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Sample records for underlying drug dependence

  1. Age at drinking onset, alcohol dependence, and their relation to drug use and dependence, driving under the influence of drugs, and motor-vehicle crash involvement because of drugs.

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    Hingson, Ralph W; Heeren, Timothy; Edwards, Erika M

    2008-03-01

    We explored among people who ever consumed alcohol whether early age at drinking onset and alcohol dependence predicted drug use and dependence. We also examined among drinkers who have used drugs whether they also predict driving under the influence of drugs and motor-vehicle crash involvement because of drugs. A U.S. national sample of 42,867 persons age 18 and older was surveyed in 1991-1992 (response rate = 90%). Logistic regression examined these potential associations among 27,616 respondents who ever drank alcohol, controlling for numerous demographic and personal characteristics. Among "ever" drinkers, 22% used drugs, 10% had driven under the influence of drugs, and nearly 1% was in a motor-vehicle crash because of drug use, the equivalent of 1 million people. The younger the age of respondents when they first began drinking and whether they ever experienced alcohol dependence were independently associated with greater odds of ever using drugs and experiencing drug dependence. Among persons who consumed alcohol and drugs, having ever experienced drug dependence was the strongest predictor of driving under the influence of drugs and motor-vehicle crash involvement because of drug use. After controlling for drug dependence and age at first drug use, having experienced alcohol dependence was also independently associated with both outcomes. Efforts to prevent drug-related crashes should include drug use prevention and treatment, as well as prevention of early alcohol use and treatment of alcohol dependence.

  2. Personality Dimensions Influencing the Relapse of Substance Abuse in Drug Dependents under Methadone Maintenance Treatment

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    Akram Asgari

    2011-11-01

    Full Text Available introduction: This study was aimed to determine the personality dimensions which can influence the relapse of opioid substance dependents that are under methadone maintenance treatment. Method: In this prospective study 210 addicts who were referred to methadone clinics in 1389 were selected through judgmental sampling. All participants completed the self made questionnaire and Temperament and Character Inventory and it was followed for 6 months. Data were analyzed by t test. Findings: Data analysis revealed that relapsed group has higher scores in novelty seeking and harm avoidance compared to non-relapsed group. Also, their scores in self directiveness and cooperativeness were lower than non-relapsed group. No significant differences were found in reward dependence and persistence. Conclusion: This personality profile due to dimensional personality model of Cloninger showed that patients who relapse are high in novelty seeking and harm avoidance and low in cooperativeness and self directiveness. has important information about nature of personality traits that effect relapse of addiction and has implications for treatment plan and relapse prevention.

  3. Women and Drug Dependence.

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    Valentich, Mary

    1982-01-01

    Presents a feminist perspective which offers a social structural framework for examining women's problematic behavior in traditional gender roles. Examines implications for treatment of women with drug dependence problems including developing the helping agent's awareness of the pervasiveness of sexism and its potentially negative effects.…

  4. FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

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    Giulia Gentile

    2016-11-01

    Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

  5. Psychostimulant drugs for cocaine dependence.

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    Castells, Xavier; Cunill, Ruth; Pérez-Mañá, Clara; Vidal, Xavier; Capellà, Dolors

    2016-09-27

    Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. We used standard methodological procedures expected by Cochrane. We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants

  6. The Comparison of Maladaptive Schema and Lifestyles in Drug Dependence and Non-Drug Dependence People

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    Vahideh Purmohammad

    2013-04-01

    Full Text Available Objective: The aim of this study was to compare early maladaptive schemas and life styles in drug dependences and normal population to recognize their role in drug dependence. Due to their importance in interpretation of special situations, cognitive schemas and life styles have a significant role in cognitive theories. Methods: The method of this research were post-facto and sectional styles. The population were included of 100 drug dependence adults and 100 non-drug dependence who were selected by at-reach methods. Young early maladaptive schema-short form and Basic Adlerian scales for interpersonal success-adult form questionnaires were used. Findings: the results showed that there were significant differences between early maladaptive schemas and life styles in groups under research. Conclusion: the study showed that drug dependence people suffer from high levels of early maladaptive schemas and their life styles are maladaptive. As a result, in prediction of dependence to drug and in treating it too much attention must be given to cognitive factors.

  7. Detection and identification of drugs and toxicants in human body fluids by liquid chromatography-tandem mass spectrometry under data-dependent acquisition control and automated database search.

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    Oberacher, Herbert; Schubert, Birthe; Libiseller, Kathrin; Schweissgut, Anna

    2013-04-03

    Systematic toxicological analysis (STA) is aimed at detecting and identifying all substances of toxicological relevance (i.e. drugs, drugs of abuse, poisons and/or their metabolites) in biological material. Particularly, gas chromatography-mass spectrometry (GC/MS) represents a competent and commonly applied screening and confirmation tool. Herein, we present an untargeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay aimed to complement existing GC/MS screening for the detection and identification of drugs in blood, plasma and urine samples. Solid-phase extraction was accomplished on mixed-mode cartridges. LC was based on gradient elution in a miniaturized C18 column. High resolution electrospray ionization-MS/MS in positive ion mode with data-dependent acquisition control was used to generate tandem mass spectral information that enabled compound identification via automated library search in the "Wiley Registry of Tandem Mass Spectral Data, MSforID". Fitness of the developed LC/MS/MS method for application in STA in terms of selectivity, detection capability and reliability of identification (sensitivity/specificity) was demonstrated with blank samples, certified reference materials, proficiency test samples, and authentic casework samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Behavioral Pharmacology of Human Drug Dependence

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    1981-07-01

    Preface John Gr bowski and J. kfichaeZ Walsh ... ........... . INTRODUCTION AND OVERVIEW Behavioral Mechanisms and Loci of Drug Dependence: An...Overview f I t£ Behavioral Mechanisms and Loci of Drug Dependence: An Overview Travis Thompson, Ph.D. The search for a more thorough understanding of the...even the output of genius . A central question revolves around the sources of unusual amounts of behavior, whether we consider that behavior good, bad, or

  9. [Drugs, a current problem. Alcohol dependency].

    Science.gov (United States)

    Amigó Tadín, Montserrat

    2006-01-01

    Alcohol is a socially accepted drug which is commercialized in multiple products including wine, cognac, gin, beer, anisette, vermouth, rum, etc. and which can be consumed in small quantities without producing harmful effects on one's health; nonetheless, women are more susceptible to alcohol's damages and an abusive consumption of alcohol creates dependence and chronic diseases. Ten percent of those people who consume alcohol develop dependency and comprise the leading group of drug addicts in many countries.

  10. [The role of cellular mediators in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence of blood under the influence of non-steroidal anti-inflammatory drugs in patients with intolerance to these drugs].

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    Chausova, S V; Gurevich, K G; Bondareva, G P; Filatov, O Ju; Malyshev, I Y

    2015-01-01

    We investigated contribution mediator mechanism in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence (SLCHL) of blood under the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with intolerance to these drugs. It was found that the phenomenon of suppression SLCHL blood under the influence of NSAIDs in patients with intolerance is mediated by the participation of mediators, and the contribution of H1--and H2--histamine receptors, 5-HT2 serotonin receptors and Cys-leukotriene receptors in the development of that phenomenon depends on the chemical nature of NSAIDs and the clinical manifestations of intolerance.

  11. Dependency Traits Among Parents of Drug Abusers

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    Tennant, Forest S., Jr.

    1976-01-01

    Studies question whether there is a significant association between parents' dependency traits and drug habits in their offspring. Reported here is a survey of 1,091 young males. The reported occurrence of parents' alcohol consumption, smoking, use of stimulants and sedatives, and overeating were compared among abusers and non-users of hashish,…

  12. Role of endocannabinoids in regulating drug dependence

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    Daniela Parolaro

    2007-01-01

    Full Text Available Daniela Parolaro, Daniela Vigano’, Natalia Realini, Tiziana RubinoNeuroscience Center, DBSF, University of Insubria, Busto Arsizio, ItalyAbstract: This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.Keywords: Endocannabinoids, drug dependence, opioids, nicotine, alcohol, psychostimulants

  13. New aquaculture drugs under FDA review

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    Bowker, James D.; Gaikowski, Mark P.

    2012-01-01

    Only eight active pharmaceutical ingredients available in 18 drug products have been approved by the U.S. Food and Drug Administration for use in aquaculture. The approval process can be lengthy and expensive, but several new drugs and label claims are under review. Progress has been made on approvals for Halamid (chloramine-T), Aquaflor (florfenicol) and 35% PeroxAid (hydrogen peroxide) as therapeutic drugs. Data are also being generated for AQUI-S 20E, a fish sedative.

  14. Evaluation on drug dependence of buprenorphine.

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    Liu, Zhi-Min; Lü, Xian-Xiang; Lian, Zhi; Mu, Yue; Guo, Ping; An, Xin

    2003-05-01

    To survey and assess the drug dependence and abuse potential liability of buprenorphine among opiate abusers. Subjects of opiate dependence with history of buprenorphine use for 3 d at least were surveyed by interview. Physical dependence of buprenorphine was assessed using 30 items opiate withdrawal scale (OWS), which composed of 30 symptoms/signs. A 4-point scale was used to rate each symptoms/signs: zero (0), mild (1), moderate (2), and severe (3). Subjects were asked to rate their symptoms according to severity of previous experienced buprenorphine withdrawal. The estimate of the degree of subjective euphoria for buprenorphine was assessed using visual analogue scale (VAS). Subjects 1235 who met the research criteria cases completed this survey in multi-detoxification treatment centers. The main initial purposes of buprenorphine use were detoxification (77.4 %) and protracted abstinence treated (26.6 %) respectively. The scores of OWS of buprenorphine were between 0.2 to 1.3; The mean scores of OWS in 3 different categories of frequency of buprenorphine use on "continuous use", "un-continuous use", and "sometimes continuous, sometimes un-continuous" were 0.9+/-0.9, 0.4+/-0.5, and 0.7+/-0.4, respectively (F=70.846, Pbuprenorphine was slight to sub-moderate (mean score of VAS was 27 mm+/-24 mm). The mean scores of VAS in different routes of buprenorphine administration of sublingual and injection were (24+/-23) mm and (27+/-24) mm, respectively. No significant difference was found between sublingual and injection use of buprenorphine (u=1.516, P>0.05). Both physical and psychic dependence of buprenorphine were low.

  15. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs.

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    Sánchez-Martínez, Concepción; Gelbert, Lawrence M; Lallena, María José; de Dios, Alfonso

    2015-09-01

    Sustained proliferative capacity is a hallmark of cancer. In mammalian cells proliferation is controlled by the cell cycle, where cyclin-dependent kinases (CDKs) regulate critical checkpoints. CDK4 and CDK6 are considered highly validated anticancer drug targets due to their essential role regulating cell cycle progression at the G1 restriction point. This review provides an overview of recent advances on cyclin dependent kinase inhibitors in general with special emphasis on CDK4 and CDK6 inhibitors and compounds under clinical evaluation. Chemical structures, structure activity relationships, and relevant preclinical properties will be described. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Commentary: New View on Treatment of Drug Dependence

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    Mina Ranjbaran

    2014-02-01

    Full Text Available In the 1960s, discovery of pleasure system (defined as reward system in the brain that may underlie drug reward and addiction encouraged many scientists to investigate the mechanisms by which drug abuse affects central nervous system function. In this regard, investigators developed several drugs targeting the brain reward system for drug dependence therapy. However, no positive results obtained in drug addiction treatment. It seems that more brain systems other than brain reward system must be considered in this regard.

  17. National Council on Alcoholism and Drug Dependence

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    ... to achieve h… Millions of Dollars Needed for Trump’s A… 15 November, 2017 The anti-drug ad campaign advocated by President Trump’s opioid commis… Combo of Acetaminophen and Ibuprofen as … ...

  18. Risk factors in prevention of drug dependences

    NARCIS (Netherlands)

    Orosova, Ol'ga; Gajdosova, Beata; Madarasova-Geckova, Andrea; Van Dijk, Jitse P.

    2007-01-01

    The study presents the state-of-art of knowledge of risk factors of drug use as a form of risk behaviour in adolescents in individual, interpersonal, and environmental domain (family, school, society). The attention is paid to general deviation syndrome and to the construct of general tendency to

  19. Cognitive and social learning models of drug dependence: implications for the assessment of tobacco dependence in adolescents.

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    Brandon, Thomas H; Herzog, Thaddeus A; Irvin, Jennifer E; Gwaltney, Chad J

    2004-06-01

    This paper is part of a series that has the goal of identifying potential approaches toward developing new instruments for assessing tobacco dependence among adolescents. The fundamental assumption underlying the series is that contemporary theories of drug dependence offer a rich source of opportunities for the development of theoretically based assessment tools. The present paper focuses on cognitive and social-learning models of drug dependence and the implications of these models for novel assessment instruments. In particular, the paper focuses on Mark Goldman's model of drug expectancies, Albert Bandura's model of self-efficacy, Thomas Wills's model of stress and coping and Stephen Tiffany's cognitive-processing model of drug urges and cravings. In addition to traditional self-report measures, naturalistic and laboratory-based assessments are identified that may yield information relevant to multi-dimensional measurement of tobacco dependence.

  20. Road rage among drug dependent patients

    OpenAIRE

    Benavidez, Daniela C.; Flores, Antonio M.; Álvarez, Francisco Javier

    2013-01-01

    Producción Científica The consumption of alcohol, cocaine and cannabis is associated with aggressive behaviour, being a victim of injuries from various causes, and suffering traffic accidents. On the other hand, there is a significant association between road rage and traffic accidents, yet this has not been studied in persons suffering a substance dependence disorder. This study analyses the prevalence of road rage in substance dependent patients undergoing treatment. 100 pati...

  1. Genes and (common pathways underlying drug addiction.

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    Chuan-Yun Li

    2008-01-01

    Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

  2. Road rage among drug dependent patients.

    Science.gov (United States)

    Benavidez, Daniela C; Flores, Antonio Marcos; Fierro, Inmaculada; Alvarez, F Javier

    2013-01-01

    The consumption of alcohol, cocaine and cannabis is associated with aggressive behaviour, being a victim of injuries from various causes, and suffering traffic accidents. On the other hand, there is a significant association between road rage and traffic accidents, yet this has not been studied in persons suffering a substance dependence disorder. This study analyses the prevalence of road rage in substance dependent patients undergoing treatment. 100 patients randomly selected at an outpatient treatment centre were included in the study. 63% of the patients had experienced road rage in the year prior to the interview, and 18% were serious perpetrators. There was a higher frequency among drivers and those who were starting treatment for cocaine and cocaine+heroin. The study shows that road rage is very frequent among patients with disorders due to substance dependence who are undergoing treatment, in particular the most severe form ("serious perpetrators"). Special attention should be addressed to the issue of driving and road rage during the treatment of these patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Family care to individuals dependent on alcohol and other drugs

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    Keity Laís Siepmann Soccol

    2013-07-01

    Full Text Available This is a qualitative, exploratory and descriptive research, which aimed to describe the family care given to the individual dependent on alcohol and other drugs. For data collection we used the interview, open, free and recorded, which was performed in August and September 2011. The 11 subjects were relatives of the individuals dependent on alcohol and other drugs, involved in family groups conducted at the Psychosocial care Center for Alcohol and Drugs. From the content analysis of these interviews, two categories were revealed: care actions in the perception of family caregivers, and care to minimize conflicts in family relations. The way the family takes care of the relative dependent on alcohol and other drugs has the purpose of meeting the physical and emotional demands, as well the interpersonal relationships, as it is concerned with the wellbeing of the chemically dependent relative.

  4. Profiling evolutionary landscapes underlying drug resistance

    DEFF Research Database (Denmark)

    Hickman, Rachel

    bacterial communities i.e. biofilms or dormant metabolic states. Antibiotic drugs are currently our best medicine to treat (against) bacterial pathogens due to antibiotics unique properties of being small molecules that are soluble and act systemically. These qualities allow for many modern medical......, the work involved in this PhD thesis, examines the evolution of antibiotic resistance in bacterial populations. Two main studies were performed: the first to elucidate the molecular mechanisms of collateral sensitive drug pairs and collateral resistance drug pairs in adaptation of Escherichia coli...

  5. Time-dependent drug-drug interaction alerts in care provider order entry: software may inhibit medication error reductions

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen); L.A. Lammers (Laureen); A. van den Tweel (Annemieke); J.E.C.M. Aarts (Jos); M. Berg (Marc); A.G. Vulto (Arnold); T. van Gelder (Teun)

    2009-01-01

    textabstractTime-dependent drug-drug interactions (TDDIs) are drug combinations that result in a decreased drug effect due to coadministration of a second drug. Such interactions can be prevented by separately administering the drugs. This study attempted to reduce drug administration errors due to

  6. Typological analysis of MMPI personality patterns of drug dependent men.

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    Tosi, D J; Eshbaugh, D M; Raines, M G; Murphy, M A

    1986-10-01

    This study replicated Types I and II of Berzins, Ross, English and Haley's (1974) initial typological research with a drug dependent sample. In this research, Minnesota Multiphasic Personality Inventory (MMPI) profiles of 447 drug dependent men were submitted to Johnson's (1967) hierarchical clustering procedure. The hierarchical clustering procedure yielded nine small but clinically meaningful personality subtypes. These types were compared to Berzin's (Berzins et al.) profiles and categorized into three diagnostic classes: character disorder, 42% of the sample; neurotic characters, 35% of the sample; and borderline disorder, 23% of the sample. The profiles were discussed with respect to the scale similarity and differences within the diagnostic class. The results were discussed, with implications for treatment and further research efforts with the drug dependent population.

  7. Pharmacological studies on drug dependence in rodents: dependence on opioids and CNS depressants.

    Science.gov (United States)

    Suzuki, T

    1990-01-01

    Physical and psychic dependence on opioids and CNS depressants in rodents were examined using the drug-admixed food (DAF) method. A comparison of several methods for developing physical dependence on opioids was made. The DAF method has the advantage of rapidly inducing a high degree of physical dependence without causing morbidity or mortality. When morphine-dependent rats were pretreated with several opioids, naloxone-precipitated weight loss was suppressed in a dose-dependent manner. A procedure for the development of severe physical dependence on CNS depressants was also established. Drug concentrations were rapidly increased until animals showed moderate to severe CNS depression, and then this condition was maintained for at least 10 days. With this procedure, animals became severely dependent on CNS depressants. Another technique, intermittent infusion, was developed that has been used to quantify short-acting CNS depressant dependence potential. The sedative effects of pentobarbital were used as an index in the determination of the injection intervals. These results suggest that the DAF method and the new approaches are useful tools for assessing the physical dependence potential of new drugs. Moreover, oral self-administration and weight pulling procedures were utilized along with the DAF method. Procedures for the oral self-administration of opioids and CNS depressants were established. Opioid-dependent rats pulled the weight to obtain the DAF even though they had free access to normal food. This weight-pulling procedure may be useful for assessing the degree of reinforcing effects for drugs in rats.

  8. THE RESOCIALIZATION OF DRUG-DEPENDENT PEOPLE IN REHABILITATION CENTERS: SOCIAL AND PEDAGOGICAL ASPECTS

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    Юлія Чернецька

    2015-12-01

    Full Text Available The article deals with the resocialization of drug-dependent people in rehabilitation centers.  In the of resocialization the restoration of social relationships (social rehabilitation and social adaptation, and the accumulation of new socially positive experience are ensured. Resocialization is possible through the study and assimilation of cultural values, norms, attitudes, patterns of behavior, and the implementation of social activity of drug-dependent people in various activities. The article explains the meaning of “resocialization” through the categories of “social environment” and “social education”. It is roved that the resocialization of drug-dependent personality is carried out directly under the influence of social conditions (environmental factors. This process is the product of direct relations between the subjects of environment (agents and is determined by the influence material culture (means which depend on the result of resocialization is dependent.

  9. Drug discrimination under a concurrent schedule.

    OpenAIRE

    Snodgrass, S H; McMillan, D E

    1996-01-01

    Three pigeons were trained to discriminate a 5.0 mg/kg dose of pentobarbital from saline under a two-key concurrent schedule with responding on the key associated with the presession injection, under both stimulus conditions, producing four times as many reinforcers as responding on the other key. This concurrent schedule resulted in approximately 70% responding to the higher reinforcement key under the pentobarbital stimulus and approximately 30% responding to that key under the saline stimu...

  10. Psychosocial aspects of drug dependence: the Nigerian experience.

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    Pela, O A

    1984-01-01

    This paper provides an operational definition and lists some psychosocial questions usually asked about drug dependence. It then reviews the literature on drug abuse in Nigeria, extracting some of the psychosocial variables involved. The review indicates that drug abuse is associated with polygamous or large monogamous families, which may be suggestive of "stressful sibling rivalry." Other factors included defiance of or rebellion against parental control, the facilitation of social intercourse, and harmful early childhood experiences. The social factors implicated include urbanization, Westernization, and migration which may weaken the traditional African support system. An important out-growth of the review is that the psychosocial variables implicated are not different from those observed in other cultures. However, an important social dimension is the prescribing and dispensing practices of Nigerian medical doctors and pharmacists which encourage drug abuse.

  11. The Study of early maladaptive Schemas in Men Dependent on Drugs and those Not Dependent

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    MR Firoozi

    2015-11-01

    Full Text Available Introduction and Objectives of the Study Dependence on drugs is a prevalent problem throughout the world, in general and in Iran, in particular. Such a phenomenon is associated with numerous negative consequences. Given the changes in the consumption patterns in different countries, especially in Iran, and the abuse of drugs, identifying the factors which may pave the way for drug abuse is absolutely essential, which can be taken into account in setting the objectives of therapy programs. Cognizant of this, the present study has sought to study early maladaptive schemas in men dependent on drugs and those that are not. Materials and Method: The research design adopted in the present study was causal-comparative. The populaiton of interest was all the men dependent on drugs in the city of Yasouj, who had presented to recovery centers affiliated to welfare organization and Yasouj University of Medical Sciences in the year 2014 and were undergoing treatment. Using multi-stage cluster sampling, initially out of 23 centers for recovery programs, four centers were randomly chosen. Following that, out of each center, 20 and in total, 80 clients were chosen as the sample through convenience sampling. In addition, 80 men not dependent on drugs were chosen through matching with the sample dependent on drugs in terms of age, gender and locality. For the purpsoe of measuing early maladaptive schemas, we made use of the short version of Young’s early maladaptive Schemas Questionnaire. In order to determine the prevalent schemas in men dependent on drugs and those not dependent and the difference between the two groups, use was made of independent-sample t-test and effect size (d. Findings: The findings suggest that mean values of those dependent on drugs in all the schemas in quesiton were significantly higher than those of men not dependent. Although the difference in effect size of all schemas fell in the domain of the large effect, the largest

  12. 21 CFR 1310.10 - Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act.

    Science.gov (United States)

    2010-04-01

    ... under the Food, Drug and Cosmetic Act. 1310.10 Section 1310.10 Food and Drugs DRUG ENFORCEMENT... Removal of the exemption of drugs distributed under the Food, Drug and Cosmetic Act. (a) The Administrator... manner of packaging of the drug product; (2) The manner of distribution and advertising of the drug...

  13. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  14. Can tobacco dependence provide insights into other drug addictions?

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    Joseph R. DiFranza

    2016-10-01

    Full Text Available Abstract Within the field of addiction research, individuals tend to operate within silos of knowledge focused on specific drug classes. The discovery that tobacco dependence develops in a progression of stages and that the latency to the onset of withdrawal symptoms after the last use of tobacco changes over time have provided insights into how tobacco dependence develops that might be applied to the study of other drugs. As physical dependence on tobacco develops, it progresses through previously unrecognized clinical stages of wanting, craving and needing. The latency to withdrawal is a measure of the asymptomatic phase of withdrawal, extending from the last use of tobacco to the emergence of withdrawal symptoms. Symptomatic withdrawal is characterized by a wanting phase, a craving phase, and a needing phase. The intensity of the desire to smoke that is triggered by withdrawal correlates with brain activity in addiction circuits. With repeated tobacco use, the latency to withdrawal shrinks from as long as several weeks to as short as several minutes. The shortening of the asymptomatic phase of withdrawal drives an escalation of smoking, first in terms of the number of smoking days/month until daily smoking commences, then in terms of cigarettes smoked/day. The discoveries of the stages of physical dependence and the latency to withdrawal raises the question, does physical dependence develop in stages with other drugs? Is the latency to withdrawal for other substances measured in weeks at the onset of dependence? Does it shorten over time? The research methods that uncovered how tobacco dependence emerges might be fruitfully applied to the investigation of other addictions.

  15. [Evaluation of educational effects on drug dependence abstinence for convicts].

    Science.gov (United States)

    Sakurai, Tomoko; Nishikawa, Kyoko; Tanaka, Takanori

    2011-06-01

    The object of this study is to evaluate the educational effects of group work sessions on drug dependence abstinence for convicts in Fukui Prison. Questionnaire surveys were conducted among participants on the first and last session. The results of surveys were analyzed quantitatively. The average ages of 50 respondents were 39 years. 95.9% of them used methamphetamine among drugs and the majority has used drugs for the past 5 years. 93.9% of respondents had no medical treatment histories and 95.8% of them have not used any formal consultations. The survey result before the sessions showed that 75.5% of respondents showed positive stances towards participations on educational group work sessions. The survey after the sessions showed 67.4% of respondents were able to talk their drug problems in group meetings and 87.0% responded that group work sessions were helpful for solving drug problems. Also, 80.0% responded that they can stop using drugs and the percentage dropped by 11.0% from the first session. In terms of the participation in self-help groups after releases from the prison, the majority responded negatively, although 78.0% showed positive responses to using consultation services. The outcomes by means of evaluation scale also showed a significant improvement on denial and no relevant change on interpersonal trusts. This study revealed that it was possible to confirm the effectiveness of drug abstinence education through group work. It is important to consider three points in further studies; 1) cooperation between judicial and medical institutions for introducing consultation and medical treatments among convicts; 2) follow-up programs for reinforcing education on drug abstinence; 3) social welfare services in cooperation with educational effects to prevent repeated offences.

  16. A theory of drug tolerance and dependence I: a conceptual analysis.

    Science.gov (United States)

    Peper, Abraham

    2004-08-21

    A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.

  17. Treatment of drug dependence with Brazilian herbal medicines

    Directory of Open Access Journals (Sweden)

    Elisaldo A. Carlini

    Full Text Available The topic "Herbal Medicines in the Treatment of Addictions" in a country must be preceded by answers to four questions: 1. Does the country in question possess a biodiversity rich enough to allow the discovery of useful medicines? 2. Do local people have tradition and culture to look for and use resources from Nature to alleviate and cure diseases, including drug dependence? 3. Is drug dependence (or addiction present in the country in question? 4. Do people of that country recognize and diagnose such problem as a serious one? Alcohol is, by far, the most serious health problem when drug abuse is considered, reaching all of Brazilian society, including the Indians. On the contrary, other drugs may be considered as minor problems and they are not the main focus of this manuscript. The people living in Brazilian hinterland don’t have access to public health systems. Consequently, these people seek assistance from "curandeiros" and "raizeiros"; the Indians are assisted by the shaman. These "folk doctors" do not know the academic medicine and therapeutics, and resort to the local plants to treat different ailments of their patients. Furthermore, alcohol abuse and dependence are not recognized by them, according to the rules and criteria of academic medicine. We have conducted a survey in many Brazilian books, Thesis concerning phytotherapy, and several databank. The results of such searches were very disappointing. No published papers from Brazilian authors concerning the use of plants for the treatment of addictions were found in the databases and there were only three very short notes in the masterly book written by Shultes and Raffauf (1990. From the Brazilian books on folk medicine employing medicinal plants, ten mentions were disclosed: most of them dealing with treatment of alcohol problems and two to counteract "Ayahuasca" dependence.

  18. Structured outpatient treatment of alcohol vs. drug dependencies.

    Science.gov (United States)

    Washton, A M

    1990-01-01

    This chapter describes the rationale, indications, design, and use of a structured outpatient treatment approach as an effective alternative to residential treatment for alcohol and drug dependencies. An increasing demand for outpatient treatment services is being created by a combination of clinical and economic factors, including the influx of employed drug abusers who do not need or desire residential care and mounting financial pressures to contain health care costs. To be effective as a primary treatment modality, outpatient programs must be highly structured and intensive and able to deal with the full spectrum of alcohol and drug addictions. Perpetuating the historical separation between alcoholism and drug abuse treatment programs is unnecessary and counterproductive, although certain modifications in treatment approaches are needed to accommodate the distinctive characteristics of particular classes of drugs and the people who use them. The "outpatient rehab," a treatment model that approximates the intensity of inpatient treatment on an outpatient basis, may help to maximize the clinical efficacy and cost-effectiveness of outpatient treatment as a viable alternative to residential care. Initial treatment results with this model are encouraging.

  19. Study of pH-dependent drugs solubility in water

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    Pobudkowska A.

    2014-01-01

    Full Text Available The solubilities of five sparingly soluble drug-compounds in water have been measured at constant temperatures (298.1K and 310.1K by the classical saturation shake-flask method. All substances presented in this work are derivatives of anthranilic acid: flufenamic acid, (FLU, mefenamic acid, (MEF, niflumic acid, (NIF, diclofenac sodium, (DIC, and meclofenamic sodium, (MEC. All of them have anti-inflammatory action. Since the aqueous solubility of the ionized drug is significantly higher than the unionized, the experimental conditions that affect equilibrium solubility values such as composition of aqueous buffer have been examined. The Henderson-Hasselbalch (HH relationship has been used to predict the pH-dependent solubility profiles of chosen drugs at two temperatures. For this purpose the pKa values of the investigated drugs have been determined with Bates-Schwarzenbach spectrophotometric method at temperature 310.1 K. At temperature 298.1K these values were reported earlier. Similar values of pKa were obtained from the solubility measurements.

  20. The Sacramento Dependency Drug Court: development and outcomes.

    Science.gov (United States)

    Boles, Sharon M; Young, Nancy K; Moore, Toni; DiPirro-Beard, Sharon

    2007-05-01

    Dependency Drug Courts (DDCs) are a growing method of addressing the functional status and reunification success of families involved in child welfare and affected by substance use disorders. Despite widespread interest in DDCs, few evaluations have appeared in the literature to help inform the discussion about their effectiveness. This article provides a description of various types of DDCs and reports 24-month reunification rates from the Sacramento DDC. Results indicated that DDC participants had higher rates of treatment participation than did comparison participants. In addition, at 24 months, 42% of the DDC children had reunified versus 27.2% of the comparison children. There were no differences in treatment completion or child reunification rates by parent's primary drug problem. Rates of recidivism were extremely low for both the DDC and comparison groups and did not differ significantly. The results of the present study are encouraging and suggest that rigorous, controlled studies are merited to further evaluate the effectiveness of DDCs.

  1. Emerging drugs for the treatment of tobacco dependence: 2014 update.

    Science.gov (United States)

    Elrashidi, Muhamad Y; Ebbert, Jon O

    2014-06-01

    Tobacco dependence remains a global epidemic and the largest preventable cause of morbidity and mortality around the world. Smoking cessation has benefits at all ages but remains challenging for several reasons, among which are the complexities of nicotine addiction and limitations of available pharmacotherapies. This review summarizes current and emerging pharmacotherapies for the treatment of tobacco dependence, including first- and second-line recommended agents. Medications with alternative primary indications that have been investigated as potential treatments for tobacco dependence are also discussed. Articles reviewed were obtained through searches of PubMed, Ovid MEDLINE, ClinicalTrials.gov and the Pharmaprojects database. Current evidence suggests that the two most effective pharmacotherapies to treat tobacco dependence are varenicline and combination nicotine replacement therapy. Alternative agents investigated demonstrate mixed rates of success in achieving long-term abstinence from smoking. No single pharmacotherapy will serve as a universally successful treatment given the complex underpinnings of tobacco dependence and individuality of smokers. The ultimate goal of tobacco research with respect to pharmacotherapeutic development continues to be providing clinicians with an armamentarium of drugs to choose from allowing for tailoring of treatment for smokers.

  2. [Psychiatric disorders induced by drug dependence other than alcohol].

    Science.gov (United States)

    Lejoyeux, M; Mourad, I; Ades, J

    2000-01-01

    Most of psychoactive substances abuse or dependence disorders are associated to another psychiatric disorders. Depression, anxiety and psychotic disorders are the more frequent comorbid disorders. Psychiatric comorbidity is induced by acute consumption of psychoactive agents, chronic consumption or withdrawal. Psychiatric disorders are more frequent when patient are assessed immediately after the withdrawal. Main biological factors implicated in the pathophysiology of psychiatric disorders associated to dependence disorders are: increase in norepinephrine activity, during withdrawal, activation of locus coeruleus, kinding induced by repeated withdrawals. Psychotic disorders in opiate dependent patients can be induced by withdrawals. These psychotic disorders are more often described after methadone discontinuation. Consumption of cocaine can provocate paranoid delusions. Phenylcyclidine provocates sensorial distortion or delusive disorders resembling schizophrenia. Flash backs, following withdrawal realized brief and transient psychotic disorders. They can occur up to one year after the end of the intoxication. The occurrence of depression in dependent patients is frequent. Depressed patients are at risk for suicide. Retrospective studies showed that near of 40% of the subjects died from suicide have presented alcohol or drug abuse or dependence. Withdrawal from opiates provocates depression. Clinical picture included apathy, blunting of the affects, sadness and loss of interest. Cocaine consumption provocates manic-like disinhibition at the beginning of the intoxication. Long term consumption and withdrawal increase the risk of depression.

  3. [Drug dependence test on a cerebral insufficiency improver, aniracetam].

    Science.gov (United States)

    Kuwahara, A; Kubota, A; Hakkei, M; Nakamura, K

    1987-01-01

    Aniracetam, 1-p-anisoyl-2-pyrrolidinone, is known to be a nootropic or cognitive activator. Aniracetam protects against memory and learning deficits without causing effects on motor function and the autonomic nervous system. A drug dependence study on aniracetam utilizing the intragastric route of administration was performed in male cynomolgus monkeys. The behavioral observation test after acute administration revealed that aniracetam at the dose of 25-400 mg/kg did not change the gross behavior. In the self-administration initiation test, animals were exposed to two or three unit doses of aniracetam and references for a total available period of 7 weeks. Aniracetam at the dose of 25, 50 and 75 mg/kg/injection did not initiate self-administration in the respective group of 4, 4 and 2 animals. In the study with d-methamphetamine hydrochloride at the dose of 0.1 mg/kg/injection, 1 out of 4 animals started to consistently self-administer the drug. Self-administration of cocaine hydrochloride at the dose of 10 mg/kg/injection was confirmed in 3 out of 5 animals, and these 3 animals died from overdosing later. In the physical dependence direct induction test, animals received aniracetam (50 mg/kg) and sodium pentobarbital (25 mg/kg: the dose inducing intermediate CNS depression) intragastrically twice a day for 31 consecutive days. Abrupt withdrawal of aniracetam did not elicit abstinent signs (including changes in appetite and body weight) in all 6 animals, whereas withdrawal of pentobarbital produced typical abstinent behavioral signs and decreases in appetite and body weight. In conclusion, aniracetam was confirmed to develop neither physical dependence nor psychic dependence in cynomolgus monkeys.

  4. "War on drugs" continues in United States under new leadership.

    OpenAIRE

    Gorman, D M

    1993-01-01

    Criticism of the "war on drugs" pursued under Republican administrations has grown in the United States. With the election of Bill Clinton many experts expected a shift from law enforcement policies to an approach favouring treatment and prevention. The budget announced in April, however, revealed no such shift in allocation of resources. Although the war on drugs has apparently failed to reduce the supply of cheap heroin and cocaine to the United States, the prevention strategy favoured by i...

  5. Alcohol and drug misuse, abuse, and dependence in women veterans.

    Science.gov (United States)

    Hoggatt, Katherine J; Jamison, Andrea L; Lehavot, Keren; Cucciare, Michael A; Timko, Christine; Simpson, Tracy L

    2015-01-01

    We conducted a systematic literature review on substance misuse, abuse, and dependence in women veterans, including National Guard/reserve members. We identified 837 articles published between 1980 and 2013. Of 56 included studies, 32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol use not meeting diagnostic criteria for abuse or dependence, and 33 reported rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among Veterans Health Administration (VA) health-care system outpatients, rates ranged from 3% to 16% for substance use disorder. Studies comparing women veterans and civilians reported no clear differences in binge or heavy drinking. Substance misuse rates were generally lower among women veterans than men veterans. Substance misuse was associated with higher rates of trauma, psychiatric and medical conditions, and increased mortality and suicide rates. Most studies included only VA patients, and many used only VA medical record data; therefore, the reported substance misuse rates likely do not reflect true prevalence. Rates also varied by assessment method, source of data, and the subgroups studied. Further efforts to develop epidemiologically valid prevalence estimates are needed to capture the true health burden of substance misuse in women veterans, particularly those not using VA care. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

    Science.gov (United States)

    Pérez-Mañá, Clara; Castells, Xavier; Torrens, Marta; Capellà, Dolors; Farre, Magi

    2013-09-02

    Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy. To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied. Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature. All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting. We used standard methodological procedures expected by The Cochrane Collaboration. Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI

  7. [2 days of drug dependence consultation in Portugal].

    Science.gov (United States)

    da Costa, N F

    1993-11-01

    This paper reports the results of a survey of all State outpatient clinics for drug addiction in Portugal. Two consecutive days of consultations in November 1992 were considered. The Health Ministry's SPTT--Service for Drug Addiction Prevention and Treatment--coordinates the activity of all the centres and promoted the inquiry. The main objective was to simultaneously evaluate the state of the population under treatment in what concerns the therapeutic methods used, their clinical costs and efficacy. This methodology may allow us to draw an accurate portrait of the Portuguese drug addiction public health program. We received 535 answers which we estimate to be two thirds of the consultations. Heroin abuse is the main problem in 91.3% of all cases plus 3.9% that associate heroin and cocaine abuse. Cannabis comes next with 2.1%, alcohol abuse with 0.8% and benzodiazepines with 0.5%. In what concerns the clinical results, 60% were abstinent: 15.1% were abstinent for longer than six months, 9.9% for longer than three months but less than six months, 19.8% were abstinent for less than that but longer than a month and 14.5% for longer than a week but less than a month. The main therapeutic approaches were psychotherapeutic in 54.1%, psychopharmacologic in 42.1% and socio-therapeutic in 2.3% of the cases. The author presents further data and discusses the results and their clinical implications.

  8. Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle.

    Science.gov (United States)

    Hossain, Kazi Jahangir; Kamal, Md Mustafa; Ahsan, Monira; Islam, S K Nazrul

    2007-04-08

    Use of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18-45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry. Results showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels. Illicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations.

  9. Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

    Directory of Open Access Journals (Sweden)

    Azita Chehri

    2014-02-01

    Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

  10. [The Nature and Issues of Drug Addiction Treatment under Constraint].

    Science.gov (United States)

    Quirion, Bastien

    2014-01-01

    This article is exploring different forms of constraint that are exerted in the field of drug addiction treatment. The objective of this article is to establish benchmarks and to stimulate reflection about the ethical and clinical implications of those constraints in the field of drug addiction treatment. This article is presenting a critical review of different forms of constraint that can be exerted in Canada in regard to the treatment of drug addiction. In the first section of the article, a definition of therapeutic intervention is proposed, that includes the dimension of power, which justifies the importance of considering the coercive aspects of treatment. The second section, which represents the core section of the paper, is devoted to the presentation of different levels of constraint that can be distinguished in regard to drug addicts who are under treatment. Three levels of constraint are exposed: judicial constraint, institutional constraint and relational constraint. The coercive aspect of treatment can then be recognized as a combination of all tree levels of constraint. Judicial constraint refers to any form of constraint in which the court or the judge is imposing or recommending treatment. This particular level of constraint can take different forms, such as therapeutic remands, conditions of a probation order, conditions of a conditional sentence of imprisonment, and coercive treatment such as the ones provided through drug courts. Institutional constraint refers to any form of constraint exerted within any institutional setting, such as correctional facilities and programs offered in community. Correctional facilities being limited by their own specific mission, it might have a major impact on the way the objectives of treatment are defined. Those limitations can then be considered as a form of constraint, in which drug users don't have much space to express their personal needs. Finally, relational constraint refers to any form of constraint in

  11. A flexible model for actuarial risks under dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim; Kallenberg, W.C.M.; Lukocius, V.

    Methods for computing risk measures, such as stop-loss premiums, tacitly assume independence of the underlying individual risks. This can lead to huge errors even when only small dependencies occur. In the present paper, a general model is developed which covers what happens in practice in a

  12. Time-dependent drug-drug interaction alerts in care provider order entry: software may inhibit medication error reductions.

    Science.gov (United States)

    van der Sijs, Heleen; Lammers, Laureen; van den Tweel, Annemieke; Aarts, Jos; Berg, Marc; Vulto, Arnold; van Gelder, Teun

    2009-01-01

    Time-dependent drug-drug interactions (TDDIs) are drug combinations that result in a decreased drug effect due to coadministration of a second drug. Such interactions can be prevented by separately administering the drugs. This study attempted to reduce drug administration errors due to overridden TDDIs in a care provider order entry (CPOE) system. In four periods divided over two studies, logged TDDIs were investigated by reviewing the time intervals prescribed in the CPOE and recorded on the patient chart. The first study showed significant drug administration error reduction from 56.4 to 36.2% (p0.05). Despite interventions, drug administration errors still occurred in more than one third of cases and prescribing errors in 79-87%. Probably the low alert specificity, the unclear alert information content, and the inability of the software to support safe and efficient TDDI alert handling all diminished correct prescribing, and consequently, insufficiently reduced drug administration errors.

  13. Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who inject drugs.

    Science.gov (United States)

    Smirnov, Andrew; Kemp, Robert; Ward, James; Henderson, Suzanna; Williams, Sidney; Dev, Abhilash; Najman, Jake M

    2016-09-01

    Despite over-representation of Indigenous Australians in sentinel studies of injecting drug use, little is known about relevant patterns of drug use and dependence. This study compares drug dependence and possible contributing factors in Indigenous and non-Indigenous Australians who inject drugs. Respondent-driven sampling was used in major cities and 'peer recruitment' in regional towns of Queensland to obtain a community sample of Indigenous (n = 282) and non-Indigenous (n = 267) injectors. Data are cross sectional. Multinomial models were developed for each group to examine types of dependence on injected drugs (no dependence, methamphetamine-dependent only, opioid-dependent only, dependent on methamphetamine and opioids). Around one-fifth of Indigenous and non-Indigenous injectors were dependent on both methamphetamine and opioids in the previous 12 months. Psychological distress was associated with dual dependence on these drugs for Indigenous [adjusted relative risk (ARR) 4.86, 95% confidence interval (CI) 2.08-11.34] and non-Indigenous (ARR 4.14, 95% CI 1.59-10.78) participants. Unemployment (ARR 8.98, 95% CI 2.25-35.82) and repeated (> once) incarceration as an adult (ARR 3.78, 95% CI 1.43-9.97) were associated with dual dependence for Indigenous participants only. Indigenous participants had high rates of alcohol dependence, except for those dependent on opioids only. The drug dependence patterns of Indigenous and non-Indigenous people who inject drugs were similar, including the proportions dependent on both methamphetamine and opioids. However, for Indigenous injectors, there was a stronger association between drug dependence and contextual factors such as unemployment and incarceration. Expansion of treatment options and community-level programs may be required. [Smirnov A, Kemp R, Ward J, Henderson S, Williams S, Dev A, Najman J M. Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who

  14. Cocaine Allergy in Drug-Dependent Patients and Allergic People.

    Science.gov (United States)

    Armentia, Alicia; Martín-Armentia, Blanca; Martín-Armentia, Sara; Ruiz-Muñoz, Pedro; Quesada, Jorge Martínez; Postigo, Idoia; Conde, Rosa; González-Sagrado, Manuel; Pineda, Fernando; Castillo, Miriam; Palacios, Ricardo; Tejedor, Jesús

    Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. [Design and implementation of virtual reality software with psychological treatment for drug-dependent patients].

    Science.gov (United States)

    Yang, Bo; Zhao, Xu; Ou, Yalin; Zhang, Jingyu; Li, Qing; Liu, Zhihong

    2012-12-01

    High relapse rate of drug-dependent patients is a serious problem in the current situation. The present article describes how to design and implement virtual reality technology for drug-dependent patients with psychological treatment, with the aim at the addiction withdrawal. The software was developed based on open-source game engine for 2D models. The form of a game simulates the actual style in the day-to-day living environment of drug-dependent patients and the temptation of using drugs. The software helps the patients deal with different scenarios and different event handling, cause their own thinking, and response to the temptation from high-risk environment and from other drug-dependent patients. The function of the software is close to the real life of drug-dependent patients, and has a prospect to become a new treatment to reduce the relapse rate of drug-dependence.

  16. [Drug Dependence and Cytotoxicity of Law-evading Drugs: Their Identities Explored from Basic Research].

    Science.gov (United States)

    Funada, Masahiko

    2016-01-01

      Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

  17. Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder in Children of Drug Dependent Parents

    OpenAIRE

    Parvaresh, Nooshin; Ziaaddini, Hassan; Kheradmand, Ali; Bayati, Hamidreza

    2010-01-01

    Background Attention deficit hyperactivity disorder and conduct disorder are amongrelatively prevalent disorders during childhood and adolescence.Considering the negative impact of the parents' drug dependency andbipolar disorder, the present study aimed to determine the prevalence ofADHD and conduct disorder in children of drug-dependent and bipolar parents. Methods In this case-control study, the case group included two groups ofpatients with drug dependency and bipolar disorder hospitalize...

  18. Pricing of path dependent derivatives with discretely monitored underlying assets

    Science.gov (United States)

    Choi, Hyomin

    This dissertation presents two different approaches to path dependent option pricing with discrete sampling. Provided the underlying asset of a path dependent derivative contract follows an affine process, we use the forward characteristic method to evaluate its fair price. Our study shows that the valuation method is numerically accessible as long as the contract payoff is a linear combination of log return of its underlying asset price. We compute various examples of such contracts and give contract-tailored formulas that we use in these examples. In the second part, we consider variance options under stochastic volatility model. We analyze the difference between variance option prices with discrete and continuous sampling as a function of N, the number of observations made in the former. We find the series expansion of the difference with respect to 1/N and find its leading term. By adding this leading term to the value of continuously sampled variance option, we obtain a simple and well-understood approximation of discretely sample variance option price.

  19. Studying the factors in dependency to substances changing the mood and behavior and effective methods in drug addiction counseling

    Directory of Open Access Journals (Sweden)

    2004-05-01

    Full Text Available Addicts to alcohol and other substances changing the mood and behavior attempt to stop their addiction and avoid its relapse because they suffer mental and physical problems, they are under the pressure of family members, employer and other individuals who influence over their life as well as negative effects of drug addiction on their performance in family, work and social relations. Since drug addicts experience physical pain when they are not using drugs, they refer, at first, to physicians and then to psychiatrists. Although emerging and applying non-medical and non-pharmaceutical approaches models is not too old, arising various addictive drugs and increasing the number of drug addicts as well as individual/social destructive consequences of drug addiction have caused that psychiatrists, psychologists and social workers to represent various non-pharmaceutical theories, models, methods and guidelines based on the conditions of their clients and their clinical experiences. The present article attempts to identify the reasons of drug addiction tendency, consumption patterns, models, theories of addiction to substances changing the mood and behavior, various methods of drug treatment, effective methods in drug addiction counseling and non-medical and non-pharmaceutical methods to give up drug addiction by using recent research findings. On this basis, the most effective methods to help those who suffer from alcohol and other drugs abuse and dependency are studied.

  20. Stigmatization of people with drug dependence in China: a community-based study in Hunan province.

    Science.gov (United States)

    Luo, Tao; Wang, Jing; Li, Yanhua; Wang, Xuyi; Tan, Linxiang; Deng, Qijian; Thakoor, Jaya Prishni Devi; Hao, Wei

    2014-01-01

    Drug abuse remains a serious problem in China, and has become a major threat to public health and social security. Since the issuance and enforcement of the new Anti-Drug law in 2008, the community has become the primary site for drug rehabilitation. However, the attitudes of members in community toward the people with drug use disorders are unclear. A random sample of household respondents was studied in two communities in Hunan province in China. A total of 848 individuals participated (response rate 83.7%). Respondents initially were asked a set of questions about their knowledge about dug dependence, and then were randomly assigned to 1 of 4 vignette conditions. Three vignettes described different type of drug dependence meeting diagnostic criteria, and the fourth depicted a "normal person." Poor knowledge of drug dependence was common. Negative attitudes towards drug dependent people were widespread. Most respondents believed that drug dependence was caused by the person's own weak will (82.0%) and own hedonistic lifestyle (81.3%), and should be punished as illegal behavior (80.4%). The vast majority labeled the person with drug dependence as an addict, rated them as having undesirable characteristics, and expressed a strong desire for social distance. There were few socio-demographic predictors of both poor knowledge and negative attitudes. A community-based rehabilitation program in China should take into account the widespread stigmatization of people with drug dependence. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Physical damage due to drug dependence : ZonMw study

    NARCIS (Netherlands)

    van Amsterdam JGC; Pennings EJM; Brunt TM; van den Brink W; GBO; vgc

    2012-01-01

    Overmatig gebruik van alcohol, tabak en drugs veroorzaakt op termijn lichamelijke gezondheidsschade. Roken verhoogt het risico op longkanker en overmatig alcoholgebruik is geassocieerd met levercirrose en tumoren in de mondholte, slokdarm en de lever. De medische behandeling daarvan brengt kosten

  2. Size-dependent structure of silver nanoparticles under high pressure

    Energy Technology Data Exchange (ETDEWEB)

    Koski, Kristie Jo [Univ. of California, Berkeley, CA (United States)

    2008-12-31

    Silver noble metal nanoparticles that are<10 nm often possess multiply twinned grains allowing them to adopt shapes and atomic structures not observed in bulk materials. The properties exhibited by particles with multiply twinned polycrystalline structures are often far different from those of single-crystalline particles and from the bulk. I will present experimental evidence that silver nanoparticles<10 nm undergo a reversible structural transformation under hydrostatic pressures up to 10 GPa. Results for nanoparticles in the intermediate size range of 5 to 10 nm suggest a reversible linear pressure-dependent rhombohedral distortion which has not been previously observed in bulk silver. I propose a mechanism for this transitiion that considers the bond-length distribution in idealized multiply twinned icosahedral particles. Results for nanoparticles of 3.9 nm suggest a reversible linear pressure-dependent orthorhombic distortion. This distortion is interpreted in the context of idealized decahedral particles. In addition, given these size-dependent measurements of silver nanoparticle compression with pressure, we have constructed a pressure calibration curve. Encapsulating these silver nanoparticles in hollow metal oxide nanospheres then allows us to measure the pressure inside a nanoshell using x-ray diffraction. We demonstrate the measurement of pressure gradients across nanoshells and show that these nanoshells have maximum resolved shear strengths on the order of 500 MPa to IGPa.

  3. The Interactive Seminar: An Educational Approach for Voluntary HIV Testing in a Drug Dependence Treatment Unit.

    Science.gov (United States)

    Sedhom, Laila; And Others

    1994-01-01

    A survey of 118 male patients in a drug dependence treatment unit before and after an interactive seminar with a nonjudgmental professional showed that seminar participants, especially intravenous drug users, had higher rates of voluntary HIV testing than nonparticipants. Drug users who completed detoxification and attended the seminar also had…

  4. Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

    DEFF Research Database (Denmark)

    Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

    2012-01-01

    Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

  5. 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).

  6. 33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

  7. 33 CFR 95.030 - Evidence of under the influence of alcohol or a dangerous drug.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or a dangerous drug. 95.030 Section 95.030 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.030 Evidence of under the influence of alcohol or a dangerous drug. Acceptable evidence of when a vessel operator is under the influence of alcohol or a dangerous drug includes...

  8. Brain Phosphorus Magnetic Resonance Spectroscopy Imaging of Sleep Homeostasis and Restoration in Drug Dependence

    OpenAIRE

    George H. Trksak; J. Eric Jensen; Perry F. Renshaw; Scott E. Lukas

    2007-01-01

    Numerous reports have documented a high occurrence of sleep difficulties in drug-dependent populations, prompting researchers to characterize sleep profiles and physiology in drug abusing populations. This mini-review examines studies indicating that drug-dependent populations exhibit alterations in sleep homeostatic and restoration processes in response to sleep deprivation. Sleep deprivation is a principal sleep research tool that results in marked physiological challenge, which provides a ...

