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Sample records for affect drug disposition

  1. FACTORS AFFECTING PHARMACOKINETIC DISPOSITION OF DRUGS

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    Mehta Hiren R

    2011-05-01

    Full Text Available Absorption of drugs from the gastrointestinal tract is a complex process the variability of which is influenced by many physicochemical and physiologic factors. The two most important physicochemical factors that affect both the extent and the rate of absorption are lipophilicity and solubility. The rate and extent of absorption are governed by the solubility, permeability and stability of the drug, with solubility being a pH-dependent parameter for weak acids and bases. The gastrointestinal tract can be viewed as discrete sections with a variety of differential local pH environments ranging from the acidic stomach to the more basic small intestine. The multiple peaking, double peaking or secondary peaking phenomena can occur in the disposition of a variety of xenobiotics during drug development (the pre-clinical phase and in subsequent clinical studies and use. The physicochemical and physiological mechanisms underlying the occurrence of this phenomenon are often multi factorial and include but are not limited to solubility-limited absorption, modified-release formulations, complexation, enterohepatic recirculation, gastric emptying and the intestinal transit time, site-specific absorption, gastric secretion-enteral reabsorption. Double peak absorption has been described with several orally administered drugs such as cimetidine furosemide, piroxicam, ranitidine, talinolol, alprazolam and phenazopyridine.

  2. Pathophysiological changes that affect drug disposition in protein-energy malnourished children

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    Oshikoya Kazeem A

    2009-12-01

    Full Text Available Abstract Protein-energy malnutrition (PEM is a major public health problem affecting a high proportion of infants and older children world-wide and accounts for a high childhood morbidity and mortality in the developing countries. The epidemiology of PEM has been extensively studied globally and management guidelines formulated by the World Health Organization (WHO. A wide spectrum of infections such as measles, malaria, acute respiratory tract infection, intestinal parasitosis, tuberculosis and HIV/AIDS may complicate PEM with two or more infections co-existing. Thus, numerous drugs may be required to treat the patients. In-spite of abundant literature on the epidemiology and management of PEM, focus on metabolism and therapeutic drug monitoring is lacking. A sound knowledge of pathophysiology of PEM and pharmacology of the drugs frequently used for their treatment is required for safe and rational treatment. In this review, we discuss the pathophysiological changes in children with PEM that may affect the disposition of drugs frequently used for their treatment. This review has established abnormal disposition of drugs in children with PEM that may require dosage modification. However, the relevance of these abnormalities to the clinical management of PEM remains inconclusive. At present, there are no good indications for drug dosage modification in PEM; but for drug safety purposes, further studies are required to accurately determine dosages of drugs frequently used for children with PEM.

  3. Dispositional affectivity and work outcomes of expatriates

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2013-01-01

    How the two components of dispositional affectivity, positive affectivity, representing the predisposition to respond positively to environmental stimuli, and negative affectivity, depicting the opposite reaction, influence work has been the focus of much research. Although dispositional affectiv......How the two components of dispositional affectivity, positive affectivity, representing the predisposition to respond positively to environmental stimuli, and negative affectivity, depicting the opposite reaction, influence work has been the focus of much research. Although dispositional...... affectivity appears to be a promising construct to explain and predict many attitudinal and behavioral outcomes in the workplace, few studies have empirically investigated dispositional affectivity and the work of expatriates. Hence, data from a net-based survey including 350 expatriates in Denmark were used...... to examine the relationship between dispositional affectivity and their work outcomes. Results showed consistent positive associations between positive affectivity and all the studied work outcomes and the opposite relationships for negative affectivity. Implications and suggestions for future...

  4. Effect of selected ABC-drug transporters and anticancer drug disposition in vitro and in vivo

    OpenAIRE

    Marchetti, S

    2013-01-01

    Studies described in the thesis that is lying in front of you aim to address the possible implications of selected ABC-drug transporters on the disposition of a number of important anticancer drugs. Although variability in drug disposition has been known for as long as pharmacological studies supported drug development and clinical therapeutics general molecular pharmacological concepts explaining the given interpatient variation in drug disposition have been lacking for many decades. Firm ex...

  5. Factors Affecting the Disposition Effect in Tehran Stock Market

    OpenAIRE

    Reza Tehrani; Niloofar Gharehkoolchian

    2012-01-01

    Given the significance and perceived inevitability of disposition effect and its impact on investment decisions, we investigate factors affecting the disposition effect in the Tehran Stock Exchange. Four hypotheses were developed and the data used in the study were collected through availability sampling. One-sample t-test, two-sample t-test and one-way ANOVA were run to analyze the data while Pearson correlation test and multiple regressions were used to assess relationships among variables ...

  6. Skin Disposition of Drugs after Topical Application in Hairless Rats

    OpenAIRE

    柳本, 剛; 林, 輝朗; 長谷川, 哲也; 関, 俊暢; 從二, 和彦; 杉林, 堅次; 森本, 雍憲

    1999-01-01

    Drug fraction transported from a topical formulation on skin to subsutaneous tissues or muscles is dependent on the physicochemical properties of the entrapped drug. Cutaneous disposition of model drugs, antipyrine(ANP), lidocaine (LC) and piroxicam (PXC) as well as flurbiprofen (FP) was thus evaluated in hairless rats in which an agar gel disc was subcutaneously inserted into abdominal region as a drug receptor and a drug donor cell was placed above it. Time courses of plasma level and agar ...

  7. Selection between Michaelis–Menten and target-mediated drug disposition pharmacokinetic models

    OpenAIRE

    Yan, Xiaoyu; Mager, Donald E.; Krzyzanski, Wojciech

    2009-01-01

    Target-mediated drug disposition (TMDD) models have been applied to describe the pharmacokinetics of drugs whose distribution and/or clearance are affected by its target due to high binding affinity and limited capacity. The Michaelis–Menten (M–M) model has also been frequently used to describe the pharmacokinetics of such drugs. The purpose of this study is to investigate conditions for equivalence between M–M and TMDD pharmacokinetic models and provide guidelines for selection between these...

  8. Transporters and drug-drug interactions: important determinants of drug disposition and effects.

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    König, Jörg; Müller, Fabian; Fromm, Martin F

    2013-07-01

    Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics. Available data on the impact of nutrition on transport processes as well as genotype-dependent, transporter-mediated drug-drug interactions will be discussed. We will also present and discuss data on the variable extent to which information on the impact of transporters on drug disposition is included in summaries of product characteristics of selected countries (SPCs). Further work is required regarding a better understanding of the role of the drug metabolism-drug transport interplay for drug-drug interactions and on the extrapolation of in vitro findings to the in vivo (human) situation. PMID:23686349

  9. The effect of grapefruit juice on drug disposition

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    Hanley, Michael J.; Cancalon, Paul; Widmer, Wilbur W.; Greenblatt, David J.

    2011-01-01

    Introduction Since their initial discovery in 1989, grapefruit juice-drug interactions have received extensive interest from the scientific, medical, regulatory, and lay communities. Although knowledge regarding the effects of grapefruit juice on drug disposition continues to expand, the list of drugs studied in the clinical setting remains relatively limited. Areas covered This article reviews the in vitro effects of grapefruit juice and its constituents on the activity of cytochrome P450 enzymes, organic anion-transporting polypeptides, P-glycoprotein, esterases and sulfotransferases. The translational applicability of the in vitro findings to the clinical setting is discussed for each drug metabolizing enzyme and transporter. Reported area under the plasma concentration-time curve ratios for available grapefruit juice-drug interaction studies are also provided. Relevant investigations were identified by searching the Pubmed electronic database from 1989 to 2010. Expert opinion Grapefruit juice increases the bioavailability of some orally-administered drugs that are metabolized by CYP3A and normally undergo extensive presystemic extraction. In addition, grapefruit juice can decrease the oral absorption of a few drugs that rely on organic anion-transporting polypeptides in the gastrointestinal tract for their uptake. The number of drugs shown to interact with grapefruit juice in vitro is far greater than the number of clinically relevant grapefruit juice-drug interactions. For the majority of patients, complete avoidance of grapefruit juice is unwarranted. PMID:21254874

  10. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele;

    2012-01-01

    penetration for a significant number of marketed central nervous system (CNS) agents. The Biopharmaceutics Drug Disposition Classification System (BDDCS) has proved useful in predicting drug disposition in the human body, particularly in the liver and intestine. Here we discuss the value of using BDDCS to...... improve BBB predictions of oral drugs. BDDCS class membership was integrated with in vitro Pgp efflux and in silico permeability data to create a simple 3-step classification tree that accurately predicted CNS disposition for more than 90% of 153 drugs in our data set. About 98% of BDDCS class 1 drugs...

  11. Job Satisfaction and Performance: The Moderating Effects of Value Attainment and Affective Disposition.

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    Hochwarter, Wayne A.; Perrewe, Pamela L.; Ferris, Gerald R.; Brymer, Robert A.

    1999-01-01

    A study of 270 hotel managers found that the strongest positive relationship between job satisfaction and performance occurred when high attainment of values associated with work was coupled with high-positive or low-negative affective disposition. (SK)

  12. Dispositional Happiness and Affective Forecasting about Academic Performance: General or Specific Effect?

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    Christophe, Virginie

    2014-01-01

    Recent findings suggest that dispositional traits can influence personal affective forecasting. In the present study, we investigated the relationship between dispositional happiness and affective prediction about academic performance among undergraduate students. Participants were asked to predict their emotional reactions on a 7-point Likert scale, ranging from 1 (very bad) to 7 (very good), two months before they will obtain their results for one examination. All the participants were cont...

  13. Tracing multiscale mechanisms of drug disposition in normal and diseased livers.

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    Park, Sunwoo; Kim, Sean H J; Ropella, Glen E P; Roberts, Michael S; Hunt, C Anthony

    2010-07-01

    Hepatic drug disposition is different in normal and diseased livers. Different disease types alter disposition differently. What are the responsible micromechanistic changes and how do they influence drug movement within the liver? We provide plausible, concrete answers for two compounds, diltiazem and sucrose, in normal livers and two different types of cirrhotic rat livers: chronic pretreatment of rats with carbon tetrachloride (CCl(4)) and alcohol caused different types of cirrhosis. We started with simulated disposition data from normal, multilevel, physiologically based, object-oriented, discrete event in silico livers (normal ISLs) that validated against diltiazem and sucrose disposition data from normal livers. We searched the parameter space of the mechanism and found three parameter vectors that enabled matching the three wet-lab data sets. They specified micromechanistic transformations that enabled converting the normal ISL into two different types of diseased ISLs. Disease caused lobular changes at three of six levels. The latter provided in silico disposition data that achieved a prespecified degree of validation against wet-lab data. The in silico transformations from normal to diseased ISLs stand as concrete theories for disease progression from the disposition perspective. We also developed and implemented methods to trace objects representing diltiazem and sucrose during disposition experiments. This allowed valuable insight into plausible disposition details in normal and diseased livers. We posit that changes in ISL micromechanistic details may have disease-causing counterparts. PMID:20406856

  14. Drug-drug interactions affecting fluoroquinolones.

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    Wijnands, G J; Vree, T B; Janssen, T J; Guelen, P J

    1989-12-29

    In a three-week study, the metabolism of the bronchodilator theophylline and its major metabolites formed by C-8 oxidation (1,3-dimethyluric acid) and N-demethylation (3-methylxanthine and 1-methyluric acid) was investigated in two healthy volunteers. Metabolic studies were performed following intravenous infusion of a single 6 mg/kg dose of aminophylline. During Week 1, theophylline was given alone (blank period), and during Weeks 2 and 3 it was given during oral coadministration of ofloxacin and enoxacin, respectively. Dosage of each quinolone was 200 mg twice daily for four days, starting three days prior to the theophylline infusion. During enoxacin coadministration, elimination half-lives of theophylline increased from 8.7 to 17.4 hours and from 6.1 to 12.3 hours, respectively. Total body clearance of theophylline decreased in both volunteers, whereas renal clearance did not alter. From this it was concluded that the decreased elimination results from a reduced metabolic clearance. During enoxacin coadministration, the formation of the metabolites 1-methyluric acid and 3-methylxanthine clearly was decreased, whereas the formation of 1,3-dimethyluric acid was less affected compared with the blank period. Interference with theophylline disposition by enoxacin is based predominantly on inhibition of microsomal N-demethylation. Ofloxacin comedication did not cause a change in the plasma parameters or renal excretion of theophylline and its metabolites compared with the blank period. PMID:2603893

  15. Regulation of Drug Disposition Gene Expression in Pregnant Mice with Car Receptor Activation

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    Amanda S. Bright

    2016-07-01

    Full Text Available More than half of pregnant women use prescription medications in order to maintain both maternal and fetal health. The constitutive androstane receptor (Car critically affects the disposition of chemicals by regulating the transcription of genes encoding metabolic enzymes and transporters. However, the effects of Car activation on chemical disposition during pregnancy are unclear. This study aims to determine the degree to which pregnancy alters the expression of drug metabolizing enzymes and transporters in response to the pharmacological activation of Car. To test this, pregnant C57BL/6 mice were administered IP doses of vehicle, or a potent Car agonist, TCPOBOP, on gestation days 14, 15 and 16. Hepatic mRNA and protein expression of Car target genes (phase I, II and transporters were quantified on gestation day 17. Pregnancy-related changes, such as induction of Cyp2b10, Ugt1a1 and Sult1a1 and repression of Ugt1a6, Gsta1, Gsta2 and Mrp6, were observed. Interestingly, the induction of Cyp2b10, Gsta1, Gsta2 and Mrp2–4 mRNAs by TCPOBOP was attenuated in maternal livers suggesting that Car activation is impeded by the biochemical and/or physiological changes that occur during gestation. Taken together, these findings suggest that pregnancy and pharmacological activation of Car can differentially regulate the expression of drug metabolism and transport genes.

  16. Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

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    Vyas, K P; Halpin, R A; Geer, L A; Ellis, J D; Liu, L; Cheng, H; Chavez-Eng, C; Matuszewski, B K; Varga, S L; Guiblin, A R; Rogers, J D

    2000-01-01

    The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%. PMID:10611145

  17. Factors Affecting the Disposition of Ivermectin in the Target Species

    OpenAIRE

    Laffont, Céline Marielle

    2003-01-01

    It was the aim of the thesis to contribute to the understanding of the diverse factors involved in the pharmacokinetics of ivermectin, a very potent antiparasitic drug widely used in both human and veterinary medicine. Ivermectin is extensively eliminated in faeces as parent drug and less active metabolites, irrespective of species and route of administration. It is currently believed that biliary secretion is the major route for the elimination of parent ivermectin from blood. However, using...

  18. Giving or Taking: The Role of Dispositional Power Motivation and Positive Affect in Profit Maximization?

    OpenAIRE

    Quirin, Markus; Beckenkamp, Martin; Kuhl, Julius

    2008-01-01

    Socio-economic decisions are commonly explained by rational cost vs. benefit considerations, whereas person variables have not usually been considered. The present study aims at investigating the degree to which dispositional power motivation and affective states predict socio-economic decisions. The power motive was assessed both indirectly and directly using a TAT-like picture test and a power motive self-report, respectively. After nine months, 62 students completed an affect rating and pe...

  19. Physiologically-based pharmacokinetic modeling of target-mediated drug disposition of bortezomib in mice.

    Science.gov (United States)

    Zhang, Li; Mager, Donald E

    2015-10-01

    Bortezomib is a reversible proteasome inhibitor with potent antineoplastic activity that exhibits dose- and time-dependent pharmacokinetics (PK). Proteasome-mediated bortezomib disposition is proposed as the primary source of its nonlinear and apparent nonstationary PK behavior. Single intravenous (IV) doses of bortezomib (0.25 and 1 mg/kg) were administrated to BALB/c mice, with blood and tissue samples obtained over 144 h, which were analyzed by LC/MS/MS. A physiologically based pharmacokinetic (PBPK) model incorporating tissue drug-target binding was developed to test the hypothesis of proteasome-mediated bortezomib disposition. The final model reasonably captured bortezomib plasma and tissue PK profiles, and parameters were estimated with good precision. The rank-order of model estimated tissue target density correlated well with experimentally measured proteasome concentrations reported in the literature, supporting the hypothesis that binding to proteasome influences bortezomib disposition. The PBPK model was further scaled-up to humans to assess the similarity of bortezomib disposition among species. Human plasma bortezomib PK profiles following multiple IV dosing (1.3 mg/m(2)) on days 1, 4, 8, and 11 were simulated by appropriately scaling estimated mouse parameters. Simulated and observed bortezomib concentrations after multiple dosing were in good agreement, suggesting target-mediated bortezomib disposition is likely for both mice and humans. Furthermore, the model predicts that renal impairment should exert minimal influence on bortezomib exposure in humans, confirming that bortezomib dose adjustment is not necessary for patients with renal impairment. PMID:26391023

  20. Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models.

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    Yan, Xiaoyu; Mager, Donald E; Krzyzanski, Wojciech

    2010-02-01

    Target-mediated drug disposition (TMDD) models have been applied to describe the pharmacokinetics of drugs whose distribution and/or clearance are affected by its target due to high binding affinity and limited capacity. The Michaelis-Menten (M-M) model has also been frequently used to describe the pharmacokinetics of such drugs. The purpose of this study is to investigate conditions for equivalence between M-M and TMDD pharmacokinetic models and provide guidelines for selection between these two approaches. Theoretical derivations were used to determine conditions under which M-M and TMDD pharmacokinetic models are equivalent. Computer simulations and model fitting were conducted to demonstrate these conditions. Typical M-M and TMDD profiles were simulated based on literature data for an anti-CD4 monoclonal antibody (TRX1) and phenytoin administered intravenously. Both models were fitted to data and goodness of fit criteria were evaluated for model selection. A case study of recombinant human erythropoietin was conducted to qualify results. A rapid binding TMDD model is equivalent to the M-M model if total target density R ( tot ) is constant, and R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 where K ( D ) represents the dissociation constant and C is the free drug concentration. Under these conditions, M-M parameters are defined as: V ( max ) = k ( int ) R ( tot ) V ( c ) and K ( m ) = K ( D ) where k ( int ) represents an internalization rate constant, and V ( c ) is the volume of the central compartment. R ( tot ) is constant if and only if k ( int ) = k ( deg,) where k ( deg ) is a degradation rate constant. If the TMDD model predictions are not sensitive to k ( int ) or k ( deg ) parameters, the condition of R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 alone can preserve the equivalence between rapid binding TMDD and M-M models. The model selection process for drugs that exhibit TMDD should involve a full mechanistic model as well as reduced models. The best model

  1. The In-Out dispositional affective style questionnaire (IN-OUT DASQ: an exploratory factorial analysis

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    Viridiana eMazzola

    2014-09-01

    Full Text Available The issue of individual differences has always been an important area of research in psychology and, more recently, neuroimaging. A major source of interindividual variability stems from differences in basic affective dispositions. In order to make a contribution to this field of research, we have developed a new type of assessment - the In-Out Dispositional Affective Style Questionnaire (IN-OUT DASQ - to measure the proneness between two different ways of feeling situated: a predominantly body-bound one in the case of the inward tendency and an externally anchored one in the case of the outward tendency (Arciero and Bondolfi, 2009. The IN-OUT DASQ contains 2 scales of 7 items each, Self-centric engagement (SCE and Other-centric engagement (OCE, as a disposition index for inwardness and outwardness respectively. The exploratory factor analysis in sample 1 (n= 292 confirmed a two-factor solution. Confirmatory factor analysis in sample 2 (n= 300 showed the good fit of this two-factor model. Next, we examined construct validity also investigating the correlations between the IN-OUT DASQ, the Big Five Questionnaire and the Positive and Negative Affect Schedule in sample 3 (n=153. The SCE and OCE scales had robust internal consistency and reliability, and therefore the capacity to discriminate higher inward and outward participants was stronger in SCE. Although further validation research is required, the present study suggests the IN-OUT DASQ has the potential to be a measurement tool for detecting individual differences in social behavior and social affective neuroscience.

  2. How Do Beta Blocker Drugs Affect Exercise?

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    ... Stroke More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  3. A mediational model of trait negative affectivity, dispositional thought suppression, and intrusive thoughts following laboratory stressors.

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    Lynch, Thomas R; Schneider, Kristin G; Rosenthal, M Zachary; Cheavens, Jennifer S

    2007-04-01

    Two studies examined the relationships among trait negative affectivity, dispositional thought suppression, and intrusions in non-clinical samples. In Study 1 (N=87), participants were presented with a series of emotionally evocative images and intrusions were examined 48 h after presentation via self-report. In Study 2 (N=118), intrusions were examined using a behavioral Key-press and self-report at two time points (5 and 20 min) following exposure to a series of emotionally evocative images. In each study, participants were assessed for trait negative affectivity and the tendency to engage in thought suppression in response to unpleasant cognitions. Results from both studies support a model in which chronic thought suppression fully mediates the relationship between negative affectivity and the frequency of intrusions. PMID:16934744

  4. Atomoxetine: A Review of Its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition.

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    Yu, Guo; Li, Guo-Fu; Markowitz, John S

    2016-05-01

    Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (≥6 years of age), adolescents, and adults. Its metabolism and disposition are fairly complex, and primarily governed by cytochrome P450 (CYP) 2D6 (CYP2D6), whose protein expression varies substantially from person to person, and by race and ethnicity because of genetic polymorphism. These differences can be substantial, resulting in 8-10-fold differences in atomoxetine exposure between CYP2D6 poor metabolizers and extensive metabolizers. In this review, we have attempted to revisit and analyze all published clinical pharmacokinetic data on atomoxetine inclusive of public access documents from the new drug application submitted to the United States Food and Drug Administration (FDA). The present review focuses on atomoxetine metabolism, disposition, and genetic polymorphisms of CYP2D6 as they specifically relate to atomoxetine, and provides an in-depth discussion of the fundamental pharmacokinetics of the drug including its absorption, distribution, metabolism, and excretion in pediatric and adult populations. Further, a summary of relationships between genetic variants of CYP2D6 and to some degree, CYP2C19, are provided with respect to atomoxetine plasma concentrations, central nervous system (CNS) pharmacokinetics, and associated clinical implications for pharmacotherapy. Lastly, dosage adjustments based on pharmacokinetic principles are discussed. PMID:26859445

  5. Anger, Anxiety, and Depression as Risk Factors for Cardiovascular Disease: The Problems and Implications of Overlapping Affective Dispositions

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    Sul, Jerry; Bunde, James

    2005-01-01

    Several recent reviews (e.g., L. C. Gallo & K. Matthews, 2003; A. Rozanski, J. A. Blumenthal, & J. Kaplan, 1999; R. Rugulies, 2002) have identified 3 affective dispositions--depression, anxiety, and anger-hostility--as putative risk factors for coronary heart disease. There are, however, mixed and negative results. Following a critical summary of…

  6. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.

    Science.gov (United States)

    Park, Soo-Jin; Yeo, Chang-Woo; Shim, Eon-Jeong; Kim, Hyunmi; Liu, Kwang-Hyeon; Shin, Jae-Gook; Shon, Ji-Hong

    2016-08-01

    Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects. The subjects took pomegranate or grapefruit juice three times per day for 3 days (900 mL/day) and on the third day, the pharmacokinetic study was executed. Blood samples were collected to 24 h post-dose and the pharmacokinetic parameters of simvastatin and simvastatin acid were compared among the study periods. In the period of grapefruit juice, the mean C max and AUCinf of simvastatin [the geometric mean ratio (90 % CI) 15.6 (11.6-21.0) and 9.1 (6.0-13.7)] were increased significantly when compared with the control period, whereas they were not significantly different in the period of pomegranate juice [C max and AUCinf 1.20 (0.89-1.62) and 1.29 (0.85-1.94)]. The mean C max and AUCinf of simvastatin acid were increased significantly after intake of grapefruit juice, but not pomegranate juice. These results suggest that pomegranate juice affects little on the disposition of simvastatin in humans. Pomegranate juice does not seem to have a clinically relevant inhibitory potential on CYP3A4 activity. PMID:25720525

  7. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications.

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    Tomson, Torbjörn; Landmark, Cecilie Johannessen; Battino, Dina

    2013-03-01

    Pregnancy is a state where pharmacokinetic changes are more pronounced and more rapid than during any other period of life. The consequences of such changes can be far reaching, not least in the management of epilepsy where the risks with uncontrolled seizures during pregnancy need to be balanced against potential teratogenic effects of antiepileptic drugs (AEDs). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AEDs and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AEDs at any level from absorption, distribution, metabolism, to elimination. The effect varies depending on the type of AED. The most pronounced decline in serum concentrations is seen for AEDs that are eliminated by glucuronidation (UGT), in particular lamotrigine where the effect may be profound. Serum concentrations of AEDs that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AEDs, such as carbamazepine seem to be affected only marginally by pregnancy. Data on pharmacokinetics during pregnancy are lacking completely for some of the newer generation AEDs: pregabalin, lacosamide, retigabine, and eslicarbazepine acetate. Where data are available, the effects of pregnancy on serum concentrations seem to vary considerably individually and are thus difficult to predict. Although large-scale systematic studies of the clinical relevance of the pharmacokinetic alterations are lacking, prospective and retrospective case series have reported an association between declining serum concentrations and deterioration in seizures control. The usefulness of routine monitoring of AED serum concentrations in pregnancy and of dose adjustments based on falling levels, are discussed in this review. We suggest that monitoring could be important, in particular when women have been titrated to the lowest effective AED

  8. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms

    Science.gov (United States)

    2013-01-01

    Synopsis Although it is widely appreciated that cats respond differently to certain drugs when compared with other companion animal species, the causes of these differences are poorly understood. This review critically evaluates published evidence for altered drug effects in cats, focusing on pharmacokinetic differences between cats, dogs and humans, and the molecular mechanisms underlying these differences. Pharmacokinetic studies indicate that acetaminophen, propofol, carprofen, and acetylsalicylic acid (aspirin) are cleared significantly more slowly in cats versus dogs and humans. All of these drugs are metabolized by conjugation. Cats lack the major phenol UDP-glucuronosyltransferase (UGT) enzymes, including UGT1A6 and UGT1A9, that glucuronidate acetaminophen and propofol. Deficient glucuronidation may also explain slower carprofen clearance, although there is no direct evidence for this. However, poor aspirin clearance in cats appears to be mainly a consequence of slower glycine conjugation. Cats are also deficient in several other conjugation enzymes, including N-acetyltransferase (NAT) 2 and thiopurine methyltransferase (TMPT). NAT2 deficiency may be the reason cats are more prone to developing methemoglobinemia rather than hepatotoxicity from acetaminophen. TMPT deficiency may predispose cats to azathioprine toxicity. No evidence was found for slower elimination of drugs cleared by oxidation or unchanged into urine or bile. Piroxicam, an oxidized drug, was cleared much more rapidly in cats than humans and dogs, although the mechanism for this difference is unclear. More work is needed to better understand drug metabolism and disposition differences in cats, thereby enabling more rational prescribing of existing medications, and the development of safer drugs for this species. PMID:23890237

  9. Variable Isoflavone Contents of Red Clover Products Affect Intestinal Disposition of Biochanin A, Formononetin, Genistein and Daidzein

    OpenAIRE

    Wang, Stephen W. J.; Chen, Yan; Joseph, Tiby; Ming HU

    2008-01-01

    Marketed red clover products use a wide variety of labels and the isoflavone contents from the lable is ambiguous. In the present study, we analyzed the content of various isoflavone products, and determined a) the content and b) how sample matrix of red clover products affects intestinal disposition of main isoflavones within it using the human intestinal Caco-2 cell model. Analysis using high and ultra-performance liquid chromatography indicates that the isoflavone content varied significan...

  10. HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition.

    Science.gov (United States)

    Kis, Olena; Sankaran-Walters, Sumathi; Hoque, M Tozammel; Walmsley, Sharon L; Dandekar, Satya; Bendayan, Reina

    2016-05-01

    This study investigated the effects of HIV-1 infection and antiretroviral therapy (ART) on the expression of intestinal drug efflux transporters, i.e., P-glycoprotein (Pgp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), and metabolic enzymes, such as cytochrome P450s (CYPs), in the human upper intestinal tract. Intestinal biopsy specimens were obtained from HIV-negative healthy volunteers, ART-naive HIV-positive (HIV(+)) subjects, and HIV(+) subjects receiving ART (10 in each group). Intestinal tissue expression of drug transporters and metabolic enzymes was examined by microarray, real-time quantitative reverse transcription-PCR (qPCR), and immunohistochemistry analyses. Microarray analysis demonstrated significantly lower expression of CYP3A4 and ABCC2/MRP2 in the HIV(+) ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV(+) naive group than in the control group and was partially restored to baseline levels in HIV(+) subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV(+) subjects on ART relative to HIV(+) ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV(+) subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV(+) subjects. This has clinical implications when using data from healthy volunteers to guide ART. PMID:26902756

  11. Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

    International Nuclear Information System (INIS)

    Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of 3H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen

  12. The impact of Organic Anion-Transporting Polypeptides (OATPs) on disposition and toxicity of antitumor drugs: Insights from knockout and humanized mice.

    Science.gov (United States)

    Durmus, Selvi; van Hoppe, Stéphanie; Schinkel, Alfred H

    2016-07-01

    It is now widely accepted that organic anion-transporting polypeptides (OATPs), especially members of the OATP1A/1B family, can have a major impact on the disposition and elimination of a variety of endogenous molecules and drugs. Owing to their prominent expression in the sinusoidal plasma membrane of hepatocytes, OATP1B1 and OATP1B3 play key roles in the hepatic uptake and plasma clearance of a multitude of structurally diverse anti-cancer and other drugs. Here, we present a thorough assessment of the currently available OATP1A and OATP1B knockout and transgenic mouse models as key tools to study OATP functions in vivo. We discuss recent studies using these models demonstrating the importance of OATPs, primarily in the plasma and hepatic clearance of anticancer drugs such as taxanes, irinotecan/SN-38, methotrexate, doxorubicin, and platinum compounds. We further discuss recent work on OATP-mediated drug-drug interactions in these mouse models, as well as on the role of OATP1A/1B proteins in the phenomenon of hepatocyte hopping, an efficient and flexible way of liver detoxification for both endogenous and exogenous substrates. Interestingly, glucuronide conjugates of both the heme breakdown product bilirubin and the protein tyrosine kinase-targeted anticancer drug sorafenib are strongly affected by this process. The clinical relevance of variation in OATP1A/1B activity in patients has been previously revealed by the effects of polymorphic variants and drug-drug interactions on drug toxicity. The development of in vivo tools to study OATP1A/1B functions has greatly advanced our mechanistic understanding of their functional role in drug pharmacokinetics, and their implications for therapeutic efficacy and toxic side effects of anticancer and other drug treatments. PMID:27449599

  13. Evacetrapib: in vitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors

    OpenAIRE

    Cannady, Ellen A.; Wang, Ming-Dauh; Friedrich, Stuart; Rehmel, Jessica L F; Yi, Ping; Small, David S; ZHANG Wei; Suico, Jeffrey G.

    2015-01-01

    Evacetrapib is an investigational cholesteryl ester transfer protein inhibitor (CETPi) for reduction of risk of major adverse cardiovascular events in patients with high-risk vascular disease. Understanding evacetrapib disposition, metabolism, and the potential for drug–drug interactions (DDI) may help guide prescribing recommendations. In vitro, evacetrapib metabolism was investigated with a panel of human recombinant cytochromes P450 (CYP). The disposition, metabolism, and excretion of evac...

  14. Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations

    OpenAIRE

    Gesquiere, Ina; Darwich, Adam S; Van der Schueren, Bart; de Hoon, Jan; Lannoo, Matthias; Matthys, Christophe; Rostami, Amin; Foulon, Veerle; Augustijns, Patrick

    2015-01-01

    The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB.

  15. Consequences of CYP2D6 polymorphism for the disposition and dynamics of tolterodine : a novel drug in the treatment of urinary bladder overactivity

    OpenAIRE

    Brynne, Niclas

    1998-01-01

    The pharmacokinetics and pharmacological effects of tolterodine were studied in man following administration of increasing oral and intravenous single-doses. The influence of metabolic phenotype in extensive and poor metabolizers of debrisoquine was determined. The effect of tolterodine on the major drug metabolizing cytochrome P450 (CYP) isozymes 1A2, 2C19, 2D6 and 3A4 was studied in vivo by measurements of metabolic ratios of probe drugs. Changes in tolterodine disposition...

  16. Affective Dispositions and PTSD Symptom Clusters in Female Interpersonal Trauma Survivors.

    Science.gov (United States)

    Brown, Wilson J; Bruce, Steven E; Buchholz, Katherine R; Artime, Tiffany M; Hu, Emily; Sheline, Yvette I

    2016-02-01

    Interpersonal trauma (IPT) against women can have dire psychological consequences including persistent maladaptive changes in the subjective experience of affect. Contemporary literature has firmly established heightened negative affect (NA) as a risk and maintenance factor for posttraumatic stress disorder (PTSD). However, the relationship between NA and PTSD symptoms is not well understood within IPT survivors, the majority of whom are female, as much of this research has focused on combat veterans. In addition, the connection between positive affect (PA) and PTSD symptoms has yet to be examined. With increased emphasis on "negative alterations in cognitions and mood . . ." as an independent symptom cluster of PTSD in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5), understanding the relationship between self-reported affectivity and the classic PTSD symptom clusters may be increasingly useful in differentiating symptom presentations of trauma-related psychopathology. The current study directly compared self-reported trait NA and PA with total severity and frequency cluster scores from the Clinician-Administered PTSD Scale (CAPS) in 54 female survivors of IPT who met criteria for PTSD. Results identify NA (but not PA) as a consistent predictor of total PTSD symptoms and, specifically, re-experiencing symptoms. PMID:25389192

  17. Effects of Uremic Toxins on Transport and Metabolism of Different Biopharmaceutics Drug Disposition Classification System (BDDCS) Xenobiotics

    OpenAIRE

    Reyes, Maribel; Benet, Leslie Z.

    2011-01-01

    Chronic kidney disease (CKD) is recognized to cause pharmacokinetic changes in renally excreted drugs; however, pharmacokinetic changes are also reported for drugs that are non-renally eliminated. Few studies have investigated how uremic toxins may affect drug transporters and metabolizing enzymes and how these may result in pharmacokinetic/metabolic changes in CKD. Here, we investigated the effects of uremic toxins and human uremic serum on the transport of the prototypical transporter subst...

  18. Contrasting roles for lateral and ventromedial prefrontal cortex in transient and dispositional affective experience

    OpenAIRE

    Gillihan, Seth J.; Xia, Chenjie; Padon, Alisa A.; Heberlein, Andrea S.; Farah, Martha J.; Lesley K Fellows

    2010-01-01

    Prefrontal cortex (PFC) has been implicated in the experience and regulation of emotional states. Emotional experience is a complex construct, encompassing a range of more specific processes. This exploratory study aimed to delineate which (if any) aspects of emotional experience rely critically on either the ventromedial frontal (VMF) or lateral frontal (LF) lobes. The affective experience of individuals with damage to these regions was surveyed in detail using several measures and compared ...

  19. Relations Between Dispositional Expressivity and Physiological Changes During Acute Positive and Negative Affect

    Directory of Open Access Journals (Sweden)

    Asmir Gračanin

    2007-12-01

    Full Text Available The aim of the present study is to examine the relations between emotional expressivity measured by Berkeley Expressivity Questionnaire and physiological response in situations where positive and negative affects were induced. On 65 participants four physiological parameters, including finger pulse amplitude, heart rate, skin conductance level and amplitude of skin conductance response were measured. In situations in which negative affect was induced, individuals higher in negative expressivity showed higher skin conductance level, higher amplitude of skin conductance response and higher heart rate compared to individuals low on negative expressivity, whereas finger pulse amplitude did not differ between these two groups. The same results were obtained even when controlling for five factor personality traits and recorded participants’ facial expression. In situation where a positive affect was induced, no differences in sympathetic responses between participants high and low in positive expressivity have been found. The results are explained in the context of Coactivation theory and possible consequences of the results on health outcomes are discussed.

  20. Factors That Affect Adolescent Drug Users' Suicide Attempts

    Science.gov (United States)

    Song, Hokwang

    2016-01-01

    Drug abuse has been widely linked to suicide risk. We examined the factors that affect adolescent drug users' suicide attempts in South Korea. This study analyzed the data of 311 adolescents who had used drugs such as inhalants, psychotropic drugs, and marijuana (195 males and 116 females). Among 311 subjects, 109 (35.0%) had attempted suicide during the last 12 months. After adjusting for other variables, depressive mood (OR=19.79) and poly-drug use (OR=2.79), and low/middle levels of academic achievement compared with a high level (OR=3.72 and 4.38) were independently associated with increased odds of a suicide attempt, while better perceived health (OR=0.32) was independently associated with reduced odds of a suicide attempt. For adolescent drug users, preventive work should be directed toward the active treatment of drug use, depression, and physical health and reinforcing proper coping strategies for academic and other stress. PMID:27247604

  1. Factors That Affect Adolescent Drug Users' Suicide Attempts.

    Science.gov (United States)

    Park, Subin; Song, Hokwang

    2016-05-01

    Drug abuse has been widely linked to suicide risk. We examined the factors that affect adolescent drug users' suicide attempts in South Korea. This study analyzed the data of 311 adolescents who had used drugs such as inhalants, psychotropic drugs, and marijuana (195 males and 116 females). Among 311 subjects, 109 (35.0%) had attempted suicide during the last 12 months. After adjusting for other variables, depressive mood (OR=19.79) and poly-drug use (OR=2.79), and low/middle levels of academic achievement compared with a high level (OR=3.72 and 4.38) were independently associated with increased odds of a suicide attempt, while better perceived health (OR=0.32) was independently associated with reduced odds of a suicide attempt. For adolescent drug users, preventive work should be directed toward the active treatment of drug use, depression, and physical health and reinforcing proper coping strategies for academic and other stress. PMID:27247604

  2. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms

    OpenAIRE

    Court, Michael H.

    2013-01-01

    Although it is widely appreciated that cats respond differently to certain drugs when compared with other companion animal species, the causes of these differences are poorly understood. This review critically evaluates published evidence for altered drug effects in cats, focusing on pharmacokinetic differences between cats, dogs and humans, and the molecular mechanisms underlying these differences. Pharmacokinetic studies indicate that acetaminophen, propofol, carprofen, and acetylsalicylic ...

  3. A Hybrid Methacrylate-Sodium Carboxymethylcellulose Interpolyelectrolyte Complex: Rheometry and in Silico Disposition for Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Viness Pillay

    2013-09-01

    Full Text Available The rheological behavioral changes that occurred during the synthesis of an interpolyelectrolyte complex (IPEC of methacrylate copolymer and sodium carboxymethylcellulose were assessed. These changes were compared with the rheological behavior of the individual polymers employing basic viscosity, yield stress, stress sweep, frequency sweep, temperature ramp as well as creep and recovery testing. The rheological studies demonstrated that the end-product of the complexation of low viscous methacrylate copolymer and entangled solution of sodium carboxymethylcellulose generated a polymer, which exhibited a solid-like behavior with a three-dimensional network. Additionally, the rheological profile of the sodium carboxymethylcellulose and methacrylate copolymer with respect to the effect of various concentrations of acetic acid on the synthesis of the IPEC was elucidated using molecular mechanics energy relationships (MMER by exploring the spatial disposition of carboxymethylcellulose and methacrylate copolymer with respect to each other and acetic acid. The computational results corroborated well with the experimental in vitro drug release data. Results have shown that the IPEC may be suitable polymeric material for achieving controlled zero-order drug delivery.

  4. Dispositional logic

    Science.gov (United States)

    Le Balleur, J. C.

    1988-01-01

    The applicability of conventional mathematical analysis (based on the combination of two-valued logic and probability theory) to problems in which human judgment, perception, or emotions play significant roles is considered theoretically. It is shown that dispositional logic, a branch of fuzzy logic, has particular relevance to the common-sense reasoning typical of human decision-making. The concepts of dispositionality and usuality are defined analytically, and a dispositional conjunctive rule and dispositional modus ponens are derived.

  5. Optimized Hepatocyte-Like Cells with Functional Drug Transporters Directly-Reprogrammed from Mouse Fibroblasts and their Potential in Drug Disposition and Toxicology

    Directory of Open Access Journals (Sweden)

    Zhi-Tao Wu

    2016-05-01

    Full Text Available Background/Aims: To develop a suitable hepatocyte-like cell model that could be a substitute for primary hepatocytes with essential transporter expression and functions. Induced hepatocyte-like (iHep cells directly reprogrammed from mice fibroblast cells were fully characterized. Methods: Naïve iHep cells were transfected with nuclear hepatocyte factor 4 alpha (Hnf4α and treated with selected small molecules. Sandwich cultured configuration was applied. The mRNA and protein expression of transporters were determined by Real Time PCR and confocal. The functional transporters were estimated by drug biliary excretion measurement. The inhibition of bile acid efflux transporters by cholestatic drugs were assessed. Results: The expression and function of p-glycoprotein (P-gp, bile salt efflux pump (Bsep, multidrug resistance-associated protein 2 (Mrp2, Na+-dependent taurocholate cotransporting polypeptide (Ntcp, and organic anion transporter polypedtides (Oatps in iHep cells were significantly improved after transfection of hepatocyte nuclear factor 4 alpha (Hnf4α and treatment with selected inducers. In vitro intrinsic biliary clearances (CLb,int of optimized iHep cells for rosuvastatin, methotrexate, d8-TCA (deuterium-labeled sodium taurocholate acid and DPDPE ([D-Pen2,5] enkephalin hydrate correlated well with that of sandwich-cultured primary mouse hepatocytes (SCMHs (r2 = 0.984. Cholestatic drugs were evaluated and the results were compared well with primary mice hepatocytes. Conclusion: The optimized iHep cells expressed functional drug transporters and were comparable to primary mice hepatocytes. This study suggested direct reprogramming could provide a potential alternative to primary hepatocytes for drug candidate hepatobiliary disposition and hepatotoxicity screening.

  6. Disruption of BSEP Function in HepaRG Cells Alters Bile Acid Disposition and Is a Susceptive Factor to Drug-Induced Cholestatic Injury.

