia.

Science.gov (United States)

Pridemore, William Alex

2002-12-01

In Russia, rates of alcohol consumption and homicide are among the highest in the world, and already-high levels increased dramatically after the breakup of the Soviet Union. Rates of both, however, vary greatly among Russia's 89 regions. We took advantage of newly available vital statistics and socioeconomic data to examine the regional covariation of drinking and lethal violence. Log-log models were employed to estimate the impact of alcohol consumption on regional homicide rates, controlling for structural factors thought to influence the spatial distribution of homicide rates. Results revealed a positive and significant relationship between alcohol consumption and homicide, with a 1% increase in regional consumption of alcohol associated with an approximately 0.25% increase in homicide rates. In Russia, higher regional rates of alcohol consumption are associated with higher rates of homicide.

Targeting the Real Exchange Rate; Theory and Evidence

OpenAIRE

Carlos A. Végh Gramont; Guillermo Calvo; Carmen Reinhart

1994-01-01

This paper presents a theoretical and empirical analysis of policies aimed at setting a more depreciated level of the real exchange rate. An intertemporal optimizing model suggests that, in the absence of changes in fiscal policy, a more depreciated level of the real exchange can only be attained temporarily. This can be achieved by means of higher inflation and/or higher real interest rates, depending on the degree of capital mobility. Evidence for Brazil, Chile, and Colombia supports the mo...

The Occurrence Rate of Hot Jupiters

Science.gov (United States)

Rampalli, Rayna; Catanzarite, Joseph; Batalha, Natalie M.

2017-01-01

As the first kind of exoplanet to be discovered, hot Jupiters have always been objects of interest. Despite being prevalent in radial velocity and ground-based surveys, they were found to be much rarer based on Kepler observations. These data show a pile-up at radii of 9-22 Rearth and orbital periods of 1-10 days. Computing accurate occurrence rates can lend insight into planet-formation and migration-theories. To get a more accurate look, the idea of reliability was introduced. Each hot Jupiter candidate was assigned a reliability based on its location in the galactic plane and likelihood of being a false positive. Numbers were updated if ground-based follow-up indicated a candidate was indeed a false positive. These reliabilities were introduced into an occurrence rate calculation and yielded about a 12% decrease in occurrence rate for each period bin examined and a 25% decrease across all the bins. To get a better idea of the cause behind the pileup, occurrence rates based on parent stellar metallicity were calculated. As expected from previous work, higher metallicity stars yield higher occurrence rates. Future work includes examining period distributions in both the high metallicity and low metallicity sample for a better understanding and confirmation of the pile-up effect.

Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

Science.gov (United States)

Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

2017-10-01

1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

Determination of sedimentation rates and absorption coefficient of ...

African Journals Online (AJOL)

2+ has a higher sedimentation rate of 5.10x10-2 s-1 while Ni2+ has the lowest sedimentation rates of 1.10 x10-3. The rate of sedimentation of the metal carbonates decreased in the order: Zn2+ > Cd2+ > Cu2+ > Co2+ > Ni2+. The order ...

Plastome-Wide Nucleotide Substitution Rates Reveal Accelerated Rates in Papilionoideae and Correlations with Genome Features Across Legume Subfamilies.

Science.gov (United States)

Schwarz, Erika N; Ruhlman, Tracey A; Weng, Mao-Lun; Khiyami, Mohammad A; Sabir, Jamal S M; Hajarah, Nahid H; Alharbi, Njud S; Rabah, Samar O; Jansen, Robert K

2017-04-01

This study represents the most comprehensive plastome-wide comparison of nucleotide substitution rates across the three subfamilies of Fabaceae: Caesalpinioideae, Mimosoideae, and Papilionoideae. Caesalpinioid and mimosoid legumes have large, unrearranged plastomes compared with papilionoids, which exhibit varying levels of rearrangement including the loss of the inverted repeat (IR) in the IR-lacking clade (IRLC). Using 71 genes common to 39 legume taxa representing all the three subfamilies, we show that papilionoids consistently have higher nucleotide substitution rates than caesalpinioids and mimosoids, and rates in the IRLC papilionoids are generally higher than those in the IR-containing papilionoids. Unsurprisingly, this pattern was significantly correlated with growth habit as most papilionoids are herbaceous, whereas caesalpinioids and mimosoids are largely woody. Both nonsynonymous (dN) and synonymous (dS) substitution rates were also correlated with several biological features including plastome size and plastomic rearrangements such as the number of inversions and indels. In agreement with previous reports, we found that genes in the IR exhibit between three and fourfold reductions in the substitution rates relative to genes within the large single-copy or small single-copy regions. Furthermore, former IR genes in IR-lacking taxa exhibit accelerated rates compared with genes contained in the IR.