  9. Drug ratio-dependent antagonism: a new category of multidrug resistance and strategies for its circumvention.

    Science.gov (United States)

    Harasym, Troy O; Liboiron, Barry D; Mayer, Lawrence D

    2010-01-01

    A newly identified form of multidrug resistance (MDR) in tumor cells is presented, pertaining to the commonly encountered resistance of cancer cells to anticancer drug combinations at discrete drug:drug ratios. In vitro studies have revealed that whether anticancer drug combinations interact synergistically or antagonistically can depend on the ratio of the combined agents. Failure to control drug ratios in vivo due to uncoordinated pharmacokinetics could therefore lead to drug resistance if tumor cells are exposed to antagonistic drug ratios. Consequently, the most efficacious drug combination may not occur at the typically employed maximum tolerated doses of the combined drugs if this leads to antagonistic ratios in vivo after administration and resistance to therapeutic effects of the drug combination. Our approach to systematically screen a wide range of drug ratios and concentrations and encapsulate the drug combination in a liposomal delivery vehicle at identified synergistic ratios represents a means to mitigate this drug ratio-dependent MDR mechanism. The in vivo efficacy of the improved agents (CombiPlex formulations) is demonstrated and contrasted with the decreased efficacy when drug combinations are exposed to tumor cells in vivo at antagonistic ratios.

  10. Exploring Neural Correlates of Different Dimensions in Drug Craving Self-Reports among Heroin Dependents

    OpenAIRE

    Hassani-Abharian, Peyman; Ganjgahi, Habib; Tabatabaei-Jafari, Hosein; Oghabian, Mohammad Ali; Mokri, Azarakhsh; Ekhtiari, Hamed

    2015-01-01

    Introduction: Drug craving could be described as a motivational state which drives drug dependents towards drug seeking and use. Different types of self-reports such as craving feeling, desire and intention, wanting and need, imagery of use, and negative affect have been attributed to this motivational state. By using subjective self-reports for different correlates of drug craving along with functional neuroimaging with cue exposure paradigm, we investigated the brain regions that could corr...

  11. Monolayer phosphorene under time-dependent magnetic field

    Science.gov (United States)

    Nascimento, J. P. G.; Aguiar, V.; Guedes, I.

    2018-02-01

    We obtain the exact wave function of a monolayer phosphorene under a low-intensity time-dependent magnetic field using the dynamical invariant method. We calculate the quantum-mechanical energy expectation value and the transition probability for a constant and an oscillatory magnetic field. For the former we observe that the Landau level energy varies linearly with the quantum numbers n and m and the magnetic field intensity B0. No transition takes place. For the latter, we observe that the energy oscillates in time, increasing linearly with the Landau level n and m and nonlinearly with the magnetic field. The (k , l) →(n , m) transitions take place only for l = m. We investigate the (0,0) →(n , 0) and (1 , l) and (2 , l) probability transitions.

  12. Testing for cubic smoothing splines under dependent data.

    Science.gov (United States)

    Nummi, Tapio; Pan, Jianxin; Siren, Tarja; Liu, Kun

    2011-09-01

    In most research on smoothing splines the focus has been on estimation, while inference, especially hypothesis testing, has received less attention. By defining design matrices for fixed and random effects and the structure of the covariance matrices of random errors in an appropriate way, the cubic smoothing spline admits a mixed model formulation, which places this nonparametric smoother firmly in a parametric setting. Thus nonlinear curves can be included with random effects and random coefficients. The smoothing parameter is the ratio of the random-coefficient and error variances and tests for linear regression reduce to tests for zero random-coefficient variances. We propose an exact F-test for the situation and investigate its performance in a real pine stem data set and by simulation experiments. Under certain conditions the suggested methods can also be applied when the data are dependent. © 2010, The International Biometric Society.

  13. A theory of drug tolerance and dependence II: the mathematical model.

    Science.gov (United States)

    Peper, Abraham

    2004-08-21

    The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behaviour to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The present paper discusses the mathematical model in terms of its design. The model is a nonlinear, learning feedback system, fully satisfying control theoretical principles. It accepts any form of the stimulus-the drug intake-and describes how the physiological processes involved affect the distribution of the drug through the body and the stability of the regulation loop. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes.

  14. Path dependence of lithium ion cells aging under storage conditions

    Science.gov (United States)

    Su, Laisuo; Zhang, Jianbo; Huang, Jun; Ge, Hao; Li, Zhe; Xie, Fengchao; Liaw, Bor Yann

    2016-05-01

    This work investigates path dependence of lithium ion cells that are stored under static and non-static conditions. In the static storage tests, the levels of temperature and state of charge (SOC) are kept constant. The results of 12 tests from a combination of three temperatures and four SOCs show that, as expected, the cell ages faster at higher temperature and higher SOC. However, the cell aging mode, while consistent for all the evaluated temperatures, is different at 95% SOC from that at lower SOCs. In the non-static storage tests, the levels of temperature and SOC vary with time during the test process. The effect of the sequence of stress levels on cell aging is studied statistically using the statistical method of analysis of variation (ANOVA). It is found that cell capacity fade is path independent of both SOC and temperature, while cell resistance increase is path dependent on SOC and path independent of temperature. Finally, rate-based empirical aging models are adopted to fit the cell aging in the static storage tests. The aging model for capacity fade is demonstrated to be applicable to the non-static tests with errors between -3% and +3% for all the tested conditions over 180 days.

  15. Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

    Science.gov (United States)

    McMillan, D E; Li, M

    2000-07-01

    Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent

  16. Memory for Drug Related Visual Stimuli in Young Adult, Cocaine Dependent Polydrug Users

    Science.gov (United States)

    Ray, Suchismita; Pandina, Robert; Bates, Marsha E.

    2015-01-01

    Background and Objectives Implicit (unconscious) and explicit (conscious) memory associations with drugs have been examined primarily using verbal cues. However, drug seeking, drug use behaviors, and relapse in chronic cocaine and other drug users are frequently triggered by viewing substance related visual cues in the environment. We thus examined implicit and explicit memory for drug picture cues to understand the relative extent to which conscious and unconscious memory facilitation of visual drug cues occurs during cocaine dependence. Methods Memory for drug related and neutral picture cues was assessed in 14 inpatient cocaine dependent polydrug users and a comparison group of 21 young adults with limited drug experience (N = 35). Participants completed picture cue exposure, free recall and recognition tasks to assess explicit memory, and a repetition priming task to assess implicit memory. Results Drug cues, compared to neutral cues were better explicitly recalled and implicitly primed, and especially so in the cocaine group. In contrast, neutral cues were better explicitly recognized, and especially in the control group. Conclusion Certain forms of explicit and implicit memory for drug cues were enhanced in cocaine users compared to controls when memory was tested a short time following cue exposure. Enhanced unconscious memory processing of drug cues in chronic cocaine users may be a behavioral manifestation of heightened drug cue salience that supports drug seeking and taking. There may be value in expanding intervention techniques to utilize cocaine users’ implicit memory system. PMID:24588421

  17. Memory for drug-related visual stimuli in young adult, cocaine-dependent polydrug users.

    Science.gov (United States)

    Ray, Suchismita; Pandina, Robert; Bates, Marsha E

    2014-03-01

    Implicit (unconscious) and explicit (conscious) memory associations with drugs have been examined primarily using verbal cues. However, drug seeking, drug use behaviors, and relapse in chronic cocaine and other drug users are frequently triggered by viewing substance-related visual cues in the environment. We thus examined implicit and explicit memory for drug picture cues to understand the relative extent to which conscious and unconscious memory facilitation of visual drug cues occurs during cocaine dependence. Memory for drug-related and neutral picture cues was assessed in 14 inpatient cocaine-dependent polydrug users and a comparison group of 21 young adults with limited drug experience (n = 35). Participants completed picture cue exposure, free recall and recognition tasks to assess explicit memory, and a repetition priming task to assess implicit memory. Drug cues, compared to neutral cues, were better explicitly recalled and implicitly primed, and especially so in the cocaine group. In contrast, neutral cues were better explicitly recognized, and especially in the control group. Certain forms of explicit and implicit memory for drug cues were enhanced in cocaine users compared to controls when memory was tested a short time following cue exposure. Enhanced unconscious memory processing of drug cues in chronic cocaine users may be a behavioral manifestation of heightened drug cue salience that supports drug seeking and taking. There may be value in expanding intervention techniques to utilize cocaine users' implicit memory system.

  18. Effect of paternal alcohol and drug dependence on offspring conduct disorder: gene-environment interplay.

    Science.gov (United States)

    Haber, Jon Randolph; Bucholz, Kathleen K; Jacob, Theodore; Grant, Julia D; Scherrer, Jeffrey F; Sartor, Carolyn E; Duncan, Alexis E; Heath, Andrew

    2010-09-01

    Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design. Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder. After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history. Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.

  19. Associations Between Family History of Substance Use, Childhood Trauma, and Age of First Drug Use in Persons With Methamphetamine Dependence.

    Science.gov (United States)

    Svingen, Leah; Dykstra, Rita E; Simpson, Jamie L; Jaffe, Anna E; Bevins, Rick A; Carlo, Gustavo; DiLillo, David; Grant, Kathleen M

    2016-01-01

    The current study examined the association among family history of substance use problems, childhood maltreatment, and age of first drug use in a sample of men and women seeking treatment for methamphetamine dependence. Various forms of childhood maltreatment were considered as mediators of the association between family history of substance use problems and age of first drug use. Participants (N = 99, 40% women, mean age 33) who were under treatment for methamphetamine dependence completed a baseline interview that obtained demographic information, past substance use by participants, history of drug/alcohol problems in their family of origin, and age at first use of any drug (excluding alcohol and tobacco). The Early Trauma Inventory Self-Report-Short Form was used to assess child maltreatment experiences before the age of 18. Family history of substance use problems and childhood physical (but not emotional or sexual) trauma significantly predicted age of first drug use. Further, childhood physical trauma mediated the association between family history of substance use problems and age of first drug use. These findings suggest that the experience of childhood physical abuse may be an important mechanism through which family history of substance use is associated with an earlier age of first drug use.

  20. 36 CFR 1004.23 - Operating under the influence of alcohol or drugs.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or drugs. 1004.23 Section 1004.23 Parks, Forests, and Public Property PRESIDIO TRUST VEHICLES AND TRAFFIC SAFETY § 1004.23 Operating under the influence of alcohol or drugs. (a) Operating or... alcohol, or a drug, or drugs, or any combination thereof, to a degree that renders the operator incapable...

  1. 36 CFR 4.23 - Operating under the influence of alcohol or drugs.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or drugs. 4.23 Section 4.23 Parks, Forests, and Public Property NATIONAL PARK SERVICE...) Under the influence of alcohol, or a drug, or drugs, or any combination thereof, to a degree that... entitled to use alcohol or another drug. (c) Tests. (1) At the request or direction of an authorized person...

  2. COMPUTER DYNAMICS SIMULATION OF DRUG DEPENDENCE THROUGH ARTIFICIAL NEURONAL NETWORK: PEDAGOGICAL AND CLINICAL IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    G. SANTOS

    2008-05-01

    Full Text Available To develop and to evaluate the efficiency of a software able to simulate a virtual patient at different stages of addition was the main goal and challenge of this work. We developed the software in Borland™ Delphi  5®  programming language. Techniques of artificial intelligence, neuronal networks and expert systems, were responsible for modeling the neurobiological structures and mechanisms of the interaction with the drugs used. Dynamical simulation and  hypermedia were designed to increase the software’s interactivity which was able to show graphical information from virtual instrumentation and from realistic functional magnetic resonance imaging display. Early, the program was designed to be used by undergraduate students to improve their neurophysiologic learn, based not only in an interaction of membrane receptors with drugs, but in such a large behavioral simulation. The experimental manipulation of the software was accomplished by: i creating a virtual patient from a normal mood to a behavioral addiction, increasing gradatively: alcohol, opiate or cocaine doses. ii designing an approach to treat the patient, to get total or partial remission of behavioral disorder by combining psychopharmacology and psychotherapy. Integration of dynamic simulation with hypermedia and artificial intelligence has been able to point out behavioral details as tolerance, sensitization and level of addiction to drugs of abuse and so on, turned into a potentially useful tool in the development of teaching activities on several ways, such as education as well clinical skills, in which it could assist patients, families and health care to improve and test their knowledge and skills about different faces supported by drugs dependency. Those features are currently under investigation.

  3. Similarity and Difference in Drug Addiction Process Between Heroin- and Methamphetamine-Dependent Users.

    Science.gov (United States)

    Wang, Ziyun; Li, Wei-Xiu; Zhi-Min, Liu

    2017-03-21

    This study aimed to compare the drug addiction process between Chinese heroin- and methamphetamine (MA)-dependent users via a modified 4-stage addiction model (experimentation, occasional use, regular use, and compulsive use). A descriptive study was conducted among 683 eligible participants. In the statistical analysis, we selected 340 heroin- and 295 MA-dependent users without illicit drug use prior to onset of heroin or MA use. The addiction process of heroin-dependent users was shorter than that of MA-dependent users, with shorter transitions from the onset of drug-use to the first drug craving (19.5 vs. 50.0 days), regular use (30.0 vs. 60.0 days), and compulsive use (50.0 vs. 85.0 days). However, no significant differences in the addiction process were observed in frequency of drug administration, except that heroin users reported more administrations of the drug (20.0 vs. 15.0) before progressing to the stage of compulsive drug use. A larger proportion of regular heroin users progressed to use illicit drugs recklessly than did MA users. Most heroin and MA users reported psychological dependence as their primary motivation for compulsive drug use, but more heroin users selected uncomfortable symptoms upon ceasing drug use as further reason to continue. Our results suggest that typical heroin and MA users may experience a similar four-stage addiction process, but MA users might undergo a longer addiction process (in days). More research is necessary to further explore factors influencing the drug addiction process.

  4. Chronic Disease and Chemical Dependency Treatment in Primary Care Patients With Problem Drug Use.

    Science.gov (United States)

    Maynard, Charles; Graves, Meredith; West, Imara I; Bumgardner, Kristin; Krupski, Antoinette; Roy-Byrne, Peter

    2015-01-01

    This article examines whether chronic disease is associated with chemical dependency treatment in primary care patients with problem drug use. Chronic disease was common in 781 disadvantaged individuals who had problem drug use and were seen in primary care clinics affiliated with a public safety-net hospital. Individuals had, on average, 5.4 chronic medical conditions, and overall 57% had low severity chronic disease. In the year following enrollment, 14% had chemical dependency treatment. Severity of chronic disease was not associated with chemical dependency treatment (p = .26). In summary, chronic disease neither hindered chemical dependency treatment, nor did it facilitate such treatment.

  5. Mode of Delivery in Drug-Dependent Pregnant Women: A Case Control Study.

    Science.gov (United States)

    Neves, Ana Raquel; Neves, Fabiane; Santos Silva, Isabel; Almeida, Maria do Céu; Monteiro, Pitorra

    2017-01-01

    Objective . To determine the contribution of drug use during pregnancy to the route of delivery. Methods . A case-control study was conducted at a hospital in Coimbra, Portugal, between 2001 and 2014. Drug-dependent pregnant women ( n = 236) were compared with a control group of low risk women ( n = 228) in terms of maternal characteristics, obstetric history, pregnancy complications, and labor details. Factors that influenced the mode of delivery were determined. Statistical analysis was performed with SPSS v. 23.0 (IBM Corp.). p values Drug-dependent women presented a lower rate of cesarean delivery (18.2 versus 28.9%, p = 0.006). After adjusting for the factors that were significantly related to the mode of delivery, drug dependency influenced the rate of cesarean section ( β = 0.567; 95% CI = 0.328-0.980). Within the drug-dependent group, the mode of delivery was significantly related to previous cesarean or vaginal delivery ( p = 0.008 and p drug, route of administration, or substitution maintenance therapy. Conclusions . The drug-dependent group presented a significantly higher rate of vaginal delivery. However, this was not associated with the behavioral factors analyzed. We hypothesize that other social and psychological factors might explain this difference.

  6. Mode of Delivery in Drug-Dependent Pregnant Women: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Ana Raquel Neves

    2017-01-01

    Full Text Available Objective. To determine the contribution of drug use during pregnancy to the route of delivery. Methods. A case-control study was conducted at a hospital in Coimbra, Portugal, between 2001 and 2014. Drug-dependent pregnant women (n=236 were compared with a control group of low risk women (n=228 in terms of maternal characteristics, obstetric history, pregnancy complications, and labor details. Factors that influenced the mode of delivery were determined. Statistical analysis was performed with SPSS v. 23.0 (IBM Corp.. p values < 0.05 were considered statistically significant. Results. Drug-dependent women presented a lower rate of cesarean delivery (18.2 versus 28.9%, p=0.006. After adjusting for the factors that were significantly related to the mode of delivery, drug dependency influenced the rate of cesarean section (β=0.567; 95% CI = 0.328–0.980. Within the drug-dependent group, the mode of delivery was significantly related to previous cesarean or vaginal delivery (p=0.008 and p<0.001, resp. and fetal presentation (p<0.001, but not with the type of drug, route of administration, or substitution maintenance therapy. Conclusions. The drug-dependent group presented a significantly higher rate of vaginal delivery. However, this was not associated with the behavioral factors analyzed. We hypothesize that other social and psychological factors might explain this difference.

  7. Attention deficit hyperactivity disorder (ADHD) and conduct disorder in children of drug dependent parents.

    Science.gov (United States)

    Parvaresh, Nooshin; Ziaaddini, Hassan; Kheradmand, Ali; Bayati, Hamidreza

    2010-01-01

    Attention deficit hyperactivity disorder and conduct disorder are amongrelatively prevalent disorders during childhood and adolescence.Considering the negative impact of the parents' drug dependency andbipolar disorder, the present study aimed to determine the prevalence ofADHD and conduct disorder in children of drug-dependent and bipolar parents. In this case-control study, the case group included two groups ofpatients with drug dependency and bipolar disorder hospitalized inShahid Beheshti hospital in Kerman who had 7 to 11-year-old children.The control group included healthy individuals without any drugdependency or other psychiatric disorders. Data were collected usingRutter scale Form A (parents' form) and a demographic questionnaire.Data were analyzed with ANOVA, Chi-square and Tamhane's post-hoc test. Rutter's abnormal scores were generally 7.11% in children of drugdependent parents, 14% in children of bipolar parents and 1.6% in childrenof healthy parents demonstrating no significant difference. The frequencyof conduct disorder in the bipolar and drug dependent group was higherthan the healthy group, but the difference was not significant. Thefrequency of ADHD was 8.9% in the drug dependency group and 1% inthe control group which shows a significant difference. Drug dependency in parents may be a leading factor to mentaldisorders such as ADHD and conduct disorder in children.

  8. Positive Selection on Loci Associated with Drug and Alcohol Dependence.

    Directory of Open Access Journals (Sweden)

    Brooke Sadler

    Full Text Available Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.

  9. Community Pharmacists’ Classification of Prescription Drugs into an Expanded Class of Nonprescription Drugs under the FDA's Proposed NSURE Initiative

    Directory of Open Access Journals (Sweden)

    Ruchitbhai M. Shah

    2017-10-01

    Full Text Available Objectives: There has been considerable debate over the last few decades about creating a third class of drugs that would not require a prescription or not be available freely over the counter, but require a pharmacist’s consultation upon purchase. These debates reignited again in 2012, when the Food and Drug Administration (FDA held a hearing about a third class of drugs positioned as an expanded nonprescription drug class under the FDAs Nonprescription Safe-Use Regulatory Expansion (NSURE Initiative. The objective of this study was to determine which prescription drugs community pharmacists believe are acceptable additions to an expanded definition of nonprescription drugs that would be available pending pharmacists’ consultation with a patient. Methods: This cross-sectional study was conducted using a self-report, web-based survey administered to a national panel of community pharmacists. The survey contained a list of 24 current “prescription-only” drugs which may be potential candidates for an expanded nonprescription drug class, based on criteria outlined by the FDA, and questions related to respondent demographic and practice characteristics. The respondents were asked to indicate whether a particular drug should be marketed as a prescription drug, nonprescription drug or as part of an expanded non-prescription drug class. Descriptive analyses were conducted to determine the drugs that community pharmacists believed would be suitable additions to an expanded non-prescription drug class under the NSURE initiative. Results: 462 completed surveys were received. Most respondents indicated that clopidogrel bisulfate (85.3% and zolpidem (86.6% should continue to be dispensed as prescription drugs. Atorvastatin, metformin, and sildenafil (among others were considered appropriate to be marketed as an expanded nonprescription drug, in other words, dispensed without a prescription but upon pharmacist consultation. Desloratadine (64.6% and

  10. Late Onset of Prescription Drug Abuse or Dependence Among Older Adults: Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Kathy Lay

    2007-12-01

    Full Text Available Prescription drug abuse and dependence is an increasing concern for older adults. This article describes issues specific to older adults with late onset abuse or dependence on prescription sedatives and/or opiates.The older adult with late onset should not be viewed as having the same issues as individuals who have a life pat- tern of drug and alcohol abuse/dependence.A chart review of older adults in a treatment program contrasts late onset prescription dependence clients (n=12 and early onset addiction clients (n=104 and outlines differences and similarities between the two samples. Social workers need to understand the specific and changing needs of older adults as they relate to assessment and treatment of drug abuse and dependence.

  11. Characterizing QALYs under a General Rank Dependent Utility Model

    NARCIS (Netherlands)

    H. Bleichrodt (Han); J. Quiggin (John)

    1997-01-01

    textabstractThis paper provides a characterization of QALYs, the most important outcome measure in medical decision making, in the context of a general rank dependent utility model. We show that both for chronic and for nonchronic health states the characterization of QALYs depends on intuitive

  12. Regulation of Multi-drug Resistance in hepatocellular carcinoma cells is TRPC6/Calcium Dependent

    Science.gov (United States)

    Wen, Liang; Liang, Chao; Chen, Enjiang; Chen, Wei; Liang, Feng; Zhi, Xiao; Wei, Tao; Xue, Fei; Li, Guogang; Yang, Qi; Gong, Weihua; Feng, Xinhua; Bai, Xueli; Liang, Tingbo

    2016-01-01

    Hepatocellular carcinoma (HCC) is notoriously refractory to chemotherapy because of its tendency to develop multi-drug resistance (MDR), whose various underlying mechanisms make it difficult to target. The calcium signalling pathway is associated with many cellular biological activities, and is also a critical player in cancer. However, its role in modulating tumour MDR remains unclear. In this study, stimulation by doxorubicin, hypoxia and ionizing radiation was used to induce MDR in HCC cells. A sustained aggregation of intracellular calcium was observed upon these stimuli, while inhibition of calcium signalling enhanced the cells’ sensitivity to various drugs by attenuating epithelial-mesenchymal transition (EMT), Hif1-α signalling and DNA damage repair. The effect of calcium signalling is mediated via transient receptor potential canonical 6 (TRPC6), a subtype of calcium-permeable channel. An in vivo xenograft model of HCC further confirmed that inhibiting TRPC6 enhanced the efficacy of doxorubicin. In addition, we deduced that STAT3 activation is a downstream signalling pathway in MDR. Collectively, this study demonstrated that the various mechanisms regulating MDR in HCC cells are calcium dependent through the TRPC6/calcium/STAT3 pathway. We propose that targeting TRPC6 in HCC may be a novel antineoplastic strategy, especially combined with chemotherapy. PMID:27011063

  13. Testing the Mean of a Normal Population Under Dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim

    1978-01-01

    Modifications of the $t$-test are considered which are robust under certain violations of the independence assumption. The additional number of observations these modified tests require in order to obtain under independence the same power as the $t$-test, is obtained asymptotically.

  14. Definition of drug resistance of Mycobacterium tuberculosis to antituberculosis drugs in patients with multidrugresistant tuberculosis and TB with extremely drug resistant depending on the case of the disease

    Directory of Open Access Journals (Sweden)

    Kryzhanovsky D.G.

    2014-11-01

    Full Text Available There was studied the profile of drug resistance to the main (I line and reserve (II line antituberculosis drugs in patients with MDR and XDR tuberculosis, depending of the case of the disease. According to the randomized retrospective research 200 patients with MDR and XDR tuberculosis, who received treatment in the clinic of hospital Municipal institution «Dnipropetrovsk rigional clinical association «Phthisiology» Dnipropetrovsk regional Council» during the period 2010 – 2012 were involved. Data about patients contained the data on a case of the disease and the results of the test of drug sensitivity to MBT. XDR – TB was revealed in 7.5% of patients with MDR tuberculosis. In patients with MDR tuberculosis as compared with patients with XDR tuberculosis «new cases» were diagnosed in 19.5% against 18.5% (p <0.05. In patients with MDR tuberculosis and with XDR tuberculosis resistance to the antituberculosis drug more commonly developed to S - 88.5%, E - 55% and Z - 24%. The presence of MDR-TB and XDR-TB prevails in patients, who underwent previous courses of treatment with anti-TB drugs in case history as compared with patients with «new cases» of treatment. The development of resistance to anti-TB drugs depends on the availability of these drugs in the previous treatment regimens.

  15. Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence.

    Science.gov (United States)

    Palmer, Rohan H C; Brick, Leslie; Nugent, Nicole R; Bidwell, L Cinnamon; McGeary, John E; Knopik, Valerie S; Keller, Matthew C

    2015-03-01

    Twin and family studies suggest that genetic influences are shared across substances of abuse. However, despite evidence of heritability, genome-wide association and candidate gene studies have indicated numerous markers of limited effects, suggesting that much of the heritability remains missing. We estimated (1) the aggregate effect of common single nucleotide polymorphisms (SNPs) on multiple indicators of comorbid drug problems that are typically employed across community and population-based samples, and (2) the genetic covariance across these measures. A total of 2596 unrelated subjects from the Study of Addiction: Genetics and Environment provided information on alcohol, tobacco, cocaine, cannabis and other illicit substance dependence. Phenotypic measures included: (1) a factor score based on DSM-IV drug dependence diagnoses (DD), (2) a factor score based on problem use (PU; i.e. 1+ DSM-IV symptoms) and (3) dependence vulnerability (DV; a ratio of DSM-IV symptoms to the number of substances used). Univariate and bivariate genome-wide complex trait analyses of this selected sample indicated that common SNPs explained 25-36% of the variance across measures, with DD and DV having the largest effects [h(2) SNP (standard error) = 0.36 (0.13) and 0.33 (0.13), respectively; PU = 0.25 (0.13)]. Genetic effects were shared across the three phenotypic measures of comorbid drug problems [rDD-PU = 0.92 (0.08), rDD-DV = 0.97 (0.08) and rPU-DV = 0.96 (0.07)]. At least 20% of the variance in the generalized vulnerability to substance dependence is attributable to common single nucleotide polymorphisms. The additive effect of common single nucleotide polymorphisms is shared across important indicators of comorbid drug problems. © 2014 Society for the Study of Addiction.

  16. Brain Phosphorus Magnetic Resonance Spectroscopy Imaging of Sleep Homeostasis and Restoration in Drug Dependence

    Directory of Open Access Journals (Sweden)

    George H. Trksak

    2007-01-01

    Full Text Available Numerous reports have documented a high occurrence of sleep difficulties in drug-dependent populations, prompting researchers to characterize sleep profiles and physiology in drug abusing populations. This mini-review examines studies indicating that drug-dependent populations exhibit alterations in sleep homeostatic and restoration processes in response to sleep deprivation. Sleep deprivation is a principal sleep research tool that results in marked physiological challenge, which provides a means to examine sleep homeostatic processes in response to extended wakefulness. A report from our laboratory demonstrated that following recovery sleep from sleep deprivation, brain high-energy phosphates particularly beta–nucleoside triphosphate (beta-NTP are markedly increased as measured with phosphorus magnetic resonance spectroscopy (MRS. A more recent study examined the effects of sleep deprivation in opiate-dependent methadone-maintained (MM subjects. The study demonstrated increases in brain beta-NTP following recovery sleep. Interestingly, these increases were of a markedly greater magnitude in MM subjects compared to control subjects. A similar study examined sleep deprivation in cocaine-dependent subjects demonstrating that cocaine-dependent subjects exhibit greater increases in brain beta-NTP following recovery sleep when compared to control subjects. The studies suggest that sleep deprivation in both MM subjects and cocaine-dependent subjects is characterized by greater changes in brain ATP levels than control subjects. Greater enhancements in brain ATP following recovery sleep may reflect a greater disruption to or impact of sleep deprivation in drug dependent subjects, whereby sleep restoration processes may be unable to properly regulate brain ATP and maintain brain high-energy equilibrium. These studies support the notion of a greater susceptibility to sleep loss in drug dependent populations. Additional sleep studies in drug abusing

  17. The impact of race, income, drug abuse and dependence on health insurance coverage among US adults.

    Science.gov (United States)

    Wang, Nianyang; Xie, Xin

    2017-06-01

    Little is known about the impact of drug abuse/dependence on health insurance coverage, especially by race groups and income levels. In this study, we examine the disparities in health insurance predictors and investigate the impact of drug use (alcohol abuse/dependence, nicotine dependence, and illicit drug abuse/dependence) on lack of insurance across different race and income groups. To perform the analysis, we used insurance data (8057 uninsured and 28,590 insured individual adults) from the National Surveys on Drug Use and Health (NSDUH 2011). To analyze the likelihood of being uninsured we performed weighted binomial logistic regression analyses. The results show that the overall prevalence of lacking insurance was 19.6 %. However, race differences in lack of insurance exist, especially for Hispanics who observe the highest probability of being uninsured (38.5 %). Furthermore, we observe that the lowest income level bracket (annual income <$20,000) is associated with the highest likelihood of being uninsured (37.3 %). As the result of this investigation, we observed the following relationship between drug use and lack of insurance: alcohol abuse/dependence and nicotine dependence tend to increase the risk of lack of insurance for African Americans and whites, respectively; illicit drug use increases such risk for whites; alcohol abuse/dependence increases the likelihood of lack of insurance for the group with incomes $20,000-$49,999, whereas nicotine dependence is associated with higher probability of lack of insurance for most income groups. These findings provide some useful insights for policy makers in making decisions regarding unmet health insurance coverage.

  18. Brief report: the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction

    Directory of Open Access Journals (Sweden)

    Roberta Biolcati

    2017-05-01

    Full Text Available The main aim of this study is to investigate the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction. From a clinical point of view Internet addiction, an excessive or poorly controlled preoccupation, urges, and/or behaviors regarding Internet use, lead to emotional and social problems in several life domains. Moreover, the increased prevalence of Internet addiction among adolescents and young adults is cause of concerns. Data was collected on 441 undergraduate students (285 female, aging from 18 to 36, using an assessment self-reporting set consisting of the Young’s Internet Addiction Test, the Leeds Dependence Questionnaire and the Dissociative Experience Scale. Results converging for the three psychological phenomena involved are interrelated, corroborating the hypothesis of the search for an altered state of consciousness as their common underlying mechanism. Findings show that the tendency to escape from reality, through dissociation and substance abuse, are risk factors for Internet addiction in youngsters. The implications of these results are discussed in a preventive and clinical perspective.

  19. Severity of club drug dependence and perceived need for treatment among a sample of adult club drug users in Shanghai, China.

    Science.gov (United States)

    Ding, Yingying; He, Na; Shoptaw, Steven; Gao, Meiyang; Detels, Roger

    2014-03-01

    Examine the severity of club drug dependence and perceived need for treatment, and further identify their determinants among a sample of club drug users in Shanghai, China. Two hundred and seventy-six club drug users were recruited using respondent-driven sampling (RDS). Severity of dependence on club drugs was measured using the Severity of Dependence Scale (SDS). 69.9% reported dependence on club drugs (i.e., SDS ≥ 4) and 36.6% reported severe dependence (i.e., SDS ≥ 6). One-eighth (12.7%) perceived need for drug treatment. Severe dependence on club drugs was more likely among those who reported recent use of ecstasy and those who had more depressive symptoms, but less likely among those reporting recent use of methamphetamine. Perceived need for treatment was more likely among those who lived with a spouse or boy/girlfriend, but less likely among those had prior drug treatment experience and more severe club drug dependence. Our findings suggest that educational activities should be implemented to raise public awareness about the powerful addictive properties of club drugs, along with efforts to reduce stigma towards drug abuse and psychiatric disorders. Programs to motivate drug users to seek treatment and encourage treatment linkage are urgently needed.

  20. Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

    Science.gov (United States)

    Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

    2018-04-15

    Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

  1. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...

  2. Initiation to the first drug use among substance-dependent persons in Iran.

    Science.gov (United States)

    Daneshmandan, Naeimeh; Narenjiha, Hooman; Tehrani, Kamal; Assari, Shervin; Khoddami-Vishteh, Hamid-Reza

    2011-01-01

    In the present study, we report the initiation to the first drug in a representative sample of drug dependents in Iran. This is a cross-sectional study with a sample size of 7,743. The participants were characterized as drug dependents according to the Diagnostic and Statistical Manual-Fourth Edition and were sampled from the medical centers, prisons, and streets of the capitals of 29 provinces in the Islamic Republic of Iran. The mean age at first drug use in the sample was 21.1 (6.5), which differed for various first drugs of abuse. Opium was the first drug of use among 46.4% of the sample, and cannabis was the first drug only among 23.5%. The most frequent place of initiation was at a friend's house (n = 2,476, 33.2%). The same-gender friend out of school (the highest rate) was the most frequent person who suggested the first use. A total of 43.5% of the participants started drug use with friends and 18.8% at a friend's party. Policymakers may benefit from considering the information provided here in designing programs with the purpose of prevention.

  3. Anti-Influenza Treatment: Drugs Currently Used and Under Development.

    Science.gov (United States)

    Amarelle, Luciano; Lecuona, Emilia; Sznajder, Jacob I

    2017-01-01

    Influenza is a very common contagious disease that carries significant morbidity and mortality. Treatment with antiviral drugs is available, which if administered early, can reduce the risk of severe complications. However, many virus types develop resistance to those drugs, leading to a notable loss of efficacy. There has been great interest in the development of new drugs to combat this disease. A wide range of drugs has shown anti-influenza activity, but they are not yet available for use in the clinic. Many of these target viral components, which others are aimed at elements in the host cell which participate in the viral cycle. Modulating host components is a strategy which minimizes the development of resistance, since host components are not subject to the genetic variability of the virus. The main disadvantage is the risk of treatment-related side effects. The aim of this review is to describe the main pharmacological agents currently available and new drugs in the pipeline with potential benefit in the treatment of influenza. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Graphical models for inference under outcome-dependent sampling

    DEFF Research Database (Denmark)

    Didelez, V; Kreiner, S; Keiding, N

    2010-01-01

    We consider situations where data have been collected such that the sampling depends on the outcome of interest and possibly further covariates, as for instance in case-control studies. Graphical models represent assumptions about the conditional independencies among the variables. By including...

  5. 76 FR 19998 - Supplemental Funding Under the Food and Drug Administration Pediatric Device Consortia Grant Program

    Science.gov (United States)

    2011-04-11

    ..., as part of the Food and Drug Administration Amendments Act of 2007 (FDAAA) legislation, Congress... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0012] Supplemental Funding Under the Food and Drug Administration Pediatric Device Consortia Grant Program AGENCY...

  6. 78 FR 21085 - Establishment of a Public Docket for Administrative Detention Under the Food and Drug...

    Science.gov (United States)

    2013-04-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No. FDA-2013-N-0365] Establishment of a Public Docket for Administrative Detention Under the Food and Drug Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of...

  7. [Drug Dependence and Toxicity of Law-Evading Drugs: Their Mechanisms Explored from Basic Research].

    Science.gov (United States)

    Funada, Masahiko

    2016-10-01

    The number of law-evading chemical substances that pose serious health risks to humans is increasing worldwide, including Japan and the Western world, and their abuse is becoming a serious social problem. Analysis of the chemical substances in these herbal products revealed the presence of synthetic cannabinoids. This review summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids as a group of chemical substances contained in these products. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids by using animals and cell cultures. In a place-conditioning study, the synthetic cannabinoids produced a significant conditioned-place preference. The rewarding effects of synthetic cannabinoids were completely suppressed by a cannabinoid CB1 receptor antagonist. Administration of synthetic cannabinoids to primary striatal culture caused cell death in a dose-dependent manner. Our findings show that the CB1 receptor might be involved in the expression of synthetic cannabinoid-induced rewarding effect. These behavioral data indicate that synthetic cannabinoids have a psychic-dependence liability. Furthermore, our data from primary striatal culture indicate that synthetic cannabinoids have strong neurotoxicity. These behavioral and neurochemical data indicate that synthetic cannabinoids might have strong adverse effects and a psychic-dependence liability.

  8. Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse

    OpenAIRE

    Roncero, Carlos; Abad, Alfonso C.; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-L?pez, Lara

    2017-01-01

    Background In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Objective Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Methods Systematic PubMed searches were conducted including December 2014, using the keywords: ?cocain...

  9. Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?

    Science.gov (United States)

    Staudacher, Alexander H; Brown, Michael P

    2017-12-05

    Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour-specific monoclonal antibodies (mAb) for the targeted delivery of highly potent cytotoxic drugs to the tumour site. The chemistry of the linker, which connects the drug to the mAb, determines how and when the drug is released from the mAb. This, as well as the chemistry of the drug, can dictate whether the drug can diffuse into surrounding cells, resulting in 'bystander killing'. Initially, any bystander killing mechanism of action of an ADC was understood to involve an essential sequence of steps beginning with surface antigen targeting, internalisation, intracellular linker cleavage, drug release, and diffusion of drug away from the targeted cell. However, recent studies indicate that, depending on the linker and drug combination, this mechanism may not be essential and ADCs can be cleaved extracellularly or via other mechanisms. In this minireview, we will examine the role of bystander killing by ADCs and explore the emerging evidence of how this can occur independently of internalisation.

  10. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  11. Withdrawal-like behavior in planarians is dependent on drug exposure duration.

    Science.gov (United States)

    Sacavage, Steve; Patel, Hiren; Zielinski, Mike; Acker, Jeneane; Phillips, Austin G; Raffa, Robert B; Rawls, Scott M

    2008-07-04

    Planarians display a concentration-related reduction in locomotor activity following their spontaneous withdrawal from opioids, cannabinoids, stimulants and benzodiazepines. This suggests that planarians display a withdrawal-like behavior that can be quantified as a reduction in locomotor activity. Because withdrawal-like behavior in previous studies has been quantified only following the cessation of a 60-min drug exposure, it is unclear whether the withdrawal response varies with drug exposure duration. Therefore, the goal of this study is to determine if the duration of drug exposure (0, 5, 15, 30, 45, 60min and 24h) to three different drugs - methamphetamine, cocaine and caffeine - affects the magnitude of withdrawal-like behavior (i.e., reduced locomotor activity) in planarians. Experiments revealed that methamphetamine (10microM) produced significant withdrawal-like behavior regardless of the exposure time (Pplanarians is dependent on both the duration and type of drug exposure, and that planarians do not display withdrawal to caffeine.

  12. Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

    Science.gov (United States)

    Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

    2017-09-01

    The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

  13. Time-dependent Drug–Drug Interaction Alerts in Care Provider Order Entry: Software May Inhibit Medication Error Reductions

    OpenAIRE

    van der Sijs, Heleen; Lammers, Laureen; van den Tweel, Annemieke; Aarts, Jos; Berg, Marc; Vulto, Arnold; van Gelder, Teun

    2009-01-01

    Time-dependent drug–drug interactions (TDDIs) are drug combinations that result in a decreased drug effect due to coadministration of a second drug. Such interactions can be prevented by separately administering the drugs. This study attempted to reduce drug administration errors due to overridden TDDIs in a care provider order entry (CPOE) system. In four periods divided over two studies, logged TDDIs were investigated by reviewing the time intervals prescribed in the CPOE and recorded on th...

  14. 77 FR 10753 - Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the...

    Science.gov (United States)

    2012-02-23

    ...] Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the Federal... industry entitled ``FDA Records Access Authority Under Sections 414 and 704 of the Federal Food, Drug...). This updated draft guidance is intended to provide individuals in the human and animal food industries...

  15. Cannabinoids: reward, dependence, and underlying neurochemical mechanisms--a review of recent preclinical data.

    Science.gov (United States)

    Tanda, Gianluigi; Goldberg, Steven R

    2003-09-01

    Starting with the discovery of an endogenous brain cannabinoid system with specific receptors and endogenous ligands, research in the cannabinoid field has accelerated dramatically over the last 15 years. Cannabis is the most used illicit psychotropic substance in the world but only recently have reliable preclinical models become available for investigating the rewarding and dependence-producing actions of its psychoactive constituent, delta9-tetrahydrocannabinol (THC). The goal of this review is to examine the various animal models currently available that are being used to facilitate our understanding of the rewarding and dependence-producing actions of cannabinoids, which are central to their abuse liability, and of the neurochemical mechanisms that may underlie these actions of cannabinoids. Recent demonstrations that strong and persistent intravenous self-administration behavior can be obtained in squirrel monkeys using a range of THC doses that are in agreement with the total intake and the single doses of THC normally self-administered by humans smoking marijuana cigarettes provides a reliable and direct tool for assessing the reinforcing effects of THC that are central to its abuse liability. In addition, recent demonstrations of persistent intravenous self-administration of synthetic cannabinoid CB1 receptor agonists by rats and mice and the development of genetically modified mice lacking specific cannabinoid receptors provide convenient rodent models for exploring underlying neurochemical mechanisms. Repeated demonstrations in rats that THC and synthetic CB1 agonists can induce conditioned place preferences or aversions, depending on details of dose and spacing, can reduce the threshold for intracranial self-stimulation behavior under certain conditions, and can serve as effective discriminative stimuli for operant behavior provide less direct, but more rapidly established, measures for investigating the rewarding effects of cannabinoids. Finally, there

  16. 38 CFR 17.80 - Alcohol and drug dependence or abuse treatment and rehabilitation in residential and...

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or abuse...

  17. Formation of drug nanocrystals under nanoconfinement afforded by liposomes

    DEFF Research Database (Denmark)

    Cipolla, D.; Wu, H.; Salentinig, Stefan

    2016-01-01

    Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonst...... physical means (e.g., freeze/thaw) is an attractive possibility, especially in highly regulated industries such as pharmaceuticals where qualitative and quantitative changes of composition would require extensive safety evaluations....

  18. Drugs currently under investigation for the treatment of invasive candidiasis.

    Science.gov (United States)

    McCarthy, Matthew W; Walsh, Thomas J

    2017-07-01

    The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

  19. Neurobiology of consummatory behavior: mechanisms underlying overeating and drug use.

    Science.gov (United States)

    Barson, Jessica R; Morganstern, Irene; Leibowitz, Sarah F

    2012-01-01

    Consummatory behavior is driven by both caloric and emotional need, and a wide variety of animal models have been useful in research on the systems that drive consumption of food and drugs. Models have included selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. This research has elucidated numerous brain areas and neurochemicals that drive consummatory behavior. Although energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate, or protein. The neurochemicals involved in controlling fat ingestion--galanin, enkephalin, orexin, melanin-concentrating hormone, and the endocannabinoids--show positive feedback with this macronutrient, as these peptides both increase fat intake and are further stimulated by its intake. This positive association offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by the neurochemical systems involved in fat intake, according to evidence that closely relates fat and ethanol consumption. Further understanding of the systems involved in consummatory behavior will enable the development of effective therapies for the treatment of both overeating and drug abuse.

  20. Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use

    Science.gov (United States)

    Barson, Jessica R.; Morganstern, Irene; Leibowitz, Sarah F.

    2013-01-01

    Consummatory behavior is driven not just by caloric need but also by emotional need. In the last several decades, a wide variety of models have been used to study the systems that drive food and drug intake. These include selective breeding for a specific trait, manipulation of gene expression, forced or voluntary exposure to a substance, and identification of biomarkers that predict which animals are prone to overconsuming specific substances. From this research, numerous brain areas and neurochemicals have been identified that drive consummatory behavior. While energy homeostasis is primarily mediated by the hypothalamus, reinforcement is more strongly mediated by nuclei outside of the hypothalamus, in mesocorticolimbic regions. Orexigenic neurochemicals that control food intake can provide a general signal for promoting caloric intake or a more specific signal for stimulating consumption of a particular macronutrient, fat, carbohydrate or protein. Those involved in controlling fat ingestion, including galanin, enkephalin, orexin, melanin-concentrating hormone and the endocannabinoids, show positive feedback with this macronutrient, with these peptides both increasing fat intake and being further stimulated by its intake. This positive relationship offers some explanation for why foods high in fat are so often overconsumed. Consumption of ethanol, a drug of abuse that also contains calories, is similarly driven by these neurochemical systems involved in fat intake, consistent with evidence closely relating fat and ethanol consumption. Further understanding of these systems involved in consummatory behavior will allow researchers to develop effective therapies for the treatment of overeating as well as drug abuse. PMID:23520598

  1. a Comparison Between Chemically Dependent Mothers and Drug-Free Mothers: Lifestyle during the Perinatal Period

    Science.gov (United States)

    Uskokovic, Lila Milica

    This study compared maternal lifestyle variables pertinent to the perinatal period in groups of chemically dependent mothers and drug-free mothers. Twenty-nine cocaine -abusing mothers were compared to 29 drug-free mothers carefully matched on age, race, education, and primipara versus multipara status. The drug history of each chemically dependent woman was explicitly documented. The chemically dependent group was subdivided into two groups, mothers who abused cocaine and those who abused cocaine with concomitant opiate use. Each of these two subgroups was compared to its respective matched drug-free control group. Finally, a comparison was made between the two drug subgroups. All subjects were interviewed within 48 hours after delivery using the following measures: State-Trait Anxiety Inventory (A-State), Center for Epidemiologic Studies - Depression Scale, The Self-Esteem Scale, Maternal Adjustment and Maternal Attitude Questionnaire, The Neonatal Perception Inventory, The Psychiatric Epidemiology Research Interview Life Events Scale, Maternal Social Support Index, and Short Marital Adjustment Test. A t-test analysis revealed significant differences (p state anxiety, depression, self-esteem, maternal adjustment and attitudes, and life events. An analysis of covariance indicated that life events was the only significant variable when the influence of all other variables was removed. Comparisons made between each drug subgroup and its respective matched control group showed similar results, except that those who abused opiates with cocaine did not differ from their controls on depression and maternal adjustment and attitudes. No significant differences were obtained in the drug subgroup comparisons. These results identify increased life events and specific negative affect states that clinical intervention programs should address to assure the best possible outcome for chemically dependent mothers and their infants.

  2. Political Journalism under Pressure - Between Autonomy and Dependence

    Directory of Open Access Journals (Sweden)

    Günther Pallaver

    2010-06-01

    Full Text Available Dieser Beitrag befasst sich mit der zunehmenden Tendenz politischer Eliten, auf die journalistische Berichterstattung und den politischen Journalismus Einfluss zu nehmen. Dabei wird gezeigt, inwieweit dadurch Handlungsspielräume im politischen Journalismus eingeschränkt werden. Untersucht werden insgesamt vier Länder, nämlich die USA, die Bundesrepublik Deutschland, Österreich und Italien. Beim diesem Vergleich stellt sich die Frage nach der Bedeutung struktureller Unterschiede angesichts der verschiedenen politischen Systeme in den untersuchten Ländern (z. B. präsidentielles vs. parlamentarische Systeme, parteien- vs. medienzentrierte Systeme. Abschließend geht es um Überlegungen zu unterschiedlichen privatrechtlich organisierten oder dualen Mediensystemen im Zusammenhang strategischer Einflussnahmen und Abwehrmaßnahmen. In this paper the proposition to be tested is whether the political elites’ attempt to exert influence on day-to-day news coverage and thus on political journalism is increasing and whether as a result political journalism’s autonomous leeway is continually diminishing. The countries examined are the United States, Germany, Austria and Italy. In this context the question whether there are structural differences due to the diverse political systems of the countries under consideration (presidential vs. parliamentary systems; systems centred more on parties vs. systems centred more on the media will also be investigated. Last but not least, the role of different media systems will be considered, too (media under private law, dual systems including the Italian version.

  3. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  4. Benzodiazepine Dependence among Young Adult Participants in the Club Scene Who Use Drugs.

    Science.gov (United States)

    Kurtz, Steven P; Buttram, Mance E; Surratt, Hilary L

    2017-01-01

    Young adults ages 18-29 report the highest rates of benzodiazepine (BZD) misuse in the United States. The majority of club drug users are also in this age group, and BZD misuse is prevalent among participants in club scenes. This article examines BZD dependence and its correlates among young adult participants in the electronic dance music (EDM) culture in Miami, Florida, who use drugs. Structured interviews were with men and women (N = 356) ages 18 to 29 who reported regular attendance at EDM venues and recent use of both club drugs and BZDs. Prevalences of BZD-related problems were 12.6% for BZD dependence, 21.1% BZD abuse, and 24.2% BZD abuse and/or dependence. In a multivariate logistic regression model, younger age (OR 0.85; 95% CI 0.76, 0.96), severe mental distress (OR 8.30; 95% CI 3.07, 22.49), daily marijuana use (OR 2.10; 95% CI 1.03, 4.27), and heavy opioid use (OR 2.33; 95% CI 1.12, 4.83) were associated with BZD dependence. BZD dependence was higher in this sample than in other populations described in the literature. The links between BZD dependence, overdose history, and heavy opioid misuse are especially worrisome among this young sample. Recommendations for intervention and research are discussed.

  5. Dependent Prior: An Application in Spinal Anaesthesia Drug Therapy on SBP in Cesarean patients.

    Directory of Open Access Journals (Sweden)

    Atanu Bhattacharjee

    2013-12-01

    Full Text Available Cesarean section is widely used operation procedure in the world. The regional anesthesia is preferred than general anesthesia. The risk of fetus is higher in general than in regional anesthesia. The drug treatment effect on regional anesthesia plays an important role to control the systolic blood pressure (SBP during the surgery. The goal of this work is to know the effective drug to control the SBP among cesarean anesthetic patients. The dependent prior with Bayesian approach is applied in the binary response data set. The secondary data in anesthesia has been applied to compare the two drug treatments, viz. (1 Phenylephrine and (2 Ephedrine, in cesarean patients with spinal anesthesia. In both drug groups the mean of SBP has been found controlled over the duration of the surgery. No rapid changes of SBP level among the patients are observed. At the end of study it is found that the means of SBP cesarean anesthetic patients are found higher in Phenylephrine group. The Bayesian dependent prior is found to offer effective tool for drug treatment effect comparison. The drug treatment effect Ephedrine is found to be more effective to control the SBP over the duration of surgery than Phenylephrine.

  6. "Too Far Gone": Dyslexia, Homelessness, and Pathways to Drug Use and Dependency

    Science.gov (United States)

    Macdonald, Stephen J.; Deacon, Lesley; Merchant, Jacqueline

    2016-01-01

    This study investigated the relationship between dyslexia, homelessness, and drug use and dependency based on data from the Multiple Exclusion Homelessness Across the United Kingdom Survey, a national survey of 443 respondents who had experienced some form of homelessness in the U.K. Of particular interest was a comparison of the various…

  7. Lack of information underlies women's perceptions of erectile dysfunction (ED) drugs in Japan.

    Science.gov (United States)

    Mita, Koji; Kakehashi, Masayuki; Hasegawa, Yasuhisa; Inoue, Yoji; Shigeta, Masanobu; Matsubara, Akio; Usui, Tsuguru

    2008-12-01

    Some Japanese women are known to have negative attitudes toward erectile dysfunction (ED) drugs, but the environment underlying these perceptions is unclear. To reveal the underlying environment that shapes women's perceptions of ED drugs in Japan. A web-based questionnaire was conducted through an Internet-based market research company. A total of 2,593 women in five age groups (20s, 30s, 40s, 50s, and 60s or older) were randomly invited to participate in this study, with an almost equal number in each age group. The questionnaire contained 30 items related to individual background and sexual information, concerns about the image of ED drugs, ED drug-related perceptions, and attitude toward sexual information media. The women's attitude and the independent predictors that affect their partner's use of ED drugs were clarified. Answers were obtained from 1,077 women, of whom 35.4% (n=381) had a negative image of ED drugs. Although 69.5% (n=749) agreed that a sexual relationship with a male partner was important, only 26.7% (n=288) agreed that this remained important if ED drugs were used. However, 56.7% (n=611) and 57.7% (n=621) of respondents, respectively, answered that they would allow their partner's use of ED drugs if they imagined that they understood the safety and effectiveness of ED drugs and that their quality of life was improved by their partner's use of the drugs. Lack of information about ED drugs was a significant predictor for acceptance of a partner's use of ED drugs among women with a negative image of ED drugs, since they were more likely to accept the use of these drugs if they were convinced about their safety and effectiveness or positive effect on quality of life. Lack of information about ED drugs may influence the perception of women in Japan regarding these drugs.

  8. Efficacy of an acquainted drug in the treatment of inflammatory low back pain: sulfasalazine under investigation

    Directory of Open Access Journals (Sweden)

    Moghimi J

    2016-09-01

    highest response to sulfasalazine was found, which was related to the underlying USpA. This study found that an adequate response to nonsteroidal anti-inflammatory drugs in patients with ILBP was potentially increased by adding sulfasalazine. Thus, the observed response rate was dependent on the nature of underlying spondyloarthropathy. Keywords: low back pain, sulfasalazine, nonsteroidal anti-inflammatory drugs

  9. Individuality and contextual influences on drug dependence: a 15-year Prospective longitudinal study of adolescents from Harlem.