    Science.gov (United States)

    Qiu, Xi; Zhang, Yueping; Liu, Tongtong; Shen, Hong; Xiao, Yongling; Bourner, Maureen J; Pratt, Jennifer R; Thompson, David C; Marathe, Punit; Humphreys, W Griffith; Lai, Yurong

    2016-04-01

    In the present study, we characterized in vitro biosynthesis and disposition of bile acids (BAs) as well as hepatic transporter expression followed by ABCB11 (BSEP) gene knockout in HepaRG cells (HepaRG-KO cells). BSEP KO in HepaRG cells led to time-dependent BA accumulation, resulting in reduced biosynthesis of BAs and altered BA disposition. In HepaRG-KO cells, the expression of NTCP, OATP1B1, OATP2B1, BCRP, P-gp, and MRP2 were reduced, whereas MRP3 and OCT1 were up-regulated. As a result, BSEP KO altered the disposition of BAs and subsequently underwent adaptive regulations of BA synthesis and homeostasis to enable healthy growth of the cells. Although BSEP inhibitors caused no or slight increase of BAs in HepaRG wild type cells (HepaRG-WT cells), excessive intracellular accumulation of BAs was observed in HepaRG-KO cells exposed to bosentan and troglitazone, but not dipyridamole. LDH release in the medium was remarkably increased in HepaRG-KO cultures exposed to troglitazone (50 μM), suggesting drug-induced cellular injury. The results revealed that functional impairment of BSEP predisposes the cells to altered BA disposition and is a susceptive factor to drug-induced cholestatic injury. In total, BSEP inhibition might trigger the processes but is not a sole determinant of cholestatic cellular injury. As intracellular BA accumulation is determined by BSEP function and the subsequent adaptive gene regulation, assessment of intracellular BA accumulation in HepaRG-KO cells could be a useful approach to evaluate drug-induced liver injury (DILI) potentials of drugs that could disrupt other BA homeostasis pathways beyond BSEP inhibition. PMID:26910619

  7. Modeling and Simulation of Intracellular Drug Transport and Disposition Pathways with Virtual Cell

    OpenAIRE

    Baik, Jason; Rosania, Gus R.

    2013-01-01

    The development of computational approaches for modeling the spatiotemporal dynamics of intracellular, small molecule drug concentrations has become an increasingly important area of pharmaceutical research. For systems pharmacology, the system dynamics of subcellular transport can be coupled to downstream pharmacological effects on biochemical pathways that impact cell structure and function. Here, we demonstrate how a widely used systems biology modeling package – Virtual Cell – can also be...

  8. Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

    Directory of Open Access Journals (Sweden)

    Jane Alcorn

    2010-10-01

    Full Text Available Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20. Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

  9. In vitro and in vivo drug disposition of cilengitide in animals and human

    OpenAIRE

    Dolgos, Hugues; Freisleben, Achim; Wimmer, Elmar; Scheible, Holger; Krätzer, Friedrich; Yamagata, Tetsuo; Gallemann, Dieter; Fluck, Markus

    2016-01-01

    Abstract Cilengitide is very low permeable (1.0 nm/sec) stable cyclic pentapeptide containing an Arg‐Gly‐Asp motif responsible for selective binding to αvβ3 and αvβ5 integrins administered intravenously (i.v.). In vivo studies in the mouse and Cynomolgus monkeys showed the major component in plasma was unchanged drug (>85%). These results, together with the absence of metabolism in vitro and in animals, indicate minimal metabolism in both species. The excretion of [14C]‐cilengitide showed pro...

  10. Development of stereoselective analytical methods of chiral drugs and biological substances and application of hepatic local drug disposition; Yakubutsu oyobi biryo seiri kassei busshitsu no rittai sentakuteki bunri bunsekiho no kaihatsu to kanzo kyokusho dotai kaiseki eno oyo

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, T. [Kyoto University, Kyoto (Japan). Faculty of Engineering

    1994-12-15

    With an objective to elucidate the structure recognizing ability possessed by living organisms, discussions were given on methods to analyze the bonds between optically active drugs and polymers, and methods to analyze drug disposition fluid-dynamically. Studies have been advanced on the following themes, and the results were obtained therefrom: development of an on-line system to quantify non-protein bonding type concentrations in drugs utilizing the high-performance fraction analysis (HPFA, using a restricted movement type HPLC column) that had been already developed, establishment of a method to analyze hepatic local drug disposition by using the MULTI (drug disposition analyzing) program, and studies on stereoselectivity by using NMR generated by interactions of local anesthetics and lipids. The following findings were obtained: using the above on-line system, a discussion was given on protein bonds between BOF-4272 (xanthine oxidase inhibitor) and serum albumins, and the discussion was found effective in analyzing the stereoselectivity in drugs with strong protein bond; and with the above analytic method, optical behavior of ketoprofen (KP) in rat liver perfusion was discussed, wherein the transfer of KP into liver tissues was estimated to have been caused by involvement of active transportation rather than physical diffusion. 7 refs., 6 figs., 4 tabs.

  11. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    International Nuclear Information System (INIS)

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)

  12. Fulvestrant up regulates UGT1A4 and MRPs through ERα and c-Myb pathways: a possible primary drug disposition mechanism.

    Science.gov (United States)

    Edavana, Vineetha K; Penney, Rosalind B; Yao-Borengasser, Aiwei; Williams, Suzanne; Rogers, Lora; Dhakal, Ishwori B; Kadlubar, Susan

    2013-01-01

    Fulvestrant (Faslodex™) is a pure antiestrogen that is effective in treating estrogen receptor-(ER) positive breast cancer tumors that are resistant to selective estrogen receptor modulators such as tamoxifen. Clinical trials investigating the utility of adding fulvestrant to other therapeutics have not been shown to affect cytochrome P450-mediated metabolism. Effects on phase II metabolism and drug resistance have not been explored. This study demonstrates that fulvestrant up regulates the expression of UDP glucuronosyltransferase 1A4 (UGT1A4) >2.5- and >3.5-fold in MCF7 and HepG2 cells, respectively. Up regulation occurred in a time- and concentration-dependent manner, and was inhibited by siRNA silencing of ERα. Fulvestrant also up regulates multidrug resistance-associated proteins (MRPs). There was an up regulation of MRP2 (1.5- and 3.5-fold), and MRP3 (5.5- and 4.5-fold) in MCF7 and HepG2 cell lines, respectively, and an up regulation of MRP1 (4-fold) in MCF7 cells. UGT1A4 mRNA up regulation was significantly correlated with UGT1A4 protein expression, anastrozole glucuronidation, ERα mRNA expression and MRP mRNA expression, but not with ERα protein expression. Genetic variants in the UGT1A4 promoter (-163A, -217G and -219T) reduced the basal activity of UGT1A4 by 40-60%. In silico analysis indicated that transcription factor c-Myb binding capacity may be affected by these variations. Luciferase activity assays demonstrate that silencing c-Myb abolished UGT1A4 up regulation by fulvestrant in promoters with the common genotype (-163G, -217 T and -219C) in MCF7 cells. These data indicate that fulvestrant can influence the disposition of other UGT1A4 substrates. These findings suggest a clinically significant role for UGT1A4 and MRPs in drug efficacy. PMID:24298433

  13. Foucaults Dispositive

    DEFF Research Database (Denmark)

    Raffnsøe, Sverre; Gudmand-Høyer, Marius T.; Thaning, Morten Sørensen

    2016-01-01

    While Foucault’s work has had a crucial impact on organizational research, the analytical potential of the dispositive has not been sufficiently developed. The purpose of this article is to reconstruct the notion of the dispositive as a key conception in Foucault’s thought, particularly in his le...

  14. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  15. Adverse affects of drugs on saliva and salivary glands

    Directory of Open Access Journals (Sweden)

    Vidhi Vinayak

    2013-01-01

    Full Text Available Saliva is the most valuable oral fluid is critical to the preservation and management of oral health. Saliva containing various organic and inorganic substances provides primary natural protection for teeth and soft tissues in the oral cavity assists in mastication, deglutition and digestion of food. The secretion of saliva can be affected due to various local and systemic causes. However if a patient is taking medication and has altered salivary secretion the differential diagnosis should include the possibility of an adverse drug reaction. The drugs may lead to alteration in the flow rate of saliva, which can be either increased or reduced, however certain drugs have been reported to cause change in the color of the saliva. Several drugs may lead to sialadenitis associated with altered salivary secretion. These symptoms may simulate systemic diseases, Hence oral physicians need to be vigilant in recognizing these adverse drug reactions in the patients and it is incumbent upon the practitioner to try to stay abreast of this ever evolving field especially as it relates to dental therapeutics.

  16. A physiologically based pharmacokinetic model to predict disposition of CYP2D6 and CYP1A2 metabolized drugs in pregnant women.

    Science.gov (United States)

    Ke, Alice Ban; Nallani, Srikanth C; Zhao, Ping; Rostami-Hodjegan, Amin; Isoherranen, Nina; Unadkat, Jashvant D

    2013-04-01

    Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age-dependent changes in maternal physiology and hepatic CYP3A activity. For verification, the disposition of CYP1A2-metabolized drug theophylline (THEO) and CYP2D6-metabolized drugs paroxetine (PAR), dextromethorphan (DEX), and clonidine (CLO) during pregnancy was predicted. Our PBPK model successfully predicted THEO disposition during the third trimester (T3). Predicted mean postpartum to third trimester (PP:T3) ratios of THEO area under the curve (AUC), maximum plasma concentration, and minimum plasma concentration were 0.76, 0.95, and 0.66 versus observed values 0.75, 0.89, and 0.72, respectively. The predicted mean PAR steady-state plasma concentration (Css) ratio (PP:T3) was 7.1 versus the observed value 3.7. Predicted mean DEX urinary ratio (UR) (PP:T3) was 2.9 versus the observed value 1.9. Predicted mean CLO AUC ratio (PP:T3) was 2.2 versus the observed value 1.7. Sensitivity analysis suggested that a 100% induction of CYP2D6 during T3 was required to recover the observed PP:T3 ratios of PAR Css, DEX UR, and CLO AUC. Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy. PMID:23355638

  17. Analysis program based on finite element method, MULTI(FEM), for evaluation of dose-dependent local disposition of drug in liver.

    Science.gov (United States)

    Fukumura, K; Yamaoka, K; Higashimori, M; Nakagawa, T

    1999-05-01

    A curve-fitting program based on the Finite Element Method, MULTI(FEM), was developed to model nonlinear local disposition of a drug in the liver under non-steady-state conditions. The program was written in FORTRAN on an IBM-compatible personal computer. The validity of MULTI(FEM) was confirmed by analyzing the outflow kinetics of oxacillin (a model drug) following a pulse input to isolated, perfused rat livers, according to both linear and nonlinear dispersion models. Four dose levels (300, 1000, 3000, and 5000 microg) of oxacillin were administered to observe the dose-dependency in the hepatic local disposition. First, the individual outflow time-profiles at the same dose were averaged, and the average time-profile was analyzed by MULTI(FEM) based on linear dispersion models to yield a single curve fit. The fitted parameters at each dose level were compared with parameters estimated using MULTI(FILT), a program based on fast inverse Laplace transform, to analyze linear pharmacokinetics. The estimated parameters by MULTI(FEM) were in good agreement with those by MULTI(FILT). The apparent elimination rate constant (ke) decreased with an increase in dose, whereas other parameters showed no discernible dependency on an increase of dose. Second, the average outflow time-profiles at the four dose levels were simultaneously analyzed by MULTI(FEM) based on dispersion models featuring Michaelis-Menten elimination. The outflow time-profiles of oxacillin were well approximated by a two-compartment dispersion model with central Michaelis-Menten elimination. The maximum elimination rate constant (Vmax) and the Michaelis constant (Km) were estimated to be 1520 microg/mL/min and 41.3 microg/mL, respectively. Thus, the capability of MULTI(FEM) was demonstrated in evaluating capacity-limited local disposition in the liver. PMID:10229646

  18. Evacetrapib: in vitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors.

    Science.gov (United States)

    Cannady, Ellen A; Wang, Ming-Dauh; Friedrich, Stuart; Rehmel, Jessica L F; Yi, Ping; Small, David S; Zhang, Wei; Suico, Jeffrey G

    2015-10-01

    Evacetrapib is an investigational cholesteryl ester transfer protein inhibitor (CETPi) for reduction of risk of major adverse cardiovascular events in patients with high-risk vascular disease. Understanding evacetrapib disposition, metabolism, and the potential for drug-drug interactions (DDI) may help guide prescribing recommendations. In vitro, evacetrapib metabolism was investigated with a panel of human recombinant cytochromes P450 (CYP). The disposition, metabolism, and excretion of evacetrapib following a single 100-mg oral dose of (14)C-evacetrapib were determined in healthy subjects, and the pharmacokinetics of evacetrapib were evaluated in the presence of strong CYP3A or CYP2C8 inhibitors. In vitro, CYP3A was responsible for about 90% of evacetrapib's CYP-associated clearance, while CYP2C8 accounted for about 10%. In the clinical disposition study, only evacetrapib and two minor metabolites circulated in plasma. Evacetrapib metabolism was extensive. A mean of 93.1% and 2.30% of the dose was excreted in feces and urine, respectively. In clinical DDI studies, the ratios of geometric least squares means for evacetrapib with/without the CYP3A inhibitor ketoconazole were 2.37 for area under the curve (AUC)(0-∞) and 1.94 for C max. There was no significant difference in evacetrapib AUC(0-τ) or C max with/without the CYP2C8 inhibitor gemfibrozil, with ratios of 0.996 and 1.02, respectively. Although in vitro results indicated that both CYP3A and CYP2C8 metabolized evacetrapib, clinical studies confirmed that evacetrapib is primarily metabolized by CYP3A. However, given the modest increase in evacetrapib exposure and robust clinical safety profile to date, there is a low likelihood of clinically relevant DDI with concomitant use of strong CYP3A or CYP2C8 inhibitors. PMID:26516590

  19. THEORIES AND FACTORS AFFECTING MUCOADHESIVE DRUG DELIVERY SYSTEMS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Alexander Amit

    2011-04-01

    Full Text Available Bioadhesion is an interfacial phenomenon in which two materials, at least one of which is biological, are held together by means of interfacial forces. When the associated biological system is mucous, it is called mucoadhesion. This property of certain polymeric systems have got place in the drug delivery research in order to prolong contact time in the various mucosal route of drug administration, as the ability to maintain a delivery system at a particular location for an extended period of time has a great appeal for both local action as well as systemic drug bioavailability. A complete and comprehensive theory that can predict adhesion based on the chemical and/or physical nature of a polymer is not yet available. Several theories have been proposed to explain the fundamental mechanisms of adhesion such as glues, adhesives, and paints, have been adopted to study the mucoadhesion. Mucoadhesion is a complex process and numerous theories have been presented to explain the mechanisms involved. These theories include mechanical-interlocking, electrostatic, diffusion–interpenetration, adsorption and fracture processes. They are Electronic theory, Adsorption theory, Wetting theory, Diffusion theory, Fracture theory. The objective of the study is to explain the different mechanisms involved in mucoadhesion and various factors affecting mucoadhesion.

  20. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. PMID:26189495

  1. A PBPK Model to Predict Disposition of CYP3A-Metabolized Drugs in Pregnant Women: Verification and Discerning the Site of CYP3A Induction.

    Science.gov (United States)

    Ke, A B; Nallani, S C; Zhao, P; Rostami-Hodjegan, A; Unadkat, J D

    2012-01-01

    Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A-metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age-dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e3; doi:10.1038/psp.2012.2; advance online publication 26 September 2012. PMID:23835883

  2. The Factors Affecting Drug Abuse Among Addicted Women

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Rahmati

    2002-10-01

    Full Text Available The aim of this article is to describe and analyse some background factors that has some effect on the formation and continuity of addictive behavior among a sample of 1500 addicted persons on the 10 provinces of Iran. The article explores the processes under which the addictive behavior occures. Based on the findings of a survey research on a sample of 1500 drug abusers, it is concluded that factors such as addiction to cigarettes, alcohol, drug type, and methods and situations of approaching and access to drugs are effective in beginning of addiction. At last , the article pays special attention to addiction among women as the drug abusers.

  3. Guide to Children Affected by Parental Drug Abuse

    Science.gov (United States)

    Davies, Leah

    2010-01-01

    A conservative estimate is that one in six children in school today has a parent dependent on or addicted to alcohol or other drugs. This places these students at high risk for social and emotional problems, as well as for school failure, drug use, and delinquency. Schools, however, are a logical place to reach them. Identifying children of those…

  4. In Silico and in Vitro Modeling of Hepatocyte Drug Transport Processes: Importance of ABCC2 Expression Levels in the Disposition of CarboxydichloroflurosceinS⃞

    OpenAIRE

    Howe, Katharine; Gibson, G Gordon; Coleman, Tanya; Plant, Nick

    2008-01-01

    The impact of transport proteins in the disposition of chemicals is becoming increasingly evident. Alteration in disposition can cause altered pharmacokinetic and pharmacodynamic parameters, potentially leading to reduced efficacy or overt toxicity. We have developed a quantitative in silico model, based upon literature and experimentally derived data, to model the disposition of carboxydichlorofluroscein (CDF), a substrate for the SLCO1A/B and ABCC subfamilies of tran...

  5. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    Science.gov (United States)

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  6. THEORIES AND FACTORS AFFECTING MUCOADHESIVE DRUG DELIVERY SYSTEMS: A REVIEW

    OpenAIRE

    Alexander Amit; Sharma Sharad; Ajazuddin,; Khan Mohammed Junaid; Swarna

    2011-01-01

    Bioadhesion is an interfacial phenomenon in which two materials, at least one of which is biological, are held together by means of interfacial forces. When the associated biological system is mucous, it is called mucoadhesion. This property of certain polymeric systems have got place in the drug delivery research in order to prolong contact time in the various mucosal route of drug administration, as the ability to maintain a delivery system at a particular location for an extended period of...

  7. Species differences in hepatobiliary disposition of taurocholic acid in human and rat sandwich-cultured hepatocytes: implications for drug-induced liver injury.

    Science.gov (United States)

    Yang, Kyunghee; Pfeifer, Nathan D; Köck, Kathleen; Brouwer, Kim L R

    2015-05-01

    The bile salt export pump (BSEP) plays an important role in bile acid excretion. Impaired BSEP function may result in liver injury. Bile acids also undergo basolateral efflux, but the relative contributions of biliary (CLBile) versus basolateral efflux (CLBL) clearance to hepatocellular bile acid excretion have not been determined. In the present study, taurocholic acid (TCA; a model bile acid) disposition was characterized in human and rat sandwich-cultured hepatocytes (SCH) combined with pharmacokinetic modeling. In human SCH, biliary excretion of TCA predominated (CLBile = 0.14 ± 0.04 ml/min per g liver; CLBL = 0.042 ± 0.019 ml/min per g liver), whereas CLBile and CLBL contributed approximately equally to TCA hepatocellular excretion in rat SCH (CLBile = 0.34 ± 0.07 ml/min per g liver; CLBL = 0.26 ± 0.07 ml/min per g liver). Troglitazone decreased TCA uptake, CLBile, and CLBL; membrane vesicle assays revealed for the first time that the major metabolite, troglitazone sulfate, was a noncompetitive inhibitor of multidrug resistance-associated protein 4, a basolateral bile acid efflux transporter. Simulations revealed that decreased CLBile led to a greater increase in hepatic TCA exposure in human than in rat SCH. A decrease in both excretory pathways (CLBile and CLBL) exponentially increased hepatic TCA in both species, suggesting that 1) drugs that inhibit both pathways may have a greater risk for hepatotoxicity, and 2) impaired function of an alternate excretory pathway may predispose patients to hepatotoxicity when drugs that inhibit one pathway are administered. Simulations confirmed the protective role of uptake inhibition, suggesting that a drug's inhibitory effects on bile acid uptake also should be considered when evaluating hepatotoxic potential. Overall, the current study precisely characterized basolateral efflux of TCA, revealed species differences in hepatocellular TCA efflux pathways, and provided insights about altered hepatic bile acid exposure

  8. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    Science.gov (United States)

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  9. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  10. Modern pharmacokinetic-pharmacodynamic techniques to study physiological mechanisms of pharmacokinetic drug-drug interactions and disposition of antibiotics and to assess clinical relevance

    OpenAIRE

    Landersdorfer, Cornelia

    2006-01-01

    There are numerous areas of application for which PKPD models are a valuable tool. We studied dose linearity, bone penetration and drug-drug interactions of antibiotics by PKPD modeling. Knowledge about possible saturation of elimination pathways at therapeutic concentrations is important for studying the probability of successful treatment of dosage regimens via MCS at various doses, other modes of administration, or both. We studied the dose linearity of flucloxacillin and piperacillin. For...

  11. Anatomical and Histological Factors Affecting Intranasal Drug and Vaccine Delivery

    OpenAIRE

    Gizurarson, Sveinbjörn

    2012-01-01

    The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive r...

  12. Analysis of variables affecting drug compliance in schizophrenia

    Directory of Open Access Journals (Sweden)

    Shakeel Ansari

    2014-01-01

    Full Text Available Context: As compliance of the patient during management of schizophrenia is crucial, the current study was conducted to find out the factors that affected compliance. Aims: The aim of the study was to analyze the prevalence of noncompliance and to find out different factors affecting compliance in schizophrenic patients. Materials and Methods: Observational cross-sectional study was conducted on 100 adult schizophrenic patients. Noncompliance was assessed using the rating of medication influence (ROMI scale. Severity of illness was measured using positive and negative syndrome scale (PANSS. Results: Prevalence of noncompliance was 37%. Using ROMI scale; positive relationship with psychiatrist, family pressure for taking medications, stigma, and substance abuse were found to be significant factors. Severity of illness was also found as determining factor. Conclusion: To improve the compliance in schizophrenia patients, roles of both psychiatrists and family members are crucial.

  13. Effect of diamorphine, delta 9-tetrahydrocannabinol and ethanol on intravenous cocaine disposition.

    Science.gov (United States)

    Vadlamani, N L; Pontani, R B; Misra, A L

    1984-08-01

    The disposition of cocaine (1 mg kg-1) was altered by diamorphine (0.1 mg kg-1) and that of morphine (1 mg kg-1) was altered after their concurrent administration as a bolus i.v. injection to rats by cocaine, without any changes in the metabolism of the drugs. delta 9-Tetrahydrocannabinol (10 mg kg-1 i.p.) did not affect the cocaine disposition. Chronic ethanol treatment (2.5 g kg-1 orally twice daily for 16 days) produced a significantly higher brain-to-plasma cocaine concentration ratio than did saline as control, without any changes in cocaine metabolism. PMID:6148403

  14. Anatomical and histological factors affecting intranasal drug and vaccine delivery.

    Science.gov (United States)

    Gizurarson, Sveinbjörn

    2012-11-01

    The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region. PMID:22788696

  15. Morphogenic regulator EFG1 affects the drug susceptibilities of pathogenic Candida albicans.

    Science.gov (United States)

    Prasad, Tulika; Hameed, Saif; Manoharlal, Raman; Biswas, Sudipta; Mukhopadhyay, Chinmay K; Goswami, Shyamal K; Prasad, Rajendra

    2010-08-01

    This study shows that the morphogenic regulator EFG1 level affects the drug susceptibilities of Candida albicans when grown on solid growth media. The Deltaefg1 mutant showed sensitivity particularly to those drugs that target ergosterol or its metabolism. Efg1p disruption showed a gene-dosage effect on drug susceptibilities and resulted in enhanced susceptibility to drugs in the homozygous mutant as compared with the wild type, heterozygous and revertant strains. The enhanced sensitivity to drugs was independent of the status of ATP-binding cassette and MFS multidrug efflux pumps of C. albicans. The Deltaefg1 mutant displayed increased membrane fluidity that coincided with the downregulation of ERG11 and upregulation of OLE1 and ERG3, leading to enhanced passive diffusion of drugs. Interestingly, Deltaefg1 mutant cells displayed enhanced levels of endogenous ROS levels. Notably, the higher levels of ROS in the Deltaefg1 mutant could be reversed by the addition of antioxidants. However, the restoration of ROS levels did not reverse the drug sensitivities of the Deltaefg1 mutant. Taken together, we, for the first time, establish a new role to EFG1 in affecting the drug susceptibilities of C. albicans cells, independent of ROS and known drug efflux mechanisms. PMID:20491944

  16. Albumin Supplement Affects the Metabolism and Metabolism-Related Drug-Drug Interaction of Fenoprofen Enantiomers.

    Science.gov (United States)

    Wang, Nan; Wang, Feng; Meng, Yu; Yang, Guo-Hui; Chen, Ju-Wu; Wang, Jia-Xiang

    2015-07-01

    The influence of albumin towards the metabolism behavior of fenoprofen enantiomers and relevant drug-drug interaction was investigated in the present study. The metabolic behavior of fenoprofen enantiomers was compared in a phase II metabolic incubation system with and without bovine serum albumin (BSA). BSA supplement increased the binding affinity parameter (Km) of (R)-fenoprofen towards human liver microsomes (HLMs) from 148.3 to 214.4 μM. In contrast, BSA supplement decreased the Km of (S)-fenoprofen towards HLMs from 218.2 to 123.5 μM. For maximum reaction velocity (Vmax), the addition of BSA increased the Vmax of (R)-fenoprofen from 1.3 to 1.6 nmol/min/mg protein. In the contrast, BSA supplement decreased the Vmax value from 3.3 to 1.5 nmol/min/mg protein. Andrographolide-fenoprofen interaction was used as an example to investigate the influence of BSA supplement towards fenoprofen-relevant drug-drug interaction. The addition of 0.2% BSA in the incubation system significantly decreased the inhibition potential of andrographolide towards (R)-fenoprofen metabolism (P andrographolide towards the metabolism of (S)-fenoprofen. BSA supplement also changed the inhibition kinetic type and parameter of andrographolide towards the metabolism of (S)-fenoprofen. In conclusion, albumin supplement changes the metabolic behavior of fenoprofen enantiomers and the fenoprofen-andrographolide interaction. PMID:26037509

  17. How could preventive therapy affect the prevalence of drug resistance? Causes and consequences.

    Science.gov (United States)

    Kunkel, Amber; Colijn, Caroline; Lipsitch, Marc; Cohen, Ted

    2015-06-01

    Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects. PMID:25918446

  18. Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism.

    Science.gov (United States)

    Anyanwagu, U; Idris, I; Donnelly, R

    2016-04-01

    Abnormalities of glucose metabolism and glucose tolerance, either because of a reduction in tissue sensitivity to insulin (e.g., in liver, skeletal muscle, and adipose tissues) and/or a reduction in pancreatic insulin secretion, are associated with a number of unwanted health outcomes. Even small increases in circulating glucose levels (often described as dysglycemia or prediabetes) may confer an increased risk of cardiovascular (CV) disease and progression to overt type 2 diabetes. A number of drug therapies, many of them used long term in chronic disease management, have adverse effects on glucose metabolism, diabetes risk, and glycemic control among patients with preexisting diabetes. In this study, we review the evidence, underlying mechanisms, and the clinical significance of drug-related adverse effects on glucose metabolism. PMID:26440603

  19. The Role of Self-regulation and Affective Control in Predicting Interpersonal Reactivity of Drug Addicts

    OpenAIRE

    Abolghasemi, Abbas; Rajabi, Saeed

    2013-01-01

    Background Due to its progressive nature in all aspects of life, addiction endangers the health of individuals, families and the society. Objectives The purpose of this study was to determine the role of self-regulation and affective control in predicting interpersonal reactivity of drug addicts. Materials and Methods This research is a correlation study. The statistical population of this study includes all drug addicts who were referred to addiction treatment centers of Ardabil in 2011 of w...

  20. The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

    Directory of Open Access Journals (Sweden)

    Yubang Wang

    2015-12-01

    Full Text Available This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123, and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.

  1. Species Differences in Hepatobiliary Disposition of Taurocholic Acid in Human and Rat Sandwich-Cultured Hepatocytes: Implications for Drug-Induced Liver Injury

    OpenAIRE

    Yang, Kyunghee; Pfeifer, Nathan D.; Köck, Kathleen; Brouwer, Kim L.R.

    2015-01-01

    The bile salt export pump (BSEP) plays an important role in bile acid excretion. Impaired BSEP function may result in liver injury. Bile acids also undergo basolateral efflux, but the relative contributions of biliary (CLBile) versus basolateral efflux (CLBL) clearance to hepatocellular bile acid excretion have not been determined. In the present study, taurocholic acid (TCA; a model bile acid) disposition was characterized in human and rat sandwich-cultured hepatocytes (SCH) combined with ph...

  2. Drug addiction: An affective-cognitive disorder in need of a cure.

    Science.gov (United States)

    Fattore, Liana; Diana, Marco

    2016-06-01

    Drug addiction is a compulsive behavioral abnormality. In spite of pharmacological treatments and psychosocial support to reduce or eliminate drug intake, addiction tends to persist over time. Preclinical and human observations have converged on the hypothesis that addiction represents the pathological deterioration of neural processes that normally serve affective and cognitive functioning. The major elements of persistent compulsive drug use are hypothesized to be structural, cellular and molecular that underlie enduring changes in several forebrain circuits that receive input from midbrain dopamine neurons and are involved in affective (e.g. ventral striatum) and cognitive (e.g. prefrontal cortex) mechanisms. Here we review recent progress in identifying crucial elements useful to understand the pathophysiology of the disease and its treatments. Manipulation of neuropeptides brain systems and pharmacological targeting of κ-opioid receptors and/or drug metabolism may hold beneficial effects at affective and cognitive level. Non-pharmacological, highly innovative approaches such as Transcranial Magnetic Stimulation may reveal unsuspected potential and promise to be the first neurobiology-based therapeutics in addiction. PMID:27095547

  3. Addictive drugs and their duration affecting on trace elements levels in men

    International Nuclear Information System (INIS)

    During the drug addiction the blood biochemistry particularly level of trace elements in blood is widely affected. Eighty male addicts of various age groups along with seventeen normal subjects were studied. The plasma Zinc and manganese concentration was high in addict person as compared to normal subjects. Where as a significant decrease in iron concentration was observed in addicts. The plasma copper concentration was also low in addicts as compared to normal subjects. In conclusion drug addiction leads to many biochemical changes that may have detritus effects on health status of addicts. (author)

  4. Deficits of Affect Mentalization in Patients with Drug Addiction: Theoretical and Clinical Aspects

    OpenAIRE

    Savov, Svetoslav; Atanassov, Nikola

    2013-01-01

    Traditionally treated with wariness, drug addictions have provoked a serious interest in psychodynamically oriented clinicians in recent decades. This paper discusses the development of contemporary psychodynamic conceptualizations of addictions, focusing specifically on mentalization-based theories. The concept of mentalization refers to a complex form of self-regulation which includes attribution of psychological meaning to one’s own behavior and affective states, as well as those of the ot...

  5. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  6. The Implementer Disposition of Teacher Certification Policy in Indonesia

    Science.gov (United States)

    Malkab, Marnih; Nawawi, Juanda; Mahmud, Alimuddin; Sujiono, Eko Hadi

    2015-01-01

    This research aims to examine and analyze the implementers disposition in the implementation of teacher certification policy in Makassar City and to know how is the disposition affects in successful implementation policy. This research is descriptive by using a qualitative approach. Sources of data in this study are primary data from the…

  7. 9 CFR 310.16 - Disposition of lungs.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Disposition of lungs. 310.16 Section... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.16 Disposition of lungs. (a) Livestock lungs shall not be saved for use as human food. (b) Lungs found to be affected with disease or pathology and...

  8. Affective Disposition, Thinking Styles, Neuroticism and Life Satisfaction / Disposición afectiva, estilos de pensamiento, neuroticismo y satisfacción vital

    Directory of Open Access Journals (Sweden)

    Cristian Zanon

    2013-06-01

    Full Text Available The way in which positive and negative affects are perceived may be associated with a distinct pattern of behaviors and attitudes. The aim of this study was to evaluate the relationship between various combinations of affections and gender along with tendencies towards neuroticism, rumination, reflection, and life satisfaction. The participants were 348 students, who answered the questionnaire in groups. The euphoric group showed the highest scores of life satisfaction and emotional stability, while the dysphoric group presented the lowest scores. The emotional and apathetic groups showed no significant differences in relation to life satisfaction, depression, anxiety and vulnerability. From these results, it can be assumed that positive affect can lessen the impact that negative affect has on the development of vulnerability and other psychopathological symptoms. Interventions based on positive affect increase might be efficient to prevent vulnerability.

  9. Enantioselective disposition of albuterol in humans.

    Science.gov (United States)

    Boulton, D W; Fawcett, J P

    1996-01-01

    The study of enantioselective disposition of chiral drugs is important to provide a rationale of plasma concentration-effect relationships, which are often misleading when based on total drug concentration. It is also important when considering new dosage routes or formulations in order to optimize therapeutic plasma concentrations of the active enantiomer. Improvements in the sensitivity and selectivity of biological assays coupled with the developments in chiral analysis have made it possible to study the enantioselective disposition of drugs. Although valuable pharmacokinetic data were obtained for the beta 2-agonists by nonenantioselective methodology, more recent chiral studies have revealed the existence of extensive enantioselectivity in the disposition of these agents. The most significant features of the enantioselective disposition of albuterol are the relatively rapid plasma clearance and low bioavailability of the eutomer. Although this in itself does not necessarily justify the development of a single enantiomer formulation, the implications of the high levels of distomer after i.v. and oral dosing await clarification. Similarly, more work is required to elucidate the consequences of the major difference in disposition between albuterol and terbutaline in humans through both in vivo and in vitro studies of the mechanisms giving rise to this phenomenon. The enantioselective disposition of the other clinically used beta 2-agonists, such as fenoterol, formoterol, and salmeterol also needs to be characterized. The metabolism of the majority of beta 2-agonists is generally by conjugation to give one major metabolite. The situation is therefore uncomplicated by multiple metabolic pathways, which may differ in the extent and direction of their enantioselectivity. Many beta 2-agonists are excreted largely unchanged in the urine making studies of urinary excretion accessible without the requirement for very sensitive assays. The realization that the enantiomers

  10. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    International Nuclear Information System (INIS)

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump. Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [11C]celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [11C]verapamil was studied. Results: [11C]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [11C]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [11C]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma. Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [11C]verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux

  11. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)], E-mail: e.f.j.de.vries@ngmb.umcg.nl; Doorduin, Janine; Vellinga, Namkje A.R.; Waarde, Aren van; Dierckx, Rudi A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); Klein, Hans C. [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands); Department of Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen (Netherlands)

    2008-05-15

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp substrates. To clarify whether Pgp is involved in the sensitizing effect of celecoxib, we investigated in vivo whether celecoxib is a substrate of Pgp and whether it can affect the efflux activity of the pump. Methods: In control rats and in rats treated with the Pgp modulator cyclosporin A (CsA), cerebral accumulation of radiolabeled [{sup 11}C]celecoxib was investigated by ex vivo biodistribution and micro-positron emission tomography imaging. In addition, the effect of unlabeled celecoxib and CsA (positive control) on the cerebral uptake of the Pgp substrate [{sup 11}C]verapamil was studied. Results: [{sup 11}C]Celecoxib uptake in rat brain was relatively high and homogeneously distributed. Treatment of rats with CsA only marginally increased cerebral tracer uptake, which is most likely due to reduced tracer clearance from plasma. [{sup 11}C]Verapamil brain uptake was more than 10-fold higher after treatment with CsA. In contrast, a high dose of celecoxib increased cerebral [{sup 11}C]verapamil uptake only twofold, which was accompanied by a similar increase in tracer concentration in plasma. Conclusions: This study shows that celecoxib is not a substrate of Pgp and does not substantially affect the Pgp-mediated efflux of [{sup 11}C]verapamil. Therefore, celecoxib-induced augmentation of the efficacy of chemotherapeutic and neurotropic drugs must be due to another mechanism than modulation of Pgp-mediated drug efflux.

  12. In vivo Pharmacokinetics of Two New Thrombin Inhibitor Prodrugs : Emphasis on Intestinal and Hepatobiliary Disposition and the Influence of Interacting Drugs

    OpenAIRE

    Matsson, Elin

    2010-01-01

    Biliary excretion is an important elimination route for many drugs and metabolites. For such compounds, it is important to know the extent of excretion and drug exposure in the bile, e.g., for the risk assessment of drug interactions, liver toxicity and the effects of genetic variants. In this thesis, duodenal aspiration of bile was performed in healthy volunteers and complemented with experiments in an in vivo model in pigs to increase the understanding of the intestinal and hepatobiliary di...

  13. Formulation variables affecting drug release from xanthan gum matrices at laboratory scale and pilot scale

    OpenAIRE

    Billa, Nashiru; Yuen, Kah-Hay

    2000-01-01

    The purpose of this research was to study processing variables at the laboratory and pilot scales that can affect hydration rates of xanthan gum matrices containing diclofenac sodium and the rate of drug release. Tablets from the laboratory scale and pilot scale proceedings were made by wet granulation. Swelling indices of xanthan gum formulations prepared with different amounts of water were measured in water under a magnifying lens. Granules were thermally treated in an oven at 60°C, 70°C, ...

  14. Genetic polymorphisms and function of the organic anion-transporting polypeptide 1A2 and its clinical relevance in drug disposition.

    Science.gov (United States)

    Zhou, Yinhui; Yuan, Jingjing; Li, Zhisong; Wang, Zhongyu; Cheng, Dan; Du, Yingying; Li, Wenlu; Kan, Quancheng; Zhang, Wei

    2015-01-01

    The solute carrier organic anion-transporting polypeptides (OATPs) are a family of transporter proteins that have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion of various drugs because of their broad substrate specificity and wide tissue distribution as well as the involvement of drug-drug interaction. Human OATP1A2 is a drug uptake transporter known for its broad substrate specificity, including many drugs in clinical use. OATP1A2 expression has been detected in the intestine, liver, brain and kidney. A considerable number of single nucleotide polymorphisms have been found for the OATP1A2 gene. A number of studies have shown that the cellular uptake and pharmacokinetic behavior of some drugs may be impaired in the case of certain OATP1A2 variants. Interestingly, some studies show that the mRNA expression of OATP1A2 is nearly 10-fold higher in breast cancer compared with adjacent healthy breast tissues. This review is, therefore, focused on the genetic polymorphisms, function and clinical relevance of OATP1A2 as well as on the substrates transported by it. PMID:25924632

  15. Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.

    Science.gov (United States)

    Velasquez, Juan C; Goeden, Nick; Herod, Skyla M; Bonnin, Alexandre

    2016-03-16

    While selective-serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed in the treatment of depression, their use during pregnancy leads to fetal drug exposures. According to recent reports, such exposures could affect fetal development and long-term offspring health. A central question is how pregnancy-induced physical and physiological changes in mothers, fetuses, and the placenta influence fetal SSRI exposures during gestation. In this study, we examined the effects of gestational stage on the maternal pharmacokinetics and fetal disposition of the SSRI (±)-citalopram (CIT) in a mouse model. We determined the maternal and fetal CIT serum concentration-time profiles following acute maternal administration on gestational days (GD)14 and GD18, as well as the fetal brain drug disposition. The results show that pregnancy affects the pharmacokinetics of CIT and that maternal drug clearance increases as gestation progresses. The data further show that CIT and its primary metabolite desmethylcitalopram (DCIT) readily cross the placenta into the fetal compartment, and fetal exposure to CIT exceeds that of the mother during gestation 2 h after maternal administration. Enzymatic activity assays revealed that fetal drug metabolic capacity develops in late gestation, resulting in elevated circulating and brain concentrations of DCIT at embryonic day (E)18. Fetal exposure to the SSRI CIT in murine pregnancy is therefore influenced by both maternal gestational stage and embryonic development, suggesting potential time-dependent effects on fetal brain development. PMID:26765210

  16. Therapeutic product disposition in at-risk populations

    International Nuclear Information System (INIS)

    In an emergency situation, such as a chemical, biological, radionuclide, nuclear or explosion (CBRNE) event, all patient populations are at increased risk of serious adverse events. Therapeutic product (TP) safety and efficacy depend on the disposition of the product through absorption, distribution, metabolism and excretion. The ability of a patient to benefit from or merely tolerate a TP can be modified by many factors, including but not limited to culture, diet, disease, environmental contaminants, genetic predisposition, stress and socioeconomic status and recent life experiences. Metabolism is considered to have the greatest effect on safety and efficacy, as chemicals not metabolised can accumulate to toxic levels. Inter-individual variances in most drug metabolism enzymes may range up to greater than 1000-fold. The fetus, neonates, infants, individuals with hormonal change, infection or prior exposure to licit or illicit products and the elderly are more susceptible to increased risk of serious adverse health effects. The critically ill are the most at risk. The at-risk populations for a serious adverse event are dependent then on the CBRNE event, their physical and cognitive states and the inter-individual intrinsic and extrinsic factors that affect TP disposition. (authors)

  17. Therapeutic product disposition in at-risk populations.

    Science.gov (United States)

    Foster, Brian C

    2009-06-01

    In an emergency situation, such as a chemical, biological, radionuclide, nuclear or explosion (CBRNE) event, all patient populations are at increased risk of serious adverse events. Therapeutic product (TP) safety and efficacy depend on the disposition of the product through absorption, distribution, metabolism and excretion. The ability of a patient to benefit from or merely tolerate a TP can be modified by many factors, including but not limited to culture, diet, disease, environmental contaminants, genetic predisposition, stress and socioeconomic status and recent life experiences. Metabolism is considered to have the greatest effect on safety and efficacy, as chemicals not metabolised can accumulate to toxic levels. Inter-individual variances in most drug metabolism enzymes may range up to greater than 1000-fold. The fetus, neonates, infants, individuals with hormonal change, infection or prior exposure to licit or illicit products and the elderly are more susceptible to increased risk of serious adverse health effects. The critically ill are the most at risk. The at-risk populations for a serious adverse event are dependent then on the CBRNE event, their physical and cognitive states and the inter-individual intrinsic and extrinsic factors that affect TP disposition. PMID:19423636

  18. Multi-walled carbon nanotubes affect drug transport across cell membrane in rat astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiao [School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, 430030, Wuhan (China); Schluesener, Hermann J, E-mail: mornsmile@yahoo.com [Institute of Brain Research, University of Tuebingen, Calwerstrasse 3, D-72076, Tuebingen (Germany)

    2010-03-12

    The impact of carbon nanotubes on the cell membrane is an aspect of particular importance and interest in the study of carbon nanotubes' interactions with living systems. One of the many functions of the cell membrane is to execute substance transport into and out of the cell. We investigated the influence of multi-walled carbon nanotubes (MWCNTs) on the transport of several compounds across in the cell membrane of rat astrocytes using flow cytometry. These compounds are fluorescein diacetate, carboxyfluorescein diacetate, rhodamine 123 and doxorubicin, which are prosubstrate/substrates of multidrug transporter proteins. Results showed that MWCNTs significantly inhibited cellular uptake of doxorubicin but not the other drugs and the mode of loading made a significant difference in doxorubicin uptake. Retention of fluorescein, carboxyfluorescein and rhodamine 123 was remarkably higher in MWCNT-exposed cells after an efflux period. A kinetics study also demonstrated slower efflux of intracellular fluorescein and rhodamine 123. Data presented in this paper suggest that MWCNTs could affect drug transport across cell membranes. The implications of the findings are discussed.