Remarks on Interest Rate Risk Management

Directory of Open Access Journals (Sweden)

Elena-Violeta DRAGOI

2016-12-01

Full Text Available Bank interest and interest rate risk management is a contemporary subject and for socio-economic environment of Romania cause serious consequences in the level of economic development. The purpose of this research is to highlight the main indicator that measures the total cost of a loan, namely the annual percentage rate (APR, because if we refer to an interest rate lower, at first glance that loan seems more advantageous, but at a closer look, taking into account the commissions charged by the bank, we see that the loan is more expensive compared to another, whose interest rate is higher.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

Science.gov (United States)

Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

2011-11-01

Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rating Emotion Communication: Display and Concealment as Effects of Culture, Gender, Emotion Type, and Relationship

Directory of Open Access Journals (Sweden)

Arne Vikan

2009-01-01

Full Text Available Students from a collectivistic (Brazilian, n= 401 and an individualistic (Norwegian, n= 418culture rated their ability to display and conceal anger, sadness, and anxiety in relation to immediate family, partner, friends, and "other persons." Norwegians showed higher display ratings for anger and sadness, and higher concealment ratings for anger and anxiety. Display ratings were much higher, and concealment ratings much lower in relation to close persons than in relation to "other persons." A culture x relationship interaction was that Brazilian' ratings suggested more emotional openness to friends than to family and partner, whereas Norwegians showed the inverse patterns. Gender differences supported previous research by showing higher display and lower concealment ratings, and less differentiation between relationships by females.

Statewide Divorce Rates and Wives' Participation in the Labor Market.

Science.gov (United States)

Yeh, Bijou Y.; Lester, David

1987-01-01

Analyzed the relationship between the participation of married women in the labor market and divorce rates in the continental states of the United States in 1980. Results showed the higher the proportion of married women working full time and the lower the proportion of married women working part time, the higher the divorce rate of the state.…

The Economic Analysis of University Participation Rates

Science.gov (United States)

Fallis, George

2015-01-01

Over the postwar period in most developed countries, the university participation rate has risen steadily to well over 30 percent, although there remain differences between countries. Students from lower income families have lower participation rates than those from higher income families. The article provides an economic analysis of these…

A Rate Adaptation Scheme According to Channel Conditions in Wireless LANs

Science.gov (United States)

Numoto, Daisuke; Inai, Hiroshi

Rate adaptation in wireless LANs is to select the most suitable transmission rate automatically according to channel condition. If the channel condition is good, a station can choose a higher transmission rate, otherwise, it should choose a lower but noise-resistant transmission rate. Since IEEE 802.11 does not specify any rate adaptation scheme, several schemes have been proposed. However those schemes provide low throughput or unfair transmission opportunities among stations especially when the number of stations increases. In this paper, we propose a rate adaptation scheme under which the transmission rate quickly closes and then stays around an optimum rate even in the presence of a large number of stations. Via simulation, our scheme provides higher throughput than existing ones and almost equal fairness.

Study success in higher education: male versus female students

NARCIS (Netherlands)

Kolster, Renze; Kaiser, Franciscus

2015-01-01

Study success is an important topic for countries concerned with the effectiveness of their higher education system. A closer look at study success outcomes suggests there are noticeable differences between male and female students: in terms of enrolment, study choices, drop‐out rates, retention

Azacitidine-lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol.