    Science.gov (United States)

    Brook, Judith S; Lee, Jung Yeon; Brown, Elaine N; Finch, Stephen J; Brook, David W

    2012-01-01

    In this 15-year longitudinal study the authors investigated individual and contextual factors that predispose adolescents from a disadvantaged urban area to drug dependence in adulthood. Adolescents were recruited from schools serving East Harlem in New York City. Of the 838 participants followed to adulthood, 59% were women, 55% were African American, and 45% were Puerto Rican. Self-report data were obtained on externalizing and internalizing problems, substance use, and contextual influences across adolescence and young adulthood. Drug dependence was assessed in adulthood. Multivariate logistic regressions of drug dependence were performed on the whole sample and separately by gender. Each of the domains was associated with adult drug dependence. Although mean gender differences were found, most associations of risk factors with drug dependence did not vary significantly by gender. Treating externalizing and internalizing problems, reducing substance use, and providing coping skills for adverse contextual influences in adolescence and young adulthood may reduce the likelihood of becoming drug dependent in adulthood.

  10. Nonmedical Use of Antihistaminergic Anxiolytics and Other Prescription Drugs among Persons with Opioid Dependence.

    Science.gov (United States)

    Dahlman, Disa; Abrahamsson, Tove; Kral, Alex H; Hakansson, Anders

    2016-01-01

    Background . Nonmedical prescription drug use (NMPDU) is an increasing problem, insufficiently studied among people in opioid maintenance treatment (OMT). This study investigates the prevalence of and factors associated with NMPDU for drug classes insufficiently described in opioid-dependent populations, including antihistaminergic anxiolytics and central stimulants. Methods . Study participants were recruited at two OMT clinics in Malmo, Sweden, between October 2014 and December 2015 ( N = 73) and interviewed about their use, motivations for use, and acquisition and administration of prescription drugs. Results . The majority of the sample reported lifetime NMPDU: 60% for benzodiazepine-like hypnotics (z-drugs), 21% for pregabalin, 19% for stimulants, and 12%-15% for antihistaminergic anxiolytics. Lower age was associated with nonmedical benzodiazepine use (Adjusted Odds Ratio = 0.89; 95% Confidence Interval = 0.82-0.97). Illicit acquisition was reported by 61% of people using z-drugs, 46% of people using pregabalin, and 38% of people using prescription stimulants, but only by 6-10% of people using antihistaminergic anxiolytics. Conclusions . The substantial nonmedical use of pregabalin, z-drugs, and prescription stimulants found in this study suggests that clinicians should prescribe these drugs with great caution. Nonmedical use of antihistaminergic anxiolytics does not seem to be a clinical issue among people in OMT in a Swedish setting, but we propose future studies to monitor their use.

  11. Relationship between drug dreams, affect, and craving during treatment for substance dependence.

    Science.gov (United States)

    Tanguay, Hélène; Zadra, Antonio; Good, Daniel; Leri, Francesco

    2015-01-01

    To explore the relationship between occurrence of drug dreams (DDs) and daytime negative affect and drug craving during the course of a 5-week treatment program for substance dependence. Using the dream journal methodology, 86 participants reported occurrence of dreams, dream content, and ratings of affect and drug craving. The relationships between the experience of DD, dream content ("active" vs "passive"), and affect and craving were analyzed using mixed model methods. The experience of DD was associated with higher levels of negative affect (P < 0.001) and craving (P < 0.001). The occurrence of DD did not decrease significantly over the 5 weeks of the study. Cocaine/crack users reported a higher occurrence of DD (P < 0.05) than the other drug groups (opiates and alcohol), and DD involving "active" drug use was associated with larger (P < 0.05) changes in negative affect. These results are consistent with the hypothesis that DD can act as drug-conditioned stimuli to elevate negative affect and craving in abstaining individuals. Although correlational, such findings support the implementation of psychological and pharmacological interventions aimed at minimizing the impact of DD on individuals in recovery from drug addiction.

  12. Potent dried drug nanosuspensions for oral bioavailability enhancement of poorly soluble drugs with pH-dependent solubility.

    Science.gov (United States)

    Mou, Dongsheng; Chen, Huabing; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

    2011-07-15

    The objective of this study was to enhance the oral bioavailability of itraconazole (ITZ) with dried drug nanosuspensions. The feasibility of using poloxamer 407 or HPMC (50 cp) as stabilizers for preparing ITZ nanosuspensions by facile acid-base neutralization was investigated. Dried ITZ nanosuspensions were prepared by spray drying. The effect of matrix former on the dissolution rate of dried ITZ nanosuspensions was investigated. Results from dissolution test revealed that spray-dried ITZ nanosuspensions (ITZ:HPMC:mannitol 1:0.5:2, w/w) preserved the high dissolution rate from nanosuspensions. After oral administration in rats, the AUC(0-36) from dried ITZ nanosuspensions was 1.5-fold and 1.8-fold higher than the AUC(0-36) from sporanox pellets (commercial product) in the fed and fasted states, respectively (pnanosuspensions showed no difference between fed/fasted states, because this formulation could enhance the adsorption of ITZ in target site (small intestine) regardless of food intake. In addition, dried ITZ nanosuspensions showed a lower inter-individual variability in terms of bioavailability. Positive results demonstrate that dried drug nanosuspensions formulation prepared by acid-base neutralization combined with spray drying may be a promising method for enhancing the oral bioavailability of poorly soluble drugs with pH-dependent solubility. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Homeless drug users and information technology: a qualitative study with potential implications for recovery from drug dependence.

    Science.gov (United States)

    Neale, Joanne; Stevenson, Caral

    2014-09-01

    Having access to information and communication technologies (ICTs) is a prerequisite to meaningful participation in society. This paper seeks to: i. explore the engagement of homeless drug users (HDUs) with ICTs and ii. discuss the findings with reference to recovery from drug dependence. The study design was qualitative and longitudinal, involving data collected in 2012-13 via 52 semi-structured interviews with 30 homeless drug users (25 men; five women). Participants were recruited from 17 hostels in two English cities. Interview data were analyzed using Framework. HDUs had access to ICTs, used ICTs, and wanted to engage with them more. Experiences of digital exclusion were a function of participants' inability to afford ICTs, the relatively cheap and poor quality technology available to them, limited knowledge about ICTs, and lack of support in using them. That HDUs were often unable to take full advantage of technology because they had nobody to explain what their devices could do or to show them how they worked was ironic given that using ICTs to (re)establish and maintain relationships were functions of technology that HDUs particularly liked. The physical, human, cultural, and social capital of HDUs influenced their access to, and use of, ICTs. Equally, ICTs were themselves an important recovery resource. Services and others should endeavor to provide HDUs with easy access to good quality technology, as well as offers of support and education so that all individuals have the knowledge and confidence to make optimum use of the technology that is available to them.

  14. High Prognostic Specificity of Antisocial Personality Disorder in Patients with Drug Dependence

    DEFF Research Database (Denmark)

    Fridell, Mats; Hesse, Morten; Johnson, Eva

    2006-01-01

    personality disorder (ASPD) at intake was associated with incarceration, continuous drug use, dependence on welfare support, and fulfilling criteria of adult ASPD at follow-up. Regardless of ASPD status, a decline was seen in drug-related convictions, but subjects with ASPD were found to continue to commit......A sample of 125 consecutive patients from a Swedish detoxification unit were followed up at five years. Register data on criminal behavior were retrieved for 99% of all subjects, including those who were deceased at follow-up, and 76%of living subjects were interviewed. A diagnosis of antisocial...

  15. Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

    Science.gov (United States)

    Kutlu, Munir Gunes; Gould, Thomas J

    2016-10-01

    It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

  16. Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

    Science.gov (United States)

    Kutlu, Munir Gunes

    2016-01-01

    It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

  17. [Contributions of SGLT-2 and new drugs under investigation].

    Science.gov (United States)

    Mediavilla Bravo, J J

    2014-07-01

    DeFronzo spoke of the "ominous octet", in which he referred to the existence of distinct pathways and organs related to the physiopathology of type 2 diabetes mellitus (DM2). One of these key organs is the kidney, which plays an important role in regulating glucose metabolism through gluconeogenesis and through glomerular filtration and glucose reabsorption in the proximal convoluted tubules. Approximately 180 g of glucose are filtered to the renal tubule from the blood stream through the glomerulus. The filtrate is subsequently reabsorbed from the tubules to the peritubular capillaries through the action of sodium glucose cotransporters (SGLT). There are 2 main cotransporters in the kidney, SGLT1 and SGLT2, which reabsorb the glucose (10% and 90%, respectively) and return it to the blood. In persons with DM2, SGLT2 is increased, leading to greater renal absorption of glucose, which has adverse effects as it contributes to the maintenance of hyperglycemia. Selective pharmacological SGLT2 inhibition increases renal glucose excretion and secondarily reduces its plasma values. SGLT2 inhibitors act exclusively on the kidney, reduce glycosylated hemoglobin (HbA1c) by about 0.66%, decrease blood pressure, and induce a weight loss of approximately 1.8 kg. These drugs have a low risk of hypoglycemia but carry an increased risk of genitourinary infections. Several clinical trials have shown that dapagliflozin (10mg/day), the first SGLT2 inhibitor commercialized in Spain, produces a statistically significant reduction in HbA1c of 0.82-0.97%, both in monotherapy and in combination with metformin, glimepiride, pioglitazone, or insulin. Its use produces a weight loss of between 2 and 3 kg and reduces both systolic and diastolic blood pressure, while the risk of hypoglycemias is low. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

  18. Exploring Neural Correlates of Different Dimensions in Drug Craving Self-Reports among Heroin Dependents.

    Science.gov (United States)

    Hassani-Abharian, Peyman; Ganjgahi, Habib; Tabatabaei-Jafari, Hosein; Oghabian, Mohammad Ali; Mokri, Azarakhsh; Ekhtiari, Hamed

    2015-10-01

    Drug craving could be described as a motivational state which drives drug dependents towards drug seeking and use. Different types of self-reports such as craving feeling, desire and intention, wanting and need, imagery of use, and negative affect have been attributed to this motivational state. By using subjective self-reports for different correlates of drug craving along with functional neuroimaging with cue exposure paradigm, we investigated the brain regions that could correspond to different dimensions of subjective reports for heroin craving. A total of 25 crystalline-heroin smokers underwent functional magnetic resonance imaging (fMRI), while viewing heroin-related and neutral cues presented in a block-design task. During trial intervals, subjects verbally reported their subjective feeling of cue induced craving (CIC). After fMRI procedure, participants reported the intensity of their "need for drug use" and "drug use imagination" on a 0-100 visual analog scale (VAS). Afterwards, they completed positive and negative affect scale (PANAS) and desire for drug questionnaire (DDQ) with 3 components of "desire and intention to drug use," "negative reinforcement," and "loss of control." The study showed significant correlation between "subjective feeling of craving" and activation of the left and right anterior cingulate cortex, as well as right medial frontal gyrus. Furthermore, the "desire and intention to drug use" was correlated with activation of the left precentral gyrus, left superior frontal gyrus, and left middle frontal gyrus. Subjects also exhibited significant correlation between the "need for drug use" and activation of the right inferior temporal gyrus, right middle temporal gyrus, and right parahippocampal gyrus. Correlation between subjective report of "heroin use imagination" and activation of the cerebellar vermis was also observed. Another significant correlation was between the "negative affect" and activation of the left precuneus, right

  19. Overcoming barriers to community participation in drug dependence treatment: An ethnography approach

    Directory of Open Access Journals (Sweden)

    Bir Singh Chavan

    2017-01-01

    Full Text Available Introduction: Substance use and dependence has been a part of Indian society for centuries. However, abuse of more hazardous drugs including intravenous use, younger age of initiation, and high prevalence has made it a major public health issue. Community-based interventions for drug/alcohol use are often hindered by a lack of community participation, which is the result of stigma associated with drug/alcohol use and its treatment. We describe our attempt to address this issue of lack of community participation in a particular community of Dhanas, Chandigarh, using an ethnography approach. Methodology: Despite drug/alcohol use being rampant in their community, the leaders of the community (Sarpanch and Medical Officer of Primary Health Centre not only denied the problem, but also refused to support community outreach team. In the absence of facilitation by community leaders and prevalent stigma, drug/alcohol users from the Dhanas village did not seek treatment even when the treatment was offered close to their homes. Using an ethnography approach, a 6 point questionnaire was developed to investigate the severity of the problem as well as to engage the community leaders in the delivery of community-based treatment. Results: The questionnaire highlighted that key leaders chose to deny existing drug/alcohol problem whereas those who were aware of the problem did not have a say in the decision-making process. The questionnaire facilitated a thorough understanding of the sociocultural and political ethos of the community which in turn helped in chalking out an action plan in this village. Conclusion: With the help of various individuals such as former and current healthcare workers, community leaders, drug users, and their family members, the community outreach team successfully mobilized the community from denial to activism. This was evident in the number of individuals seeking treatment for drug/alcohol use that showed an increasing trend over the

  20. The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms.

    Directory of Open Access Journals (Sweden)

    Andrew C Kotze

    Full Text Available Current efforts to control human soil-transmitted helminth (STH infections involve the periodic mass treatment of people, particularly children, in all endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that high levels of resistance have developed to these same drugs in roundworms of livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg count reduction test (FECRT, in which faecal egg output is measured pre- and post-drug treatment, is presently under examination by WHO as a means of detecting the emergence of resistance. We have examined the potential impact of density dependent fecundity on FECRT data. Recent evidence with the canine hookworm indicates that the density dependent egg production phenomenon shows dynamic properties in response to drug treatment. This will impact on measurements of drug efficacy, and hence drug resistance. It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels. These cases will therefore underestimate drug efficacy in the FECRT. The degree of underestimation will depend on the ability of the worms within particular hosts to increase their egg output, which will in turn depend on the extent to which their egg output is constrained prior to the drug treatment. As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates. Measurement of relative drug efficacy may be improved by attempting to ensure a consistent degree of underestimation in groups of people involved in separate FECRTs. This may be partly achieved by omission of cases with the heaviest infections

  1. Effect of quality chronic disease management for alcohol and drug dependence on addiction outcomes.

    Science.gov (United States)

    Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

    2012-12-01

    We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. 38 CFR 17.81 - Contracts for residential treatment services for veterans with alcohol or drug dependence or...

    Science.gov (United States)

    2010-07-01

    ... treatment services for veterans with alcohol or drug dependence or abuse disabilities. 17.81 Section 17.81... Federal Agencies § 17.81 Contracts for residential treatment services for veterans with alcohol or drug... “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part II) and the “Confidentiality of Certain...

  3. Existing drugs and agents under investigation for pulmonary arterial hypertension.

    Science.gov (United States)

    Sharma, Mala; Pinnamaneni, Sowmya; Aronow, Wilbert S; Jozwik, Bartosz; Frishman, William H

    2014-01-01

    Pulmonary arterial hypertension is a progressive and debilitating disorder with an associated high morbidity and mortality rate. Significant advances in our understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary hypertension have occurred over the past several decades. This has allowed the development of new therapeutic options in this disease. Today, our selection of therapeutic modalities is broader, including calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase inhibitors, and soluble guanylate cyclase stimulators, but the disease remains fatal. This underscores the need for a continued search for novel therapies. Several potential pharmacologic agents for the treatment of pulmonary arterial hypertension are under clinical development and some promising results with these treatments have been reported. These agents include rho-kinase inhibitors, long-acting nonprostanoid prostacyclin receptor agonists, tyrosine protein kinase inhibitors, endothelial nitric oxide synthase couplers, synthetically produced vasoactive intestinal peptide, antagonists of the 5-HT2 receptors, and others. This article will review several of these promising new therapies and will discuss the current evidence regarding their potential benefit in pulmonary arterial hypertension.

  4. Mechanisms Underlying the Risk to Develop Drug Addiction, Insights From Studies in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Julia Ryvkin

    2018-04-01

    Full Text Available The ability to adapt to environmental changes is an essential feature of biological systems, achieved in animals by a coordinated crosstalk between neuronal and hormonal programs that allow rapid and integrated organismal responses. Reward systems play a key role in mediating this adaptation by reinforcing behaviors that enhance immediate survival, such as eating or drinking, or those that ensure long-term survival, such as sexual behavior or caring for offspring. Drugs of abuse co-opt neuronal and molecular pathways that mediate natural rewards, which under certain circumstances can lead to addiction. Many factors can contribute to the transition from drug use to drug addiction, highlighting the need to discover mechanisms underlying the progression from initial drug use to drug addiction. Since similar responses to natural and drug rewards are present in very different animals, it is likely that the central systems that process reward stimuli originated early in evolution, and that common ancient biological principles and genes are involved in these processes. Thus, the neurobiology of natural and drug rewards can be studied using simpler model organisms that have their systems stripped of some of the immense complexity that exists in mammalian brains. In this paper we review studies in Drosophila melanogaster that model different aspects of natural and drug rewards, with an emphasis on how motivational states shape the value of the rewarding experience, as an entry point to understanding the mechanisms that contribute to the vulnerability of drug addiction.

  5. Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target

    Czech Academy of Sciences Publication Activity Database

    Kryštof, Vladimír; Baumli, S.; Fürst, R.

    2012-01-01

    Roč. 18, č. 20 (2012), s. 2883-2890 ISSN 1381-6128 R&D Projects: GA ČR GAP305/12/0783 Institutional research plan: CEZ:AV0Z50380511 Keywords : Cancer * inflammation * kinase Subject RIV: ED - Physiology Impact factor: 3.311, year: 2012 http://www.benthamdirect.org/pages/article/1/3177374/perspective-of-cyclin-dependent-kinase-9-cdk9-as-a- drug -target.html

  6. Differential pathway dependency discovery associated with drug response across cancer cell lines* | Office of Cancer Genomics

    Science.gov (United States)

    The effort to personalize treatment plans for cancer patients involves the identification of drug treatments that can effectively target the disease while minimizing the likelihood of adverse reactions. In this study, the gene-expression profile of 810 cancer cell lines and their response data to 368 small molecules from the Cancer Therapeutics Research Portal (CTRP) are analyzed to identify pathways with significant rewiring between genes, or differential gene dependency, between sensitive and non-sensitive cell lines.

  7. Brief report: the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction

    OpenAIRE

    Roberta Biolcati; Giacomo Mancini; Elena Trombini

    2017-01-01

    The main aim of this study is to investigate the influence of dissociative experiences and alcohol/drugs dependence on Internet addiction. From a clinical point of view Internet addiction, an excessive or poorly controlled preoccupation, urges, and/or behaviors regarding Internet use, lead to emotional and social problems in several life domains. Moreover, the increased prevalence of Internet addiction among adolescents and young adults is cause of concerns. Data was collected on 441 undergra...

  8. Paradoxical dopaminergic drug effects in extraversion: Dose- and time-dependent effects of Sulpiride on EEG theta activity

    Directory of Open Access Journals (Sweden)

    Mira-Lynn eChavanon

    2013-04-01

    Full Text Available Dopaminergic drugs frequently produce paradoxical effects depending on baseline performance levels, genotype or personality traits. The present study for the first time aimed to specify the mechanisms underlying such opposite effects using the following recently reported scenario as an example: Depending on the personality trait agentic extraversion (aE; i.e. assertiveness, dominance, ambition, positive emotionality the selective dopamine D2 receptor antagonist sulpiride (200 mg had opposite effects on resting posterior versus anterior theta activity in the electroencephalogram (EEG. In order to better describe these opposite pharmaco-EEG effects and to generate hypotheses regarding the underlying mechanisms, we measured the EEG intermittently over five hours in 80 healthy male volunteers extremely high or low in aE who had received either placebo or one of three doses of sulpiride (50 mg, 200 mg, or 400 mg. The findings suggest a model postulating stronger pre- versus postsynaptic subreceptor effects in high aE individuals compared to low aE individuals. Future studies may now systematically apply the model to other examples of paradoxical dopaminergic drug effects and examine the molecular basis of individual differences in pre- versus postsynaptic dopamine D2 subreceptor sensitivities and densities.

  9. 38 CFR 17.83 - Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment and...

  10. Benefits of Exercise for the Quality of Life of Drug-Dependent Patients.

    Science.gov (United States)

    Giménez-Meseguer, Jorge; Tortosa-Martínez, Juan; de los Remedios Fernández-Valenciano, María

    2015-01-01

    This study combined quantitative and qualitative research methods to evaluate quality-of-life changes in drug-dependent patients after participation in a group-based exercise program. Quality of life (SF-36) and physical fitness (six-minute Walk Test, Timed Get Up and Go Test, and Chair Stand Test) were quantitatively determined in a group (n=37) of drug-dependent patients before and after a 12-week group exercise program (n=18) or routine care (n=19). Additionally, in-depth interviews were conducted at the end of the program with a subsample of 11 participants from the exercise group. Quantitative results showed improvements in fitness and different aspects of quality of life, such as physical function, mental health, vitality, social function, and general health perception. Qualitative results showed specific physical benefits (decreased injuries and muscle pain, decreased weight, and increased vitality with improvement in activities of daily living), psychological benefits (forgetting about everyday problems, improved mood, decreased stress and anxiety), social benefits, and a reduction in craving. The results of this study provide insight into the importance of exercise for the quality of life and recovery process of drug-dependent patients.

  11. The obesity epidemic and food addiction: clinical similarities to drug dependence.

    Science.gov (United States)

    Fortuna, Jeffrey L

    2012-01-01

    As of 2010 nearly 70% of adult Americans were overweight or obese. Specifically, 35.7% of adult Americans are obese, and this is the highest level of obesity in the recorded history of the United States. A number of environmental factors, most notably the number of fast food outlets, have contributed to the obesity epidemic as well as to the binge prone dynamic. There is evidence that bingeing on sugar-dense, palatable foods increases extracellular dopamine in the striatum and thereby possesses addictive potential. Moreover, elevated blood glucose levels catalyze the absorption of tryptophan through the large neutral amino acid (LNAA) complex and its subsequent conversion into the mood-elevating chemical serotonin. There appear to be several biological and psychological similarities between food addiction and drug dependence including craving and loss of control. Nonetheless there is at least one apparent difference: acute tryptophan depletion does not appear to induce a relapse in recovering drug-dependent individuals, although it may induce dysphoria. In some individuals, palatable foods have palliative properties and can be viewed as a form of self medication. This article will examine environmental factors that have contributed to the obesity epidemic, and will compare the clinical similarities and differences of food addiction and drug dependence.

  12. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

    Science.gov (United States)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

    2017-06-01

    Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R 2 =0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Genome-wide discovery of drug-dependent human liver regulatory elements.

    Directory of Open Access Journals (Sweden)

    Robin P Smith

    2014-10-01

    Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

  14. Willingness to treat drug dependence and depression: comparisons of future health professionals

    Directory of Open Access Journals (Sweden)

    Ríos-Bedoya CF

    2011-03-01

    Full Text Available Brian K Ahmedani1,2, Sheryl Pimlott Kubiak2, Carlos F Rios-Bedoya3, Maureen Mickus4, James C Anthony51Center for Health Services Research, Henry Ford Health System, Detroit, MI, USA; 2School of Social Work, Michigan State University, East Lansing, MI, USA; 3Department of Family Medicine, Michigan State University, East Lansing, MI, USA; 4Occupational Therapy, Western Michigan University, Kalamazoo, MI, USA; 5Department of Epidemiology, Michigan State University, East Lansing, MI, USAPurpose: Stigma-related feelings, including degree of enthusiasm and willingness to work with alcohol, drug, and mental disorder (ADM patients, as well as anticipated success in such work, will be required for the United States to be successful in its new initiatives for ADM screening, brief intervention, and effective referral to treatment and rehabilitation services (SBIRT. This study investigates students of medicine and social work with respect to their stigma-related feelings and degree of enthusiasm or willingness to treat patients affected by alcohol dependence, nicotine dependence, or major depression. Inference is strengthened by an anonymous online survey approach, with use of randomized reinforcers to gain at least partial experimental control of nonparticipation biases that otherwise are present in student survey data.Material and methods: All students on required course rosters were asked to participate in a two-part in-class and online assessment; 222 participated, with a gradient of participation induced via randomly drawn reinforcers for online survey participation. Between-group comparisons were made with a multivariate generalized linear model and generalized estimating equations approach that adjusts for covariates.Results: Medical and social work students did not differ from each other with respect to their willingness to treat patients affected by major depression, alcohol dependence, or nicotine dependence, but together were less willing to

  15. Women, Drug Dependency and Consequences: A Study from a Developing Country

    Directory of Open Access Journals (Sweden)

    Mohammad Khajedaluee

    2015-01-01

    Full Text Available Introduction. Addiction in women can expose them to malnutrition, high blood pressure, cancer, and some other dangerous diseases like hepatitis, AIDS, or other sexual transmitted diseases. The aim of this study was to assess illegal sexual relations in three groups of women. Methods. This is a cross-sectional study that was done on 236 girls and young women aged 16–25 years in 2012 in three groups: vulnerable women who have substance dependency (crimes that had made women incarcerated were considered as vulnerability in this study, invulnerable women who have substance dependency (substance dependent women without a history of incarceration, and a control group (women with no history of substance dependency or being in prison. Results. 43.8% of vulnerable women who have substance dependency had extramarital sexual relations; this percentage was 55.8% in invulnerable women who have substance dependency and 1.4% in the control group. Crystal and methamphetamine abuse was higher in addicts who had extramarital sexual relations and alcohol abuse was correlated with unsafe sexual intercourse (r=;0.36, P=0.001. There was a statistically significant difference in extramarital sexual relation based on marital status (P<0.001. Conclusions. Poverty, drug dependency, divorce, and alcohol consumption make women prone to other high risk behaviors that need more attention.

  16. Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse.

    Science.gov (United States)

    Roncero, Carlos; Abad, Alfonso C; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

    2017-01-01

    In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia"). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable.

  17. Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells.

    Science.gov (United States)

    Díaz-Valdivia, Natalia I; Calderón, Claudia C; Díaz, Jorge E; Lobos-González, Lorena; Sepulveda, Hugo; Ortíz, Rina J; Martinez, Samuel; Silva, Veronica; Maldonado, Horacio J; Silva, Patricio; Wehinger, Sergio; Burzio, Verónica A; Torres, Vicente A; Montecino, Martín; Leyton, Lisette; Quest, Andrew F G

    2017-12-19

    Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits. Here, we used in vitro [2D, invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question. Colon and breast cancer cells were identified where CAV1 levels were low due to epigenetic suppression and could be reverted by treatment with the methyltransferase inhibitor 5'-azacytidine. Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48 h) increased CAV1 expression through ROS production and MEK/ERK activation. In colon cancer cells, increased CAV1 expression enhanced migration and invasion in vitro via pathways requiring Src-family kinases, as well as Rac-1 activity. Finally, elevated CAV1 expression in colon cancer cells following exposure in vitro to sub-cytotoxic drug concentrations increased their metastatic potential in vivo . Therefore exposure of cancer cells to anti-neoplastic drugs at non-lethal drug concentrations induces signaling events and changes in transcription that favor CAV1-dependent migration, invasion and metastasis. Importantly, this may occur in the absence of selection for drug-resistance.

  18. Red blood cell aggregation changes are depended on its initial value: Effect of long-term drug treatment and short-term cell incubation with drug.

    Science.gov (United States)

    Muravyov, A V; Tikhomirova, I A; Maimistova, A A; Bulaeva, S V; Mikhailov, P V; Kislov, N V

    2011-01-01

    This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group - adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb RBCA. On the other hand in the patients with initially high RBCA treatment with pentoxifylline reduced it markedly (p RBCA by 47% (p RBCA it increased. It was observed that after 4 weeks of epoetin-beta treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p RBCA increase (p RBCA was reduced by 47% (p RBCA was increased in sub-group of subjects with initially low aggregation and it was decreased in sub-group with initially high one. The similar RBCA changes were observed when RBC suspensions were incubated with vinpocetine, calcium ionophore (A23187), Phorbol 12-myristate 13-acetate (PMA) as a protein kinase C (PKC) stimulator. A major finding of this study is that the red cell aggregation effects of some drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism.

  19. Barriers to community-based drug dependence treatment: implications for police roles, collaborations and performance indicators.

    Science.gov (United States)

    Ma, Yi; Du, Chunhua; Cai, Thomas; Han, Qingfeng; Yuan, Huanhuan; Luo, Tingyan; Ren, Guoliang; Mburu, Gitau; Wang, Bangyuan; Golichenko, Olga; Zhang, Chaoxiong

    2016-01-01

    Worldwide, people who use drugs (PWUD) are among the populations at highest risk for HIV infection. In China, PWUD are primarily sentenced to compulsory detainment centres, in which access to healthcare, including HIV treatment and prevention services, is limited or non-existent. In 2008, China's 2008 Anti-Drug Law encouraged the development and use of community-based drug dependence rehabilitation, yet there is limited evidence evaluating the efficacy and challenges of this model in China. In this study, we explore these challenges and describe how cooperation between law enforcement and health departments can meet the needs of PWUD. In 2015, we conducted semi-structured, in-depth interviews with all four staff members and 16 clients of the Ping An Centre No. 1 for community-based drug treatment, three local police officers and three officials from the local Centre for Disease Control. Interviews explored obstacles in implementing community-based drug dependence treatment and efforts to resolve these difficulties. Transcripts were coded and analyzed with qualitative data analysis software (MAXQDA 11). We identified three challenges to community-based drug treatment at the Ping An Centre No. 1: (1) suboptimal coordination among parties involved, (2) a divergence in attitudes towards PWUD and harm reduction between law enforcement and health officials and (3) conflicting performance targets for police and health officials that undermine the shared goal of treatment. We also identified the take-home methadone maintenance treatment model at the Ping An Centre No. 1 as an example of an early successful collaboration between the police, the health department and PWUD. To overcome barriers to effective community-based drug treatment, we recommend aligning the goals of law enforcement and public health agencies towards health-based performance indicators. Furthermore, tensions between PWUD and police need to be addressed and trust between them fostered, using community

  20. Personality Traits and Psychopathology in Nicotine and Opiate Dependents Using the Gateway Drug Theory

    Directory of Open Access Journals (Sweden)

    Bahareh Amirabadi

    2015-03-01

    Full Text Available Objectives: According to the gateway drug theory, tobacco use is a predisposing factor for future substance abuse. This study was conducted to compare nicotine and opiate dependents to identify the differences between their personality traits and psychopathology that makes them turn to other substances after cigarette smoking. Methods: A causal-comparative study was conducted. Three groups were randomly selected: nicotine dependents, opiate dependents and ordinary individuals (non-dependent population. Cloninger’s Temperament and Character Inventory-Revised, the Fagerstrom Test for Nicotine Dependence, Maudsley Addiction Profile, the Beck Depression Inventory, and Beck Anxiety Inventory were used to collect data. Analysis of variance was used to analyze data. Results: Opiate dependents had higher ‘novelty seeking’ and lower ‘cooperativeness’ scores as compared to the other two groups. They also had higher anxiety and depression scores than the other two groups. Discussion: Higher ‘novelty seeking’ and lower ‘cooperativeness’ scores are important personality traits predicting

  1. Personality disturbances in drug-dependent women: relationship to childhood abuse.

    Science.gov (United States)

    Haller, Deborah L; Miles, Donna R

    2004-05-01

    This study examined associations between childhood abuse and personality disturbances in 228 drug-dependent women. Thirty-six percent denied abuse, 50% reported emotional, 42% physical, and 42% sexual abuse. Million Clinical Multiarial Inventory (MCMI-III) scores > 74 provided evidence of personality disturbance and scores on Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales measuring somatic complaints, depression, anxiety and postraumatic stress disorder (PTSD) served as covariates. Emotional and physical abuse survivors were at increased risk for borderline, masochistic, and avoidant disturbances and decreased risk for narcissistic disturbances. Emotional abuse survivors were also less likely to be sadistic whereas physical abuse survivors were more likely to be paranoid. Sexual abuse survivors were twice as likely be antisocial; however, no association was found with borderline personality. Finally, an increased prevalence of severe personality disturbances was observed among those experiencing multiple types of abuse. Childhood trauma predisposes drug-dependent women to develop troublesome personality characteristics that are independent of drug addiction and other psychological problems associated with childhood trauma.

  2. Undocumented Immigration, Drug Problems, and Driving Under the Influence in the United States, 1990-2014.

    Science.gov (United States)

    Light, Michael T; Miller, Ty; Kelly, Brian C

    2017-09-01

    To examine the influence of undocumented immigration in the United States on 4 different metrics of drug and alcohol problems: drug arrests, drug overdose fatalities, driving under the influence (DUI) arrests, and DUI deaths. We combined newly developed state-level estimates of the undocumented population between 1990 and 2014 from the Center for Migration Studies with arrest data from the Federal Bureau of Investigation Uniform Crime Reports and fatality information from the Fatality Analysis Reporting System and the Centers for Disease Control and Prevention Underlying Cause of Death database. We used fixed-effects regression models to examine the longitudinal association between increased undocumented immigration and drug problems and drunk driving. Increased undocumented immigration was significantly associated with reductions in drug arrests, drug overdose deaths, and DUI arrests, net of other factors. There was no significant relationship between increased undocumented immigration and DUI deaths. This study provides evidence that undocumented immigration has not increased the prevalence of drug or alcohol problems, but may be associated with reductions in these public health concerns.

  3. Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

    Science.gov (United States)

    Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

    2014-01-01

    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

  4. Evolution of male life histories and age-dependent sexual signals under female choice

    Directory of Open Access Journals (Sweden)

    Joel J. Adamson

    2013-12-01

    Full Text Available Sexual selection theory models evolution of sexual signals and preferences using simple life histories. However, life-history models predict that males benefit from increasing sexual investment approaching old age, producing age-dependent sexual traits. Age-dependent traits require time and energy to grow, and will not fully mature before individuals enter mating competition. Early evolutionary stages pose several problems for these traits. Age-dependent traits suffer from strong viability selection and gain little benefit from mate choice when rare. Few males will grow large traits, and they will rarely encounter choosy females. The evolutionary origins of age-dependent traits therefore remain unclear. I used numerical simulations to analyze evolution of preferences, condition (viability and traits in an age-structured population. Traits in the model depended on age and condition (“good genes” in a population with no genetic drift. I asked (1 if age-dependent indicator traits and their preferences can originate depending on the strength of selection and the size of the trait; (2 which mode of development (age-dependent versus age-independent eventually predominates when both modes occur in the population; and (3 if age-independent traits can invade a population with age-dependent traits. Age-dependent traits evolve under weaker selection and at smaller sizes than age-independent traits. This result held in isolation and when the types co-occur. Evolution of age-independent traits depends only on trait size, whereas evolution of age-dependent traits depends on both strength of selection and growth rate. Invasion of age-independence into populations with established traits followed a similar pattern with age-dependence predominating at small trait sizes. I suggest that reduced adult mortality facilitates sexual selection by favoring the evolution of age-dependent sexual signals under weak selection.

  5. Association between Experience of Child Abuse and Severity of Drug Addiction Measured by the Addiction Severity Index among Japanese Drug-Dependent Patients

    Science.gov (United States)

    Ogai, Yasukazu; Senoo, Eiichi; Gardner, Fumiyuki Chin; Haraguchi, Ayako; Saito, Tamaki; Morita, Nobuaki; Ikeda, Kazutaka

    2015-01-01

    The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence. PMID:25741639

  6. Association between experience of child abuse and severity of drug addiction measured by the Addiction Severity Index among Japanese drug-dependent patients.

    Science.gov (United States)

    Ogai, Yasukazu; Senoo, Eiichi; Gardner, Fumiyuki Chin; Haraguchi, Ayako; Saito, Tamaki; Morita, Nobuaki; Ikeda, Kazutaka

    2015-03-03

    The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence.

  7. Association between Experience of Child Abuse and Severity of Drug Addiction Measured by the Addiction Severity Index among Japanese Drug-Dependent Patients

    Directory of Open Access Journals (Sweden)

    Yasukazu Ogai

    2015-03-01

    Full Text Available The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J. One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA had a significantly higher severity of drug use than men who did not experience it (MNEA. Female participants who experienced child abuse (FEA had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA. Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence.

  8. Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence.

    Science.gov (United States)

    Button, Tanya M M; Hewitt, John K; Rhee, Soo Hyun; Young, Susan E; Corley, Robin P; Stallings, Michael C

    2006-02-01

    Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both phenotypes are highly heritable and a common genetic influence on the covariation has been suggested. The aim of this study was to determine the extent to which genes and environment contribute to the covariance between CD and drug dependence using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male, 116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18 (mean = 15.65) were included in the analysis. CD was assessed by lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) symptom count and a polysubstance dependence vulnerability index was developed from responses to the Composite International Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition model was used to partition the cause of variation and covariation of the two phenotypes. No sex-limitation was observed in our data, and male and female parameter estimates were constrained to be equal. Both CD symptoms and dependence vulnerability were significantly heritable, and genes, shared environment and nonshared environment all contributed to the covariation between them. Genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and nonshared environmental influences contributed the remaining 19% to the phenotypic covariance. Therefore, there appears to be pleiotropic genetic influence on CD symptoms and dependence vulnerability.

  9. Substance abuse and pharmacy practice: what the community pharmacist needs to know about drug abuse and dependence

    Directory of Open Access Journals (Sweden)

    Tommasello Anthony C

    2004-04-01

    Full Text Available Abstract Pharmacists, the most accessible of health care professionals, are well positioned to help prevent and treat substance use disorders and should prepare themselves to perform these functions. New research improves our knowledge about the pharmacological and behavioral risks of drug abuse, supports the clinical impression that drug dependence is associated with long-lasting neurochemical changes, and demonstrates effective pharmacological treatments for certain kinds of drug dependencies. The profession is evolving. Pharmacists are engaging in new practice behaviors such as helping patients manage their disease states. Collaborative practice agreements and new federal policies set the stage for pharmacists to assist in the clinical management of opioid and other drug dependencies. Pharmacists need to be well informed about issues related to addiction and prepared not only to screen, assess, and refer individual cases and to collaborate with physicians caring for chemically dependent patients, but also to be agents of change in their communities in the fight against drug abuse. At the end of this article the pharmacist will be better able to: 1. Explain the disease concept of chemical dependence 2. Gather the information necessary to conduct a screen for chemical dependence 3. Inform patients about the treatment options for chemical dependence 4. Locate resources needed to answer questions about the effects of common drugs of abuse (alcohol, marijuana, narcotics, "ecstasy", and cocaine 5. Develop a list of local resources for drug abuse treatment 6. Counsel parents who are concerned about drug use by their children 7. Counsel individuals who are concerned about drug use by a loved one. 8. Counsel individuals who are concerned about their own drug use

  10. Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach.

    Science.gov (United States)

    Agrawal, A; Neale, M C; Jacobson, K C; Prescott, C A; Kendler, K S

    2005-06-01

    Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

  11. Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

    Science.gov (United States)

    Meunier, David; Ersche, Karen D; Craig, Kevin J; Fornito, Alex; Merlo-Pich, Emilio; Fineberg, Naomi A; Shabbir, Shaila S; Robbins, Trevor W; Bullmore, Edward T

    2012-01-16

    There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

    Science.gov (United States)

    Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana

    2016-03-01

    Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.

  13. [Reincarceration of drug-dependent prisoners released into a therapeutic community, according to pretreatment variables].

    Science.gov (United States)

    Ramos Barbero, Victoria; Carcedo González, Rodrigo J

    2012-01-01

    The main aim of this paper is to identify the criminal and penitentiary pretreatment variables associated with re-entry into prison in a population of drug-dependent inmates who had been released from different prisons in Castilla and Leon (Spain) to finish their prison sentence in a Therapeutic Community. The study population was 120 male inmates. The documentary sources consulted for collecting information were the prison record, the classification and treatment protocol and the social record. These official records were consulted in the Burgos Penitentiary, responsible for custody of the documents. Applying a descriptive statistical analysis with contingency tables, the pre-treatment variables that showed the strongest association with re-entry into prison were family prison history, total sentence exceeding five years, imprisonments prior to the sentence in question, change to a higher security level, revocation of parole, breach of the terms of a sentence, completion of sentence in prison and, especially, age at first entry into prison between 16 and 21 years. It was confirmed through logistic regression analysis that the variable age at which participants entered prison for the first time is critical, given the impact that prison can have at an early age. These results provide a profile of the drug-dependent inmate at greatest risk of making poor use of measures alternative to prison.

  14. The insula: a critical neural substrate for craving and drug seeking under conflict and risk

    Science.gov (United States)

    Naqvi, Nasir H.; Gaznick, Natassia; Tranel, Daniel; Bechara, Antoine

    2014-01-01

    Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking—the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments. PMID:24690001

  15. The insula: a critical neural substrate for craving and drug seeking under conflict and risk.

    Science.gov (United States)

    Naqvi, Nasir H; Gaznick, Natassia; Tranel, Daniel; Bechara, Antoine

    2014-05-01

    Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking-the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments. © 2014 New York Academy of Sciences.

  16. Effectiveness of Cognitive-Behavioral Therapy in the Improvement of Coping Strategies and Addiction Symptoms in Drug-Dependent Patients

    OpenAIRE

    H BrockieMilan; H Kamarzarrin; H Zare

    2014-01-01

    Objective: This study was carried out to determine the effectiveness of cognitive-behavioral therapy in improving coping strategies and symptoms of drug addiction patients. Method: In a quasi-experimental study, the number of 90drug-dependent patients referring to clinics to stop taking drugs existing in the city of Urmia were divided into two experimental (n=45) groups and control (n=45) using random sampling. The experimental group received 12 sessions of cognitive-behavioral treatment in C...

  17. Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes

    NARCIS (Netherlands)

    Filip, Malgorzata; Spampinato, Umberto; McCreary, Andrew C.; Przegalinski, Edmund

    2012-01-01

    The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT2C receptors on the effects of different classes of addictive drugs, illustrated by reference to data using

  18. Driving under the effect of drugs: Hair analysis in order to evaluate recidivism.

    Science.gov (United States)

    Tassoni, Giovanna; Cippitelli, Marta; Mirtella, Dora; Froldi, Rino; Ottaviani, Giovanni; Zampi, Massimiliano; Cingolani, Mariano

    2016-10-01

    Under Italian law drug addiction and regular drug abuse are incompatible with driving ability. One important problem with the enforcement of the impaired driving law is the large number of people that re-offend. To regain their license, offenders must be drug-free for the duration of an observation period, according to the judgement of a medical commission. The exclusion of illicit drug use is determined by toxicological analysis. A few studies exist that have used a hair matrix to monitor recidivism. Hair is an attractive matrix for monitoring drug recidivism, due to the large time window for drug detection, and to the non-alterability of this matrix. We report the results of several years of experience at our forensic toxicology laboratory in the use of hair analysis for the assessment of past exposure to drugs in persons suspected of driving under the influence of drugs. 5592 subjects were analyzed for opiates, cocaine and delta-9-tetrahydrocannabinol (Δ 9 -THC) using a GC/MS method. 1062 (19.0%) subjects resulted positive. From this group, the individuals that resulted positive at least at the second control were considered recidivists (243, 22.9%). 79.7% of recidivist subjects were positive for cocaine and metabolites, 14.9% for morphine and metabolites, 5.4% for Δ 9 -THC. We also studied the time frame of the abuse, as well as gender and age distribution of recidivist subjects. Furthermore, we analyzed risk factors associated with recidivist behaviour. Our results show that cocaine consumption was the only factor that showed significance with regard to increased likelihood of being a recidivist. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Perceptions of neighborhood social environment and drug dependence among incarcerated women and men: a cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Rogers Jessica D

    2012-09-01

    Full Text Available Abstract Background Perception of neighborhood social environment can influence an individual’s susceptibility to drug dependence. However, this has never been examined with a jailed sample, where frequent transitions between local jails and disadvantaged neighborhoods are common. Understanding these associations could aid in the design of targeted programs to decrease drug dependence and recidivism among the incarcerated. Methods For this study, 596 women and men from three Kansas City jails were surveyed over the course of six months in 2010. Drug dependence was assessed with DSM-IV criteria. Independent variables included fear of one’s neighborhood, perceived level of neighborhood violence, and social capital. All data were self-reported and were analyzed using logistic regression. Results Controlling for gender and age, fear of neighborhood violence was associated with increased odds of having drug dependence (OR = 1.27, CI 1.02, 1.58 and a higher level of social capital prior to incarceration was associated with lower odds of drug dependence (OR = 0.65, CI 0.44, 0.96. Mental health problem diagnosis and past year intimate partner violence were significant mediating factors. Gender and race/ethnicity were significant moderating factors between neighborhood disadvantage and drug dependence. Conclusions Our study suggests that drug dependence programs for women and men who cycle between jails and communities require both individual- and community-level interventions. To be most effective, programs at the community-level should focus on helping specific groups navigate their communities, as well as address individual health needs associated with drug dependence.

  20. Facilitating a transition from compulsory detention of people who use drugs towards voluntary community-based drug dependence treatment and support services in Asia.

    Science.gov (United States)

    Tanguay, Pascal; Kamarulzaman, Adeeba; Aramrattana, Apinun; Wodak, Alex; Thomson, Nicholas; Ali, Robert; Vumbaca, Gino; Lai, Gloria; Chabungbam, Anand

    2015-10-16

    Evidence indicates that detention of people who use drugs in compulsory centers in the name of treatment is common in Cambodia, China, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Thailand, and Vietnam. The expansion of such practices has been costly, has not generated positive health outcomes, and has not reduced supply or demand for illicit drugs. United Nations agencies have convened several consultations with government and civil society stakeholders in order to facilitate a transition to voluntary evidence- and community-based drug dependence treatment and support services. In an effort to support such efforts, an informal group of experts proposes a three-step process to initiate and accelerate national-level transitions. Specifically, the working group recommends the establishment of a national multisectoral decision-making committee to oversee the development of national transition plans, drug policy reform to eliminate barriers to community-based drug dependence treatment and support services, and the integration of community-based drug dependence treatment in existing national health and social service systems.In parallel, the working group recommends that national-level transitions should be guided by overarching principles, including ethics, human rights, meaningful involvement of affected communities, and client safety, as well as good governance, transparency, and accountability. The transition also represents an opportunity to review the roles and responsibilities of various agencies across the public health and public security sectors in order to balance the workload and ensure positive results. The need to accelerate national-level transitions to voluntary community-based drug dependence treatment and support services is compelling--on economic, medical, sustainable community development, and ethical grounds--as extensively documented in the literature. In this context, the expert working group fully endorses initiation of a transition

  1. Cell cycle stage dependent variations in drug-induced topoisomerase II mediated DNA cleavage and cytotoxicity

    International Nuclear Information System (INIS)

    Estey, E.; Adlakha, R.C.; Hittelman, W.N.; Zwelling, L.A.

    1987-01-01

    The DNA cleavage produced by 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) in mammalian cells is putatively mediated by topoisomerase II. The authors found that in synchronized HeLa cells the frequency of such cleavage was 4-15-fold greater in mitosis than in S while the DNA of G 1 and G 2 cells exhibited an intermediate susceptibility to cleavage. The hypersensitivity of mitotic DNA to m-AMSA-induced cleavage was acquired relatively abruptly in late G 2 and was lost similarly abruptly in early G 1 . The susceptibility of mitotic cells to m-AMSA-induced DNA cleavage was not clearly paralleled by an increase in topoisomerase II activity in 350 mM NaCl extracts from mitotic cells compared to similar extracts from cells in G 1 , S, or G 2 . Furthermore, equal amounts of decatenating activity from cells in mitosis and S produced equal amounts of m-AMSA-induced cleavage of simian virus 40 (SV40) DNA; i.e., the interaction between m-AMSA and extractable enzyme was similar in mitosis and S. The DNA of mitotic cells was also hypersensitive to cleavage by 4'-demethylepipodophyllotoxin 4-(4,6-O-ethylidene-β-D-glucopyranoside) (etoposide), a drug that produces topoisomerase II mediated DNA cleavage without binding to DNA. Cell cycle stage dependent fluctuations in m-AMSA-induced DNA cleavage may result from fluctuations in the structure of chromatin per se that occur during the cell cycle. Surprisingly, cell cycle stage dependent differences in m-AMSA-induced DNA cleavage did not correlate with differences in the susceptibility to the cytotoxic effects of the drug. In fact, cells in S were most sensitive to these effects. These results are an exception to the previously observed parallel between the susceptibility of mammalian cells to drug-induced DNA cleavage and the susceptibility of the cells to drug-induced cytotoxicity and indicate the complexity of any relationship between the two phenomena

  2. Chronic disease and recent addiction treatment utilization among alcohol and drug dependent adults

    Directory of Open Access Journals (Sweden)

    Samet Jeffrey

    2011-10-01

    Full Text Available Abstract Background Chronic medical diseases require regular and longitudinal care and self-management for effective treatment. When chronic diseases include substance use disorders, care and treatment of both the medical and addiction disorders may affect access to care and the ability to focus on both conditions. The objective of this paper is to evaluate the association between the presence of chronic medical disease and recent addiction treatment utilization among adults with substance dependence. Methods Cross-sectional secondary data analysis of self-reported baseline data from alcohol and/or drug-dependent adults enrolled in a randomized clinical trial of a disease management program for substance dependence in primary care. The main independent variable was chronic medical disease status, categorized using the Katz Comorbidity Score as none, single condition of lower severity, or higher severity (multiple conditions or single higher severity condition, based on comorbidity scores determined from self-report. Asthma was also examined in secondary analyses. The primary outcome was any self-reported addiction treatment utilization (excluding detoxification in the 3 months prior to study entry, including receipt of any addiction-focused counseling or addiction medication from any healthcare provider. Logistic regression models were adjusted for sociodemographics, type of substance dependence, recruitment site, current smoking, and recent anxiety severity. Results Of 563 subjects, 184 (33% reported any chronic disease (20% low severity; 13% higher severity and 111 (20% reported asthma; 157 (28% reported any addiction treatment utilization in the past 3 months. In multivariate regression analyses, no significant effect was detected for chronic disease on addiction treatment utilization (adjusted odds ratio [AOR] 0.88 lower severity vs. none, 95% confidence interval (CI: 0.60, 1.28; AOR 1.29 higher severity vs. none, 95% CI: 0.89, 1.88 nor for

  3. Sex and HIV serostatus differences in decision making under risk among substance-dependent individuals.

    Science.gov (United States)

    Martin, Eileen; Gonzalez, Raul; Vassileva, Jasmin; Maki, Pauline M; Bechara, Antoine; Brand, Matthias

    2016-01-01

    HIV+ individuals with and without substance use disorders make significantly poorer decisions when information about the probability and magnitude of wins and losses is not available. We administered the Game of Dice Task, a measure of decision making under risk that provides this information explicitly, to 92 HIV+ and 134 HIV- substance-dependent men and women. HIV+ participants made significantly poorer decisions than HIV- participants, but this deficit appeared more prominent among HIV+ women. These data indicate that decision making under risk is impaired among HIV+ substance-dependent individuals (SDIs). Potential factors for the HIV+ women's relatively greater impairment are discussed.