  19. Multi-walled carbon nanotubes affect drug transport across cell membrane in rat astrocytes

    Science.gov (United States)

    Chen, Xiao; Schluesener, Hermann J.

    2010-03-01

    The impact of carbon nanotubes on the cell membrane is an aspect of particular importance and interest in the study of carbon nanotubes' interactions with living systems. One of the many functions of the cell membrane is to execute substance transport into and out of the cell. We investigated the influence of multi-walled carbon nanotubes (MWCNTs) on the transport of several compounds across in the cell membrane of rat astrocytes using flow cytometry. These compounds are fluorescein diacetate, carboxyfluorescein diacetate, rhodamine 123 and doxorubicin, which are prosubstrate/substrates of multidrug transporter proteins. Results showed that MWCNTs significantly inhibited cellular uptake of doxorubicin but not the other drugs and the mode of loading made a significant difference in doxorubicin uptake. Retention of fluorescein, carboxyfluorescein and rhodamine 123 was remarkably higher in MWCNT-exposed cells after an efflux period. A kinetics study also demonstrated slower efflux of intracellular fluorescein and rhodamine 123. Data presented in this paper suggest that MWCNTs could affect drug transport across cell membranes. The implications of the findings are discussed.

  20. Multi-walled carbon nanotubes affect drug transport across cell membrane in rat astrocytes

    International Nuclear Information System (INIS)

    The impact of carbon nanotubes on the cell membrane is an aspect of particular importance and interest in the study of carbon nanotubes' interactions with living systems. One of the many functions of the cell membrane is to execute substance transport into and out of the cell. We investigated the influence of multi-walled carbon nanotubes (MWCNTs) on the transport of several compounds across in the cell membrane of rat astrocytes using flow cytometry. These compounds are fluorescein diacetate, carboxyfluorescein diacetate, rhodamine 123 and doxorubicin, which are prosubstrate/substrates of multidrug transporter proteins. Results showed that MWCNTs significantly inhibited cellular uptake of doxorubicin but not the other drugs and the mode of loading made a significant difference in doxorubicin uptake. Retention of fluorescein, carboxyfluorescein and rhodamine 123 was remarkably higher in MWCNT-exposed cells after an efflux period. A kinetics study also demonstrated slower efflux of intracellular fluorescein and rhodamine 123. Data presented in this paper suggest that MWCNTs could affect drug transport across cell membranes. The implications of the findings are discussed.

  1. A Disposition for Benevolence

    Science.gov (United States)

    O'Shea, Joseph

    2011-01-01

    This article presents the first half of an address at the 2011 Jon C. Dalton Institution on College Student Values. Drawing on personal reflections regarding his higher education experiences, the author argues that cultivating a robust disposition for benevolence requires a synthesis of intellectual engagement, critical self-reflection, and…

  2. What is a Dispositive?

    DEFF Research Database (Denmark)

    Raffnsøe, Sverre; Gudmand-Høyer, Marius T.; Thaning, Morten Sørensen

    This article advances the ‘dispositive’ (le dispositif) as a key conception in Foucault’s work. As developed in his annual lectures in 1978 and 1979, the dispositive represents a crucial constituent of societal analysis on par with the familiar analytics of power/knowledge and the governmentality...

  3. PF-4 actinide disposition strategy

    International Nuclear Information System (INIS)

    The dwindling amount of Security Category I processing and storage space across the DOE Complex has driven the need for more effective storage of nuclear materials at LANL's Plutonium Facility's (PF-4's) vault. An effort was begun in 2009 to create a strategy, a roadmap, to identify all accountable nuclear material and determine their disposition paths, the PF-4 Actinide Disposition Strategy (PADS). Approximately seventy bins of nuclear materials with similar characteristics - in terms of isotope, chemical form, impurities, disposition location, etc. - were established in a database. The ultimate disposition paths include the material to remain at LANL, disposition to other DOE sites, and disposition to waste. If all the actions described in the document were taken, over half of the containers currently in the PF-4 vault would been eliminated. The actual amount of projected vault space will depend on budget and competing mission requirements, however, clearly a significant portion of the current LANL inventory can be either dispositioned or consolidated.

  4. Research & market strategy: how choice of drug discovery approach can affect market position.

    Science.gov (United States)

    Sams-Dodd, Frank

    2007-04-01

    In principal, drug discovery approaches can be grouped into target- and function-based, with the respective aims of developing either a target-selective drug or a drug that produces a specific biological effect irrespective of its mode of action. Most analyses of drug discovery approaches focus on productivity, whereas the strategic implications of the choice of drug discovery approach on market position and ability to maintain market exclusivity are rarely considered. However, a comparison of approaches from the perspective of market position indicates that the functional approach is superior for the development of novel, innovative treatments. PMID:17395091

  5. Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor.

    Science.gov (United States)

    Dickinson, Paul A; Cantarini, Mireille V; Collier, Jo; Frewer, Paul; Martin, Scott; Pickup, Kathryn; Ballard, Peter

    2016-08-01

    Preclinical and clinical studies were conducted to determine the metabolism and pharmacokinetics of osimertinib and key metabolites AZ5104 and AZ7550. Osimertinib was designed to covalently bind to epidermal growth factor receptors, allowing it to achieve nanomolar cellular potency (Finlay et al., 2014). Covalent binding was observed in incubations of radiolabeled osimertinib with human and rat hepatocytes, human and rat plasma, and human serum albumin. Osimertinib, AZ5104, and AZ7550 were predominantly metabolized by CYP3A. Seven metabolites were detected in human hepatocytes, also observed in rat or dog hepatocytes at similar or higher levels. After oral administration of radiolabeled osimertinib to rats, drug-related material was widely distributed, with the highest radioactivity concentrations measured at 6 hours postdose in most tissues; radioactivity was detectable in 42% of tissues 60 days postdose. Concentrations of [(14)C]-radioactivity in blood were lower than in most tissues. After the administration of a single oral dose of 20 mg of radiolabeled osimertinib to healthy male volunteers, ∼19% of the dose was recovered by 3 days postdose. At 84 days postdose, mean total radioactivity recovery was 14.2% and 67.8% of the dose in urine and feces. The most abundant metabolite identified in feces was AZ5104 (∼6% of dose). Osimertinib accounted for ∼1% of total radioactivity in the plasma of non-small cell lung cancer patients after 22 days of 80-mg osimertinib once-daily treatment; the most abundant circulatory metabolites were AZ7550 and AZ5104 (<10% of total osimertinib-related material). Osimertinib is extensively distributed and metabolized in humans and is eliminated primarily via the fecal route. PMID:27226351

  6. Psychoactive-drug response is affected by acute low-level microwave irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1983-01-01

    The effects of various psychoactive drugs were studied in rats exposed for 45 min in a circularly polarized, pulsed microwave field (2450 MHz; SAR 0.6 W/kg; 2-microseconds pulses, 500 pps). Apomorphine-induced hypothermia and stereotypy were enhanced by irradiation. Amphetamine-induced hyperthermia was attenuated while stereotypy was unaffected. Morphine-induced catalepsy and lethality were enhanced by irradiation at certain dosages of the drug. Since these drugs have different modes of action on central neural mechanisms and the effects of microwaves depend on the particular drug studied, these results show the complex nature of the effect of microwave irradiation on brain functions.

  7. 25 CFR 11.1011 - Dispositional hearing.

    Science.gov (United States)

    2010-04-01

    ... ORDER CODE Juvenile Offender Procedure § 11.1011 Dispositional hearing. (a) A dispositional hearing... prepared by the minor and his or her attorney, if any. (e) The dispositional order constitutes a...

  8. Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study

    NARCIS (Netherlands)

    De Vries, Erik F. J.; Doorduin, Janine; Vellinga, Namkje A. R.; Van Waarde, Aren; Dierckx, Rudi A.; Klein, Hans C.

    2008-01-01

    Introduction: P-glycoprotein (Pgp) is an efflux pump that protects vital organs like the brain from toxic substances, but which is also associated with therapy resistance. The anti-inflammatory drug celecoxib potentiates the efficacy of several cytostatic and neurotropic drugs that are known Pgp sub

  9. Modulators of drug dependence phenomena : factors affecting morphine withdrawal syndrome and cocaine-intake in rodents

    NARCIS (Netherlands)

    S.L.T. Cappendijk (Susanne)

    1995-01-01

    textabstractThis thesis compiles the experimental studies on several drugs, which modulate drug dependence phenomena in rodents. The main part of the studies is related to the morphine withdrawal (chapters 3-7), while a minor part is dealing with cocaine psychic dependence (chapter 9).

  10. Microvesicle formulations used in topical drugs and cosmetics affect product efficiency, performance and allergenicity

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Ejner Andersen, Klaus

    2010-01-01

    Attempts to improve the formulations of topical products are continuing processes (ie, to increase cosmetic performance, enhance effects, and protect ingredients from degradation). The development of micro- and nanovesicular systems has led to the marketing of topical drugs and cosmetics that use...... these technologies. Several articles have reported improved clinical efficacy by the encapsulation of pharmaceuticals in vesicular systems, and the numbers of publications and patents are rising. Some vesicular systems may deliver the drug deeper in the skin as compared to conventional vehicles, or even make...... transdermal delivery more efficient for a number of drugs. Vesicular systems may also allow a more precise drug delivery to the site of action (ie, the hair follicles) and thereby minimize the applied drug concentration, reducing potential side effects. On the other hand, this may increase the risk of other...

  11. How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

    Science.gov (United States)

    Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

    2016-06-01

    Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

  12. Possible NMDA antagonist properties of drugs that affect high pressure neurological syndrome.

    OpenAIRE

    Shuker, M. A.; Bowser-Riley, F.; Davies, S. N.

    1994-01-01

    1. Previous studies have suggested that a series of drugs modelled on part of the strychnine molecule interfere with the development of high pressure neurological syndrome (HPNS) and it was presumed that this effect was via an action on inhibitory glycinergic transmission. We have now used the rat hippocampal slice preparation to examine the possibility that some of these drugs might instead have an action at the strychnine-insensitive (SI) glycine binding site associated with the NMDA recept...

  13. Changes of pathological and physiological indicators affecting drug metabolism in rats after acute exposure to high altitude

    OpenAIRE

    Li, Wenbin; Wang, Rong; Xie, Hua; ZHANG, JUANHONG; Jia, Zhengping

    2014-01-01

    High altitude environments cause the human body to undergo a series of pathological, physiological and biochemical changes, which have a certain effect on drug pharmacokinetics. The objective of the present study was to observe changes in factors affecting pharmacokinetics in rats following acute exposure to high altitude and return to low altitude. A total of 21 male Wistar rats were randomly assigned to three groups. The rats in group A were maintained at low altitude in Shanghai, 55 m abov...

  14. "Narco" Emotions: Affect and Desensitization in Social Media during the Mexican Drug War

    OpenAIRE

    De Choudhury, Munmun; Monroy-Hernández, Andrés; Mark, Gloria

    2015-01-01

    Social media platforms have emerged as prominent information sharing ecosystems in the context of a variety of recent crises, ranging from mass emergencies, to wars and political conflicts. We study affective responses in social media and how they might indicate desensitization to violence experienced in communities embroiled in an armed conflict. Specifically, we examine three established affect measures: negative affect, activation, and dominance as observed on Twitter in relation to a numb...

  15. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    OpenAIRE

    Chandra Prakash; Baltazar Zuniga; Chung Seog Song; Shoulei Jiang; Jodie Cropper; Sulgi Park; Bandana Chatterjee

    2015-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D recep...

  16. Beyond Job Satisfaction: A Five-Year Prospective Analysis of the Dispositional Approach to Work Attitudes

    Science.gov (United States)

    Bowling, Nathan A.; Beehr, Terry A.; Lepisto, Lawrence R.

    2006-01-01

    Mounting evidence indicates a dispositional component to global job satisfaction. Unfortunately, however, relatively little attention has been given to the potential effects of dispositions on work-related attitudes other than global job satisfaction. We used a five-year prospective design to investigate the relationships of affective disposition…

  17. Maternal Drug Use during Pregnancy: Are Preterm and Full-Term Infants Affected Differently?

    Science.gov (United States)

    Brown, Josephine V.; Bakeman, Roger; Coles, Claire D.; Sexson, William R.; Demi, Alice S.

    1998-01-01

    Examined effects of prenatal drug exposure on infants born preterm and full-term to African American mothers. Found more extreme fetal growth deficits in later-born infants, and more extreme irritability increases in earlier-born infants. Gestation length did not moderate cardiorespiratory reactivity effects. Exposure effects occurred for…

  18. FS65 Disposition Option Report

    Energy Technology Data Exchange (ETDEWEB)

    Wenz, Tracy R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-09-25

    This report outlines the options for dispositioning the MOX fuel stored in FS65 containers at LANL. Additional discussion regarding the support equipment for loading and unloading the FS65 transport containers is included at the end of the report.

  19. Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

    Directory of Open Access Journals (Sweden)

    Youcef M. Rustum

    2010-01-01

    Full Text Available Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.

  20. Seizure Clustering during Drug Treatment Affects Seizure Outcome and Mortality of Childhood-Onset Epilepsy

    Science.gov (United States)

    Sillanpaa, Matti; Schmidt, Dieter

    2008-01-01

    To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases)…

  1. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis

    Science.gov (United States)

    Wang, Bo; Franklin, Jessica M.; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S.

    2016-01-01

    Background Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved (“off-label”) uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Methods Retrospective, segmented time-series analysis using new prescription claims during 2003–2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. Results During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). Conclusions The FDA’s sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency’s expert judgments to clinical practice. PMID:27032095

  2. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

    OpenAIRE

    Clayton, T. Andrew; Baker, David; Lindon, John C.; Everett, Jeremy R.; Nicholson, Jeremy K

    2009-01-01

    We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by 1H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarker...

  3. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

    OpenAIRE

    Morte, Maria I.; Carreira, Bruno P.; Falcão, Maria J.; Ambrosio, António M.; Soares-da-Silva, Patrício; Araújo, Inês M.; Carvalho, Caetana M.

    2013-01-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic p...

  4. Biases affecting injected doses of an experimental drug during clinical trials

    OpenAIRE

    Perrottet, Nancy; Brunner-Ferber, Françoise; Grouzmann, Eric; Spertini, François; Biollaz, Jérôme; Buclin, Thierry; Widmer, Nicolas

    2016-01-01

    Background During clinical trials, researchers rarely question nominal doses specified on labels of investigational products, overlooking the potential for inaccuracies that may result when calculating pharmacokinetic and pharmacodynamic parameters. This study evaluated the disparity between nominal doses and the doses actually administered in two Phase I trials of a biosimilar drug. Methods In Trial A, 12 healthy volunteers received various doses of an interferon β-1a biosimilar via either s...

  5. Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

    Science.gov (United States)

    Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

    2016-05-30

    The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. PMID:27025293

  6. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    International Nuclear Information System (INIS)

    PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested. These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies

  7. Study of Excipients Affecting Dissolution Profile of Drug with Special Emphasis on Co Processed Excipients

    Directory of Open Access Journals (Sweden)

    Parmar K

    2013-06-01

    Full Text Available The main aim of present work is to study the impact of various excipients and co-processed excipientson dissolution rate. Direct compression is the preferred method for the preparation of tablets. Coprocessing is the one of the most widely explored and commercially utilized method for the preparationof directly compressible vehicle. The objective of present study is to prepare and characterize various coprocessed excipients and its application in tablet formulation. Co-processed excipient prepared wascharacterized by flow properties, solubility, Hardness, Friability, % drug content in tablet formulation.FTIR and SEM show no physical interaction between them with no chemical change. Co processing ofexcipients was evaluated for Drug release, mean dissolution time and dissolution efficiency Sucrose:MCC (2:1 used to extend the drug release up to 6 hr, we can prepare sustain release tablet of this COprocessing by incorporation of sustain release polymer. MCC: Kyron was used to prepare immediatedrug release. So based on these properties we was prepared immediate release formulation and sustainrelease formulation. Co-processing of Sucrose: MCC have been used to achieve sustain release byincorporation of pectin, by using this combination we can achieve sustain release up to 10 hr similarlyKyron: MCC was used in immediate release formulation. Comparison with both IR and SR marketedproduct and evaluated for F2 test shows there is similarity in dissolution profile between both thebatches.

  8. Visual, Critical, and Scientific Thinking Dispositions in a 3rd Grade Science Classroom

    Science.gov (United States)

    Foss, Stacy

    Many American students leave school without the required 21st century critical thinking skills. This qualitative case study, based on the theoretical concepts of Facione, Arheim, and Vygotsky, explored the development of thinking dispositions through the arts in science on the development of scientific thinking skills when used as a conceptual thinking routine in a rural 3rd grade classroom. Research questions examined the disposition to think critically through the arts in science and focused on the perceptions and experiences of 25 students with the Visual Thinking Strategy (VTS) process. Data were collected from classroom observations (n = 10), student interviews (n = 25), teacher interviews ( n = 1), a focus group discussion (n = 3), and artifacts of student work (n = 25); these data included perceptions of VTS, school culture, and classroom characteristics. An inductive analysis of qualitative data resulted in several emergent themes regarding disposition development and students generating questions while increasing affective motivation. The most prevalent dispositions were open-mindedness, the truth-seeking disposition, the analytical disposition, and the systematicity disposition. The findings about the teachers indicated that VTS questions in science supported "gradual release of responsibility", the internalization of process skills and vocabulary, and argumentation. This case study offers descriptive research that links visual arts inquiry and the development of critical thinking dispositions in science at the elementary level. A science curriculum could be developed, that emphasizes the development of thinking dispositions through the arts in science, which in turn, could impact the professional development of teachers and learning outcomes for students.

  9. Glucose cryoprotectant affects glutathione-responsive antitumor drug release from polysaccharide nanoparticles.

    Science.gov (United States)

    Curcio, Manuela; Blanco-Fernández, Bárbara; Costoya, Alejandro; Concheiro, Angel; Puoci, Francesco; Alvarez-Lorenzo, Carmen

    2015-06-01

    The aim of this work was to prepare polysaccharide-based nanoparticles (NPs) sensitive to glutathione (GSH), and to elucidate the effect of the concentration of glucose used as cryoprotectant during freeze-drying on the GSH-responsiveness. NPs were obtained via ionic interaction between negatively charged polysaccharides, chondroitin sulfate and dermatan sulfate, and the positively charged thiolated chitosan (CSSH), and crosslinking of CSSH before or after the nanoparticles formation with a disulfide-bond containing crosslinker, N,N'-bis(acryloyl)cystamine (BAC). NPs were freeze-dried with glucose at two different concentrations (0.5 and 5.0%w/w) and then characterized as methotrexate delivery systems, studying the effect of GSH concentration on drug release, efficacy against tumor cells and cellular internalization. Non-loaded NPs were highly compatible with murine fibroblasts and showed a suitable size for being used in anticancer therapy. When methotrexate-loaded NPs were freeze-dried with the highest glucose concentration, they lost their responsiveness to GSH concentration in vitro. Drug-loaded NPs were shown to inhibit the growth of tumor cells (HeLa and CHO-K1) with greater efficiency than free methotrexate, disregarding the concentration of glucose used for freeze-drying. Nevertheless, confocal microscopy studies revealed that cellular internalization of NPs freeze-dried with 5.0% glucose is more difficult than for NPs freeze-dried with lower glucose concentration. Thus, concentration of glucose cryoprotectant should be taken into account during development of NPs intended to release the drug as a function of GSH levels, due to the specific interactions of glucose with GSH. PMID:25917641

  10. Plutonium Disposition by Immobilization

    International Nuclear Information System (INIS)

    The ultimate goal of the Department of Energy (DOE) Immobilization Project is to develop, construct, and operate facilities that will immobilize between 17 to 50 tonnes (MT) of U.S. surplus weapons-usable plutonium materials in waste forms that meet the ''spent fuel'' standard and are acceptable for disposal in a geologic repository. Using the ceramic can-in-canister technology selected for immobilization, surplus plutonium materials will be chemically combined into ceramic forms which will be encapsulated within large canisters of high level waste (HLW) glass. Deployment of the immobilization capability should occur by 2008 and be completed within 10 years. In support of this goal, the DOE Office of Fissile Materials Disposition (MD) is conducting development and testing (D and T) activities at four DOE laboratories under the technical leadership of Lawrence Livermore National Laboratory (LLNL). The Savannah River Site has been selected as the site for the planned Plutonium Immobilization Plant (PIP). The D and T effort, now in its third year, will establish the technical bases for the design, construction, and operation of the U. S. capability to immobilize surplus plutonium in a suitable and cost-effective manner. Based on the D and T effort and on the development of a conceptual design of the PIP, automation is expected to play a key role in the design and operation of the Immobilization Plant. Automation and remote handling are needed to achieve required dose reduction and to enhance operational efficiency

  11. Drug membrane transporters and CYP3A4 are affected by hypericin, hyperforin or aristoforin in colon adenocarcinoma cells.

    Science.gov (United States)

    Šemeláková, M; Jendželovský, R; Fedoročko, P

    2016-07-01

    Our previous results have shown that the combination of hypericin-mediated photodynamic therapy (HY-PDT) at sub-optimal dose with hyperforin (HP) (compounds of Hypericum sp.), or its stable derivative aristoforin (AR) stimulates generation of reactive oxygen species (ROS) leading to antitumour activity. This enhanced oxidative stress evoked the need for an explanation for HY accumulation in colon cancer cells pretreated with HP or AR. Generally, the therapeutic efficacy of chemotherapeutics is limited by drug resistance related to the overexpression of drug efflux transporters in tumour cells. Therefore, the impact of non-activated hypericin (HY), HY-PDT, HP and AR on cell membrane transporter systems (Multidrug resistance-associated protein 1-MRP1/ABCC1, Multidrug resistance-associated protein 2-MRP2/ABCC2, Breast cancer resistance protein - BCRP/ABCG2, P-glycoprotein-P-gp/ABCC1) and cytochrome P450 3A4 (CYP3A4) was evaluated. The different effects of the three compounds on their expression, protein level and activity was determined under specific PDT light (T0+, T6+) or dark conditions (T0- T6-). We found that HP or AR treatment affected the protein levels of MRP2 and P-gp, whereas HP decreased MRP2 and P-gp expression mostly in the T0+ and T6+ conditions, while AR decreased MRP2 in T0- and T6+. Moreover, HY-PDT treatment induced the expression of MRP1. Our data demonstrate that HP or AR treatment in light or dark PDT conditions had an inhibitory effect on the activity of individual membrane transport proteins and significantly decreased CYP3A4 activity in HT-29 cells. We found that HP or AR significantly affected intracellular accumulation of HY in HT-29 colon adenocarcinoma cells. These results suggest that HY, HP and AR might affect the efficiency of anti-cancer drugs, through interaction with membrane transporters and CYP3A4. PMID:27261575

  12. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    Directory of Open Access Journals (Sweden)

    De Maria Ruggero

    2008-07-01

    Full Text Available Abstract Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w had a mean size Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  13. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons.

    Science.gov (United States)

    Morte, Maria I; Carreira, Bruno P; Falcão, Maria J; Ambrósio, António F; Soares-da-Silva, Patrício; Araújo, Inês M; Carvalho, Caetana M

    2013-12-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3mM, for 24h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK. These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent. PMID:24055897

  14. Comparing Teacher Dispositions in China and the USA

    Science.gov (United States)

    Shao, Kun; Tamashiro, Roy

    2013-01-01

    In studies conducted in the USA, teacher dispositional factors such as enthusiasm, professional esteem and learning motivation often emerge as the most significant variables affecting student learning and achievement from the primary grades through higher education. Do these factors play as significant a role in student learning and achievement in…

  15. Determination The Critical Thinking and Empathy Disposition of Nursing Students

    OpenAIRE

    Günaydın, Nevin; Ünsal Barlas, Gül

    2015-01-01

    AbstractObjective: The aim of this study was to determine the factors affecting critical thinking and empathic disposition of nursing students and the relationships between the empathy and critical thinking disposition in nursing education.Methods: The study was carried out on undergraduate students at nursing school during 2011-2012 academic years. The sample consisted of 276 students who had agreed to participate in the research, 30.7% of them were the first year students (freshman),  27.4 ...

  16. Challenges and Opportunities for Increasing the Knowledge Base Related to Drug Biotransformation and Pharmacokinetics during Growth and Development.

    Science.gov (United States)

    Leeder, J Steven; Meibohm, Bernd

    2016-07-01

    It is generally acknowledged that there is a need and role for informative pharmacokinetic models to improve predictions and simulation as well as individualization of drug therapy in pediatric populations of different ages and developmental stages. This special issue contains more than 20 papers responding to the challenge of providing new information on scaling factors, ontogeny functions for drug metabolizing enzymes and transporters, the mechanisms underlying the observed developmental trajectories for these gene products, age-dependent changes in physiologic processes affecting drug disposition in children, as well as in vitro and in vivo studies describing the relative contribution of ontogeny and genetic factors as sources of variability in drug disposition in children. Considered together, these contributions serve to illustrate some of the current limitations regarding sample availability, number, and quality, but also provide a framework that allows for the potential value of the results of a given study to be interpreted within the context of these limitations. Among the challenges for the future are improving our understanding of the mechanisms regulating age-dependent changes in factors influencing drug disposition and response, thereby facilitating generalization to systems lacking detailed data, better integrating age-dependent changes in pharmacokinetics with age-dependent changes in pharmacodynamics, and allowing better predictability and individualization of drug disposition and response across the pediatric age spectrum. PMID:27302933

  17. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    Title 44 United States Code, ''Public Printing and Documents,'' regulations cited in the General Services Administration's (GSA) ''Federal Information Resources Management Regulations'' (FIRMR), Part 201-9, ''Creation, Maintenance, and Use of Records,'' and regulation issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter XII, Subchapter B, ''Records Management,'' require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA's General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 2, contains ''NRC's Comprehensive Records Disposition Schedule,'' and the original authorized approved citation numbers issued by NARA. Rev. 2 totally reorganizes the records schedules from a functional arrangement to an arrangement by the host office. A subject index and a conversion table have also been developed for the NRC schedules to allow staff to identify the new schedule numbers easily and to improve their ability to locate applicable schedules

  18. How treatment affects the brain: meta-analysis evidence of neural substrates underpinning drug therapy and psychotherapy in major depression.

    Science.gov (United States)

    Boccia, Maddalena; Piccardi, Laura; Guariglia, Paola

    2016-06-01

    The idea that modifications of affect, behavior and cognition produced by psychotherapy are mediated by biological underpinnings predates the advent of the modern neurosciences. Recently, several studies demonstrated that psychotherapy outcomes are linked to modifications in specific brain regions. This opened the debate over the similarities and dissimilarities between psychotherapy and pharmacotherapy. In this study, we used activation likelihood estimation meta-analysis to investigate the effects of psychotherapy (PsyTh) and pharmacotherapy (DrugTh) on brain functioning in Major Depression (MD). Our results demonstrate that the two therapies modify different neural circuits. Specifically, PsyTh induces selective modifications in the left inferior and superior frontal gyri, middle temporal gyrus, lingual gyrus and middle cingulate cortex, as well as in the right middle frontal gyrus and precentral gyrus. Otherwise, DrugTh selectively affected brain activation in the right insula in MD patients. These results are in line with previous evidence of the synergy between psychotherapy and pharmacotherapy but they also demonstrate that the two therapies have different neural underpinnings. PMID:26164169

  19. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Ippokratis Pountos

    2012-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

  20. Dispositional Optimism: A Psychological Resource for Mexican-Origin Mothers Experiencing Economic Stress

    OpenAIRE

    Taylor, Zoe E.; Widaman, Keith F.; Robins, Richard W; Jochem, Rachel; Early, Dawnte R.; Conger, Rand D.

    2011-01-01

    Dispositional optimism is believed to be an important psychological resource that buffers families against the deleterious consequences of economic adversity. Using data from a longitudinal study of Mexican-origin families (N = 674), we tested a family stress model specifying that maternal dispositional optimism and economic pressure affect maternal internalizing symptoms, which, in turn, affects parenting behaviors and children’s social adjustment. As predicted, maternal optimism and economi...

  1. Generic substitution of antidiabetic drugs in the elderly does not affect adherence

    Directory of Open Access Journals (Sweden)

    Francesco Trotta

    2014-12-01

    Full Text Available INTRODUCTION: The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. MATERIALS AND METHODS: All elderly residents of the Umbria Region who received at least 2 prescriptions of antidiabetics in 2010 and 2011 were included in the study. Switching was defined as the dispensing of two different products of the same substance in a series of two prescriptions. Single and multiple switchers were identified according to the number of switches during 2011. Switching relevant to the three off-patent substances with generic use ≥ 5% (metformin, gliclazide and repaglinide was quantified. The effect of switching on adherence, defined as the proportion of days in 2011 covered by prescriptions (Medication Possession Ratio, MPR, was estimated. RESULTS: Among the 15 964 patients receiving antidiabetics (14.4% of the elderly population 9211 were prescribed at least one of the generic substances. Of these patients, 23.3% experienced a single switch and 15.7% were multiple switchers (61.0% never switched. The proportion of multiple switchers increased with the number of prescriptions, reaching 26% among patients with ≥ 11 prescriptions. MPR was 62%, 62% and 72%, respectively among non-switchers, single and multiple switchers. CONCLUSIONS: In elderly patients treated with antidiabetics, the substitution between branded and unbranded products (as well as between generics of the same substance, did not negatively affect adherence.

  2. Waste forms for plutonium disposition

    International Nuclear Information System (INIS)

    The field of plutonium disposition is varied and of much importance, since the Department of Energy has decided on the hybrid option for disposing of the weapons materials. This consists of either placing the Pu into mixed oxide fuel for reactors or placing the material into a stable waste form such as glass. The waste form used for Pu disposition should exhibit certain qualities: (1) provide for a suitable deterrent to guard against proliferation; (2) be of minimal volume, i.e., maximize the loading; and (3) be reasonably durable under repository-like conditions. This paper will discuss several Pu waste forms that display promising characteristics

  3. Disposition Options for Uranium-233

    International Nuclear Information System (INIS)

    The U.S. Department of Energy (DOE) Fissile Materials Disposition Program (MD), in support of the U.S. arms-control and nonproliferation policies, has initiated a program to disposition surplus weapons-usable fissile material by making it inaccessible and unattractive for use in nuclear weapons. Weapons-usable fissile materials include plutonium, high-enriched uranium (HEU), and uranium-233 (sup 233)U. In support of this program, Oak Ridge National Laboratory led DOE's contractor efforts to identify and characterize options for the long-term storage and disposal of excess (sup 233)U. Five storage and 17 disposal options were identified and are described herein

  4. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    Effective January 1, 1982, NRC will institute records retention and disposal practices in accordance with the approved Comprehensive Records Disposition Schedule (CRDS). CRDS is comprised of NRC Schedules (NRCS) 1 to 4 which apply to the agency's program or substantive records and General Records Schedules (GRS) 1 to 22 which apply to housekeeping or facilitative records. The schedules are assembled functionally/organizationally to facilitate their use. Preceding the records descriptions and disposition instructions for both NRCS and GRS, there are brief statements on the organizational units which accumulate the records in each functional area, and other information regarding the schedules' applicability

  5. Happiness, Dispositions and the Self

    DEFF Research Database (Denmark)

    Klausen, Søren Harnow

    2016-01-01

    I argue that happiness is an exclusively categorical mental state. Daniel Haybron’s inclusion of dispositions into his emotional state theory rests of a confusion of constituents of happiness in the narrow psychological sense with objects of prudential concern, to which obviously belong “mood...... propensities” and other dispositional states. I further argue that while it is probably correct to require of a constituent of happiness that it must in some sense be “deep” and belong to, or directly impact on, a persons’ self, the importance of depth may be overrated by the emotional state theory, which also...

  6. What drives the disposition effect?

    OpenAIRE

    Zuchel, Heiko

    2001-01-01

    Why do some investors tend to ''sell winners too early and ride losers too long''? Such behavior, labeled the disposition effect, has been attributed to biases in return expectations, time-varying risk-aversion based on the value function of prospect theory, and regret theory. I review these explanations and argue that none of them is satisfactory because they either fail to capture the disposition effect or because they are not supported by emprical evidence. I point out that there is a larg...

  7. Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism.

    Science.gov (United States)

    Imbert, L; Cojean, S; Libong, D; Chaminade, P; Loiseau, P M

    2014-09-01

    This study focuses on the mechanism of sitamaquine-resistance in Leishmania donovani. Sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (WT) and of sitamaquine-resistant (Sita-R160) L. donovani promastigotes, respectively. The sitamaquine accumulation was a concentration-dependent process in WT whereas a saturation occurred in Sita-R160 suggesting a reduced uptake or an increase of the sitamaquine efflux. Membrane negative phospholipids being the main target for sitamaquine uptake, a lipidomic analysis showed that sitamaquine-resistance did not rely on a decrease of membrane negative phospholipid rate in Sita-R160, discarding the hypothesis of reduced uptake. However, sterol and phospholipid metabolisms were strongly affected in Sita-R160 suggesting that sitamaquine-resistance could be related to an alteration of phosphatidylethanolamine-N-methyl-transferase and choline kinase activities and to a decrease in cholesterol uptake and of ergosterol biosynthesis. Preliminary data of proteomics analysis exhibited different protein profiles between WT and Sita-160R remaining to be characterized. PMID:25201056

  8. A disposition of interpolation techniques

    NARCIS (Netherlands)

    Knotters, M.; Heuvelink, G.B.M.

    2010-01-01

    A large collection of interpolation techniques is available for application in environmental research. To help environmental scientists in choosing an appropriate technique a disposition is made, based on 1) applicability in space, time and space-time, 2) quantification of accuracy of interpolated v

  9. Regulation of drug-metabolizing enzymes by local and systemic liver injuries

    Science.gov (United States)

    Guo, Yan; Hu, Bingfang; Xie, Yang; Billiar, Timothy R.; Sperry, Jason L.; Huang, Min; Xie, Wen

    2016-01-01

    Introduction Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver. Areas covered This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed. Expert opinion Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients. PMID:26751558

  10. Emotion-based Dispositions to Rash Action: Positive and Negative Urgency

    OpenAIRE

    Cyders, Melissa A; Smith, Gregory T.

    2008-01-01

    Under heightened emotional states, individuals are more inclined to engage in ill-considered or rash actions than at other times. The authors present evidence for the existence of two related traits called positive and negative urgency. The traits refer to individual differences in the disposition to engage in rash action when experiencing extreme positive and negative affect, respectively. The authors provide evidence that these traits are distinct from other dispositions toward rash action,...

  11. CRITICAL THINKING DISPOSITION IN STUDENTS OF VOCATIONAL SCHOOL OF HEALTH SERVICES

    OpenAIRE

    Ayşe GÜROL; USLU, Seval; Özlem EROL POLAT; Nimet YİĞİT; YÜCEL, Osman

    2013-01-01

    The purpose of this study is to analyze the critical thinking dispositions of the students attending at the associate degree program of Vocational School of Health Services and to determine the factors affecting their critical thinking dispositions. All the students, attending at the associate degree program at Vocational School of Health Services of a university in 2010-2011 academic year, constituted the population of the study. 413 students, who were accessible and accepted to participate ...

  12. Critical Thinking Disposition in Students of Vocational School of Health Services

    OpenAIRE

    Ayşe GÜROL; USLU, Seval; POLAT, Özlem EROL; Nimet YİĞİT; YÜCEL, Osman

    2013-01-01

    The purpose of this study is to analyze the critical thinking dispositions of the students attending at the associate degree program of Vocational School of Health Services and to determine the factors affecting their critical thinking dispositions. All the students, attending at the associate degree program at Vocational School of Health Services of a university in 2010-2011 academic year, constituted the population of the study. 413 students, who were accessible and accepted to participate ...

  13. A disposition of interpolation techniques

    OpenAIRE

    Knotters, M.; Heuvelink, G.B.M.

    2010-01-01

    A large collection of interpolation techniques is available for application in environmental research. To help environmental scientists in choosing an appropriate technique a disposition is made, based on 1) applicability in space, time and space-time, 2) quantification of accuracy of interpolated values, 3) incorporation of ancillary information, and 4) incorporation of process knowledge. The described methods include inverse distance weighting, nearest neighbour methods, geostatistical inte...

  14. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    Science.gov (United States)

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. PMID:25224362

  15. Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges.

    Science.gov (United States)

    Haque, Shadabul; Whittaker, Michael R; McIntosh, Michelle P; Pouton, Colin W; Kaminskas, Lisa M

    2016-08-01

    The inhaled delivery of nanomedicines can provide a novel, non-invasive therapeutic strategy for the more localised treatment of lung-resident diseases and potentially also enable the systemic delivery of therapeutics that are otherwise administered via injection alone. However, the clinical translation of inhalable nanomedicine is being hampered by our lack of understanding about their disposition and clearance from the lungs. This review provides a comprehensive overview of the biodegradable nanomaterials that are currently being explored as inhalable drug delivery systems and our current understanding of their disposition within, and clearance from the lungs. The safety of biodegradable nanomaterials in the lungs is discussed and latest updates are provided on the impact of inflammation on the pulmonary pharmacokinetics of inhaled nanomaterials. Overall, the review provides an in-depth and critical assessment of the lung clearance mechanisms for inhaled biodegradable nanomedicines and highlights the opportunities and challenges for their translation into the clinic. PMID:27033834

  16. 19 CFR 174.22 - Accelerated disposition of protest.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Accelerated disposition of protest. 174.22 Section... OF THE TREASURY (CONTINUED) PROTESTS Review and Disposition of Protests § 174.22 Accelerated disposition of protest. (a) Request for accelerated disposition. Accelerated disposition of a protest filed...

  17. Alcohol use and incarceration adversely affect HIV-1 RNA suppression among injection drug users starting antiretroviral therapy

    OpenAIRE

    Palepu, Anita; Tyndall, Mark W.; Li, Kathy; Yip, Benita; O’Shaughnessy, Michael V.; Schechter, Martin T.; Montaner, Julio S.G.; Hogg, Robert S.

    2003-01-01

    We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment ...

  18. The interaction between motivational disposition and participative budgeting

    DEFF Research Database (Denmark)

    Sandalgaard, Niels; Bukh, Per Nikolaj; Poulsen, Carsten Stig

    2011-01-01

    The purpose of the paper is to report the findings of a study of how dispositional factors of motivation rooted in personality interact with participative budgeting to affect budget goal commitment. The results indicate that the effect of increased budgetary participation on budget goal commitment...... is largest for subordinates with a high need for power or a low need for affiliation. For subordinates with a low need for power or a high need for affiliation the effect of budgetary participation is small....