Science.gov (United States)

Mittelman, Moshe; Filanovsky, Kalman; Ofran, Yishai; Rosenbaum, Hanna; Raanani, Pia; Braester, Andrei; Goldschmidt, Neta; Kirgner, Ilya; Herishanu, Yair; Perri, Chava; Ellis, Martin; Oster, Howard S

2016-10-01

Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76.3 years old (60-87), and 88 % with major comorbidities. Thirteen patients completed induction, 7 proceeded for consolidation, and 2 for maintenance. The overall response rate (ORR) was 72 % (18/25), with 6 (24 %) for CR, 3 (12 %) for marrow CR, and 9 (36 %) for hematologic improvement (HI). The 7 non-responding patients were on the study 3 days to 4.1 months. At 6 months, 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del (5q) at diagnosis. Adverse events (AEs) were as expected in these patients: grades III-IV, mainly hematologic-thrombocytopenia (20 patients) and neutropenia (13 patients). The common non-hematologic AEs were infections (14 patients), nausea (7), vomiting (7), diarrhea (7), and skin reactions (5). The median progression-free survival (PFS) was 12 ± 1.36 months, with median overall survival (OS) of 12 ± 1.7 months. Quality of life (FACT questionnaire) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high (72 %) response rate and a reasonable expected safety profile but a relatively short PFS and OS.

All My Rowdy "Friends": The Use of Social Media in Higher Education

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Lenartz, Andrew J.

2012-01-01

The use of social media in higher education is escalating at a rapid rate, with previous records for numbers of users being continuously broken. Institutions of higher education have responded by increasingly using social media to connect with students. At the same time, media horror stories about cyberbullying, suicides, and professional…

Dealing with China's future population decline: a proposal for replacing low birth rates with sustainable rates.

Science.gov (United States)

Cao, Shixiong; Wang, Xiuqing

2009-09-01

Decreasing population levels due to declining birth rates are becoming a potentially serious social problem in developed and rapidly developing countries. China urgently needed to reduce birth rates so that its population would decline to a sustainable level, and the family planning policy designed to achieve this goal has largely succeeded. However, continuing to pursue this policy is leading to serious, unanticipated problems such as a shift in the country's population distribution towards the elderly and increasing difficulty supporting that elderly population. Social and political changes that promoted low birth rates and the lack of effective policies to encourage higher birth rates suggest that mitigating the consequences of the predicted population decline will depend on a revised approach based on achieving sustainable birth rates.

Outlook on Student Retention in Higher Education University Reforms in Morocco

Directory of Open Access Journals (Sweden)

Zoulal Mansouri

2017-04-01

Full Text Available High student attrition rates at university have become one of the most challenging issues in higher education worldwide in the last five decades. Moroccan universities are no exception. At-risk students drop out of studies for a plethora of reasons, and the attrition rate is increasing despite the efforts made in education reforms carried out since 1999. This article reviews the most important components of the higher education reforms that have been adopted in Moroccan higher education in their endeavor to enhance student retention in university. These components are chronologically reviewed, first in the National Charter of Education and Training (NCET launched in 1999, second in the Emergency Plan conducted in 2009-2012, and finally in the latest Strategic Vision of Reform 2015-2030. It is concluded that more efforts are necessary to strike a balance between quantity and quality in terms of student retention in university education.

47 CFR 17.54 - Rated lamp voltage.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Rated lamp voltage. 17.54 Section 17.54... voltage. To insure the necessary lumen output by obstruction lights, the rated voltage of incandescent lamps used shall correspond to be within 3 percent higher than the voltage across the lamp socket during...

Weaker gun state laws are associated with higher rates of suicide secondary to firearms.

Science.gov (United States)

Alban, Rodrigo F; Nuño, Miriam; Ko, Ara; Barmparas, Galinos; Lewis, Azaria V; Margulies, Daniel R

2018-01-01

Firearm-related suicides comprise over two-thirds of gun-related violence in the United States, and gun laws and policies remain under scrutiny, with many advocating for revision of the regulatory map for lawful gun ownership, aiming at restricting access and distribution of these weapons. However, the quantitative relationship between how strict gun laws are and the incidence of firearm violence with their associated mortality is largely unknown. We therefore, sought to explore the impact of firearm law patterns among states on the incidence and outcomes of firearm-related suicide attempts, utilizing established objective criteria. The National Inpatient Sample for the years 1998-2011 was queried for all firearm-related suicides. Discharge facilities were stratified into five categories (A, B, C, D, and F, with A representing states with the most strict and F representing states with the least strict laws) based on the Brady Campaign to prevent Gun Violence that assigns scorecards for every state. The primary outcomes were suicide attempts and in-hospital mortality per 100,000 populations by Brady state grade. During the 14-year study period, 34,994 subjects met inclusion criteria. The mean age was 42.0 years and 80.1% were male. A handgun was utilized by 51.8% of patients. The overall mortality was 33.3%. Overall, 22.0% had reported psychoses and 19.3% reported depression. After adjusting for confounding factors and using group A as reference, there were higher adjusted odds for suicide attempts for patients admitted in group C, D, and F category states (1.73, 2.09, and 1.65, respectively, all P gun laws, and these injuries tend to be associated with a higher mortality. Efforts aimed at nationwide standardization of firearm state laws are warranted, particularly for young adults and suicide-prone populations. III. Trauma Outcomes study. Copyright © 2017 Elsevier Inc. All rights reserved.