  4. Prevention and treatment in prison law: women prisoners drug dependence in Spain

    Directory of Open Access Journals (Sweden)

    Francisco José del Pozo Serrano

    2015-05-01

    Full Text Available The penitentiary drug dependence treatment for women has been traditionally generic (applied for most masculine penitentiary and with few differentiating empiric studies in an spanish level.Based on a regulatory framework, this research focuses on the study of the main elements of risk and protection implied in the relation between the drug dependant female prisoners and the treatment programs, as well as the recovery processes, in order to propose specific actions.The research has a multimethod approach, inserted within the Project I+D+I named “Mujeres reclusas drogodependientes y su reinserción social. Estudio socioeducativo y propuestas de acción” [EDU2009-13408], with a national sample of second and third degree (Central Government and Community of Catalonia, corresponding to an estimate of 15% of the female prisoners nationally. 538 valid questionnaires, 61 semi-structured interviews has been obtained, in which informatic analytical methods, specific programs for quantitative data (SPSS, V. 15 y 20, and analytical content methods for qualitative data has been applied. The analysis has been developed before and after the internment, including four profiles of female prisioners (AA: Active addicted (8'20%, EX: ex addicted (EX: 67'21%, NA: non addicted (NA: 14.75% and PMM (9.84% addicted within methadone maintenance programs .Among the main results found, it is relevant to mention the elements of risk related to the absence of participation of ex addicted women in relapse prevention programs. In fact, this is a relevant issue since 70% of the women are ex addicted. There is a large number of women not receiving any treatment in prision and not participating in any program due to lack of information, mistrust and overlap with other activities. Aditionally, theres is a perception of gender discrimination towards the access and permanece of women in the programs, compared with men.  Also, within the main elements of protection, it has been

  5. The importance of biological rhythms in drug treatment of hypertension and sex-dependent modifications

    Directory of Open Access Journals (Sweden)

    Lemmer B

    2012-04-01

    Full Text Available Björn LemmerInstitute of Experimental and Clinical Pharmacology and Toxicology, Ruprecht-Karls-University of Heidelberg, Mannheim, GermanyAbstract: The cardiovascular system is highly organized in time. Blood pressure, heart rate, peripheral resistance, pressure, and vasodilating hormones display pronounced circadian variations. New data presented here demonstrate also sex-dependent differences in vasodilating hormones, with higher NOχ excretion in females than males and a steeper early morning rise in norepinephrine in males, whereas the 24-hour blood pressure and heart-rate profiles were not different. Various antihypertensive drugs were investigated in crossover studies – morning versus evening dosing – in hypertensive patients; however, consistent data were only described for angiotensin-converting-enzyme (ACE inhibitors, calcium channel blockers, and angiotensin II type 1 (AT1 receptor blockers. Whereas in dippers ACE inhibitors had a superdipping effect when dosed at night, no difference in the blood pressure lowering effect or on the 24-hour blood pressure profile was found with calcium channel blockers after morning and evening dosing. In nondippers, the calcium channel blockers isradipine and amlodipine transformed nondippers into dippers, similar after evening dosing. The effects of AT1-receptor blockers are similar to those of ACE inhibitors. Also, diuretics are able to normalize non dipping behavior. Moreover, a circadian phase dependency in their pharmacokinetics has been demonstrated for various cardiovascular-active drugs, such as beta blockers, calcium channel blockers, oral nitrates, and ACE inhibitors, modified by the galenic formulation. There is evidence that in hypertensive dippers, antihypertensive drugs should be given during early morning hours, whereas in non dippers it can be necessary to add an evening dose or even to apply a single evening dose in order not only to reduce high blood pressure, but also to

  6. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  7. Location-Dependent Query Processing Under Soft Real-Time Constraints

    Directory of Open Access Journals (Sweden)

    Zoubir Mammeri

    2009-01-01

    Full Text Available In recent years, mobile devices and applications achieved an increasing development. In database field, this development required methods to consider new query types like location-dependent queries (i.e. the query results depend on the query issuer location. Although several researches addressed problems related to location-dependent query processing, a few works considered timing requirements that may be associated with queries (i.e., the query results must be delivered to mobile clients on time. The main objective of this paper is to propose a solution for location-dependent query processing under soft real-time constraints. Hence, we propose methods to take into account client location-dependency and to maximize the percentage of queries respecting their deadlines. We validate our proposal by implementing a prototype based on Oracle DBMS. Performance evaluation results show that the proposed solution optimizes the percentage of queries meeting their deadlines and the communication cost.

  8. Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.

    Science.gov (United States)

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

    2012-11-01

    Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. The first case of drug-dependent memory: the biblical Lot in Talmudic and Midrashic exegesis.

    Science.gov (United States)

    Schnall, Eliezer; Saperstein, Yair; Saperstein, Yona

    2013-01-01

    The literature on alcohol and alcoholism has long noted how the effects of alcohol are reported in early sources, including religious texts such as the Bible and Talmud. In that vein, we suggest that the Bible, as elucidated according to long-established rabbinic interpretation, contains the earliest recorded case of drug-dependent memory, in the account of Lot's alcohol-facilitated incestuous relationships with his daughters (Genesis 19:29-38). We posit that the Talmudic, Midrashic, and traditional rabbinic commentaries that support our reading of the Lot narrative convey keen understanding of the effects of alcohol on recall. These Jewish sources, written centuries ago, demonstrate insight into the nature of alcohol-influenced cognitive function, which was thought to have been unknown prior to contemporary times.

  10. Dependence on prescription benzodiazepines and Z-drugs among young to middle-aged patients in France.

    Science.gov (United States)

    Guerlais, Marylène; Grall-Bronnec, Marie; Feuillet, Fanny; Gérardin, Marie; Jolliet, Pascale; Victorri-Vigneau, Caroline

    2015-02-01

    Benzodiazepines (BZD) and nonbenzodiazepines hypnotics (z-drugs) are recognized as one of the most widely prescribed medications in the world. The purpose of the study was to assess the BZD and z-drugs dependence in young to middle-aged outpatients who were taking BZD/z-drugs on a chronic basis, and to characterize their profile. This is a forward-looking cross-sectional epidemiological study. Data were collected through a semi-structured interview within a network of partner pharmacies from the Nantes area, in France. All data were obtained exclusively through patients' declarations. 212 patients (19-64 years old) were included: they were considered dependent when they answered positively to at least three items of the DSM IV. A multivariate logistic regression and a principal component analysis (PCA) were carried out to determine their profile. Almost half of the patients met criteria for BZD/z-drugs dependence. The risk to develop BZD/z-drugs dependence is significantly associated with psychiatric history and with the quantity of BZD/z-drugs that is taken. A two factor concept of dependence could be identified according to the PCA: one axis with items of "tolerance" and "long term administration or higher doses", and a second axis with "concerned by treatment" and "somatic consequences". Conclusions/Importance: Among this BZD/z-drug dependent population, the two axes identified in the PCA represent two profiles of dependence: being in positive conditioning or suffering from negative consequences. Clinicians need to know them: these two clinical profiles may have an influence in terms of decision-making, especially to manage discontinuation.

  11. [Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

    Science.gov (United States)

    Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

    1991-01-01

    On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

  12. History-dependent coupled growth of creep damage under variable stress conditions

    Science.gov (United States)

    Kawai, M.

    1998-08-01

    A multiaxial constitutive model is presented for the description of the history-dependent inelastic and damage behavior of polycrystalline metallic materials in the high-temperature range under variable loading conditions. A particular emphasis is placed on a new formulation for the history-dependent material degradation which is based on a coupling between hardening and damage. The total damage is given by the sum of damage components which have different history dependence. The associated continuum damage variables are defined through their evolution equations coupled with hardening parameters involved with a kinematic hardening model. The non-classical coupling between hardening and damage is incorporated into the modified kinematic hardening model which has. been developed for describing the complicated hardening and softening behavior under repeated stress changes. Numerical simulations for different material parameters show that the proposed damage-coupled constitutive model can predict an acceleration as well as a deceleration of creep damage growth due to stress variations.

  13. Determinants of nonmedical use, abuse or dependence on prescription drugs, and use of substance abuse treatment.

    Science.gov (United States)

    Bali, Vishal; Raisch, Dennis W; Moffett, Maurice L; Khan, Nasreen

    2013-01-01

    Previous studies have found a negative association between health insurance and nonmedical use of prescription drugs (NMUPD), and abuse or dependence on prescription drugs (ADPD); and mixed associations between health insurance and use of substance abuse treatment (SAT). However, effect of health insurance in the specific subgroups of population is largely unknown. To estimate the relationship between health insurance and (1) NMUPD, (2) ADPD, and (3) use of SAT services among 12-64 years old, noninstitutionalized individuals and to see if these relationships are different in different subgroups of population. This study used cross-sectional survey data from 2007 National Survey on Drug Use and Health. Bivariate and multiple logistic regression analyses were conducted. In 2007, self-reported prevalence of NMUPD was approximately 10% (N=15,509,703). In multivariate analysis, NMUPD was negatively associated with health insurance, age, race other than non-Hispanic White, education, marital status, and income ($40,000-$74,999). Past year use of tobacco and alcohol were positively associated with NMUPD. Among those with private health insurance, Hispanics and individuals with family income less than $20,000 and $40,000-$74,999 were more likely prone to NMUPD than others. High school graduates with public health insurance were less likely prone to NMUPD. Approximately, 13% of nonmedical users reported ADPD (N=2,011,229). Health insurance and age were negatively associated with ADPD. However, people who were unmarried, reported fair/poor health, and used tobacco were more likely to report ADPD. Lastly, the use of substance abuse treatment programs was approximately 73% and 76% between NMUPD and ADPD population, respectively. Health insurance was not associated with use of substance abuse treatment. Individuals with high school education were 2.6 times more likely to use substance abuse treatment than the college graduates. Additionally, no significant interaction effects

  14. An estimator of the survival function based on the semi-Markov model under dependent censorship.

    Science.gov (United States)

    Lee, Seung-Yeoun; Tsai, Wei-Yann

    2005-06-01

    Lee and Wolfe (Biometrics vol. 54 pp. 1176-1178, 1998) proposed the two-stage sampling design for testing the assumption of independent censoring, which involves further follow-up of a subset of lost-to-follow-up censored subjects. They also proposed an adjusted estimator for the survivor function for a proportional hazards model under the dependent censoring model. In this paper, a new estimator for the survivor function is proposed for the semi-Markov model under the dependent censorship on the basis of the two-stage sampling data. The consistency and the asymptotic distribution of the proposed estimator are derived. The estimation procedure is illustrated with an example of lung cancer clinical trial and simulation results are reported of the mean squared errors of estimators under a proportional hazards and two different nonproportional hazards models.

  15. On the Comparison of Interpersonal Sensitivity and Assertiveness between Drug-Dependent Persons and Ordinary People

    Directory of Open Access Journals (Sweden)

    Babak Vojudi

    2015-02-01

    Full Text Available Objective: The present study was aimed at comparing interpersonal sensitivity and assertiveness between drug-dependent persons and ordinary people. Method: The research method was causal-comparative. The statistical population of the study consisted of all narcotic addicts of Tabriz City who referred to Addiction Treatment Centers while the research was being conducted. The number of 30 addicted persons was selected through cluster sampling and 30 ordinary persons as control group through convenience sampling method. Gmbryl & Ritchie’s assertiveness questionnaire (1975 and Boyce & Parker’s Interpersonal Sensitivity Measure (IPSM 1989 were used for data collection purposes. Results: The results showed that there was a statistically significant difference between two groups in terms of interpersonal sensitivity and assertiveness. The addicts showed less assertiveness and more interpersonal sensitivity in comparison with their healthy counterparts. Conclusion: The findings show that people who are unable to express themselves and exert sensitivity in interpersonal relationships are more likely at high risk of substance dependence. However, it is possible to prevent these persons from turning to addiction by teaching them these skills.

  16. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

    NARCIS (Netherlands)

    Passamonti, L.; Luijten, M.; Ziauddeen, H.; Coyle-Gilchrist, I.T.S.; Rittman, T.; Brain, S.A.E.; Regenthal, R.; Franken, I.H.A.; Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.; Ersche, K.D.

    2017-01-01

    Rationale: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as

  17. Drivers under the influence of drugs of abuse: quantification of cocaine and impaired driving.

    Science.gov (United States)

    Arroyo, Amparo; Sánchez, Marta; Barberia, Eneko; Barbal, Maria; Marrón, M Teresa; Mora, Agustí

    2013-01-01

    In recent years, the interest in oral fluid as a biological matrix has significantly increased, particularly for detecting driving under the influence of drugs. In this study, the concentration of cocaine and its relationship with clinical symptoms in drivers suspected of driving under the influence of drugs was evaluated. A total of 154 samples of oral fluid, which tested positive for cocaine in previous immunoassay screening, Cozart Drug Detector System, were confirmed using gas chromatography/mass spectrometry method. In Catalonia, during 2007-2010, there were 1791 samples positive for cocaine among a total of 3468 samples taken from drivers who tested positive for any drug of abuse. The evaluation of clinical symptoms was through a questionnaire that was filled in by the police officers who collected the samples. The mean concentration of cocaine was 4.11 mg/l and median concentration was 0.38 mg/l (range 0.01-345.64 mg/l). Clinical impairment symptoms such as motor coordination, walking, speech, mood and state of pupils were not significant. The testing of oral fluids presents fewer ethical problems than blood or urine.

  18. Effectiveness of Gross Model-Based Emotion Regulation Strategies Training on Anger Reduction in Drug-Dependent Individuals and its Sustainability in Follow-up.

    Science.gov (United States)

    Massah, Omid; Sohrabi, Faramarz; A'azami, Yousef; Doostian, Younes; Farhoudian, Ali; Daneshmand, Reza

    2016-03-01

    Emotion plays an important role in adapting to life changes and stressful events. Difficulty regulating emotions is one of the problems drug abusers often face, and teaching these individuals to express and manage their emotions can be effective on improving their difficult circumstances. The present study aimed to determine the effectiveness of the Gross model-based emotion regulation strategies training on anger reduction in drug-dependent individuals. The present study had a quasi-experimental design wherein pretest-posttest evaluations were applied using a control group. The population under study included addicts attending Marivan's methadone maintenance therapy centers in 2012 - 2013. Convenience sampling was used to select 30 substance-dependent individuals undergoing maintenance treatment who were then randomly assigned to the experiment and control groups. The experiment group received its training in eight two-hour sessions. Data were analyzed using analysis of co-variance and paired t-test. There was significant reduction in anger symptoms of drug-dependent individuals after gross model based emotion regulation training (ERT) (P emotion regulation strategies training. Based on the results of this study, we may conclude that the gross model based emotion regulation strategies training can be applied alongside other therapies to treat drug abusers undergoing rehabilitation.

  19. Role of novelty seeking personality traits as mediator of the association between COMT and onset age of drug use in Chinese heroin dependent patients.

    Directory of Open Access Journals (Sweden)

    Ting Li

    Full Text Available Personality traits such as novelty seeking (NS are associated with substance dependence but the mechanism underlying this association remains uncertain. Previous studies have focused on the role of the dopamine pathway.Examine the relationships between allelic variants of the catechol-O-methyltransferase (COMT gene, NS personality traits, and age of onset of drug use in heroin-dependent subjects in China.The 478 heroin dependent subjects from four drug rehabilitation centers in Shanghai who were genotyped for eight tagging single nucleotide polymorphisms (SNP on the COMT gene completed the NS subscale from the Temperament and Character Inventory. Multivariate analyses were used to assess the potential mediating role of NS personality traits in the association between COMT gene variants and the age of onset of heroin use.In the univariate analysis the COMT rs737866 gene variants were independently associated with both NS and age of onset of drug use: those with the TT genotype had higher NS subscale scores and an earlier onset age of heroin use than individuals with CT or CC genotypes. In the multivariate analysis the inclusion of the NS subscore variable weakened the relationship between the COMT rs737866 TT genotype and an earlier age of onset of drug use. Our findings that COMT is associated with both NS personality traits and with the age of onset of heroin use helps to clarify the complex relationship between genetic and psychological factors in the development of substance abuse.

  20. How does the quality of a prediction depend on the magnitude of the events under study?

    Directory of Open Access Journals (Sweden)

    S. Hallerberg

    2008-04-01

    Full Text Available We investigate the predictability of extreme events in time series. The focus of this work is to understand, under which circumstances large events are better predictable than smaller events. Therefore we use a simple prediction algorithm based on precursory structures which are identified via the maximum likelihood principle. Using theses precursory structures we predict threshold crossings in autocorrelated processes of order one, which are either Gaussian, exponentially or Pareto distributed. The receiver operating characteristic curve is used as a measure for the quality of predictions we find that the dependence on the event magnitude is closely linked to the probability distribution function of the underlying stochastic process. We evaluate this dependence on the probability distribution function numerically and in the Gaussian case also analytically. Furthermore, we study predictions of threshold crossings in correlated data, i.e., velocity increments of a free jet flow. The velocity increments in the free jet flow are in dependence on the time scale either asymptotically Gaussian or asymptotically exponential distributed. If we assume that the optimal precursory structures are used to make the predictions, we find that large threshold crossings are for all different types of distributions better predictable. These results are in contrast to previous results, obtained for the prediction of large increments, which showed a strong dependence on the probability distribution function of the underlying process.

  1. Evolution of dominance under frequency-dependent intraspecific competition in an assortatively mating population.

    Science.gov (United States)

    Peischl, Stephan; Schneider, Kristan A

    2010-02-01

    We study the evolution of higher levels of dominance as a response to negative frequency-dependent selection. In contrast to previous studies, we focus on the effect of assortative mating on the evolution of dominance under frequency-dependent intraspecific competition. We analyze a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under a mixture of frequency-independent stabilizing selection, density-dependent selection, and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The second (modifier) locus determines the degree of dominance at the trait level. Additionally, the population mates assortatively with respect to similarities in the ecological trait. Our analysis shows that the parameter region in which dominance can be established decreases if small levels of assortment are introduced. In addition, the degree of dominance that can be established also decreases. In contrast, if assortment is intermediate, sexual selection for extreme types can be established, which leads to evolution of higher levels of dominance than under random mating. For modifiers with large effects, intermediate levels of assortative mating are most favorable for the evolution of dominance. For large modifiers, the speed of fixation can even be higher for intermediate levels of assortative mating than for random mating.

  2. Problems of Drug Dependence, 2002: Proceedings of the 64th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc.

    Science.gov (United States)

    Dewey, William L., Ed.; Harris, Louis S., Ed.

    This publication summarizes the activities of the most recent meeting of the nation's most influential drug abuse professionals and measures progress in a variety of areas. Outcomes of symposia, meetings, and presentations are discussed. Symposia include: (1) "Is Dopamine the Answer? Evidence for the Importance of Other Systems in the…

  3. Relationships between self-reported unfair treatment and prescription medication use, illicit drug use, and alcohol dependence among Filipino Americans.

    Science.gov (United States)

    Gee, Gilbert C; Delva, Jorge; Takeuchi, David T

    2007-05-01

    We examined associations between self-reported unfair treatment and prescription medication use, illicit drug use, and alcohol dependence. We used data from the Filipino American Community Epidemiological Survey, a cross-sectional investigation involving 2217 Filipino Americans interviewed in 1998-1999. Multinomial logistic and negative binomial regression analyses were used in assessing associations between unfair treatment and the substance use categories. Reports of unfair treatment were associated with prescription drug use, illicit drug use, and alcohol dependence after control for age, gender, location of residence, employment status, educational level, ethnic identity level, nativity, language spoken, marital status, and several health conditions. Unfair treatment may contribute to illness and subsequent use of prescription medications. Furthermore, some individuals may use illicit drugs and alcohol to cope with the stress associated with such treatment. Addressing the antecedents of unfair treatment may be a potential intervention route.

  4. 40 CFR 2.308 - Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic Act.

    Science.gov (United States)

    2010-07-01

    ... information obtained under the Federal Food, Drug and Cosmetic Act. 2.308 Section 2.308 Protection of... § 2.308 Special rules governing certain information obtained under the Federal Food, Drug and Cosmetic... Cosmetic Act, as amended, 21 U.S.C. 301 et seq. (2) Petition means a petition for the issuance of a...

  5. 40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

  6. Validation for Persian Versions of "Desire for Drug Questionnaire" and "Obsessive Compulsive Drug Use Scale" in Heroin Dependents.

    Science.gov (United States)

    Hassani-Abharian, Peyman; Mokri, Azarakhsh; Ganjgahi, Habib; Oghabian, Mohammad-Ali; Ekhtiari, Hamed

    2016-09-01

    Drug Craving could be defined as a subjective motivational state associated with a strong desire to consume drugs. Craving is a subjective phenomenon; therefore, self-report (subjective) craving measures are usually referenced. Two well-known questionnaires for measurement of drug craving severity are Desire for Drug Questionnaire or DDQ (for instant craving) and Obsessive Compulsive Drug Use Scale or OCDUS [for craving in a period of time (periodic craving), usually one week]. In this study, we evaluated the content-related validity of these questionnaires for Persian-language speaking crystalline-heroin abusers. After translation by two different groups, back translation and retranslation process of the DDQ and OCDUS questionnaires were achieved by an expert team in English language; we used them for evaluation of instant and periodic craving among 131 male crystalline-heroin abusers. Then, both DDQ and OCDUS questionnaire's scores were subjected to an exploratory principal components factor analysis (PCA). The criterion for factor extraction was an eigenvalue equal to or more than 1. The factor analysis of DDQ and OCDUS led to three factors for DDQ and four factors for OCDUS; each group of factors together explained 62% and 65% of the common factor variance, respectively. There was no significant correlation between different DDQ and OCDUS components and demographic factors. Nevertheless, approximately all of the seven OCDUS and DDQ components were significantly correlated to each other. The Persian version of DDQ and OCDUS questionnaires could be considered as valid and reliable instruments for evaluation of drug craving in male crystalline-heroin Persian-language speaking abusers.

  7. The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    Mahmoud Shirazi

    2015-06-01

    Full Text Available Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of the study. Difficulties in Emotion Regulation Scale, Self-Control Scale, and Addiction Susceptibility Questionnaire were used for data collection purposes. Results: The results indicated that difficulties engaging in goal directed behavior, impulse control difficulties, lack of emotional awareness, and lack of emotional clarity (dimensions of difficulties in emotion regulation had a significant positive correlation with potential for addiction. In addition, there was a negative significant relationship between self-control and potential for addiction among drug-dependent individuals. Conclusion: In addition to common methods of abstinence from drug dependence, teaching self-control and emotional control techniques to addicted patients can help them reduce their dependence.

  8. Robotic system for i.v. antineoplastic drug preparation: description and preliminary evaluation under simulated conditions.

    Science.gov (United States)

    Cote, D D; Torchia, M G

    1989-11-01

    A robotic system for preparing doses of i.v. antineoplastic drugs is described, and measurements made with the system are compared for accuracy and reproducibility with those made by pharmacists and technicians. System hardware consists of a robotic arm, a 16-bit microcomputer, a bar-code reader, a voice synthesizer, and an electronic balance. The software includes a menu-driven main program, executable files for each robotic activity, and an interface to allow control to pass between the program and the files. The program has routines for matching the software to the hardware; for entering information about the patient, the name of the drug ordered, and the dose; for checking the dose; for selecting the number and size of the vials to be used; for specifying the manipulations of the robotic arm; for printing labels; and for maintaining records. The robot fills an order by getting and placing a vial, inserting a needle into it and withdrawing the drug, weighing the vial, agitating the container to dissolve its contents, reading a bar code, placing a syringe in a syringe manipulator, and getting an i.v. container and injecting the drug into it. Detection of any errors by a series of self-checks arrests execution of an order. No significant differences in accuracy and precision were found between the robotic system and humans performing the same tasks under simulated conditions. The robotic system required less time than humans and eliminated the possibility of direct human contact with the i.v. admixture. Under simulated conditions, a robotic system developed to assist in the preparation of i.v. antineoplastic drugs was as accurate as a manual system and was more time efficient.

  9. Marijuana use and achievement of abstinence from alcohol and other drugs among people with substance dependence: a prospective cohort study.

    Science.gov (United States)

    Mojarrad, Mohammadali; Samet, Jeffrey H; Cheng, Debbie M; Winter, Michael R; Saitz, Richard

    2014-09-01

    Many with alcohol and other drug dependence have concurrent marijuana use, yet it is not clear how to address it during addiction treatment. This is partially due to the lack of clarity about whether marijuana use impacts one's ability to achieve abstinence from the target of addiction treatment. We examined the association between marijuana use and abstinence from other substances among individuals with substance dependence. A secondary analysis of the Addiction Health Evaluation And Disease management study, a randomized trial testing the effectiveness of chronic disease management. Individuals met criteria for drug or alcohol dependence and reported recent drug (i.e. opioid or stimulant) or heavy alcohol use. Recruitment occurred largely at an inpatient detoxification unit, and all participants were referred to primary medical care. The association between marijuana use and later abstinence from drug and heavy alcohol use was assessed using longitudinal multivariable models. Of 563 study participants, 98% completed at least one follow-up assessment and 535 (95%) had at least one pair of consecutive assessments and were included. In adjusted analyses, marijuana use was associated with a 27% reduction in the odds of abstinence from drug and heavy alcohol use (adjusted odds ratio 0.73 [95% CI, 0.56-0.97], P=0.03). Marijuana use among individuals with alcohol or other drug dependence is associated with a lower odds of achieving abstinence from drug and heavy alcohol use. These findings add evidence that suggests concomitant marijuana use among patients with addiction to other drugs merits attention from clinicians. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Willingness to pay for opioid agonist treatment among opioid dependent people who inject drugs in Ukraine.

    Science.gov (United States)

    Makarenko, Iuliia; Mazhnaya, Alyona; Marcus, Ruthanne; Bojko, Martha J; Madden, Lynn; Filippovich, Sergii; Dvoriak, Sergii; Altice, Frederick L

    2017-07-01

    In the context of decreasing external and limited Ukrainian governmental funding for opioid agonist treatments (OAT) for opioid dependent people who inject drugs in Ukraine, information on sustainable financial models is needed. Data on 855 opioid dependent people who inject drugs (PWID) were drawn from a cross-sectional nationwide survey of 1613 PWID. They comprised 434 participants who were receiving OAT and 421 who were on OAT in the past or have never been on OAT and were interested in receiving the treatment. Multivariate logistic regression was used to examine factors associated with willingness-to-pay (WTP) for OAT, stratified by OAT experience. Variation in the price which respondents were willing to pay for OAT and its effect on their monthly income among PWID with different OAT experience were assessed as a continuous variable using one-way ANOVA and Kruskal-Wallis test. Overall, 378 (44%) expressed WTP for OAT. Factors independently associated with WTP differed by OAT experience. Among those using OAT, independent predictors of WTP included: city (Dnipro - aOR=1.9; 95%CI=1.1-4.8 and Lviv - (aOR=2.2; 95%CI=1.1-4.8) compared to those elsewhere in Ukraine), higher income (aOR=1.8; 95%CI=1.2-2.7) and receiving psychosocial counseling (aOR=1.8; 95%CI=1.2-2.7). Among those who had previously been on OAT, positive attitude towards OAT (aOR=1.3; 95%CI=1.1-1.6) and family support of OAT (aOR=2.5; 95%CI=1.1-5.7) were independently associated with WTP. Among PWID who had never been on OAT, being male (aOR=2.2; 95%CI=1.1-4.2), younger age (aOR=1.9; 95%CI=1.2-3.2), higher income (aOR=2.0; 95%CI=1.2-3.4) and previous unsuccessful attempts to enter OAT (aOR=2.3; 95%CI=1.1-4.7) were independently associated with WTP. PWID were willing to commit a large percentage of their monthly income for OAT, which, however, varied significantly based on OAT experience: current OAT: 37% of monthly income, previous OAT: 53%, and never OAT: 60% (p-value=0.0009). WTP for OAT was

  11. Determinants of under-reporting of adverse drug reactions: a systematic review.

    Science.gov (United States)

    Lopez-Gonzalez, Elena; Herdeiro, Maria T; Figueiras, Adolfo

    2009-01-01

    A voluntary reporting system of adverse drug reactions (ADRs) is fundamental to drug safety surveillance but under-reporting is its major limitation. This bibliographic review sought to assess the influence of personal and professional characteristics on ADR reporting and to identify knowledge and attitudes associated with ADR reporting. A systematic review was conducted using the MEDLINE and EMBASE databases. We included papers that were published in English, French and Spanish, and covered a study population made up of health professionals. In each case, the following data were extracted: study population; workplace; study type; sample size; type of questionnaire; type of scale for measuring knowledge; response rate; personal and professional factors; and knowledge and attitudes (based on Inman's 'seven deadly sins') associated with reporting. Based on a search of computerized databases, we identified a total of 657 papers in MEDLINE and 973 in EMBASE. In all, the review covered 45 papers that fulfilled the inclusion criteria. Medical specialty was the professional characteristic most closely associated with under-reporting in 76% of studies involving physicians. Other factors associated with under-reporting were ignorance (only severe ADRs need to be reported) in 95%; diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 72%; lethargy (an amalgam of procrastination, lack of interest or time to find a report card, and other excuses) in 77%; indifference (the one case that an individual doctor might see could not contribute to medical knowledge) and insecurity (it is nearly impossible to determine whether or not a drug is responsible for a particular adverse reaction) in 67%; and complacency (only safe drugs are allowed on the market) in 47% of studies. While personal and professional factors display a weak influence, the knowledge and attitudes of health professionals appear to be strongly related with reporting in a high proportion of

  12. The use of drugs and medicines behind the wheel. [Previously called Driving under the influence of drugs and medicines.

    NARCIS (Netherlands)

    2009-01-01

    Research shows that about 4% of drivers in Europe participate in traffic after having taken drugs and/or medicines. With 3.4% this share was lower in the Netherlands; traces of drugs were found in approximately 2.8% of the car drivers and traces of drugs were found in 0.6%. Substance use is highest

  13. Inventory Model for Deteriorating Items with Quadratic Time Dependent Demand under Trade Credits

    Directory of Open Access Journals (Sweden)

    Rakesh Tripathi

    2016-02-01

    Full Text Available In this paper, an EOQ model is developed for a deteriorating item with quadratic time dependent demand rate under trade credit. Mathematical models are also derived under two different situations i.e. Case I; the credit period is less than the cycle time for settling the account and Case II; the credit period is greater than or equal to the cycle time for settling the account. The numerical examples are also given to validate the proposed model. Sensitivity analysis is given to study the effect of various parameters on ordering policy and optimal total profit. Mathematica 7.1 software is used for finding optimal numerical solutions.

  14. Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs.

    Science.gov (United States)

    Sharma, Raman; Strelevitz, Timothy J; Gao, Hongying; Clark, Alan J; Schildknegt, Klaas; Obach, R Scott; Ripp, Sharon L; Spracklin, Douglas K; Tremaine, Larry M; Vaz, Alfin D N

    2012-03-01

    The pharmacokinetic properties of drugs may be altered by kinetic deuterium isotope effects. With specifically deuterated model substrates and drugs metabolized by aldehyde oxidase, we demonstrate how knowledge of the enzyme's reaction mechanism, species differences in the role played by other enzymes in a drug's metabolic clearance, and differences in systemic clearance mechanisms are critically important for the pharmacokinetic application of deuterium isotope effects. Ex vivo methods to project the in vivo outcome using deuterated carbazeran and zoniporide with hepatic systems demonstrate the importance of establishing the extent to which other metabolic enzymes contribute to the metabolic clearance mechanism. Differences in pharmacokinetic outcomes in guinea pig and rat, with the same metabolic clearance mechanism, show how species differences in the systemic clearance mechanism can affect the in vivo outcome. Overall, to gain from the application of deuteration as a strategy to alter drug pharmacokinetics, these studies demonstrate the importance of understanding the systemic clearance mechanism and knowing the identity of the metabolic enzymes involved, the extent to which they contribute to metabolic clearance, and the extent to which metabolism contributes to the systemic clearance.

  15. United Nations Office on Drugs and Crime International Network of Drug Dependence Treatment and Rehabilitation Resource Centres: Treatnet

    Science.gov (United States)

    Tomas-Rossello, Juana; Rawson, Richard A.; Zarza, Maria J.; Bellows, Anne; Busse, Anja; Saenz, Elizabeth; Freese, Thomas; Shawkey, Mansour; Carise, Deni; Ali, Robert; Ling, Walter

    2010-01-01

    Key to the dissemination of evidence-based addiction treatments is the exchange of experiences and mutual support among treatment practitioners, as well as the availability of accurate addiction training materials and effective trainers. To address the shortage of such resources, the United Nations Office on Drugs and Crime (UNODC) created…

  16. Race/Ethnic Disparities in the Utilization of Treatment for Drug Dependent Inmates in U.S. State Correctional Facilities

    Science.gov (United States)

    Nowotny, Kathryn M.

    2014-01-01

    This study examines race/ethnic disparities in treatment for drug dependent inmates in state correctional facilities. The data come from the 2004 Survey of Inmates in State Correctional Facilities. Fixed effects logistic regression is used to analyze treatment outcomes for 5,180 inmates housed within 286 prisons. The analysis accounts for differences in background characteristics (i.e., age, gender, marital status, foreign born status, veteran status), socioeconomic characteristics (i.e., education, employment prior to incarceration), mental health (i.e., diagnosis with a serious mental illness), and incarceration experiences (i.e., current conviction, previous incarceration episodes, time served, additional sentencing requirements, external social support, disciplinary violations). The findings identify a remarkable unmet need among drug dependent inmates in that less than one-half of drug dependent inmates had received any type of treatment in prison at the time of the interview with the most common treatment type being self-help groups. Compared to whites, drug dependent Latino inmates have significantly lower odds of utilizing treatment, yet there are no significant black-white disparities found. Implications for drug treatment within prisons are discussed. PMID:25270722

  17. Role of the activation gate in determining the extracellular potassium dependency of block of HERG by trapped drugs.

    Science.gov (United States)

    Pareja, Kristeen; Chu, Elaine; Dodyk, Katrina; Richter, Kristofer; Miller, Alan

    2013-01-01

    Drug induced long QT syndrome (diLQTS) results primarily from block of the cardiac potassium channel HERG (human-ether-a-go-go related gene). In some cases long QT syndrome can result in the lethal arrhythmia torsade de pointes, an arrhythmia characterized by a rapid heart rate and severely compromised cardiac output. Many patients requiring medication present with serum potassium abnormalities due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, and aging. Extracellular potassium influences HERG channel inactivation and can alter block of HERG by some drugs. However, block of HERG by a number of drugs is not sensitive to extracellular potassium. In this study, we show that block of WT HERG by bepridil and terfenadine, two drugs previously shown to be trapped inside the HERG channel after the channel closes, is insensitive to extracellular potassium over the range of 0 mM to 20 mM. We also show that bepridil block of the HERG mutant D540K, a mutant channel that is unable to trap drugs, is dependent on extracellular potassium, correlates with the permeant ion, and is independent of HERG inactivation. These results suggest that the lack of extracellular potassium dependency of block of HERG by some drugs may in part be related to the ability of these drugs to be trapped inside the channel after the channel closes.

  18. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

    Full Text Available Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1 is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for

  19. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Science.gov (United States)

    Ojo, Kayode K; Reid, Molly C; Kallur Siddaramaiah, Latha; Müller, Joachim; Winzer, Pablo; Zhang, Zhongsheng; Keyloun, Katelyn R; Vidadala, Rama Subba Rao; Merritt, Ethan A; Hol, Wim G J; Maly, Dustin J; Fan, Erkang; Van Voorhis, Wesley C; Hemphill, Andrew

    2014-01-01

    Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine

  20. Dependence of molecular properties on proteomic family for marketed oral drugs.

    Science.gov (United States)

    Vieth, Michal; Sutherland, Jeffrey J

    2006-06-15

    An association of drugs with their proteomic family reveals that molecular properties of drugs targeting proteases, lipid and peptide G-protein-coupled receptors (GPCRs), and nuclear hormone receptors significantly exceed limits for some properties in the "rule of five", while drugs targeting cytochrome P450s, biogenic amine GPCRs, and transporters have significantly lower values for certain properties. Also, the variation in drug targets appears to be a factor explaining increasing molecular weight over time.

  1. Plane strain bending under tension as an ideal flow process in pressure – dependent plasticity

    Directory of Open Access Journals (Sweden)

    Alexandrov Sergei

    2017-01-01

    Full Text Available Ideal plastic flows are those for which all material elements follow minimum work paths. Ideal flow solutions are widely used as the basis for inverse methods for the preliminary design of metalworking processes. The present paper provides the first ideal flow solution in pressure-dependent plasticity. In particular, the process of bending under tension is considered and it is shown that there are relations between the bending moment and tensile force that result in ideal flow paths.

  2. On Critical Buckling Loads of Columns under End Load Dependent on Direction.

    Science.gov (United States)

    Başbük, Musa; Eryılmaz, Aytekin; Atay, M Tarık

    2014-01-01

    Most of the phenomena of various fields of applied sciences are nonlinear problems. Recently, various types of analytical approximate solution techniques were introduced and successfully applied to the nonlinear differential equations. One of the aforementioned techniques is the Homotopy analysis method (HAM). In this study, we applied HAM to find critical buckling load of a column under end load dependent on direction. We obtained the critical buckling loads and compared them with the exact analytic solutions in the literature.

  3. Sex differences and ovarian hormones in animal models of drug dependence.

    Science.gov (United States)

    Carroll, Marilyn E; Anker, Justin J

    2010-06-01

    Increasing evidence indicates the presence of sex differences in many aspects of drug abuse. Most studies reveal that females exceed males during the initiation, escalation, extinction, and reinstatement (relapse) of drug-seeking behavior, but males are more sensitive than females to the aversive effects of drugs such as drug withdrawal. Findings from human and animal research indicate that circulating levels of ovarian steroid hormones account for these sex differences. Estrogen (E) facilitates drug-seeking behavior, while progesterone (P) and its metabolite, allopregnanalone (ALLO), counteract the effects of E and reduce drug seeking. Estrogen and P influence other behaviors that are affiliated with drug abuse such as drug-induced locomotor sensitization and conditioned place preference. The enhanced vulnerability to drug seeking in females vs. males is also additive with the other risk factors for drug abuse (e.g., adolescence, sweet preference, novelty reactivity, and impulsivity). Finally, treatment studies using behavioral or pharmacological interventions, including P and ALLO, also indicate that females show greater treatment effectiveness during several phases of the addiction process. The neurobiological basis of sex differences in drug abuse appears to be genetic and involves the influence of ovarian hormones and their metabolites, the hypothalamic pituitary adrenal (HPA) axis, dopamine (DA), and gamma-hydroxy-butyric acid (GABA). Overall, sex and hormonal status along with other biological risk factors account for a continuum of addiction-prone and -resistant animal models that are valuable for studying drug abuse prevention and treatment strategies. Copyright 2009. Published by Elsevier Inc.

  4. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

    NARCIS (Netherlands)

    Passamonti, L. (Luca); M. Luijten (Maartje); Ziauddeen, H.; I. Coyle-Gilchrist (Ian); Rittman, T.; Brain, S.A.E.; Regenthal, R.; I.H.A. Franken (Ingmar); Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.; Ersche, K.D.

    2017-01-01

    textabstractRationale: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by

  5. La vivencia de la dependencia en un consumidor de drogas psicoactivas The experience of the dependence to a psychoactive drug in a consumer drug

    Directory of Open Access Journals (Sweden)

    Liliana Basso Musso

    2011-06-01

    Full Text Available Investigación cualitativa, de trayectoria fenomenológica, siguiendo el referencial sociológico de Schutz, cuyo objetivo es conocer la vivencia del fenómeno de la dependencia o adicción, en un consumidor de drogas psicoactivas en tratamiento en un Centro Abierto, teniendo como base las siguientes preguntas orientadoras: ¿Cómo se inició la experiencia de consumo de drogas? ¿Cuáles fueron los motivos para consumir drogas? ¿Cómo se va instalando la dependencia a ellas? ¿Cómo se dio cuenta que se había hecho dependiente a la droga? En el discurso de los consumidores se identificaron siete categorías del referencial de Shutz, que muestran aspectos significativos de la vivencia. Al analizarlas se pudo comprender al tipo vivido del consumidor de drogas psicoactivas que presenta adicción y el entendimiento de los motivos existenciales que influyeron en la instalación de esta dependencia, profundizándose así el conocimiento del fenómeno, lo que permitirá otorgarles un mejor cuidado.Qualitative, phenomenological research following Schutz, referential sociological, whose objective is to know the experience of the phenomenon of dependence or addiction to a consumer of drugs in treatment in an open centre, based on the following questions guide path: How do you start drug experience? What were the reasons for drug use? You how is it installing dependence to them? How gave account which had become dependent drug? The speech of consumers identified seven categories Schutz, referential, that showing significant aspects of the experience. To analyze them lived type drugs featuring addiction and understanding of the existential reasons that influenced the installation of this dependency, deepening the understanding of the phenomenon, thereby granting consumer could understand better care.

  6. Use and dependence on opioid drugs in the Spanish population with chronic pain: Prevalence and differences according to sex.

    Science.gov (United States)

    Coloma-Carmona, A; Carballo, J L; Rodríguez-Marín, J; Pérez-Carbonell, A

    To analyse the prevalence in the use and dependence on opioid drugs in the Spanish population with chronic pain and evaluate the differences according to sex. The demographic variables, opioid treatment characteristics and use of other substances were assessed in 229 users of opioid drugs. A descriptive bivariate analysis of the data was performed. Forty-six percent of the patients met the criteria of dependence on opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates of dependence on the use of opioid drugs were significantly higher in the extended treatments. Planning for treatments with opioids and strategies for preventing inappropriate use should not depend on the patient's sex. We need further studies on the medical and psychological variables related to the use of and dependence on opioids. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  7. The role of conduct disorder in explaining the comorbidity between alcohol and illicit drug dependence in adolescence.

    Science.gov (United States)

    Button, Tanya M M; Rhee, Soo Hyun; Hewitt, John K; Young, Susan E; Corley, Robin P; Stallings, Michael C

    2007-02-23

    Conduct disorder (CD), alcohol dependence (AD), and illicit drug dependence (IDD) frequently co-occur. This paper describes the result of an investigation of the extent to which comorbid alcohol and illicit drug dependence in adolescents are explained by etiological factors in common with conduct disorder. Participants were 645 MZ twin pairs, 702 DZ twin pairs, 429 biological sibling pairs, and 96 adoptive sibling pairs, aged 12-18 years, from a community based sample. Conduct disorder was measured using the Diagnostic Interview Schedule for Children-IV. Alcohol and illicit drug dependence were assessed using the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). For each outcome, subjects were categorized into those with no symptoms, those with one or more symptoms but no diagnosis, and those with a diagnosis. The heritability estimates for CD, AD, and IDD were 58, 66, and 36%, respectively. The genetic correlation between AD and IDD was partially explained by the genetic risk they both share with conduct disorder. We conclude that conduct disorder in adolescents explains, in part, the co-occurrence of alcohol and illicit drug dependence. Specifically, the genetic contribution to their covariation is explained partially by the genetic contribution in common with conduct disorder.

  8. Drug Dependence and Psychotic Symptoms: A Retrospective Study of Adolescents Who Abuse Drugs at Al-Amal Hospital in Jeddah, Saudi Arabia.

    Science.gov (United States)

    Alibrahim, Osama; Elawad, Nagi; Misau, Yusuf A; Shaikh, Tarteel M; Allam, Nedal

    2012-03-07

    Drug abuse is reported to be on the increase among young persons using illicit substances but little is known about the frequency with which they occur, the symptoms on presentation to health institutions, and the different substances abused. To establish this, we reviewed patient data collected at Al-Amal Hospital in Jeddah Kingdom of Saudi Arabia on young persons who are refered to the hospital for problems related to drug abuse. Data on 69 adolescent drug users were reviewed and analyzed using the Composite International Diagnostic Interview - Substance Abuse Model (CIDI-SAM) to assess dependence on substances including amphetamines, cannabis, cocaine, and opioids. Furthermore, we assessed the adolescents' data on history of delusions and hallucinations in the context of use of, or withdrawal from, these specific substances. Our analysis shows that 10 to 79.6% of users of amphetamines, cannabis, cocaine, and opiates met DSM-III-R dependence criteria for each specific substance. The prevalence of psychotic symptoms associated with each specific substance ranged from users with no diagnosis to users with severe dependence as follows: amphetamines (3-100%), cannabis (7-60.0%), cocaine (5-70.7%), and opiates (4-88%). The risk of psychotic symptoms increased for respondents who abused (OR=7.2) or had mild (OR=8.1), moderate (OR=20.0), or severe dependence (OR=14.0) on cocaine when compared to those who were users with no diagnosis. A similar pattern was evident in cannabis, opiate, and amphetamine users. In conclusion, most adolescent drug users in Saudi Arabia who are dependent on illicit substances experience psychotic symptoms in the context of use of, or withdrawal from, these substances. Psychotic symptoms increased with the severity of the disorders associated with use of all four substances. These findings underscore the importance of developing services to target this population; a population at risk of developing psychotic symptoms.

  9. Drug dependence and psychotic symptoms: a retrospective study of adolescents who abuse drugs at Al-Amal Hospital in Jeddah, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Osama Alibrahim

    2012-03-01

    Full Text Available Drug abuse is reported to be on the increase among young persons using illicit substances but little is known about the frequency with which they occur, the symptoms on presentation to health institutions, and the different substances abused. To establish this, we reviewed patient data collected at Al-Amal Hospital in Jeddah Kingdom of Saudi Arabia on young persons who are refered to the hospital for problems related to drug abuse. Data on 69 adolescent drug users were reviewed and analyzed using the Composite International Diagnostic Interview - Substance Abuse Model (CIDI-SAM to assess dependence on substances including amphetamines, cannabis, cocaine, and opioids. Furthermore, we assessed the adolescents’ data on history of delusions and hallucinations in the context of use of, or withdrawal from, these specific substances. Our analysis shows that 10 to 79.6% of users of amphetamines, cannabis, cocaine, and opiates met DSM-III-R dependence criteria for each specific substance. The prevalence of psychotic symptoms associated with each specific substance ranged from users with no diagnosis to users with severe dependence as follows: amphetamines (3-100%, cannabis (7- 60.0%, cocaine (5-70.7%, and opiates (4- 88%. The risk of psychotic symptoms increased for respondents who abused (OR=7.2 or had mild (OR=8.1, moderate (OR=20.0, or severe dependence (OR=14.0 on cocaine when compared to those who were users with no diagnosis. A similar pattern was evident in cannabis, opiate, and amphetamine users. In conclusion, most adolescent drug users in Saudi Arabia who are dependent on illicit substances experience psychotic symptoms in the context of use of, or withdrawal from, these substances. Psychotic symptoms increased with the severity of the disorders associated with use of all four substances. These findings underscore the importance of developing services to target this population; a population at risk of developing psychotic symptoms.

  10. Changing drug markets under new intellectual property regimes: the view from Central America.

    Science.gov (United States)

    Godoy, Angelina Snodgrass; Cerón, Alejandro

    2011-07-01

    The intellectual property rules inscribed in the Central American Free Trade Agreement have generated concern about access to medicines. We examined the implementation of the new intellectual property regime by tracking the policies and practices in place across 4 Central American countries. Although all 4 were responding to the same requirements under the agreement, their implementation of intellectual property rules differed. Not only were institutional practices different, but the lists of drugs to which intellectual property protection was applied varied in both volume and content. We also found that even without the influence of intellectual property, drug pricing in the region was often unpredictable and that lower cost was not the only motivation driving governments' purchasing decisions.

  11. Hydrolysis of cephalexin and meropenem by New Delhi metallo-β-lactamase: the substrate protonation mechanism is drug dependent

    Science.gov (United States)

    Das, Chandan Kumar; Nair, Nisanth N.

    Emergence of antibiotic resistance due to New Delhi Metallo $\\beta$-lactamase (NDM-1) bacterial enzymes is of great concern due to their ability to hydrolyze wide range of antibiotics. Efforts are ongoing to obtain the atomistic details of the hydrolysis mechanism in order to develop novel drugs and inhibitors against NDM-1. Especially, it remains elusive how drug molecules of different family of antibiotics are hydrolyzed by NDM-1 in an efficient manner. Here we report the detailed molecular mechanism of NDM-1 catalyzed hydrolysis of cephalexin, a cephalosporin family drug, and meropenem, a carbapenem family drug. This study employs molecular dynamics (MD) simulations using hybrid quantum mechanical/molecular mechanical (QM/MM) methods at the density functional theory level, based on which reaction pathways and the associated free energies are obtained. We find that the mechanism and the free energy barrier for the ring-opening step are the same for both the drug molecules, while the subsequent protonation step differs. In particular, we observe that the mechanism of the protonation step depends on the R2 group of the drug molecule. Our simulations show that allylic carbon protonation occurs in the case of cephalexin drug molecule where Lys211 is the proton donor and the proton transfer occurs via a water chain formed (only) at the ring-opened intermediate structure. Based on the free energy profiles, the overall kinetics of the drug hydrolysis is discussed. Finally, we show that the proposed mechanisms and free energy profiles could explain various experimental observations.

  12. Institutional stakeholder perceptions of barriers to addiction treatment under Mexico's drug policy reform.

    Science.gov (United States)

    Werb, Dan; Strathdee, Steffanie A; Meza, Emilo; Rangel Gomez, Maria Gudelia; Palinkas, Lawrence; Medina-Mora, Maria Elena; Beletsky, Leo

    2017-05-01

    Mexico has experienced disproportionate drug-related harms given its role as a production and transit zone for illegal drugs destined primarily for the USA. In response, in 2009, the Mexican federal government passed legislation mandating pre-arrest diversion of drug-dependent individuals towards addiction treatment. However, this federal law was not specific about how the scale-up of the addiction treatment sector was to be operationalised. We therefore conducted in-depth qualitative interviews with key 'interactors' in fields affected by the federal legislation, including participants from the law enforcement, public health, addiction treatment, and governmental administration sectors. Among 19 participants from the municipal, state and federal levels were interviewed and multiple barriers to policy reform were identified. First, there is a lack of institutional expertise to implement the reform. Second, the operationalisation of the reform was not accompanied by a coordinated action plan. Third, the law is an unfunded mandate. Institutional barriers are likely hampering the implementation of Mexico's policy reform. Addressing the concerns expressed by interactors through the scale-up of services, the provision of increased training and education programmes for stakeholders and a coordinated action plan to operationalise the policy reform are likely needed to improve the policy reform process.

  13. Time-dependent scattering of incident light of various wavelengths in ferrofluids under external magnetic field

    Science.gov (United States)

    Jin, Jingyu; Song, Dongxing; Geng, Jiafeng; Jing, Dengwei

    2018-02-01

    Ferrofluids can exhibit the anisotropic thermodynamic properties under magnetic fields. The dynamic optical properties of ferrofluids in the presence of magnetic fields are of particular interest due to their potential application as various optical devices. Although time-dependent light scattering by ferrofluids have been extensively studied, the effect of wavelength of incident light have been rarely considered. Here, for the first time, we investigated both the time- and wavelength-dependent light scattering in water based ferrofluids containing Fe3O4 nanoparticles under an external magnetic field. The field-induced response behavior of the prepared ferrofluid samples was determined and verified first by thermal conductivity measurement and numerical simulation. Double-beam UV-Vis spectrophotometer was employed to record the temporal evolution of transmitted intensity of incident light of various wavelengths passing through the ferrofluid sample and propagating parallel to the applied field. As expected, the light intensity decreases to a certain value right after the field is turned on due to the thermal fluctuation induced disorder inside the flexible particle chains. Then the light intensity further decreases with time until the appearance of a minimum at time τ0 followed by an inversed increase before finally reaches equilibrium at a particular time. More importantly, the characteristic inversion time τ0 was found to follow a power law increase with the wavelength of incident light (τ0 ∼ λα, where α = 2.07). A quantitative explanation for the wavelength dependence of characteristic time was proposed based on the finite-difference time-domain (FDTD) method. The simulation results are in good agreement with our experimental observations. The time-dependent light scattering in ferrofluids under different incident wavelengths was rationalized by considering both the coarsening process of the particle chains and the occurrence of resonance within the

  14. Toward the virtual screening of potential drugs in the homology modeled NAD+ dependent DNA ligase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Singh, Vijai; Somvanshi, Pallavi

    2010-02-01

    DNA ligase is an important enzyme and it plays vital role in the replication and repair; also catalyzes nick joining between adjacent bases of DNA. The NAD(+) dependent DNA ligase is selectively present in eubacteria and few viruses; but missing in humans. Homology modeling was used to generate 3-D structure of NAD(+) dependent DNA ligase (LigA) of Mycobacterium tuberculosis using the known template (PDB: 2OWO). Furthermore, the stereochemical quality and torsion angle of 3-D structure was validated. Numerous effective drugs were selected and the active amino acid residue in LigA was targeted and virtual screening through molecular docking was done. In this analysis, four drugs Chloroquine, Hydroxychloroquine, Putrienscine and Adriamycin were found more potent in inhibition of M. tuberculosis through the robust binding affinity between protein-drug interactions in comparison with the other studied drugs. A phylogenetic tree was constructed and it was observed that homology of LigA in M. tuberculosis resembled with other Mycobacterium species. The conserved active amino acids of LigA may be useful to target these drugs. These findings could be used as the starting point of a rational design of novel antibacterial drugs and its analogs.

  15. Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study.

    Science.gov (United States)

    Rapeli, Pekka; Fabritius, Carola; Kalska, Hely; Alho, Hannu

    2012-11-02

    Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST) is associated with their drug treatment variables. Opioid-dependent patients (N = 104) who were treated either with buprenorphine or methadone (n = 52 in both groups) were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis. Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD) and frequent substance abuse during the past month predicted about 20% of verbal memory performance. Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

  16. Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

    Science.gov (United States)

    Barateau, Lucie; Jaussent, Isabelle; Lopez, Régis; Boutrel, Benjamin; Leu-Semenescu, Smaranda; Arnulf, Isabelle; Dauvilliers, Yves

    2016-03-01

    Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other

  17. Chemical dependence - resources

    Science.gov (United States)

    Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... organizations are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd. ...

  18. Alcohol and Drug Use, Abuse, and Dependence in Urban Areas and Colonias of the Texas-Mexico Border

    Science.gov (United States)

    Wallisch, Lynn S.; Spence, Richard T.

    2006-01-01

    This study describes the prevalence of alcohol and drug use, abuse, and dependence among adults on the Texas-Mexico border in 2002-2003. The findings are based on survey responses from a random sample of 1,200 adults living in households in three communities: El Paso, a densely populated city in west Texas; the less dense urbanized areas of the…

  19. Individuality and Contextual Influences on Drug Dependence: A 15-Year Prospective Longitudinal Study of Adolescents from Harlem

    Science.gov (United States)

    Brook, Judith S.; Lee, Jung Yeon; Brown, Elaine N.; Finch, Stephen J.; Brook, David W.