  19. Derivation of plutonium-239 materials disposition categories

    International Nuclear Information System (INIS)

    At this time, the Office of Fissile Materials Disposition within the DOE, is assessing alternatives for the disposition of excess fissile materials. To facilitate the assessment, the Plutonium-Bearing Materials Feed Report for the DOE Fissile Materials Disposition Program Alternatives report was written. The development of the material categories and the derivation of the inventory quantities associated with those categories is documented in this report

  20. The Difficulty of Teacher Dispositions: Considering Professional Dispositions for Preservice English Teachers

    Science.gov (United States)

    Shoffner, Melanie; Sedberry, Tiffany; Alsup, Janet; Johnson, Tara Star

    2014-01-01

    This article explores the place of teacher dispositions in English teacher preparation by contextualizing the issue of dispositions in English teacher preparation. This allows consideration for the importance of developing professional dispositions during English teacher preparation by recognizing that various stakeholders (teacher educators,…

  1. Surplus plutonium disposition draft environmental impact statement. Volume 1, Part A

    International Nuclear Information System (INIS)

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel. This volume includes background information; purpose of and need for the proposed action; alternatives for disposition of surplus weapons useable plutonium; and

  2. Metabolism and Disposition of Prescription Opioids: A Review.

    Science.gov (United States)

    DePriest, A Z; Puet, B L; Holt, A C; Roberts, A; Cone, E J

    2015-07-01

    Opioid analgesics are commonly prescribed for acute and chronic pain, but are subject to abuse. Consequently, toxicology testing programs are frequently implemented for both forensic and clinical applications. Understanding opioid metabolism and disposition is essential for assessing risk of toxicity and, in some cases, providing additional information regarding risk of therapeutic failure. Opioids significantly metabolized by the cytochromeP450 (CYP450) enzyme system maybe subjectto drug-drug interactions, including codeine, hydrocodone, oxycodone, fentanyl, meperidine, methadone, buprenorphine, and tramadol. CYP2D6 metabolism is polymorphic, and pharmacogenetic testing has been investigated for codeine, tramadol, oxycodone, and hydrocodone. CYP2B6 pharmacogenetic testing of methadone may reduce the risk of cardiac toxicity associated with the S-enantiomer. Opioids metabolized primarily by uridine 5'-diphospho-glucuronsyltransferase (UGT) enzymes include morphine, hydromorphone, dihydrocodeine, oxymorphone, levorphanol, and tapentadol. Parent and metabolite disposition is described for blood, oral fluid, and urine. Parent drug is most commonly detected in blood and oral fluid, whereas metabolites typically predominate in urine. Oral fluid/blood ratios exceed 1 for most opioids, making this an excellent alternative matrix for testing of this drug class. Metabolites of codeine, hydrocodone, and oxycodone are commercially available, and knowledge of metabolism is necessary for correct interpretation. PMID:26227254

  3. Brain regions involved in dispositional mindfulness during resting state and their relation with well-being.

    Science.gov (United States)

    Kong, Feng; Wang, Xu; Song, Yiying; Liu, Jia

    2016-08-01

    Mindfulness can be viewed as an important dispositional characteristic that reflects the tendency to be mindful in daily life, which is beneficial for improving individuals' both hedonic and eudaimonic well-being. However, no study to date has examined the brain regions involved in individual differences in dispositional mindfulness during the resting state and its relation with hedonic and eudaimonic well-being. To investigate this issue, the present study employed resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional homogeneity (ReHo) that measures the local synchronization of spontaneous brain activity in a large sample. We found that dispositional mindfulness was positively associated with the ReHo in the left orbitofrontal cortex (OFC), left parahippocampal gyrus (PHG), and right insula implicated in emotion processing, body awareness, and self-referential processing, and negatively associated with the ReHo in right inferior frontal gyrus (IFG) implicated in response inhibition and attentional control. Furthermore, we found different neural associations with hedonic (i.e., positive and negative affect) and eudaimonic well-being (i.e., the meaningful and purposeful life). Specifically, the ReHo in the IFG predicted eudaimonic well-being whereas the OFC predicted positive affect, both of which were mediated by dispositional mindfulness. Taken together, our study provides the first evidence for linking individual differences in dispositional mindfulness to spontaneous brain activity and demonstrates that dispositional mindfulness engages multiple brain mechanisms that differentially influence hedonic and eudaimonic well-being. PMID:26360907

  4. Does Federal Financial Aid Affect College Enrollment? Evidence from Drug Offenders and the Higher Education Act of 1998

    OpenAIRE

    Lovenheim, Michael F.; Emily G. Owens

    2013-01-01

    In 2001, amendments to the Higher Education Act made people convicted of drug offenses ineligible for federal financial aid for up to two years after their conviction. Using rich data on educational outcomes and drug charges in the NLSY 1997, we show that this law change had a large negative impact on the college attendance of students with drug convictions. On average, the temporary ban on federal financial aid increased the amount of time between high school graduation and college enrollmen...

  5. Do dispositional attributions regarding peer endorsers influence product evaluations?

    Science.gov (United States)

    Sørum, Kim André; Grape, Kjetil Marius; Silvera, David

    2003-02-01

    The effect of a peer endorsement advertisement on research participants' attitudes toward the advertised product was examined. An advertisement for a Seiko watch and a questionnaire were administered to participants. The degree of dispositional attributions regarding the endorser's motivation and participants' subsequent attitudes associated with the Seiko watch were measured. In addition, other factors that might affect product evaluation were measured. Whether product evaluation could be accounted for by correspondence bias was investigated. The results showed that the degree of dispositional attributions correlated with product evaluations. There was no correspondence bias. Possible causes for the lack of correspondence bias are discussed and a model suggesting factors accounting for participants' product evaluations is presented. PMID:12603002

  6. Music and Emotion: the Dispositional or Arousal theory

    Directory of Open Access Journals (Sweden)

    Alessandra Buccella

    2012-05-01

    Full Text Available One of the ways of analysing the relationship between music and emotions in through musical expressiveness.As the theory I discuss in this paper puts it, expressiveness in a particular kind of music's secondary quality or, to use the term which gives the theory its name, a disposition of music to arouse a certain emotional response in listeners.The most accurate version of the dispositional theory is provided by Derek Matravers in his book Art and Emotion and in other papers: what I will try to do, then, is to illustrate Matravers theory and claim that it is a good solution to many problems concerning music and its capacity to affect our inner states.

  7. PAN-811 Blocks Chemotherapy Drug-Induced In Vitro Neurotoxicity, While Not Affecting Suppression of Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Jiang

    2016-01-01

    Full Text Available Chemotherapy often results in cognitive impairment, and no neuroprotective drug is now available. This study aimed to understand underlying neurotoxicological mechanisms of anticancer drugs and to evaluate neuroprotective effects of PAN-811. Primary neurons in different concentrations of antioxidants (AOs were insulted for 3 days with methotrexate (MTX, 5-fluorouracil (5-FU, or cisplatin (CDDP in the absence or presence of PAN-811·Cl·H2O. The effect of PAN-811 on the anticancer activity of tested drugs was also examined using mouse and human cancer cells (BNLT3 and H460 to assess any negative interference. Cell membrane integrity, survival, and death and intramitochondrial reactive oxygen species (ROS were measured. All tested anticancer drugs elicited neurotoxicity only under low levels of AO and elicited a ROS increase. These results suggested that ROS mediates neurotoxicity of tested anticancer drugs. PAN-811 dose-dependently suppressed increased ROS and blocked the neurotoxicity when neurons were insulted with a tested anticancer drug. PAN-811 did not interfere with anticancer activity of anticancer drugs against BNLT3 cells. PAN-811 did not inhibit MTX-induced death of H460 cells but, interestingly, demonstrated a synergistic effect with 5-FU or CDDP in reducing cancer cell viability. Thus, PAN-811 can be a potent drug candidate for chemotherapy-induced cognitive impairment.

  8. 25 CFR 11.1012 - Dispositional alternatives.

    Science.gov (United States)

    2010-04-01

    ... LAW AND ORDER CODE Juvenile Offender Procedure § 11.1012 Dispositional alternatives. (a) If a minor has been adjudged a juvenile offender, the children's court may make the following disposition: (1) Place the minor on probation subject to conditions set by the children's court; (2) Place the minor...

  9. Knowledge, Skills, and Dispositions for Diversity

    Science.gov (United States)

    Jones, Anne

    2011-01-01

    The purposes of this research are to explore how currently assessed diversity knowledge, diversity skills, and diversity dispositions of pre-service teachers (PST) relate to each other and further to surmise if the presence of diversity knowledge, diversity skills, and diversity dispositions manifests in cultural efficacy and a general cultural…

  10. Overview of surplus weapons plutonium disposition

    Energy Technology Data Exchange (ETDEWEB)

    Rudy, G.

    1996-05-01

    The safe disposition of surplus weapons useable plutonium is a very important and urgent task. While the functions of long term storage and disposition directly relate to the Department`s weapons program and the environmental management program, the focus of this effort is particularly national security and nonproliferation.

  11. Reclaiming the Moral in the Dispositions Debate

    Science.gov (United States)

    Burant, Terry J.; Chubbuck, Sharon M.; Whipp, Joan L.

    2007-01-01

    This article addresses the current debates about the definition and assessment of dispositions in teacher education. Competing perspectives on the definitions and assessment of dispositions in teacher education are examined and critiqued, and a renewed commitment to foregrounding the moral nature of teaching is suggested. Recommendations for…

  12. Dispositional optimism and loneliness in older men

    NARCIS (Netherlands)

    Rius-Ottenheim, N.; Kromhout, D.; Mast, van der R.C.; Zitman, F.G.; Geleijnse, J.M.; Giltay, E.J.

    2012-01-01

    Background: Dispositional optimism, defined as a generalized tendency to positive outcome expectancies, is associated with well-being and successful aging. However, it remains unclear whether optimism is also correlated to less feelings of loneliness over time. We aimed to determine whether disposit

  13. ESTIMATING IMPURITIES IN SURPLUS PLUTONIUM FOR DISPOSITION

    Energy Technology Data Exchange (ETDEWEB)

    Allender, J.; Moore, E.

    2013-07-17

    The United States holds at least 61.5 metric tons (MT) of plutonium that is permanently excess to use in nuclear weapons programs, including 47.2 MT of weapons-grade plutonium. Surplus inventories will be stored safely by the Department of Energy (DOE) and then transferred to facilities that will prepare the plutonium for permanent disposition. The Savannah River National Laboratory (SRNL) operates a Feed Characterization program for the Office of Fissile Materials Disposition of the National Nuclear Security Administration and the DOE Office of Environmental Management. Many of the items that require disposition are only partially characterized, and SRNL uses a variety of techniques to predict the isotopic and chemical properties that are important for processing through the Mixed Oxide Fuel Fabrication Facility and alternative disposition paths. Recent advances in laboratory tools, including Prompt Gamma Analysis and Peroxide Fusion treatment, provide data on the existing inventories that will enable disposition without additional, costly sampling and destructive analysis.

  14. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    Effective January 1, 1982, NRC will institute records retention and disposal practives in accordance with the approved Comprehensive Records Disposition Schedule (CRDS). CRDS is comprised of NRC Schedules (NRCS) 1 to 4 which apply to the agency's program or substantive records and General Records Schedules (GRS) 1 to 24 which apply to housekeeping or facilitative records. NRCS-I applies to records common to all or most NRC offices; NRCS-II applies to program records as found in the various offices of the Commission, Atomic Safety and Licensing Board Panel, and the Atomic Safety and Licensing Appeal Panel; NRCS-III applies to records accumulated by the Advisory Committee on Reactor Safeguards; and NRCS-IV applies to records accumulated in the various NRC offices under the Executive Director for Operations. The schedules are assembled functionally/organizationally to facilitate their use. Preceding the records descriptions and disposition instructions for both NRCS and GRS, there are brief statements on the organizational units which accumulate the records in each functional area, and other information regarding the schedules' applicability

  15. When bad things happen to bad people: using disposition theory to explore the effects of cautionary tales.

    Science.gov (United States)

    Marett, Emily Garrigues

    2015-01-01

    Cautionary tales are a prevalent form of entertainment narrative in media-saturated environments, yet they have received little empirical examination. Using disposition theory, this study manipulated affective disposition toward the protagonist in order to explore the effects of exposure to a cautionary tale on adoption of prosocial attitudes and behavioral intentions. A between-subjects experimental design was used with 2 conditions (positive/negative) and a control group (n = 305). Results provide evidence that exposure to cautionary tales positively influences adoption of attitudes and intentions to purchase a carbon monoxide detector and talk about accidental carbon monoxide poisoning. Affective disposition influenced identification with the protagonist, and perceptions that the protagonist deserved the negative consequences experienced in the cautionary tale narrative. Findings also suggest that identification mediates the relationship between affective disposition and perceived risk. PMID:25495266

  16. Disposition of diminazene aceturate (Berenil) in trypanosome-infected pregnant and lactating cows.

    Science.gov (United States)

    Mdachi, R E; Murilla, G A; Omukuba, J N; Cagnolati, V

    1995-06-01

    Three cows were repeatedly infected with different strains of Trypanosoma congolense and treated intramuscularly each time with a different dose of diminazene aceturate (Berenil). Biphasic decline was observed of the maximal plasma drug levels, which were attained at 15 min after the first treatment and at 30 min after the second and third treatments. The rate constants for the distribution and terminal phases depended on the period of exposure to parasitaemia of the animal at the time of treatment. Maximal diminazene aceturate residue levels were found in milk 8 h post treatment and declined biexponentially to 4.56 ng ml-1 and 8.76 ng ml-1 at 21 days post treatment after 3.5 mg kg-1 and 7.0 mg kg-1 doses, respectively. In the three cows, higher drug residues were found in the kidney (7.04, 3.92 and 7.99 micrograms g-1) than in liver (3.26, 2.87 and 1.24 micrograms g-1) and heart (1.79, 1.25 and 1.03 micrograms g-1). The results of this study indicate that the level of parasitaemia (degree of anaemia) in the animal at the time of treatment affects the distribution, disposition and elimination of diminazene aceturate in the animal. Furthermore, the residue level in milk after treatment depends on the treatment dose and could easily be bioavailable to the consumer. PMID:7571326

  17. Three contextual frameworks for siblingships: nonlinear thinking, disposition, and phallocentrism.

    Science.gov (United States)

    Lament, Claudia

    2013-01-01

    This discussion of Juliet Mitchell's paper "Siblings: Thinking Theory" places her work within the context of three frameworks: nonlinear thinking, disposition, and phallocentrism. The nonlinear dimension of the developmental process demonstrates how the sibling experience is not static, but rather is subject to a natural transmogrification toward new adaptive forms and meanings that occur over the sequential progress of organizational growth. Secondly, dispositional variables tend to be overlooked in their role in how brothers and sisters engage one another, titrate closeness and separateness, and creatively live out their love, admiration, hate, envy, and rivalry with each other. Sensitivities in dispositional leanings, such as special empathic qualities, may even serve to mitigate sibling turbulence. Lastly, the phallocentricity in Western societies privileges an implicitly male perspective that envisions sibling relationships in terms of threatening competitors, as the common linguistic phrase sibling rivalry suggests. This inflection in culture disregards more-expanding qualities in object relationships and aim-giving strategies that are exchanged in sibling play. These variables are not the sole contributors to the sibling experience, but a sampling of influences both from within and outside the child that affect that experience. PMID:26072559

  18. Fernald waste management and disposition

    International Nuclear Information System (INIS)

    Historically waste management within the Department of Energy complex has evolved around the operating principle of packaging waste generated and storing until a later date. In many cases wastes were delivered to onsite waste management organizations with little or no traceability to origin of generation. Sites then stored their waste for later disposition offsite or onsite burial. While the wastes were stored, sites incurred additional labor costs for maintaining, inspecting and repackaging containers and capital costs for storage warehouses. Increased costs, combined with the inherent safety hazards associated with storage of hazardous material make these practices less attractive. This paper will describe the methods used at the Department of Energy's Fernald site by the Waste Programs Management Division to integrate with other site divisions to plan in situ waste characterization prior to removal. This information was utilized to evaluate and select disposal options and then to package and ship removed wastes without storage

  19. Critical thinking dispositions among newly graduated nurses

    OpenAIRE

    Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

    2010-01-01

    wangensteen s., johansson i.s., björkström m.e. & nordström g. (2010) Critical thinking dispositions among newly graduated nurses. Journal of Advanced Nursing 66(10), 2170–2181. Aim The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Background Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are descri...

  20. Proliferation resistance criteria for fissile material disposition

    International Nuclear Information System (INIS)

    The 1994 National Academy of Sciences study open-quotes Management and Disposition of Excess Weapons Plutoniumclose quotes defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This report proposes criteria for assessing the proliferation resistance of these options. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  1. Cocaine disposition in discrete regions of rat brain.

    Science.gov (United States)

    Javaid, J I; Davis, J M

    1993-05-01

    It has been proposed that various effects of psychoactive drugs on the central nervous system may be related to the capacity of the drug to selectively concentrate in specific regions of the brain. In rat brain, cocaine effects on striatal and nucleus accumbens dopaminergic systems show quantitative differences. However, the disposition of cocaine in various brain regions has not been reported. In the present studies we examined the cocaine concentrations over time in serum and discrete brain regions of the rat after single intraperitoneal (i.p.) injection. At different time points (5, 10, 20, 30, 60, 120, and 240 min) after i.p. injection of cocaine hydrochloride (10 mg kg-1, free base) the rats were decapitated and cocaine in serum and various brain regions was quantitated by a specific gas liquid chromatographic method. There was large inter-individual variability in different rats at each time-point. The disposition pattern of cocaine in rats after i.p. administration was similar to that observed in humans after intranasal administration. Initial absorption rate was rapid and, on average, the peak levels of cocaine were achieved in 10 min. The cocaine levels remained relatively high over the next 50 min indicating continual absorption, and then declined with a rate such that the levels 4 h after cocaine administration were undetectable in most of the animals. The overall changes in cocaine levels in various brain regions paralleled the serum concentrations. The area under the cocaine concentration-time curve (AUC) revealed more than three-fold differences in cocaine accumulation in various brain regions. This unequal disposition of cocaine may be responsible in part for differential biochemical effects in different brain regions. PMID:8499585

  2. Dispositional optimism: a psychological resource for Mexican-origin mothers experiencing economic stress.

    Science.gov (United States)

    Taylor, Zoe E; Widaman, Keith F; Robins, Richard W; Jochem, Rachel; Early, Dawnte R; Conger, Rand D

    2012-02-01

    Dispositional optimism is believed to be an important psychological resource that buffers families against the deleterious consequences of economic adversity. Using data from a longitudinal study of Mexican-origin families (N = 674), we tested a family stress model specifying that maternal dispositional optimism and economic pressure affect maternal internalizing symptoms, which, in turn, affects parenting behaviors and children's social adjustment. As predicted, maternal optimism and economic pressure had both independent and interactive effects on maternal internalizing symptoms, and the effects of these variables on changes over time in child social adjustment were mediated by nurturant and involved parenting. The findings replicate and extend previous research on single-parent African American families (Taylor, Larsen-Rife, Conger, Widaman, & Cutrona, 2010), and demonstrate the generalizability of the positive benefits of dispositional optimism in another ethnic group and type of family structure. PMID:22201249

  3. What Affects Reintegration of Female Drug Users after Prison Release? Results of a European Follow-Up Study

    Science.gov (United States)

    Zurhold, Heike; Moskalewicz, Jacek; Sanclemente, Cristina; Schmied, Gabriele; Shewan, David; Verthein, Uwe

    2011-01-01

    The main objective of this follow-up study is to explore factors influencing the success or failure of women in reintegrating after their release from prison. Female drug users in five European cities were tracked after being released from prison. Out of 234 female prisoners contacted in prisons, 59 were included in the follow-up study. Structured…

  4. FACTORS AFFECT THE RELEASE OF PSEUDOEPHDRINE HYDROCHLORIDE FROM THE UNCOATED CATION EXCHANGE RESIN-BASED DRUG DELIVERY SYSTEM IN VITRO

    Institute of Scientific and Technical Information of China (English)

    LI Zhenhua; PI Hongqiong; HE Binglin

    2001-01-01

    In this paper, it was investigated that the effect of parameters such as the ionic strength,pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model drug pseudoephedrine hydrochloride (PE) from uncoated drug-resin complex.The drug-resin complex was prepared by the reaction of PE with strongly acidic cation exchange resin (001 ×4, 001 ×7, 001 ×14). The result showed that the loading of PE increased with the increase of temperatures. The release of PE from drug-resin complex at 37 ℃ was monitored in vitro.From the experiments, it was found that the release rate of PE depends on the pH, composition of the releasing media, increased at lower pH media or with increase of ionic strength of media. Moreover,the release rate of PE was inversely proportional to the cross-linkage and particle size of the cation exchange resin.

  5. Alternative technical summary report for immobilized disposition in deep boreholes: Immobilized disposal of plutonium in coated ceramic pellets in grout without canisters, Version 4.0. Fissile materials disposition program

    Energy Technology Data Exchange (ETDEWEB)

    Wijesinghe, A.M.

    1996-08-23

    This paper summarizes and compares the immobilized and direct borehole disposition alternatives previously presented in the alternative technical summary. The important design concepts, facility features and operational procedures are first briefly described. This is followed by a discussion of the issues that affect the evaluation of each alternative against the programmatic assessment criteria that have been established for selecting the preferred alternatives for plutonium disposition.

  6. Alternative technical summary report for immobilized disposition in deep boreholes: Immobilized disposal of plutonium in coated ceramic pellets in grout without canisters, Version 4.0. Fissile materials disposition program

    International Nuclear Information System (INIS)

    This paper summarizes and compares the immobilized and direct borehole disposition alternatives previously presented in the alternative technical summary. The important design concepts, facility features and operational procedures are first briefly described. This is followed by a discussion of the issues that affect the evaluation of each alternative against the programmatic assessment criteria that have been established for selecting the preferred alternatives for plutonium disposition

  7. KE Basin water dispositioning engineering study

    International Nuclear Information System (INIS)

    This engineering study is a feasibility study of KE Basin water treatment to an acceptable level and dispositioning the treated water to Columbia River, ground through ETF or to air through evaporation

  8. Excess plutonium disposition using ALWR technology

    International Nuclear Information System (INIS)

    The Office of Nuclear Energy of the Department of Energy chartered the Plutonium Disposition Task Force in August 1992. The Task Force was created to assess the range of practicable means of disposition of excess weapons-grade plutonium. Within the Task Force, working groups were formed to consider: (1) storage, (2) disposal,and(3) fission options for this disposition,and a separate group to evaluate nonproliferation concerns of each of the alternatives. As a member of the Fission Working Group, the Savannah River Technology Center acted as a sponsor for light water reactor (LWR) technology. The information contained in this report details the submittal that was made to the Fission Working Group of the technical assessment of LWR technology for plutonium disposition. The following aspects were considered: (1) proliferation issues, (2) technical feasibility, (3) technical availability, (4) economics, (5) regulatory issues, and (6) political acceptance

  9. Teachers’ Critical Thinking Level and Dispositions

    OpenAIRE

    KORKMAZ, Özgen

    2009-01-01

    The purpose of this study was to examine critical thinking level and dispositions of teachers. Participants of this descriptive study were 110 teachers and lecturers. Data of the study were based on literature review and on scores on California Critical Thinking Disposition Inventory. Its alpha coefficient for internal consistency was 0.88. Data analyses were involve determination of descriptive statistics, use of t-test, analysis of variance and Scheffe’s test (p

  10. A causal dispositional account of fitness.

    Science.gov (United States)

    Triviño, Vanessa; Nuño de la Rosa, Laura

    2016-09-01

    The notion of fitness is usually equated to reproductive success. However, this actualist approach presents some difficulties, mainly the explanatory circularity problem, which have lead philosophers of biology to offer alternative definitions in which fitness and reproductive success are distinguished. In this paper, we argue  that none of these alternatives is satisfactory and, inspired by Mumford and Anjum's dispositional theory of causation, we offer a definition of fitness as a causal dispositional property. We argue that, under this framework, the distinctiveness that biologists usually attribute to fitness-namely, the fact that fitness is something different from both the physical traits of an organism and the number of offspring it leaves-can be explained, and the main problems associated with the concept of fitness can be solved. Firstly, we introduce Mumford and Anjum's dispositional theory of causation and present our definition of fitness as a causal disposition. We explain in detail each of the elements involved in our definition, namely: the relationship between fitness and the functional dispositions that compose it, the emergent character of fitness, and the context-sensitivity of fitness. Finally, we explain how fitness and realized fitness, as well as expected and realized fitness are distinguished in our approach to fitness as a causal disposition. PMID:27338570

  11. A Genomewide Screen in Schizosaccharomyces pombe for Genes Affecting the Sensitivity of Antifungal Drugs That Target Ergosterol Biosynthesis

    OpenAIRE

    Fang, Yue; Hu, Lingling; Zhou, Xin; Jaiseng, Wurentuya; Zhang, Ben; Takami, Tomonori; Kuno, Takayoshi

    2012-01-01

    We performed a genomewide screen for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine, that target ergosterol biosynthesis using a Schizosaccharomyces pombe gene deletion library consisting of 3,004 nonessential haploid deletion mutants. We identified 109 mutants that were hypersensitive and 11 mutants that were resistant to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories,...

  12. Teacher Dispositions Affecting Self-Esteem and Student Performance

    Science.gov (United States)

    Helm, Carroll

    2007-01-01

    Research supports several factors related to student success. Darling-Hammond (2000) indicated that the quality of teachers, as measured by whether the teachers were fully certified and had a major in their teaching field, was related to student performance. Measures of teacher preparation and certification were the strongest predictors of student…

  13. Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs.

    Science.gov (United States)

    Lopez, Soledad; Gomez, Enrique; Torres, Maria J; Pozo, David; Fernandez, Tahia D; Ariza, Adriana; Sanz, Maria L; Blanca, Miguel; Mayorga, Cristobalina

    2015-11-01

    The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKs and activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. PMID:26254762

  14. BDDCS Applied to Over 900 Drugs

    DEFF Research Database (Denmark)

    Benet, Leslie Z.; Broccatelli, Fabio; Oprea, Tudor

    2011-01-01

    Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513...

  15. An Evaluation of Personality Traits and Negative Life Events in Explaining Negative Coping Strategies among Drug Dependent People: The Mediating Role of Negative Affects

    Directory of Open Access Journals (Sweden)

    A beigi

    2016-02-01

    Full Text Available Objective: This study aimed to examine the relationship of personality traits and negative life events with coping styles with the mediating role of negative affects in drug dependent people. Method: This was a correlational study wherein the number of 152 participants (drug users completed Cloninger temperament and character inventory, Paykel life events inventory, positive and negative affect schedule (PANAS, and Endler & Parker’s coping inventory for stressful situations. Results: Novelty seeking had an indirect effect on emotional coping styles. Although anger had a mediating role in this relationship, it did not play such a role in the relationship of low self-directedness and negative life events with emotional coping styles. Harm avoidance had a direct effect on avoidant coping styles. Fear and sadness played a mediating role in the structural relationship of harm avoidance and negative events with avoidant coping styles. Reward dependence had an indirect effect on avoidant coping styles. Sadness had a mediating role in the structural relationship between reward dependence and avoidant coping styles. Conclusion: People with traumatic personality traits show negative affects by experiencing stressful negative events which leads to traumatic coping style, including addiction.

  16. The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.

    OpenAIRE

    Rössle, M; Herz, R; Mullen, K D; Jones, D b

    1986-01-01

    The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume ...

  17. Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression.

    Science.gov (United States)

    Hirschberg, Cosima; Sun, Changquan Calvin; Rantanen, Jukka

    2016-09-01

    Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability was investigated using a ring shear tester and tablets were prepared at four different compression pressures using a single punch tablet press. Thereby, a material sparing screening approach was developed to estimate the influence of APIs on behaviour of a given DC formulation. Additionally, this approach is useful for estimating the low threshold amount of API (wt%), at which the properties of an API start affecting the powder behaviour of a given formulation (API-excipient mixture). This threshold will be referred to as critical drug loading. The flowability of microcrystalline cellulose (reference grade pH 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2MPa. Simultaneous visual presentation of both- flowability and tabletability were used for a fast evaluation of manufacturability of a given formulation. The results confirmed that flowability is more sensitive to drug loading than tabletability, and that the critical drug loading for a DC formulation is strongly affected by particulate properties of API. For example, decreasing the particle size of paracetamol led to rapid decrease in flowability index, whereas the tabletability was not affected. PMID:27368089

  18. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Science.gov (United States)

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (Phospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.

  19. Comparison research on stakeholders analysis of disposition of medical dispute between China and abroad

    Directory of Open Access Journals (Sweden)

    Qin Chen

    2015-01-01

    Full Text Available Objective: We learn about the methods, process, effects of each stakeholder and the principles of the disposition of medical dispute home and abroad through stakeholder analysis. Methods: We investigate the methods, process and the principles of the disposition of medical dispute home and abroad by literature retrieval, key informant interview and depth interview. Results: The stakeholders of medical disputes mainly include patients and families, medical staff and hospitals, pharmaceutical companies, governments, laws, non-government organizations and media. They play different roles in medical disputes and have different effects. Over all, patients and families, medical staff and hospitals have the greatest effect and then laws, media, government, non-government organizations and pharmaceutical companies. Conclusion: Different stakeholders affect the disposition of medical disputes differently. It is crucial to establish harmonious relationship between patients and doctors and to build harmonious society by untangling the responsibility between all the stakeholders and dispose medical disputes quickly and effectively.

  20. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Directory of Open Access Journals (Sweden)

    Mugoša S

    2016-08-01

    Full Text Available Snežana Mugoša,1,2 Nataša Djordjević,3 Nina Djukanović,4 Dragana Protić,5 Zoran Bukumirić,6 Ivan Radosavljević,7 Aneta Bošković,8 Zoran Todorović5,9 1Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro, 2Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro; 3Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 4High Medical School “Milutin Milanković”, Belgrade, 5Department of Pharmacology, Clinical Pharmacology and Toxicology, 6Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, 7Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 8Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro; 9Department of Clinical Immunology and Allergy, Medical Center “Bežanijska kosa”, Belgrade, Serbia Abstract: The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6 poor metabolizer alleles (*3, *4, *5, and *6 on a Montenegrin population and its impact on developing adverse drug reactions (ADRs of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9% patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001, with ADRs’ occurrence significantly

  1. NRC comprehensive records disposition schedule. Revision 3

    International Nuclear Information System (INIS)

    Title 44 US Code, ''Public Printing and Documents,'' regulations issued by the General Service Administration (GSA) in 41 CFR Chapter 101, Subchapter B, ''Management and Use of Information and Records,'' and regulations issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter 12, Subchapter B, ''Records Management,'' require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA's General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 3, contains ''NRC's Comprehensive Records Disposition Schedule,'' and the original authorized approved citation numbers issued by NARA. Rev. 3 incorporates NARA approved changes and additions to the NRC schedules that have been implemented since the last revision dated March, 1992, reflects recent organizational changes implemented at the NRC, and includes the latest version of NARA's General Records Schedule (dated August 1995)

  2. NRC comprehensive records disposition schedule. Revision 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    Title 44 US Code, ``Public Printing and Documents,`` regulations issued by the General Service Administration (GSA) in 41 CFR Chapter 101, Subchapter B, ``Management and Use of Information and Records,`` and regulations issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter 12, Subchapter B, ``Records Management,`` require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA`s General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 3, contains ``NRC`s Comprehensive Records Disposition Schedule,`` and the original authorized approved citation numbers issued by NARA. Rev. 3 incorporates NARA approved changes and additions to the NRC schedules that have been implemented since the last revision dated March, 1992, reflects recent organizational changes implemented at the NRC, and includes the latest version of NARA`s General Records Schedule (dated August 1995).

  3. Is drug discontinuation risk of adalimumab compared with etanercept affected by concomitant methotrexate dose in patients with rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    Chen HH

    2016-02-01

    Full Text Available Hsin-Hua Chen,1–6 Der-Yuan Chen,1–3,6–8 Yi-Ming Chen,1–3 Chao-Hsiun Tang9 1Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 4Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6School of Medicine, Chung-Shan Medical University, Taichung, Taiwan, Republic of China; 7Institute of Biomedical Science, Chung-Hsing University, Taichung, Taiwan, Republic of China; 8Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 9School of Health Care Administration, Taipei Medical University, Taipei, Taiwan, Republic of China Objective: To compare drug discontinuation risk between adalimumab (ADA and etanercept (ETN treatment among anti-tumor necrosis factor (anti-TNF-naïve rheumatoid arthritis (RA patients, in particular the influence of concomitant dose of methotrexate (MTX.Methods: This retrospective nationwide population-based cohort study identified 4,592 anti-TNF-naïve RA patients in whom ETN (n=2,609 or ADA (n=1,983 was initiated using National Health Insurance claims data. After adjustment for prior medication, concomitant medication, and baseline demographic data, the relative risk of drug discontinuation in ADA users compared with ETN users was quantified by calculating adjusted hazard ratios (aHRs with 95% confidence intervals (CIs using Cox proportional hazard regression analyses, stratified by the follow-up time (≤1 year, >1 year and/or concomitant MTX dose (≤10 mg/wk, >10 mg/wk.Results: ADA users

  4. Efflux and uptake transporters involved in the disposition of bazedoxifene.

    Science.gov (United States)

    Lušin, Tina Trdan; Mrhar, Aleš; Stieger, Bruno; Kristl, Albin; Berginc, Katja; Trontelj, Jurij

    2016-06-01

    Bazedoxifene, a novel selective estrogen receptor modulator, has complex pharmacokinetics with rapid absorption, high metabolic clearance, low oral bioavailability (6.25 %) and a slow elimination phase. Our hypothesis is that drug uptake and efflux transporters may play an important role in its disposition. To adequately cover all aspects of bazedoxifene transport, several approaches were undertaken: PAMPA assay, ATPase assay, membrane inside-out vesicles and Caco-2 and CHO cell lines. The results obtained from PAMPA experiments showed moderate passive permeability of bazedoxifene (P app ≈ 2 × 10(-6)cm/s), suggesting the existence of an active transport during the rapid absorption phase. The Caco-2 transport assay showed large and significant changes in the measured efflux ratios of bazedoxifene when selective transporter inhibitors were applied: verapamil (a Pgp inhibitor), MK571 (an MRP inhibitor), Ko143 (a BCRP inhibitor) and DIDS (an OATP inhibitor). Additionally, membrane preparation experiments demonstrated the interaction of bazedoxifene with P-gp, MRP2 and BCRP. CHO experiments did not show any interactions of bazedoxifene with OATP1B1 or OATP1B3; therefore, bazedoxifene may be a substrate of other OATP isoform(s). The comprehensive in vitro study indicates a strong involvement of Pgp, MRP, BCRP and OATP in bazedoxifene disposition. PMID:25631963

  5. Excess plutonium disposition: The deep borehole option

    International Nuclear Information System (INIS)

    This report reviews the current status of technologies required for the disposition of plutonium in Very Deep Holes (VDH). It is in response to a recent National Academy of Sciences (NAS) report which addressed the management of excess weapons plutonium and recommended three approaches to the ultimate disposition of excess plutonium: (1) fabrication and use as a fuel in existing or modified reactors in a once-through cycle, (2) vitrification with high-level radioactive waste for repository disposition, (3) burial in deep boreholes. As indicated in the NAS report, substantial effort would be required to address the broad range of issues related to deep bore-hole emplacement. Subjects reviewed in this report include geology and hydrology, design and engineering, safety and licensing, policy decisions that can impact the viability of the concept, and applicable international programs. Key technical areas that would require attention should decisions be made to further develop the borehole emplacement option are identified

  6. Excess plutonium disposition: The deep borehole option

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, K.L.

    1994-08-09

    This report reviews the current status of technologies required for the disposition of plutonium in Very Deep Holes (VDH). It is in response to a recent National Academy of Sciences (NAS) report which addressed the management of excess weapons plutonium and recommended three approaches to the ultimate disposition of excess plutonium: (1) fabrication and use as a fuel in existing or modified reactors in a once-through cycle, (2) vitrification with high-level radioactive waste for repository disposition, (3) burial in deep boreholes. As indicated in the NAS report, substantial effort would be required to address the broad range of issues related to deep bore-hole emplacement. Subjects reviewed in this report include geology and hydrology, design and engineering, safety and licensing, policy decisions that can impact the viability of the concept, and applicable international programs. Key technical areas that would require attention should decisions be made to further develop the borehole emplacement option are identified.

  7. Value-Added Measures of Teacher Candidates' Dispositions

    Science.gov (United States)

    Cosgrove, Maryellen; Carpenter, Barbara

    2012-01-01

    This article describes how a teacher preparation program can positively impact professional dispositions. Pre and post essays from a sample of sixty candidates were qualitatively analyzed to determine the value-added growth of their professional dispositions.

  8. Affective Development in University Education

    Science.gov (United States)

    Grootenboer, Peter

    2010-01-01

    There seems to be an increasing requirement for university courses and programs to develop students' affective qualities (beliefs, values, dispositions and attitudes). This study explored the ways academics determined what the desirable qualities were for their particular disciplines and the pedagogical strategies and approaches they used to…

  9. Pharmacokinetics and disposition of WR-1065 in the rhesus monkey

    International Nuclear Information System (INIS)

    The pharmacokinetics of WR-1065 [S-2-(3-aminopropylamino)ethanethiol] were investigated following iv, intraduodenal, and intraportal administrations in the rhesus monkey. Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from 10-min and 120-min iv infusions. Higher apparent volumes of distribution (Vc and Vss) and higher mean residence time (MRT) were observed at the slower infusion rate but a constant total dose. The values reflect a change in the distribution of WR-1065, possibly due to to saturation of binding in plasma and tissue. However, clearance remained unchanged. For a monkey administered approximately twice the 60 mg/kg dose infused over 120 min, data analysis indicates a disproportional increase in AUC and a substantial decrease in clearance. Low and erratic plasma concentrations of free drug (analytically determined without reductive cleavage) were observed following intraduodenal administration of WR-1065, demonstrating the drug's poor oral bioavailability. Results of intraduodenal administrations of radiolabeled drug indicated than an appreciable amount of the radiolabel in the dose reached the systemic circulation. However, after either intraduodenal or iv administration, only 31% of the AUC (radiolabel) could be accounted for as total (free and disulfide-bound) WR-1065 by specific analysis in separate experiments. Low levels of total cysteamine strongly suggest it to be a minor contributor to the disposition of the drug. Free WR-1065 AUC values following intraportal administration were similar to values obtained after iv administration

  10. Surplus Highly Enriched Uranium Disposition Program plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-10-01

    The purpose of this document is to provide upper level guidance for the program that will downblend surplus highly enriched uranium for use as commercial nuclear reactor fuel or low-level radioactive waste. The intent of this document is to outline the overall mission and program objectives. The document is also intended to provide a general basis for integration of disposition efforts among all applicable sites. This plan provides background information, establishes the scope of disposition activities, provides an approach to the mission and objectives, identifies programmatic assumptions, defines major roles, provides summary level schedules and milestones, and addresses budget requirements.

  11. SLIGHTLY IRRADIATED FUEL (SIF) INTERIM DISPOSITION PROJECT

    International Nuclear Information System (INIS)

    CH2M HILL Plateau Remediation Company (CH2M HILL PRC) is proud to submit the Slightly Irradiated Fuel (SIF) Interim Disposition Project for consideration by the Project Management Institute as Project of the Year for 2010. The SIF Project was a set of six interrelated sub-projects that delivered unique stand-alone outcomes, which, when integrated, provided a comprehensive and compliant system for storing high risk special nuclear materials. The scope of the six sub-projects included the design, construction, testing, and turnover of the facilities and equipment, which would provide safe, secure, and compliant Special Nuclear Material (SNM) storage capabilities for the SIF material. The project encompassed a broad range of activities, including the following: Five buildings/structures removed, relocated, or built; Two buildings renovated; Structural barriers, fencing, and heavy gates installed; New roadways and parking lots built; Multiple detection and assessment systems installed; New and expanded communication systems developed; Multimedia recording devices added; and A new control room to monitor all materials and systems built. Project challenges were numerous and included the following: An aggressive 17-month schedule to support the high-profile Plutonium Finishing Plant (PFP) decommissioning; Company/contractor changeovers that affected each and every project team member; Project requirements that continually evolved during design and construction due to the performance- and outcome-based nature ofthe security objectives; and Restrictions imposed on all communications due to the sensitive nature of the projects In spite of the significant challenges, the project was delivered on schedule and $2 million under budget, which became a special source of pride that bonded the team. For years, the SIF had been stored at the central Hanford PFP. Because of the weapons-grade piutonium produced and stored there, the PFP had some of the tightest security on the Hanford

  12. SLIGHTLY IRRADIATED FUEL (SIF) INTERIM DISPOSITION PROJECT

    Energy Technology Data Exchange (ETDEWEB)

    NORTON SH

    2010-02-23

    CH2M HILL Plateau Remediation Company (CH2M HILL PRC) is proud to submit the Slightly Irradiated Fuel (SIF) Interim Disposition Project for consideration by the Project Management Institute as Project of the Year for 2010. The SIF Project was a set of six interrelated sub-projects that delivered unique stand-alone outcomes, which, when integrated, provided a comprehensive and compliant system for storing high risk special nuclear materials. The scope of the six sub-projects included the design, construction, testing, and turnover of the facilities and equipment, which would provide safe, secure, and compliant Special Nuclear Material (SNM) storage capabilities for the SIF material. The project encompassed a broad range of activities, including the following: Five buildings/structures removed, relocated, or built; Two buildings renovated; Structural barriers, fencing, and heavy gates installed; New roadways and parking lots built; Multiple detection and assessment systems installed; New and expanded communication systems developed; Multimedia recording devices added; and A new control room to monitor all materials and systems built. Project challenges were numerous and included the following: An aggressive 17-month schedule to support the high-profile Plutonium Finishing Plant (PFP) decommissioning; Company/contractor changeovers that affected each and every project team member; Project requirements that continually evolved during design and construction due to the performance- and outcome-based nature ofthe security objectives; and Restrictions imposed on all communications due to the sensitive nature of the projects In spite of the significant challenges, the project was delivered on schedule and $2 million under budget, which became a special source of pride that bonded the team. For years, the SIF had been stored at the central Hanford PFP. Because of the weapons-grade piutonium produced and stored there, the PFP had some of the tightest security on the Hanford

  13. Ceruloplasmin Alters the Tissue Disposition and Neurotoxicity of Manganese, but not its Loading onto Transferrin

    OpenAIRE

    Jursa, Thomas; Smith, Donald R.

    2008-01-01

    Manganese (Mn) is a redox-active element, and whereas its uptake, disposition, and toxicity in mammals may depend in part on its oxidation state, the proteins affecting manganese oxidation state and speciation in vivo are not well known. Studies have suggested that the oxidase protein ceruloplasmin (Cp) mediates iron and manganese oxidation and loading onto plasma transferrin (Tf), as well as cellular iron efflux. We hypothesized that ceruloplasmin may also affect the tissue distribution and ...

  14. 50 CFR 30.2 - Disposition of surplus range animals.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Disposition of surplus range animals. 30.2... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Range Animals § 30.2 Disposition of surplus range animals. Disposition shall be made only during regularly scheduled...

  15. Mission Need Statement: Calcine Disposition Project Major Systems Acquisition Project

    International Nuclear Information System (INIS)

    This document identifies the need to establish the Calcine Disposition Project to determine and implement the final disposition of calcine including characterization, retrieval, treatment (if necessary), packaging, loading, onsite interim storage pending shipment to a repository or interim storage facility, and disposition of related facilities

  16. 12 CFR 34.83 - Disposition of real estate.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Disposition of real estate. 34.83 Section 34.83 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REAL ESTATE LENDING AND APPRAISALS Other Real Estate Owned § 34.83 Disposition of real estate. (a) Disposition. A national bank...

  17. 43 CFR 16.2 - Applications for helium disposition agreements.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Applications for helium disposition... HELIUM § 16.2 Applications for helium disposition agreements. The application for a helium disposition... Secretary to determine that the proposal will conserve helium that will otherwise be wasted, drained,...