Water Exchange Produces Significantly Higher Adenoma Detection Rate Than Water Immersion: Pooled Data From 2 Multisite Randomized Controlled Trials.

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Leung, Felix W; Koo, Malcolm; Cadoni, Sergio; Falt, Premysl; Hsieh, Yu-Hsi; Amato, Arnaldo; Erriu, Matteo; Fojtik, Petr; Gallittu, Paolo; Hu, Chi-Tan; Leung, Joseph W; Liggi, Mauro; Paggi, Silvia; Radaelli, Franco; Rondonotti, Emanuele; Smajstrla, Vit; Tseng, Chih-Wei; Urban, Ondrej

2018-03-02

To test the hypothesis that water exchange (WE) significantly increases adenoma detection rates (ADR) compared with water immersion (WI). Low ADR was linked to increased risk for interval colorectal cancers and related deaths. Two recent randomized controlled trials of head-to-head comparison of WE, WI, and traditional air insufflation (AI) each showed that WE achieved significantly higher ADR than AI, but not WI. The data were pooled from these 2 studies to test the above hypothesis. Two trials (5 sites, 14 colonoscopists) that randomized 1875 patients 1:1:1 to AI, WI, or WE were pooled and analyzed with ADR as the primary outcome. The ADR of AI (39.5%) and WI (42.4%) were comparable, significantly lower than that of WE (49.6%) (vs. AI P=0.001; vs. WI P=0.033). WE insertion time was 3 minutes longer than that of AI (Prate (vs. AI) of the >10 mm advanced adenomas. Right colon combined advanced and sessile serrated ADR of AI (3.4%) and WI (5%) were comparable and were significantly lower than that of WE (8.5%) (vs. AI P<0.001; vs. WI P=0.039). Compared with AI and WI, the superior ADR of WE offsets the drawback of a significantly longer insertion time. For quality improvement focused on increasing adenoma detection, WE is preferred over WI. The hypothesis that WE could lower the risk of interval colorectal cancers and related deaths should be tested.

Structural elucidation of in vitro and in vivo metabolites of emodin in rats by LC -ESI-MS/MS

International Nuclear Information System (INIS)

Wang, D.; Zhu, Q.; Chen, G.; Liu, B.; Chen, L.

2013-01-01

Emodin is a widely occurring natural product and has been studied extensively for its varieties of pharmacological activity. In attempt to know more deeply about its metabolism, this paper investigated the metabolites of emodin in rats, including its in vitro conversion product by intestinal microflora and urinary metabolites. The detection of emodin metabolites was performed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with negative ion mode. By comparing the changes of metabolites in molecular masses (delta M), product ions and retention times with those of the parent drug, six metabolites (8-O-methylemodin, omega-hydroxyemodin, x-hydroxyemodin, emodin glucuronide, hydroxyemodin glucuronide and emodin sulfate) were observed,and what is more, the metabolite hydroxyemodin glucuronide was first reported in this article. For some metabolites, identification of their precise structure needs to be confirmed by other techniques such as the 1H and 13C NMR. (author)

Influence of metabolism on endocrine activities of bisphenol S.

Science.gov (United States)

Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

2016-08-01

Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Absorption and pharmacokinetics of grapefruit flavanones in beagles.