    2012-01-01

    In this 15-year longitudinal study the authors investigated individual and contextual factors that predispose adolescents from a disadvantaged urban area to drug dependence in adulthood. Adolescents were recruited from schools serving East Harlem in New York City. Of the 838 participants followed to adulthood, 59% were women, 55% were African…

  20. The Effect of Group Therapy With Transactional Analysis Approach on Emotional Intelligence, Executive Functions and Drug Dependency.

    Science.gov (United States)

    Forghani, Masoomeh; Ghanbari Hashem Abadi, Bahram Ali

    2016-06-01

    The aim of the present study was to evaluate the effect of group psychotherapy with transactional analysis (TA) approach on emotional intelligence (EI), executive functions and substance dependency among drug-addicts at rehabilitation centers in Mashhad city, Iran, in 2013. In this quasi-experimental study with pretest, posttest, case- control stages, 30 patients were selected from a rehabilitation center and randomly divided into two groups. The case group received 12 sessions of group psychotherapy with transactional analysis approach. Then the effects of independent variable (group psychotherapy with TA approach) on EI, executive function and drug dependency were assessed. The Bar-on test was used for EI, Stroop test for measuring executive function and morphine test, meth-amphetamines and B2 test for evaluating drug dependency. Data were analyzed using multifactorial covariance analysis, Levenes' analysis, MANCOVA, t-student and Pearson correlation coefficient tests t with SPSS software. Our results showed that group psychotherapy with the TA approach was effective in improving EI, executive functions and decreasing drug dependency (P psychotherapy with TA approach has significant effects on addicts and prevents addiction recurrence by improving the coping capabilities and some mental functions of the subjects. However, there are some limitations regarding this study including follow-up duration and sample size.

  1. Driving under the influence of drugs -- evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms.

    Science.gov (United States)

    Toennes, Stefan W; Kauert, Gerold F; Steinmeyer, Stefan; Moeller, Manfred R

    2005-09-10

    A study was performed to acquire urine, serum and oral fluid samples in cases of suspected driving under the influence of drugs of abuse. Oral fluid was collected using a novel sampling/testing device (Dräger DrugTest System). The aim of the study was to evaluate oral fluid and urine as a predictor of blood samples positive for drugs and impairment symptoms. Analysis for cannabinoids, amphetamine and its derivatives, opiates and cocaine was performed in urine using the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography-mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and medical officer observations of impairment symptoms were rated and evaluated using a threshold value for the classification of driving inability. Accuracy in correlating drug detection in oral fluid and serum were >90% for all substances and also >90% in urine and serum except for THC (71.0%). Of the cases with oral fluid positive for any drug 97.1% of corresponding serum samples were also positive for at least one drug; of drug-positive urine samples this were only 82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired which were the same with drug-positive oral fluid while more persons with drug-positive urine samples appeared uninfluenced (32.7%). The data demonstrate that oral fluid is superior to urine in correlating with serum analytical data and impairment symptoms of drivers under the influence of drugs of abuse.

  2. FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action inMalassezia.

    Science.gov (United States)

    Ianiri, Giuseppe; Applen Clancey, Shelly; Lee, Soo Chan; Heitman, Joseph

    2017-10-24

    The genus Malassezia includes yeasts that are commonly found on the skin or hair of animals and humans as commensals and are associated with a number of skin disorders. We have previously developed an Agrobacterium tumefaciens transformation system effective for both targeted gene deletion and insertional mutagenesis in Malassezia furfur and M. sympodialis In the present study, these molecular resources were applied to characterize the immunophilin FKBP12 as the target of tacrolimus (FK506), ascomycin, and pimecrolimus, which are calcineurin inhibitors that are used as alternatives to corticosteroids in the treatment of inflammatory skin disorders such as those associated with Malassezia species. While M. furfur and M. sympodialis showed in vitro sensitivity to these agents, fkb1 Δ mutants displayed full resistance to all three of them, confirming that FKBP12 is the target of these calcineurin inhibitors and is essential for their activity. We found that calcineurin inhibitors act additively with fluconazole through an FKBP12-dependent mechanism. Spontaneous M. sympodialis isolates resistant to calcineurin inhibitors had mutations in the gene encoding FKBP12 in regions predicted to affect the interactions between FKBP12 and FK506 based on structural modeling. Due to the presence of homopolymer nucleotide repeats in the gene encoding FKBP12, an msh2 Δ hypermutator of M. sympodialis was engineered and exhibited an increase of more than 20-fold in the rate of emergence of resistance to FK506 compared to that of the wild-type strain, with the majority of the mutations found in these repeats. IMPORTANCE Malassezia species are the most abundant fungal components of the mammalian and human skin microbiome. Although they belong to the natural skin commensal flora of humans, they are also associated with a variety of clinical skin disorders. The standard treatment for Malassezia -associated inflammatory skin infections is topical corticosteroids, although their use

  3. Hospitalizations for Endocarditis and Associated Health Care Costs Among Persons with Diagnosed Drug Dependence - North Carolina, 2010-2015.

    Science.gov (United States)

    Fleischauer, Aaron T; Ruhl, Laura; Rhea, Sarah; Barnes, Erin

    2017-06-09

    Opioid dependence and overdose have increased to epidemic levels in the United States. The 2014 National Survey on Drug Use and Health estimated that 4.3 million persons were nonmedical users of prescription pain relievers (1). These users are 40 times more likely than the general population to use heroin or other injection drugs (2). Furthermore, CDC estimated a near quadrupling of heroin-related overdose deaths during 2002-2014 (3). Although overdose contributes most to drug-associated mortality, infectious complications of intravenous drug use constitute a major cause of morbidity leading to hospitalization (4). In addition to infections from hepatitis C virus (HCV) and human immunodeficiency virus (HIV), injecting drug users are at increased risk for acquiring invasive bacterial infections, including endocarditis (5,6). Evidence that hospitalizations for endocarditis are increasing in association with the current opioid epidemic exists (7-9). To examine trends in hospitalizations for endocarditis among persons in North Carolina with drug dependence during 2010-2015, data from the North Carolina Hospital Discharge database were analyzed. The incidence of hospital discharge diagnoses for drug dependence combined with endocarditis increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from $1.1 million in 2010 to $22.2 million in 2015. To reduce the risk for morbidity and mortality related to opioid-associated endocarditis, public health programs and health care systems should consider collaborating to implement syringe service programs, harm reduction strategies, and opioid treatment programs.

  4. Consumption of antihypertensive drugs dispensed under the pharmacy benefit management program

    Directory of Open Access Journals (Sweden)

    Aline Pereira Rocha

    2011-12-01

    Full Text Available Pharmacy benefit management (PBM programs provide attractive discounts for drug purchase, a relevant measure to address costs, mainly of drugs for the treatment of chronic diseases. This study investigated whether PBM may be used as a tool to provide information about the use of antihypertensive medications when they are purchased. The profile of medicines taken to treat high blood pressure by large IT company employees and their dependents was evaluated from January to December 2009. The mean rate of drug boxes purchased to control hypertension was 9.4 ± 10.0 in 2009. Men purchased more drugs than women. The number of drugs purchased for the treatment of hypertension was lower than expected in all age groups except for individuals aged 54-58 and >59 years. Among men, the purchase of drugs to treat hypertension was higher than expected in the 24-28, 34-38 and 54-58 age groups. Among women, results matched expectations, except for the age group 34-38 years, in which purchase was lower than expected. Individuals in the age group 0-18 years were found to consume antihypertensive drugs. Although the PBM system may be used to identify drugs purchased by users, it does not ensure patient adherence to recommended drug treatment to control hypertension.O objetivo do Programa de Benefícios em Medicamentos (PBM é proporcionar descontos atraentes para aquisição de medicamentos, um fator relevante para o custo, principalmente no tratamento de doenças crônicas. O objetivo deste estudo é comprovar se o PBM pode ser utilizado como ferramenta para o fornecimento de informações sobre o consumo de medicamentos antihipertensivos através da aquisição dos mesmos. Foi realizada análise do perfil de medicamentos adquiridos para o tratamento de hipertensão arterial sistêmica por funcionários e seus dependentes de uma empresa de grande porte na área de tecnologia de informação (TI no período compreendido entre janeiro a dezembro de 2009. A taxa de

  5. Temperature-dependent dynamic mechanical properties of magnetorheological elastomers under magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Benxiang, E-mail: jubenxiang@qq.com [National Instrument Functional Materials Engineering Technology Research Center, Chongqing 400707 (China); Tang, Rui; Zhang, Dengyou; Yang, Bailian [National Instrument Functional Materials Engineering Technology Research Center, Chongqing 400707 (China); Yu, Miao; Liao, Changrong [College of Optoelectronic Engineering, Chongqing University, Chongqing 400044 (China)

    2015-01-15

    Both anisotropic and isotropic magnetorheological elastomer (MRE) samples were fabricated by using as-prepared polyurethane (PU) matrix and carbonyl iron particles. Temperature-dependent dynamic mechanical properties of MRE were investigated and analyzed. Due to the unique structural features of as-prepared matrix, temperature has a greater impact on the properties of as-prepared MRE, especially isotropic MRE. With increasing of temperature and magnetic field, MR effect of isotropic MRE can reach up to as high as 4176.5% at temperature of 80 °C, and the mechanism of the temperature-dependent in presence of magnetic field was discussed. These results indicated that MRE is a kind of temperature-dependent material, and can be cycled between MRE and MR plastomer (MRP) by varying temperature. - Highlights: • Both anisotropic and isotropic MRE were fabricated by using as-prepared matrix. • Temperature-dependent properties of MRE under magnetic field were investigated. • As-prepared MRE can transform MRE to MRP by adjusting temperature.

  6. Dynamic phase transitions in a cylindrical Ising nanowire under a time-dependent oscillating magnetic field

    International Nuclear Information System (INIS)

    Deviren, Bayram; Kantar, Ersin; Keskin, Mustafa

    2012-01-01

    The dynamic phase transitions in a cylindrical Ising nanowire system under a time-dependent oscillating external magnetic field for both ferromagnetic and antiferromagnetic interactions are investigated within the effective-field theory with correlations and the Glauber-type stochastic dynamics approach. The effective-field dynamic equations for the average longitudinal magnetizations on the surface shell and core are derived by employing the Glauber transition rates. Temperature dependence of the dynamic magnetizations, the dynamic total magnetization, the hysteresis loop areas and the dynamic correlations are investigated in order to characterize the nature (first- or second-order) of the dynamic transitions as well as the dynamic phase transition temperatures and the compensation behaviors. The system strongly affected by the surface situations. Some characteristic phenomena are found depending on the ratio of the physical parameters in the surface shell and the core. According to the values of Hamiltonian parameters, five different types of compensation behaviors in the Néel classification nomenclature exist in the system. The system also exhibits a reentrant behavior. - Highlights: ► The dynamic aspects of a cylindrical Ising nanowire are investigated in detail. ► The dynamic magnetizations, hysteresis loop areas and correlations are calculated. ► We studied both the FM and AFM interactions within the EFT with correlations. ► Some characteristic phenomena are found depending on the interaction parameters. ► We obtained five different types of compensation behaviors and reentrant behavior.

  7. Dynamic phase transitions in a cylindrical Ising nanowire under a time-dependent oscillating magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Deviren, Bayram [Department of Physics, Nevsehir University, 50300 Nevsehir (Turkey); Kantar, Ersin [Department of Physics, Erciyes University, 38039 Kayseri (Turkey); Keskin, Mustafa, E-mail: keskin@erciyes.edu.tr [Department of Physics, Erciyes University, 38039 Kayseri (Turkey)

    2012-07-15

    The dynamic phase transitions in a cylindrical Ising nanowire system under a time-dependent oscillating external magnetic field for both ferromagnetic and antiferromagnetic interactions are investigated within the effective-field theory with correlations and the Glauber-type stochastic dynamics approach. The effective-field dynamic equations for the average longitudinal magnetizations on the surface shell and core are derived by employing the Glauber transition rates. Temperature dependence of the dynamic magnetizations, the dynamic total magnetization, the hysteresis loop areas and the dynamic correlations are investigated in order to characterize the nature (first- or second-order) of the dynamic transitions as well as the dynamic phase transition temperatures and the compensation behaviors. The system strongly affected by the surface situations. Some characteristic phenomena are found depending on the ratio of the physical parameters in the surface shell and the core. According to the values of Hamiltonian parameters, five different types of compensation behaviors in the Neel classification nomenclature exist in the system. The system also exhibits a reentrant behavior. - Highlights: Black-Right-Pointing-Pointer The dynamic aspects of a cylindrical Ising nanowire are investigated in detail. Black-Right-Pointing-Pointer The dynamic magnetizations, hysteresis loop areas and correlations are calculated. Black-Right-Pointing-Pointer We studied both the FM and AFM interactions within the EFT with correlations. Black-Right-Pointing-Pointer Some characteristic phenomena are found depending on the interaction parameters. Black-Right-Pointing-Pointer We obtained five different types of compensation behaviors and reentrant behavior.

  8. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  9. pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery.

    Science.gov (United States)

    Varma, Manthena V; Gardner, Iain; Steyn, Stefanus J; Nkansah, Paul; Rotter, Charles J; Whitney-Pickett, Carrie; Zhang, Hui; Di, Li; Cram, Michael; Fenner, Katherine S; El-Kattan, Ayman F

    2012-05-07

    The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts have been extended in the Biopharmaceutics Drug Disposition Classification System (BDDCS) to explain the potential mechanism of drug clearance and understand the effects of uptake and efflux transporters on absorption, distribution, metabolism, and elimination. The objective of present work is to establish criteria for provisional biopharmaceutics classification using pH-dependent passive permeability and aqueous solubility data generated from high throughput screening methodologies in drug discovery settings. The apparent permeability across monolayers of clonal cell line of Madin-Darby canine kidney cells, selected for low endogenous efflux transporter expression, was measured for a set of 105 drugs, with known BCS and BDDCS class. The permeability at apical pH 6.5 for acidic drugs and at pH 7.4 for nonacidic drugs showed a good correlation with the fraction absorbed in human (Fa). Receiver operating characteristic (ROC) curve analysis was utilized to define the permeability class boundary. At permeability ≥ 5 × 10(-6) cm/s, the accuracy of predicting Fa of ≥ 0.90 was 87%. Also, this cutoff showed more than 80% sensitivity and specificity in predicting the literature permeability classes (BCS), and the metabolism classes (BDDCS). The equilibrium solubility of a subset of 49 drugs was measured in pH 1.2 medium, pH 6.5 phosphate buffer, and in FaSSIF medium (pH 6.5). Although dose was not considered, good concordance of the measured solubility with BCS and BDDCS solubility class was achieved, when solubility at pH 1.2 was used for acidic compounds and FaSSIF solubility was used for basic, neutral, and zwitterionic compounds. Using a cutoff of 200 μg/mL, the data set suggested a 93% sensitivity and 86% specificity in predicting both the BCS and BDDCS solubility classes. In conclusion, this study identified

  10. Recognition of Immune Reconstitution Syndrome Necessary for Better Management of Patients with Severe Drug Eruptions and Those under Immunosuppressive Therapy

    Directory of Open Access Journals (Sweden)

    Tetsuo Shiohara

    2010-01-01

    Full Text Available The immune reconstitution syndrome (IRS is an increasingly recognized disease concept and is observed with a broad-spectrum of immunosuppressive therapy-related opportunistic infectious diseases and severe drug eruptions complicated by viral reactivations. Clinical illness consistent with IRS includes tuberculosis, herpes zoster, herpes simples, cytomegalovirus infections and sarcoidosis: thus, the manifestations of this syndrome and diverse and depend on the tissue burden of the preexisting infectious agents during the immunosuppressive state, the nature of the immune system being restored, and underlying diseases of the hosts. Although IRS has originally been reported to occur in the setting of HIV infection, it has become clear that the development of IRS can also be in HIV-negative hosts receiving immunosuppressive agents, such as prednisolone and tumor necrosis factor α inhibitors, upon their reduction and withdrawal. Drug-induced hypersensitivity syndrome, a life-threatening multiorgan system reaction, is another manifestation of the newly observed IRS. Clinical recognition of the IRS is especially important in improving the outcome for diseases with an otherwise life-threatening progenosis. Clinicians should be aware of the implications of IRS and recognize that relieving the symptoms and signs of immune recovery by anti-inflammatory therapies needs to be balanced with anti-microbial therapies aiming at reducing the amplitude and duration of tissue burden of preexisting microbes.

  11. MDMA enhances hippocampal-dependent learning and memory under restrictive conditions, and modifies hippocampal spine density.

    Science.gov (United States)

    Abad, Sònia; Fole, Alberto; del Olmo, Nuria; Pubill, David; Pallàs, Mercè; Junyent, Fèlix; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena

    2014-03-01

    Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes. Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration. One week later, when acquisition or reference memory was evaluated in a standard Morris water maze (MWM), no differences were obtained between groups. However, MDMA-exposed animals performed better when the MWM was implemented under more difficult conditions. Animals of MDMA group were less anxious and were more prepared to take risks, as in the open field test they ventured more frequently into the central area. We have demonstrated that MDMA caused an increase in brain-derived neurotrophic factor (BDNF) expression. When spine density was evaluated, MDMA-treated rats presented a reduced density when compared with saline, but overall, training increased the total number of spines, concluding that in MDMA-group, training prevented a reduction in spine density or induced its recovery. This study provides support for the conclusion that binge administration of MDMA, known to be associated to neurotoxic damage of hippocampal serotonergic terminals, increases BDNF expression and stimulates synaptic plasticity when associated with training. In these conditions, adolescent rats perform better in a more difficult water maze task under restricted conditions of learning and memory. The effect on this task could be modulated by other behavioural changes provoked by MDMA.

  12. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  13. Modeling the state dependent impulse control for computer virus propagation under media coverage

    Science.gov (United States)

    Liang, Xiyin; Pei, Yongzhen; Lv, Yunfei

    2018-02-01

    A state dependent impulsive control model is proposed to model the spread of computer virus incorporating media coverage. By the successor function, the sufficient conditions for the existence and uniqueness of order-1 periodic solution are presented first. Secondly, for two classes of periodic solutions, the geometric property of successor function and the analogue of the Poincaré criterion are employed to obtain the stability results. These results show that the number of the infective computers is under the threshold all the time. Finally, the theoretic and numerical analysis show that media coverage can delay the spread of computer virus.

  14. Drug Dependence and Abuse in Kenyan Secondary Schools: Strategies for Intervention

    Science.gov (United States)

    Ngesu, Lewis M.; Ndiku, Judah; Masese, Alice

    2008-01-01

    There may have been a time when we in Kenya considered the use or abuse of drugs as a problem relating only to Western world. Today it has become an African problem to the extent that a month hardly passes without media reports on large quantities of drugs having been intercepted in a number of African cities and towns. The results of the study…

  15. [The use of prescription drugs with dependence potential in Germany : A prospective analysis of prescriptions in the public healthcare system between 2006 and 2010].

    Science.gov (United States)

    Buth, Sven; Holzbach, Rüdiger; Rosenkranz, Moritz; Verthein, Uwe

    2017-08-01

    In Germany, about 1.4 to 2.6 million people are dependent on prescription drugs, mainly benzodiazepine derivatives and opioid analgesics. Despite this large number of affected people, studies on prescription behaviour and drug intake are scarce. There are particularly few empirical findings available with regard to elderly people age 65 and over who are disproportionally affected by prescription drug abuse. The North German Pharmacy Computing Centre (Norddeutsches Apothekenrechenzentrum, NARZ) collects the prescription data of about 11 million citizens and covers over 80% of drug pharmacies in North Germany. Based on the data from NARZ, we evaluate person-related prescriptions of benzodiazepines, Z‑drugs and opioid analgesics. By means of incremental calculations, we determine the prevalence of prescription drug use, the long-term intake, the average daily dose of these medications and present this information as a five-year trend (2006-2010). In 2006, 10.6% of the members of public healthcare system were prescribed at least one of the medications under study. This proportion hardly changed within the five-year span. The share of patients with benzodiazepine prescription steadily decreased from 2006 (5.5%) to 2010 (5.1%), especially among elderly people. While the prevalence of Z‑drug prescriptions remained the same at about 1%, there was a slight increase in prescriptions of opioid analgesics with 5.4% in 2006 to 5.7% in 2010. The proportion of patients with long-term prescriptions decreased with regard to benzodiazepines (from 17.0 to 12.8%) and Z‑drugs (from 24.3 to 21.2%), but increased for opioid analgesics (from 19.2 to 21.2%). The analytical method used in this study is an innovative epidemiological approach to evaluate person-related register data over the course of several years. Establishing a monitoring system of prescription drugs with potential for dependence may allow for a quicker identification of trends and initiation of appropriate

  16. Varsity Medical Ethics Debate 2015: should nootropic drugs be available under prescription on the NHS?

    Science.gov (United States)

    Thorley, Emma; Kang, Isaac; D'Costa, Stephanie; Vlazaki, Myrto; Ayeko, Olaoluwa; Arbe-Barnes, Edward H; Swerner, Casey B

    2016-09-13

    The 2015 Varsity Medical Ethics debate convened upon the motion: "This house believes nootropic drugs should be available under prescription". This annual debate between students from the Universities of Oxford and Cambridge, now in its seventh year, provided the starting point for arguments on the subject. The present article brings together and extends many of the arguments put forward during the debate. We explore the current usage of nootropic drugs, their safety and whether it would be beneficial to individuals and society as a whole for them to be available under prescription. The Varsity Medical Debate was first held in 2008 with the aim of allowing students to engage in discussion about ethics and policy within healthcare. The event is held annually and it is hoped that this will allow future leaders to voice a perspective on the arguments behind topics that will feature heavily in future healthcare and science policy. This year the Oxford University Medical Society at the Oxford Union hosted the debate.

  17. Photoinduced Dynamics and Toxicity of a Cancer Drug in Proximity of Inorganic Nanoparticles under Visible Light.

    Science.gov (United States)

    Chaudhuri, Siddhi; Sardar, Samim; Bagchi, Damayanti; Dutta, Shreyasi; Debnath, Sushanta; Saha, Partha; Lemmens, Peter; Pal, Samir Kumar

    2016-01-18

    Drug sensitization with various inorganic nanoparticles (NPs) has proved to be a promising and an emergent concept in the field of nanomedicine. Rose bengal (RB), a notable photosensitizer, triggers the formation of reactive oxygen species under green-light irradiation, and consequently, it induces cytotoxicity and cell death. In the present study, the effect of photoinduced dynamics of RB upon complexation with semiconductor zinc oxide NPs is explored. To accomplish this, we successfully synthesized nanohybrids of RB with ZnO NPs with a particle size of 24 nm and optically characterized them. The uniform size and integrity of the particles were confirmed by high-resolution transmission electron microscopy. UV/Vis absorption and steady-state fluorescence studies reveal the formation of the nanohybrids. ultrafast picosecond-resolved fluorescence studies of RB-ZnO nanohybrids demonstrate an efficient electron transfer from the photoexcited drug to the semiconductor NPs. Picosecond-resolved Förster resonance energy transfer from ZnO NPs to RB unravel the proximity of the drug to the semiconductor at the molecular level. The photoinduced ROS formation was monitored using a dichlorofluorescin oxidation assay, which is a conventional oxidative stress indicator. It is observed that the ROS generation under green light illumination is greater at low concentrations of RB-ZnO nanohybrids compared with free RB. Substantial photodynamic activity of the nanohybrids in bacterial and fungal cell lines validated the in vitro toxicity results. Furthermore, the cytotoxic effect of the nanohybrids in HeLa cells, which was monitored by MTT assay, is also noteworthy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Angle-dependent light emission from aligned multiwalled carbon nanotubes under CO2 laser irradiation

    International Nuclear Information System (INIS)

    Zhang, Y; Gong, T; Liu, W J; Wei, J Q; Zhang, X F; Wang, K L; Zhong, M L; Wu, D H

    2007-01-01

    This paper reports the light emission from aligned multiwalled carbon nanotubes (MWNTs) under continuous wave CO 2 laser (λ = 10.6 μm) irradiation. Results indicate that the light emission is dependent on the angle θ between the laser incident direction and the nanotube axis. The relative intensity of the light emission at certain wavelengths shows a Lorentzian feature when θ varies from 0 0 to 90 0 . The Lorentzian fitting curve displays a distinct tendency between shorter (λ 700 nm). A minimum intensity was observed at θ m close to 67 0 under shorter wavelength, whereas a maximum intensity was shown at θ m of about 60 0 at longer wavelength. These results show the anisotropic property of aligned MWNTs

  19. Negative mood reverses devaluation of goal-directed drug-seeking favouring an incentive learning account of drug dependence.

    Science.gov (United States)

    Hogarth, Lee; He, Zhimin; Chase, Henry W; Wills, Andy J; Troisi, Joseph; Leventhal, Adam M; Mathew, Amanda R; Hitsman, Brian

    2015-09-01

    Two theories explain how negative mood primes smoking behaviour. The stimulus-response (S-R) account argues that in the negative mood state, smoking is experienced as more reinforcing, establishing a direct (automatic) association between the negative mood state and smoking behaviour. By contrast, the incentive learning account argues that in the negative mood state smoking is expected to be more reinforcing, which integrates with instrumental knowledge of the response required to produce that outcome. One differential prediction is that whereas the incentive learning account anticipates that negative mood induction could augment a novel tobacco-seeking response in an extinction test, the S-R account could not explain this effect because the extinction test prevents S-R learning by omitting experience of the reinforcer. To test this, overnight-deprived daily smokers (n = 44) acquired two instrumental responses for tobacco and chocolate points, respectively, before smoking to satiety. Half then received negative mood induction to raise the expected value of tobacco, opposing satiety, whilst the remainder received positive mood induction. Finally, a choice between tobacco and chocolate was measured in extinction to test whether negative mood could augment tobacco choice, opposing satiety, in the absence of direct experience of tobacco reinforcement. Negative mood induction not only abolished the devaluation of tobacco choice, but participants with a significant increase in negative mood increased their tobacco choice in extinction, despite satiety. These findings suggest that negative mood augments drug-seeking by raising the expected value of the drug through incentive learning, rather than through automatic S-R control.

  20. Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Alatawi, Yasser M; Hansen, Richard A

    2017-07-01

    To examine how closely reporting rates in the FDA Adverse Event Reporting System (FAERS) reflect expected rates of known adverse drug events (ADEs). We selected three groups of drugs to reflect hypothesized variation in sensitivity to reporting, including statins, biologics, and narrow therapeutics index drugs (NTI). The numbers of ADEs in FAERS were divided by utilization estimates from ambulatory health care data (NAMCS/NHAMCS) to calculate a reported proportion. One sample z-test for proportions compared the proportion of ADEs reported to an expected ADE proportion derived from drug labels, reference databases, and peer-reviewed papers. The majority of drug-ADE pairs showed significant under-reporting. For example, roughly 0.01% to 44% of statin events were reported (z-test p 100%) and NTI (20% to >100%) drugs had relatively higher reporting rates. Roughly 20% to 33% of the minimum number of expected serious events were reported with biologics and NTI drugs. This study supports previous evidence of under-reporting of ADEs in spontaneous reporting data. But, under-reporting varies considerably by the type of drug and the type of ADEs, and this variability in under-reporting should be considered when interpreting safety signals.

  1. FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

    Science.gov (United States)

    Lublin, Alex; Isoda, Fumiko; Patel, Harshil; Yen, Kelvin; Nguyen, Linda; Hajje, Daher; Schwartz, Marc; Mobbs, Charles

    2011-01-01

    Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

  2. FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

    Directory of Open Access Journals (Sweden)

    Alex Lublin

    Full Text Available Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

  3. Current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients

    Directory of Open Access Journals (Sweden)

    Suhail Ahmed Almani

    2017-01-01

    Full Text Available Objective: The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. Study Design: This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Subjects and Methods: Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA was also used for identification. Data were analyzed on Statisti × 8.1 (USA. Results: Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female (P = 0.0001. Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8% patients showed growth of A. baumannii. Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. Conclusion: The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

  4. Current Trends of Drug Resistance Patterns of Acinetobacter baumannii Infection in Blood Transfusion-dependent Thalassemia Patients.

    Science.gov (United States)

    Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan

    2017-01-01

    The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

  5. Field angle dependence of voltage-induced ferromagnetic resonance under DC bias voltage

    International Nuclear Information System (INIS)

    Shiota, Yoichi; Miwa, Shinji; Tamaru, Shingo; Nozaki, Takayuki; Kubota, Hitoshi; Fukushima, Akio; Suzuki, Yoshishige; Yuasa, Shinji

    2016-01-01

    We studied the rectification function of microwaves in CoFeB/MgO-based magnetic tunnel junctions using voltage-induced ferromagnetic resonance (FMR). Our findings reveal that the shape of the structure of the spectrum depends on the rotation angle of the external magnetic field, providing clear evidence that FMR dynamics are excited by voltage-induced magnetic anisotropy changes. Further, enhancement of the rectified voltage was demonstrated under a DC bias voltage. In our experiments, the highest microwave detection sensitivity obtained was 350 mV/mW, at an RF frequency of 1.0 GHz and field angle of θ H =80°, ϕ H =0°. The experimental results correlated with those obtained via simulation, and the calculated results revealed the magnetization dynamics at the resonance state. - Highlights: • Examined voltage-induced ferromagnetic resonance (FMR) under various field angles. • FMR dynamics are excited by voltage-induced magnetic anisotropy changes. • Microwave detection sensitivity depends on input RF and elevation angle. • Microwave detection sensitivity=350 mV/mW at RF=1.0 GHz, θ H =80°, ϕ H =0°.

  6. Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

    Directory of Open Access Journals (Sweden)

    Emilie Rouaud

    2010-02-01

    Full Text Available An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-Methyl-D-Aspartate receptors (NMDA-R by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of D-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

  7. Differences in pediatric dental services under general anesthesia for Medicaid and military dependent children.

    Science.gov (United States)

    Johnson, M B; Cappelli, D P; Bradshaw, B S; Mabry, J C

    2010-01-01

    This study's purpose was to compare pediatric dental services provided for Medicaid and military dependent children to determine if differences in dental treatment choices exist based on site and payment method. Subjects included 120 Medicaid patients at the University of Texas Health Science Center at San Antonio and 120 military dependents at Lackland Air Force Base, Texas. Demographic data and treatment information were abstracted for children younger than 6 years old receiving dental treatment under general anesthesia between 2002 and 2006. Data was analyzed using Wilcoxon rank sum, Kruskal-Wallis, and Fisher's exact tests. The Medicaid recipients were younger (40.2 vs 49.8 months, Psealants (P<.001). Age and gender did not affect decay rates, but those of Hispanic ethnicity did experience more decay than non-Hispanics (9.5 vs 8.6, P=.02). This study found no difference in the number of less conservative, albeit more costly, procedures performed with Medicaid children at a university compared to military dependents at a military base.

  8. Rate Dependent Multicontinuum Progressive Failure Analysis of Woven Fabric Composite Structures under Dynamic Impact

    Directory of Open Access Journals (Sweden)

    James Lua

    2004-01-01

    Full Text Available Marine composite materials typically exhibit significant rate dependent response characteristics when subjected to extreme dynamic loading conditions. In this work, a strain-rate dependent continuum damage model is incorporated with multicontinuum technology (MCT to predict damage and failure progression for composite material structures. MCT treats the constituents of a woven fabric composite as separate but linked continua, thereby allowing a designer to extract constituent stress/strain information in a structural analysis. The MCT algorithm and material damage model are numerically implemented with the explicit finite element code LS-DYNA3D via a user-defined material model (umat. The effects of the strain-rate hardening model are demonstrated through both simple single element analyses for woven fabric composites and also structural level impact simulations of a composite panel subjected to various impact conditions. Progressive damage at the constituent level is monitored throughout the loading. The results qualitatively illustrate the value of rate dependent material models for marine composite materials under extreme dynamic loading conditions.

  9. Spin-dependent phonon-assisted optical transition in Si and Ge under strain

    Science.gov (United States)

    Li, Pengke; Trivedi, Dhara; Dery, Hanan

    2013-03-01

    In indirect bandgap semiconductors like Si and Ge, the transfer of angular momentum between free carriers and photons is intricate since they involve both radiation-matter and electron-phonon interactions. Moreover, the multi-valley conduction band of Si and Ge leads to dependence on light propagation. By breaking the degeneracies of conduction valleys and of valence bands, strain could be used as an experimental tool to regulate and validate the relation between the measured circular polarization degree of photons and the spin polarization of charge carriers. Using symmetry arguments, we present a theoretical study of the spin-dependent selection rules for various phonon-assisted optical transitions. We show how these selection rules are changed under different configurations of strain. These selection rules are verified by rigorous numerical calculation of the spin-dependent luminescence spectra in strained Si and Ge, as well as in relaxed SiGe alloys. Lastly, we also provide results of the inverse process, namely optical orientation. NSF-NRI Contract DMR-1124601 (NEB 2020), NSF Contract ECCS-1231570

  10. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis

    NARCIS (Netherlands)

    Qiu, W.; Wang, X.; Leibowitz, B.; Liu, H.; Barker, N.; Okada, H.; Oue, N.; Yasui, W.; Clevers, H.; Schoen, R.E.; Yu, J.; Zhang, L.

    2010-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets and underlying mechanisms have remained elusive. We found that dietary sulindac induced apoptosis to remove the intestinal stem cells with

  11. 38 CFR 17.82 - Contracts for outpatient services for veterans with alcohol or drug dependence or abuse...

    Science.gov (United States)

    2010-07-01

    ... Department of Veterans Affairs sponsored patients will be mentally and physically capable of leaving the... disabilities. (a) Contracts for treatment services authorized under § 17.80 may be awarded in accordance with...) Comply with the requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR...

  12. Long-term evolution of polygenic traits under frequency-dependent intraspecific competition.

    Science.gov (United States)

    Schneider, Kristan A

    2007-05-01

    We analytically investigate the long-term evolution of a continuously varying quantitative character in a diploid population that is determined additively by a finite number of loci. The trait is under a mixture of frequency-dependent disruptive selection induced by intraspecific competition and frequency-independent stabilizing selection. Moreover, the trait is restricted to a finite range by constraints on the particular loci. Our investigations are based on explicit analytical results (provided by Bürger [2005. A multilocus analysis of intraspecific competition and stabilizing selection on a quantitative trait. J. Math. Biol. 50, 355-396]; Schneider [2006. A multilocus-multiallele analysis of frequency-dependent selection induced by intraspecific competition. J. Math. Biol. 52, 483-523]) on the short-term dynamics under the assumption of linkage equilibrium. We show that the population always reaches a long-term equilibrium (LTE), i.e., an equilibrium that is resistant against perturbations of mutations of sufficiently small effect. In general, several LTEs can coexist. They can be calculated explicitly, and we provide necessary and sufficient conditions for their existence. In the case that more than one LTE exists, we exemplify numerically that the evolutionary outcome depends crucially on the initial genetic architecture, on the joint distribution of mutational effects across loci, and on the particular realization of the mutation process. Therefore, long-term evolution cannot be predicted from the ecology alone. We further show that a partial order exists for the LTEs. The set of LTEs has a 'largest' element, an LTE which is reached during long-term evolution if the effects of the occurring mutant alleles are sufficiently large.

  13. Psychosocial functioning, quality of life and clinical correlates of comorbid alcohol and drug dependence syndromes in people with schizophrenia across Europe.

    Science.gov (United States)

    Carrà, Giuseppe; Johnson, Sonia; Crocamo, Cristina; Angermeyer, Matthias C; Brugha, Traolach; Azorin, Jean-Michel; Toumi, Mondher; Bebbington, Paul E

    2016-05-30

    Little is known about the correlates of comorbid drug and alcohol dependence in people with schizophrenia outside the USA. We tested hypotheses that dependence on alcohol/drugs would be associated with more severe symptoms, and poorer psychosocial functioning and quality of life. The EuroSC Cohort study (N=1204), based in France, Germany and the UK, used semi-structured clinical interviews for diagnoses, and standardized tools to assess correlates. We used mixed models to compare outcomes between past-year comorbid dependence on alcohol/drugs, controlling for covariates and modelling both subject and country-level effects. Participants dependent on alcohol or drugs had fewer negative symptoms on PANSS than their non-dependent counterparts. However, those dependent on alcohol scored higher on PANSS general psychopathology than those who were not, or dependent only on drugs. People with schizophrenia dependent on drugs had poorer quality of life, more extrapyramidal side effects, and scored worse on Global Assessment of Functioning (GAF) than those without dependence. People with alcohol dependence reported more reasons for non-compliance with medication, and poorer functioning on GAF, though not on Global Assessment of Relational Functioning. In people with schizophrenia, comorbid dependence on alcohol or drugs is associated with impaired clinical and psychosocial adjustment, and poorer quality of life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

    DEFF Research Database (Denmark)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati

    2017-01-01

    Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough...... physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196 kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.......7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half...

  15. Nitrate-dependent shoot sodium accumulation and osmotic functions of sodium in Arabidopsis under saline conditions.

    Science.gov (United States)

    Álvarez-Aragón, Rocío; Rodríguez-Navarro, Alonso

    2017-07-01

    Improving crop plants to be productive in saline soils or under irrigation with saline water would be an important technological advance in overcoming the food and freshwater crises that threaten the world population. However, even if the transformation of a glycophyte into a plant that thrives under seawater irrigation was biologically feasible, current knowledge about Na + effects would be insufficient to support this technical advance. Intriguingly, crucial details about Na + uptake and its function in the plant have not yet been well established. We here propose that under saline conditions two nitrate-dependent transport systems in series that take up and load Na + into the xylem constitute the major pathway for the accumulation of Na + in Arabidopsis shoots; this pathway can also function with chloride at high concentrations. In nrt1.1 nitrate transport mutants, plant Na + accumulation was partially defective, which suggests that NRT1.1 either partially mediates or modulates the nitrate-dependent Na + transport. Arabidopsis plants exposed to an osmotic potential of -1.0 MPa (400 mOsm) for 24 h showed high water loss and wilting in sorbitol or Na/MES, where Na + could not be accumulated. In contrast, in NaCl the plants that accumulated Na + lost a low amount of water, and only suffered transitory wilting. We discuss that in Arabidopsis plants exposed to high NaCl concentrations, root Na + uptake and tissue accumulation fulfil the primary function of osmotic adjustment, even if these processes lead to long-term toxicity. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  16. Time-dependent convective flows with high viscosity contrasts under micro gravity conditions.

    Science.gov (United States)

    Zaussinger, Florian; Egbers, Christoph; Krebs, Andreas; Schwarzbach, Felix; Kunze, Christian

    2015-04-01

    Thermal driven convection in spherical geometry is of main interest in geo- and astrophysical research. To capture certain aspects of temperature dependent viscosity we investigate the micro-gravity experiment GeoFlow-IIb, located on the ISS. This unique experimental setup consists of a bottom heated and top cooled spherical gap, filled with the silicon oil 1-Nonanol. However, rotation and varying temperature gradients can be applied, to spread the experimental parameter space. The main focus of the current mission is the investigation of time dependent convective flow structures. Since the ISS requirements makes it impossible to use tracer particles, the flow structures are captured by interferometry, whose outcome is analysed by an ground based adapted image processing technique. To guarantee valid results the experimental time of each parameter is in the order of the thermal time scale, which is about 40 min. We are presenting latest results of plume-like and sheet-like time-dependent convective patterns in the spherical shell, their evolution and temporal behaviour under high viscosity contrasts. Due to an unexpected nonlinear coupling between the temperature dependent viscosity of the working fluid and the applied dielectrophoretic force field, we are able to maintain a viscosity contrast of 50 and more. This gives the chance to compare cautiously our experimental results with theoretical assumptions of the mantle convection theory. Besides, numerical simulations in the same parameter regime are performed, which give the opportunity to deduce the internal structure of the experimental flow flied. The main focus of the presented results are the long time temporal evolution of convective plumes in the spherical gap, image capturing- and processing techniques and the deduction of the internal flow field based on planar interferometry pictures.

  17. Frequency dependence of dielectric characteristics of seawater ionic solution under static magnetic field

    Science.gov (United States)

    Guo, Shaoshuai; Peng, Yufeng; Han, Xueyun; Li, Jiangting

    2017-09-01

    In order to study the electromagnetic wave transmission characteristics in seawater under external physical effects, we present a study of seawater ionic solution and perform a theoretical basis of magnetic field on water molecules and ionic motion to investigate the variation of dielectric properties with frequency under static magnetic field (0.38 T). Seawater is a naturally multi-component electrolyte solution, the main ingredients in seawater are inorganic salts, such as NaCl, MgSO4, MgCl2, CaCl2, KCl, NaHCO3, etc. The dielectric properties of these electrolyte solutions with different salinity values (0.01-5%) were measured in frequencies ranging from 40 to 5 MHz at 12∘C. The results show that the dielectric constant decreases with increasing frequencies no matter with magnetic field or without it. Frequency dependence of the dielectric constant of NaCl solution increases under magnetic field at measure concentrations. In a solution of MgCl2 ṡ 6H2O, KCl and NaHCO3 are consistent with NaCl solution, while CaCl2 ṡ 2H2O solution is in contrast with it. We also find that dielectric loss plays a major role in complex permittivity. With the effect of magnetic field, the proportion of dielectric loss is reducing in complex permittivity. On this basis it was concluded that the magnetic field influences the orientation of dipoles and the variation is different in salt aqueous solution.

  18. Time-dependent elastohydrodynamic lubrication analysis of total knee replacement under walking conditions.

    Science.gov (United States)

    Su, Yonglin; Yang, Peiran; Fu, Zengliang; Jin, Zhongmin; Wang, Chengtao

    2011-06-01

    This work is concerned with the lubrication analysis of artificial knee joints, which plays an increasing significant role in clinical performance and longevity of components. Time-dependent elastohydrodynamic lubrication analysis for normal total knee replacement is carried out under the cyclic variation in both load and speed representative of normal walking. An equivalent ellipsoid-on-plane model is adopted to represent an actual artificial knee. A full numerical method is developed to simultaneously solve the Reynolds and elasticity equations using the multigrid technique. The elastic deformation is based on the constrained column model. Results show that, under the combined effect of entraining and squeeze-film actions throughout the walking cycle, the predicted central film thickness tends to decrease in the stance phase but keeps a relatively larger value at the swing phase. Furthermore, the geometry of knee joint implant is verified to play an important role under its lubrication condition, and the length of time period is a key point to influence the lubrication performance of joint components.

  19. Pharmacovigilance in oncology: pattern of spontaneous notifications, incidence of adverse drug reactions and under-reporting

    Directory of Open Access Journals (Sweden)

    Marília Berlofa Visacri

    2014-04-01

    Full Text Available The high toxicity and narrow therapeutic window of antineoplastic agents makes pharmacovigilance studies essential in oncology. The objectives of the current study were to analyze the pattern of spontaneous notifications of adverse drug reactions (ADRs in oncology patients and to analyze the incidence of ADRs reported by outpatients on antineoplastic treatment in a tertiary care teaching hospital. To compose the pattern of ADR, the notification forms of reactions in oncology patients in 2010 were reviewed, and the reactions were classified based on the drug involved, mechanism, causality, and severity. To evaluate the incidence of reactions, a questionnaire at the time of chemotherapy was included, and the severity was classified based on the Common Terminology Criteria. The profiles of the 10 responses reported to the Pharmacovigilance Sector were type B, severe, possible, and they were primarily related to platinum compounds and taxanes. When the incidence of reactions was analyzed, it was observed that nausea, alopecia, fatigue, diarrhea, and taste disturbance were the most frequently reported reactions by oncology patients, and the grade 3 and 4 reactions were not reported. Based on this analysis, it is proposed that health professionals should be trained regarding notifications and clinical pharmacists should increasingly be brought on board to reduce under-reporting of ADRs.

  20. Palbociclib can overcome mutations in cyclin dependent kinase 6 that break hydrogen bonds between the drug and the protein.

    Science.gov (United States)

    Hernandez Maganhi, Stella; Jensen, Patrizia; Caracelli, Ignez; Zukerman Schpector, Julio; Fröhling, Stefan; Friedman, Ran

    2017-04-01

    Inhibition of cyclin dependent kinases (CDKs) 4 and 6 prevent cells from entering the synthesis phase of the cell cycle. CDK4 and 6 are therefore important drug targets in various cancers. The selective CDK4/6 inhibitor palbociclib is approved for the treatment of breast cancer and has shown activity in a cellular model of mixed lineage leukaemia (MLL)-rearranged acute myeloid leukaemia (AML). We studied the interactions of palbociclib and CDK6 using molecular dynamics simulations. Analysis of the simulations suggested several interactions that stabilized the drug in its binding site and that were not observed in the crystal structure of the protein-drug complex. These included a hydrogen bond to His 100 that was hitherto not reported and several hydrophobic contacts. Evolutionary-based bioinformatic analysis was used to suggest two mutants, D163G and H100L that would potentially yield drug resistance, as they lead to loss of important protein-drug interactions without hindering the viability of the protein. One of the mutants involved a change in the glycine of the well-conserved DFG motif of the kinase. Interestingly, CDK6-dependent human AML cells stably expressing either mutant retained sensitivity to palbociclib, indicating that the protein-drug interactions are not affected by these. Furthermore, the cells were proliferative in the absence of palbociclib, indicating that the Asp to Gly mutation in the DFG motif did not interfere with the catalytic activity of the protein. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  1. Who benefits from additional drug counseling among prescription opioid-dependent patients receiving buprenorphine-naloxone and standard medical management?

    Science.gov (United States)

    Weiss, Roger D; Griffin, Margaret L; Potter, Jennifer Sharpe; Dodd, Dorian R; Dreifuss, Jessica A; Connery, Hilary S; Carroll, Kathleen M

    2014-07-01

    In the multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted within the National Drug Abuse Clinical Trials Network, participants randomly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes. However, research with other substance-dependent populations shows that subgroups of participants may benefit from a treatment although the entire population does not. We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management, either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence. Problem severity was measured by a history of heroin use, higher Addiction Severity Index drug composite score, and chronic pain. Adequate treatment adherence was defined a priori as attending at least 60% of all offered sessions. Patients who had ever used heroin and received drug counseling were more likely to be successful (i.e., abstinent or nearly abstinent from opioids) than heroin users who received medical management alone, but only if they were adherent to treatment and thus received adequate exposure to counseling (OR=3.7, 95% CI=1.1-11.8, p=0.03). The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score. These findings emphasize the importance of treatment adherence, and suggest that patients with prescription opioid dependence are a heterogeneous group, with different optimal treatment strategies for different subgroups. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Effectiveness of Cognitive-Behavioral Therapy in the Improvement of Coping Strategies and Addiction Symptoms in Drug-Dependent Patients

    Directory of Open Access Journals (Sweden)

    H BrockieMilan

    2014-12-01

    Full Text Available Objective: This study was carried out to determine the effectiveness of cognitive-behavioral therapy in improving coping strategies and symptoms of drug addiction patients. Method: In a quasi-experimental study, the number of 90drug-dependent patients referring to clinics to stop taking drugs existing in the city of Urmia were divided into two experimental (n=45 groups and control (n=45 using random sampling. The experimental group received 12 sessions of cognitive-behavioral treatment in Carroll style while the control group received only methadone and the physical pills. All the participants completed coping strategies questionnaire at the beginning, during (after three months, and three months after treatment (follow-up. As well, they were assessed for the rate of improvement in symptoms of addiction and process of addiction treatment using by Madzly’s addiction profile questionnaire. Findings: The results proved the effectiveness of cognitive-behavioral therapy and its survival. Conclusion: Cognitive behavioral therapy is very influential in the boost of coping strategies and the improvement of mental and physical health in drug-dependent patients.

  3. Explaining long-term outcomes among drug dependent mothers treated in women-only versus mixed-gender programs.

    Science.gov (United States)

    Evans, Elizabeth; Li, Libo; Pierce, Jennifer; Hser, Yih-Ing

    2013-09-01

    Specialized substance abuse treatment for parenting women is thought to improve outcomes, but long-term impacts and how they occur are poorly understood. Utilizing a sample of 789 California mothers followed for 10 years after admission to women-only (WO) or mixed-gender (MG) drug treatment, we examine the relationship between WO treatment and outcomes and whether it is mediated by post-treatment exposures to criminal justice and health services systems. At follow-up, 48% of mothers had a successful outcome (i.e., no use of illicit drugs, not involved with the criminal justice system, alive). Controlling for patient characteristics, WO (vs. MG) treatment increased the odds of successful outcome by 44%. In the structural equation model WO treatment was associated with fewer post-treatment arrests, which was associated with better outcomes. Women-only substance abuse treatment has long-term benefits for drug-dependent mothers, a relationship that may be partially explained by post-treatment exposure to the criminal justice system. Findings underscore additional leverage points for relapse prevention and recovery-supportive efforts for drug-dependent mothers. Published by Elsevier Inc.

  4. The Effect of Group Therapy With Transactional Analysis Approach on Emotional Intelligence, Executive Functions and Drug Dependency

    OpenAIRE

    Forghani, Masoomeh; Ghanbari Hashem Abadi, Bahram Ali

    2016-01-01

    Objectives The aim of the present study was to evaluate the effect of group psychotherapy with transactional analysis (TA) approach on emotional intelligence (EI), executive functions and substance dependency among drug-addicts at rehabilitation centers in Mashhad city, Iran, in 2013. Patients and Methods In this quasi-experimental study with pretest, posttest, case- control stages, 30 patients were selected from a rehabilitation center and randomly divided into two groups. The case group rec...

  5. Strain-dependent partial slip on rock fractures under seismic-frequency torsion

    Science.gov (United States)

    Saltiel, Seth; Bonner, Brian P.; Ajo-Franklin, Jonathan B.

    2017-05-01

    Measurements of nonlinear modulus and attenuation of fractures provide the opportunity to probe their mechanical state. We have adapted a low-frequency torsional apparatus to explore the seismic signature of fractures under low normal stress, simulating low effective stress environments such as shallow or high pore pressure reservoirs. We report strain-dependent modulus and attenuation for fractured samples of Duperow dolomite (a carbon sequestration target reservoir in Montana), Blue Canyon Dome rhyolite (a geothermal analog reservoir in New Mexico), and Montello granite (a deep basement disposal analog from Wisconsin). We use a simple single effective asperity partial slip model to fit our measured stress-strain curves and solve for the friction coefficient, contact radius, and full slip condition. These observations have the potential to develop into new field techniques for measuring differences in frictional properties during reservoir engineering manipulations and estimate the stress conditions where reservoir fractures and faults begin to fully slip.

  6. A Dependent Insurance Risk Model with Surrender and Investment under the Thinning Process

    Directory of Open Access Journals (Sweden)

    Wenguang Yu

    2015-01-01

    Full Text Available A dependent insurance risk model with surrender and investment under the thinning process is discussed, where the arrival of the policies follows a compound Poisson-Geometric process, and the occurrences of the claim and surrender happen as the p-thinning process and the q-thinning process of the arrival process, respectively. By the martingale theory, the properties of the surplus process, adjustment coefficient equation, the upper bound of ruin probability, and explicit expression of ruin probability are obtained. Moreover, we also get the Laplace transformation, the expectation, and the variance of the time when the surplus reaches a given level for the first time. Finally, various trends of the upper bound of ruin probability and the expectation and the variance of the time when the surplus reaches a given level for the first time are simulated analytically along with changing the investment size, investment interest rates, claim rate, and surrender rate.

  7. A Guide for the Management of Special Education Programs. 3.0 Educational Simulations. Newday Operations Guide for Drug Dependent Minor Programs.

    Science.gov (United States)

    Santa Cruz County Superintendent of Schools, CA.

    Presented is the third component, Educational Simulations, of a special day class educational program for drug dependent minors. One objective of the project is said to have been the identification of instructional methods and materials suited to drug dependent minors. Educational games and simulations designed to provide practice in reading and…

  8. A Global Synthesis of Managing Groundwater Dependent Ecosystems Under Sustainable Groundwater Policy.

    Science.gov (United States)

    Rohde, Melissa M; Froend, Ray; Howard, Jeanette

    2017-05-01

    Groundwater is a vital water supply worldwide for people and nature. However, species and ecosystems that depend on groundwater for some or all of their water needs, known as groundwater dependent ecosystems (GDEs), are increasingly becoming threatened worldwide due to growing human water demands. Over the past two decades, the protection and management of GDEs have been incorporated into several water management policy initiatives worldwide including jurisdictions within Australia, the European Union, South Africa, and the United States. Among these, Australia has implemented the most comprehensive framework to manage and protect GDEs through its water policy initiatives. Using a science-based approach, Australia has made good progress at reducing uncertainty when selecting management thresholds for GDEs in their water management plans. This has been achieved by incorporating appropriate metrics for GDEs into water monitoring programs so that information gathered over time can inform management decisions. This adaptive management approach is also accompanied by the application of the "Precautionary Principle" in cases where insufficient information on GDEs exist. Additionally, the integration of risk assessment into Australia's approach has enabled water managers to prioritize the most valuable and vulnerable ecologic assets necessary to manage GDEs under Australia's national sustainable water management legislation. The purpose of this paper is to: (1) compare existing global policy initiatives for the protection and management of GDEs; (2) synthesize Australia's adaptive management approach of GDEs in their state water plans; and (3) highlight opportunities and challenges of applying Australia's approach for managing GDEs under other water management policies worldwide. © 2017 The Authors. Groundwater published by Wiley Periodicals, Inc. on behalf of National Ground Water Association.