  18. Disposition of firocoxib in late pregnant and early postpartum mares.

    Science.gov (United States)

    Giguère, S; Macpherson, M L; Benson, S M; Cox, S; McNaughten, J W; Pozor, M A

    2016-04-01

    Pregnancy induces several physiologic changes that might impact the bioavailability, distribution, metabolism, and excretion of drugs. The objective of this study was to determine the effects of pregnancy on the disposition of oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib concentrations were measured in plasma by HPLC with ultraviolet detection. Maximum plasma concentrations were significantly lower in pregnant (50.0 ± 21.8 ng/mL) than in postpartum (73.7 ± 25.6 ng/mL) mares. Plasma concentrations 24 h after administration, time to maximum plasma concentrations, and area under the plasma concentration versus time curve were not significantly different between late pregnancy and the postpartum period in mares. PMID:26202842

  19. Effect of Disposition of Mannich Antimalarial Agents on Their Pharmacology and Toxicology

    OpenAIRE

    Ruscoe, J. E.; Tingle, M. D.; O’Neill, P. M.; S.A. Ward; Park, B K

    1998-01-01

    The use of the antimalarial agent amodiaquine has been curtailed due to drug-induced idiosyncratic reactions. These have been attributed to the formation of a protein-reactive quinoneimine species via oxidation of the 4-aminophenol group. Therefore, the effects of chemical modifications on the disposition of amodiaquine in relation to its metabolism, distribution, and pharmacological activity have been investigated. The inclusion of a group at the C-5′ position of amodiaquine reduced or elimi...

  20. Building 003 decontamination and disposition. Final report

    International Nuclear Information System (INIS)

    The decontamination and disposition (D and D) of the contaminated facilities in Building 003 are complete. The Hot Cave, the building radioactive exhaust system, the radioactive liquid waste system, and the fume hoods were removed. The more significant D and D activities are summarized, special techniques are noted, and problems and their resolution are discussed. Results of the radiological monitoring are presented

  1. Characterizing surplus US plutonium for disposition

    Energy Technology Data Exchange (ETDEWEB)

    Allender, Jeffrey S.; Moore, Edwin N.

    2013-02-26

    The United States (US) has identified 61.5 metric tons (MT) of plutonium that is permanently excess to use in nuclear weapons programs, including 47.2 MT of weapons-grade plutonium. Surplus inventories will be stored safely by the Department of Energy (DOE) and then transferred to facilities that will prepare the plutonium for permanent disposition. The Savannah River National Laboratory (SRNL) operates a Feed Characterization program for the Office of Fissile Materials Disposition (OFMD) of the National Nuclear Security Administration (NNSA) and the DOE Office of Environmental Management (DOE-EM). SRNL manages a broad program of item tracking through process history, laboratory analysis, and non-destructive assay. A combination of analytical techniques allows SRNL to predict the isotopic and chemical properties that qualify materials for disposition through the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). The research also defines properties that are important for other disposition paths, including disposal to the Waste Isolation Pilot Plant (WIPP) as transuranic waste (TRUW) or to high-level waste (HLW) systems.

  2. Understanding Dispositions toward Reading on the Internet

    Science.gov (United States)

    Coiro, Julie

    2012-01-01

    Students' perceptions about the Internet's usefulness and potential to engage them in academic learning tasks have been found to influence their success in reading for information in online tasks. This article helps to understand the types of dispositions that adolescents may have toward reading on the Internet and how to characterize these…

  3. Critical Dispositions: Evidence and Expertise in Education

    Science.gov (United States)

    Dimitriadis, Greg

    2011-01-01

    Set against the current proliferation of global "difference" and economic realignment, "Critical Dispositions" explores the notions of "evidence" and "expertise" in times of material scarcity. Both have come to the forefront of national and international debate in education as "evidence" and "evidence-based" research and pedagogical practices…

  4. Characterizing surplus US plutonium for disposition

    International Nuclear Information System (INIS)

    The United States (US) has identified 61.5 metric tons (MT) of plutonium that is permanently excess to use in nuclear weapons programs, including 47.2 MT of weapons-grade plutonium. Surplus inventories will be stored safely by the Department of Energy (DOE) and then transferred to facilities that will prepare the plutonium for permanent disposition. The Savannah River National Laboratory (SRNL) operates a Feed Characterization program for the Office of Fissile Materials Disposition (OFMD) of the National Nuclear Security Administration (NNSA) and the DOE Office of Environmental Management (DOE-EM). SRNL manages a broad program of item tracking through process history, laboratory analysis, and non-destructive assay. A combination of analytical techniques allows SRNL to predict the isotopic and chemical properties that qualify materials for disposition through the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). The research also defines properties that are important for other disposition paths, including disposal to the Waste Isolation Pilot Plant (WIPP) as transuranic waste (TRUW) or to high-level waste (HLW) systems

  5. 31 CFR 401.5 - Disposition.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Disposition. 401.5 Section 401.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) SECRET SERVICE... requested it for the official use of the Secret Service (b) Or, if the Secret Service does not desire...

  6. Drug eruption caused by the nonionic contrast medium iohexol. "Recall-like phenomenon" appearing on an area previously affected by herpes zoster.

    Science.gov (United States)

    Matsumura, Takumi; Watanabe, Hideaki; Batchelor, Jonathan; Sueki, Hirohiko; Iijima, Masafumi

    2006-10-01

    We report a case of "recall-like phenomenon" caused by nonionic contrast medium. A 62-year-old woman suffering from postherpetic neuralgia developed erythematous plaques 12 h after an intercostal nerve block under X-ray guidance using iohexol (Omnipaque) as contrast medium. The erythematous plaques were preferentially located in the sites where she had experienced herpes zoster 4 months previously. The lesions cleared spontaneously leaving no pigmentation. Both patch testing and intradermal testing with iohexol and ioversol were positive. We postulate that local immunological changes in the skin, such as an increased number and/or accelerated activity of Langerhans cells and mast cells in the herpes zoster lesions, were responsible for this phenomenon. This "recall-like phenomenon", occurring preferentially in skin previously affected by herpes zoster, could facilitate understanding of the pathology of drug eruptions. PMID:17040501

  7. Comparative physiological disposition of two nitrofuran anti-microbial agents.

    Science.gov (United States)

    Labaune, J P; Moreau, J P; Byrne, R

    1986-01-01

    The physiological disposition of two nitrofuran derivatives used as antimicrobial agents for the treatment of acute infectious diarrhoea was evaluated in humans and animals. Upon administration of a single oral dose (600 mg) of nifurzide or nifuroxazide, no unchanged parent drug was detected in human blood or urine. In rats given 14C-nifurzide and 14C-nifuroxazide at a dose of 10 mg kg-1, 5 per cent and 17 per cent of the dose of nifurzide and nifuroxazide, respectively, were excreted in urine over a 48-hour period. None of this radioactivity was present as unchanged drug, indicating that renal excretion of both drugs occurs as metabolites. In the faeces 20 per cent of the radioactivity recovered was associated with unchanged nifuroxazide as compared with 100 per cent for nifurzide. Whole body autoradiography using rats showed that after oral administration of 14C-nifurzide and 14C-nifuroxazide, most of the radioactivity remained in the gastrointestinal lumen. PMID:3779034

  8. Pharmacogenomics and adverse drug reactions in children

    OpenAIRE

    Rieder, Michael J; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators...

  9. Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats

    International Nuclear Information System (INIS)

    The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC-reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl-H2B1a, its monosaccharide, and 24-hydroxymethyl-H2B1b

  10. Disposition of amopyroquin in rats and rabbits and in vitro activity against Plasmodium falciparum.

    OpenAIRE

    Pussard, E; Verdier, F; Faurisson, F; Clavier, F; Simon, F; Gaudebout, C

    1988-01-01

    The disposition of amopyroquin was studied in rats after a single 50-mg/kg (body weight) oral dose of amopyroquin base. After a rapid absorption phase, the drug concentrations decreased in the plasma, with a terminal half-life of 14.5 h. The drug was widely distributed in the liver and lungs and, to a lesser extent, in the kidneys and spleen. In rabbits, the kinetic parameters were compared after a single 10-mg/kg dose of amopyroquin base through intravenous, intramuscular (i.m.), and oral ro...

  11. Disposition Kinetic of Moxifloxacin following Intravenous, Intramuscular, and Subcutaneous Administration in Goats

    OpenAIRE

    Patel, Harshad B.; Shailesh K. Mody; Patel, Hitesh B.; Patel, Vipul A.; Urvesh D. Patel

    2011-01-01

    The present study was carried out to investigate disposition kinetics of moxifloxacin following single-dose intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) administration at a dose rate of 5 mg/kg of body weight (b.wt.) in goats. Plasma samples collected after treatments were analyzed for drug concentration using high-performance liquid chromatography (HPLC). After i.v. administration, distribution of the drug was rapid and wide as reflected by high steady-state volume of di...

  12. Historicizing security - entering the conspiracy dispositive

    OpenAIRE

    de Graaf, B.A.; Zwierlein, C.

    2013-01-01

    This introduction offers a brief historiographic account on current histories of security. A case is made for historians to rely more on and profit from recent theories and concepts in political science, most notably the concepts invented by the Copenhagen School on securitization. Furthermore, an attempt is made to ‘historicize security’ and provide some new methodological perspectives, in particular the idea of connecting security to conspiracy as an operational dispositive for analyzing in...

  13. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  14. Dispositional optimism and coping with pain

    OpenAIRE

    Bargiel-Matusiewicz K; Krzyszkowska A

    2009-01-01

    Abstract Objective The aim of this article is to analyze the relation between dispositional optimism and coping with chronic pain. The study seeks to define the relation between life orientation (optimism vs. pessimism) and coping with pain (believes about pain control and the choice of coping strategy). Material and methods The following questionnaires were used: LOT-R - Life Orientation Test, BPCQ - The Beliefs about Pain Control Questionnaire and CSQ - The Pain Coping Strategies Questionna...

  15. Dispositional Mindfulness, Meditation, and Conditional Goal Setting

    OpenAIRE

    Crane, Catherine; Jandric, Danka; Barnhofer, Thorsten; Williams, J. Mark G.

    2010-01-01

    Conditional goal setting (CGS, the tendency to regard high order goals such as happiness, as conditional upon the achievement of lower order goals) is observed in individuals with depression and recent research has suggested a link between levels of dispositional mindfulness and conditional goal setting in depressed patients. Since interventions which aim to increase mindfulness through training in meditation are used with patients suffering from depression it is of interest to examine whethe...

  16. Attitudes Toward Diabetes Affect Maintenance of Drug-Free Remission in Patients With Newly Diagnosed Type 2 Diabetes After Short-Term Continuous Subcutaneous Insulin Infusion Treatment

    Science.gov (United States)

    Chen, Ailing; Huang, Zhimin; Wan, Xuesi; Deng, Wanping; Wu, Jiyan; Li, Licheng; Cai, Qiuling; Xiao, Haipeng; Li, Yanbing

    2012-01-01

    OBJECTIVE Short-term intensive insulin treatment in patients with newly diagnosed type 2 diabetes can improve β-cell function and insulin sensitivity, which results in long-term remission without need for further antidiabetes medication. Patient attitudes toward their disease were assessed using the Diabetes Care Profile (DCP) tool to evaluate the potential impact on maintaining long-term remission. RESEARCH DESIGN AND METHODS Newly diagnosed patients with type 2 diabetes were recruited and treated with continuous subcutaneous insulin infusion (CSII) for 2–3 weeks. They were also invited to participate in diabetes self-management intervention during hospitalization and complete a DCP questionnaire on attitudes toward diabetes at baseline and 3, 6, and 12 months after suspension of CSII. RESULTS Near normoglycemia was achieved by 118 patients after short-term CSII, with 65 remaining in drug-free remission for >1 year. They had significantly better glycemic control and greater restoration of acute insulin response after CSII as well as higher educational attainment compared with patients experiencing relapse. They also achieved higher scores in positive attitude, (belief in) importance of care, care ability, self-care adherence, and less negative attitude. Differences between the two groups became greater over time. Cox proportional hazards model analysis indicated that greater self-care adherence (hazard ratio 0.184, P < 0.001) and homeostasis model assessment of insulin resistance before treatment (0.854, P = 0.053) were independent predictors for long-term remission, whereas elevated 2-h postprandial plasma glucose after CSII (1.156, P = 0.015) was a risk factor for relapse. CONCLUSIONS Attitudes toward diabetes affect long-term drug-free remission in newly diagnosed patients with type 2 diabetes after short-term CSII. PMID:22228747

  17. DISPOSITION EFFECT AMONG BRAZILIAN EQUITY FUND MANAGERS

    Directory of Open Access Journals (Sweden)

    Eduardo Pozzi Lucchesi

    2015-01-01

    Full Text Available The disposition effect predicts that investors tend to sell winning stocks too soon and ride losing stocks too long. Despite the wide range of research evidence about this issue, the reasons that lead investors to act this way are still subject to much controversy between rational and behavioral explanations. In this article, the main goal was to test two competing behavioral motivations to justify the disposition effect: prospect theory and mean reversion bias. To achieve it, an analysis of monthly transactions for a sample of 51 Brazilian equity funds from 2002 to 2008 was conducted and regression models with qualitative dependent variables were estimated in order to set the probability of a manager to realize a capital gain or loss as a function of the stock return. The results brought evidence that prospect theory seems to guide the decision-making process of the managers, but the hypothesis that the disposition effect is due to mean reversion bias could not be confirmed.

  18. Regulatory issues for deep borehole plutonium disposition

    International Nuclear Information System (INIS)

    As a result of recent changes throughout the world, a substantial inventory of excess separated plutonium is expected to result from dismantlement of US nuclear weapons. The safe and secure management and eventual disposition of this plutonium, and of a similar inventory in Russia, is a high priority. A variety of options (both interim and permanent) are under consideration to manage this material. The permanent solutions can be categorized into two broad groups: direct disposal and utilization. The deep borehole disposition concept involves placing excess plutonium deep into old stable rock formations with little free water present. Issues of concern include the regulatory, statutory and policy status of such a facility, the availability of sites with desirable characteristics and the technologies required for drilling deep holes, characterizing them, emplacing excess plutonium and sealing the holes. This white paper discusses the regulatory issues. Regulatory issues concerning construction, operation and decommissioning of the surface facility do not appear to be controversial, with existing regulations providing adequate coverage. It is in the areas of siting, licensing and long term environmental protection that current regulations may be inappropriate. This is because many current regulations are by intent or by default specific to waste forms, facilities or missions significantly different from deep borehole disposition of excess weapons usable fissile material. It is expected that custom regulations can be evolved in the context of this mission

  19. 14 CFR 61.15 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... the growing, processing, manufacture, sale, disposition, possession, transportation, or importation of... vehicle while intoxicated by alcohol or a drug, while impaired by alcohol or a drug, or while under the influence of alcohol or a drug; (2) The cancellation, suspension, or revocation of a license to operate...

  20. Reclaiming English Education: Rooting Social Justice in Dispositions.

    OpenAIRE

    Alsup, Janet; Miller, sj

    2014-01-01

    This article addresses the importance of foregrounding social justice in teaching and assessing dispositions for preservice teachers in secondary English language arts. We provide a historical overview of dispositions and their politicization, and we address NCATE’s removal of social justice and its impending return. We conclude with possibilities for assessing dispositions for social justice and reflections on the implications for accreditation and consider what might be in store for the fut...

  1. Medical Consequences of Drug Abuse

    Science.gov (United States)

    ... Home » Related Topics » Medical Consequences Medical Consequences of Drug Abuse Email Facebook Twitter Drug addiction is a brain ... and lung disease can all be affected by drug abuse. Some of these effects occur when drugs are ...

  2. Drug: D08765 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available category: 4300 ATC code: V09BA03 Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radio...active drugs 430 Radioactive drugs 4300 Radioactive drugs

  3. Drug: D08766 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ory of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radio...active drugs 4300 Radioactive drugs D08766 Sodium phytate hydrate - technetium (99mTc)

  4. 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

    2015-11-01

    Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-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. PMID:26378985

  5. Relationship of embryotoxicity to disposition of 2-methoxyethanol in mice

    Energy Technology Data Exchange (ETDEWEB)

    Sleet, R.B.; Greene, J.A.; Welsch, F.

    1988-04-01

    Paw development of CD-1 mice is uniquely sensitive to 2-methoxyethanol (ME) given by gavage (po) on gestation day (gd) 11 (copulation plug day = gd 0). The relation between induction of paw dysmorphogenesis and disposition of po ME in the maternal and conceptus compartments was investigated. The expression of digit malformations depends on metabolism of ME to methoxyacetic acid (MAA). ME and MAA were equipotent in causing teratogenicity. Alcohol dehydrogenase (ADH) catalyzes the initial rate-limiting oxidation that leads to embryotoxicity. The ADH inhibitor 4-methylpyrazole or ethanol reduced the incidence of malformations 60-100%, depending on the dosing regimen. Elimination of 14C from 1,2-14C-ME occurred predominantly via urine where 80% of a teratogenic dose was excreted and 6% appeared in CO2. Oxidation of ME to MAA was nearly complete after 1 hr when approximately 90% of 14C in maternal plasma and conceptus coeluted with authentic 14C-MAA upon HPLC. 14C-MAA levels in embryos were 1.2 X those in plasma 1 and 6 hr after dosing, although by 6 hr concentrations had declined to approximately 50% of 1-hr values. Concomitant ethanol did not affect 14C kinetics as measured in maternal blood after oral 14C-ME, but retarded ME conversion to MAA by about 2 hr. Furthermore, embryo 14C-MAA levels then reached only 50% of the peak in embryos from dams dosed with ME alone, an effect that coincided with less 14C incorporation into macromolecules synthesized by the embryo within 6 hr. These data imply that the attenuation of digit malformations by concomitant ethanol may be explained by changes in MAA disposition. However, delayed ethanol reduced teratogenicity by 25%, although MAA was present in the embryo up to 5 hr.

  6. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  7. KEWB facilities decontamination and disposition. Final report

    International Nuclear Information System (INIS)

    The decontamination and disposition of the KEWB facilities, Buildings 073, 643, 123, and 793, are complete. All of the facility equipment, including reactor enclosure, reactor vessel, fuel handling systems, controls, radioactive waste systems, exhaust systems, electrical services, and protective systems were removed from the site. Buildings 643, 123, and 793 were completely removed, including foundations. The floor and portions of the walls of Building 073 were covered over by final grading. Results of the radiological monitoring and the final survey are presented. 9 tables, 19 figures

  8. The disposition of ketoprofen enantiomers in man.

    OpenAIRE

    Sallustio, B C; Purdie, Y J; Whitehead, A G; Ahern, M.J.; Meffin, P J

    1988-01-01

    1. The disposition of ketoprofen enantiomers was studied in 21 patients taking racemic ketoprofen (Orudis SR). 2. In each patient the plasma concentrations of the R- and S-enantiomers were similar at all times over a 24 h dosing interval. The mean (+/- s.e. mean) time-averaged plasma ketoprofen concentrations over the dosage interval were 0.76 (+/- 0.06) mg l-1 for R-ketoprofen and 0.78 (+/- 0.06) mg l-1 for S-ketoprofen. 3. Creatinine clearances for the 21 patients ranged from 6-162 ml min-1...

  9. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

    Science.gov (United States)

    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS. PMID:26894935

  10. Disposition and transportation of surplus radioactive low specific activity nitric acid. Volume 1, Environmental Assessment

    International Nuclear Information System (INIS)

    DOE is deactivating the PUREX plant at Hanford; this will involve the disposition of about 692,000 liters (183,000 gallons) of surplus nitric acid contaminated with low levels of U and other radionuclides. The nitric acid, designated as low specific activity, is stored in 4 storage tanks at PUREX. Five principal alternatives were evaluated: transfer for reuse (sale to BNF plc), no action, continued storage in Hanford upgraded or new facility, consolidation of DOE surplus acid, and processing the LSA nitric acid as waste. The transfer to BNF plc is the preferred alternative. From the analysis, it is concluded that the proposed disposition and transportation of the acid does not constitute a major federal action significantly affecting the quality of the human environment within the meaning of NEPA; therefore an environmental impact statement is not required

  11. Stereoselectivity in the disposition and metabolism of the uricosuric-diuretic agent, indacrinone, in Rhesus monkeys

    International Nuclear Information System (INIS)

    The physiological disposition following intravenous dosing of the separate enantiomers of indacrinone-14C (I), and of their major metabolite, 4'-hydroxyindacrinone-14C (M), was studied in the rhesus monkey. Pharmacokinetic analysis indicated that the disposition of I and M was stereoselective. In the case of the enantiomers of I, the areas under the curves of plasma concentration vs. time were about sevenfold greater for the (S)(+)- as compared to the (R)(-)-enantiomer. Renal and plasma clearances of (R)(-)-I were five to seven times greater than those of (S)(+)-I. Total urinary recovery of unchanged drug and metabolite accounted for 70% of the administered dose of either enantiomer. The systemic availability of (R)(-)-M from (R)(-)-I was approximately 21% of the dose, whereas that of (S)(+)-M from (S)(+)-I was only 4%. More pronounced differences were noted in the kinetics of metabolite disposition. The AUC values were about 27 times greater for (S)(+)-M than (R)(-)-M, and the renal and plasma clearances were approximately 25-fold higher for (R)(-)-M as compared to (S)(+)-M. The volume of distribution of (S)(+)-M was only 12% of that observed with (R)(+)-M. There was no evidence of glucuronide or sulfate conjugates of any of the enantiomers. These findings are consistent with the pharmacological activity attributed to the different enantiomers

  12. Applying Gadamer's Concept of Disposition to Science and Science Education

    Science.gov (United States)

    Borda, Emily J.

    2007-01-01

    In this paper, I recall previous arguments for a hermeneutic approach to science and claim that such an approach necessitates attention to the development of dispositions. I undertake an analysis of Hans-Georg Gadamer's philosophical hermeneutics to identify and describe dispositions relevant to a hermeneutic approach to science. I then apply…

  13. 42 CFR 67.16 - Evaluation and disposition of application.

    Science.gov (United States)

    2010-10-01

    ... Health Services Research, Evaluation, Demonstration, and Dissemination Projects § 67.16 Evaluation and disposition of application. (a) Evaluation. After appropriate peer review in accordance with § 67.15, the... 42 Public Health 1 2010-10-01 2010-10-01 false Evaluation and disposition of application....

  14. 50 CFR 30.12 - Disposition of feral animals.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Disposition of feral animals. 30.12... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.12 Disposition of feral animals. Feral animals taken on wildlife refuge areas may be disposed of by sale on...

  15. 25 CFR 242.5 - Disposition of unmarketable fish.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Disposition of unmarketable fish. 242.5 Section 242.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE COMMERCIAL FISHING ON RED LAKE INDIAN RESERVATION § 242.5 Disposition of unmarketable fish. All unmarketable live fish...

  16. 40 CFR 142.43 - Disposition of a variance request.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Disposition of a variance request. 142... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Variances Issued by the Administrator Under Section 1415(a) of the Act § 142.43 Disposition of a variance request. (a) If...

  17. 7 CFR 3401.7 - Evaluation and disposition of applications.

    Science.gov (United States)

    2010-01-01

    ... detriment of applicants during the peer evaluation process. To ensure a comprehensive evaluation, all... 7 Agriculture 15 2010-01-01 2010-01-01 false Evaluation and disposition of applications. 3401.7... General § 3401.7 Evaluation and disposition of applications. (a) Evaluation. All proposals received...

  18. 7 CFR 3411.5 - Evaluation and disposition of applications.

    Science.gov (United States)

    2010-01-01

    ... poorly organized applications will work to the detriment of applicants during the peer evaluation process... 7 Agriculture 15 2010-01-01 2010-01-01 false Evaluation and disposition of applications. 3411.5... COMPETITIVE GRANTS PROGRAM General § 3411.5 Evaluation and disposition of applications. (a) Evaluation....

  19. 7 CFR 3400.5 - Evaluation and disposition of applications.

    Science.gov (United States)

    2010-01-01

    ... applications will work to the detriment of applicants during the peer evaluation process. To ensure a... 7 Agriculture 15 2010-01-01 2010-01-01 false Evaluation and disposition of applications. 3400.5... General § 3400.5 Evaluation and disposition of applications. (a) Evaluation. All proposals received...

  20. 7 CFR 3415.5 - Evaluation and disposition of applications.

    Science.gov (United States)

    2010-01-01

    ... organized applications will work to the detriment of applicants during the peer evaluation process. To... 7 Agriculture 15 2010-01-01 2010-01-01 false Evaluation and disposition of applications. 3415.5... RESEARCH GRANTS PROGRAM General § 3415.5 Evaluation and disposition of applications. (a) Evaluation....

  1. Attending to Ethical and Moral Dispositions in Teacher Education

    Science.gov (United States)

    Osguthorpe, Richard D.

    2013-01-01

    The purpose of this article is to identify some issues related to ethical and moral dispositions in teacher education programs. My intent is to provide a starting point for gaining a professional consensus on the ways that teacher educators approach the definition, assessment, and development of dispositions in their teacher education programs. To…

  2. Dispositional Statements on Student Teacher Evaluation Instruments: Commonalities across Institutions

    Science.gov (United States)

    Young, Alice; Wilkins, Elizabeth

    2008-01-01

    The purpose of this study was to investigate summative student teacher evaluation instruments to determine the most common dispositions evaluated by teacher preparatory programs. Thirty-two (32) final student teaching instruments were purposely selected from across the United States and examined. Thirteen disposition categories emerged from the…

  3. 19 CFR 162.50 - Forfeiture by court decree: Disposition.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Forfeiture by court decree: Disposition. 162.50....50 Forfeiture by court decree: Disposition. (a) Sale. Forfeited property decreed by the court for... cleared for sale. (c) Destruction—(1) Proceeds of sale not sufficient. Property forfeited under a...

  4. 30 CFR 879.15 - Disposition of reclaimed land.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Disposition of reclaimed land. 879.15 Section 879.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER §...

  5. 42 CFR 35.47 - Disposition of Government checks.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Disposition of Government checks. 35.47 Section 35... Disposition of Government checks. Notwithstanding any other provisions of this subpart, immediately upon... to the department, agency, or establishment of the Government of the United States issuing...

  6. Critical Thinking Dispositions of Pre-Service Teachers

    Science.gov (United States)

    Bakir, Selda

    2015-01-01

    This study investigated the critical thinking dispositions of pre-service teachers in terms of various variables. The study included 1106 participants and used the survey model and the Turkish version (CCTDI-T) of the California Critical Thinking Disposition Inventory (CCTDI). The reliability of the scale for this study was found to be 0.82. The…

  7. Investigating Academic Achievements and Critical Thinking Dispositions of Teacher Candidates

    Science.gov (United States)

    Karagöl, Ibrahim; Bekmezci, Sinan

    2015-01-01

    The aim of this study is to examine the relationship between academic achievements and critical thinking dispositions of teacher candidates in Faculty of Education and to find out whether critical thinking dispositions and academic achievements scores of teacher candidates differ according to different variables. The population consists of the…

  8. Urban High School Teachers' Beliefs Concerning Essential Science Teaching Dispositions

    Science.gov (United States)

    Miranda, Rommel

    2012-01-01

    This qualitative study addresses the link between urban high school science teachers' beliefs about essential teaching dispositions and student learning outcomes. The findings suggest that in order to help students to do well in science in urban school settings, science teachers should possess essential teaching dispositions which include…

  9. Building a Conceptual Framework for Online Educator Dispositions

    Science.gov (United States)

    Kirwan, Jeral R.; Roumell, Elizabeth Anne

    2015-01-01

    It has been argued that online instruction is distinctive from the conventional classroom. If an effective online practice is to emerge, the roles, characteristics and dispositions of the educators themselves should be studied more closely. The aim of this paper was to present an online educator dispositions model that addresses the underlying…

  10. 48 CFR 945.570-7 - Disposition of motor vehicles.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disposition of motor... Disposition of motor vehicles. (a) The contractor shall dispose of DOE-owned motor vehicles as directed by the contracting officer. (b) DOE-owned motor vehicles may be disposed of as exchange/sale items when directed...

  11. Contribution of Emotional Intelligence towards Graduate Students’ Critical Thinking Disposition

    Directory of Open Access Journals (Sweden)

    Fong-Luan Kang

    2015-10-01

    Full Text Available Good critical thinkers possess a core set of cognitive thinking skills, and a disposition towards critical thinking. They are able to think critically to solve complex, real-world problems effectively. Although personal emotion is important in critical thinking, it is often a neglected issue. The emotional intelligence in this study concerns our sensitivity to and artful handling of our own and others’ emotions. Engaging students emotionally is the key to strengthening their dispositions toward critical thinking. Hence, a study involving 338 male and female graduate students from a public university was carried out. They rated the Emotional Intelligence Scale and Critical Thinking Disposition Scale. Findings suggested that emotional intelligence and critical thinking disposition were positively correlated (r=.609. Differences in terms of age, gender, and course of study also formed part of the analysis.Keywords: emotional intelligence, critical thinking disposition, graduate students

  12. Disposition of citral in male Fischer rats

    International Nuclear Information System (INIS)

    The disposition of citral, an essential oil occurring in many foods and fragrances, was studied in male Fischer rats after iv, po, and dermal treatments. The pattern of distribution and elimination was the same after iv or oral exposure. Urine was the major route of elimination of citral-derived radioactivity, followed by feces, 14CO2, and expired volatiles. However, after dermal exposure, relatively less of the material was eliminated in the urine and more in the feces, suggesting a role for first-pass metabolism through the skin. Citral was almost completely absorbed orally; due to its extreme volatility, much of an applied dermal dose was lost. The citral remaining on the skin was fairly well absorbed. No effect of oral dose, from 5 to 500 mg/kg, was detected on disposition. Although the feces was a minor route of excretion, approximately 25% of the administered dose was eliminated via the bile within 4 hr of an iv dose. The metabolism of citral was both rapid and extensive. Within 5 min of an iv dose, no unmetabolized citral could be detected in the blood. Repeated exposure to citral resulted in an increase in biliary elimination, without any significant change in the pattern of urinary, fecal, or exhaled excretion. This suggests that citral may induce at least one pathway of its own metabolism. The rapid metabolism and excretion of this compound suggest that significant bioaccumulation of citral would not occur

  13. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    Directory of Open Access Journals (Sweden)

    Chandra Prakash

    2015-12-01

    Full Text Available Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs, and transport proteins coordinate drug influx (phase 0 and drug/drug-metabolite efflux (phase III. Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs, i.e. PXR (pregnane X receptor and CAR (constitutive androstane receptor, and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR, due to transactivation of xenobiotic-response elements (XREs present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug's impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse

  14. Combination Lopinavir and Ritonavir Alter Exogenous and Endogenous Bile Acid Disposition in Sandwich-Cultured Rat Hepatocytes

    OpenAIRE

    Griffin, LaToya M.; Watkins, Paul B.; Perry, Cassandra H.; Robert L St Claire; Brouwer, Kim L.R.

    2013-01-01

    Inhibition of the bile salt export pump (BSEP) can cause intracellular accumulation of bile acids and is a risk factor for drug-induced liver injury in humans. Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors. However, the consequences of LPV and RTV, alone and combined (LPV/r), on hepatocyte viability, bile acid transport, and endogenous bile acid disposition in rat hepatocytes have not been examined. The effect of LPV, RTV, and LPV/r on cel...

  15. Food-Drug Interactions

    OpenAIRE

    Arshad Yar Khan; Nousheen Aslam; Rabia Bushra

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on i...

  16. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel;

    2013-01-01

    affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and...... lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of...

  17. Can "Hybrid stent implantation" improve long-term safety without adversely affecting efficacy when treating multilesion coronary artery disease in the drug-eluting stent era?

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dong; XU Bo; DOU Ke-fei; YANG Yue-jin; CHEN Ji-lin; QIAO Shu-bin; WANG Yang

    2013-01-01

    Background Though drug-eluting stent (DES) almost solved a problem of restenosis,safety issues related to stent thrombosis are still the major concern of DES.We hypothesized that hybrid stent implantation may decrease the use of DES,probably improving the long-term safety but not affecting efficacy adversely when treating multilesion coronary artery disease in the DES era.Methods From April 2004 to October 2006,848 patients with multilesion disease underwent hybrid stent implantation.During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital.According to propensity score matching,we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study.We obtained the 24-month clinical outcome including death,myocardial infarction (MI),thrombosis,target lesion revascularization (TLR),target vessel revascularization (TVR),and major adverse cardiac events (MACE,the composite of death,MI,and TVR).We used Cox's proportional-hazard models to assess relative risks of all the outcome measures after propensity match.Results At 24 months,patients in the hybrid stent implantation group showed a significantly higher risk of TLR (8.39%vs.3.28%,HR2.38,95% CI:1.50-3.70),TVR (11.07% vs.6.32%,HR 1.61,95% CI:1.15-2.27) and MACE (13.75% vs.8.75%,HR 1.37,95% CI:1.02-1.85).No significant difference was apparent in terms of mortality (1.22% vs.1.70%,HR 0.55,95% CI:0.24-1.25),MI (1.95% vs.2.31%,HR0.73,95% CI:0.37-1.42),or thrombosis (definite+probable) (0.73% vs.1.58%,HR0.40,95% CI:0.15-1.05).Conclusions In patients with multilesion coronary artery disease,the exclusive DES implantation was associated with significantly lower risks of TLR,TVR and MACE,and the hybrid stent implantation did not result in any significant improvements regarding safety issues.Prospective studies are needed to confirm our results.

  18. “First, do no harm”: legal guidelines for health programmes affecting adolescents aged 10–17 who sell sex or inject drugs

    Directory of Open Access Journals (Sweden)

    Brendan Conner

    2015-02-01

    Full Text Available Introduction: There is a strong evidence base that the stigma, discrimination and criminalization affecting adolescent key populations (KPs aged 10–17 is intensified due to domestic and international legal constructs that rely on law-enforcement-based interventions dependent upon arrest, pre-trial detention, incarceration and compulsory “rehabilitation” in institutional placement. While there exists evidence and rights-based technical guidelines for interventions among older cohorts, these guidelines have not yet been embraced by international public health actors for fear that international law applies different standards to adolescents aged 10–17 who engage in behaviours such as selling sex or injecting drugs. Discussion: As a matter of international human rights, health, juvenile justice and child protection law, interventions among adolescent KPs aged 10–17 must not involve arrest, prosecution or detention of any kind. It is imperative that interventions not rely on law enforcement, but instead low-threshold, voluntary services, shelter and support, utilizing peer-based outreach as much as possible. These services must be mobile and accessible, and permit alternatives to parental consent for the provision of life-saving support, including HIV testing, treatment and care, needle and syringe programmes, opioid substitution therapy, safe abortions, antiretroviral therapy and gender-affirming care and hormone treatment for transgender adolescents. To ensure enrolment in services, international guidance indicates that informed consent and confidentiality must be ensured, including by waiver of parental consent requirements. To remove the disincentive to health practitioners and researchers to engaging with adolescent KPs aged 10–17 government agencies and ethical review boards are advised to exempt or grant waivers for mandatory reporting. In the event that, in violation of international law and guidance, authorities seek to

  19. Drug allergy

    OpenAIRE

    Warrington Richard; Silviu-Dan Fanny

    2012-01-01

    Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR) not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis a...

  20. Effects of cigarette smoke and 3-methylcholanthrene on the disposition of phencyclidine and its N-ethylamine analogue in the isolated perfuse lung of rats

    International Nuclear Information System (INIS)

    The isolated perfused lung (IPL) of rats were used to examine the pulmonary disposition and metabolism of tritium-labeled phencyclidine (PCP) and N-ethyl-1-phenylcyclohexylamine (PCE). The IPL removed PCP and PCE from the perfusate and converted them to free and conjugated metabolities. At the conclusion of a 1-h perfusion, the lung accumulated at least 20% of the administered radioactivity and metabolized more than 30% of the added drug. Pretreatment of rats with 3-MC or cigarette smoke enhanced significantly PCP and PCE metabolism by the IPL. The concentration of conjugated PCE metabolite in the perfusate of the IPL was increased significantly by both 3-MC and cigarette smoke pretreatments whereas the concentration of conjugated PCP metabolite was not affected by cigarette smoke exposure and increased only slightly after 3-MC pretreatment. Pretreatment of rats with 3-MC or cigarette smoke also altered the amount of radioactivity accumulated by the lung tissue at the conclusion of a 1-h perfusion. Inasmuch as PCP and PCE are often abused by humans via smoke inhalation, a significant amount of these drugs may be stored or metabolized by the lung. (author)

  1. Weapons-grade plutonium dispositioning. Volume 2: Comparison of plutonium disposition options

    International Nuclear Information System (INIS)

    The Secretary of Energy requested the National Academy of Sciences (NAS) Committee on International Security and Arms Control to evaluate disposition options for weapons-grade plutonium. The Idaho National Engineering Laboratory (INEL) offered to assist the NAS in this evaluation by investigating the technical aspects of the disposition options and their capability for achieving plutonium annihilation levels greater than 90%. This report was prepared for the NAS to document the gathered information and results from the requested option evaluations. Evaluations were performed for 12 plutonium disposition options involving five reactor and one accelerator-based systems. Each option was evaluated in four technical areas: (1) fuel status, (2) reactor or accelerator-based system status, (3) waste-processing status, and (4) waste disposal status. Based on these evaluations, each concept was rated on its operational capability and time to deployment. A third rating category of option costs could not be performed because of the unavailability of adequate information from the concept sponsors. The four options achieving the highest rating, in alphabetical order, are the Advanced Light Water Reactor with plutonium-based ternary fuel, the Advanced Liquid Metal Reactor with plutonium-based fuel, the Advanced Liquid Metal Reactor with uranium-plutonium-based fuel, and the Modular High Temperature Gas-Cooled Reactor with plutonium-based fuel. Of these four options, the Advanced Light Water Reactor and the Modular High Temperature Gas-Cooled Reactor do not propose reprocessing of their irradiated fuel. Time constraints and lack of detailed information did not allow for any further ratings among these four options. The INEL recommends these four options be investigated further to determine the optimum reactor design for plutonium disposition

  2. Weapons-grade plutonium dispositioning. Volume 2: Comparison of plutonium disposition options

    Energy Technology Data Exchange (ETDEWEB)

    Brownson, D.A.; Hanson, D.J.; Blackman, H.S. [and others

    1993-06-01

    The Secretary of Energy requested the National Academy of Sciences (NAS) Committee on International Security and Arms Control to evaluate disposition options for weapons-grade plutonium. The Idaho National Engineering Laboratory (INEL) offered to assist the NAS in this evaluation by investigating the technical aspects of the disposition options and their capability for achieving plutonium annihilation levels greater than 90%. This report was prepared for the NAS to document the gathered information and results from the requested option evaluations. Evaluations were performed for 12 plutonium disposition options involving five reactor and one accelerator-based systems. Each option was evaluated in four technical areas: (1) fuel status, (2) reactor or accelerator-based system status, (3) waste-processing status, and (4) waste disposal status. Based on these evaluations, each concept was rated on its operational capability and time to deployment. A third rating category of option costs could not be performed because of the unavailability of adequate information from the concept sponsors. The four options achieving the highest rating, in alphabetical order, are the Advanced Light Water Reactor with plutonium-based ternary fuel, the Advanced Liquid Metal Reactor with plutonium-based fuel, the Advanced Liquid Metal Reactor with uranium-plutonium-based fuel, and the Modular High Temperature Gas-Cooled Reactor with plutonium-based fuel. Of these four options, the Advanced Light Water Reactor and the Modular High Temperature Gas-Cooled Reactor do not propose reprocessing of their irradiated fuel. Time constraints and lack of detailed information did not allow for any further ratings among these four options. The INEL recommends these four options be investigated further to determine the optimum reactor design for plutonium disposition.

  3. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Bladeren, van P.J.; Rietjens, I.M.C.M.

    2006-01-01

    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be high

  4. Does a Permissive Workplace Substance Use Climate Affect Employees Who Do Not Use Alcohol and Drugs at Work? A U.S. National Study

    OpenAIRE

    Frone, Michael R.

    2009-01-01

    The goal of this study was to begin exploring the relations of multiple dimensions of workplace substance use climate (substance availability, workplace descriptive norms, and workplace injunctive norms) to perceived workplace safety, work strain, and employee morale among employees who do not use alcohol or drugs at work. Data were collected from a probability sample of employed adults in the U.S. (N = 2051) who do not engage in workplace alcohol or drug use. The results showed that all thre...

  5. The mind as skills and dispositions

    DEFF Research Database (Denmark)

    Brinkmann, Svend

    2012-01-01

    broaden Harré’s hybrid psychology by including not just the brain, but also the body, social practices, and technological artifacts as mediators of the mind. The mind is understood not as a substance of any kind, but as a set of skills and dispositions to act, think, and feel. This implies a normative......On the occasion of the critique of Alfredo Gaete and Carlos Cornejo, this article explains and extends the hybrid theory of the mind that I recently presented in this journal. Taking inspiration from Rom Harré’s program for a hybrid psychology, the theory is supposed to be integrative and aims to...... view of the mind, according to which psychological phenomena do not simply happen, but are done, and can consequently be done more or less well. I provide arguments in favor of grounding psychology in normativity rather than conscious experience, and I explain why the emphasis on mediators does not...

  6. Fissile material disposition and proliferation risk

    International Nuclear Information System (INIS)

    The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium

  7. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  8. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    Significant amounts of the depleted uranium (DU) created by past uranium enrichment activities have been sold, disposed of commercially, or utilized by defense programs. In recent years, however, the demand for DU has become quite small compared to quantities available, and within the US Department of Energy (DOE) there is concern for any risks and/or cost liabilities that might be associated with the ever-growing inventory of this material. As a result, Martin Marietta Energy Systems, Inc. (Energy Systems), was asked to review options and to develop a comprehensive plan for inventory management and the ultimate disposition of DU accumulated at the gaseous diffusion plants (GDPs). An Energy Systems task team, under the chairmanship of T. R. Lemons, was formed in late 1989 to provide advice and guidance for this task. This report reviews options and recommends actions and objectives in the management of working inventories of partially depleted feed (PDF) materials and for the ultimate disposition of fully depleted uranium (FDU). Actions that should be considered are as follows. (1) Inspect UF{sub 6} cylinders on a semiannual basis. (2) Upgrade cylinder maintenance and storage yards. (3) Convert FDU to U{sub 3}O{sub 8} for long-term storage or disposal. This will include provisions for partial recovery of costs to offset those associated with DU inventory management and the ultimate disposal of FDU. Another recommendation is to drop the term tails'' in favor of depleted uranium'' or DU'' because the tails'' label implies that it is waste.'' 13 refs.