Science.gov (United States)

Mata-Bilbao, Maria de Lourdes; Andrés-Lacueva, Cristina; Roura, Elena; Jáuregui, Olga; Escribano, Elvira; Torre, Celina; Lamuela-Raventós, Rosa Maria

2007-07-01

The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites naringenin and naringenin glucuronide, was detected in dog plasma. Blood samples were collected between 0 and 24 h after administration of the extract. Naringin reached its maximun plasma concentration at around 80 min, whereas naringenin and naringenin glucuronide reached their maximun plasma concentrations at around 20 and 30 min, respectively. Maximum plasma concentrations of naringin, naringenin and naringenin glucuronide (medians and ranges) were 0.24 (0.05-2.08), 0.021 (0.001-0.3) and 0.09 (0.034-0.12) micromol/l, respectively. The areas under the curves were 23.16 l (14.04-70.62) min x micromol/for nariningin, 1.78 (0.09-4.95) min x micromol/l for naringenin and 22.5 (2.74-99.23) min x micromol/l for naringenin glucuronide. The median and range values for mean residence time were 3.3 (1.5-9.3), 2.8 (0.8-11.2) and 8.0 (2.3-13.1) h for naringin, naringenin and naringenin glucuronide, respectively. The results of the present study demonstrate the absorption of grapefruit flavanones via the presence of their metabolites in plasma, thus making an important contribution to the field since the biological activities ascribed to these compounds rely on their specific forms of absorption.

CK2 activity is modulated by growth rate in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Tripodi, Farida; Cirulli, Claudia; Reghellin, Veronica; Marin, Oriano; Brambilla, Luca; Schiappelli, Maria Patrizia; Porro, Danilo; Vanoni, Marco; Alberghina, Lilia; Coccetti, Paola

2010-01-01

Research highlights: → CK2 subunits are nuclear both in glucose and in ethanol growing yeast cells. → CK2 activity is modulated in S. cerevisiae. → CK2 activity is higher in conditions supporting higher growth rates. → V max is higher in faster growing cells, while K m is not affected. -- Abstract: CK2 is a highly conserved protein kinase controlling different cellular processes. It shows a higher activity in proliferating mammalian cells, in various types of cancer cell lines and tumors. The findings presented herein provide the first evidence of an in vivo modulation of CK2 activity, dependent on growth rate, in Saccharomyces cerevisiae. In fact, CK2 activity, assayed on nuclear extracts, is shown to increase in exponential growing batch cultures at faster growth rate, while localization of catalytic and regulatory subunits is not nutritionally modulated. Differences in intracellular CK2 activity of glucose- and ethanol-grown cells appear to depend on both increase in molecule number and k cat . Also in chemostat cultures nuclear CK2 activity is higher in faster growing cells providing the first unequivocal demonstration that growth rate itself can affect CK2 activity in a eukaryotic organism.

Pedalling rate affects endurance performance during high-intensity cycling

DEFF Research Database (Denmark)

Nielsen, Jens Steen; Hansen, Ernst Albin; Sjøgaard, Gisela

2004-01-01

The purpose of this study into high-intensity cycling was to: (1) test the hypothesis that endurance time is longest at a freely chosen pedalling rate (FCPR), compared to pedalling rates 25% lower (FCPR-25) and higher (FCPR+25) than FCPR, and (2) investigate how physiological variables......, and endurance time at W90 with FCPR-25, FCPR, and FCPR+25. Power reserve was calculated as the difference between applied power output at a given pedalling rate and peak crank power at this same pedalling rate. W90 was 325 (47) W. FCPR at W90 was 78 (11) rpm, resulting in FCPR-25 being 59 (8) rpm and FCPR+25...... time was negatively related to VO(2max), W90 and % MHC I, while positively related to power reserve. In conclusion, at group level, endurance time was longer at FCPR and at a pedalling rate 25% lower compared to a pedalling rate 25% higher than FCPR. Further, inter-individual physiological variables...

Comparing replacement rates under private and federal retirement systems.

Science.gov (United States)

Martin, Patricia P

(100 percent) high earners (160 percent), and maximum earners (earnings at the taxable maximum amount). Overall, this analysis found that: Excluding Social Security benefits and TSP and defined contribution annuities, CSRS retirees have a higher pre-retirement salary replacement rate than either FERS or private-sector retirees. Private-sector retirees, however, have higher replacement rate than their FERS counterparts. Including Social Security benefits but not TSP and defined contribution plan annuities, CSRS retirees who are maximum earners have a higher pre-retirement salary replacement rate (despite receiving no Social Security benefits) than FERS retirees with the same earnings. Private-sector retirees in all earnings categories have a higher replacement rate than federal retirees with the same earnings. Including Social Security and TSP and defined contribution plan annuities, private-sector retirees in all earnings categories have a higher replacement rate than federal retirees, but their rate is close to that of FERS retirees. The rate is higher for FERS retirees than for CSRS retirees in all earnings categories. This analysis shows that replacement creates could exceed 100 percent for FERS employees who contribute who contribute 6 percent of earnings to the TSP over full working career. Private-sector replacement rates were quite similar for those with both a defined benefit and a defined contribution pension plan. Social Security replacement rates make up the highest proportion of benefits for th private sector's lowest income quartile group. The replacement rate for 401(k) plans and the TSP account for a higher proportion of benefits than does Social Security for all other income groups, assuming the absence of a defined benefit plan.