  9. Relationships of Behavioral Measures of Frontal Lobe Dysfunction with Underlying Electrophysiology in Cocaine-Dependent Patients

    Science.gov (United States)

    Gjini, Klevest; Qazi, Aisha; Greenwald, Mark K.; Sandhu, Ravinder; Gooding, Diane C.; Boutros, Nash N.

    2013-01-01

    Background and Objectives Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. Methods Using the Frontal System Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N=49) and healthy controls (N=32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. Results Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition and apathy than controls. Lower TMS-based resting motor thresholds (i.e., hyperexcitability) were significantly associated with higher Executive Dysfunction scores in the patients. Conclusions and Scientific Significance Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior. PMID:24724884

  10. Conformational dependence of hemoglobin reactivity under high viscosity conditions: the role of solvent slaved dynamics.

    Science.gov (United States)

    Samuni, Uri; Roche, Camille J; Dantsker, David; Friedman, Joel M

    2007-10-24

    The concept of protein dynamic states is introduced. This concept is based on (i) protein dynamics being organized hierarchically with respect to solvent slaving and (ii) which tier of dynamics is operative over the time window of a given measurement. The protein dynamic state concept is used to analyze the kinetic phases derived from the recombination of carbon monoxide to sol-gel-encapsulated human adult hemoglobin (HbA) and select recombinant mutants. The temperature-dependent measurements are made under very high viscosity conditions obtained by bathing the samples in an excess of glycerol. The results are consistent with a given tier of solvent slaved dynamics becoming operative at a time delay (with respect to the onset of the measurement) that is primarily solvent- and temperature-dependent. However, the functional consequences of the dynamics are protein- and conformation-specific. The kinetic traces from both equilibrium populations and trapped allosteric intermediates show a consistent progression that exposes the role of both conformation and hydration in the control of reactivity. Iron-zinc symmetric hybrid forms of HbA are used to show the dramatic difference between the kinetic patterns for T state alpha and beta subunits. The overall results support a model for allostery in HbA in which the ligand-binding-induced transition from the deoxy T state to the high -affinity R state proceeds through a progression of T state intermediates.

  11. SHUTTER-LESS TEMPERATURE-DEPENDENT CORRECTION FOR UNCOOLED THERMAL CAMERA UNDER FAST CHANGING FPA TEMPERATURE

    Directory of Open Access Journals (Sweden)

    D. Lin

    2017-05-01

    Full Text Available Conventional temperature-dependant correction methods for uncooled cameras are not so valid for images under the condition of fast changing FPA temperature as usual, therefore, a shutter-less temperature-dependant correction method is proposed here to compensate for these errors and stabilize camera's response only related to the object surface temperature. Firstly, sequential images are divided into the following three categories according to the changing speed of FPA temperature: stable (0°C/min, relatively stable (<0.5°C/min, unstable (>0.5°C/min. Then all of the images are projected into the same level using a second order polynomial relation between FPA temperatures and gray values from stable images. Next, a third order polynomial relation between temporal differences of FPA temperatures and the above corrected images is implemented to eliminate the deviation caused by fast changing FPA temperature. Finally, radiometric calibration is applied to convert image gray values into object temperature values. Experiment results show that our method is more effective for fast changing FPA temperature data than FLIR GEV.

  12. Gastrointestinal Complications Depending on the Selectivity of Non-Steroidal Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    G.V. Dzyak

    2013-02-01

    Full Text Available The article deals with the problem of gastrointestinal complications during administration of nonsteroidal anti-inflammatory drugs, commonly used to treat a range of conditions, particularly rheumatic diseases. The results of own researches, which served to define the characteristics of changes in the state of gastric secretory function in patients receiving non-selective and selective anti-inflammatory agent and their comparative analysis, are provided. The data obtained demonstrated a certain contribution to the understanding of the mechanism of development of complications from the gastrointestinal tract when taken drugs of above group.

  13. Leishmania resistant to sodium stibogluconate: drug-associated macrophage-dependent killing

    DEFF Research Database (Denmark)

    Ibrahim, M E; Hag-Ali, M; el-Hassan, A M

    1994-01-01

    . The results indicated that the conventional promastigote screening assay did not correlate with the clinical picture, whereas the amastigote/macrophage system produced results that pertained to the in vivo responses to the drug. A laboratory-generated resistant strain of L. major was adapted to grow at a high...... concentration of Pentostam (1000 micrograms/ml) as promastigotes but was quite sensitive to the drug at much lower concentrations in the amastigote/(macrophage system (20 micrograms/ml), thus suggesting that Pentostam's inhibitory action is mediated through the macrophage rather than through a direct toxic...

  14. Common single nucleotide variants underlying drug addiction: more than a decade of research.

    Science.gov (United States)

    Bühler, Kora-Mareen; Giné, Elena; Echeverry-Alzate, Victor; Calleja-Conde, Javier; de Fonseca, Fernando Rodriguez; López-Moreno, Jose Antonio

    2015-09-01

    Drug-related phenotypes are common complex and highly heritable traits. In the last few years, candidate gene (CGAS) and genome-wide association studies (GWAS) have identified a huge number of single nucleotide polymorphisms (SNPs) associated with drug use, abuse or dependence, mainly related to alcohol or nicotine. Nevertheless, few of these associations have been replicated in independent studies. The aim of this study was to provide a review of the SNPs that have been most significantly associated with alcohol-, nicotine-, cannabis- and cocaine-related phenotypes in humans between the years of 2000 and 2012. To this end, we selected CGAS, GWAS, family-based association and case-only studies published in peer-reviewed international scientific journals (using the PubMed/MEDLINE and Addiction GWAS Resource databases) in which a significant association was reported. A total of 371 studies fit the search criteria. We then filtered SNPs with at least one replication study and performed meta-analysis of the significance of the associations. SNPs in the alcohol metabolizing genes, in the cholinergic gene cluster CHRNA5-CHRNA3-CHRNB4, and in the DRD2 and ANNK1 genes, are, to date, the most replicated and significant gene variants associated with alcohol- and nicotine-related phenotypes. In the case of cannabis and cocaine, a far fewer number of studies and replications have been reported, indicating either a need for further investigation or that the genetics of cannabis/cocaine addiction are more elusive. This review brings a global state-of-the-art vision of the behavioral genetics of addiction and collaborates on formulation of new hypothesis to guide future work. © 2015 Society for the Study of Addiction.

  15. EXPRESSION OF CALCIUM-DEPENDENT PROTEIN KINASE (CDPK GENES IN VITIS AMURENSIS UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Dubrovina A.S.

    2012-08-01

    Full Text Available Abiotic stresses, such as extreme temperatures, soil salinity, or water deficit, are one of the major limiting factors of crop productivity worldwide. Examination of molecular and genetic mechanisms of abiotic stress tolerance in plants is of great interest to plant biologists. Calcium-dependent protein kinases (CDPKs, which are the most important Ca2+ sensors in plants, are known to play one of the key roles in plant adaptation to abiotic stress. CDPK is a multigene family of enzymes. Analysis of CDPK gene expression under various abiotic stress conditions would help identify those CDPKs that might play important roles in plant adaptation to abiotic stress. We focused on studying CDPK gene expression under osmotic, water deficit, and temperature stress conditions in a wild-growing grapevine Vitis amurensis Rurp., which is native to the Russian Far East and is known to possess high adaptive potential and high level of resistance against adverse environmental conditions. Healthy V. amurensis cuttings (excised young stems with one healthy leaf were used for the treatments. For the non-stress treatment, we placed the cuttings in distilled water for 12 h at room temperature. For the water-deficit stress, detached cuttings were laid on a paper towel for 12 h at room temperature. For osmotic stress treatments, the cuttings were placed in 0.4 М NaCl and 0.4 М mannitol solutions for 12 h at room temperature. To examine temperature stress tolerance, the V. amurensis cuttings were placed in a growth chamber at +10oC and +37oC for 12 h. The total expression of VaCDPK genes was examined by semiquantitative RT-PCR with degenerate primers designed to the CDPK kinase domain. The total level of CDPK gene expression increased under salt and decreased under low temperature stress conditions. We sequenced 300 clones of the amplified part of different CDPK transcripts obtained from the analyzed cDNA probes. Analysis of the cDNA sequences identified 8 different

  16. Missing continuous outcomes under covariate dependent missingness in cluster randomised trials.

    Science.gov (United States)

    Hossain, Anower; Diaz-Ordaz, Karla; Bartlett, Jonathan W

    2017-06-01

    Attrition is a common occurrence in cluster randomised trials which leads to missing outcome data. Two approaches for analysing such trials are cluster-level analysis and individual-level analysis. This paper compares the performance of unadjusted cluster-level analysis, baseline covariate adjusted cluster-level analysis and linear mixed model analysis, under baseline covariate dependent missingness in continuous outcomes, in terms of bias, average estimated standard error and coverage probability. The methods of complete records analysis and multiple imputation are used to handle the missing outcome data. We considered four scenarios, with the missingness mechanism and baseline covariate effect on outcome either the same or different between intervention groups. We show that both unadjusted cluster-level analysis and baseline covariate adjusted cluster-level analysis give unbiased estimates of the intervention effect only if both intervention groups have the same missingness mechanisms and there is no interaction between baseline covariate and intervention group. Linear mixed model and multiple imputation give unbiased estimates under all four considered scenarios, provided that an interaction of intervention and baseline covariate is included in the model when appropriate. Cluster mean imputation has been proposed as a valid approach for handling missing outcomes in cluster randomised trials. We show that cluster mean imputation only gives unbiased estimates when missingness mechanism is the same between the intervention groups and there is no interaction between baseline covariate and intervention group. Multiple imputation shows overcoverage for small number of clusters in each intervention group.

  17. Adsorption of vitamin K-dependent proteins to live cell membranes measured under flow conditions.

    Science.gov (United States)

    McGee, M P; Teuschler, H

    1999-07-01

    Mechanisms mediating initial adsorption of coagulation proteins to live cells were investigated. Adsorption kinetics were examined under varying flow conditions using tracer-dilution techniques in perfused spherical monolayers of cells expressing tissue factor. At biologically relevant time and concentration ranges, rates exceeded by 2-12 fold the theoretical maximum calculated for steady-state diffusion. Rates were correlated with aqueous-phase flux of reactants and were found to be largely independent of the density of reactive sites on the membrane. Average adsorption rate of factor VIIa at 4 etaM and flow velocity of 0.8 etam s(-1) was 5 x 10(7) s(-1) cm(-2). Adsorption rates of homologous coagulation factors IX and X under similar conditions were 5 and 9 x 10(7) s(-1)cm(-2). Results indicate that flow can effectively increase the rate of coagulation factor adsorption to the membrane of live cells. They also imply that factors affecting blood flow velocity and vessel permeability influence the rate of membrane-dependent coagulation reactions.

  18. Latina Mother–Daughter Dyads: Relations Between Attachment and Sexual Behavior Under the Influence of Alcohol or Drugs

    Science.gov (United States)

    Dillon, Frank R.; Rojas, Patria; Schwartz, Seth J.; Duan, Rui

    2009-01-01

    Associations among mother-daughter attachment, mother and daughter substance abuse, and daughter’s sexual behavior under the influence of drugs and alcohol were investigated among 158 adult U.S. Latina daughters. Latina daughters were sampled from four mother–daughter dyad types: substance abusing mother and daughter, substance abusing mother only, substance abusing daughter only, and nonsubstance-abusing mother and daughter. Substance abusing daughters with substance abusing mothers, and daughters who were less strongly attached to their mothers, reported more sex under the influence of drugs. Age, marital status, substance abuse, and mother’s substance abuse all influenced the daughter’s sex under the influence of alcohol. An unexpected positive association between attachment and sex under the influence of alcohol was found for daughters who were more closely attached to a substance abusing mother. Implications for future research, and HIV/AIDS and drug prevention and treatment programs for Latinas are discussed. PMID:19399605

  19. Drug Dependence in Adolescents: Changing Trends at a De-Addiction Centre in North India

    Science.gov (United States)

    Grover, Sandeep; Basu, Debasish; Mattoo, Surendra Kumar

    2007-01-01

    Introduction: There is scarcity of Indian data on substance dependence in children and adolescents. Methods: Case records of 85 adolescents with the final diagnosis of substance dependence were analyzed (out of 115 registrations during 1978-2003). Results: Time trends showed an increase in individuals with good social support and higher family…

  20. [Peer pressure and motivation of alcoholic and drug dependent patients to accept treatment].

    Science.gov (United States)

    Danis, D; D'Epagnier, C; Udry, C

    1997-11-01

    This study evaluates the kind of pressure put on 136 chemically dependent patients to enter treatment in a specialized chemical dependency residential program at the Clinique La Métairie. The results show that patients' motivation to enter treatment is directly linked to the pressure significant others exerce on them.

  1. Medicare prescription drug plan coverage of pharmacotherapies for opioid and alcohol dependence in WA.

    Science.gov (United States)

    Kennedy, Jae; Dipzinski, Aaron; Roll, John; Coyne, Joseph; Blodgett, Elizabeth

    2011-04-01

    Pharmacotherapeutic treatments for drug addiction offer new options, but only if they are affordable for patients. The objective of this study is to assess the current availability and cost of five common antiaddiction medications in the largest federal medication insurance program in the US, Medicare Part D. In early 2010, we collected coverage and cost data from 41 Medicare Part D prescription drug plans (PDPs) and 45 Medicare Advantage Plans (MAPs) in Washington State. The great majority of Medicare plans (82-100%) covered common pharmacotherapeutic treatments for drug addiction. These Medicare plans typically placed patent protected medications on their highest formulary tiers, leading to relatively high patient co-payments during the initial Part D coverage period. For example, median monthly co-payments for buprenorphine (Suboxone®) were about $46 for PDPs, and about $56 for MAPs. While Medicare prescription plans usually cover pharmacotherapeutic treatments for drug addiction, high co-payments can limit access. For example, beneficiaries without supplemental coverage who use Vivitrol® would exceed their initial coverage cap in 7-8 months, reaching the "doughnut hole" in their Part D coverage and becoming responsible for the full cost of the medication (over $900 per month). The 2010 Patient Protection and Affordable Care Act will gradually eliminate this coverage gap, and loss of patent protection for other antiaddiction medications (Suboxone® and Campral®) should also drive down patient costs, improving access and compliance. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. The RNA-dependent-RNA polymerase, an emerging antiviral drug target for the Hendra virus.

    Science.gov (United States)

    Velkov, Tony; Carbone, Vincenzo; Akter, Jesmin; Sivanesan, Sivashangarie; Li, Jian; Beddoe, Travis; Marsh, Glenn A

    2014-01-01

    Australia is facing a major national medical challenge with the emergence of the Hendra virus (HeV) as a medically and economically important pathogen of humans and animals. Clinical symptoms of human HeV infection can include fever, hypotension, dizziness, encephalitis, respiratory haemorrhage and edema. The window of opportunity for successful patient treatment remains unknown, but is likely to be very narrow. Currently, very few effective therapeutic options are available for the case management of severe HeV infections or the rapid silencing of local outbreaks. This underscores the need for more activity in the drug discovery arena to develop much needed therapeutics that specifically targets this deadly disease. The structural analysis of HeV is very much in its infancy, which leaves many gaps in our understanding of the biology of HeV and makes structure-guided drug design difficult. Structural studies of the viral RNAdependent- RNA polymerase (RdRp), which is the heart of the viral replication machinery, will set the stage for rational drug design and fill a major gap in our understanding of the HeV replication machinery. This review examines the current knowledge based on the multi-domain architecture of the Hendra RdRp and highlights which essential domain functions represent tangible targets for drug development against this deadly disease.

  3. THE LACTOCOCCAL LMRP GENE ENCODES A PROTON MOTIVE FORCE-DEPENDENT DRUG TRANSPORTER

    NARCIS (Netherlands)

    Bolhuis, H; Poelarends, G.J.; van Veen, H.W.; Poolman, B.; Driessen, A.J.M.; Konings, W.N

    1995-01-01

    To genetically dissect the drug extrusion systems of Lactococcus lactis, a chromosomal. DNA library was made in Escherichia coli and recombinant strains were selected for resistance to high concentrations of ethidium bromide. Recombinant strains were found to be resistant not only to ethidium

  4. Self-Derogation, Peer Factors, and Drug Dependence among a Multiethnic Sample of Young Adults

    Science.gov (United States)

    Taylor, John; Lloyd, Donald A.; Warheit, George J.

    2006-01-01

    Previous research suggests that self-derogation/rejection and peer factors are strongly related to adolescent substance use. However, much less is known about the role and significance of these risk factors in the escalation of drug use over time. In the current study, we examined whether early reports of self-derogation and peer approval…

  5. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation

    NARCIS (Netherlands)

    Mackus, W. J. M.; Kater, A. P.; Grummels, A.; Evers, L. M.; Hooijbrink, B.; Kramer, M. H. H.; Castro, J. E.; Kipps, T. J.; van Lier, R. A. W.; van Oers, M. H. J.; Eldering, E.

    2005-01-01

    We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgV(H) mutation status, and (3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL

  6. Size-dependent chemical ageing of oleic acid aerosol under dry and humidified conditions

    Directory of Open Access Journals (Sweden)

    S. S. Al-Kindi

    2016-12-01

    Full Text Available A chemical reaction chamber system has been developed for the processing of oleic acid aerosol particles with ozone under two relative humidity conditions: dry and humidified to 65 %. The apparatus consists of an aerosol flow tube, in which the ozonolysis occurs, coupled to a scanning mobility particle sizer (SMPS and an aerosol time-of-flight mass spectrometer (ATOFMS which measure the evolving particle size and composition. Under both relative humidity conditions, ozonolysis results in a significant decrease in particle size and mass which is consistent with the formation of volatile products that partition from the particle to the gas phase. Mass spectra derived from the ATOFMS reveal the presence of the typically observed reaction products: azelaic acid, nonanal, oxononanoic acid and nonanoic acid, as well as a range of higher molecular weight products deriving from the reactions of reaction intermediates with oleic acid and its oxidation products. These include octanoic acid and 9- and 10-oxooctadecanoic acid, as well as products of considerably higher molecular weight. Quantitative evaluation of product yields with the ATOFMS shows a marked dependence upon both particle size association (from 0.3 to 2.1 µm diameter and relative humidity. Under both relative humidity conditions, the percentage residual of oleic acid increases with increasing particle size and the main lower molecular weight products are nonanal and oxononanoic acid. Under dry conditions, the percentage of higher molecular weight products increases with increasing particle size due to the poorer internal mixing of the larger particles. Under humidified conditions, the percentage of unreacted oleic acid is greater, except in the smallest particle fraction, with little formation of high molecular weight products relative to the dry particles. It is postulated that water reacts with reactive intermediates, competing with the processes which produce high molecular weight

  7. Office bladder distention with Electromotive Drug Administration (EMDA is equivalent to distention under General Anesthesia (GA

    Directory of Open Access Journals (Sweden)

    Azevedo Kathryn J

    2005-11-01

    Full Text Available Abstract Background Bladder distention is commonly used in diagnosis and treatment of interstitial cystitis (IC. Traditionally performed in the operating room under general or spinal anesthesia (GA, it is expensive and associated with short term morbidity. Office bladder distention using electromotive drug administration (EMDA has been suggested as an alternative that is well tolerated by patients. We report the first comparative findings of patients undergoing both office distention with EMDA and distention in the operating room (OR with GA. Methods This retrospective chart review identified 11 patients participating in two protocols of EMDA bladder distention who also underwent bladder distention under GA either prior to or after the EMDA procedure. Results The median absolute difference in bladder capacity between GA and EMDA was only 25 cc; the median percent difference was 5%. Cystoscopic findings, while not prospectively compiled, appear to have been similar. Conclusion This study represents the first comparison between distention with EMDA versus GA and confirms the technical feasibility of performing bladder distention in an office setting. The distention capacity achieved in the office was nearly identical to that in the OR and the cystoscopic findings very similar. Further investigation into the comparative morbidity, cost, and other outcome measures is warranted to define the ultimate role of EMDA bladder distention in the clinical evaluation and care of patients with IC.

  8. Bibliography [On Drugs].

    Science.gov (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  9. Reducing Sex under the Influence of Drugs or Alcohol for Patients in Substance Abuse Treatment

    Science.gov (United States)

    Calsyn, Donald A.; Crits-Christoph, Paul; Hatch-Maillette, Mary A.; Doyle, Suzanne R.; Song, Yong S.; Coyer, Susan; Pelta, Sara

    2009-01-01

    Aims In a previous report, the effectiveness of the Real Men Are Safe (REMAS) intervention in reducing the number of unprotected sexual occasions among male drug abuse treatment patients was demonstrated. A secondary aim of REMAS was to reduce the frequency with which men engage in sex under the influence (SUI) of drugs or alcohol. Design Men in methadone maintenance (n=173) or outpatient psychosocial treatment (n=104) completed assessments at baseline, 3- and 6-months post intervention. Participants were randomly assigned to attend either REMAS (five sessions containing information, motivational exercises and skills training, including one session specifically targeting reducing SUI), or HIV education (HIV-Ed; one session containing HIV prevention information). SUI during the most recent sexual event served as the primary outcome in a repeated measures logistic regression model. Findings Men assigned to the REMAS condition reporting SUI at the most recent sexual event decreased from 36.8% at baseline to 25.7% at 3 months compared to a increase from 36.9% to 38.3% in the HIV-Ed condition (tintervention=−2.16, p=.032). No difference between the treatment groups was evident at 6-month follow-up. At each assessment time point, sex with a casual partner versus a regular partner, and being in methadone maintenance versus psychosocial outpatient treatment, were associated with engaging in SUI. Conclusions Overall a motivational and skills training HIV prevention intervention designed for men was associated with greater reduction in SUI than standard HIV education at the 3-month follow-up. PMID:20078464

  10. Physiologically based pharmacokinetic modeling to predict complex drug-drug interactions: a case study of AZD2327 and its metabolite, competitive and time-dependent CYP3A inhibitors.

    Science.gov (United States)

    Guo, Jian; Zhou, Diansong; Li, Yan; Khanh, Bui H

    2015-11-01

    4-{(R)-(3-Aminophenyl)[4-(4-fluorobenzyl)-piperazin-1-yl]methyl}-N,N-diethylbenzamide (AZD2327) is a highly potent and selective agonist of the δ-opioid receptor. AZD2327 and N-deethylated AZD2327 (M1) are substrates of cytochrome P450 3A (CYP3A4) and comprise a complex multiple inhibitory system that causes competitive and time-dependent inhibition of CYP3A4. The aim of the current work was to develop a physiologically based pharmacokinetic (PBPK) model to predict quantitatively the magnitude of CYP3A4 mediated drug-drug interaction with midazolam as the substrate. Integrating in silico, in vitro and in vivo PK data, a PBPK model was successfully developed to simulate the clinical accumulation of AZD2327 and its primary metabolite. The inhibition of CYP3A4 by AZD2327, using midazolam as a probe drug, was reasonably predicted. The predicted maximum concentration (Cmax) and area under the concentration-time curve (AUC) for midazolam were increased by 1.75 and 2.45-fold, respectively, after multiple dosing of AZD2327, indicating no or low risk for clinically relevant drug-drug interactions (DDI). These results are in agreement with those obtained in a clinical trial with a 1.4 and 1.5-fold increase in Cmax and AUC of midazolam, respectively. In conclusion, this model simulated DDI with less than a two-fold error, indicating that complex clinical DDI associated with multiple mechanisms, pathways and inhibitors (parent and metabolite) can be predicted using a well-developed PBPK model. Copyright © 2015 John Wiley & Sons, Ltd.

  11. 76 FR 29183 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

    Science.gov (United States)

    2011-05-20

    ... utilization of drugs with orphan designations by the affected covered entities, the elasticity of demand by... Prices of Drugs Purchased by Covered Entities.'' Section 340B implemented a drug pricing program by which... entities listed in the statute and must agree to charge a price that will not exceed the amount determined...

  12. [Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

    Science.gov (United States)

    Zhiliuk, V I; Levykh, A É; Mamchur, V I

    2012-01-01

    The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.

  13. Patterns of use of other drugs among those with alcohol dependence: Associations with drinking behavior and psychopathology.

    Science.gov (United States)

    Moss, Howard B; Goldstein, Risë B; Chen, Chiung M; Yi, Hsiao-Ye

    2015-11-01

    Alcohol dependence (AD) presents with substantial clinical heterogeneity, including concurrent use of non-alcohol drugs. Here, we examine specific patterns of concurrent non-alcohol substance use during the previous year among a nationally representative sample of adults with DSM-IV AD, and estimate their population prevalence in the U.S. We then evaluate alcohol use behavior and comorbid psychopathology among respondents with AD according to their patterns of concurrent non-alcohol substance use. These analyses utilized data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Latent class analyses classified respondents with AD into four clinically meaningful patterns of concurrent substance use: (1) use of alcohol only; (2) use of alcohol and tobacco only; (3) use of alcohol, tobacco and cannabis; and (4) use of alcohol, tobacco, cannabis, cocaine, and other illicit drug(s). Among AD respondents, the most prevalent pattern was the use of alcohol and tobacco only (weighted percentage, 32.4%), followed by the use of alcohol only (weighted percentage, 27.5%). AD respondents who used alcohol, tobacco, cannabis, cocaine, and other illicit drug(s) (weighted percentage, 25.3%) manifested the most severe pattern of alcohol consumption, and had significant overrepresentations of major depression, panic, and other anxiety disorders as well as paranoid, schizotypal, borderline, antisocial, and histrionic personality disorders compared with those who used alcohol alone. Specific patterns of concurrent substance use convey important information regarding the clinical presentation and prognosis for AD. In particular, concurrent use of illicit drugs over the past year by AD individuals was associated with greater severity and comorbid psychopathology. These data suggest the need for pragmatic trials of AD interventions that take into account patterns of substance use behavior in addition to an AD diagnosis. Published by Elsevier Ltd.

  14. The Relationship between Demographic Factors and Substance Craving Among Drug-Dependents

    Directory of Open Access Journals (Sweden)

    F PoorSeyedMousaiee

    2015-03-01

    Full Text Available Objective: This study was conducted with the aim of examining the role of demographic factors such as age, marital status, education degree, the age of initiating addiction, duration of addiction, monthly cost of drug use, and an incarceration history in the intensity of addicts’ craving for substance use. Method: In this descriptive and cross-sectional study, 195 male addicts, after being interviewed, were selected as the participants of the study via convenience sampling method. They constituted six groups of opium smokers, heroin inhalers, heroin smokers, heroin injectors, methamphetamine smokers, and crack smokers and answered the questions of demographic characteristics and Franken’s desire for drug questionnaire. Indeed, substance craving of the respondents was measured by the computerized test of measuring visual indicators of substance craving. Results: The results showed that there is a significant positive relationship between education degree and induced substance craving, monthly cost of drug use and induced substance craving, and also between education degree and instantaneous substance craving. Conclusion: Some demographic factors can be important factors in predicting substance craving in addicts, which is, in itself, among the significant dimensions in treatment process.

  15. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

    2014-01-01

    The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

  16. Acetaminophen - Dose-dependent Drug Hepatotoxicity and Acute Liver Failure in Patients

    Science.gov (United States)

    Jaeschke, Hartmut

    2015-01-01

    Background Drug-induced liver injury (DILI) is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure (ALF) at therapeutic doses in a very limited number of patients (paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and ALF after intentional and unintentional overdoses. Key Messages APAP overdose is responsible for more ALF cases in the US or UK than all other etiologies combined. Because APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late presenting patients. Conclusions The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent ALF and to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome. PMID:26159260

  17. Mitochondrial permeabilisation engages NF-κB dependent anti-tumour activity under caspase deficiency

    Science.gov (United States)

    Giampazolias, Evangelos; Bock, Florian; Cloix, Catherine; Cao, Kai; Roca, Alba; Lopez, Jonathan; Ichim, Gabriel; Proïcs, Emma; Rubio-Patiño, Camila; Fort, Loic; Yatim, Nader; Woodham, Emma; Orozco, Susana; Taraborrelli, Lucia; Peltzer, Nieves; Lecis, Daniele; Machesky, Laura; Walczak, Henning; Albert, Matthew L.; Milling, Simon; Oberst, Andrew; Ricci, Jean-Ehrland; Ryan, Kevin M.; Blyth, Karen; Tait, Stephen W.G.

    2017-01-01

    Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilisation (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA-damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the down-regulation of inhibitor of apoptosis (IAP) proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies. PMID:28846096

  18. Domain decomposition method for dynamic faulting under slip-dependent friction

    International Nuclear Information System (INIS)

    Badea, Lori; Ionescu, Ioan R.; Wolf, Sylvie

    2004-01-01

    The anti-plane shearing problem on a system of finite faults under a slip-dependent friction in a linear elastic domain is considered. Using a Newmark method for the time discretization of the problem, we have obtained an elliptic variational inequality at each time step. An upper bound for the time step size, which is not a CFL condition, is deduced from the solution uniqueness criterion using the first eigenvalue of the tangent problem. Finite element form of the variational inequality is solved by a Schwarz method assuming that the inner nodes of the domain lie in one subdomain and the nodes on the fault lie in other subdomains. Two decompositions of the domain are analyzed, one made up of two subdomains and another one with three subdomains. Numerical experiments are performed to illustrate convergence for a single time step (convergence of the Schwarz algorithm, influence of the mesh size, influence of the time step), convergence in time (instability capturing, energy dissipation, optimal time step) and an application to a relevant physical problem (interacting parallel fault segments)

  19. Study of the energy dependence of the underlying event in proton-antiproton collisions

    Energy Technology Data Exchange (ETDEWEB)

    Nodulman, L.; Aaltonen, T; Albrow, M; Amerio, S.; Amidei, D; Anastassov, A.; Annovi, A; Antos, J; Apollinari, G.; Appel, J A; Arisawa, T

    2015-11-23

    We study charged particle production (p(T) > 0.5 GeV/c, vertical bar eta vertical bar < 0.8) in proton-antiproton collisions at total center-of-mass energies root s = 300 GeV, 900 GeV, and 1.96 TeV. We use the direction of the charged particle with the largest transverse momentum in each event to define three regions of eta - phi space: "toward", "away", and "transverse." The average number and the average scalar pT sum of charged particles in the transverse region are sensitive to the modeling of the "underlying event." The transverse region is divided into a MAX and MIN transverse region, which helps separate the "hard component" (initial and final-state radiation) from the "beam-beam remnant" and multiple parton interaction components of the scattering. The center-of-mass energy dependence of the various components of the event is studied in detail. The data presented here can be used to constrain and improve QCD Monte Carlo models, resulting in more precise predictions at the LHC energies of 13 and 14 TeV.

  20. A Study of the Energy Dependence of the Underlying Event in Proton-Antiproton Collisions

    CERN Document Server

    Aaltonen, Timo Antero; Amidei, Dante E; Anastassov, Anton Iankov; Annovi, Alberto; Antos, Jaroslav; Apollinari, Giorgio; Appel, Jeffrey A; Arisawa, Tetsuo; Artikov, Akram Muzafarovich; Asaadi, Jonathan A; Ashmanskas, William Joseph; Auerbach, Benjamin; Aurisano, Adam J; Azfar, Farrukh A; Badgett, William Farris; Bae, Taegil; Barbaro-Galtieri, Angela; Barnes, Virgil E; Barnett, Bruce Arnold; Barria, Patrizia; Bartos, Pavol; Bauce, Matteo; Bedeschi, Franco; Behari, Satyajit; Bellettini, Giorgio; Bellinger, James Nugent; Benjamin, Douglas P; Beretvas, Andrew F; Bhatti, Anwar Ahmad; Bland, Karen Renee; Blumenfeld, Barry J; Bocci, Andrea; Bodek, Arie; Bortoletto, Daniela; Boudreau, Joseph Francis; Boveia, Antonio; Brigliadori, Luca; Bromberg, Carl Michael; Brucken, Erik; Budagov, Ioulian A; Budd, Howard Scott; Burkett, Kevin Alan; Busetto, Giovanni; Bussey, Peter John; Butti, Pierfrancesco; Buzatu, Adrian; Calamba, Aristotle; Camarda, Stefano; Campanelli, Mario; Canelli, Florencia; Carls, Benjamin; Carlsmith, Duncan L; Carosi, Roberto; Carrillo Moreno, Salvador; Casal Larana, Bruno; Casarsa, Massimo; Castro, Andrea; Catastini, Pierluigi; Cauz, Diego; Cavaliere, Viviana; Cerri, Alessandro; Cerrito, Lucio; Chen, Yen-Chu; Chertok, Maxwell Benjamin; Chiarelli, Giorgio; Chlachidze, Gouram; Cho, Kihyeon; Chokheli, Davit; Clark, Allan Geoffrey; Clarke, Christopher Joseph; Convery, Mary Elizabeth; Conway, John Stephen; Corbo, Matteo; Cordelli, Marco; Cox, Charles Alexander; Cox, David Jeremy; Cremonesi, Matteo; Cruz Alonso, Daniel; Cuevas Maestro, Javier; Culbertson, Raymond Lloyd; D'Ascenzo, Nicola; Datta, Mousumi; de Barbaro, Pawel; Demortier, Luc M; Marchese, Luigi; Deninno, Maria Maddalena; Devoto, Francesco; D'Errico, Maria; Di Canto, Angelo; Di Ruzza, Benedetto; Dittmann, Jay Richard; D'Onofrio, Monica; Donati, Simone; Dorigo, Mirco; Driutti, Anna; Ebina, Koji; Edgar, Ryan Christopher; Erbacher, Robin D; Errede, Steven Michael; Esham, Benjamin; Farrington, Sinead Marie; Fernández Ramos, Juan Pablo; Field, Richard D; Flanagan, Gene U; Forrest, Robert David; Franklin, Melissa EB; Freeman, John Christian; Frisch, Henry J; Funakoshi, Yujiro; Galloni, Camilla; Garfinkel, Arthur F; Garosi, Paola; Gerberich, Heather Kay; Gerchtein, Elena A; Giagu, Stefano; Giakoumopoulou, Viktoria Athina; Gibson, Karen Ruth; Ginsburg, Camille Marie; Giokaris, Nikos D; Giromini, Paolo; Glagolev, Vladimir; Glenzinski, Douglas Andrew; Gold, Michael S; Goldin, Daniel; Golossanov, Alexander; Gomez, Gervasio; Gomez-Ceballos, Guillelmo; Goncharov, Maxim T; González López, Oscar; Gorelov, Igor V; Goshaw, Alfred T; Goulianos, Konstantin A; Gramellini, Elena; Grosso-Pilcher, Carla; Guimaraes da Costa, Joao; Hahn, Stephen R; Han, Ji-Yeon; Happacher, Fabio; Hara, Kazuhiko; Hare, Matthew Frederick; Harr, Robert Francis; Harrington-Taber, Timothy; Hatakeyama, Kenichi; Hays, Christopher Paul; Heinrich, Joel G; Herndon, Matthew Fairbanks; Hocker, James Andrew; Hong, Ziqing; Hopkins, Walter Howard; Hou, Suen Ray; Hughes, Richard Edward; Husemann, Ulrich; Hussein, Mohammad; Huston, Joey Walter; Introzzi, Gianluca; Iori, Maurizio; Ivanov, Andrew Gennadievich; James, Eric B; Jang, Dongwook; Jayatilaka, Bodhitha Anjalike; Jeon, Eun-Ju; Jindariani, Sergo Robert; Jones, Matthew T; Joo, Kyung Kwang; Jun, Soon Yung; Junk, Thomas R; Kambeitz, Manuel; Kamon, Teruki; Karchin, Paul Edmund; Kasmi, Azeddine; Kato, Yukihiro; Ketchum, Wesley Robert; Keung, Justin Kien; Kilminster, Benjamin John; Kim, DongHee; Kim, Hyunsoo; Kim, Jieun; Kim, Min Jeong; Kim, Soo Bong; Kim, Shin-Hong; Kim, Young-Kee; Kim, Young-Jin; Kimura, Naoki; Kirby, Michael H; Knoepfel, Kyle James; Kondo, Kunitaka; Kong, Dae Jung; Konigsberg, Jacobo; Kotwal, Ashutosh Vijay; Kreps, Michal; Kroll, IJoseph; Kruse, Mark Charles; Kuhr, Thomas; Kurata, Masakazu; Laasanen, Alvin Toivo; Lammel, Stephan; Lancaster, Mark; Lannon, Kevin Patrick; Latino, Giuseppe; Lee, Hyun Su; Lee, Jaison; Leo, Sabato; Leone, Sandra; Lewis, Jonathan D; Limosani, Antonio; Lipeles, Elliot David; Lister, Alison; Liu, Qiuguang; Liu, Tiehui Ted; Lockwitz, Sarah E; Loginov, Andrey Borisovich; Lucà, Alessandra; Lucchesi, Donatella; Lueck, Jan; Lujan, Paul Joseph; Lukens, Patrick Thomas; Lungu, Gheorghe; Lys, Jeremy E; Lysak, Roman; Madrak, Robyn Leigh; Maestro, Paolo; Malik, Sarah Alam; Manca, Giulia; Manousakis-Katsikakis, Arkadios; Margaroli, Fabrizio; Marino, Christopher Phillip; Matera, Keith; Mattson, Mark Edward; Mazzacane, Anna; Mazzanti, Paolo; McNulty, Ronan; Mehta, Andrew; Mehtala, Petteri; Mesropian, Christina; Miao, Ting; Mietlicki, David John; Mitra, Ankush; Miyake, Hideki; Moed, Shulamit; Moggi, Niccolo; Moon, Chang-Seong; Moore, Ronald Scott; Morello, Michael Joseph; Mukherjee, Aseet; Muller, Thomas; Murat, Pavel A; Mussini, Manuel; Nachtman, Jane Marie; Nagai, Yoshikazu; Naganoma, Junji; Nakano, Itsuo; Napier, Austin; Nett, Jason Michael; Nigmanov, Turgun S; Nodulman, Lawrence J; Noh, Seoyoung; Norniella Francisco, Olga; Oakes, Louise Beth; Oh, Seog Hwan; Oh, Young-do; Okusawa, Toru; Orava, Risto Olavi; Ortolan, Lorenzo; Pagliarone, Carmine Elvezio; Palencia, Jose Enrique; Palni, Prabhakar; Papadimitriou, Vaia; Parker, William Chesluk; Pauletta, Giovanni; Paulini, Manfred; Paus, Christoph Maria Ernst; Phillips, Thomas J; Piacentino, Giovanni M; Pianori, Elisabetta; Pilot, Justin Robert; Pitts, Kevin T; Plager, Charles; Pondrom, Lee G; Poprocki, Stephen; Potamianos, Karolos Jozef; Prokoshin, Fedor; Pranko, Aliaksandr Pavlovich; Ptohos, Fotios K; Punzi, Giovanni; Redondo Fernández, Ignacio; Renton, Peter B; Rescigno, Marco; Rimondi, Franco; Ristori, Luciano; Robson, Aidan; Rodriguez, Tatiana Isabel; Rolli, Simona; Ronzani, Manfredi; Roser, Robert Martin; Rosner, Jonathan L; Ruffini, Fabrizio; Ruiz Jimeno, Alberto; Russ, James S; Rusu, Vadim Liviu; Sakumoto, Willis Kazuo; Sakurai, Yuki; Santi, Lorenzo; Sato, Koji; Saveliev, Valeri; Savoy-Navarro, Aurore; Schlabach, Philip; Schmidt, Eugene E; Schwarz, Thomas A; Scodellaro, Luca; Scuri, Fabrizio; Seidel, Sally C; Seiya, Yoshihiro; Semenov, Alexei; Sforza, Federico; Shalhout, Shalhout Zaki; Shears, Tara G; Shepard, Paul F; Shimojima, Makoto; Shochet, Melvyn J; Shreyber-Tecker, Irina; Simonenko, Alexander V; Sliwa, Krzysztof Jan; Smith, John Rodgers; Snider, Frederick Douglas; Sorin, Maria Veronica; Song, Hao; Stancari, Michelle Dawn; St Denis, Richard Dante; Stentz, Dale James; Strologas, John; Sudo, Yuji; Sukhanov, Alexander I; Suslov, Igor M; Takemasa, Ken-ichi; Takeuchi, Yuji; Tang, Jian; Tecchio, Monica; Teng, Ping-Kun; Thom, Julia; Thomson, Evelyn Jean; Thukral, Vaikunth; Toback, David A; Tokar, Stanislav; Tollefson, Kirsten Anne; Tomura, Tomonobu; Tonelli, Diego; Torre, Stefano; Torretta, Donatella; Totaro, Pierluigi; Trovato, Marco; Ukegawa, Fumihiko; Uozumi, Satoru; Vázquez-Valencia, Elsa Fabiola; Velev, Gueorgui; Vellidis, Konstantinos; Vernieri, Caterina; Vidal Marono, Miguel; Vilar Cortabitarte, Rocio; Vizán Garcia, Jesus Manuel; Vogel, Marcelo; Volpi, Guido; Wagner, Peter; Wallny, Rainer S; Wang, Song-Ming; Waters, David S; Wester, William Carl; Whiteson, Daniel O; Wicklund, Arthur Barry; Wilbur, Scott; Williams, Hugh H; Wilson, Jonathan Samuel; Wilson, Peter James; Winer, Brian L; Wittich, Peter; Wolbers, Stephen A; Wolfe, Homer; Wright, Thomas Roland; Wu, Xin; Wu, Zhenbin; Yamamoto, Kazuhiro; Yamato, Daisuke; Yang, Tingjun; Yang, Un-Ki; Yang, Yu Chul; Yao, Wei-Ming; Yeh, Gong Ping; Yi, Kai; Yoh, John; Yorita, Kohei; Yoshida, Takuo; Yu, Geum Bong; Yu, Intae; Zanetti, Anna Maria; Zeng, Yu; Zhou, Chen; Zucchelli, Stefano

    2015-11-23

    We study charged particle production in proton-antiproton collisions at 300 GeV, 900 GeV, and 1.96 TeV. We use the direction of the charged particle with the largest transverse momentum in each event to define three regions of eta-phi space; toward, away, and transverse. The average number and the average scalar pT sum of charged particles in the transverse region are sensitive to the modeling of the underlying event. The transverse region is divided into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The center-of-mass energy dependence of the various components of the event are studied in detail. The data presented here can be used to constrain and improve QCD Monte Carlo models, resulting in more precise predictions at the LHC energies of 13 and 14 TeV.

  1. Numerical simulation of time-dependent deformations under hygral and thermal transient conditions

    International Nuclear Information System (INIS)

    Roelfstra, P.E.

    1987-01-01

    Some basic concepts of numerical simulation of the formation of the microstructure of HCP are outlined. The aim is to replace arbitrary terms like aging by more realistic terms like bond density in the xerogel and bonds between hydrating particles of HCP. Actual state parameters such as temperature, humidity and degree of hydration can be determined under transient hygral and thermal conditions by solving numerically a series of appropriate coupled differential equations with given boundary conditions. Shrinkage of a composite structure without crack formation, based on calculated moisture distributions, has been determined with numerical concrete codes. The influence of crack formation, tensile strain-hardening and softening on the total deformation of a quasi-homogeneous drying material has been studied by means of model based on FEM. The difference between shrinkage without crack formation and shrinkage with crack formation can be quantified. Drying shrinkage and creep of concrete cannot be separated. The total deformation depends on the superimposed stress fields. Transient hygral deformation can be realistically predicted if the concept of point properties is applied rigorously. Transient thermal deformation has to be dealt with in the same way. (orig./HP)

  2. Single Machine Problem with Multi-Rate-Modifying Activities under a Time-Dependent Deterioration

    Directory of Open Access Journals (Sweden)

    M. Huang

    2013-01-01

    Full Text Available The single machine scheduling problem with multi-rate-modifying activities under a time-dependent deterioration to minimize makespan is studied. After examining the characteristics of the problem, a number of properties and a lower bound are proposed. A branch and bound algorithm and a heuristic algorithm are used in the solution, and two special cases are also examined. The computational experiments show that, for the situation with a rate-modifying activity, the proposed branch and bound algorithm can solve situations with 50 jobs within a reasonable time, and the heuristic algorithm can obtain the near-optimal solution with an error percentage less than 0.053 in a very short time. In situations with multi-rate-modifying activities, the proposed branch and bound algorithm can solve the case with 15 jobs within a reasonable time, and the heuristic algorithm can obtain the near-optimal with an error percentage less than 0.070 in a very short time. The branch and bound algorithm and the heuristic algorithm are both shown to be efficient and effective.

  3. Concentration Dependent Ion-Protein Interaction Patterns Underlying Protein Oligomerization Behaviours

    Science.gov (United States)

    Batoulis, Helena; Schmidt, Thomas H.; Weber, Pascal; Schloetel, Jan-Gero; Kandt, Christian; Lang, Thorsten

    2016-04-01

    Salts and proteins comprise two of the basic molecular components of biological materials. Kosmotropic/chaotropic co-solvation and matching ion water affinities explain basic ionic effects on protein aggregation observed in simple solutions. However, it is unclear how these theories apply to proteins in complex biological environments and what the underlying ionic binding patterns are. Using the positive ion Ca2+ and the negatively charged membrane protein SNAP25, we studied ion effects on protein oligomerization in solution, in native membranes and in molecular dynamics (MD) simulations. We find that concentration-dependent ion-induced protein oligomerization is a fundamental chemico-physical principle applying not only to soluble but also to membrane-anchored proteins in their native environment. Oligomerization is driven by the interaction of Ca2+ ions with the carboxylate groups of aspartate and glutamate. From low up to middle concentrations, salt bridges between Ca2+ ions and two or more protein residues lead to increasingly larger oligomers, while at high concentrations oligomers disperse due to overcharging effects. The insights provide a conceptual framework at the interface of physics, chemistry and biology to explain binding of ions to charged protein surfaces on an atomistic scale, as occurring during protein solubilisation, aggregation and oligomerization both in simple solutions and membrane systems.

  4. Statistical inference for the additive hazards model under outcome-dependent sampling.

    Science.gov (United States)

    Yu, Jichang; Liu, Yanyan; Sandler, Dale P; Zhou, Haibo

    2015-09-01

    Cost-effective study design and proper inference procedures for data from such designs are always of particular interests to study investigators. In this article, we propose a biased sampling scheme, an outcome-dependent sampling (ODS) design for survival data with right censoring under the additive hazards model. We develop a weighted pseudo-score estimator for the regression parameters for the proposed design and derive the asymptotic properties of the proposed estimator. We also provide some suggestions for using the proposed method by evaluating the relative efficiency of the proposed method against simple random sampling design and derive the optimal allocation of the subsamples for the proposed design. Simulation studies show that the proposed ODS design is more powerful than other existing designs and the proposed estimator is more efficient than other estimators. We apply our method to analyze a cancer study conducted at NIEHS, the Cancer Incidence and Mortality of Uranium Miners Study, to study the risk of radon exposure to cancer.

  5. Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.

    1997-01-01

    The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

  6. Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence?

    Science.gov (United States)

    Biederman, J; Wilens, T E; Mick, E; Faraone, S V; Spencer, T

    1998-08-15

    The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.

  7. The conduct of in vitro studies to address time-dependent inhibition of drug-metabolizing enzymes: a perspective of the pharmaceutical research and manufacturers of America.

    Science.gov (United States)

    Grimm, Scott W; Einolf, Heidi J; Hall, Steven D; He, Kan; Lim, Heng-Keang; Ling, Kah-Hiing John; Lu, Chuang; Nomeir, Amin A; Seibert, Eleanore; Skordos, Konstantine W; Tonn, George R; Van Horn, Robert; Wang, Regina W; Wong, Y Nancy; Yang, Tian J; Obach, R Scott

    2009-07-01

    Time-dependent inhibition (TDI) of cytochrome P450 (P450) enzymes caused by new molecular entities (NMEs) is of concern because such compounds can be responsible for clinically relevant drug-drug interactions (DDI). Although the biochemistry underlying mechanism-based inactivation (MBI) of P450 enzymes has been generally understood for several years, significant advances have been made only in the past few years regarding how in vitro time-dependent inhibition data can be used to understand and predict clinical DDI. In this article, a team of scientists from 16 pharmaceutical research organizations that are member companies of the Pharmaceutical Research and Manufacturers of America offer a discussion of the phenomenon of TDI with emphasis on the laboratory methods used in its measurement. Results of an anonymous survey regarding pharmaceutical industry practices and strategies around TDI are reported. Specific topics that still possess a high degree of uncertainty are raised, such as parameter estimates needed to make predictions of DDI magnitude from in vitro inactivation parameters. A description of follow-up mechanistic experiments that can be done to characterize TDI are described. A consensus recommendation regarding common practices to address TDI is included, the salient points of which include the use of a tiered approach wherein abbreviated assays are first used to determine whether NMEs demonstrate TDI or not, followed by more thorough inactivation studies for those that do to define the parameters needed for prediction of DDI.

  8. [IgG anti HSV I antibodies in saliva in a drug dependent population].

    Science.gov (United States)

    Urquía, M; Ceballos, A; Ruiz, M; Pérez-Alférez, N

    1989-11-01

    It is known the presence of receptors for the morphine products on the Lymphocytes B. These receptors could have a modulator action on the production of antibodies in drug addicts. We have determined the existence of IgG anti-HSV I in saliva and serum in a heroin population. Our results show that here is not significant differences between the heroin population and the control group, when the antibodies are detected in serum. But significant differences do exist between the number of people with antibodies anti-HSV I in saliva.

  9. Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug - Drug Interaction Studies.

    Science.gov (United States)

    Litou, Chara; Vertzoni, Maria; Goumas, Constantinos; Vasdekis, Vassilis; Xu, Wei; Kesisoglou, Filippos; Reppas, Christos

    2016-06-01

    Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults. Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am. Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen. Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

  10. The clinical implication of drug dependency in children and adults with inflammatory bowel disease: a review

    DEFF Research Database (Denmark)

    Duricova, Dana; Pedersen, Natalia; Lenicek, Martin

    2011-01-01

    cessation or dose decrease. However, a quick restoration of remission and sustained response is achieved when the therapy is re-introduced or dose increased. Population-based studies have demonstrated that 22-36% of adults and 14-50% of children become corticosteroid dependent. Approximately 1/4-1/3...

  11. Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment.

    Directory of Open Access Journals (Sweden)

    Margot A Cousin

    Full Text Available Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.

  12. [Users' perception of a harm reduction program in an outpatient drug dependency treatment center].

    Science.gov (United States)

    Daigre, Constanza; Comín, Marina; Rodríguez-Cintas, Laia; Voltes, Nuria; Alvarez, Alba; Roncero, Carlos; Gonzalvo, Begoña; Casas, Miguel

    2010-01-01

    We analyzed the perspective of users enrolled in a harm reduction program that provides syringe exchange, an educational room for «warmth and coffee», a methadone maintenance program, a room for supervised drug consumption, a place for personal hygiene, and medical and psychosocial follow-up. The particularity of this program lies in its integration within an outpatient drug treatment center forming part of a general hospital. We performed a descriptive study using qualitative methods. Theoretical sampling was conducted. Twelve in-depth interviews and one focus group composed of eight users were carried out. Information analysis was based on grounded theory. Literal transcriptions were coded and subsequently sorted into broad categories. Three researchers participated in this process and finally a fourth researcher triangulated the results. Five dimensions were identified in the users' discourse: accessibility, service, relationship, localization, and identity. Each consisted of several topics that were evaluated based on the participants' experiences and expectations. The dimension of identity emerged as a distinctive element in patient-program bonding. The users' overall evaluation of the program was positive. Facilitators and barriers influencing patient-program bonding were identified and participants suggested ways to remove barriers. The coexistence among users of the harm reduction program and patients treated conventionally provoked ambivalence but the team's management was deemed helpful in easing the difficulties arising from this situation. Copyright © 2010 SESPAS. Published by Elsevier Espana. All rights reserved.

  13. Planning deficits in polysubstance dependent users: Differential associations with severity of drug use and intelligence.