  9. Proliferation resistance criteria for fissile material disposition issues

    International Nuclear Information System (INIS)

    The 1994 National Acdaemy of Sciences study ''Management and Disposition of Excess Weapons Plutonium'' defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This paper proposes criteria for assessing the proliferation resistance of these options as well defining the ''Standards'' from the report. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  10. Spectroscopic study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein?

    Energy Technology Data Exchange (ETDEWEB)

    Moradi, Nastaran [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ashrafi-Kooshk, Mohammad Reza [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ghobadi, Sirous [Department of Biology, Faculty of Sciences, Razi University, Kermanshah (Iran, Islamic Republic of); Shahlaei, Mohsen [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Khodarahmi, Reza, E-mail: rkhodarahmi@mbrc.ac.ir [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)

    2015-04-15

    Human serum albumin (HSA) is the most prominent extracellular protein in blood plasma. There are several binding sites on the protein which provide accommodation for structurally-unrelated endogenous and exogenous ligands and a wide variety of drugs. “Esterase-like” activity (hydrolysis of p-nitrophenyl esters) by the protein has been also reported. In the current study, we set out to investigate the interaction of indomethacin and ibuprofen with the unmodified and modified HSA (pNPA-modified HSA) using various spectroscopic techniques. Fluorescence data showed that 1:1 binding of drug to HSA is associated with quenching of the protein intrinsic fluorescence. Decrease of protein surface hydrophobicity (PSH), alteration in drug binding affinity and change of the protein stability, after esterase-like activity and permanent acetylation of HSA, were also documented. Analysis of the quenching and thermodynamic parameters indicated that forces involved in drug–HSA interactions change upon the protein modification. - Highlights: • Binding propensity of indomethacin extremely decreased upon the protein acetylation. • There is no ibuprofen binding after protein acetylation. • Protein stability changes upon drug binding as well as protein acetylation. • Drug pharmacokinetics may be influenced under co-administration of HSA-modifier drugs.

  11. Spectroscopic study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein?

    International Nuclear Information System (INIS)

    Human serum albumin (HSA) is the most prominent extracellular protein in blood plasma. There are several binding sites on the protein which provide accommodation for structurally-unrelated endogenous and exogenous ligands and a wide variety of drugs. “Esterase-like” activity (hydrolysis of p-nitrophenyl esters) by the protein has been also reported. In the current study, we set out to investigate the interaction of indomethacin and ibuprofen with the unmodified and modified HSA (pNPA-modified HSA) using various spectroscopic techniques. Fluorescence data showed that 1:1 binding of drug to HSA is associated with quenching of the protein intrinsic fluorescence. Decrease of protein surface hydrophobicity (PSH), alteration in drug binding affinity and change of the protein stability, after esterase-like activity and permanent acetylation of HSA, were also documented. Analysis of the quenching and thermodynamic parameters indicated that forces involved in drug–HSA interactions change upon the protein modification. - Highlights: • Binding propensity of indomethacin extremely decreased upon the protein acetylation. • There is no ibuprofen binding after protein acetylation. • Protein stability changes upon drug binding as well as protein acetylation. • Drug pharmacokinetics may be influenced under co-administration of HSA-modifier drugs

  12. Ruminative Self-Focus and Negative Affect

    OpenAIRE

    Moberly, Nicholas J.; Watkins, Edward R.

    2008-01-01

    The authors conducted an experience sampling study to investigate the relationship between momentary ruminative self-focus and negative affect. Ninety-three adults recorded these variables at quasi-random intervals 8 times daily for 1 week. Scores on questionnaire measures of dispositional rumination were associated with mean levels of momentary ruminative self-focus over the experience sampling week. Concurrently, momentary ruminative self-focus was positively associated with negative affect...

  13. 7 CFR 984.64 - Disposition of substandard walnuts.

    Science.gov (United States)

    2010-01-01

    ... walnuts meeting the minimum kernel content requirements effective pursuant to § 984.50(e), may be pooled... production and holdings of substandard walnuts and (b) the disposition of all substandard walnuts to...

  14. Legacy sample disposition project. Volume 2: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gurley, R.N.; Shifty, K.L.

    1998-02-01

    This report describes the legacy sample disposition project at the Idaho Engineering and Environmental Laboratory (INEEL), which assessed Site-wide facilities/areas to locate legacy samples and owner organizations and then characterized and dispositioned these samples. This project resulted from an Idaho Department of Environmental Quality inspection of selected areas of the INEEL in January 1996, which identified some samples at the Test Reactor Area and Idaho Chemical Processing Plant that had not been characterized and dispositioned according to Resource Conservation and Recovery Act (RCRA) requirements. The objective of the project was to manage legacy samples in accordance with all applicable environmental and safety requirements. A systems engineering approach was used throughout the project, which included collecting the legacy sample information and developing a system for amending and retrieving the information. All legacy samples were dispositioned by the end of 1997. Closure of the legacy sample issue was achieved through these actions.

  15. Hearing Office Dispositions Per ALJ Per Day Rate Ranking Report

    Data.gov (United States)

    Social Security Administration — A ranking of ODAR hearing offices by the average number of hearings dispositions per ALJ per day. The average shown will be a combined average for all ALJs working...

  16. Americium/Curium Disposition Life Cycle Planning Study

    International Nuclear Information System (INIS)

    At the request of the Department of Energy Savannah River Office (DOE- SR), Westinghouse Savannah River Company (WSRC) evaluated concepts to complete disposition of Americium and Curium (Am/Cm) bearing materials currently located at the Savannah River Site (SRS)

  17. Legacy sample disposition project. Volume 2: Final report

    International Nuclear Information System (INIS)

    This report describes the legacy sample disposition project at the Idaho Engineering and Environmental Laboratory (INEEL), which assessed Site-wide facilities/areas to locate legacy samples and owner organizations and then characterized and dispositioned these samples. This project resulted from an Idaho Department of Environmental Quality inspection of selected areas of the INEEL in January 1996, which identified some samples at the Test Reactor Area and Idaho Chemical Processing Plant that had not been characterized and dispositioned according to Resource Conservation and Recovery Act (RCRA) requirements. The objective of the project was to manage legacy samples in accordance with all applicable environmental and safety requirements. A systems engineering approach was used throughout the project, which included collecting the legacy sample information and developing a system for amending and retrieving the information. All legacy samples were dispositioned by the end of 1997. Closure of the legacy sample issue was achieved through these actions

  18. Crosslinked electrospun PVA nanofibrous membranes: elucidation of their physicochemical, physicomechanical and molecular disposition

    International Nuclear Information System (INIS)

    The effects of modifying electrospun poly(vinyl alcohol) (PVA) nanofibers through crosslinking using glutaraldehyde (GA) are explored in this paper. Various concentrations of PVA solutions containing model drugs rifampicin (RIF) and isoniazid (INH) were electrospun and thereafter crosslinked using GA vapors. PVA nanofibers demonstrated high drug entrapment efficiency of 98.77% ± 1.384% and 95.07% ± 1.988% for the INH- and RIF-loaded PVA nanofibers, respectively. The surface morphology, molecular vibrational transitions, tensile attributes and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results indicated that crosslinking caused a significant reduction in the rate of drug release where 81.11% ± 2.35% of INH and 59.31% ± 2.57% of RIF were released after 12 h. Tensile properties such as the ultimate strength and Young's modulus increased after crosslinking, caused by crosslinks forming between PVA nanofibers as was revealed through scanning electron microscopy analysis. Fourier Transform infrared analysis was conducted to further support the mode of crosslinking. Additionally, image processing analysis was carried out to quantify the effect of formulation variables on the morphology of nanofibers. Furthermore, the effect of GA-induced crosslinking and addition of drugs on the performance of electrospun fibers was further elucidated and conceptualized using a molecular mechanics assisted model building and energy refinement approach via molecular mechanics energy relationships by exploring the spatial disposition of energy-minimized molecular structures of the polymer, crosslinker and the drugs. (paper)

  19. Renal Disposition of Colistin in the Isolated Perfused Rat Kidney▿

    OpenAIRE

    Ma, Zheng; Wang, Jiping; Nation, Roger L; Jian LI; Turnidge, John D.; Coulthard, Kingsley; Milne, Robert W.

    2009-01-01

    Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 μg/ml) or in the presence...

  20. Surplus plutonium disposition draft environmental impact statement. Summary

    International Nuclear Information System (INIS)

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel

  1. The Relationship between Critical Thinking Disposition and Self-Esteem

    OpenAIRE

    Shirin Iranfar; Vida Sepahi; Ahmad Khoshay; Farahnaz Keshavarzi

    2013-01-01

    Introduction: Critical Thinking Disposition indicates individual’s inclination to Critical Thinking, which is one of the domains of personality. Individual characteristics are important and influential factors in the growth and development of students’ Critical Thinking. One of these influential characteristics might be self-esteem, thus this study was to determine the correlation between Critical Thinking Disposition and self-esteem in medical students. Methods: In an analytical cross-sec...

  2. Guide for disposition of radioactive-material sources

    International Nuclear Information System (INIS)

    This guide has been prepared to assist DOE Energy Technology Centers in disposing of radioactive-material sources. The guide describes the steps and requirements necessary to dispose of unwanted sources. The steps include obtaining approvals, source characterization, source disposition, packaging requirements, and shipment preparation. A flow chart is provided in the guide to assist the user in the necessary sequential steps of source disposition

  3. Contributions of Thinking Styles to Critical Thinking Dispositions

    OpenAIRE

    Zhang, LF

    2003-01-01

    The main purpose of the author's research was to investigate whether thinking styles significantly contribute to critical thinking dispositions. Two samples of Chinese university students, one from Beijing and the other from Nanjing, participated in the study. The participants responded to the Thinking Styles Inventory (R. J. Sternberg & R. K. Wagner, 1992) based on Sternberg's theory of mental self-government and to the California Critical Thinking Disposition Inventory (P. Facione & N. Faci...

  4. Contribution of Emotional Intelligence towards Graduate Students’ Critical Thinking Disposition

    OpenAIRE

    Fong-Luan Kang

    2015-01-01

    Good critical thinkers possess a core set of cognitive thinking skills, and a disposition towards critical thinking. They are able to think critically to solve complex, real-world problems effectively. Although personal emotion is important in critical thinking, it is often a neglected issue. The emotional intelligence in this study concerns our sensitivity to and artful handling of our own and others’ emotions. Engaging students emotionally is the key to strengthening their dispositions towa...

  5. Surplus plutonium disposition draft environmental impact statement. Volume 2

    International Nuclear Information System (INIS)

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel. Volume 2 contains the appendices to the report and describe the following: Federal Register notices; contractor nondisclosure statement; adjunct melter

  6. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA ( ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of Abuse Commonly Abused Drugs Charts Emerging Trends Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA ( ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

  8. Effect of acute and chronic ethanol pre-treatment on the disposition of phencyclidine (PCP) in the rat.

    Science.gov (United States)

    Vadlamani, N L; Pontani, R B; Misra, A L

    1982-05-01

    Disposition of [H] Phencyclidine in brain, plasma and adipose tissue of rats acutely and chronically-treated with ethanol was studied using a method possessing high sensitivity and specificity for PCP. In rats acutely-treated with ethanol (5 g/kg PO dose) and PCP (10 mg/kg IP dose), dispositional factors did not play a role in the intensifies pharmacological and behavioral effects of PCP. However in rats chronically-treated with 2.5 g/kg PO dose of ethanol twice a day for 19 days, the disposition of PCP (5 mg/kg IP dose) was significantly altered and the values of PCP in brain, plasma and adipose tissue were significantly higher than those in the control group. Although inhibition of PCP metabolism and a comparatively slower rate of its elimination appear to account for the potentiation of drug effects in animals chronically-treated with ethanol, interaction of drugs at the level of the central nervous system cannot be ruled out. PMID:7089042

  9. A Growth Curve Analysis of the Joint Influences of Parenting Affect, Child Characteristics and Deviant Peers on Adolescent Illicit Drug Use

    Science.gov (United States)

    Pires, Paulo; Jenkins, Jennifer M.

    2007-01-01

    This study purports that parental rejection and warmth are critical to the development of adolescent drug use, and investigates a model that also considers children's vulnerability and deviant peer affiliations. It tests mediation through the proximal risk factor of deviant peers. Poisson growth curve modeling was used to examine participants from…

  10. Turkish counselor educators’ opinions about counselor candidates’ dispositions

    Directory of Open Access Journals (Sweden)

    Fidan Korkut Owen

    2014-05-01

    Full Text Available Counselor candidates are assessed though homework, exams, projects and thesis during their education. On the other hand, there are some discussions about assessments of their dispositions besides their academic achievement. Even though here is no consensus about what these characteristics are, openness, self-awareness, honesty can be given as an example. The purpose of this study is three­fold: a to describe what Turkish counselor educators think about which dispositions counselor candidates should have, b how these dispositions can be developed or enriched and c how they can be assessed. Researchers developed a questionnaire with five open ended questions and it was sent to 48 counselor educators via email, 34 of them from 23 universities (three of them were private sent their feedback, so return rate was 71%. The findings were analyzed by using descriptive statistics such as frequencies. According to findings, counselor educators mainly revealed that honesty, being open for communication, empathetic understanding, self-awareness, being flexible and helpful are fundamental dispositions. According to counselor educators these dispositions can be developed by increasing the number of practicum courses, adding counseling supervision courses and practices to education program, being a role model as counselor educators. Counselor educators suggested that dispositions can be assessed by evaluating students’ performance during practicum courses, using test and non-test assessment techniques, observing them and interviewing. Results were discussed in light of current literature.

  11. Plasma and Ocular Prednisolone Disposition after Oral Treatment in Cats

    Directory of Open Access Journals (Sweden)

    María J. Del Sole

    2013-01-01

    Full Text Available Objective. To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. Methods. Six cats were administered with a single oral dose of prednisolone (10 mg. Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. Results. Mean ± standard error (SE of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC was 553.3 ± 120.0 ng*h/mL and 378.8 ± 64.9 ng*h/mL, respectively. A high AUCaqueous humor/AUCplasma ratio was observed (0.68 ± 0.13. The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. Clinical Significance. The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.

  12. Porfiromycin disposition in oxygen-modulated P388 cells.

    Science.gov (United States)

    Pan, S S

    1990-01-01

    The cytotoxicity, metabolism, and DNA alkylation of porfiromycin (PFM) under aerobic and hypoxic conditions were evaluated in P388 murine leukemia cells. Clonogenic assays showed that the IC50 value for a 1-h exposure to PFM was 4 microM for aerobic cells and 0.5 microM for hypoxic cells. After a 1-h exposure to concentrations of 1, 5, and 10 microM [14C]-PFM, the accumulation of total radioactivity in hypoxic cells was 10 to 20 times that in aerobic cells. The disposition of radioactivity in cells that had been treated for 1 h with 5 microM PFM under aerobic or hypoxic conditions showed that (a) under either condition, internal free-PFM concentration equalled the external drug concentration; (b) DNA-, RNA-, and protein-bound radioactivity were at least 10 times greater in hypoxic cells than in aerobic cells; and (c) known metabolites and unidentified radioactive products were also generated in greater amounts in hypoxic cells than in aerobic cells. Thus, the increased amounts of radioactivity accumulated by hypoxic P388 cells after exposure to [14C]-PFM resulted from the accumulation of nonexchangeable protein and nucleic-acid adducts and metabolites rather than free PFM. Determinations of DNA adducts formed in P388 cells revealed five possible adducts: (1) N2-(2'-deoxyguanosyl)-7-methylaminomitosene, (2) a second monofunctional PFM-guanine adduct, (3) a PFM cross-linked dinucleotide, (4) possibly a nucleoprotein-related adduct, and (5) an unknown. We conclude that the enhancement of PFM-induced cytotoxicity by hypoxia appears to be primarily due to increased alkylation of macromolecules. PMID:2265454

  13. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  14. A Role for Naturally Occurring Alleles of Endoplasmic Reticulum Aminopeptidases in Tumor Immunity and Cancer Pre-Disposition

    OpenAIRE

    Stratikos, Efstratios; Stamogiannos, Athanasios; Zervoudi, Efthalia; Fruci, Doriana

    2014-01-01

    Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) are key components on the pathway that generates antigenic epitopes for presentation to cytotoxic T-lymphocytes (CTLs). Coding single nucleotide polymorphisms (SNPs) in these enzymes have been associated with pre-disposition to several major human diseases including inflammatory diseases with autoimmune etiology, viral infections, and virally induced cancer. The function of these enzymes has been demonstrated to affect CTL and nat...

  15. Routes of Motivation: Stable Psychological Dispositions Are Associated with Dynamic Changes in Cortico-Cortical Functional Connectivity

    OpenAIRE

    Viola, Vanda; Tosoni, Annalisa; Kruglanski, Arie W.; Galati, Gaspare; Mannetti, Lucia

    2014-01-01

    The present study provides a neurobiological framework to the theory of epistemic motivation that has been extensively studied for the last three decades in the domain of social cognition. Epistemic motivations affect the way people generate and validate hypotheses, and ultimately form and modify knowledge. Strong dispositional measures such as need for cognitive closure (NCC), the desire for a quick firm answer (any answer) to a question, show gross and stable inter-individual differences. T...

  16. TRACKING SURPLUS PLUTONIUM FROM WEAPONS TO DISPOSITION

    Energy Technology Data Exchange (ETDEWEB)

    Allender, J.; Beams, J.; Sanders, K.; Myers, L.

    2013-07-16

    Supporting nuclear nonproliferation and global security principles, beginning in 1994 the United States has withdrawn more than 50 metric tons (MT) of government-controlled plutonium from potential use in nuclear weapons. The Department of Energy (DOE), including the National Nuclear Security Administration, established protocols for the tracking of this "excess" and "surplus" plutonium, and for reconciling the current storage and utilization of the plutonium to show that its management is consistent with the withdrawal policies. Programs are underway to ensure the safe and secure disposition of the materials that formed a major part of the weapons stockpile during the Cold War, and growing quantities have been disposed as waste, after which they are not included in traditional nuclear material control and accountability (NMC&A) data systems. A combination of resources is used to perform the reconciliations that form the basis for annual reporting to DOE, to U.S. Department of State, and to international partners including the International Atomic Energy Agency.

  17. Diphenhydramine disposition in chronic liver disease.

    Science.gov (United States)

    Meredith, C G; Christian, C D; Johnson, R F; Madhavan, S V; Schenker, S

    1984-04-01

    Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was induced in all subjects by a 0.8 mg/kg iv dose without an apparent increase in cerebral sensitivity in the patients with cirrhosis. Protein binding as determined by equilibrium dialysis (3H-DPHM) revealed a 15% decrease in the cirrhotic patients, while recovery of unchanged DPHM in urine (2%) was of the same order in the two groups. Computerized biexponential curve analysis was used to compare the plasma profiles for five of the patients and six of the normal subjects. Monoexponential curve analysis of the terminal beta-phase, including all subjects, was also used to compare the two groups. The means of plasma clearance and apparent volume of distribution in cirrhotic patients were respectively less and greater than in normal subjects, but these differences were not significant. The t1/2 for the beta-phase (t1/2 beta), which reflects this reciprocal trend, was increased in the patients (15.2 +/- 1.5 and 9.3 +/- 0.9 hr). This correlated in part with severity of disease, with r = 0.723 between t1/2 beta and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis. PMID:6705445

  18. ISS Logistics Hardware Disposition and Metrics Validation

    Science.gov (United States)

    Rogers, Toneka R.

    2010-01-01

    I was assigned to the Logistics Division of the International Space Station (ISS)/Spacecraft Processing Directorate. The Division consists of eight NASA engineers and specialists that oversee the logistics portion of the Checkout, Assembly, and Payload Processing Services (CAPPS) contract. Boeing, their sub-contractors and the Boeing Prime contract out of Johnson Space Center, provide the Integrated Logistics Support for the ISS activities at Kennedy Space Center. Essentially they ensure that spares are available to support flight hardware processing and the associated ground support equipment (GSE). Boeing maintains a Depot for electrical, mechanical and structural modifications and/or repair capability as required. My assigned task was to learn project management techniques utilized by NASA and its' contractors to provide an efficient and effective logistics support infrastructure to the ISS program. Within the Space Station Processing Facility (SSPF) I was exposed to Logistics support components, such as, the NASA Spacecraft Services Depot (NSSD) capabilities, Mission Processing tools, techniques and Warehouse support issues, required for integrating Space Station elements at the Kennedy Space Center. I also supported the identification of near-term ISS Hardware and Ground Support Equipment (GSE) candidates for excessing/disposition prior to October 2010; and the validation of several Logistics Metrics used by the contractor to measure logistics support effectiveness.

  19. Material disposition - a revival for shortcomers?

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, W.

    2005-03-01

    Nuclear disarmament is an enduring and costly activity among the former Superpowers. This flow of money attracts many of the now suffering niche-concepts for reactors and fuel cycles, having survived so far from early enthusiastic times, in praising their merits for just this material disposition. While stringent MD-criteria could be met in standard LWR with very simple and conventional MOX fuels, both nuclear military powers are tempted to use this expensive exercise to a covert modernisation of their fuel cycles for a later economic cycle closure, in Russia even with an eye on later uranium savings by near breeder concepts. The demonstrated Russian reluctance in 'wasting' their costly Plutonium must be sweetened by a generous US support of a variety of research topics, including the mentioned near-breeder concepts, keeping Russian scientists on the peaceful track. Earlier principles of never embarking into a 'Plutonium economy' are softened into a bilateral exception for both weapon's superpowers, as most of the industrialized non-nuclear weapon states have been pushed into abandoning the closed fuel cycle already and a general ban for new national fuel cycle activities is on the agenda of the coming NPT review conference. It remains to be seen, whether those concessions to the still martial behaviour of Russia will ever bear fruit or whether later generations will have to pay the price for a potentially unwarranted appeasement. (orig.)

  20. Material disposition - a revival for shortcomers?

    International Nuclear Information System (INIS)

    Nuclear disarmament is an enduring and costly activity among the former Superpowers. This flow of money attracts many of the now suffering niche-concepts for reactors and fuel cycles, having survived so far from early enthusiastic times, in praising their merits for just this material disposition. While stringent MD-criteria could be met in standard LWR with very simple and conventional MOX fuels, both nuclear military powers are tempted to use this expensive exercise to a covert modernisation of their fuel cycles for a later economic cycle closure, in Russia even with an eye on later uranium savings by near breeder concepts. The demonstrated Russian reluctance in 'wasting' their costly Plutonium must be sweetened by a generous US support of a variety of research topics, including the mentioned near-breeder concepts, keeping Russian scientists on the peaceful track. Earlier principles of never embarking into a 'Plutonium economy' are softened into a bilateral exception for both weapon's superpowers, as most of the industrialized non-nuclear weapon states have been pushed into abandoning the closed fuel cycle already and a general ban for new national fuel cycle activities is on the agenda of the coming NPT review conference. It remains to be seen, whether those concessions to the still martial behaviour of Russia will ever bear fruit or whether later generations will have to pay the price for a potentially unwarranted appeasement. (orig.)

  1. Tracking surplus plutonium from weapons to disposition

    International Nuclear Information System (INIS)

    Supporting nuclear nonproliferation and global security principles, beginning in 1994 the United States has withdrawn more than 50 metric tons (MT) of government-controlled plutonium from potential use in nuclear weapons. The Department of Energy (DOE), including the National Nuclear Security Administration, established protocols for the tracking of this ''excess'' and ''surplus'' plutonium, and for reconciling the current storage and utilization of the plutonium to show that its management is consistent with the withdrawal policies. Programs are underway to ensure the safe and secure disposition of the materials that formed a major part of the weapons stockpile during the Cold War, and growing quantities have been disposed as waste, after which they are not included in traditional nuclear material control and accountability (NMC and A) data systems. A combination of resources is used to perform the reconciliations that form the basis for annual reporting to DOE, to U.S. Department of State, and to international partners including the International Atomic Energy Agency.

  2. Tissue disposition of carbon disulfide: I

    International Nuclear Information System (INIS)

    Occupational exposure to carbon disulfide (CS2) is associated with several adverse effects such as neurotoxicity, atherosclerosis, liver injury and endocrinal disturbances. In the present study, the distribution of CS2 and its metabolites after inhalation of 35S- or 14C-labelled CS2 was studied in adult male mice with whole-body autoradiography. CS2 itself was registered in body fat and in well-perfused tissues at survival times up to 2 hours. Very little CS2 was taken up by the brain. The distribution patterns of CS2 metabolites were very different after administration of C35S2 or 14CS2. 35S-Labelled metabolites were initially concentrated in the liver and kidney, but were rapidly eliminated from the body. There was evidence of an extensive metabolic incorporation of sulfur split off from CS2 during its biotransformation. 14C-Labelled metabolites were likewise concentrated in the liver and kidney, but were also observed in large amounts in the nasal mucosa, bronchi, bone, pancreas, thyroid, adrenal cortex and testis. A marked retention of non-extractable 14C-labelled metabolites was seen in the liver and thyroid. The results point to several sites of specific CS2-induced toxicity due to the tissue disposition of metabolites of CS2. (author)

  3. The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer

    International Nuclear Information System (INIS)

    The ubiquitin-proteasome pathway is responsible for most eukaryotic intracellular protein degradation. This pathway has been validated as a target for antineoplastic therapy using both in vitro and preclinical models of human malignancies, and is influenced as part of the mechanism of action of certain chemotherapeutic agents. Drugs whose primary action involves modulation of ubiquitin-proteasome activity, most notably the proteasome inhibitor PS-341, are currently being evaluated in clinical trials, and have already been found to have significant antitumor efficacy. On the basis of the known mechanisms by which these agents work, and the available clinical data, they would seem to be well suited for the treatment of breast neoplasms. Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer

  4. [Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?].

    Science.gov (United States)

    Gumieniczek, Anna

    2016-01-01

    Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs' action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs - analogs of glucagon-like peptide 1 (GLP-1), inhibitors of dipeptidyl peptidase IV (DPPIV) and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2) - has been made, based on a review of the literature over the past five years (2010-2014). The information included in the present review concerns the structure and activity relationship, therapeutic efficacy, side effects and the observed additional therapeutic effects, which can determine new standards in therapy of diabetes and also facilitate the development of better antidiabetic drugs. PMID:27180961

  5. The disposition of weapon grade plutonium: costs and tradeoffs

    International Nuclear Information System (INIS)

    This paper explores some of the economic issues surrounding a major area of expenditures now facing the nuclear powers: the disposition of weapon-grade plutonium either through 'burning' in nuclear reactors for power generation or by other means. Under the current budgeting philosophy in the United States, programs managed by the Department of Energy (DOE) tend to compete with one another for the total funds assigned to that agency. For example, in the FY1995 DOE budget a tradeoff was made between increased funding for nuclear weapons and reduced funding for site cleanup. No matter which disposition alternative is chosen, if disposition funds are controlled by the DOE in the US or by a government agency in any other country, disposition is likely to compete directly or indirectly with other alternatives for energy funding. And if they are subsidized by any government, research into plutonium as reactor fuel or the operations associated with such use are likely to consume funds that might otherwise be available to support sustainable energy alternatives. When all costs are considered, final waste disposal costs will be incurred whatever disposal option is taken. These costs could potentially be offset by doing something profitable with the plutonium prior to final storage, but this paper has shown that finding a profitable use for plutonium is unlikely. Thus, the more probable case is one where the costs of basic waste storage are increased by whatever costs are associated with the disposition option chosen. The factors most likely to significantly increase costs appear to arise from four areas: (1) The level of subsidization in the 'profitable' parts of the disposition program. (2) Those items (such as reprocessing) that increase the volume of waste and thus, the cost of waste disposal. (3) The cost of security and its direct relationship to the number of times plutonium is handled or moved. (4) The cost of research and development of new and unproven methods of

  6. A Quantitative Review and Meta-models of the Variability and Factors Affecting Oral Drug Absorption-Part II: Gastrointestinal Transit Time.

    Science.gov (United States)

    Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

    2016-09-01

    This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) transit times of non-disintegrating single-unit ("tablet") and multiple-unit ("pellets/multi-unit tablet") solid dosage forms, characterize the effect of food on the values and variability in these parameters and present quantitative meta-models of the distributions of GI transit times in the respective GI regions to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, gastric, small intestinal and colonic transit times under fed and fasted conditions. Meta-analysis used the "metafor" package of the R language. Meta-models of GI transit were assumed to be log-normally distributed between the studied populations. Twenty-nine studies including 125 reported means and standard deviations were used in the meta-analysis. Caloric content of administered food increased variability and delayed the gastric transit of both pellets and tablets. Conversely, food caloric content reduced the variability but had no significant influence on the mean small intestinal transit time (SITT). Food had no significant effect on the transit time through the colon. The transit of pellets through the colon was significantly slower than that of single-unit tablets which is most likely related to their smaller size. GI transit times may influence the dissolution and absorption of oral drugs. The meta-models of GI transit times may be used as part of semi-physiological absorption models to characterize the influence of transit time on the dissolution, absorption and in vivo pharmacokinetic profiles of oral drugs. PMID:27439620

  7. A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption-Part I: Gastrointestinal pH.

    Science.gov (United States)

    Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

    2016-09-01

    This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) pH in the different GI segments; characterize the effect of food on the values and variability in these parameters; and present quantitative meta-models of distributions of GI pH to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions. The GI tract was categorized into the following 10 distinct regions: stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and ileum (proximal, mid, and distal small intestine), and colon (ascending, transverse, and descending colon). Meta-analysis used the "metafor" package of the R language. The time course of postprandial stomach pH was modeled using NONMEM. Food significantly influenced the estimated meta-mean stomach and duodenal pH but had no significant influence on small intestinal and colonic pH. The time course of postprandial pH was described using an exponential model. Increased meal caloric content increased the extent and duration of postprandial gastric pH buffering. The different parts of the small intestine had significantly different pH. Colonic pH was significantly different for descending but not for ascending and transverse colon. Knowledge of GI pH is important for the formulation design of the pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH may also be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics. PMID:27495120

  8. Embryo disposition and the new death scene

    Directory of Open Access Journals (Sweden)

    Ellison, David

    2011-01-01

    Full Text Available In the IVF clinic - a place designed principally for the production and implantation of embryos - scientists and IVF recipients are faced with decisions regarding the disposition of frozen embryos. At this time there are hundred of thousands of cryopreserved embryos awaiting such determinations. They may be thawed for transfer to the woman herself, they may be donated for research or for use by other infertile couples, they may remain in frozen storage, or they may variously be discarded by being allowed to 'succumb', or 'perish'. Where the choice is discard, some IVF clients have chosen to formalise the process through ceremony. A new language is emerging in response to the desires of the would-be-parents who might wish to characterise the discard experience as a ‘good death’. This article examines the procedure known as ‘compassionate transfer’ where the embryo to be discarded is placed in the woman’s vagina where it is clear that it will not develop further. An alternate method has the embryo transferred in the usual manner but without the benefit of fertility-enhancing hormones at a point in the cycle unreceptive to implantation. The embryo destined for disposal is thus removed from the realm of technological possibility and ‘returned’ to the female body for a homely death. While debates continue about whether or not embryos constitute life, new practices are developing in response to the emotional experience of embryo discard. We argue that compassionate transfer is a death scene taking shape. In this article, we take the measure of this new death scene’s fabrication, and consider the form, significance, and legal complexity of its ceremonies.

  9. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental ...

  10. Measuring teacher dispositions using the DAATS battery: a multifaceted Rasch analysis of rater effect.

    Science.gov (United States)

    Lang, W Steve; Wilkerson, Judy R; Rea, Dorothy C; Quinn, David; Batchelder, Heather L; Englehart, Dierdre S; Jennings, Kelly J

    2014-01-01

    The purpose of this study was to examine the extent to which raters' subjectivity impacts measures of teacher dispositions using the Dispositions Assessments Aligned with Teacher Standards (DAATS) battery. This is an important component of the collection of evidence of validity and reliability of inferences made using the scale. It also provides needed support for the use of subjective affective measures in teacher training and other professional preparation programs, since these measures are often feared to be unreliable because of rater effect. It demonstrates the advantages of using the Multi-Faceted Rasch Model as a better alternative to the typical methods used in preparation programs, such as Cohen's Kappa. DAATS instruments require subjective scoring using a six-point rating scale derived from the affective taxonomy as defined by Krathwohl, Bloom, and Masia (1956). Rater effect is a serious challenge and can worsen or drift over time. Errors in rater judgment can impact the accuracy of ratings, and these effects are common, but can be lessened through training of raters and monitoring of their efforts. This effort uses the multifaceted Rasch measurement models (MFRM) to detect and understand the nature of these effects. PMID:24992248

  11. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals

    Science.gov (United States)

    Zhang, Ming-Duo; Li, Xin-He; Nie, Mao-Xiao; Feng, Ting-Ting; Zhao, Xin; Wang, Lu-Ya; Zhao, Quan-Ming

    2016-01-01

    Objective In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion Our results indirectly suggest that

  12. “First, do no harm”: legal guidelines for health programmes affecting adolescents aged 10–17 who sell sex or inject drugs

    OpenAIRE

    Brendan Conner

    2015-01-01

    Introduction: There is a strong evidence base that the stigma, discrimination and criminalization affecting adolescent key populations (KPs) aged 10–17 is intensified due to domestic and international legal constructs that rely on law-enforcement-based interventions dependent upon arrest, pre-trial detention, incarceration and compulsory “rehabilitation” in institutional placement. While there exists evidence and rights-based technical guidelines for interventions among older cohorts, these g...

  13. Morphine metabolism, transport and brain disposition

    OpenAIRE

    De Gregori, Simona; De Gregori, Manuela; Ranzani, Guglielmina Nadia; Allegri, Massimo; Minella, Cristina; Regazzi, Mario

    2011-01-01

    The chemical structures of morphine and its metabolites are closely related to the clinical effects of drugs (analgesia and side-effects) and to their capability to cross the Blood Brain Barrier (BBB). Morphine-6-glucuronide (M6G) and Morphine-3-glucuronide (M3G) are both highly hydrophilic, but only M6G can penetrate the BBB; accordingly, M6G is considered a more attractive analgesic than the parent drug and the M3G. Several hypotheses have been made to explain these differences. In this rev...

  14. PBL and critical thinking disposition in Chinese medical students

    DEFF Research Database (Denmark)

    Du, Xiangyun; Emmersen, Jeppe; Toft, Egon;

    2013-01-01

    ) were randomized to PBL or non-PBL teaching at the commencement of the study. After five years of study, CT was scored by a Chinese version of the California Critical Thinking Disposition Inventory (CCTDI-CV). The score achieved on a Computer Case Simulation (CCS) test evaluated academic performance......The purpose of this study was to explore the relationship of problem-based learning (PBL) and the development of critical thinking disposition (CT) and academic achievement in Chinese medical students using a cross-sectional randomized design. Medical students from China Medical University (CMU...... scores and CCTDI-CV results. Male students scored slightly higher on the CCS test compared to female students (male 113.4±18.9 vs. female 109.7±19.7), but the difference was not significant. This study concludes that in Chinese medical students, PBL teaching was related to a higher disposition of...

  15. Dispositional empathy and the hierarchical structure of personality.

    Science.gov (United States)

    Mooradian, Todd A; Davis, Mark; Matzler, Kurt

    2011-01-01

    Personality psychology has recognized a fundamental 5-factor structure that has integrated and organized theory and research. Nevertheless, personality-like differences beyond that structure have been identified. In heretofore unrelated research, dispositional empathy has been an essential construct in understanding human development, behavior, and interpersonal relationships. Addressing a gap in the literature, we map multidimensional dispositional empathy into 2 versions of the 5-factor space. Empathic concern is closely related to agreeableness, and personal distress is closely related to neuroticism. Perspective taking has complex, interstitial relationships with the 5 factors. In contrast, fantasy is not well explained by the 5 factors. We discuss the implications of these findings for understanding dispositional empathy and for understanding the 5-factor structure, its correlates in emotional processes and experiences, and its limits. PMID:21506454

  16. Options For The Disposition Of UK Civil Plutonium Stocks

    Energy Technology Data Exchange (ETDEWEB)

    Moore, R.G.; Zimmerman, C.H.; Scales, C.; Worrall, A.; Sims, H.E.; Fowler, L. [Nexia Solutions Ltd (United Kingdom)

    2008-07-01

    The UK Civil Pu Disposition project will identify and assess the viability of several technical options for dealing with the UK's civil separated Pu stockpile and the discriminators that will support technology option down-selection decisions. The overall aim will be to deliver feasible technical options and comprehensive information on political, economic, sociological, environmental and technical factors for each strategic option. This paper briefly describes the work completed to date to assess immobilisation and re-use technologies as disposition strategies and on the work that will identify discriminators to support technology down-selection. The Pu disposition project is anticipated to continue for several years while the necessary investigations are made to fully understand the various options. The work planned over this period is discussed. (authors)

  17. Holding Periods, Illiquidity and Disposition Effect in a Developing Economy

    Directory of Open Access Journals (Sweden)

    Muhammad Aftab,

    2012-01-01

    Full Text Available This paper aims to empirically investigate holding periods, illiquidity and disposition effect in Karachi Stock Exchange (KSE. KSE 100 Index Companies daily data were collected for a period of five year i.e. 2003-2007. Daily returns, holding periods, illiquidity and volatility were calculated through this data. These variables were regressed in models used by Visaltanachoti et al. (2007 to calculate annual holding periods, illiquidity and disposition effect. The results have revealed that there exists disposition effect in KSE. Holding periods were found positively related to illiquidity and negatively associated with stock returns. Further, holding periods were long for illiquid stocks and short for less illiquid stocks. The study is significant in the sense that it’s perhaps the first study conducted in a developing country like Pakistan.

  18. Dispositional anxiety blocks the psychological effects of power.

    Science.gov (United States)

    Maner, Jon K; Gailliot, Matthew T; Menzel, Andrew J; Kunstman, Jonathan W

    2012-11-01

    A growing body of research demonstrates that power promotes a fundamental orientation toward approach and agency. The current studies suggest that this tendency is moderated by dispositional anxiety. In two experiments, high levels of dispositional anxiety blocked the psychological effects of power. Although people low in anxiety responded to a power prime with greater willingness to take risks, those high in anxiety did not (Experiment 1). Similarly, whereas those low in social anxiety responded to power with increased sexual attraction toward a confederate, individuals high in social anxiety failed to show the same effect (Experiment 2). In both studies, the interaction between power and anxiety was statistically mediated by perceptions of reward. Although power enhanced people's perceptions of reward, this effect was eliminated by high levels of dispositional anxiety. This research provides insight into how, and in whom, power promotes approach and agentic behavior. PMID:22854791

  19. Options For The Disposition Of UK Civil Plutonium Stocks

    International Nuclear Information System (INIS)

    The UK Civil Pu Disposition project will identify and assess the viability of several technical options for dealing with the UK's civil separated Pu stockpile and the discriminators that will support technology option down-selection decisions. The overall aim will be to deliver feasible technical options and comprehensive information on political, economic, sociological, environmental and technical factors for each strategic option. This paper briefly describes the work completed to date to assess immobilisation and re-use technologies as disposition strategies and on the work that will identify discriminators to support technology down-selection. The Pu disposition project is anticipated to continue for several years while the necessary investigations are made to fully understand the various options. The work planned over this period is discussed. (authors)

  20. Explanatory style, dispositional optimism, and reported parental behavior.

    Science.gov (United States)

    Hjelle, L A; Busch, E A; Warren, J E

    1996-12-01

    The relationship between two cognitive personality constructs (explanatory style and dispositional optimism) and retrospective self-reports of maternal and paternal behavior were investigated. College students (62 men and 145 women) completed the Life Orientation Test, Attributional Style Questionnaire, and Parental Acceptance-Rejection Questionnaire in a single session. As predicted, dispositional optimism was positively correlated with reported maternal and paternal warmth/acceptance and negatively correlated with aggression/hostility, neglect/indifference, and undifferentiated rejection during middle childhood. Unexpectedly, explanatory style was found to be more strongly associated with retrospective reports of paternal as opposed to maternal behavior. The implications of these results for future research concerning the developmental antecedents of differences in explanatory style and dispositional optimism are discussed. PMID:8955430

  1. Drug: D01221 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01221 Drug gamma Oryzanol (JAN); Hi-Z (TN) C40H58O4 602.4335 602.8861 D01221.gif Therapeutic ca ... of drugs in Japan [BR:br08301] 2 Agents affecting individual ... organs 29 Other agents affecting individual ... organs ... 290 Other agents affecting individual ... organs 2900 Other agents affecting individual ... orga ...

  2. Drug: D01035 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01035 Drug Cepharanthine (JAN); Cepharanthine (TN) C37H38N2O6 606.273 606.7074 D01035.gif Same ... of drugs in Japan [BR:br08301] 2 Agents affecting individual ... organs 29 Other agents affecting individual ... organs ... 290 Other agents affecting individual ... organs 2900 Other agents affecting individual ... orga ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts ... and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were ...

  5. New regulatory dispositions for public buildings; Les nouvelles dispositions reglementaires pour les ERP

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2004-07-01

    Cegibat, the Gaz de France (GdF) information centre for building industry professionals, has organized in October 12, 2004, an information meeting devoted to the updates of the regulation relative to public buildings. The regulatory texts in force today are the by-law from August 2, 1977 for the residential sector, the labour code for non-public tertiary buildings and the regulation from June 25, 1980 for the public buildings. This last text has been reworked recently and several major changes have been made. The other texts are also completed by complementary dispositions concerning some specific types of buildings. This article details and explains more thoroughly these important regulatory changes. (J.S.)