Species differences in biliary excretion of benzo[a]pyrene

International Nuclear Information System (INIS)

Weyand, E.H.; Bevan, D.R.

1986-01-01

Biliary excretion of benzo[a]pyrene (B[a]P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. [ 3 H]-B[a]P, in amounts of approximately 150 ng or 350 μg, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of [ 3 H]-B[a]P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B[a]P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B[a]P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B[a]P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose

Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice.

Science.gov (United States)

Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Wolc, Anna; Grześkowiak, Edmund

2017-05-01

Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them. The aim of the study was to investigate the effect of paracetamol on the pharmacokinetic parameters of erlotinib, as well as the influence of erlotinib on the pharmacokinetics of paracetamol. The rabbits were divided into three groups: the rabbits receiving erlotinib (I ER ), the group receiving paracetamol (II PR ), and the rabbits receiving erlotinib+paracetamol (III ER+PR ). A single dose of erlotinib was administered orally (25mg) and was administered intravenously (35mg/kg). Plasma concentrations of erlotinib, its metabolite (OSI420), paracetamol and its metabolites - glucuronide and sulphate were measured with the validated method. During paracetamol co-administration we observed increased erlotinib maximum concentration (C max ) and area under the plasma concentration-time curve from time zero to infinity (AUC 0-∞ ) by 87.7% and 31.1%, respectively. In turn, erlotinib lead to decreased paracetamol AUC 0-∞ by 35.5% and C max by 18.9%. The mean values of paracetamol glucuronide/paracetamol ratios for C max were 32.2% higher, whereas paracetamol sulphate/paracetamol ratios for C max and AUC 0-∞ were 37.1% and 57.1% lower in the II PR group, when compared to the III ER+PR group. Paracetamol had significant effect on the enhanced plasma exposure of erlotinib. Additionally, erlotinib contributed to the lower concentrations of paracetamol. Decreased glucuronidation and increased sulphation of paracetamol after co-administration of erlotinib were also observed. Copyright © 2017. Published by Elsevier B.V.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Science.gov (United States)

Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

2015-04-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

The Reasons of School Dropouts in Higher Education: Babaeski Vocational College Case

Science.gov (United States)

Can, Ertug; Aktas, Fatma Oya; Arpacioglu, Isil Tuzun

2017-01-01

In Turkey, nearly 400.000 higher education students have left university education in the last 3 years. This figure is an indication of a negative situation. Turkey is in the first place in terms of school dropout rates within the European Higher Education Area (EHEA). After completing primary and secondary education and passing the necessary…

The influence of incline and speed on work rate, gross efficiency and kinematics of roller ski skating.

Science.gov (United States)

Sandbakk, Øyvind; Ettema, Gertjan; Holmberg, Hans-Christer

2012-08-01

During competitions, elite cross-country skiers produce higher external work rates on uphill than on flat terrain. However, it is not presently known whether this reflects solely higher energy expenditure. Furthermore, the kinematic factors associated with these higher rates of uphill work have not yet been examined. Therefore, in the present investigation the work rate and associated kinematic parameters at similar metabolic rates during roller ski skating on flat and uphill terrains have been compared. Seven elite male skiers performed six 5-min sub-maximal exercise bouts at the same low, moderate and high metabolic rates on 2 and 8% inclines, while roller skiing on a treadmill employing the G3 skating technique. The work rate was calculated as work against gravity and friction, whereas the energetic equivalent of VO(2) was taken as the metabolic rate. Gross efficiency was defined as work rate divided by metabolic rate. Kinematic parameters were analyzed in three dimensions. At the same metabolic rate, the work rate, cycle rate, work per cycle and relative duration of propulsive phases during a cycle of movement were all higher on the 8% than on the 2% incline at all speeds (all P < 0.05). At similar work rates, gross efficiency was greater on the 8% incline (P < 0.05). In conclusion, these elite skiers consistently demonstrated higher work rates on the 8% incline. To achieve the higher work rates on the steeper incline, these elite skiers employed higher cycle rates and performed more work per cycle, in association with a longer relative propulsive phase.