    Science.gov (United States)

    Valls-Serrano, C; Verdejo-García, A; Caracuel, A

    2016-05-01

    Polysubstance use is associated with alterations in different components of executive functioning such as working memory and response inhibition. Nevertheless, less attention has been given to executive planning skills, which are required to benefit of low structured interventions. This study examines the association between severity of use of cocaine, heroin, alcohol, fluid and crystallized intelligence and planning tasks varying on degree of structure. Data were collected from 60 polysubstance users and 30 healthy controls. Cognitive assessment consisted of three planning tasks with different structure levels: Stockings of Cambridge, Zoo Map test, and Multiple Errands Test. Polysubstance users had significant planning deficits across the three tasks compared to healthy controls. Hierarchical regression models showed that severity of drug use and fluid and crystallized intelligence significantly explained performance in all the planning tasks. However, these associations were higher for low-structured real world tasks. These low-structured tasks also showed a unique association with crystallized but not fluid intelligence. Drug abuse is negatively associated with planning abilities, and intelligence is positively associated with planning performance in real-world tasks. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Addiction research centres and the nurturing of creativity: National Drug Dependence Treatment Centre, India--a profile.

    Science.gov (United States)

    Ray, Rajat; Dhawan, Anju; Chopra, Anita

    2013-10-01

    The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post-graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre-clinical studies. Capacity-building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  15. Effectiveness of group cognitive therapy about opium addict complications on attitude of adolescents with drug dependent parents

    Directory of Open Access Journals (Sweden)

    Kaveh Hojjat

    2015-12-01

    Full Text Available Background and Aim: Statistics show that 30% to 40 % of  opium addicted fathers’ children are prone to substance abuse in the future. The present study aimed at assessing the effectiveness of cognitive therapy approach  to attitude changing of adolescents with substance dependent fathers. Materials and Methods:  In this controlled. field-trail randomized study. .data collection tool was “attitude to addiction questionnaire”. The study population was all male students in the first grade of high school in Maneh - Samalghan city. . Six sessions of group cognitive therapy based on the effectiveness of drug side-effects in drug-addicted fathers’ adolescent children’s attitude were held. The above-mentioned questionnaire was filled out before and after intervention. The obtained data  was fed into SPSS software (V: 16 using. Independent t-test .and paired t-test were used for analysis and P<0.05 was taken as the significant level. Results:  There were no significant differences between the two groups in pre-test regarding their attitude about drug abuse (P=.20%. Mean score variance from pre-test to post-test in the intervention group decreased, but in the control group, it showed a slight increase. This means that the intervention reduced the positive attitude towards drugs, but the changes were not statistically significant (p=0.57. Besides, among ten factors decisive in an individual’s attitude about addiction, only group cognitive therapy  was able  to decrease mean points of an individual’s attitude about drug abuse .. Significantly (P = 0.04. Conclusion: It was found that group cognitive therapy education about opium  addict complicationsdidn`t have a significant effect on the attitude of the students with addicted fathers. Thus, a change of adolescents’ attitude requires more research.

  16. Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models.

    Science.gov (United States)

    Bunik, Victoria I; Tylicki, Adam; Lukashev, Nikolay V

    2013-12-01

    Bringing a knowledge of enzymology into research in vivo and in situ is of great importance in understanding systems biology and metabolic regulation. The central metabolic significance of thiamin (vitamin B1 ) and its diphosphorylated derivative (thiamin diphosphate; ThDP), and the fundamental differences in the ThDP-dependent enzymes of metabolic networks in mammals versus plants, fungi and bacteria, or in health versus disease, suggest that these enzymes are promising targets for biotechnological and medical applications. Here, the in vivo action of known regulators of ThDP-dependent enzymes, such as synthetic structural analogs of the enzyme substrates and thiamin, is analyzed in light of the enzymological data accumulated during half a century of research. Mimicking the enzyme-specific catalytic intermediates, the phosphonate analogs of 2-oxo acids selectively inhibit particular ThDP-dependent enzymes. Because of their selectivity, use of these compounds in cellular and animal models of ThDP-dependent enzyme malfunctions improves the validity of the model and its predictive power when compared with the nonselective and enzymatically less characterized oxythiamin and pyrithiamin. In vitro studies of the interaction of thiamin analogs and their biological derivatives with potential in vivo targets are necessary to identify and attenuate the analog selectivity. For both the substrate and thiamin synthetic analogs, in vitro reactivities with potential targets are highly relevant in vivo. However, effective concentrations in vivo are often higher than in vitro studies would suggest. The significance of specific inihibition of the ThDP-dependent enzymes for the development of herbicides, antibiotics, anticancer and neuroprotective strategies is discussed. © 2013 FEBS.

  17. Sexuality Under the Influence: The Queer Pleasures of Illicit Drugs in Transatlantic Gay and Lesbian Culture

    OpenAIRE

    Randolph, Patrick

    2011-01-01

    Recently, popular culture has been riveted by depictions of addiction, overdose, and recovery in multiple media formats. These representations obsess over a before-and-after concept aligning drug use strictly with death and destruction and recovery with health and happiness. This mimics traditional examples of drug users as anti-social found in stories rooted in moral panic ubiquitous in mainstream media. Most examples connect both sexual exploration and drug use, arguing they are inherently ...

  18. Antimalarial Drug Artemether Inhibits Neuroinflammation in BV2 Microglia Through Nrf2-Dependent Mechanisms.

    Science.gov (United States)

    Okorji, Uchechukwu P; Velagapudi, Ravikanth; El-Bakoush, Abdelmeneim; Fiebich, Bernd L; Olajide, Olumayokun A

    2016-11-01

    Artemether, a lipid-soluble derivative of artemisinin has been reported to possess anti-inflammatory properties. In this study, we have investigated the molecular mechanisms involved in the inhibition of neuroinflammation by the drug. The effects of artemether on neuroinflammation-mediated HT22 neuronal toxicity were also investigated in a BV2 microglia/HT22 neuron co-culture. To investigate effects on neuroinflammation, we used LPS-stimulated BV2 microglia treated with artemether (5-40 μM) for 24 h. ELISAs and western blotting were used to detect pro-inflammatory cytokines, nitric oxide, prostaglandin E 2 (PGE 2 ), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1). Beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity and Aβ levels were measured with ELISA kits. Protein levels of targets in nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling, as well as heme oxygenase-1 (HO-1), NQO1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) were also measured with western blot. NF-κB binding to the DNA was investigated using electrophoretic mobility shift assays (EMSA). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), DNA fragmentation and reactive oxygen species (ROS) assays in BV2-HT22 neuronal co-culture were used to evaluate the effects of artemether on neuroinflammation-induced neuronal death. The role of Nrf2 in the anti-inflammatory activity of artemether was investigated in BV2 cells transfected with Nrf2 siRNA. Artemether significantly suppressed pro-inflammatory mediators (NO/iNOS, PGE 2 /COX-2/mPGES-1, tumour necrosis factor-alpha (TNFα) and interleukin (IL)-6); Aβ and BACE-1 in BV2 cells following LPS stimulation. These effects of artemether were shown to be mediated through inhibition of NF-κB and p38 MAPK signalling. Artemether produced increased levels of HO-1, NQO1 and GSH in BV2 microglia. The drug

  19. Parental and offspring assessment of driving capability under the influence of drugs or alcohol: gender and inter-generational differences.

    Science.gov (United States)

    Rosenbloom, Tova; Beigel, Ariela; Perlman, Amotz; Eldror, Ehud

    2010-11-01

    The current study set to examine whether there are inter-generational and gender-based differences between family members self-assessing their ability to drive under normal conditions and while under the influence of either alcohol or drugs. Participants were 135 young-adults and both their parents, consisting 45 family triads, who received self-assessment questionnaires relating to their driving skills in various road scenarios. Each family triad was randomly assigned to one of three groups: either requested to base the assessments on normal driving conditions, or under the influence of either drugs or alcohol, thus forming a control group, and two experimental groups (alcohol and drugs), respectively. The findings indicate the assessments of both the alcohol and drugs groups were more severe than those of the control group. The alcohol group assessments were less strict than the drug group assessment (non-significantly). Inter-generational differences indicated that the parents' driving-skills assessments were lower than those of their offspring, corresponding with previous findings (Elkind, 1967; Finn and Bragg, 1986). A significant within-subject interaction has been found between the respondent's gender and familial relations regarding the self-assessment of driving skills: male respondents assessed better driving skills compared to the self estimates of both parents (which did not significantly differ). In contrast, female respondents' estimates did not differ from their fathers' and both fathers' and daughters' estimates were significantly higher than that of the mothers in each family. 2010 Elsevier Ltd. All rights reserved.

  20. Evaluations of in vitro metabolism, drug-drug interactions mediated by reversible and time-dependent inhibition of CYPs, and plasma protein binding of MMB4 DMS.

    Science.gov (United States)

    Hong, S Peter; Lusiak, Bozena D; Burback, Brian L; Johnson, Jerry D

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Drug metabolism and plasma protein binding for MMB4 DMS were examined using various techniques and a wide range of species. When (14)C-MMB4 DMS was incubated in liver microsomes, 4-pyridine aldoxime (4-PA) and an additional metabolite were detected in all species tested. Identity of the additional metabolite was postulated to be isonicotinic acid (INA) based on liquid chromatography with a tandem mass spectrometry analysis, which was confirmed by comparison with authentic INA. Formation of INA was dependent on species, with the highest level found in monkey liver microsomes. The MMB4 DMS exhibited reversible inhibition in a concentration-dependent manner toward cytochrome P450 1A2 (CYP1A2), CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in human liver microsomes showing the highest inhibition for CYP2D6. Human recombinant CYPs were used to evaluate inhibitory curves more adequately and determine detailed kinetic constants for reversible inhibition and potential time-dependent inhibition (TDI). The MMB4 DMS exhibited reversible inhibition toward human-recombinant CYP2D6 with an inhibition constant (K i) value of 66.6 µmol/L. Based on the k inact/K I values, MMB4 DMS was found to exhibit the most potent TDI toward CYP2D6. The MMB4 DMS at 5 different concentrations was incubated in plasma for 5 hours using an equilibrium dialysis device. For all species tested, there were no concentration-dependent changes in plasma protein binding, ranging from 10% to 17%. These results suggest that MMB4 was not extensively bound to plasma protein, and there were no overt species-related differences in the extent of MMB4 bound to plasma protein.

  1. CO2 -dependent metabolic modulation in red blood cells stored under anaerobic conditions.

    Science.gov (United States)

    Dumont, Larry J; D'Alessandro, Angelo; Szczepiorkowski, Zbigniew M; Yoshida, Tatsuro

    2016-02-01

    Anaerobic red blood cell (RBC) storage reduces oxidative damage, maintains adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) levels, and has superior 24-hour recovery at 6 weeks compared to standard storage. This study will determine if removal of CO2 during O2 depletion by gas exchange may affect RBCs during anaerobic storage. This is a matched three-arm study (n = 14): control, O2 and CO2 depleted with Ar (AN), and O2 depleted with 95%Ar/5%CO2 (AN[CO2 ]). RBCs in additives AS-3 or OFAS-3 were evenly divided into three bags, and anaerobic conditions were established by gas exchange. Bags were stored at 1 to 6°C in closed chambers under anaerobic conditions or ambient air, sampled weekly for up to 9 weeks for a panel of in vitro tests. A full metabolomics screening was conducted for the first 4 weeks of storage. Purging with Ar (AN) results in alkalization of the RBC and increased glucose consumption. The addition of 5% CO2 to the purging gas prevented CO2 loss with an equivalent starting and final pH and lactate to control bags (p > 0.5, Days 0-21). ATP levels are higher in AN[CO2 ] (p CO2 ] arms (p = 0.6). Maintenance of ATP in the AN[CO2 ] arm demonstrates that ATP production is not solely a function of the pH effect on glycolysis. CO2 in anaerobic storage prevented the maintenance of DPG, and DPG production appears to be pH dependent. CO2 as well as O2 depletion provides metabolic advantage for stored RBCs. © 2015 AABB.

  2. [An evaluation of a symposium via satellite on alcoholism and drug dependence].

    Science.gov (United States)

    Ríos-Espinosa, E; Martínez-Salgado, H; Ruíz-Tapia, R; Domínguez-Cherit, L

    1993-01-01

    Results of a test given to participants in a symposium on alcoholism and drug abuse are presented. The symposium was broadcast via satellite simultaneously to five cities in Mexico, and included 8 pretaped panels covering topics on alcoholism and drug abuse. The methodology used for broadcasting the symposium allowed the interactive exchange of information between expert lecturers and participants. The quantitative and qualitative evaluation used the pretest-posttest design. Most of the participants were physicians (28.9%) followed by psychologists (25.7%) and social workers (18.1%). The global cognitive change among participants was 6 per cent. Almost 77 per cent of participants had scores between 51 and 70 points (over a possible maximum score of 100) in the pre-evaluation test, and 76.4 per cent had scores between 61 and 80 points in the postevaluation test. Health professionals with 1-3 years of experience had the largest change in scores (9%), followed by those with 3 to 5 years experience (8%). Professionals with 5 to 10 years of experience had a change of 5 per cent. Physicians showed the greatest cognitive change (7%) followed by psychologists and social workers with 5 per cent change. In the qualitative evaluation, 87.6 per cent of participants thought that the educational method used was "Excellent" of "Good". With respect to the satellite transmission, 79.4 per cent of participants thought it was "Excellent" or "Good". It is concluded that this type of educational events are useful in reaching health professionals who otherwise would not have access to specialized and updated information.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Characterizing the intersection of Co-occurring risk factors for illicit drug abuse and dependence in a U.S. nationally representative sample.

    Science.gov (United States)

    Kurti, Allison N; Keith, Diana R; Noble, Alyssa; Priest, Jeff S; Sprague, Brian; Higgins, Stephen T

    2016-11-01

    Few studies have attempted to characterize how co-occurring risk factors for substance use disorders intersect. A recent study examined this question regarding cigarette smoking and demonstrated that co-occurring risk factors generally act independently. The present study examines whether that same pattern of independent intersection of risk factors extends to illicit drug abuse/dependence using a U.S. nationally representative sample (National Survey on Drug Use and Health, 2011-2013). Logistic regression and classification and regression tree (CART) modeling were used to examine risk of past-year drug abuse/dependence associated with a well-established set of risk factors for substance use (age, gender, race/ethnicity, education, poverty, smoking status, alcohol abuse/dependence, mental illness). Each of these risk factors was associated with significant increases in the odds of drug abuse/dependence in univariate logistic regressions. Each remained significant in a multivariate model examining all eight risk factors simultaneously. CART modeling of these 8 risk factors identified subpopulation risk profiles wherein drug abuse/dependence prevalence varied from 80% corresponding to differing combinations of risk factors present. Alcohol abuse/dependence and cigarette smoking had the strongest associations with drug abuse/dependence risk. These results demonstrate that co-occurring risk factors for illicit drug/abuse dependence generally intersect in the same independent manner as risk factors for cigarette smoking, underscoring further fundamental commonalities across these different types of substance use disorders. These results also underscore the fundamental importance of differences in the presence of co-occurring risk factors when considering the often strikingly different prevalence rates of illicit drug abuse/dependence in U.S. population subgroups. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A State-by-State Analysis of Laws Dealing With Driving Under the Influence of Drugs

    Science.gov (United States)

    2009-12-01

    This study reviewed each State statute regarding drug-impaired driving as of December 2008. There : is a high degree of variability across the States in the ways they approach drug-impaired driving. : Current laws in many States contain provisions ma...

  5. Interaction between drug delivery vehicles and cells under the effect of shear stress

    DEFF Research Database (Denmark)

    Godoy-Gallardo, Maria; Ek, Pramod Kumar; Jansman, M. M. T.

    2015-01-01

    Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs...

  6. A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions

    NARCIS (Netherlands)

    Blanquet, S.; Zeijdner, E.; Beyssac, E.; Meunier, J.-P.; Denis, S.; Havenaar, R.; Alric, M.

    2004-01-01

    Purpose. The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. Methods. Two

  7. On the assessment of adverse drug reactions from spontaneous reporting systems: The influence of under-reporting on odds ratios

    NARCIS (Netherlands)

    Heijden, P.G.M. van der; Puijenbroek, E.P. van; Buuren, S. van; Hofstede, J.W. van der

    2002-01-01

    A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting

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

    International Nuclear Information System (INIS)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M.

    2006-01-01

    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)

  9. Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.

    Science.gov (United States)

    Louis, John M; Roche, Julien

    2016-07-03

    Using high-pressure NMR spectroscopy and differential scanning calorimetry, we investigate the folding landscape of the mature HIV-1 protease homodimer. The cooperativity of unfolding was measured in the absence or presence of a symmetric active site inhibitor for the optimized wild type protease (PR), its inactive variant PRD25N, and an extremely multidrug-resistant mutant, PR20. The individual fit of the pressure denaturation profiles gives rise to first order, ∆GNMR, and second order, ∆VNMR (the derivative of ∆GNMR with pressure); apparent thermodynamic parameters for each amide proton considered. Heterogeneity in the apparent ∆VNMR values reflects departure from an ideal cooperative unfolding transition. The narrow to broad distribution of ∆VNMR spanning the extremes from inhibitor-free PR20D25N to PR-DMP323 complex, and distinctively for PRD25N-DMP323 complex, indicated large variations in folding cooperativity. Consistent with this data, the shape of thermal unfolding transitions varies from asymmetric for PR to nearly symmetric for PR20, as dimer-inhibitor ternary complexes. Lack of structural cooperativity was observed between regions located close to the active site, including the hinge and tip of the glycine-rich flaps, and the rest of the protein. These results strongly suggest that inhibitor binding drastically decreases the cooperativity of unfolding by trapping the closed flap conformation in a deep energy minimum. To evade this conformational trap, PR20 evolves exhibiting a smoother folding landscape with nearly an ideal two-state (cooperative) unfolding transition. This study highlights the malleability of retroviral protease folding pathways by illustrating how the selection of mutations under drug pressure remodels the free-energy landscape as a primary mechanism. Published by Elsevier Ltd.

  10. Predicting Inpatient Detoxification Outcome of Alcohol and Drug Dependent Patients: The Influence of Sociodemographic Environment, Motivation, Impulsivity, and Medical Comorbidities

    Directory of Open Access Journals (Sweden)

    Yvonne Sofin

    2017-01-01

    Full Text Available Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1% of the patients completed detoxification treatment whereas 307 (36.9% dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention.

  11. Expressive writing for high-risk drug dependent patients in a primary care clinic: A pilot study

    Directory of Open Access Journals (Sweden)

    Wedgwood Lucinda

    2006-11-01

    Full Text Available Abstract Background Previous research has shown that expressive writing is beneficial in terms of both physical and emotional health outcomes. This study aimed to investigate the effectiveness and acceptability of a brief expressive writing intervention for high-risk drug dependent patients in a primary care clinic, and to determine the relationship between linguistic features of writing and health outcomes. Methods Participants completed four 15-minute expressive writing tasks over a week, in which they described their thoughts and feelings about a recent stressful event. Self-report measures of physical (SF-12 and psychological health (DASS-21 were administered at baseline and at a two-week follow-up. Fifty-three participants were recruited and 14 (26% completed all measures. Results No statistically significant benefits in physical or psychological health were found, although all outcomes changed in the direction of improvement. The intervention was well-received and was rated as beneficial by participants. The use of more positive emotion words in writing was associated with improvements in depression and stress, and flexibility in first person pronoun use was associated with improvements in anxiety. Increasing use of cognitive process words was associated with worsening depressive mood. Conclusion Although no significant benefits in physical and psychological health were found, improvements in psychological wellbeing were associated with certain writing styles and expressive writing was deemed acceptable by high-risk drug dependent patients. Given the difficulties in implementing psychosocial interventions in this population, further research using a larger sample is warranted.

  12. CHEMICAL DEPENDENCE AND FAMILY RELATIONSHIPS: THE FAMILY IMPORTANCE IN THE DRUG ADDICTION TREATMENT

    OpenAIRE

    GISELE ALELUIA VIEIRA ALVES DO CARMO

    2003-01-01

    O objetivo deste trabalho é compreender as características da dinâmica da família em que um ou mais de seus componentes é adicto a álcool e outras drogas. Utilizamos, para este fim, o referencial sistêmico. Entendemos que a dependência química seja tanto uma patologia em si quanto um sintoma de um sistema familiar. Nas relações que se estabelecem entre o dependente químico e os outros membros da família, vai-se construindo uma teia relacional que, mu...

  13. Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances.

    Science.gov (United States)

    Jones, Alan Wayne

    2005-12-01

    This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified

  14. Anxiety and Depression in Drug-Dependent Patients with Cluster C Personality Disorders

    Directory of Open Access Journals (Sweden)

    Carlos Roncero

    2018-02-01

    Full Text Available ObjectiveComorbidity between personality disorders (PD and substance-use disorders (SUD is one of the most common findings in the psychiatric field. The patients with Cluster C disorders present maladjustment traits often characterized by high levels of anxiety. The main aim of this study was to find evidences about higher anxiety and depression prevalence on Cluster C than others Clusters, analyzing similarities and differences within, with other Cluster A and B PD patients and patients without PD.MethodA total of 822 substance dependent patients (ages18–78; Mean = 38.35, SD = 10.14 completed the structured clinical interview for DSM-IV Axis I and Axis II disorders, Beck Depression Inventory, and State-Trait Anxiety Inventory.ResultsResults supported poly-consumption in Cluster C patients, being greater alcohol consumption as well as abuse of both stimulants and depressants. Anxiety and depression did not show just one pattern for all patients with SUD-Cluster C PD. There was a relation between anxiety and depression for all the groups except for the Dependent-PD.ConclusionInterventions should focus on aspects like depression and anxiety more than on the substance consumed.

  15. Developments in harmine pharmacology--implications for ayahuasca use and drug-dependence treatment.

    Science.gov (United States)

    Brierley, Daniel I; Davidson, Colin

    2012-12-03

    Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT(2A) and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Severe Psychosis, Drug Dependence, and Hepatitis C Related to Slamming Mephedrone

    Directory of Open Access Journals (Sweden)

    Helen Dolengevich-Segal

    2016-01-01

    Full Text Available Background. Synthetic cathinones (SCs, also known as “bath salts,” are β-ketone amphetamine compounds derived from cathinone, a psychoactive substance found in Catha edulis. Mephedrone is the most representative SC. Slamming is the term used for the intravenous injection of these substances in the context of chemsex parties, in order to enhance sex experiences. Using IV mephedrone may lead to diverse medical and psychiatric complications like psychosis, aggressive behavior, and suicide ideation. Case. We report the case of a 25-year-old man admitted into a psychiatric unit, presenting with psychotic symptoms after slamming mephedrone almost every weekend for the last 4 months. He presents paranoid delusions, intense anxiety, and visual and kinesthetic hallucinations. He also shows intense craving, compulsive drug use, general malaise, and weakness. After four weeks of admission and antipsychotic treatment, delusions completely disappear. The patient is reinfected with hepatitis C. Discussion. Psychiatric and medical conditions related to chemsex and slamming have been reported in several European cities, but not in Spain. Psychotic symptoms have been associated with mephedrone and other SCs’ consumption, with the IV route being prone to produce more severe symptomatology and addictive conducts. In the case we report, paranoid psychosis, addiction, and medical complications are described.

  17. Drug Dissolution under Physiologically Relevant Conditions In Vitro and In Vivo

    OpenAIRE

    Persson, Eva

    2006-01-01

    The general aim of the present project was to increase the understanding of the in vivo dissolution of poorly soluble drugs and thereby improve possibility to predict in vivo solubility from substance properties. Increased understanding of the in vivo limitations of drug solubility could potentially also generate ideas for improved formulation principles for poorly soluble compounds and more relevant in vitro dissolution test methods used in formulation development. The dynamic gastrointestin...

  18. Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

    Science.gov (United States)

    Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

    2011-01-01

    Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state. PMID:21386972

  19. Sensitive versus Rough Dependence under Initial Conditions in Atmospheric Flow Regimes

    Directory of Open Access Journals (Sweden)

    Anthony R. Lupo

    2016-12-01

    Full Text Available In this work, we will identify the existence of “rough dependence on initial conditions” in atmospheric phenomena, a concept which is a problem for weather analysis and forecasting. Typically, two initially similar atmospheric states will diverge slowly over time such that forecasting the weather using the Navier-Stokes equations is useless after some characteristic time scale. With rough dependence, two initial states diverge very quickly, implying forecasting may be impossible. Using previous research in atmospheric science, rough dependence is characterized by using quantities that can be calculated using atmospheric data and quantities. Rough dependence will be tested for and identified in atmospheric phenomena at different time scales using case studies. Data were provided for this project by archives outside the University of Missouri (MU and by using the MU RADAR at the South Farm experiment station.

  20. Evaluation of time-dependent void nucleation theory under ion bombardment conditions

    International Nuclear Information System (INIS)

    Sprague, J.A.; Russell, K.C.; Choi, Y.H.

    1975-01-01

    The applicability of a steady state and time-dependent homogeneous void nucleation theory to charged-particle irradiation experiments was investigated. The steady-state theory was found to be inappropriate, since significant changes in a metal's microstructure would likely occur before the void nucleation rate could reach steady state. Two types of time dependence were examined, that of the point defect concentrations at the beginning of an irradiation and the longer-term time dependence of void nucleation. It was found that vacancy and interstitial clustering significantly reduce the relaxation time for the point defect concentrations. An efficient form of time-dependent homogeneous nucleation theory was applied to ion bombardment conditions to predict void size distributions

  1. Drugs and having babies: an exploration of how a specialist clinic meets the needs of chemically dependent pregnant women.

    Science.gov (United States)

    Morris, Michelle; Seibold, Carmel; Webber, Ruth

    2012-04-01

    to explore the extent to which a specialist clinic meets the needs of chemically dependent women. a critical ethnography informed by theorists such as Habermas and feminists' interpretation of Foucault. a specialist antenatal clinic for chemically dependent pregnant women at a major metropolitan women's hospital in Melbourne, Australia. a purposive sample of twenty (20) chemically dependent pregnant women who attended the clinic. Data collection and analysis included three taped interviews (two preceding the birth and one post birth), observation of the interactions between the women and the clinic staff over a 25-month period and chart audits. similar to other studies there were multiple factors influencing development and maintenance of chemical dependency in this group of women, including family instability, family history of drug and alcohol abuse, childhood sexual abuse, having a chemically dependent partner and having a dual diagnosis of both drug addiction and mental illness. Initially there was considerable variation between the women and the clinic staff's expectations with regard to attending for antenatal care and conforming to a set regime as the women struggled with the contradictions inherent in their lifestyle and that of the 'normal' expectant mother. Aspects of that struggle included their belief that their opinions and knowledge of their lives was largely ignored, leading to episodes of resistance. Several women alleged the clinics staff's relationship with them was influenced by a belief that the women were 'hopeless addicts in need of expert medical and midwifery care' and that the clinic staff exercised control in an authoritarian manner. However, as they explored possibilities for collaboration, they realised they could exercise power and work towards a more equal relationship with staff. The quality of relationships in most instances improved over time, and if not always strictly collaborative, was situated at various points along a continuum

  2. Investigating the factor structure of the Illness Perception Questionnaire-revised for substance dependence among injecting drug users in China.

    Science.gov (United States)

    Mo, Phoenix K H; Lau, Joseph T F; Cheng, Kit Man; Mak, Winnie W S; Gu, Jing; Wu, Anise M S; Li, Jinghua

    2015-03-01

    The Illness Perception Questionnaire-Revised (IPQ-R) has commonly been used to measure illness representations of various diseases. The present study examined whether the original factor structure of the IPQ-R could be confirmed or a new structure could be established on substance dependence among injecting drug users (IDU) in China. A total of 257 IDU completed the 38-item IPQ-R on substance dependence. Results of confirmatory factor analysis (CFA) showed that the 7-factor structure as proposed by the original IPQ-R reported poor goodness-of-fit statistics. Although removal of 12 items improved the model fit, the goodness-of-fit statistics were still below acceptable standards. Furthermore, factors obtained from the exploratory factor analysis (EFA) of the IPQ-R were not interpretable. The CFA found that the original IPQ-R factor structure fit the data poorly. Factors derived from EFA were also not interpretable. Use of the IPQ-R for assessment of illness representations of substance dependence among IDU in China is cautioned until further validation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. The Effectiveness of Cognitive Behavioral Therapy on Increasing of Self-Efficacy and Improving of Addiction Symptoms among Drug Dependency Patients

    Directory of Open Access Journals (Sweden)

    Hamid Kamarzarin

    2012-08-01

    Full Text Available Introduction: The aim of this study was to determine the effectiveness of cognitive behavior therapy on increasing of self efficacy and improving of addiction symptoms among drug dependency patients. Method: For this purpose, 90 substance abusers were selected of private addiction center, Central Prison and drop in center by using of random sampling, and they were divided into two experimental (45 subjects and witness groups (45 subjects randomly. The members of experimental group were under 12 sessions of cognitive behavioral therapy by Carol method, and control group only have taken Methadone and other physical drugs. All participants at the beginning of research, during the study (after three months and three months after treatment completed self-efficacy questionnaire and Maudsley addiction profile (Map by a psychologist were assessed. The symptoms of addiction recovery and addiction treatment process. Results: Analysis of covariance indicated the treatment effectiveness and its maintenance on increasing of efficacy and reducing of the symptoms of Maudsley addiction profile. Conclusion: Cognitive behavior therapy is effective to increase self-efficacy and improve symptoms in substance abusers.

  4. FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action in Malassezia

    Directory of Open Access Journals (Sweden)

    Giuseppe Ianiri

    2017-10-01

    Full Text Available The genus Malassezia includes yeasts that are commonly found on the skin or hair of animals and humans as commensals and are associated with a number of skin disorders. We have previously developed an Agrobacterium tumefaciens transformation system effective for both targeted gene deletion and insertional mutagenesis in Malassezia furfur and M. sympodialis. In the present study, these molecular resources were applied to characterize the immunophilin FKBP12 as the target of tacrolimus (FK506, ascomycin, and pimecrolimus, which are calcineurin inhibitors that are used as alternatives to corticosteroids in the treatment of inflammatory skin disorders such as those associated with Malassezia species. While M. furfur and M. sympodialis showed in vitro sensitivity to these agents, fkb1Δ mutants displayed full resistance to all three of them, confirming that FKBP12 is the target of these calcineurin inhibitors and is essential for their activity. We found that calcineurin inhibitors act additively with fluconazole through an FKBP12-dependent mechanism. Spontaneous M. sympodialis isolates resistant to calcineurin inhibitors had mutations in the gene encoding FKBP12 in regions predicted to affect the interactions between FKBP12 and FK506 based on structural modeling. Due to the presence of homopolymer nucleotide repeats in the gene encoding FKBP12, an msh2Δ hypermutator of M. sympodialis was engineered and exhibited an increase of more than 20-fold in the rate of emergence of resistance to FK506 compared to that of the wild-type strain, with the majority of the mutations found in these repeats.

  5. Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.

    Science.gov (United States)

    Tsuzuki, K; Takeuchi, T; Ozawa, S

    1992-11-01

    GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor.

  6. FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action in Malassezia

    Science.gov (United States)

    Ianiri, Giuseppe; Applen Clancey, Shelly; Lee, Soo Chan

    2017-01-01

    ABSTRACT The genus Malassezia includes yeasts that are commonly found on the skin or hair of animals and humans as commensals and are associated with a number of skin disorders. We have previously developed an Agrobacterium tumefaciens transformation system effective for both targeted gene deletion and insertional mutagenesis in Malassezia furfur and M. sympodialis. In the present study, these molecular resources were applied to characterize the immunophilin FKBP12 as the target of tacrolimus (FK506), ascomycin, and pimecrolimus, which are calcineurin inhibitors that are used as alternatives to corticosteroids in the treatment of inflammatory skin disorders such as those associated with Malassezia species. While M. furfur and M. sympodialis showed in vitro sensitivity to these agents, fkb1Δ mutants displayed full resistance to all three of them, confirming that FKBP12 is the target of these calcineurin inhibitors and is essential for their activity. We found that calcineurin inhibitors act additively with fluconazole through an FKBP12-dependent mechanism. Spontaneous M. sympodialis isolates resistant to calcineurin inhibitors had mutations in the gene encoding FKBP12 in regions predicted to affect the interactions between FKBP12 and FK506 based on structural modeling. Due to the presence of homopolymer nucleotide repeats in the gene encoding FKBP12, an msh2Δ hypermutator of M. sympodialis was engineered and exhibited an increase of more than 20-fold in the rate of emergence of resistance to FK506 compared to that of the wild-type strain, with the majority of the mutations found in these repeats. PMID:29066552

  7. Temperature dependence of the rate constant of hydrogen isotope interactions with a lithium capillary-porous system under reactor irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tazhibayeva, Irina, E-mail: tazhibayeva@ntsc.kz [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Kulsartov, Timur; Gordienko, Yuri [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Mukanova, Aliya [Al’ Farabi Kazakh National University, Almaty (Kazakhstan); Ponkratov, Yuri; Barsukov, Nikolay; Tulubaev, Evgeniy [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Platacis, Erik [University of Latvia (IPUL), Riga (Latvia); Kenzhin, Ergazy [Shakarim Semey State University, Semey (Kazakhstan)

    2013-10-15

    Highlights: • The experiments with Li CPS sample were carried out at reactor IVG-1.M. • The gas absorption technique was used to study hydrogen isotope interaction with lithium CPS. • The temperature dependence of constants of interaction rate was obtained for various power rates of the reactor. • Determination of the activation energies, and pre-exponents of Arrhenius dependence. • The effect of increase of the rate constant under reaction irradiation. -- Abstract: Experiments with a sample of a lithium capillary-porous system (CPS) were performed at the reactor IVG-1.M of the Institute of Atomic Energy NNC RK to study the effects of neutron irradiation on the parameters of hydrogen isotope interactions with a lithium CPS. The absorption technique was used during the experiments, and this technique allowed the temperature dependences of the hydrogen isotope interaction rate constants with the lithium CPS to be obtained under various reactor powers. The obtained dependencies were used to determine the main interaction parameters: the activation energies and the pre-exponents of the Arrhenius dependence of the hydrogen interaction rate constants with lithium and the lithium CPS. An increase of the hydrogen isotope interaction rate with the lithium CPS was observed under reactor irradiation.

  8. The association between overweight and illegal drug consumption in adolescents: is there an underlying influence of the sociocultural environment?

    Directory of Open Access Journals (Sweden)

    Francesca Denoth

    Full Text Available BACKGROUND: The aims of the study were to: a Examine the distribution of gender-stratified body mass index (BMI, eating attitudes and use of addictive substances, under the hypothesis of a confluent prevalence of weight abnormalities, eating disorders and substance abuse. b Demonstrate the extent to which family, peer-related and psychosocial factors are common elements in categories of compulsive behaviour. METHODOLOGY/PRINCIPAL FINDINGS: In the present cross-sectional study, data were collected through self reported questionnaires administered to a large sample of 33,185 15-19 years old adolescents (ESPAD®Italia, divided into weight categories based on the BMI percentile distribution. Multinomial analyses were adopted to address the influence of social, family, leisure time factors, Eating Attitude Test (EAT26 on the association between weight categories and drug use. Recent drugs use was more frequent in overweight and underweight adolescents (p<0.05, especially in females. An EAT26 score ≥20 was more common in overweight adolescents. Multinomial analysis abolished the relationship between overweight and the use of most drugs, implicating self-esteem, parents' educational level, and friendships as mediators of the association. Within the overweight category, adolescents reporting recent drug use, showed greater frequency of having drug-abusing friends (∼80%, and severe problems with parents and school (∼30% compared to overweight adolescents without recent drug use. CONCLUSION: The frequent association of overweight and substance use and the presence of common underlying social factors, highlights the need for an interdisciplinary approach involving individual-focused treatment models as well as public health, social and environmental changes to reduce food- and substances-related problems.

  9. The association between overweight and illegal drug consumption in adolescents: is there an underlying influence of the sociocultural environment?

    Science.gov (United States)

    Denoth, Francesca; Siciliano, Valeria; Iozzo, Patricia; Fortunato, Loredana; Molinaro, Sabrina

    2011-01-01

    The aims of the study were to: a) Examine the distribution of gender-stratified body mass index (BMI), eating attitudes and use of addictive substances, under the hypothesis of a confluent prevalence of weight abnormalities, eating disorders and substance abuse. b) Demonstrate the extent to which family, peer-related and psychosocial factors are common elements in categories of compulsive behaviour. In the present cross-sectional study, data were collected through self reported questionnaires administered to a large sample of 33,185 15-19 years old adolescents (ESPAD®Italia), divided into weight categories based on the BMI percentile distribution. Multinomial analyses were adopted to address the influence of social, family, leisure time factors, Eating Attitude Test (EAT26) on the association between weight categories and drug use. Recent drugs use was more frequent in overweight and underweight adolescents (pEAT26 score ≥20 was more common in overweight adolescents. Multinomial analysis abolished the relationship between overweight and the use of most drugs, implicating self-esteem, parents' educational level, and friendships as mediators of the association. Within the overweight category, adolescents reporting recent drug use, showed greater frequency of having drug-abusing friends (∼80%), and severe problems with parents and school (∼30%) compared to overweight adolescents without recent drug use. The frequent association of overweight and substance use and the presence of common underlying social factors, highlights the need for an interdisciplinary approach involving individual-focused treatment models as well as public health, social and environmental changes to reduce food- and substances-related problems.

  10. Yoga: As an adjunct therapy to trim down the Ayurvedic drug requirement in non insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Sharma, Rohit; Amin, Hetal; Prajapati, P K

    2014-01-01

    In spite of a large number of drugs showing anti-hyperglycemic activities, none of them have been successful in complete management of diabetes mellitus (DM). Yoga and Ayurveda are the two schools of thought in India, which have a history of curing diseases since thousands of years. Yogic techniques and Ayurvedic herbs have proven their anti-diabetic potential without inducing untoward effects. The present study combines Ayurvedic medication with Yoga techniques as a new approach toward healing DM. To assess the effect of Yoga therapy in the management of non insulin-dependent DM (NIDDM) and to decrease the oral drug dose requirement of guḍūcī ghana Tablet. Thirty known NIDDM patients of both genders, who were on guḍūcī ghana (solidified aqueous extract of Tinospora cordifolia (Willd.) Miers.) tablets from past 2 months as Ayurvedic remedy for DM were selected. Along with guḍūcī ghana administration, the subjects were instructed to follow Yogic procedures including Āsanas, prāṇāyāma, and śuddhi kriyās. The study was conducted for 8 weeks, wherein fasting blood sugar (FBS) and postprandial blood sugar (PPBS) levels along with relief in sign and symptoms were assessed at every 2 weeks intervals, and according to relief in sign and symptoms, tapering of drug dosage was carried out. The obtained data were analyzed statistically by applying paired t-test. The results obtained were promising as the relief in diabetic symptomatology was highly significant in terms of P value. 80.83% reduction in dose of guḍūcī ghana tablets and 7.85% and 8.78% fall in FBS and PPBS levels, respectively, after the complete course of treatment. The obtained P value showed highly significant results.

  11. Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering : abstinence rates and withdrawal distress experiences

    NARCIS (Netherlands)

    Krabbe, Paul F M; Koning, Jeroen P F; Heinen, Nadia; Laheij, Robert J F; van Cauter, R M Victory; De Jong, Cor A J

    The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the

  12. Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences.

    NARCIS (Netherlands)

    Krabbe, P.F.M.; Koning, J.P.; Heinen, N.; Laheij, R.J.F.; Cauter, R.M.V. van; Jong, C.A.J. de

    2003-01-01

    The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the

  13. A Preliminary Study of Sexual Dysfunction in Male Opioid-Dependants under Methadone Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Masoudeh Babakhanian

    2011-08-01

    Full Text Available Introduction: Sexual dysfunction is one of the prevalent problems of opiate-dependent patients. The current preliminarily study examines sexual dysfunction in a group of opiate-dependent patients before and after 6 months of MMT. Methods: The current study is a cross-sectional study. The numbers of 30 opiate-dependent patients were selected of Cheraghiyan clinic in Damghan, Iran. Demographics questionnaire and the International Index of Erectile Function were administered before and after treatment. Results: Erectile function showed an increase and intercourse satisfactions completely improved. Sexual desire and overall satisfaction increased, showing slight improvement while orgasmic function increased showing no improvement. Discussion: The findings revealed the prevalence of sexual dysfunction and improvement of some component in patients after treatment. Future studies are needed to explore the roles of other factors.

  14. Immobilized pH gradient gel cell to study the pH dependence of drug lipophilicity.

    Science.gov (United States)

    Lam, Hoang-Trang; Pereira, Carlos M; Roussel, Christophe; Carrupt, Pierre-Alain; Girault, Hubert H

    2006-03-01

    An experimental setup to study the pH dependence of standard ion-transfer potentials at the water/NPOE interface is presented. The system is composed of a microhole generated by laser photoablation in a 12-microm polyethylene terephthalate film, the aqueous phase consisting of a commercial immobilized pH gradient gel reswelled in electrolyte solution and a droplet of organic solution. Two electrodes are used, an Ag/AgCl aqueous electrode and an Ag/AgTPBCl organic electrode. This setup is applied to the study of two ionizable compounds (pyridine, 2,4-dinitrophenol). Thermodynamic parameters such as the standard transfer potential, the Gibbs energy of transfer, and the partition coefficients of the ionized forms as well as the neutral forms of these drug compounds are evaluated by differential pulse voltammetry. The data obtained are summarized in ionic partition diagrams, which are a useful tool for predicting and interpreting the transfer behavior of ionized drugs at the liquid/liquid interfaces mimicking the biological membranes.

  15. Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

    Science.gov (United States)

    Nunes, Amanda A; Dos Santos, Rafael G; Osório, Flávia L; Sanches, Rafael F; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-01-01

    Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.

  16. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction.

    Science.gov (United States)

    Jeannot, Katy; Sobel, Mara L; El Garch, Farid; Poole, Keith; Plésiat, Patrick

    2005-08-01

    MexXY is an inducible efflux system that contributes to the natural resistance of Pseudomonas aeruginosa to antibiotics. Experiments involving real-time PCR after reverse transcription in reference strain PAO1 showed concentration-dependent induction of gene mexY by various ribosome inhibitors (e.g., chloramphenicol, tetracycline, macrolides, and aminoglycosides) but not by antibiotics acting on other cellular targets (e.g., beta-lactams, fluoroquinolones). Confirming a functional link between the efflux system and the translational machinery, ribosome protection by plasmid-encoded proteins TetO and ErmBP increased the resistance of a DeltamexAB-oprM mutant of PAO1 to tetracycline and erythromycin, respectively, as well as the concentrations of both drugs required to induce mexY. Furthermore, spontaneous mutations resulting in specific resistance to dihydrostreptomycin or spectinomycin also raised the minimal drug concentration for mexXY induction in strain PAO1. While strongly upregulated in a PAO1 mutant defective in gene mexZ (which codes for a putative repressor of operon mexXY), gene mexY remained inducible by agents such as tetracycline, chloramphenicol, and spectinomycin, suggesting additional regulatory loci for mexXY. Altogether, these data demonstrate physiological interplays between MexXY and the ribosome and are suggestive of an alternative function for MexXY beyond antibiotic efflux.

  17. Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

    Science.gov (United States)

    Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

    2017-03-01

    Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

  18. 75 FR 80114 - Agency Information Collection (Status of Dependents Questionnaire) Activity Under OMB Review

    Science.gov (United States)

    2010-12-21

    ... of Review: Extension of a currently approved collection. Abstract: Veterans receiving compensation...) complete VA Form 21-0538 to certify the status of the dependents for whom additional compensation is being...Lamb, Program Analyst, Enterprise Records Service. BILLING CODE 8320-01-P ...

  19. Autonomous and advertising-dependent 'word of mouth' under costly dynamic pricing

    NARCIS (Netherlands)

    El Ouardighi, Fouad; Feichtinger, G.; Grass, D.; Hartl, R.F.; Kort, Peter M.

    2016-01-01

    Autonomous 'word of mouth', as a channel of social influence that is out of firms' direct control, has acquired particular importance with the development of the Internet. Depending on whether a given product or service is a good or a bad deal, this can significantly contribute to commercial success

  20. Take control : Developing and testing novel treatments of substance dependence by targeting underlying neurocognitive processes

    NARCIS (Netherlands)

    Schulte, M.H.J.

    2018-01-01

    In this PhD project we investigated the effect of N-acetylcysteine (NAC) and working memory (WM) training on substance use, and associated changes in neural correlates of substance dependence. N-acetylcysteine is a glutamatergic agent that reduces craving by restoring the imbalance in the brain

  1. Driving under the influence of alcohol or drugs among adolescents: the role of urban and rural environments.

    Science.gov (United States)

    Font-Ribera, Laia; Garcia-Continente, Xavier; Pérez, Anna; Torres, Rosa; Sala, Núria; Espelt, Albert; Nebot, Manel

    2013-11-01

    This study aimed to describe driving under the influence of alcohol or drugs (DUIAD) and riding in a vehicle with a driver under the influence of alcohol or drugs (RDUIAD) and their associated factors among rural and urban adolescents in Spain. We performed a cross-sectional study including 2067 students from Barcelona and a rural area 60 km north of this city. The prevalences of ever DUIAD and RDUIAD were 17% and 41% among 17-18 year-old adolescents. DUIAD was more common in boys. Living in the rural area was independently associated with these behaviours. Exposure to these behaviours is common among Spanish adolescents, especially in rural areas. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. The location- and depth-dependent mechanical response of the human cornea under shear loading.

    Science.gov (United States)

    Sloan, Stephen R; Khalifa, Yousuf M; Buckley, Mark R

    2014-10-30

    To characterize the depth-dependent shear modulus of the central and peripheral human cornea along the superior-inferior and nasal-temporal directions with a high spatial resolution. Cylindrical explants from the central and peripheral corneas of 10 human donors were subjected to a 5% shear strain along the superior-inferior and nasal-temporal directions using a microscope-mounted mechanical testing device. Depth-dependent shear strain and shear modulus were computed through force measurements and displacement tracking. The shear modulus G of the human cornea varied continuously with depth, with a maximum occurring roughly 25% of the way from the anterior surface to the posterior surface. G also varied with direction in the superior region and (at some depths) was significantly higher for superior-inferior shear loading. In the anterior half of the cornea, the shear modulus along the nasal-temporal direction (GNT) did not vary with location; however, the superior region had significantly higher GNT in posterior cornea. In contrast, the shear modulus along the superior-inferior direction (GSI) was independent of location at all depths. This study demonstrates that the peak shear modulus of the human cornea occurs at a substantial distance within the corneal stroma. Depth-dependent differences between central and peripheral cornea possibly reflect the location-dependent mechanical environment of the cornea. Moreover, the cornea is not a transverse isotropic material, and must be characterized by more than a single shear modulus due to its dependence on loading direction. The material properties measured in this study are critical for developing accurate mechanical models to predict the vision-threatening morphological changes that can occur in the cornea. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  3. 75 FR 74063 - Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product...

    Science.gov (United States)

    2010-11-30

    ... dissemination of Patient Medication Information (PMI). With this FOA, FDA proposes to further expand the scope... paragraphs. Patient Medication Information (PMI) To be able to use prescription medications safely, consumers... Guides. Such changes to the delivery of PMI may require changes to the Federal Food, Drug, and Cosmetics...

  4. [Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency].

    Science.gov (United States)

    Voloshchuk, O N; Kopylchuk, G P

    2016-01-01

    Activity of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD(+)/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD(+)/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD(+)-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD(+)/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage.

  5. The comparition of Personality Patterns, irrational beliefs and impulsivity in males with with drug abuse disorder under Treatment

    Directory of Open Access Journals (Sweden)

    samere asadi

    2015-03-01

    Full Text Available Objective: the aim of this research was to determine the difference between personality Patterns, irrational beliefs and impulsivity in men with drug abuse disorder under Treatment. Method: in this casual- comparative research, 80 men ( 40 males with drug abuse under Treatment and 40 of normal males that were selected with available sampling .Groups were matched in terms of demoghraphy characteristics ( age, sexuality, education level and marital status and were valued with means of Eysenk Perceived Stress Inventory, Jonze Irrational Beliefs Scale and Baret Impulsivity Inventory. Results: The result of variance analysis showed that addicts compared to normal people, get more scores on extraversion, neuroticism and psychosis. Addicts group had Higher men scores in irrational beliefs compare of other group. There was significant difference between groups in impulsivity and impulsivity in addicts persons is the most. Conclussion: The traits of Personality, irrational beliefs and Unrealistic and high level impulsivity are factors that propel individuals toward more drug abuse and finally addict and aiming this factors in individuals with abuse disorder under Treatment can lead to prevent of Substance Abuse Relapse.

  6. Approval of raxibacumab for the treatment of inhalation anthrax under the US Food and Drug Administration Animal rule

    Directory of Open Access Journals (Sweden)

    Chia-Wei eTsai

    2015-12-01

    Full Text Available On December 14, 2012, the FDA approved raxibacumab, the first product developed under Project BioShield to achieve this milestone, and the first biologic product to be approved through the FDA animal efficacy rule (or Animal Rule. Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. The approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues.

  7. The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

    Science.gov (United States)

    Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

    2015-07-15

    The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. System Estimation of Panel Data Models under Long-Range Dependence

    DEFF Research Database (Denmark)

    Ergemen, Yunus Emre

    using conditional-sum-of-squares criteria based on projected series by which latent characteristics are proxied. Resulting estimates are consistent and asymptotically normal at standard parametric rates. A simulation study provides reliability on the estimation method. The method is then applied......A general dynamic panel data model is considered that incorporates individual and interactive fixed effects allowing for contemporaneous correlation in model innovations. The model accommodates general stationary or nonstationary long-range dependence through interactive fixed effects...

  9. Time-Dependent Response of Polypropylene/Clay Nanocomposites Under Tension and Retraction

    DEFF Research Database (Denmark)

    Drozdov, Aleksey; Christiansen, Jesper de Claville

    2013-01-01

    –strain relations are found by fitting the observations. Ability of the constitutive equations to describe characteristic features of the timedependent behavior of nanocomposites under cyclic deformation is confirmed by numerical simulation. POLYM. ENG. SCI., 00:000–000, 2012. ª2012 Society of Plastics Engineers......Observations are reported in relaxation tests under tension and retraction on polypropylene/clay nanocomposites with various contents of filler. A two-phase constitutive model is developed in cyclic viscoelasticity and viscoplasticity of nanocomposites. Adjustable parameters in the stress...

  10. Spin-dependent delay time and Hartman effect in asymmetrical graphene barrier under strain

    Science.gov (United States)

    Sattari, Farhad; Mirershadi, Soghra

    2018-01-01

    We study the spin-dependent tunneling time, including group delay and dwell time, in a graphene based asymmetrical barrier with Rashba spin-orbit interaction in the presence of strain, sandwiched between two normal leads. We find that the spin-dependent tunneling time can be efficiently tuned by the barrier width, and the bias voltage. Moreover, for the zigzag direction strain although the oscillation period of the dwell time does not change, the oscillation amplitude increases by increasing the incident electron angle. It is found that for the armchair direction strain unlike the zigzag direction the group delay time at the normal incidence depends on the spin state of electrons and Hartman effect can be observed. In addition, for the armchair direction strain the spin polarization increases with increasing the RSOI strength and the bias voltage. The magnitude and sign of spin polarization can be manipulated by strain. In particular, by applying an external electric field the efficiency of the spin polarization is improved significantly in strained graphene, and a fully spin-polarized current is generated.

  11. Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch.

    Science.gov (United States)

    Luo, De-Yi; Wazir, Romel; Du, Caigan; Tian, Ye; Yue, Xuan; Wei, Tang-Qiang; Wang, Kun-Jie

    2015-11-01

    The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch's amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers. HBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner. We described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

  12. The anaerobic conversion of methanol under thermophilic conditions: pH and bicarbonate dependence

    NARCIS (Netherlands)

    Paulo, P.L.; Villa, G.; Lier, van J.B.; Lettinga, G.

    2003-01-01

    The thermophilic (55degreesC) anaerobic conversion of methanol was studied in an unbuffered medium (pH 4 +/- 0.2) and in a phosphate buffered medium (pH 6.4 +/- 0.1), in both cases without bicarbonate addition. Our cultivated sludge consortium was unable to degrade methanol under acidic conditions.

  13. Time-dependent behavior of cracked concrete beams under sustained loading

    NARCIS (Netherlands)

    Sarkhosh, R.; Walraven, J.C.; Den Uijl, J.A.

    2013-01-01

    Under sustained loading, the propagation of cracks in concrete is assumed to be related to the elastic deformation, material parameters and time. Based on the fictitious crack model (FCM), a finite element method is proposed to explain the behavior of cracks in time using current constitutive

  14. Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

    Science.gov (United States)

    Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

    2015-06-01

    This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

  15. Drug Dependence and Psychotic Symptoms: A Retrospective Study of Adolescents Who Abuse Drugs at Al-Amal Hospital in Jeddah, Saudi Arabia

    OpenAIRE

    Alibrahim, Osama; Elawad, Nagi; Misau, Yusuf A.; Shaikh, Tarteel M.; Allam, Nedal

    2012-01-01

    Drug abuse is reported to be on the increase among young persons using illicit substances but little is known about the frequency with which they occur, the symptoms on presentation to health institutions, and the different substances abused. To establish this, we reviewed patient data collected at Al-Amal Hospital in Jeddah Kingdom of Saudi Arabia on young persons who are refered to the hospital for problems related to drug abuse. Data on 69 adolescent drug users were reviewed and analyzed u...