  6. High-Level Waste Salt Disposition Systems Engineering Team Final Report, Volumes I, II, and III

    International Nuclear Information System (INIS)

    This report describes the process used and results obtained by the High Level Waste Salt Disposition Systems Engineering Team to select a primary and backup alternative salt disposition method for the Savannah River Site

  7. Decision model for evaluating reactor disposition of excess plutonium

    International Nuclear Information System (INIS)

    The US Department of Energy is currently considering a range of technologies for disposition of excess weapon plutonium. Use of plutonium fuel in fission reactors to generate spent fuel is one class of technology options. This report describes the inputs and results of decision analyses conducted to evaluate four evolutionary/advanced and three existing fission reactor designs for plutonium disposition. The evaluation incorporates multiple objectives or decision criteria, and accounts for uncertainty. The purpose of the study is to identify important and discriminating decision criteria, and to identify combinations of value judgments and assumptions that tend to favor one reactor design over another

  8. Music and Emotion: the Dispositional or Arousal theory

    OpenAIRE

    Alessandra Buccella

    2012-01-01

    One of the ways of analysing the relationship between music and emotions in through musical expressiveness.As the theory I discuss in this paper puts it, expressiveness in a particular kind of music's secondary quality or, to use the term which gives the theory its name, a disposition of music to arouse a certain emotional response in listeners.The most accurate version of the dispositional theory is provided by Derek Matravers in his book Art and Emotion and in other papers: what I will try ...

  9. Fissile material disposition program final immobilization form assessment and recommendation

    International Nuclear Information System (INIS)

    Lawrence Livermore National Laboratory (LLNL), in its role as the lead laboratory for the development of plutonium immobilization technologies for the Department of Energy's Office of Fissile Materials Disposition (MD), has been requested by MD to recommend an immobilization technology for the disposition of surplus weapons- usable plutonium. The recommendation and supporting documentation was requested to be provided by September 1, 1997. This report addresses the choice between glass and ceramic technologies for immobilizing plutonium using the can-in-canister approach. Its purpose is to provide a comparative evaluation of the two candidate technologies and to recommend a form based on technical considerations

  10. Dispositional factors and work mastery among shift workers.

    Science.gov (United States)

    Foldal, Vegard; Langvik, Eva; Saksvik-Lehouillier, Ingvild

    2016-01-01

    The aim of the present study was to investigate how broad personality dimensions and dispositional resistance to change are associated with mastery of work among shift workers. A total of 285 shift workers employed in rotating shifts with morning, evening and night work and night shift schedules in a municipality in Norway completed electronic questionnaires. The findings suggest that the broad personality dimensions neuroticism and conscientiousness were significant predictors of perceived work mastery among shift workers in this sample, whereas the narrow trait dispositional resistance to change was not. PMID:27093576

  11. IAEA activities. Disposition of plutonium: an international perspective

    International Nuclear Information System (INIS)

    Among disposition options to reduce Pu stockpiles, the use as a fuel in nuclear power reactors seems the most promising and the most technically mature. The international community would welcome early actions at either national or international level. Interim storage for extended period may be needed before implementing disposition options. International arrangements to deposit with IAEA seem preferable to enhance the transparency and thus establish public confidence. Through close international cooperation, states can help to ensure that wherever Pu is stored, used, or disposed of, practices will be carried out according to the highest standards of safety, environmental protection, security and safeguards. (author) figs

  12. Computational Analysis of the SRS Phase III Salt Disposition Alternatives

    International Nuclear Information System (INIS)

    Completion of the Phase III evaluation and comparison of salt disposition alternatives was supported with enhanced computer models and analysis for each case on the ''short list'' of four options. SPEEDUP(TM) models and special purpose models describing mass and energy balances and flow rates were developed and used to predict performance and production characteristics for each of the options. Results from the computational analysis were a key part of the input used to select a primary and an alternate salt disposition alternative

  13. The costs and benefits of optimistic explanations and dispositional optimism.

    Science.gov (United States)

    Tennen, H; Affleck, G

    1987-06-01

    Explanatory style and dispositional optimism have been linked to physical health. In this issue, Peterson and Seligman and Carver and Scheier review an impressive series of studies which together suggest that there may be health risks associated with attributing bad outcomes to internal, stable, and global causes and with failing to maintain a generalized expectancy for good outcomes. We attempt to broaden the scope of these studies by describing the situational constraints on the observed relations and by presenting evidence that there may be health risks, as well as benefits, associated with dispositional optimism and an optimistic explanatory style. PMID:3612476

  14. History of the US weapons-usable plutonium disposition program leading to DOE's record of decision

    International Nuclear Information System (INIS)

    This report highlights important events and studies concerning surplus weapons-usable plutonium disposition in the United States. Included are major events that led to the creation of the U.S. Department of Energy (DOE) Office of Fissile Materials Disposition in 1994 and to that DOE office issuing the January 1997 Record of Decision for the Storage and Disposition of Weapons-Useable Fissile Materials Final Programmatic Environmental Impact Statement. Emphasis has been given to reactor-based plutonium disposition alternatives

  15. Sensitive radioenzymatic assay for catechol drugs

    International Nuclear Information System (INIS)

    This assay measures picogram quantities of catechol drugs and endogenous catecholamines in body tissues and fluids. The catechols are converted to their 3H-O-methyl metabolites during incubation with 3H-S-adenosylmethionine then separated by solvent extraction and thin-layer chromatography. Most drugs containing the catechol structure can be radiolabeled and separated from norepinephrine and epinephrine by this technique to provide simultaneous measurement of endogenous and exogenously administered catechols. The disposition of isoproterenol in tissues and fluids of man and experimental animals is measured to illustrate the utility of this assay. The reactivity of several commonly administered catechol drugs with COMT is described and the possible implications discussed

  16. Assessment of drug metabolism enzyme and transporter pharmacogenetics in drug discovery and early development: perspectives of the I-PWG.

    Science.gov (United States)

    Brian, William; Tremaine, Larry M; Arefayene, Million; de Kanter, Ruben; Evers, Raymond; Guo, Yingying; Kalabus, James; Lin, Wen; Loi, Cho-Ming; Xiao, Guangqing

    2016-04-01

    Genetic variants of drug metabolism enzymes and transporters can result in high pharmacokinetic and pharmacodynamic variability, unwanted characteristics of efficacious and safe drugs. Ideally, the contributions of these enzymes and transporters to drug disposition can be predicted from in vitro experiments and in silico modeling in discovery or early development, and then be utilized during clinical development. Recently, regulatory agencies have provided guidance on the preclinical investigation of pharmacogenetics, for application to clinical drug development. This white paper summarizes the results of an industry survey conducted by the Industry Pharmacogenomics Working Group on current practice and challenges with using in vitro systems and in silico models to understand pharmacogenetic causes of variability in drug disposition. PMID:27045656

  17. Critical Thinking Dispositions of Undergraduate Nursing Students and Nursing Faculty in Southwestern Nigeria

    Science.gov (United States)

    Ojewole, Foluso O.

    2013-01-01

    The purpose of this quantitative research study was to identify the critical thinking dispositions of undergraduate nursing students and nursing faculty in Southwestern Nigeria. Critical thinking dispositions are required for critical thinking skills. People who have critical thinking disposition exhibit seven traits: truth-seeking,…

  18. Contributions of Teachers' Thinking Styles to Critical Thinking Dispositions (Istanbul-Fatih Sample)

    Science.gov (United States)

    Emir, Serap

    2013-01-01

    The main purpose of the research was to determine the contributions of the teachers' thinking styles to critical thinking dispositions. Hence, it is aimed to determine whether thinking styles are related to critical thinking dispositions and thinking styles measure critical thinking dispositions or not. The research was designed in relational…

  19. Antiepileptic drugs: newer targets and new drugs

    OpenAIRE

    Vihang S. Chawan; Abhishek M. Phatak; Kalpesh V. Gawand; Sagar V. Badwane; Sagar S. Panchal

    2016-01-01

    Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and...

  20. Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

    OpenAIRE

    Spiro, Adena S.; Alexander Wong; Boucher, Aurélie A.; Arnold, Jonathon C.

    2012-01-01

    The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9)-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to ca...

  1. Cocaine: analysis, pharmacokinetics, and metabolic disposition.

    OpenAIRE

    Jatlow, P.

    1988-01-01

    The ability to measure concentrations of cocaine in body fluids can contribute substantially to any investigation of cocaine's pharmacological effects. Design of research which involves the administration of cocaine must take into account current knowledge regarding the drug's pharmacokinetics. Cocaine's very rapid elimination from the body should be considered in attempting to understand patterns of cocaine abuse, and such phenomena as bingeing and acute tolerance. Accurate analysis of cocai...

  2. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice.

    Science.gov (United States)

    Merentie, Mari; Lipponen, Jukka A; Hedman, Marja; Hedman, Antti; Hartikainen, Juha; Huusko, Jenni; Lottonen-Raikaslehto, Line; Parviainen, Viktor; Laidinen, Svetlana; Karjalainen, Pasi A; Ylä-Herttuala, Seppo

    2015-12-01

    Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2-3 months), middle-aged (14 months) and old (20-24 months) mice. The ECG changes associated with pharmacological interventions and common cardiac pathologies, that is, acute myocardial infarction (AMI) and progressive left ventricular hypertrophy (LVH), were studied. The ECG raw data were analyzed with an in-house ECG analysis program, modified specially for mouse ECG. Aging led to increases in P-wave duration, atrioventricular conduction time (PQ interval), and intraventricular conduction time (QRS complex width), while the R-wave amplitude decreased. In addition, the prevalence of arrhythmias increased during aging. Anticholinergic atropine shortened PQ time, and beta blocker metoprolol and calcium-channel blocker verapamil increased PQ interval and decreased heart rate. The ECG changes after AMI included early JT elevation, development of Q waves, decreased R-wave amplitude, and later changes in JT/T segment. In progressive LVH model, QRS complex width was increased at 2 and especially 4 weeks timepoint, and also repolarization abnormalities were seen. Aging, drugs, AMI, and LVH led to similar ECG changes in mice as seen in humans, which could be reliably detected with this new algorithm. The developed method will be very useful for studies on cardiovascular diseases in mice. PMID:26660552

  3. The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

    Directory of Open Access Journals (Sweden)

    Patrick A Randall

    Full Text Available Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2 inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA. Rats were assessed using a concurrent progressive ratio (PROG/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1 and eticlopride (D2, but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a

  4. Cognitive Style Predictors of Affect Change in Older Adults

    Science.gov (United States)

    Isaacowitz, Derek M.; Seligman, Martin E. P.

    2002-01-01

    Cognitive styles are the lenses through which individuals habitually process information from their environment. In this study, we evaluated whether different cognitive style individual difference variables, such as explanatory style and dispositional optimism, could predict changes in affective state over time in community-dwelling older adults.…

  5. Dispositional Resistance to Change and Occupational Interests and Choices

    Science.gov (United States)

    Oreg, Shaul; Nevo, Ofra; Metzer, Hila; Leder, Naftali; Castro, Dotan

    2009-01-01

    Through two field studies, we examine the role that individuals' orientation toward change has in determining their occupational choices and interests. In Study 1, 139 job applicants' dispositional resistance to change (RTC) scores were associated with occupational choice, such that individuals applying for investigative and enterprising jobs…

  6. Measurement equivalence of the dispositional resistance to change scale

    Czech Academy of Sciences Publication Activity Database

    Oreg, S.; Bayazıt, M.; Vakola, M.; Arciniega, L.; Armenakis, A.; Barkauskiene, R.; Bozionelos, N.; Fujimoto, Y.; González, L.; Han, J.; Hřebíčková, Martina; Jimmieson, N.; Kordačová, J.; Mitsuhashi, H.; Mlačić, B.; Ferič, I.; Kotrla Topič, M.; Ohly, S.; Oystein Saksvik, P.; Hetland, H.; Saksvik, I.B.; van Dam, K.

    New York : Routledge, 2011 - (Davidov, E.; Schmidt, P.; Billiet, J.), s. 249-278 ISBN 978-1-84872-823-3 R&D Projects: GA AV ČR IAA700250702 Institutional research plan: CEZ:AV0Z70250504 Keywords : dispositional resistance to change * measurement * validation across cultures Subject RIV: AN - Psychology

  7. Oppressors or Emancipators: Critical Dispositions for Preparing Inclusive School Leaders

    Science.gov (United States)

    Theoharis, George; Causton-Theoharis, Julie N.

    2008-01-01

    Leadership from school administrators is essential in creating inclusive schools. The purpose of this article is to outline the dispositions necessary for school leaders in order to develop and maintain inclusive educational services for all students. This work comes from a qualitative study of university-based experts who teach courses in…

  8. MINIMIZING WASTE AND COST IN DISPOSITION OF LEGACY RESIDUES

    International Nuclear Information System (INIS)

    Research is being conducted at the Los Alamos National Laboratory (LANL) which is directed toward development of a quantitative basis for disposition of actinide-bearing process residues (both legacy residues and residues generated from ongoing programmatic operations). This research is focused in two directions: (1) identifying minimum negative consequence (waste, dose, cost) dispositions working within regulatory safeguards termination criteria, and (2) evaluating logistics/consequences of across-the-board residue discards such as authorized at Rocky Flats under a safeguards termination variance. The first approach emphasizes Laboratory commitments to environmental stewardship, worker safety, and fiscal responsibility. This approach has been described as the Plutonium Disposition Methodology (PDM) in deference to direction provided by DOE Albuquerque. The second approach is born of the need to expedite removal of residues from storage for programmatic and reasons and residue storage safety concerns. Any disposition path selected must preserve the legal distinction between residues as Special Nuclear Material (SNM) and discardable materials as waste in order to insure the continuing viability of Laboratory plutonium processing facilities for national security operations

  9. 25 CFR 11.1013 - Modification of dispositional order.

    Science.gov (United States)

    2010-04-01

    ... OFFENSES AND LAW AND ORDER CODE Juvenile Offender Procedure § 11.1013 Modification of dispositional order... minor or the minor's parents, guardian or custodian. (c) If the modification involves a change of...'s court shall review the performance of the minor, the minor's parents, guardian or custodian,...

  10. Learning Modules to Develop Dispositions in Pre-Service Teachers

    Science.gov (United States)

    Stall, Patricia; Elsbree, Anne Rene; Lawler, Brian R.

    2010-01-01

    The purpose of this qualitative research was to develop professional dispositions in secondary pre-service teachers. Throughout the one year credential program, we infused a repetitive and deliberate learning sequence directed at practicing habits of reflection. Scenarios, case studies, role plays, simulations and discussions included questions,…

  11. Helping Behavior, Dispositional Empathic Concern, and the Principle of Care

    Science.gov (United States)

    Wilhelm, Mark Ottoni; Bekkers, Rene

    2010-01-01

    This research investigates the relative strength of two correlates of helping behavior: dispositional empathic concern and a moral principle to care about others. The empathy-helping and care-helping relationships are investigated using data from the General Social Survey, a nationally representative random sample of the U.S. adult population. Ten…

  12. 31 CFR 535.540 - Disposition of certain tangible property.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Disposition of certain tangible property. 535.540 Section 535.540 Money and Finance: Treasury Regulations Relating to Money and Finance... a full accounting of the transaction, including the costs, any payment to lienholders or...

  13. 25 CFR 173.22 - Disposition of revenue.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Disposition of revenue. 173.22 Section 173.22 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER CONCESSIONS, PERMITS AND LEASES ON... revenue. Funds derived from concessions or leases under this part except those so derived from...

  14. 9 CFR 11.22 - Records required and disposition thereof.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Records required and disposition thereof. 11.22 Section 11.22 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE HORSE PROTECTION REGULATIONS § 11.22 Records required...

  15. 19 CFR 123.25 - Certification and disposition of manifests.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Certification and disposition of manifests. 123.25 Section 123.25 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS RELATIONS WITH CANADA AND MEXICO Shipments in Transit Through Canada or Mexico § 123.25 Certification...

  16. High volatility eliminates the disposition effect in a market crisis

    Directory of Open Access Journals (Sweden)

    Raymond Dacey

    2013-12-01

    Full Text Available The disposition effect is an effect whereby investors tend to sell winning stocks and tend to hold losing stocks. This inclination is detrimental for investment results. Dacey and Zielonka (2008 showed the impact of the probability of further stock price rise under low stock price volatility on the disposition effect. Specifically, they showed that under low volatility, in the case of a gain, the investor is more likely to sell the winner even if the probability of the further gain is high, whereas in the case of a loss, the investor is more likely to hold the loser even when the probability of a further gain is small. In this paper we examined the disposition effect under high volatility. The general conclusion is that under high volatility, in the case of a gain, the investor behaves in the same way as for low volatility, whereas in the case of a loss, the investor is less and less likely to hold the loser as volatility increases. Thus, in the case of a loss under high volatility, the investor acts contrary to the disposition effect. This result explains the panic selling of stocks during a market collapse.

  17. 50 CFR 216.73 - Disposition of fur seal parts.

    Science.gov (United States)

    2010-10-01

    ... 50 CFR 216.23(c) for the purpose of processing, and will be returned directly to the Alaskan Native..., or to an agent registered under 50 CFR 216.23(c) for resale or transfer to an Alaskan Native, who... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Disposition of fur seal parts....

  18. Cultivating Critical-Thinking Dispositions throughout the Business Curriculum

    Science.gov (United States)

    Bloch, Janel; Spataro, Sandra E.

    2014-01-01

    Critical thinking is an essential component of managerial literacy, yet business school graduates struggle to apply critical-thinking skills at work to the level that employers desire. This article argues for a dispositional approach to teaching critical thinking, rooted in cultivating a critical-thinking culture. We suggest a two-pronged approach…

  19. Sweet vs. Snap! Effective Dispositions in the Media Center

    Science.gov (United States)

    Standard, April

    2011-01-01

    In "What Defines an Exemplary School Librarian," Jami Jones and Gail Bush make a strong argument that professional disposition is the key to a successful library media program. The authors emphasize the relevance of INTASC standards which specify that teachers must promote "positive social interaction and (develop) healthy and helping…

  20. Cultivating a Disposition for Sociospatial Justice in English Teacher Preparation

    Science.gov (United States)

    Miller, S. J.

    2014-01-01

    This study highlights one semester of ongoing research reflecting how preservice English students performed dispositions for social justice. This work draws on a postmethod approach, observing participants' artifacts and participation in a variety of classroom activities. By tapping into participants' funds of social justice knowledge,…

  1. Disposition of excess fissile materials in deep boreholes

    International Nuclear Information System (INIS)

    As a result of recent changes throughout the world, a substantial inventory of excess separated plutonium is expected to result from dismantlement of US nuclear weapons. The safe and secure management and eventual disposition of this plutonium, and of a similar inventory in Russia, is a high priority. A variety of options (both interim and permanent) are under consideration to manage this material. The permanent solutions can be categorized into two broad groups: direct disposal and utilization. Plutonium utilization options have in common the generation of high-level radioactive waste which will be disposed of in a mined geologic disposal system to be developed for spent reactor fuel and defense high level waste. Other final disposition forms, such as plutonium metal, plutonium oxide and plutonium immobilized without high-level radiation sources may be better suited to placement in a custom facility. This paper discusses a leading candidate for such a facility; deep (several kilometer) borehole disposition. The deep borehole disposition concept involves placing excess plutonium deep into old stable rock formations with little free water present. The safety argument centers around ancient groundwater indicating lack of migration, and thus no expected communication with the accessible environment until the plutonium has decayed

  2. The disposition of weapons plutonium in MOX fuel

    International Nuclear Information System (INIS)

    During the years 1994 and 1995, increasing interest has been shown worldwide in the management and disposition of excess weapons plutonium. Several basic solutions have been proposed and the U.S. Government has initiated preparation of a Programmatic Environmental Impact Statement (PEIS) on plutonium disposition options. This presentation addresses aspects of the primary alternative that is favored by the National Academy of Sciences and by the ANS Blue Ribbon panel's report on plutonium disposition options, the use of plutonium from weapons in mixed uranium/plutonium oxide (MOX) fuel to generate electricity in presently operating Light Water Reactors (LWRs). The advantages of such an option are two-fold. First, an analogous large-scale industrial activity exists nowadays: civilian plutonium, separated in reprocessing plants, is steadily recycled in existing PWR and BWR European reactors. This gives the opportunity, if decided, to go ahead almost immediately with an effective disposition of military plutonium. On the other hand, several benefits can be withdrawn from this strategy, such as economic soundness, resource and energy conservation, environment credibility and proliferation resistance

  3. Preparing Students for a Diverse Workplace: Strategies to Improve Dispositions

    Science.gov (United States)

    Melton, Deana; Dail, Teresa

    2010-01-01

    The curriculum for kinesiology students typically includes foundation courses focused on the scientific principles underlying human movement. Modifications for gender, age, and physical ability are also commonly included in these courses. Rarely addressed, however, are students' dispositions toward diverse groups. This article examines several…

  4. Effect of chronic nicotine pre-treatment on phencyclidine (PCP) disposition in the rat.

    Science.gov (United States)

    Vadlamani, N L; Pontani, R B; Misra, A L

    1983-09-01

    Disposition of [3H] phencyclidine (5 mg kg-1 i.p.) in brain, liver and plasma of rats treated chronically with 0.9% saline or nicotine (1 mg kg-1 s.c. twice a day for 11 days) was studied using a method possessing high sensitivity and specificity for PCP. No significant differences were observed in the values of PCP in plasma and tissues and in brain or liver to plasma PCP concentration ratios in the 2 groups 0.5, 1, 2 hr after [3H] PCP injection. With the exception of the value of PCP metabolites in plasma at 0.5 hr, the PCP metabolites concentrations were also not significantly different in the 2 groups. Data suggested that chronic nicotine pretreatment of rats did not affect the disposition of PCP and the potentiation of PCP-induced locomotor stimulant effects by nicotine possibly involves the additive pharmacodynamic interaction of 2 compounds at the level of the central nervous system. PMID:6651404

  5. Current bioanalytical methods for pharmacokinetic studies of drugs used in neglected tropical diseases.

    Science.gov (United States)

    dos Santos Magalhães, Igor Rafael

    2014-01-01

    Neglected tropical diseases are conditions directly associated to poverty and affect millions of people in tropical areas. Considering the necessity of pharmacokinetic and therapeutic drug monitoring studies to assess the disposition of agents clinically employed in the treatment of these diseases, especially in the involved population, this article will overview the current bioanalytical methods developed in the last 10 years, particularly those fully validated and using standard techniques, such as chromatographic procedures combined or not with mass spectrometry. The characteristics of each assay reported will be summarized and critically discussed. Furthermore, emphasis will also be given to the pros and cons in order to highlight the application of each method, especially in routine laboratories. PMID:25077629

  6. Clinical relevance of drug binding to plasma proteins

    Science.gov (United States)

    Ascenzi, Paolo; Fanali, Gabriella; Fasano, Mauro; Pallottini, Valentina; Trezza, Viviana

    2014-12-01

    Binding to plasma proteins highly influences drug efficacy, distribution, and disposition. Serum albumin, the most abundant protein in plasma, is a monomeric multi-domain macromolecule that displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds, such as fatty acids and most acidic drugs. α-1-Acid glycoprotein, the second main plasma protein, is a glycoprotein physiologically involved in the acute phase reaction and is the main carrier for basic and neutral drugs. High- and low-density lipoproteins play a limited role in drug binding and are natural drug delivery system only for few lipophilic drugs or lipid-based formulations. Several factors influence drug binding to plasma proteins, such as pathological conditions, concurrent administration of drugs, sex, and age. Any of these factors, in turn, influences drug efficacy and toxicity. Here, biochemical, biomedical, and biotechnological aspects of drug binding to plasma proteins are reviewed.

  7. Is your mood more contagious if you are likeable? The role of liking in the social induction of affect

    Directory of Open Access Journals (Sweden)

    Wróbel Monika

    2015-09-01

    Full Text Available In the present study, we explored the role of liking in the social induction of affect. Dispositional likeability was manipulated by written reports describing a sender as a likeable or dislikeable character. Afterwards participants watched short videos presenting the sender displaying happy or sad emotional expressions. We expected that exposure to the likeable sender would lead to reactions concordant with his emotional expression (assimilation, whereas exposure to the dislikeable sender would result in discordant reactions (contrast. The results indicated that dispositional likeability influenced the social induction of affect when the sender expressed positive emotions. Moreover, liking mediated the effects of the happy sender’s dispositional likeability on participants’ affective state. Exposure to the sad sender, however, led to assimilation regardless of the sender’s dispositional likeability.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn ...

  10. Drug: D05189 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Meditec (TN) TcO4. Na 185.8757 185.8936 D05189.gif Radioactive agent Therapeutic category: 4300 ATC code: V...09FX01 Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radio...active drugs 4300 Radioactive drugs D05189 Sodium pertechnetate

  11. Drug: D08758 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available apeutic category: 4300 Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radio...active drugs 430 Radioactive drugs 4300 Radioactive drugs D08758 Technetium (99mTc) N-pyridoxyl-5-methyltryptophan PubChem: 96025441 ...

  12. Drug: D06339 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06339 Drug Xenon Xe 133 (JAN/USP/INN); Xenon (133Xe); Xenon Xe 133 (TN) Xe 132.9059 131.293 D06339.gif Radi...gory of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  13. Drug: D08764 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available apeutic category: 4300 Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radio...active drugs 430 Radioactive drugs 4300 Radioactive drugs D08764 Technetium (99mTc) hydroxymethylene diphosphonate PubChem: 96025447 ...

  14. Drug: D08757 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Neurolite (TN) C12H21N2O5S2. Tc. 433.9956 436.3417 Therapeutic category: 4300 Therapeutic category of drugs... in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radioactive drugs

  15. Drug: D08767 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available cetylglycylglycylglycine technetium (99mTc) Therapeutic category: 4300 Therapeutic category of drugs in Japa...n [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs... 4300 Radioactive drugs D08767 Benzoylmercaptoacetylglycylglycylglycine - mercaptoacetylglycylglycylglycine technetium (99mTc) mixt PubChem: 96025450 ...

  16. The comparison of critical thinking and problem solving disposition of athletes according to gender and sport type

    Directory of Open Access Journals (Sweden)

    Hakan Kolayiş

    2014-10-01

    Full Text Available The terms “critical thinking and problem solving” are crucial for cognitive processes of athletes. It could also be said that these two concepts are likely to affect athletic performance of individuals. Therefore, the aim of this research is to investigate critical thinking and problem solving disposition of athletes. For this purpose 432 athletes (Xage: 20.53±3.85; Xsportexperience: 9.47±4.22 who comprise of 261 males (60.4% and 171 females (39.6% participated to the research. Problem Solving Inventory and California Scale of Disposition to Think Critically. The data was analysed by SPSS 17.0 by using descriptive statistics and t-test Level of significance was determined to be 0.05. Results showed that mean score for critical thinking was 3,82±,41 and the mean was 3,83±,46 for problem solving skill of the athletes. It was also found that there was not a significant difference between males and females according to critical thinking (p>0,05. However, males’ and females’ scores for problem solving significantly differed (p<0,05. Any significant difference was not obtained according to sport type. Overall, it could be said that gender can act as a determiner role among athletes in terms of problem solving disposition.

  17. Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms.

    Science.gov (United States)

    Dahl, M L; Llerena, A; Bondesson, U; Lindström, L; Bertilsson, L

    1994-01-01

    A large interindividual variability has previously been demonstrated in the bioavailability, steady-state plasma concentrations and clearance of clozapine, an atypical neuroleptic drug. To evaluate the importance of genetic factors in the metabolism of clozapine, its disposition after a single oral dose of 10 mg was studied in 15 healthy Caucasian volunteers. Five of the subjects were poor metabolisers (PM) of debrisoquine, five were PM of S-mephenytoin, and the remaining five were extensive metabolisers (EM) of both probe drugs. There was a 10-fold interindividual variation in Cmax and a 14-fold variation in AUC(0, 24) of clozapine among the 15 subjects studied. The mean (s.d.) Cmax was 117 (81) nmol l-1 and the mean AUC(0,24) value was 890 (711) nmol l-1 h. The value of t1/2,z varied 3-fold with a mean (s.d.) of 13.3 (5.0) h. There were no significant differences in the plasma concentrations or any of the pharmacokinetic parameters of clozapine between PM and EM of debrisoquine, or between the two S-mephenytoin hydroxylation phenotypes. We conclude that neither of the major genetic polymorphisms of oxidative drug metabolism contribute to the large interindividual variability in clozapine pharmacokinetics. PMID:8148222

  18. Treatment course and outcomes following drug and alcohol-related traumatic injuries

    Directory of Open Access Journals (Sweden)

    Cowperthwaite Matthew C

    2011-01-01

    Full Text Available Abstract Background Alcohol and drug use is known to be a major factor affecting the incidence of traumatic injury. However, the ways in which immediate pre-injury substance use affects patients' clinical care and outcomes remains unclear. The goal of the present study is to determine the associations between pre-injury use of alcohol or drugs and patient injury severity, hospital course, and clinical outcome. Materials and methods This study used more than 200,000 records from the National Trauma Data Bank (NTDB, which is the largest trauma registry in the United States. Incidents in the NTDB were placed into one of four classes: alcohol related, drug related, alcohol-and-drug related, and substance negative. Logistic regression models were used to determine comorbid conditions or treatment complications that were significantly associated with pre-injury substance use. Hospital charges were associated with the presence or absence of drugs and alcohol, and patient outcomes were assessed using discharge disposition as delimited by the NTDB. Results The rates of complications arising during treatment were 8.3, 10.9, 9.9 and 8.6 per one hundred incidents in the alcohol related, drug related, alcohol-and-drug related, and substance-negative classes, respectively. Regression models suggested that pre-injury alcohol use is associated with a 15% higher risk of infection, whereas pre-injury drug use is associated with a 30% higher risk of infection. Pre-injury substance use did not appear to significantly impact clinical outcomes following treatment for traumatic injury, however. Conclusion This study suggests that pre-injury drug use is associated with a significantly higher complication rate. In particular, infection during hospitalization is a significant risk for both alcohol and drug related trauma visits, and drug-related trauma incidents are associated with increased risk for additional circulatory complications. Although drug and alcohol related

  19. Drug: D03238 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nts 234 Antacids 2343 Aluminum-containing agents D03238 Hydrotalcite (JAN/INN) Anat...07038 Antiulcer drugs Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 23 Digestive organ age

  20. Drug: D02402 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available SP); Thallous chloride Tl 201 (TN) Tl. Cl 235.9397 239.8363 D02402.gif Diagnostic aid [radiopaque medium]; Radio...8301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  1. Drug: D02259 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 259.gif Antineoplastic; Diagnostic aid [thyroid function determination]; Radioactive agent [DS:H00032] Thera... affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  2. Drug: D00289 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tagonists Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 24 Hormones...drug classification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Sex Hormones/Modifiers) A

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... drugs, which can alter judgment and inhibition and lead people to engage in impulsive and unsafe behaviors. ... Drug and alcohol intoxication affect judgment and can lead to unsafe sexual practices, which put people at ...

  4. Drugs that may cause impotence

    Science.gov (United States)

    Impotence caused by medications; Drug-induced erectile dysfunction; Prescription medicines and impotence ... Many medicines and recreational drugs can affect a man's sexual arousal and sexual performance. What causes impotence in one ...

  5. INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT

    OpenAIRE

    Won, Christina S.; Oberlies, Nicholas H.; Paine, Mary F.

    2010-01-01

    Successful delivery of promising new chemical entities via the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potential...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug Abuse and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? ...

  7. Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

    Directory of Open Access Journals (Sweden)

    Adena S Spiro

    Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

  8. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... vomiting to life-threatening anaphylaxis . A true drug allergy is caused by a series of chemical steps ...

  9. HANFORD CANYON DISPOSITION INITIATIVE (CDI). A BETTER SOLUTION TO AN EXPENSIVE WASTE DISPOSAL PROBLEM

    International Nuclear Information System (INIS)

    Environmental cleanup that is occurring at most U.S. Department of Energy (DOE) sites is going to be long and expensive. How expensive can really only be answered when cleanup paths forward have been identified, agreed to, and planned. In addition, all the major issues must have been identified. This also means being able to answer the question ''What about the waste?'' Where the waste goes and how it will be handled greatly affects the cost. However, within the mandatory safety and legal envelope, ingenuity can play a huge role in keeping the cost down, getting necessary decisions made earlier in the process, and being protective of the worker, public, and the environment. This paper examines how ingenuity addressed a cleanup action that had no agreed to and identified path forward and resulted in a decision made early that has spurred thinking on what to do with the other similar waste cleanup situations. The Canyon Disposition Initiative (CDI) is an example of finding a better way to address a specific problem, getting agreement on a path forward, opening the options for waste disposal, and reducing the time line for final disposition. For the CDI, the challenge was whether an old inactive building designed for reprocessing and used for multiple missions during its lifetime could be economically and sufficiently characterized to satisfy and bring consensus among groups with vastly different view points. The CDI has actively involved members of various DOE offices (i.e., Waste Management, Science and Technology, Environmental Restoration, and Facility Transition), the U.S. Environmental Protection Agency (EPA), Washington State Department of Ecology (Ecology), Hanford Advisory Board (HAB), and the three affected Tribal Nations. The ability to partner between these diverse groups has allowed the CDI to go from a concept, to a funded priority project, to a complete review of various alternatives, and finally to a proposed plan to demonstrate the wisdom of finding a

  10. IAEA safeguards for the Fissile Materials Disposition Project

    International Nuclear Information System (INIS)

    This document is an overview of International Atomic Energy Agency (IAEA) safeguards and the basic requirements or elements of an IAEA safeguards regime. The primary objective of IAEA safeguards is the timely detection of the diversion of a significant quantity of material and the timely detection of undeclared activities. The two important components of IAEA safeguards to accomplish their primary objective are nuclear material accountancy and containment and surveillance. This overview provides guidance to the Fissile Materials Disposition Project for IAEA inspection requirements. IAEA requirements, DOE Orders, and Nuclear Regulatory Commission regulations will be used as the basis for designing a safeguards and security system for the facilities recommended by the Fissile Materials Disposition Project

  11. Studies on Fuzzy Logic and Dispositions for Medical Diagnosis

    Directory of Open Access Journals (Sweden)

    Prof. Sripati Mukhopadhyay

    2011-09-01

    Full Text Available For designing and developing a knowledge-based system we need to store expert’s knowledge in a suitable form, known as knowledge base, and then applying a suitable reasoning process to arrive at a decision. Formal logic, a two-valued logic, known as predicate logic, is suitable for developing and inferring for systems like mechanical theorem proving. But if we want to develop a serious real life knowledge-based system like Medical Diagnosis, formal logic fails to describe the knowledge-base, and obviously Fuzzy logic and extension of Fuzzy logic, known as dispositions as proposed by Zadeh, come in to rescue and ultimately enabling us to use linguistic variables. In this article an attempt has been made to show how fuzzy logic and it’s extension, particularly dispositions, can be used for modeling a medical diagnosis system.

  12. Joint U.S./Russian plutonium disposition study: Nonproliferation issues

    International Nuclear Information System (INIS)

    In an effort to establish joint activities in the disposition of fissile materials from nuclear materials, the US and Russia agreed to conduct joint work to develop consistent comparisons of various alternatives for the disposition of weapons-grade plutonium. Joint working groups were established for the analysis of alternatives for plutonium management for water reactors, fast reactors, storage, geological formations, immobilization and stabilization of solutions and other forms. In addition cross-cutting working groups were established for economic analysis and nonproliferation (NP). This paper reviews the activities of the NP working group in support of these studies. The NP working group provided integrated support in the area of nuclear NP to the other US/Russian Study teams. It involved both domestic safeguards and security and international safeguards. The analysis of NP involved consideration of the resistance to theft or diversion and resistance to retrieval, extraction or reuse

  13. First-year university students’ disposition and approaches to learning

    Directory of Open Access Journals (Sweden)

    María Victoria Pérez Villalobos

    2011-05-01

    Full Text Available Research on self-regulated learning has recognized cognitive processes that students select and execute to achieve their goals. When performing a task, the student analyzes the task characteristics, context and his own capacities, employing resource planning and management, adopting either deep or superficial learning approaches. To describe the relationship between “disposition to learning strategies and” and “deep and superficial learning approaches”, the “Cuestionario de Formas de Estudio” questionnaire was applied to 344 1st year students from eight study programs of a Chilean university. The results show significant correlation (r greater than 0.30, p lower than 0.001 between disposition to learning strategies and usage ofdeep learning approaches, and between the aforementioned variables andthe amount of weekly study time.

  14. Can Dispositionalism about Belief Vindicate Doxasticism about Delusion?

    Directory of Open Access Journals (Sweden)

    José Eduardo Porcher

    2015-12-01

    Full Text Available Clinical delusions have traditionally been characterized as beliefs in psychiatry. However, philosophers have recently engaged with the empirical literature and produced a number of objections to the so-called doxastic status of delusion, stemming mainly from the mismatch between the functional role of delusions and that expected of beliefs. In response to this, an appeal to dispositionalism about the nature of belief has been proposed to vindicate the doxastic status of delusion. In this paper, I first present the objections to attributing beliefs to delusional patients and the application of dispositionalism in the attempt to vindicate doxasticism. I then assess this application and some responses to the objections to the doxastic characterization. Finally, I offer some conclusions about the limits of folk-psychological concepts in the characterization and explanation of complex psychological phenomena such as delusions.

  15. Alternatives for the disposition of PUREX organic solution

    International Nuclear Information System (INIS)

    This Supporting Document submits options and recommendations for final management of Tank 40 Plutonium-Uranium Extraction (PUREX) Plant organic solution per Tri-Party Agreement Milestorm Number M-80-00-T03. Hanford is deactivating the PUREX Plant for the US DOE. One the key element of this Deactivation is disposition of approximately 81,300 liters (21,500 gallons) of slightly radioactively contaminated organic solution to reduce risk to the environment, reduce cost of long-term storage, and assure regulatory compliance. An announcement in the Commerce Business Daily (CBD) on October 14, 1994 has resulted in the submission of proposals from two facilities capabLe of receiving and thermally destroying the solution. Total decomposition by thermal destruction is the recommended option for the disposition of the PUREX organic solution and WHC is evaluating the proposals from the two facilities

  16. Update of the Used Fuel Disposition Campaign Implementation Plan

    Energy Technology Data Exchange (ETDEWEB)

    Jens Birkholzer; Robert MacKinnon; Kevin McMahon; Sylvia Saltzstein; Ken Sorenson; Peter Swift

    2014-09-01

    This Campaign Implementation Plan provides summary level detail describing how the Used Fuel Disposition Campaign (UFDC) supports achievement of the overarching mission and objectives of the Department of Energy Office of Nuclear Energy Fuel Cycle Technologies Program The implementation plan begins with the assumption of target dates that are set out in the January 2013 DOE Strategy for the Management and Disposal of Used Nuclear Fuel and High-Level Radioactive Waste (http://energy.gov/downloads/strategy-management-and-disposal-used-nuclear-fuel-and-high-level-radioactive-waste). These target dates and goals are summarized in section III. This implementation plan will be maintained as a living document and will be updated as needed in response to progress in the Used Fuel Disposition Campaign and the Fuel Cycle Technologies Program.

  17. Optimum Disposition of Metal Particles in the Propellant Grain

    Directory of Open Access Journals (Sweden)

    Leonid L. Minkov

    2014-01-01

    Full Text Available Using the dispersed metal in solid propellants to increase the temperature of combustion products leads to such a problem as the specific impulse loss due to the incomplete combustion of metal particles in the exhaust products. A redistribution of metal loaded into the propellant grain is one of the methods to decrease the specific impulse loss. This paper reports on the ways to obtain the optimum metal particle disposition for the case-bounded propellant grain of tube cross-sectional type. Three different approaches to analyze the metal combustion efficiency are discussed. The influence of the dynamic nonequilibrium of two-phase flow on the optimum metal particles disposition in the propellant grain of tube cross-sectional type is investigated.

  18. Plutonium disposition via immobilization in ceramic or glass

    Energy Technology Data Exchange (ETDEWEB)

    Gray, L.W.; Kan, T.; Shaw, H.F.; Armantrout, A.

    1997-03-05

    The management of surplus weapons plutonium is an important and urgent task with profound environmental, national, and international security implications. In the aftermath of the Cold War, Presidential Policy Directive 13, and various analyses by renown scientific, technical, and international policy organizations have brought about a focused effort within the Department of Energy to identify and implement paths for the long term disposition of surplus weapons- usable plutonium. The central goal of this effort is to render surplus weapons plutonium as inaccessible and unattractive for reuse in nuclear weapons as the much larger and growing stock of plutonium contained in spent fuel from civilian reactors. One disposition option being considered for surplus plutonium is immobilization, in which the plutonium would be incorporated into a glass or ceramic material that would ultimately be entombed permanently in a geologic repository for high-level waste.

  19. DOE Plutonium Disposition Study: Pu consumption in ALWRs

    International Nuclear Information System (INIS)

    The Department of Energy (DOE) has contracted with Asea Brown Boveri-Combustion Engineering (ABB-CE) to provide information on the capability of ABB-CE's System 80 + Advanced Light Water Reactor (ALWR) to transform, through reactor burnup, 100 metric tonnes (MT) of weapons grade plutonium (Pu) into a form which is not readily useable in weapons. This information is being developed as part of DOE's Plutonium Disposition Study, initiated by DOE in response to Congressional action. This document, Volume 1, presents a technical description of the various elements of the System 80 + Standard Plant Design upon which the Plutonium Disposition Study was based. The System 80 + Standard Design is fully developed and directly suited to meeting the mission objectives for plutonium disposal. The bass U02 plant design is discussed here

  20. Gastrointestinal distribution of albendazole metabolites following netobimin administration to cattle: relationship with plasma disposition kinetics.