A Review of the Contemporary International Literature on Student Retention in Higher Education

Directory of Open Access Journals (Sweden)

Othman Aljohani

2016-01-01

Full Text Available One of the major issues that concerns tertiary institutions around the world is the student retention rate. In general, higher rates of completion give more positive image about the academic, administrative and financial statues of these institutions. However, improving the student completion and retention rates can be a challenging task. One way toward this goal is utilising strategies and techniques that are informed by the findings of theoretical models and empirical studies. Therefore, this paper reviews some of the contemporary studies in the student retention literature from different higher educational contexts around the world followed by a list of the variables that are commonly linked to the student retention phenomenon in higher education and a discussion of the factors that are most frequently associated with student attrition as reported by these studies. A summary of the factors associated with the student attrition phenomenon suggested that, the central factors were the quality of students’ institutional experiences and their level of integration into the academic and social systems of their academic institutions. These factors relate to students’ experiences with the administrative system of their academic institution, including the admission, registration and disciplinary rules and policies and the availability and quality of student services and facilities. Keywords: Higher education, student retention, attrition, persistence

Trauma centers with higher rates of angiography have a lesser incidence of splenectomy in the management of blunt splenic injury.

Science.gov (United States)

Capecci, Louis M; Jeremitsky, Elan; Smith, R Stephen; Philp, Frances

2015-10-01

Nonoperative management (NOM) for blunt splenic injury (BSI) is well-established. Angiography (ANGIO) has been shown to improve success rates with NOM. Protocols for NOM are not standardized and vary widely between centers. We hypothesized that trauma centers that performed ANGIO at a greater rate would demonstrate decreased rates of splenectomy compared with trauma centers that used ANGIO less frequently. A large, multicenter, statewide database (Pennsylvania Trauma Systems Foundation) from 2007 to 2011 was used to generate the study cohort of patients with BSI (age ≥ 13). The cohort was divided into 2 populations based on admission to centers with high (≥13%) or low (Splenectomy rates were then compared between the 2 groups, and multivariable logistic regression for predictors of splenectomy (failed NOM) were also performed. The overall rate of splenectomy in the entire cohort was 21.0% (1,120 of 5,333 BSI patients). The high ANGIO group had a lesser rate of splenectoy compared with the low ANGIO group (19% vs 24%; P splenectomy compared with low ANGIO centers (odds ratio, 0.68; 95% CI 0.58-0.80; P splenectomy rates compared with centers with lesser rate of ANGIO. Inclusion of angiographic protocols for NOM of BSI should be considered strongly. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanics of arterial subfailure with increasing loading rate.

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Stemper, Brian D; Yoganandan, Narayan; Pintar, Frank A

2007-01-01

Arterial subfailure leads to delayed symptomatology and high morbidity and mortality rates, particularly for the thoracic aorta and carotid arteries. Although arterial injuries occur during high-velocity automotive collisions, previous studies of arterial subfailure focused on quasi-static loading. This investigation subjected aortic segments to increasing loading rates to quantify effects on elastic, subfailure, and ultimate vessel mechanics. Sixty-two specimens were axially distracted, and 92% demonstrated subfailure before ultimate failure. With increasing loading rate, stress at initial subfailure and ultimate failure significantly increased, and strain at initial subfailure and ultimate failure significantly decreased. Present results indicate increased susceptibility for arterial subfailure and/or dissection under higher-rate extension. According to the present results, automotive occupants are at greater risk of arterial injury under higher velocity impacts due to greater body segment motions in addition to decreased strain tolerance to subfailure and catastrophic failure.

Pentose pathway in human liver

International Nuclear Information System (INIS)

Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

1988-01-01

[1- 14 C]Ribose and [1- 14 C]glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of 14 C were determined in the carbons of the excreted glucoronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the 14 C from [1- 14 C]ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when [2- 14 C]glucose was given, 3.5-8.1% of the 14 C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

Directory of Open Access Journals (Sweden)

Mohamed eOuzzine

2014-10-01

Full Text Available UDP-glucuronosyltransferases (UGTs form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-Dglucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds by the linkage of glucuronic acid from the high energy donor, UDP-αD-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier. They are also associated to brain interfaces devoid of blood-brain barrier, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.