    Science.gov (United States)

    Lanusse, C E; Gascon, L H; Prichard, R K

    1993-03-01

    The gastrointestinal (GI) distribution and plasma disposition kinetics of albendazole (ABZ) metabolites after oral administration of netobimin (NTB) to cattle were studied. Eight Holstein steers (150-180 kg) were surgically fitted with permanent cannulae in the rumen, abomasum and ileum. After post-surgical recovery, the animals were treated orally with a suspension of netobimin zwitterion (400 mg/ml) at 20 mg/kg. Jugular blood and ruminal, abomasal and ileal fluid samples were taken serially over a 96 h period and analysed by HPLC for NTB and its metabolites, including ABZ, ABZ sulphoxide (ABZSO), ABZ sulphone (ABZSO2) and amino-albendazole sulphone (NH2ABZSO2). NTB parent drug was only found in the GI tract and for only 12-18 h post-treatment. ABZSO and ABZSO2 were the main metabolites found in plasma, being present for 30-36 h. These metabolites were exchanged between plasma and different GI fluids and were greatly concentrated in the abomasum. This phenomenon may account for the presence of ABZ, ABZSO and ABZSO2 in the GI tract for 72 h post-treatment despite the fact that ABZ was not detected in plasma and ABZSO and ABZSO2 were detected for only 30-36 h in plasma. The presence of ABZ and ABZSO in the abomasum and intestine for this extended period of time is probably relevant for anthelmintic efficacy against GI parasites. The NH2 ABZSO2 metabolite was detected in plasma, abomasum and ileum and its disposition kinetics were characterized for the first time. PMID:8478999

  1. The comparison of critical thinking and problem solving disposition of athletes according to gender and sport type

    OpenAIRE

    Hakan Kolayiş; İhsan Sarı; Nurullah Çelik

    2014-01-01

    The terms “critical thinking and problem solving” are crucial for cognitive processes of athletes. It could also be said that these two concepts are likely to affect athletic performance of individuals. Therefore, the aim of this research is to investigate critical thinking and problem solving disposition of athletes. For this purpose 432 athletes (Xage: 20.53±3.85; Xsportexperience: 9.47±4.22) who comprise of 261 males (60.4%) and 171 females (39.6%) participated to the research. Problem Sol...

  2. MPC&A for plutonium disposition in the Russian federation

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, W.G.

    1995-08-08

    The issue of what to do with excess fissile materials from dismantled nuclear weapons has been discussed for a number of years. The options or alternatives commanding the most attention were identified by the American National Academy of Sciences. For plutonium these options are: (1) the fabrication and use of mixed-oxide (MOX) reactor fuel followed by the disposal of the spent fuel, or (2) vitrification (immobilization) of plutonium combined with highly radioactive material followed by direct disposal. The Academy report also identified the alternative of disposal in a deep borehole as requiring further study before being eliminated or accepted. The report emphasized security of nuclear materials as a principal factor in considering management and disposition decisions. Security of materials is particularly important in the near term-now-long before ultimate disposition can be accomplished. The MOX option was the subject of a NATO workshop held at Obninsk, Russia in October 1994. Hence this paper does not deal with the MOX alternative in detail. It deals with the following: materials protection, control, and accounting (MPC&A) for immobilization and disposal; the immobilization vs MOX alternatives; the security of disposed plutonium; the need to demonstrate MTC&A for plutonium disposition; and, finally, a recommended investment to quickly and inexpensively improve the protection of fissile materials in Russia. It is the author`s view that near-term management is of overriding importance. That is, with respect to the ultimate disposition of excess nuclear materials, how we get there is more important than where we are going.

  3. Preliminary siting characterization Salt Disposition Facility - Site B

    International Nuclear Information System (INIS)

    A siting and reconnaissance geotechnical program has been completed in S-Area at the Savannah River Site in South Carolina. This program investigated the subsurface conditions for the area known as ''Salt Disposition Facility (SDF), Site B'' located northeast of H-Area and within the S-Area. Data acquired from the Site B investigation includes both field exploration and laboratory test data

  4. Preliminary siting characterization Salt Disposition Facility - Site B

    Energy Technology Data Exchange (ETDEWEB)

    Wyatt, D.

    2000-01-04

    A siting and reconnaissance geotechnical program has been completed in S-Area at the Savannah River Site in South Carolina. This program investigated the subsurface conditions for the area known as ``Salt Disposition Facility (SDF), Site B'' located northeast of H-Area and within the S-Area. Data acquired from the Site B investigation includes both field exploration and laboratory test data.

  5. Krebs als Funktion von Disposition, Exposition und Alter

    Science.gov (United States)

    Schmähl, D.; Habs, M.

    1982-07-01

    Essential parameters in carcinogenesis are the genetic and extragenetic disposition of an individual, its exposure to chemical, physical or viral influences in the environment as well as its age as the time that is needed to induce cancer. Cancer prevention seems only possible by reducing the exposure. It will be discussed whether the increase in life expectancy has become so important during the past decades that it compensates all efforts of reducing the exposure.

  6. Disposition Index, Glucose Effectiveness, and Conversion to Type 2 Diabetes

    OpenAIRE

    Lorenzo, Carlos; Wagenknecht, Lynne E.; Rewers, Marian J.; Karter, Andrew J; Bergman, Richard N.; Hanley, Anthony J.G.; Haffner, Steven M.

    2010-01-01

    OBJECTIVE Disposition index (DI) and glucose effectiveness (SG) are risk factors for diabetes. However, the effect of DI and SG on future diabetes has not been examined in large epidemiological studies using direct measures. RESEARCH DESIGN AND METHODS Insulin sensitivity index (SI), acute insulin response (AIR), and SG were measured in 826 participants (aged 40–69 years) in the Insulin Resistance Atherosclerosis Study (IRAS) by the frequently sampled intravenous glucose tolerance test. DI wa...

  7. Drug: D06050 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available kit (TN) map04976 Bile secretion Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radio...active drugs 430 Radioactive drugs 4300 Radioactive drugs D...trofosmin 99mTc-complex Radioactive agent Therapeutic category: 4300 ATC code: V09GA02 Component of Myoview ...D06050 Drug Technetium Tc 99m tetrofosmin (USP); Technetium (99mTc) tetrofosmin; Te

  8. Drug Testing in Oral Fluid

    OpenAIRE

    Drummer, Olaf H

    2006-01-01

    Over the last decade there have been considerable developments in the use of oral fluid (saliva) for drug testing. Oral fluid can provide a quick and non-invasive specimen for drug testing. However, its collection may be thwarted by lack of available fluid due to a range of physiological factors, including drug use itself. Food and techniques designed to stimulate production of oral fluid can also affect the concentration of drugs. Current applications are mainly focused on drugs of abuse tes...

  9. Radium Disposition Options for the Department of Energy

    Energy Technology Data Exchange (ETDEWEB)

    Parks, D. L.; Thiel, E. C.; Seidel, B. R.

    2002-02-26

    The Department of Energy (DOE) has developed plans to disposition its excess nuclear materials, including radium-containing materials. Within DOE, there is no significant demand for radium at this time. However, DOE is exploring reuse options, including uses that may not exist at this time. The Nonactinide Isotopes and Sealed Sources Management Group (NISSMG) has identified 654 radium-containing items, and concluded that there are no remaining radium items that do not have a pathway to disposition. Unfortunately, most of these pathways end with disposal, whereas reuse would be preferable. DOE has a number of closure sites that must remove the radium at their sites as part of their closure activities. NISSMG suggests preserving the larger radium sources that can easily be manufactured into targets for future reuse, and disposing the other items. As alternatives to disposal, there exist reuse options for radium, especially in nuclear medicine. These options were identified by NISSMG. The NISSMG recommends that DOE set up receiver sites to store these radium materials until reuse options become available. The NISSMG recommends two pathways for dispositioning radium sources, depending on the activity and volume of material. Low activity radium sources can be managed as low level radioactive waste per DOE Order 5820.2A. Higher activity radium sources are more appropriate for reuse in nuclear medicine applications and other applications.

  10. Safeguards and security issues for the disposition of fissile materials

    International Nuclear Information System (INIS)

    The Department of Energy's Office of Fissile Material Disposition (FMD) is analyzing long-term storage and disposition options for surplus weapons-usable fissile materials, preparing a programmatic environmental impact statement (PEIS), preparing for a record of decision (ROD) regarding this material and conducting other activities. The primary security objectives of this program are to reduce major security risks and strengthen arms reduction and nonproliferation (NP). To help achieve these objectives, a safeguards and security (S ampersand S) team consisting of participants from Sandia, Los Alamos, and Lawrence Livermore National Laboratories was established. The S ampersand S activity for this program is a cross-cutting task which addresses all of the FMD program options. It includes both domestic and international safeguards and includes areas such as physical protection, nuclear materials accountability and material containment and surveillance. This paper will discuss the activities of the Fissile Materials Disposition Program (FMDP) S ampersand S team as well as some specific S ampersand S issues associated with various FMDP options/facilities. Some of the items to be discussed include the threat, S ampersand S requirements, S ampersand S criteria for assessing risk, S ampersand S issues concerning fissile material processing/facilities, and international and domestic safeguards

  11. Immobilization as a route to surplus fissile materials disposition

    International Nuclear Information System (INIS)

    In the aftermath of the Cold War, the US and Russia have agreed to large reductions in nuclear weapons. To aid in the selection of long-term management options, DOE has undertaken a multifaceted study to select options for storage and disposition of plutonium (Pu) in keeping with the national policy that Pu must be subjected to the highest standards of safety, security, and accountability. One alternative being considered is immobilization. To arrive at a suitable immobilization form, the authors first reviewed published information on high-level waste (HLW) immobilization technologies in order to identify 72 possible Pu immobilization forms to be prescreened. Surviving forms were screened using multiattribute analysis to determine the most promising technologies. Promising immobilization families were further evaluated to identify chemical, engineering, environmental, safety, and health problems that remain to be solved prior to making technical decisions as to the viability of using the form for long-term disposition of plutonium. All data, analyses, and reports are being provided to the DOE Fissile Materials Disposition Project Office to support the Record of Decision that is anticipated in the fourth quarter of FY96

  12. Liposome disposition in vivo. VI: Delivery to the lung

    International Nuclear Information System (INIS)

    The effect of negatively charged liposome components and vesicle size on the time course and dose dependency of liposome disposition in mice was studied with a view to optimizing liposome delivery to the lung. The disposition of large multilamellar liposomes was followed using 125I-labeled p-hydroxybenzamidine phosphatidyl ethanolamine. Of the three negatively charged liposome compositions studied (phosphatidyl choline-X-cholesterol-alpha-tocopherol, molar ratio: 4:1:5:0.1; X . phosphatidyl serine, dipalmitoyl phosphatidic acid, or phosphatidyl glycerol), phosphatidyl serine liposomes resulted in the greatest accumulation in lungs. Lung levels decreased up to 95 h postdose, at which time 6% of the liposome dose present at 2 h still remained. The disposition of phosphatidyl serine-containing liposomes was independent of dose for the range 0.04-21 mumol/animal. When liposomes containing phosphatidyl choline were prepared using a variety of extrusion and dialysis conditions, a strong link between liposome size and lung accumulation was revealed. A maximum lung accumulation of 30.9% of the administered dose was achieved with no detectable gross pathological lung lesions up to 24 h postdose

  13. Drug Facts

    Science.gov (United States)

    ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  14. Generic Drugs

    Science.gov (United States)

    ... name drug. A brand- name drug has a patent. When the patent runs out— usually after 10 to 14 years— ... if you do not have drug coverage. Condition Diabetes Heart failure High cholesterol Migraine Brand-name drug ...

  15. Physiologically based synthetic models of hepatic disposition.

    Science.gov (United States)

    Hunt, C Anthony; Ropella, Glen E P; Yan, Li; Hung, Daniel Y; Roberts, Michael S

    2006-12-01

    Current physiologically based pharmacokinetic (PBPK) models are inductive. We present an additional, different approach that is based on the synthetic rather than the inductive approach to modeling and simulation. It relies on object-oriented programming. A model of the referent system in its experimental context is synthesized by assembling objects that represent components such as molecules, cells, aspects of tissue architecture, catheters, etc. The single pass perfused rat liver has been well described in evaluating hepatic drug pharmacokinetics (PK) and is the system on which we focus. In silico experiments begin with administration of objects representing actual compounds. Data are collected in a manner analogous to that in the referent PK experiments. The synthetic modeling method allows for recognition and representation of discrete event and discrete time processes, as well as heterogeneity in organization, function, and spatial effects. An application is developed for sucrose and antipyrine, administered separately and together. PBPK modeling has made extensive progress in characterizing abstracted PK properties but this has also been its limitation. Now, other important questions and possible extensions emerge. How are these PK properties and the observed behaviors generated? The inherent heuristic limitations of traditional models have hindered getting meaningful, detailed answers to such questions. Synthetic models of the type described here are specifically intended to help answer such questions. Analogous to wet-lab experimental models, they retain their applicability even when broken apart into sub-components. Having and applying this new class of models along with traditional PK modeling methods is expected to increase the productivity of pharmaceutical research at all levels that make use of modeling and simulation. PMID:17051440

  16. The Role of Temperament in Children's Affective and Behavioral Responses in Achievement Situations

    Science.gov (United States)

    Hirvonen, Riikka; Aunola, Kaisa; Alatupa, Saija; Viljaranta, Jaana; Nurmi, Jari-Erik

    2013-01-01

    Although students' affects and behaviors in achievement situations have been shown to be influenced by their previous learning experiences, less is known about how they relate to students' dispositional characteristics, such as temperament. This study examined to what extent children's temperament is related to their affective and behavioral…

  17. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children ... a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free ...

  18. In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans.

    Science.gov (United States)

    Cui, Donghui; Cabalu, Tamara; Yee, Ka Lai; Small, James; Li, Xiaodong; Liu, Bo; Maciolek, Cheri; Smith, Sheri; Liu, Wen; McCrea, Jacqueline B; Prueksaritanont, Thomayant

    2016-10-01

    1. Suvorexant (MK-4305, Belsomra®) is a first-in-class dual orexin receptor antagonist approved in the USA and Japan for the treatment of insomnia. The current studies describe suvorexant's absorption, disposition and potential for CYP-mediated drug interactions in humans. 2. Following single oral administration of [(14)C]suvorexant to healthy human subjects, 90% of the radioactivity was recovered (66% in faeces, 23% in urine), primarily as oxidative metabolites. 3. In plasma, suvorexant and M9 were predominant, accounting for 30 and 37% of the total radioactivity, respectively. Metabolite M17 became more prominent (approaching 10%) following multiple daily doses of unlabelled suvorexant. M9 and M17 are not expected to contribute to the pharmacological activity of suvorexant due to reduced orexin receptor binding affinity and limited brain penetration. 4. CYP3A was determined to be the predominant enzyme mediating suvorexant oxidation. In vitro, suvorexant demonstrated reversible inhibition of CYP3A4 and 2C19 (IC50 ∼ 4-5 μM), and weak time-dependent inhibition of CYP3A4 (KI = 12 μM, kinact = 0.14 min(-1)). Suvorexant was also a weak inducer of CYP3A4, 1A2 and 2B6. Given the low plasma concentrations at clinical doses, suvorexant was not anticipated to cause significant drug interactions via inhibition and/or induction of major CYPs in vivo. PMID:26864332

  19. The effect of acetaminophen administration on its disposition and body stores of sulphate.

    Science.gov (United States)

    Hendrix-Treacy, S; Wallace, S M; Hindmarsh, K W; Wyant, G M; Danilkewich, A

    1986-01-01

    This investigation was designed to investigate the effects of ingestion of multiple therapeutic doses of acetaminophen on the disposition of the drug and on the cosubstrate, sulfate. Nine healthy volunteers and nine outpatients receiving acetaminophen for chronic pain were involved in the study. Volunteers were given a single 650 mg oral dose of acetaminophen. One week later they were given 650 mg of acetaminophen every six hours for five doses. Patients were maintained on their normal treatment and dosage schedules (600 mg every 3 to 8 h) for the study. In healthy volunteers the half-life of acetaminophen after single and multiple dosing was not significantly different. However, the fraction of acetaminophen recovered in the urine as the sulfate conjugate was less and the glucuronide conjugate greater after multiple dosing than after a single of the drug. There was no difference in the percentage recovered as the parent compound between single and multiple dosing. Serum sulfate levels fluctuated over the 6-h period following administration of single and multiple doses of acetaminophen to volunteers. The mean serum sulfate concentration was less after administration of five sequential 650 mg doses of acetaminophen than after a single dose. The renal clearance of inorganic sulfate showed a corresponding decrease. Unexpectedly, patients on chronic acetaminophen therapy exhibited elevated serum sulfate levels (levels higher than the maximum sulfate concentration seen in volunteers). PMID:3732362

  20. A community study on the relationship between stress, coping, affective dispositions and periodontal attachment loss

    OpenAIRE

    Leung, WK; Ng, SKS

    2006-01-01

    Background: Psychological factors may increase the risk for periodontal diseases. Contemporary conceptualization of the stress process supports the evaluation of stress at three levels: stressors, moderating and mediating factors, and stress reactions. Objective: This study was undertaken to investigate the relationship of periodontal disease in terms of clinical attachment level (CAL) to psychosocial stress, making reference to the major components of stress process. Methods: A cross-section...

  1. Developing a Disposition for Social Innovations: An Affective-Socio-Cognitive Co-Design Model

    Science.gov (United States)

    Lee, Chien-Sing; Wong, Kuok-Shoong Daniel

    2015-01-01

    Advancements in technology and liberalization of educational opportunities have transformed the knowledge landscape into an emergent innovation incubator, where sense-making and creativity in and for ill-structured environments are especially relevant. In addition, opportunities are often "found" or "made." The quality of…

  2. Drug: D08748 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available herapeutic category of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents... affecting metabolism 391 Liver disease agents 3919 Others D08748 Liver hydrolysate - cystein

  3. Drug: D01730 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ing sensory organs 131 Ophthalmic agents 1319 Others D01730 Silver nitrate (JP16/...ategory of drugs in Japan [BR:br08301] 1 Agents affecting nervous system and sensory organs 13 Agents affect

  4. Drug: D01017 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available s affecting nervous system and sensory organs 13 Agents affecting sensory organs 131 Ophthalmic agents 1311 ...ride (JAN/USP) USP drug classification [BR:br08302] Ophthalmic Agents Ophthalmic Antiglaucoma Agents Dipivef

  5. Update to the Fissile Materials Disposition program SST/SGT transportation estimation

    International Nuclear Information System (INIS)

    This report is an update to ''Fissile Materials Disposition Program SST/SGT Transportation Estimation,'' SAND98-8244, June 1998. The Department of Energy Office of Fissile Materials Disposition requested this update as a basis for providing the public with an updated estimation of the number of transportation loads, load miles, and costs associated with the preferred alternative in the Surplus Plutonium Disposition Final Environmental Impact Statement (EIS)

  6. Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug-Drug Interactions

    Czech Academy of Sciences Publication Activity Database

    Mandíková, J.; Volková, M.; Pávek, P.; Navrátilová, L.; Hyršová, L.; Janeba, Zlatko; Pavlík, J.; Bárta, P.; Trejtnar, F.

    2016-01-01

    Roč. 6, Jan 5 (2016), 304/1-304/11. ISSN 1663-9812 Institutional support: RVO:61388963 Keywords : antivirals * nephrotoxicity * renal disposition * drug-drug interactions Subject RIV: CC - Organic Chemistry Impact factor: 3.802, year: 2014 http://journal.frontiersin.org/article/10.3389/fphar.2015.00304/full

  7. Characterization of human metabolism and disposition of levo-tetrahydropalmatine: Qualitative and quantitative determination of oxidative and conjugated metabolites.

    Science.gov (United States)

    Xiao, Weibin; Shen, Guolin; Zhuang, Xiaomei; Ran, Xiaorong; Zhu, Mingshe; Li, Hua

    2016-09-01

    Levo-tetrahydropalmatine (l-THP) is a tetrahydroprotoberberine isoquinoline alkaloid and has been used as an analgesic agent in China for over 50 years. Recent studies revealed that l-THP was effective in the treatment of drug addiction. However, the plasma metabolic profile, mass balance and clearance pathways of l-THP in human remain unknown. In the present study, an analytical strategy was developed for qualitative and quantitative investigation of metabolism and disposition of l-THP in human. Detection and structural characterization of l-THP metabolites were performed using liquid chromatography-quadrupole time-of-flight mass spectrometry. Selected major metabolites in plasma, urine and feces determined by liquid chromatography with UV detection were further quantified using a triple quadruple mass spectrometry and reference standards. A total of 20 metabolites were identified, most of which were formed via demethylation, mono-hydroxylation, and glucuronidation and sulfonation of desmethyl metabolites. Five major metabolites accounted for over 10% of the parent drug concentration in plasma. Major urinary and fecal metabolites and the parent drug that were monitored for 72h accounted for 46.3% of the dose, while only 0.16% of the dose was the unchanged drug. Multiple demethylations followed by glucuronide and sulfate conjugations and renal excretion were the major drug clearance pathways of l-THP in human. PMID:27343900

  8. Antiepileptic drugs: newer targets and new drugs

    Directory of Open Access Journals (Sweden)

    Vihang S. Chawan

    2016-06-01

    Full Text Available Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs, but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and drug administration (USFDA has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have shown a promising future as better AEDs and drugs like ganaxolone, intranasal diazepam, ICA- 105665, valnoctamide, VX-765, naluzotan are in the pipeline. [Int J Basic Clin Pharmacol 2016; 5(3.000: 587-592

  9. Expressive writing and the role of alexythimia as a dispositional deficit in self-disclosure and psychological health.

    Science.gov (United States)

    Páez, D; Velasco, C; González, J L

    1999-09-01

    Psychology students were randomly assigned to a condition in which they had to write for 20 min on 3 days or for 3 min on 1 day a factual description of disclosed traumas, undisclosed traumas, or recent social events. In the case of undisclosed traumatic events, intensive writing about these events showed a beneficial effect on affect and on the affective impact of remembering the event and appraisal. Participants who wrote briefly about an undisclosed traumatic event showed a more negative appraisal. Participants who wrote intensively about a traumatic event and had a dispositional deficit in self-disclosure, measured by a Toronto Alexithymia Scale subscale, showed a positive effect on self-reported measures of affect. Difficulty in describing feelings, an alexythimia dimension, correlated with psychological health problems, emotional inhibition, and a less introspective content of written essays about the emotional events. PMID:10510512

  10. Legislative dispositions relative to the clearness and security in nuclear matter; Dispositions legislatives relatives a la transparence et a la securite en matiere nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-11-01

    This file treats the legislative dispositions devoted to the clearness and security in the nuclear field. It is divided in four great parts. The first part is devoted to the general dispositions, the second part concerns public information, the third part is relative to the local information commissions, a special point is noticed for the creation of a high comity of clearness in nuclear safety, a fourth part is devoted to the nuclear facilities and the transport of nuclear materials, control and monitoring are included, legal dispositions and sanctions are tackled. (N.C.)

  11. Drugs: What You Should Know

    Science.gov (United States)

    ... the influence or having unprotected sex . How drugs affect people depends on lots of things: the kind of drug taken how much is taken how often someone uses it how quickly it gets to the brain what other drugs, food, or substances are taken at the same time ...

  12. Drug: D03418 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 23 Digestive organ agents 235 Purgatives...DRUGS FOR CONSTIPATION A06A DRUGS FOR CONSTIPATION A06AB Contact laxatives A06AB05 Castor oil D03418 Aromatic castor oil (JP16) PubChem: 17397558 ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs of abuse and HIV both affect the brain. Research has shown that HIV causes greater injury to ... shown to increase the amount of HIV in brain cells 1 . Drug abuse treatment. Since the late 1980s, research has shown that treating drug abuse is an ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... HIV or transmitting it to someone else. Biological effects of drugs. Drug abuse and addiction can affect a person's ... the discussion between friends, and the importance of family. For more information, read a ... Drug Abuse, Dr. Nora D. Volkow. Message from the ...

  15. Drug: D04656 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available N) Kr 80.9166 83.798 D04656.gif Radioactive agent Therapeutic category: 4300 ATC code: V09EX01 Therapeutic c...ategory of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  16. Drug: D02107 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Indiclor (TN) InCl3 219.8104 221.177 D02107.gif Radioactive agent Therapeutic category: 4300 Therapeutic ca...tegory of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  17. Drug: D02284 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02284 Drug Technetium Tc 99m exametazime (USP) C13H25N4O2. TcO 384.0989 384.2688 D02284.gif Radio...gs in Japan [BR:br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  18. A role for naturally occurring alleles of endoplasmic reticulum aminopeptidases in tumor immunity and cancer pre-disposition.

    Science.gov (United States)

    Stratikos, Efstratios; Stamogiannos, Athanasios; Zervoudi, Efthalia; Fruci, Doriana

    2014-01-01

    Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) are key components on the pathway that generates antigenic epitopes for presentation to cytotoxic T-lymphocytes (CTLs). Coding single nucleotide polymorphisms (SNPs) in these enzymes have been associated with pre-disposition to several major human diseases including inflammatory diseases with autoimmune etiology, viral infections, and virally induced cancer. The function of these enzymes has been demonstrated to affect CTL and natural killer cell responses toward healthy and malignant cells as well as the production of inflammatory cytokines. Recent studies have demonstrated that SNPs in ERAP1 and ERAP2 can affect their ability to generate or destroy antigenic epitopes and define the immunopeptidome. In this review, we examine the potential role of these enzymes and their polymorphic states on the generation of cytotoxic responses toward malignantly transformed cells. Given the current state-of-the-art, it is possible that polymorphic variation in these enzymes may contribute to the individual's pre-disposition to cancer through altered generation or destruction of tumor antigens that can facilitate tumor immune evasion. PMID:25566501

  19. Prescription Drugs

    Science.gov (United States)

    ... Us Search Search close Teens Teachers Parents Drugs & Health Blog NDAFW Enter Search Term(s): Teens / Drug Facts / Prescription Drugs Prescription Drugs Print What Is Prescription Drug Abuse? Also known as: Opioids: Hillbilly heroin, oxy, OC, oxycotton, percs, happy pills, vikes Depressants: ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Work? Types of Drug Treatment What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were Once Addicted Drug Abuse Prevention Phone ... English ...

  1. Drug: D02086 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02086 Drug Lidocaine injection (JP16); Lidocaine hydrochloride (JAN/USP); Dalcaine...1 D04AB01] D02086 Lidocaine hydrochloride (JAN/USP) CAS: 73-78-9 PubChem: 7849147 DrugBank: DB00281 LigandBo...CYP2D6 [HSA:1565] Transporter: SLC22A3 [HSA:6581] map07037 Antiarrhythmic drugs m...ap07231 Sodium channel blocking drugs Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting...Xylidines D02086 Lidocaine injection (JP16); Lidocaine hydrochloride (JAN/USP) 2 Agents affecting individual

  2. Drug: D04905 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04905 Drug Memantine hydrochloride (JAN/USAN); Namenda (TN); Memary (TN) C12H21N. ...-aspartic acid receptor antagonists Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting n...ervous system and sensory organs 11 Agents affecting central nervous system 119 Miscellaneous 1190 Miscellan...TC) classification [BR:br08303] N NERVOUS SYSTEM N06 PSYCHOANALEPTICS N06D ANTI-DEMENTIA DRUGS N06DX Other anti-dementia dr...ugs N06DX01 Memantine D04905 Memantine hydrochloride (JAN/USAN) USP drug classification [BR:b

  3. Plasma and Tissue Disposition of Moxifloxacin in Japanese Quail ( Coturnix japonica ).

    Science.gov (United States)

    Goudah, Ayman; Hasabelnaby, Sherifa

    2016-06-01

    Plasma disposition and depletion of moxifloxacin were investigated in Japanese quail ( Coturnix japonica ) after single intravenous, intramuscular, and oral administration of 5 mg/kg and after intramuscular and oral administration of 5 mg/kg q24h for 5 consecutive days, respectively. Drug concentrations in plasma and tissues were measured by high-performance liquid chromatography with fluorescence detection. After intravenous injection, plasma drug concentration-time curves were best described by a 2-compartment open model. The decline in plasma drug concentration was biexponential with half-lives of 0.3 hours and 2.18 hours for distribution and elimination phases, respectively. Steady-state volume of distribution and total body clearance after intravenous administration were estimated to be 1.12 L/kg and 0.41 L/h per kilogram, respectively. After intramuscular and oral administration of moxifloxacin at the same dose, the peak plasma concentrations were 2.14 and 1.94 μg/mL and were obtained at 1.4 and 1.87 hours, respectively, and the elimination half-lives were 2.56 and 1.97 hours, respectively. The systemic bioavailabilities were 92.48% and 87.94%, respectively. Tissue levels after intramuscular and oral administration were highest in liver and kidneys, respectively, and decreased in the following order: plasma, lungs, and muscle. Moxifloxacin concentrations after intramuscular and oral administration were below the detection limit of the assay in tissues and plasma after 120 hours. PMID:27315376

  4. Drug: D00625 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ose metabolism hsa04973(8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic categ...ory of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic...Miglitol (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic

  5. Drug: D01799 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01799 Drug Glyclopyramide (JAN/INN); Deamelin-S (TN) C11H14ClN3O3S 303.0444 303.7652 D01799.gif Antidiabeti...erapeutic category of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic

  6. Drug: D01168 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01168 Drug Potassium hydroxide (JP16/NF); Potassium hydroxide (TN) KOH 55.9664 56....Glycerin and potash solution [DR:D04809] Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affect...ing individual organs 26 Epidermides 266 Emollients 2662 Alkaline agents D01168 Potassium hydr

  7. HIV Infection Seems to Affect Nervous System

    Science.gov (United States)

    ... fullstory_159344.html HIV Infection Seems to Affect Nervous System But symptoms tend to subside once antiretroviral drugs ... mild, it is clear that HIV affects the nervous system within days of infection," she said in a ...

  8. Supplement to the Surplus Plutonium Disposition Draft Environmental Impact Statement

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1999-05-14

    On May 22, 1997, DOE published a Notice of Intent in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the ''Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS)''. ''The Surplus Plutonium Disposition Draft Environmental Impact Statement'' (SPD Draft EIS) (DOWEIS-0283-D) was prepared in accordance with NEPA and issued in July 1998. It identified the potential environmental impacts of reasonable alternatives for the proposed siting, construction, and operation of three facilities for plutonium disposition. These three facilities would accomplish pit disassembly and conversion, immobilization, and MOX fuel fabrication. For the alternatives that included MOX fuel fabrication, the draft also described the potential environmental impacts of using from three to eight commercial nuclear reactors to irradiate MOX fuel. The potential impacts were based on a generic reactor analysis that used actual reactor data and a range of potential site conditions. In May 1998, DCE initiated a procurement process to obtain MOX fuel fabrication and reactor irradiation services. The request for proposals defined limited activities that may be performed prior to issuance of the SPD EIS Record of Decision (ROD) including non-site-specific work associated with the development of the initial design for the MOX fuel fabrication facility, and plans (paper studies) for outreach, long lead-time procurements, regulatory management, facility quality assurance, safeguards, security, fuel qualification, and deactivation. No construction on the proposed MOX facility would begin before an SPD EIS ROD is issued. In March 1999, DOE awarded a contract to Duke Engineering & Services; COGEMA, Inc.; and Stone & Webster (known as DCS) to provide the requested

  9. DOE plutonium disposition study: Pu consumption in ALWRs

    International Nuclear Information System (INIS)

    The Department of Energy (DOE) has contracted with Asea Brown Boveri-Combustion Engineering (ABB-CE) to provide information on the capability of ABB-CE's System 80 + Advanced Light Water Reactor (ALWR) to transform, through reactor burnup, 100 metric tonnes (MT) of weapons grade plutonium (Pu) into a form which is not readily useable in weapons. This information is being developed as part of DOE's Plutonium Disposition Study, initiated by DOE in response to Congressional action. This document Volume 2, provides a discussion of: Plutonium Fuel Cycle; Technology Needs; Regulatory Considerations; Cost and Schedule Estimates; and Deployment Strategy

  10. Club Drugs

    Science.gov (United States)

    ... Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can cause serious health problems and sometimes death. ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  12. Club Drugs

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Learn more Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800-662- ...

  15. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  16. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  17. Drug: D02200 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02200 Drug Pilocarpine hydrochloride (JP16/USP); Isopto carpine (TN); Pilopine HS ...ergic and anticholinergic drugs Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting nervo...ents 1312 Miotic agents D02200 Pilocarpine hydrochloride (JP16/USP) 2 Agents affecting individual organs 23 ...Digestive organ agents 239 Miscellaneous 2399 Others D02200 Pilocarpine hydrochloride (JP16/USP) Anatomical ...PARASYMPATHOMIMETICS N07AX Other parasympathomimetics N07AX01 Pilocarpine D02200 Pilocarpine hydr

  18. Drug abuse

    International Nuclear Information System (INIS)

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  19. Standardization of the Czech version of the Snyder´s Adult dispositional hope scale

    Directory of Open Access Journals (Sweden)

    Marie Ocisková

    2016-01-01

    Full Text Available Hope is one of important factors affecting the psychological state of individuals. It influences well-being and self-esteem, academic and athletic performance, and even the probability of repeated incarceration of offenders. It also predicts the efficacy of the systematic psychotherapy of mental disorders, as well as the supportive psychotherapy in patients with oncologic illnesses. Hope has a central position in positive and clinical psychology. The aim of the presented work was to translate the adult dispositional hope scale into Czech, verify its psychometric properties and develop the norms for interpreting the resulting scores. The scale could be helpful both in mental health research and practice. 394 healthy adults participated in the study. The average age of the probands was 27.1 + 11.7 years. There were more women (n = 303; i.e. 76.9 % than men. The most common level of education was secondary (n = 309; 78.4 %. The participants were mainly students (n = 273; 69.3 % or employees and self-employed individuals (n = 113; 28.7 %. Most of them were single (n = 300; 76.1 % or married (n = 84; 21.3 %. The Adult Dispositional Hope Scale consists of 12 items. Four items measure pathways thinking (i.e. the ability to find ways to achieve one's goals and four items assess agency (i.e. goal-directed energy. The remaining four items are fillers that are not interpreted. Apart from this scale, all participants completed a demographic questionnaire and the second version of the Beck Depression Inventory. The statistical analyses consisted of the Cronbach's alpha and Spearman-Brown coefficient analysis, the exploratory and confirmatory factor analysis, the correlation between the standardized scale and the Beck Depression Inventory-II, and finally the creation of the norms based on the stens. The overall rate of hope was not statistically significantly associated with the subjects' age (Spearman r = -0.06, non-significant, nor with their sex (Mann

  20. Preservice Teachers' Critical Thinking Dispositions and Web 2.0 Competencies

    Science.gov (United States)

    Sendag, Serkan; Erol, Osman; Sezgin, Sezan; Dulkadir, Nihal

    2015-01-01

    The aim of this study was to investigate the associations between preservice teachers' Web 2.0 competencies and their critical thinking disposition (CTD). The study employed an associational research design using California Critical Thinking Disposition-Inventory (CCTD-I) and a Web 2.0 competency questionnaire including items related to Web 2.0…

  1. Carnap versus Quine, or Aprioristic versus Naturalized Epistemology, or a Lesson from Dispositions

    OpenAIRE

    Spohn, Wolfgang

    2003-01-01

    In his influential paper "Epistemology Naturalized" Quine argues that Carnap's failure to define disposition predicates and his subsequent preference for reduction sentences naturally lead to an entirely naturalized epistemology. This conclusion is too hasty, I object. Applying the account of dispositional predicates developed in No. 26 I defend Carnap's aprioristic epistemology against Quine's attacks.

  2. 28 CFR 541.18 - Dispositions of the Discipline Hearing Officer.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Dispositions of the Discipline Hearing... INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Inmate Discipline and Special Housing Units § 541.18 Dispositions of the Discipline Hearing Officer. The Discipline Hearing Officer has available...

  3. Cross-Cultural Equivalency of the California Critical Thinking Disposition Inventory

    Science.gov (United States)

    Iskifoglu, Gökhan

    2014-01-01

    This study describes the cross-cultural applicability of a multidimensional inventory of students' evaluation of critical thinking dispositions (California Critical Thinking Disposition Inventory). The goal was to assess the cross-cultural psychometric equivalency of the CCTDI through testing measurement invariance across American and Turkish…

  4. 22 CFR 211.8 - Disposition of commodities unfit for authorized use.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Disposition of commodities unfit for authorized... COMMODITIES FOR FOOD USE IN DISASTER RELIEF, ECONOMIC DEVELOPMENT AND OTHER ASSISTANCE § 211.8 Disposition of commodities unfit for authorized use. (a) Prior to delivery to cooperating sponsor at discharge port or...

  5. 10 CFR 709.17 - Final disposition of CI evaluation findings and recommendations.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Final disposition of CI evaluation findings and recommendations. 709.17 Section 709.17 Energy DEPARTMENT OF ENERGY COUNTERINTELLIGENCE EVALUATION PROGRAM CI Evaluation Protocols and Protection of National Security § 709.17 Final disposition of CI evaluation...

  6. 31 CFR 100.19 - Disposition of counterfeit notes and coins.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Disposition of counterfeit notes and... EXCHANGE OF PAPER CURRENCY AND COIN Other Information § 100.19 Disposition of counterfeit notes and coins. All counterfeit notes and coin found in remittances are cancelled and delivered to the U.S....

  7. 26 CFR 1.453-9 - Gain or loss on disposition of installment obligations.

    Science.gov (United States)

    2010-04-01

    ... gains and capital losses of individuals. (g) Disposition of installment obligations to life insurance... life insurance company as defined in section 801(a). P realized a loss upon the transfer of the... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Gain or loss on disposition of...

  8. 24 CFR 247.10 - Inapplicability to substantial rehabilitation or demolition; right of disposition unimpaired.

    Science.gov (United States)

    2010-04-01

    ... rehabilitation or demolition; right of disposition unimpaired. 247.10 Section 247.10 Housing and Urban... FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE AND... or demolition; right of disposition unimpaired. This subpart shall not apply in any case in which...

  9. RESEARCH ON THE DOF DISPOSITION AND MECHANISMS DESIGN OF HUMANOID ROBOT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The DOF of human being was analyzed in this paper. Three reasonable kinds of DOF disposition programs came up to design a humanoid robot and an optimal DOF disposition program was chosen according to configuration appearance, realizing the balance and torsion movement and analysis of torque of the humanoid. Three special mechanisms were designed so that the humanoid robot has some special function.

  10. 7 CFR 767.52 - Disposition of personal property from real estate inventory property.

    Science.gov (United States)

    2010-01-01

    .... Property of value may be sold at a public sale. (b) Reclaiming personal property. The owner or lienholder... 7 Agriculture 7 2010-01-01 2010-01-01 false Disposition of personal property from real estate... Property Abandonment and Personal Property Removal § 767.52 Disposition of personal property from...

  11. 7 CFR 981.65 - Prohibition on the use or disposition of reserve almonds.

    Science.gov (United States)

    2010-01-01

    ... almonds. 981.65 Section 981.65 Agriculture Regulations of the Department of Agriculture (Continued... AGRICULTURE ALMONDS GROWN IN CALIFORNIA Order Regulating Handling Disposition of Reserve § 981.65 Prohibition on the use or disposition of reserve almonds. Except as provided in §§ 981.66 and 981.67,...

  12. 47 CFR 6.20 - Review and disposition of informal complaints.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Review and disposition of informal complaints... TELECOMMUNICATIONS SERVICE, TELECOMMUNICATIONS EQUIPMENT AND CUSTOMER PREMISES EQUIPMENT BY PERSONS WITH DISABILITIES Enforcement § 6.20 Review and disposition of informal complaints. (a) Where it appears from the...

  13. 15 CFR 705.12 - Disposition of an investigation and report to the Congress.

    Science.gov (United States)

    2010-01-01

    ... report to the Congress. 705.12 Section 705.12 Commerce and Foreign Trade Regulations Relating to Commerce... Disposition of an investigation and report to the Congress. (a) Upon the disposition of each request... to the Congress and published in the Federal Register. (b) As required by Section 232(e) of the...

  14. 26 CFR 1.1254-1 - Treatment of gain from disposition of natural resource recapture property.

    Science.gov (United States)

    2010-04-01

    ... Capital Gains and Losses § 1.1254-1 Treatment of gain from disposition of natural resource recapture... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Treatment of gain from disposition of natural... geothermal property, and natural resource recapture property, see paragraph (b)(2) of this section. For...

  15. 32 CFR 736.5 - Disposition of real and personal property under special statutory authority.

    Science.gov (United States)

    2010-07-01

    ... transferred for the conduct of basic or applied scientific research to (1) non-profit institutions of higher education or (2) non-profit organizations whose primary purpose is the conduct of scientific research. An... Disposition Manual. (g) Disposition of equipment for research. Under the act of September 6, 1958 (72...

  16. Repeated investigations of cyclophosphamide disposition in myeloma patients receiving intermittent chemotherapy.

    OpenAIRE

    Edwards, G.; Calvert, R T; Crowther, D.; Bramwell, V; Scarffe, H.

    1980-01-01

    1 The disposition of cyclophosphamide was investigated in a group of myeloma patients. 2 Marked changes in clearance and volume of distribution of cyclophosphamide occurred between investigations. 3 The observed changes in disposition did not correlate with biochemical estimates of renal and hepatic function or plasma protein status.

  17. Construct Validity Examination of Critical Thinking Dispositions for Undergraduate Students in University Putra Malaysia

    Science.gov (United States)

    Ghadi, Ibrahim; Alwi, Nor Hayati; Bakar, Kamariah Abu; Talib, Othman

    2012-01-01

    This research aims to evaluate the psychology properties of the construct validity for the Critical Thinking Disposition (CTD) instrument. The CTD instrument consists of 39 Likert-type items measuring seven dispositions, namely analyticity, open-mind, truth-seeking, systematicity, self-confidence inquisitiveness and maturity. The study involves…

  18. 25 CFR 11.608 - Final decree; disposition of property; maintenance; child support; custody.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Final decree; disposition of property; maintenance; child... AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Domestic Relations § 11.608 Final decree; disposition of property; maintenance; child support; custody. (a) A decree of dissolution of marriage or...

  19. 14 CFR 125.405 - Disposition of load manifest, flight release, and flight plans.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Disposition of load manifest, flight release, and flight plans. 125.405 Section 125.405 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... AIRCRAFT Records and Reports § 125.405 Disposition of load manifest, flight release, and flight plans....

  20. 19 CFR 144.7 - Disposition of merchandise after expiration of warehousing period.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Disposition of merchandise after expiration of... General Provisions § 144.7 Disposition of merchandise after expiration of warehousing period. Merchandise remaining in a bonded warehouse after the expiration of the warehousing period shall be disposed of...