Increased traffic accident rates associated with shale gas drilling in Pennsylvania.

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Graham, Jove; Irving, Jennifer; Tang, Xiaoqin; Sellers, Stephen; Crisp, Joshua; Horwitz, Daniel; Muehlenbachs, Lucija; Krupnick, Alan; Carey, David

2015-01-01

We examined the association between shale gas drilling and motor vehicle accident rates in Pennsylvania. Using publicly available data on all reported vehicle crashes in Pennsylvania, we compared accident rates in counties with and without shale gas drilling, in periods with and without intermittent drilling (using data from 2005 to 2012). Counties with drilling were matched to non-drilling counties with similar population and traffic in the pre-drilling period. Heavily drilled counties in the north experienced 15-23% higher vehicle crash rates in 2010-2012 and 61-65% higher heavy truck crash rates in 2011-2012 than control counties. We estimated 5-23% increases in crash rates when comparing months with drilling and months without, but did not find significant effects on fatalities and major injury crashes. Heavily drilled counties in the southwest showed 45-47% higher rates of fatal and major injury crashes in 2012 than control counties, but monthly comparisons of drilling activity showed no significant differences associated with drilling. Vehicle accidents have measurably increased in conjunction with shale gas drilling. Copyright © 2014. Published by Elsevier Ltd.

Parental Cognitive Errors Mediate Parental Psychopathology and Ratings of Child Inattention.

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Haack, Lauren M; Jiang, Yuan; Delucchi, Kevin; Kaiser, Nina; McBurnett, Keith; Hinshaw, Stephen; Pfiffner, Linda

2017-09-01

We investigate the Depression-Distortion Hypothesis in a sample of 199 school-aged children with ADHD-Predominantly Inattentive presentation (ADHD-I) by examining relations and cross-sectional mediational pathways between parental characteristics (i.e., levels of parental depressive and ADHD symptoms) and parental ratings of child problem behavior (inattention, sluggish cognitive tempo, and functional impairment) via parental cognitive errors. Results demonstrated a positive association between parental factors and parental ratings of inattention, as well as a mediational pathway between parental depressive and ADHD symptoms and parental ratings of inattention via parental cognitive errors. Specifically, higher levels of parental depressive and ADHD symptoms predicted higher levels of cognitive errors, which in turn predicted higher parental ratings of inattention. Findings provide evidence for core tenets of the Depression-Distortion Hypothesis, which state that parents with high rates of psychopathology hold negative schemas for their child's behavior and subsequently, report their child's behavior as more severe. © 2016 Family Process Institute.

Contribution of Patient Characteristics to Differences in Readmission Rates

Science.gov (United States)

Barnett, Michael L.; Hsu, John; McWilliams, J. Michael

2016-01-01

Importance Medicare penalizes hospitals with higher than expected readmission rates by up to 3% of annual inpatient payments. Expected rates are adjusted only for patients’ age, sex, discharge diagnosis, and recent diagnoses. Objective To assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates. Design and Setting Using survey data from the nationally representative Health and Retirement Study (HRS) and linked Medicare claims, we assessed 29 patient characteristics from survey data and claims as potential predictors of 30-day readmission when added to standard Medicare adjustments of hospital readmission rates. We then compared the distribution of these characteristics between participants admitted to hospitals with higher vs. lower hospital-wide readmission rates reported by Medicare. Finally, we estimated differences in the probability of readmission between these groups of participants before vs. after adjusting for the additional patient characteristics. Participants HRS participants enrolled in Medicare who were hospitalized from 2009–2012 (n=8,067 admissions). Main Outcomes and Measures All-cause readmission within 30 days of discharge. Results Of the additional 29 patient characteristics assessed, 22 significantly predicted readmission beyond standard adjustments, and 17 of these were distributed differently between hospitals in the highest vs. lowest quintiles of publicly reported hospital-wide readmission rates (p≤0.04 for all). Almost all of these differences (16 of 17) indicated that participants admitted to hospitals in the highest quintile of readmission rates were more likely to have characteristics that were associated with a higher probability of readmission. The difference in the probability of readmission between participants admitted to hospitals in the highest vs. lowest quintile of hospital-wide readmission rates was reduced by 48% from 4.41 percentage points with