  16. Evaluation of drug permeation under fed state conditions using mucus-covered Caco-2 cell epithelium.

    Science.gov (United States)

    Birch, Ditlev; Diedrichsen, Ragna G; Christophersen, Philip C; Mu, Huiling; Nielsen, Hanne M

    2018-03-07

    The absence of a surface-lining mucus layer is a major pitfall for the Caco-2 epithelial model. However, this can be alleviated by applying biosimilar mucus (BM) to the apical surface of the cell monolayer, thereby constructing a mucosa mimicking in vivo conditions. This study aims to elucidate the influence of BM as a barrier towards exogenic compounds such as permeation enhancers, and components of fed state simulated intestinal fluid (FeSSIF). Caco-2 cell monolayers surface-lined with BM were exposed to several compounds with distinct physicochemical properties, and the cell viability and permeability of the cell monolayer was compared to that of cell monolayers without BM and well-established mucus-secreting epithelial models (HT29 monolayers and HT29/Caco-2 co-culture monolayers). Exposure of BM-covered cells to constituents from FeSSIF revealed that it comprised a strong, hydrophilic barrier effect as 90% of BM-covered cells remained viable for >4 h, and the permeation rate of hydrophobic drugs was reduced. In contrast, the permeation rate of hydrophilic drugs was largely unaffected. Control monolayers displayed a loss of barrier function and Caco-2 cell monolayers surface-lined with BM constitute a valuable in vitro model that makes it possible to mimic intestinal fed state conditions when studying drug permeation. Copyright © 2017. Published by Elsevier B.V.

  17. An update on CRF mechanisms underlying alcohol use disorders and dependence.

    Directory of Open Access Journals (Sweden)

    Isabel Marian Hartmann Quadros

    2016-10-01

    Full Text Available Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin Releasing Factor (CRF systems have been critically implied in the transition towards problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF binding protein and Urocortins, a family of CRF-related peptides.

  18. On the role of resonance in drug failure under HIV treatment interruption.

    Science.gov (United States)

    Oña, Leonardo; Kouyos, Roger D; Lachmann, Michael; Bonhoeffer, Sebastian

    2013-07-11

    The application of highly active antiretroviral therapy (HAART) against HIV can reduce and maintain viral load below detection limit in many patients. Continuous HAART, however, can have severe side effects. In this context, structured treatment interruptions (STI) were considered to be a promising strategy. However, using CD4 cell count to guide intermittent therapy starting and stopping points, the SMART study (strategies for management of antiretroviral therapy), revealed that STI were associated with increased risk of AIDS and other complications. Additionally, short-term periodic (e.g. one week on / one week off) interruption therapies have shown virus rebound exceeding a given "failure threshold", without any evidence for the evolution of drug resistance. Currently, the only hypothesis explaining the failure of STI is the "resonance hypothesis", which posits that treatment failure is due to a resonance effect between the drug treatment and the viral population. In the present study we used a mathematical model to analyse the parameters affecting the output of drug treatment interruption and the premises of the resonance hypothesis. We used a population dynamic model of HIV infection. Simulations and analytical approximations of deterministic and stochastic versions of the model were studied. The present study examines the roles of the most important parameters affecting the viral rebound, responsible for drug failure. We related these findings to the resonance hypothesis, and showed that the degree of sustainability of damping oscillations present in the model after the acute phase is strongly linked to their amplitude, which determines the resonance level. Stochastic simulations of the same model even revealed sustained oscillations in virus population for small virus population sizes. Given that pronounced viral load oscillations have not been observed in HIV-1 patients, the link between oscillations and resonance level suggests that treatment failure due

  19. Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity.

    Science.gov (United States)

    Chen, Qiang; Pei, Zhe; Koren, David; Wei, Wei

    2016-12-08

    The dendrites of starburst amacrine cells (SACs) in the mammalian retina are preferentially activated by motion in the centrifugal direction, a property that is important for generating direction selectivity in direction selective ganglion cells (DSGCs). A candidate mechanism underlying the centrifugal direction selectivity of SAC dendrites is synaptic inhibition onto SACs. Here we disrupted this inhibition by perturbing distinct sets of GABAergic inputs onto SACs - removing either GABA release or GABA receptors from SACs. We found that lateral inhibition onto Off SACs from non-SAC amacrine cells is required for optimal direction selectivity of the Off pathway. In contrast, lateral inhibition onto On SACs is not necessary for direction selectivity of the On pathway when the moving object is on a homogenous background, but is required when the background is noisy. These results demonstrate that distinct sets of inhibitory mechanisms are recruited to generate direction selectivity under different visual conditions.

  20. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

    Directory of Open Access Journals (Sweden)

    Takasugi Masaki

    2010-08-01

    Full Text Available Abstract Background Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA, and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes has not been comprehensively analyzed. Results We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs. These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain. Conclusions A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.

  1. Association and mycorrhizal dependency in Jatropha curcas L. seedlings under salt stress

    Directory of Open Access Journals (Sweden)

    Dilliani Felipe Barros de Oliveira

    Full Text Available ABSTRACT The cultivation of Jatropha curcas L. for biodiesel production is possible in salinized areas; however, biomass production is limited in these soils. Arbuscular mycorrhizal fungi (AMF are a promising alternative for bioremediation in salinized soils. Yet, salinity also affects the AMF at the time of colonization and, in this case, the symbiosis is not always established. Therefore, the aim of this study was to test the hypotheses that three AMF species commonly found in saline soils are associated with J. curcas and if seedlings previously inoculated with these AMF are more tolerant to salt stress. Two trials were performed: the first one was carried out in a completely randomized design with five treatments (control, Rhizophagus intraradices, Gigaspora albida, Claroideoglomus etunicatum, and the three species together and six repetitions to investigate the formation of symbiosis among species; and the second trial was carried out in randomized blocks in a 4 × 2 factorial scheme (2, 5, 8, and 10 dS m-1, with and without mycorrhizae with eight repetitions to verify the development and mycorrhizal dependency (MD of the seedlings previously inoculated, in salinized environment. The three species of AMF are associated with J. curcas both alone and together. Mycorrhizal dependency increased with salinity, indicating that J. curcas is a facultative species. The pre-colonized seedlings with AMF are an alternative to the establishment of J. curcas in salinized soils.

  2. Delay-Dependent Response in Weakly Electric Fish under Closed-Loop Pulse Stimulation.

    Directory of Open Access Journals (Sweden)

    Caroline Garcia Forlim

    Full Text Available In this paper, we apply a real time activity-dependent protocol to study how freely swimming weakly electric fish produce and process the timing of their own electric signals. Specifically, we address this study in the elephant fish, Gnathonemus petersii, an animal that uses weak discharges to locate obstacles or food while navigating, as well as for electro-communication with conspecifics. To investigate how the inter pulse intervals vary in response to external stimuli, we compare the response to a simple closed-loop stimulation protocol and the signals generated without electrical stimulation. The activity-dependent stimulation protocol explores different stimulus delivery delays relative to the fish's own electric discharges. We show that there is a critical time delay in this closed-loop interaction, as the largest changes in inter pulse intervals occur when the stimulation delay is below 100 ms. We also discuss the implications of these findings in the context of information processing in weakly electric fish.

  3. Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

    Science.gov (United States)

    Llorente-Berzal, Alvaro; Puighermanal, Emma; Burokas, Aurelijus; Ozaita, Andrés; Maldonado, Rafael; Marco, Eva M.; Viveros, Maria-Paz

    2013-01-01

    Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs. PMID:24223797

  4. Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption.

    Directory of Open Access Journals (Sweden)

    Alvaro Llorente-Berzal

    Full Text Available Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46, MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB, whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.

  5. A dependability modeling of software under hardware faults digitized system in nuclear power plants

    International Nuclear Information System (INIS)

    Choi, Jong Gyun

    1996-02-01

    An analytic approach to the dependability evaluation of software in the operational phase is suggested in this work with special attention to the physical fault effects on the software dependability : The physical faults considered are memory faults and the dependability measure in question is the reliability. The model is based on the simple reliability theory and the graph theory with the path decomposition micro model. The model represents an application software with a graph consisting of nodes and arcs that probabilistic ally determine the flow from node to node. Through proper transformation of nodes and arcs, the graph can be reduced to a simple two-node graph and the software failure probability is derived from this graph. This model can be extended to the software system which consists of several complete modules without modification. The derived model is validated by the computer simulation, where the software is transformed to a probabilistic control flow graph. Simulation also shows a different viewpoint of software failure behavior. Using this model, we predict the reliability of an application software and a software system in a digitized system(ILS system) in the nuclear power plant and show the sensitivity of the software reliability to the major physical parameters which affect the software failure in the normal operation phase. The derived model is validated by the computer simulation, where the software is transformed to a probabilistic control flow graph. Simulation also shows a different viewpoint of software failure behavior. Using this model, we predict the reliability of an application software and a software system in a digitized system (ILS system) is the nuclear power plant and show the sensitivity of the software reliability to the major physical parameters which affect the software failure in the normal operation phase. This modeling method is particularly attractive for medium size programs such as software used in digitized systems of

  6. Raft-dependent endocytosis of autocrine motility factor/phosphoglucose isomerase: a potential drug delivery route for tumor cells.

    Directory of Open Access Journals (Sweden)

    Liliana D Kojic

    and following intravenous injection in vivo where AMF/PGI-FITC was selectively internalized by subcutaneous B16-F1 tumor cells.The raft-dependent endocytosis of AMF/PGI may therefore represent a tumor cell specific endocytic pathway of potential value for drug delivery to tumor cells.

  7. Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain.

    Directory of Open Access Journals (Sweden)

    David A Barrière

    Full Text Available The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404 and that this metabolite contributes to paracetamol's antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA, both of which may undergo a fatty acid amide hydrolase (FAAH-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl-9Z-octadecenamide (HPODA and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol's analgesic activity via

  8. Time-Dependent Behavior of Reinforced Polymer Concrete Columns under Eccentric Axial Loading

    Directory of Open Access Journals (Sweden)

    Valentino Paolo Berardi

    2012-11-01

    Full Text Available Polymer concretes (PCs represent a promising alternative to traditional cementitious materials in the field of new construction. In fact, PCs exhibit high compressive strength and ultimate compressive strain values, as well as good chemical resistance. Within the context of these benefits, this paper presents a study on the time-dependent behavior of polymer concrete columns reinforced with different bar types using a mechanical model recently developed by the authors. Balanced internal reinforcements are considered (i.e., two bars at both the top and bottom of the cross-section. The investigation highlights relevant stress and strain variations over time and, consequently, the emergence of a significant decrease in concrete’s stiffness and strength over time. Therefore, the results indicate that deferred effects due to viscous flow may significantly affect the reliability of reinforced polymer concrete elements over time.

  9. Study on variation in ship's forward speed under regular waves depending on rudder controller

    Directory of Open Access Journals (Sweden)

    Sung-Soo Kim

    2015-03-01

    Full Text Available The purpose of this research is to compare and analyze the advanced speed of ships with different rudder controller in wavy condition by using a simulation. The commercial simulation tool named AQWA is used to develop the simulation of ship which has 3 degree of freedom. The nonlinear hydrodynamic force acting on hull, the propeller thrust and the rudder force are calculated by the additional subroutine which interlock with the commercial simulation tool, and the regular wave is used as the source of the external force for the simulation. Rudder rotational velocity and autopilot coefficients vary to make the different rudder controller. An advanced speed of ships depending on the rudder controller is analyzed after the autopilot simulations.

  10. A hybrid method for decision making with dependence & feedback under incomplete information

    Directory of Open Access Journals (Sweden)

    Chen Weijie

    2016-01-01

    Full Text Available This paper presents a hybrid method to tackle multiple criteria decision making problems with incomplete weight information in the context of fuzzy soft sets. In order to determine the weights of criteria, we develop a comprehensive two-stage framework. Stage One: We first define the distance between two fuzzy soft numbers. Next, we establish an optimization model based on ideal point of attribute values, by which the attrib-ute weights can be determined. Stage Two: To get the global weights, we use fuzzy cognitive maps to depict the dependent and feedback effect among criteria. Next, we require constructing fuzzy soft set to decide the desirable alternative. Finally, a case study is given to clarify the proposed approach of this paper.

  11. Gaussian Mixture Random Coefficient model based framework for SHM in structures with time-dependent dynamics under uncertainty

    Science.gov (United States)

    Avendaño-Valencia, Luis David; Fassois, Spilios D.

    2017-12-01

    The problem of vibration-based damage diagnosis in structures characterized by time-dependent dynamics under significant environmental and/or operational uncertainty is considered. A stochastic framework consisting of a Gaussian Mixture Random Coefficient model of the uncertain time-dependent dynamics under each structural health state, proper estimation methods, and Bayesian or minimum distance type decision making, is postulated. The Random Coefficient (RC) time-dependent stochastic model with coefficients following a multivariate Gaussian Mixture Model (GMM) allows for significant flexibility in uncertainty representation. Certain of the model parameters are estimated via a simple procedure which is founded on the related Multiple Model (MM) concept, while the GMM weights are explicitly estimated for optimizing damage diagnostic performance. The postulated framework is demonstrated via damage detection in a simple simulated model of a quarter-car active suspension with time-dependent dynamics and considerable uncertainty on the payload. Comparisons with a simpler Gaussian RC model based method are also presented, with the postulated framework shown to be capable of offering considerable improvement in diagnostic performance.

  12. Nonlinear dynamic response of a simply supported rectangular functionally graded material plate under the time-dependent thermal mechanical loads

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y. X. [Beijing Information Science and Technology University, Beijing (China); Zhang, W. [Beijing University of Technology, Beijing (China); Yang, J. [RMIT University, Bundoora (Australia); Li, S. Y. [Ttianjin University of Technology and Education, Tianjin (China)

    2011-07-15

    An analysis on nonlinear dynamic characteristics of a simply supported functionally graded materials (FGMs) rectangular plate subjected to the transversal and in-plane excitations is presented in the time dependent thermal environment. Here we look the FGM Plates as isotropic materials which is assumed to be temperature dependent and graded in the thickness direction according to the power-law distribution in terms of volume fractions of the constituents. The geometrical nonlinearity using Von Karman's assumption is introduced. The formulation also includes in-plane and rotary inertia effects. In the framework of Reddy's third-order shear deformation plate theory, the governing equations of motion for the FGM plate are derived by the Hamilton's principle. Then the equations of motion with two degree- of-freedom under combined the time-dependent thermomechanical loads can be obtained by using Galerkin's method. Using numerical method, the control equations are analyzed to obtain the response curves. Under certain conditions the periodic and chaotic motions of the FGM plate are found. It is found that because of the existence of the temperature which relate to the time the motions of the FGM plate show the great difference. A period motion can be changed into the chaotic motions which are affected by the time dependent temperature.

  13. EOQ Model for Deteriorating Items with exponential time dependent Demand Rate under inflation when Supplier Credit Linked to Order Quantity

    Directory of Open Access Journals (Sweden)

    Rakesh Prakash Tripathi

    2014-05-01

    Full Text Available In paper (2004 Chang studied an inventory model under a situation in which the supplier provides the purchaser with a permissible delay of payments if the purchaser orders a large quantity. Tripathi (2011 also studied an inventory model with time dependent demand rate under which the supplier provides the purchaser with a permissible delay in payments. This paper is motivated by Chang (2004 and Tripathi (2011 paper extending their model for exponential time dependent demand rate. This study develops an inventory model under which the vendor provides the purchaser with a credit period; if the purchaser orders large quantity. In this chapter, demand rate is taken as exponential time dependent. Shortages are not allowed and effect of the inflation rate has been discussed. We establish an inventory model for deteriorating items if the order quantity is greater than or equal to a predetermined quantity. We then obtain optimal solution for finding optimal order quantity, optimal cycle time and optimal total relevant cost. Numerical examples are given for all different cases. Sensitivity of the variation of different parameters on the optimal solution is also discussed. Mathematica 7 software is used for finding numerical examples.

  14. Driving under the influence of alcohol and drugs in the eastern part of Denmark in 2015 and 2016: Abuse patterns and trends.

    Science.gov (United States)

    Simonsen, Kirsten Wiese; Linnet, Kristian; Rasmussen, Brian Schou

    2018-01-25

    The objective of this study was to examine the frequency of psychoactive drugs and alcohol in drivers under suspicion of driving under the influence of drugs and alcohol in 2015 and 2016 in the eastern part of Denmark. The trends in the number of traffic cases sent for drug analysis since 2000 and alcohol analysis since 2011 are also discussed. Blood samples from drivers suspected of being under the influence of alcohol and/or medication and/or illicit drugs in 2015 and 2016 were investigated as requested by the police. The blood samples were screened for alcohol and/or tetrahydrocannabinol (THC) alone, for other drugs (covering all drugs, except THC, listed in the Danish list of narcotic drugs) or for THC and other drugs. Age and gender were also recorded. The number of drug traffic cases since 2000 and the number of alcohol cases since 2011 were extracted from our LIMS system (laboratory information management system). In total, 11,493 traffic cases were investigated. Alcohol and/or drugs exceeded the legal limit in 9,657 (84%) cases. Men constituted 95% of the drivers investigated for drugs and 88% of the alcohol cases. The drivers investigated for drugs consisted primarily of young men, whereas drivers investigated for alcohol were older. The frequency was higher for positive alcohol cases above the legal limit (87%) than for drug cases (76%) above the fixed concentration limit. THC (67-69%) was the most frequently detected drug above the legal limit, followed by cocaine (27-28.5%), amphetamine (17%) and clonazepam (6-7%) in both years. Morphine (5.4%), included among the five most frequent drugs in 2015, was replaced by methadone (4.6%) in 2016. Few new psychoactive drugs (NPS) were detected. The number of traffic cases sent for drug analysis has increased more than 30-fold since 2000-2006, and the number of traffic cases submitted in 2016 for drug analysis was higher than the number for alcohol analysis; the latter has decreased since 2011. Overall, alcohol

  15. Chain length and temperature dependence of alkanedithiol molecular conductance under ultra high vacuum.

    Science.gov (United States)

    Pires, Ellis; Macdonald, J Emyr; Elliott, Martin

    2013-10-07

    We report scanning tunnelling microscope (STM) measurements of the single molecule conductance of α,ω-alkanedithiols for a large range of molecular chain lengths (N = 3-10) and temperatures (180-390 K) under ultra high vacuum. Two STM-based measurement techniques were employed on molecules trapped between tip and substrate: (i) the well established current-distance or I(z) technique and (ii) a new I(V,z) technique in which the current-voltage characteristics are determined as the tip-substrate distance z is varied. Low, medium, and high conductance groups were observed for each molecular length, which were temperature independent over the range examined, consistent with off-resonance tunnelling. For N > 4 the current-voltage characteristics and conductance trend with chain length is well described using a simple rectangular tunnel barrier model with parameters in excellent agreement with previously reported values. However, both 1,3-propanedithiol (N = 3) and 1,4-butanedithiol (N = 4) show an anomalous behaviour which is qualitatively similar to, but much less pronounced than, that reported by Haiss et al. (Phys. Chem. Chem. Phys., 2009, 11, 10831) for measurements performed under air and nitrogen gas.

  16. Watershed response and land energy feedbacks under climate change depend upon groundwater.

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, R M; Kollet, S J

    2008-06-10

    Human induced climate change will have a significant impact on the hydrologic cycle, creating changes in fresh water resources, land cover, and feedbacks that are difficult to characterize, which makes it an issue of global importance. Previous studies have not included subsurface storage in climate change simulations and feedbacks. A variably-saturated groundwater flow model with integrated overland flow and land surface model processes is used to examine the interplay between coupled water and energy processes under climate change conditions. A case study from the Southern Great Plains (SGP) USA, an important agricultural region that is susceptible to drought, is used as the basis for three scenarios simulations using a modified atmospheric forcing dataset to reflect predicted effects due to human-induced climate change. These scenarios include an increase in the atmospheric temperature and variations in rainfall amount and are compared to the present-day climate case. Changes in shallow soil saturation and groundwater levels are quantified as well as the corresponding energy fluxes at the land surface. Here we show that groundwater and subsurface lateral flow processes are critical in understanding hydrologic response and energy feedbacks to climate change and that certain regions are more susceptible to changes in temperature, while others to changes in precipitation. This groundwater control is critical for understanding recharge and drought processes, possible under future climate conditions.

  17. Experience with second line drugs in frequently relapsing and steroid dependent childhood nephrotic syndrome in a large Saudi center

    Directory of Open Access Journals (Sweden)

    Khalid Alsaran, M.D.

    2017-06-01

    Conclusion: All the second line drugs in our study were equally effective. However, we recommend that the initial treatment of FR/SD nephrotic syndrome should be chosen with the least toxic yet equally efficacious drug Levamisole.

  18. Reporting of adverse drug reactions: predictors of under-reporting in Malaysia.

    Science.gov (United States)

    Aziz, Zoriah; Siang, Tan Ching; Badarudin, Nurul Suhaida

    2007-02-01

    Malaysia like many other countries worldwide uses spontaneous reporting systems as a mean of collecting data on suspected adverse drug reaction (ADR). However, compared to other countries, which use the system, the reporting rate in Malaysia is very low. Why some physicians do not report ADRs is not well understood. To identify factors, which would predict physicians' failure to send ADR reports. Face-to-face interview using a structured questionnaire involving physicians working at the University of Malaya Medical Centre, Malaysia. About a third of the physicians in the Centre participated. Sixty-five of the 415 approached refused to participate. A high proportion of the respondents (81.4%) indicated that they had suspected an ADR but did not report it, while about 40% of the respondents were not aware of the existence of the national reporting system in Malaysia. Logistic regression modelling identified the variable 'ADR considered to be too trivial or too well known to report' as the strongest predictor of not reporting, followed by physicians' category and uncertainty that the reaction had been definitely caused by a drug. Important predictor variables, which limit physicians from reporting ADR in Malaysia, were related to uncertainty of types of reaction to report, lack of awareness about the existence, function and purpose of national ADR reporting. The findings could be useful for planning strategies to improve the reporting rate.

  19. Dynamics of electron plasma vortex under time-dependent external strain

    Science.gov (United States)

    Hurst, N. C.; Danielson, J. R.; Dubin, D. H. E.; Surko, C. M.

    2016-10-01

    The behavior of two-dimensional vortex structures is of key interest in a number of important physical systems, including geophysical fluids and strongly magnetized plasmas. Specifically, vortices can be stripped and destroyed by external forcing (for example, from boundaries or other nearby vortices). The research presented here focuses on the behavior of an initially axisymmetric vortex subjected to external straining flow fields which vary in time. Experimental results are obtained using an electron plasma confinement device, which models the 2D Euler equations for ideal fluid flow. Vortex-in-cell simulation results are also presented to complement and extend the laboratory results. Specific behaviors under consideration include details of the vortex destruction mechanism, vortex adiabaticity, and vortex splitting via the Kelvin-Helmholtz instability.

  20. Strain rate dependent energy absorption capacity of reinforced concrete members under aircraft impact

    International Nuclear Information System (INIS)

    Brandes, K.; Limberger, E.; Herter, J.

    1983-01-01

    The safety analysis of nuclear power plants includes the impact of an aircraft on the reinforced concrete containment structure. The load characteristics of this event are more or less standardized. In order to reduce the construction costs and to come to a realistic design of anti-impact structures, it is of interest to take advantage of the potential plastic behaviour of reinforced concrete structural members under impact and impulsive loading. But up to now gaps in the knowledge in this field restrain a realistic design. To close these gaps a R and D-programme supported by the governments has been initiated in the Federal Republic of Germany. Some work in this respect carried out since 1977 in BAM is part of this programme. (orig./WL)

  1. mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells.

    Science.gov (United States)

    Pusapati, Raju V; Daemen, Anneleen; Wilson, Catherine; Sandoval, Wendy; Gao, Min; Haley, Benjamin; Baudy, Andreas R; Hatzivassiliou, Georgia; Evangelista, Marie; Settleman, Jeff

    2016-04-11

    Although glycolysis is substantially elevated in many tumors, therapeutic targeting of glycolysis in cancer patients has not yet been successful, potentially reflecting the metabolic plasticity of tumor cells. In various cancer cells exposed to a continuous glycolytic block, we identified a recurrent reprogramming mechanism involving sustained mTORC1 signaling that underlies escape from glycolytic addiction. Active mTORC1 directs increased glucose flux via the pentose phosphate pathway back into glycolysis, thereby circumventing a glycolysis block and ensuring adequate ATP and biomass production. Combined inhibition of glycolysis and mTORC1 signaling disrupted metabolic reprogramming in tumor cells and inhibited their growth in vitro and in vivo. These findings reveal novel combinatorial therapeutic strategies to realize the potential benefit from targeting the Warburg effect. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

    Science.gov (United States)

    Coller, Janet K; Hutchinson, Mark R

    2012-05-01

    In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Mg2+-dependent gating of bacterial MgtE channel underlies Mg2+ homeostasis

    Science.gov (United States)

    Hattori, Motoyuki; Iwase, Norihiko; Furuya, Noritaka; Tanaka, Yoshiki; Tsukazaki, Tomoya; Ishitani, Ryuichiro; Maguire, Michael E; Ito, Koichi; Maturana, Andres; Nureki, Osamu

    2009-01-01

    The MgtE family of Mg2+ transporters is ubiquitously distributed in all phylogenetic domains. Recent crystal structures of the full-length MgtE and of its cytosolic domain in the presence and absence of Mg2+ suggested a Mg2+-homeostasis mechanism, in which the MgtE cytosolic domain acts as a ‘Mg2+ sensor' to regulate the gating of the ion-conducting pore in response to the intracellular Mg2+ concentration. However, complementary functional analyses to confirm the proposed model have been lacking. Moreover, the limited resolution of the full-length structure precluded an unambiguous characterization of these regulatory divalent-cation-binding sites. Here, we showed that MgtE is a highly Mg2+-selective channel gated by Mg2+ and elucidated the Mg2+-dependent gating mechanism of MgtE, using X-ray crystallographic, genetic, biochemical, and electrophysiological analyses. These structural and functional results have clarified the control of Mg2+ homeostasis through cooperative Mg2+ binding to the MgtE cytosolic domain. PMID:19798051

  4. Flow angle dependent photoacoustic Doppler power spectra under intensity-modulated continuous wave laser excitation

    Directory of Open Access Journals (Sweden)

    Yu Tong

    2016-02-01

    Full Text Available Photoacoustic Doppler (PAD power spectra showing an evident Doppler shift represent the major characteristics of the continuous wave-excited or burst wave-excited versions of PAD flow measurements. In this paper, the flow angle dependences of the PAD power spectra are investigated using an experiment setup that was established based on intensity-modulated continuous wave laser excitation. The setup has an overall configuration that is similar to a previously reported configuration, but is more sophisticated in that it accurately aligns the laser illumination with the ultrasound detection process, and in that it picks up the correct sample position. In the analysis of the power spectra data, we find that the background power spectra can be extracted by combining the output signals from the two channels of the lock-in amplifier, which is very useful for identification of the PAD power spectra. The power spectra are presented and analyzed in opposite flow directions, at different flow speeds, and at different flow angles. The power spectra at a 90° flow angle show the unique properties of symmetrical shapes due to PAD broadening. For the other flow angles, the smoothed power spectra clearly show a flow angle cosine relationship.

  5. Temperature dependence of underdense nanostructure formation in tungsten under helium irradiation

    International Nuclear Information System (INIS)

    Valles, G.; Martin-Bragado, I.; Nordlund, K.; Lasa, A.; Björkas, C.; Safi, E.; Perlado, J.M.; Rivera, A.

    2017-01-01

    Recently, tungsten has been found to form a highly underdense nanostructured morphology (“W fuzz”) when bombarded by an intense flux of He ions, but only in the temperature window 900–2000 K. Using object kinetic Monte Carlo simulations (pseudo-3D simulations) parameterized from first principles, we show that this temperature dependence can be understood based on He and point defect clustering, cluster growth, and detrapping reactions. At low temperatures (<900 K), fuzz does not grow because almost all He is trapped in very small He-vacancy clusters. At high temperatures (>2300 K), all He is detrapped from clusters, preventing the formation of the large clusters that lead to fuzz growth in the intermediate temperature range. - Highlights: •OKMC simulation of temperature window for fuzz formation. •Stable He-V clusters prevent fuzz formation at low temperatures. •Dissociation of He-V clusters prevent fuzz formation at high temperatures. •Fuzz formation rate increases with increasing temperature. •An incubation fluence observed in the simulations, similar to experimental observations.

  6. Sense of control under uncertainty depends on people's childhood environment: a life history theory approach.

    Science.gov (United States)

    Mittal, Chiraag; Griskevicius, Vladas

    2014-10-01

    Past research found that environmental uncertainty leads people to behave differently depending on their childhood environment. For example, economic uncertainty leads people from poor childhoods to become more impulsive while leading people from wealthy childhoods to become less impulsive. Drawing on life history theory, we examine the psychological mechanism driving such diverging responses to uncertainty. Five experiments show that uncertainty alters people's sense of control over the environment. Exposure to uncertainty led people from poorer childhoods to have a significantly lower sense of control than those from wealthier childhoods. In addition, perceptions of control statistically mediated the effect of uncertainty on impulsive behavior. These studies contribute by demonstrating that sense of control is a psychological driver of behaviors associated with fast and slow life history strategies. We discuss the implications of this for theory and future research, including that environmental uncertainty might lead people who grew up poor to quit challenging tasks sooner than people who grew up wealthy. 2014 APA, all rights reserved

  7. Mechanisms underlying vestibulo‐cerebellar motor learning in mice depend on movement direction

    Science.gov (United States)

    Voges, Kai; Wu, Bin; Post, Laura

    2017-01-01

    Key points Directionality, inherent to movements, has behavioural and neuronal correlates.Direction of vestibular stimulation determines motor learning efficiency.Vestibulo‐ocular reflex gain–increase correlates with Purkinje cell simple spike potentiation.The locus of neural correlates for vestibulo‐ocular reflex adaptation is paradigm specific. Abstract Compensatory eye movements elicited by head rotation, also known as vestibulo‐ocular reflex (VOR), can be adapted with the use of visual feedback. The cerebellum is essential for this type of movement adaptation, although its neuronal correlates remain to be clarified. In the present study, we show that the direction of vestibular input determines the magnitude of eye movement adaptation induced by mismatched visual input in mice, with larger changes during contraversive head rotation. Moreover, the location of the neural correlate of this changed behaviour depends on the type of paradigm. Gain–increase paradigms induce increased simple spike (SS) activity in ipsilateral cerebellar Purkinje cells (PC), which is in line with eye movements triggered by optogenetic PC activation. By contrast, gain–decrease paradigms do not induce changes in SS activity, indicating that the murine vestibulo‐cerebellar cortical circuitry is optimally designed to enhance ipsiversive eye movements. PMID:28586131

  8. Generalized time-dependent Schrödinger equation in two dimensions under constraints

    Science.gov (United States)

    Sandev, Trifce; Petreska, Irina; Lenzi, Ervin K.

    2018-01-01

    We investigate a generalized two-dimensional time-dependent Schrödinger equation on a comb with a memory kernel. A Dirac delta term is introduced in the Schrödinger equation so that the quantum motion along the x-direction is constrained at y = 0. The wave function is analyzed by using Green's function approach for several forms of the memory kernel, which are of particular interest. Closed form solutions for the cases of Dirac delta and power-law memory kernels in terms of Fox H-function, as well as for a distributed order memory kernel, are obtained. Further, a nonlocal term is also introduced and investigated analytically. It is shown that the solution for such a case can be represented in terms of infinite series in Fox H-functions. Green's functions for each of the considered cases are analyzed and plotted for the most representative ones. Anomalous diffusion signatures are evident from the presence of the power-law tails. The normalized Green's functions obtained in this work are of broader interest, as they are an important ingredient for further calculations and analyses of some interesting effects in the transport properties in low-dimensional heterogeneous media.

  9. Calendar aging of commercial graphite/LiFePO4 cell - Predicting capacity fade under time dependent storage conditions

    Science.gov (United States)

    Grolleau, Sébastien; Delaille, Arnaud; Gualous, Hamid; Gyan, Philippe; Revel, Renaud; Bernard, Julien; Redondo-Iglesias, Eduardo; Peter, Jérémy

    2014-06-01

    In applications such as electrical transportation, most of the battery life is spent under storage. Understanding and estimating aging under storage, also named as calendar aging, is therefore a prerequisite for cell life prediction. This work investigates aging behavior upon storage of a commercial 15 Ah lithium-ion graphite/iron phosphate cell. Performance decline during 450 days of storage under nine stationary conditions is analyzed using non-destructive electrochemical tests. Temperature is found to be more detrimental than State of Charge (SoC). Most often, degradation models express the accumulated degradation with respect to time and aging conditions. In this article, a simple modeling approach is proposed focusing on the degradation rate to predict capacity fade. This permits predicting cell degradation under time dependent storage conditions (SoC and temperature) which are usually experienced in real applications. Model prediction is compared to experimental calendar aging data obtained over 625 days in a controlled time dependent temperature storage conditions. Predictions are in good agreement with experimental results as the absolute error on capacity prediction never exceeds 3% over 400 days and 5% over 625 days.

  10. Retention of under-represented minorities in drug abuse treatment studies.

    Science.gov (United States)

    Magruder, Kathryn M; Bichun Ouyang; Miller, Scott; Tilley, Barbara C

    2009-06-01

    Differential attrition by minority participants can be as limiting to interpreting final results as poor initial recruitment of minority participants. This is especially important in drug abuse treatment studies, as minorities are over-represented in substance abuse clinical treatment programs. The specific aims of this secondary data analysis were to: (1) determine if there are differences in study retention rates by race/ethnicity and age, and (2) explore other client characteristics, as well as protocol and treatment program factors, that could account for differential retention rates. We conducted a secondary analysis using data from 1737 participants in the first six clinical trials whose databases were locked in the NIDA Clinical Trials Network. Protocol level characteristics were also abstracted from these studies, and we used data from a study which assessed characteristics of community treatment programs that participated in these studies. Logistic regression was used to study the effect on retention of: client, protocol, and program characteristics. In the model of client characteristics, a significant age by race/ethnicity interaction term was detected based on a threshold of 0.1, with younger African Americans having the lowest odds of retention. Primary drug of abuse was also a significant factor in determining study retention, with heroin, methadone, and opiate users having the greatest odds of retention and polydrug users the lowest. Similar analyses testing treatment program characteristics found that only the presence of HIV risk screening and decreasing levels of female admissions (as a percent of total admissions) were related to study retention. In our final model, there was an effect of age, but not race/ethnicity, with younger participants having lower odds of retention. A multivariable model including protocol variables could not be developed due to the high correlation among protocol variables. We excluded those of multi-race/ethnicity and

  11. Kombucha brewing under the Food and Drug Administration model Food Code: risk analysis and processing guidance.

    Science.gov (United States)

    Nummer, Brian A

    2013-11-01

    Kombucha is a fermented beverage made from brewed tea and sugar. The taste is slightly sweet and acidic and it may have residual carbon dioxide. Kombucha is consumed in many countries as a health beverage and it is gaining in popularity in the U.S. Consequently, many retailers and food service operators are seeking to brew this beverage on site. As a fermented beverage, kombucha would be categorized in the Food and Drug Administration model Food Code as a specialized process and would require a variance with submission of a food safety plan. This special report was created to assist both operators and regulators in preparing or reviewing a kombucha food safety plan.

  12. Mycorrhizal dependency of mangaba tree under increasing phosphorus levels Dependência micorrízica de mangabeira em doses crescentes de fósforo

    Directory of Open Access Journals (Sweden)

    Júlio Alves Cardoso Filho

    2008-07-01

    Full Text Available The objective of this study was to evaluate the mycorrhizal dependency of mangaba tree (Hancornia speciosa plantlets, under increasing levels of phosphorus fertilization. The experimental design was completely randomized in a 4×5 factorial arrangement with three mycorrhizal fungi inocula - Gigaspora margarita, Glomus etunicatum, or a pool of native mycorrhizal fungi (Acaulospora longula, Glomus clarum, Gigaspora albida, Paraglomus sp. -, and a nonmycorrhizal control, in combination with five levels of phosphorus applied to the substrate: 0, 25, 50, 75, and 100 mg kg-1. After 180 days of growth, plantlets with inoculation of native mycorrhizal pool produced more shoot and root dry biomass and had higher shoot phosphorus content and accumulation. The noninoculated control showed the lowest values, independently of the phosphorus level. The highest relative mycorrhizal dependency occurred with the inoculation of native mycorrhizal fungi. Plants with mycorrhizal fungi did not respond to phosphorus addition above 50 mg kg-1. Mangaba tree is highly dependent on mycorrhiza, but the degree of dependency varies according to phosphorus levels and fungal inocula. In general, mangaba tree is more responsive to mycorrhizal fungi inoculation than to phosphorus addition.O objetivo deste trabalho foi avaliar a dependência micorrízica de mudas de mangaba (Hancornia speciosa, em doses crescentes de fósforo. O delineamento experimental foi inteiramente casualizado, em arranjo fatorial 4´5 com três inóculos de fungos micorrízicos - Gigaspora margarita, Glomus etunicatum, ou uma mistura de espécies de fungos micorrízicos nativos (Acaulospora longula, Glomus clarum, Gigaspora albida e Paraglomus sp. -, e um controle não micorrízico, combinados a cinco doses de fósforo no substrato: 0, 25, 50, 75 e 100 mg kg-1. Após 180 dias, as mudas com inoculação dos fungos micorrízicos nativos produziram mais biomassa seca de parte aérea e raízes e apresentaram

  13. Spin dynamics and spin-dependent recombination of a polaron pair under a strong ac drive

    Science.gov (United States)

    Malla, Rajesh K.; Raikh, M. E.

    2017-08-01

    We study theoretically the recombination within a pair of two polarons in magnetic field subject to a strong linearly polarized ac drive. Strong drive implies that the Zeeman frequencies of the pair partners are much smaller than the Rabi frequency, so that the rotating wave approximation does not apply. What makes the recombination dynamics nontrivial is that the partners recombine only when they form a singlet S . By admixing singlet to triplets, the drive induces the triplet recombination as well. We calculate the effective decay rate of all four spin modes. Our main finding is that, under the strong drive, the major contribution to the decay of the modes comes from short time intervals when the driving field passes through zero. When the recombination time in the absence of drive is short, fast recombination from S leads to anomalously slow recombination from the other spin states of the pair. We show that, with strong drive, this recombination becomes even slower. The corresponding decay rate falls off as a power law with the amplitude of the drive.

  14. Micromechanism Underlying Nonlinear Stress-Dependent K0 of Clays at a Wide Range of Pressures

    Directory of Open Access Journals (Sweden)

    Xiang-yu Shang

    2015-01-01

    Full Text Available In order to investigate the mechanism underlying the reported nonlinear at-rest coefficient of earth pressure, K0 of clays at high pressure, a particle-scale model which can be used to calculate vertical and horizontal repulsion between clay particles has been proposed. This model has two initial states which represent the clays at low pressure and high pressure, and the particles in this model can undergo rotation and vertical translation. The computation shows that the majority of particles in a clay sample at high pressure state would experience rotation during one-dimensional compression. In addition, rotation of particles which tends to form a parallel structure causes an increase of the horizontal interparticle force, while vertical translation leads to a decrease in it. Finally, the link between interparticle force, microstructure, and macroscopic K0 is analyzed and it can be used to interpret well the nonlinear changes in K0 with both vertical consolidation stress and height-diameter ratio.

  15. Frictional systems under periodic loads — History-dependence, non-uniqueness and energy dissipation

    International Nuclear Information System (INIS)

    Barber, J R

    2012-01-01

    Nominally static contacts such as bolted or shrink-fit joints typically experience regions of microslip when subjected to oscillatory loading. This results in energy dissipation, reflected as apparent hysteretic damping of the system, and also may cause the initiation of fretting fatigue cracks. Early theoretical studies of the Hertzian contact problem by Cattaneo and Mindlin were confirmed experimentally by Johnson, who identified signs of fretting damage in the slip annulus predicted by the theory. For many years, tribologists assumed that Melan's theorem in plasticity could be extended to frictional systems — i.e. that if there exists a state of residual stress associated with frictional slip that is sufficient to prevent periodic slip in the steady state, then the system will shake down, regardless of the initial condition. However, we now know that this is true only if there is no coupling between the normal and tangential loading problems, as will be the case notably when contact occurs on a symmetry plane. For all other cases, periodic loading scenarios can be devised such that shakedown occurs for some initial conditions and not for others. The initial condition here might be determined by the assembly protocol — e.g. the order in which a set of bolts is tightened — or by the exact loading path before the steady cycle is attained. This non-uniqueness of the steady state persists at load amplitudes above the shakedown limit, in which case there is always some dissipation, but the dissipation per cycle (and hence both the effective damping and the susceptibility to fretting damage) depends on the initial conditions. This implies that fretting fatigue experiments need to follow a well-defined assembly protocol if reproducible results are to be obtained. We shall also present results showing that when both normal and tangential forces vary in time, the energy dissipation is very sensitive to the relative phase of the oscillatory components, being greatest

  16. 75 FR 52957 - Supplemental Funding Under the Food and Drug Administration's Food Emergency Response Laboratory...

    Science.gov (United States)

    2010-08-30

    .../PAR-09-215.html . The program is further described in the Catalog of Federal Domestic Assistance under... agreements are to enable the analyses of foods and food products in the event that laboratory surge capacity... training and proficiency testing for each method/platform. Minimal quality management systems will be...

  17. How color difference formulas depend on reference pairs in the underlying constant stimuli experiment.

    Science.gov (United States)

    Kirchner, Eric; Dekker, Niels; Lucassen, Marcel; Njo, Lan; van der Lans, Ivo; Koeckhoven, Pim; Urban, Philipp; Huertas, Rafael

    2015-12-01

    For calculating color differences, the CIEDE2000 and CIE94 equations are widely used and recommended. These equations were derived more than a decade ago, based for a large part on the RIT-Dupont set of visual data. This data was collected from a series of psychophysical tests that use the method of constant stimuli. In this method, observers need to compare the color difference within a sample pair to that between a reference pair. In the current investigation, we show that the color difference equation significantly changes if reference pairs are chosen in the underlying visual experiments that differ from what was used when creating the RIT-Dupont dataset. The investigation is done using metallic paint samples representing two color centers, red and yellow-green. We show that the reproducibility differs for three different reference pairs, and that for modeling the visual data for the yellow-green color center, extra model terms are required as compared to the CIEDE2000 equation. Our results suggest that observers differ in their ability to mentally convert a color difference recognized in a sample pair into an equivalent color difference along the color difference direction represented by the reference pair. We also find that in these tests the tolerance to lightness differences is widened by a factor of 1.3 to 1.6, and that for the red color center the tolerance ellipsoid is rotated by 30° as compared to the CIEDE2000 equation. The latter observations are possibly due to the metallic texture in the samples used for the current experiment.

  18. [Dependency syndrome].

    Science.gov (United States)

    Vuorisalo, Sailaritta

    2013-01-01

    The most common causes of lower limb edema include cardiac insufficiency, venous insufficiency, insufficiency of lymph flow, and side effects of drugs. It can also be due to dependency syndrome, in which the edema and skin changes can only be explained by a passive calf muscle pump and the resulting venous hypertension. Underlying the drop foot is always immobilization for one reason or other. The patient must be given an explanation about the situation, activated to move if possible, and in any case guided to the use of support stockings and postural therapy.

  19. Explicating the Conditions Under Which Multilevel Multiple Imputation Mitigates Bias Resulting from Random Coefficient-Dependent Missing Longitudinal Data.

    Science.gov (United States)

    Gottfredson, Nisha C; Sterba, Sonya K; Jackson, Kristina M

    2017-01-01

    Random coefficient-dependent (RCD) missingness is a non-ignorable mechanism through which missing data can arise in longitudinal designs. RCD, for which we cannot test, is a problematic form of missingness that occurs if subject-specific random effects correlate with propensity for missingness or dropout. Particularly when covariate missingness is a problem, investigators typically handle missing longitudinal data by using single-level multiple imputation procedures implemented with long-format data, which ignores within-person dependency entirely, or implemented with wide-format (i.e., multivariate) data, which ignores some aspects of within-person dependency. When either of these standard approaches to handling missing longitudinal data is used, RCD missingness leads to parameter bias and incorrect inference. We explain why multilevel multiple imputation (MMI) should alleviate bias induced by a RCD missing data mechanism under conditions that contribute to stronger determinacy of random coefficients. We evaluate our hypothesis with a simulation study. Three design factors are considered: intraclass correlation (ICC; ranging from .25 to .75), number of waves (ranging from 4 to 8), and percent of missing data (ranging from 20 to 50%). We find that MMI greatly outperforms the single-level wide-format (multivariate) method for imputation under a RCD mechanism. For the MMI analyses, bias was most alleviated when the ICC is high, there were more waves of data, and when there was less missing data. Practical recommendations for handling longitudinal missing data are suggested.

  20. A novel magnetic nanoparticle hyperthermia combined with ACMF-dependant drug release by DAMMs injection in VX-2 liver tumors.

    Science.gov (United States)

    Zhang, Quanan; Tong, Jinlong; Chen, Huijuan; Jiang, Linlin; Zhu, Huiping; Zhu, Xiaofang; Yu, Hui; Liu, Jiwei; Liu, Baorui

    2012-01-01

    In this paper, we investigated the feasibility and effect of a novel combination therapy of magnetic nanoparticles (MNPs) hyperthermia with anticancer drugs for solid malignancies using doxorubicin-loaded alginate-templated magnetic microcapsules (DAMMs) in an animal liver cancer model. Firstly, DAMMs containing 18 nm gamma-Fe2O3 with doxorubicin (Dox) were synthesized and characterized. Then, the particular behavior of Dox release under external alternating current magnetic filed (ACMF) was tested in vitro. Moreover, to obtain accurate thermotherapy, the dose of DAMMs and temperature rise were computed by Hyperthermia treatment plan (HTP) and a fiber optic temperature sensor (FOTS) was used to monitor the temperature rise during treatments on VX-2 liver tumor-bearing rabbits. Furthermore, the therapeutic effect was studied by histopathological examinations and animal survival. The results showed that ACMF can induce Dox fast release during the treatment and the high MNPs content of DMMAs guaranteed the temperature rise for hyperthermia in tumors. The rabbits bearing VX-2 tumors in the magnetic hyperthermia using DMMAs group gained the most tumor necrosis and survival time. It was indicated that DAMMs-based magnetic hyperthermia could be a feasible and effective remedy which could be targeted at liver tumors by dual effects of hyperthermia and chemotherapy.

  1. Growing Season Conditions Mediate the Dependence of Aspen on Redistributed Snow Under Climate Change.

    Science.gov (United States)

    Soderquist, B.; Kavanagh, K.; Link, T. E.; Seyfried, M. S.; Strand, E. K.

    2016-12-01

    Precipitation regimes in many semiarid ecosystems are becoming increasingly dominated by winter rainfall as a result of climate change. Across these regions, snowpack plays a vital role in the distribution and timing of soil moisture availability. Rising temperatures will result in a more uniform distribution of soil moisture, advanced spring phenology, and prolonged growing seasons. Productive and wide ranging tree species like aspen, Populus tremuloides, may experience increased vulnerability to drought and mortality resulting from both reduced snowpack and increased evaporative demand during the growing season. We simulated the net primary production (NPP) of aspen stands spanning the rain:snow transition zone in the Reynolds Creek Critical Zone Observatory (RCCZO) in southwest Idaho, USA. Within the RCCZO, the total amount of precipitation has remained unchanged over the past 50 years, however the percentage of the precipitation falling as snow has declined by approximately 4% per decade at mid-elevation sites. The biogeochemical process model Biome-BGC was used to simulate aspen NPP at three stands located directly below snowdrifts that provide melt water late into the spring. After adjusting precipitation inputs to account for the redistribution of snow, we assessed climate change impacts on future aspen productivity. Mid-century (2046-2065) aspen NPP was simulated using temperature projections from a multi-model average under high emission conditions using the Multivariate Adaptive Constructed Analogs (MACA) data set. While climate change simulations indicated over a 20% decrease in annual NPP for some years, NPP rates for other mid-century years remained relatively unchanged due to variations in growing season conditions. Mid-century years with the largest decreases in NPP typically showed increased spring transpiration rates resulting from earlier leaf flush combined with warmer spring conditions. During these years, the onset of drought stress occurred

  2. Robust Adaptive Synchronization of Ring Configured Uncertain Chaotic FitzHugh–Nagumo Neurons under Direction-Dependent Coupling

    Directory of Open Access Journals (Sweden)

    Muhammad Iqbal

    2018-02-01

    Full Text Available This paper exploits the dynamical modeling, behavior analysis, and synchronization of a network of four different FitzHugh–Nagumo (FHN neurons with unknown parameters linked in a ring configuration under direction-dependent coupling. The main purpose is to investigate a robust adaptive control law for the synchronization of uncertain and perturbed neurons, communicating in a medium of bidirectional coupling. The neurons are assumed to be different and interconnected in a ring structure. The strength of the gap junctions is taken to be different for each link in the network, owing to the inter-neuronal coupling medium properties. Robust adaptive control mechanism based on Lyapunov stability analysis is employed and theoretical criteria are derived to realize the synchronization of the network of four FHN neurons in a ring form with unknown parameters under direction-dependent coupling and disturbances. The proposed scheme for synchronization of dissimilar neurons, under external electrical stimuli, coupled in a ring communication topology, having all parameters unknown, and subject to directional coupling medium and perturbations, is addressed for the first time as per our knowledge. To demonstrate the efficacy of the proposed strategy, simulation results are provided.

  3. Robust Adaptive Synchronization of Ring Configured Uncertain Chaotic FitzHugh–Nagumo Neurons under Direction-Dependent Coupling

    Science.gov (United States)

    Iqbal, Muhammad; Rehan, Muhammad; Hong, Keum-Shik

    2018-01-01

    This paper exploits the dynamical modeling, behavior analysis, and synchronization of a network of four different FitzHugh–Nagumo (FHN) neurons with unknown parameters linked in a ring configuration under direction-dependent coupling. The main purpose is to investigate a robust adaptive control law for the synchronization of uncertain and perturbed neurons, communicating in a medium of bidirectional coupling. The neurons are assumed to be different and interconnected in a ring structure. The strength of the gap junctions is taken to be different for each link in the network, owing to the inter-neuronal coupling medium properties. Robust adaptive control mechanism based on Lyapunov stability analysis is employed and theoretical criteria are derived to realize the synchronization of the network of four FHN neurons in a ring form with unknown parameters under direction-dependent coupling and disturbances. The proposed scheme for synchronization of dissimilar neurons, under external electrical stimuli, coupled in a ring communication topology, having all parameters unknown, and subject to directional coupling medium and perturbations, is addressed for the first time as per our knowledge. To demonstrate the efficacy of the proposed strategy, simulation results are provided. PMID:29535622

  4. Drug use study for acute respiratory infection in children under 10 years of age

    OpenAIRE

    Iwan Dwiprahasto, Iwan Dwiprahasto

    2015-01-01

    Background: Acute respiratory infection (ARI) is the commonest illness in children and the leading cause of morbidity and mortality in many developing countries. It comprises approximately 50 % of all illness in children under five years. Even though usually viral in origin and of a self-limiting nature, various study indicate that antibiotic prescribing for ARI is inappropriately high.Objective: This study was aimed to assess general practitioners' (GPs) prescribing pattern for acute respira...

  5. Time-dependent phosphate dynamics in reclaimed lignite-mine soils under Robinia pseudoacacia L.

    Science.gov (United States)

    Freese, Dirk; Slazak, Anna

    2017-04-01

    . With increasing age of trees the ratio of available P to total P decreased in tendency for all soil layers. The total P content increased slightly over time in all soil layers. But the amount of Fe and Al oxides increased also over time and therefore the overall P sorption capacity increased, too. Hence, the ratio between available P and total P shifted more to the less available forms of P in soil. Within a period of 20 years, R. pseudoacacia L. cultivation on post mining sites increased the contents of available P and total P, repectively. The P sorption increased with time of soil development showing the maximum at the oldest site. Nevertheless, P sorption of these initial post mining soils is still rather low. The results suggest, that the SRC of R. pseudoacacia L. on post mining sites have a positive influence on the P dynamics. References Freese, D., Van Riemsdijk, W.H., Van Der Zee, S.E.A.T.M., 1995. Modelling phosphate-sorption kinetics in acid soils. European Journal of Soil Science 46(2), 239-245. Matos, E.S., Freese, D., Böhm, C., Quinkenstein, A., Hüttl, R.F., 2012. Organic Matter Dynamics in Reclaimed Lignite Mine Soils under Robinia pseudoacacia L. Plantations of Different Ages in Germany. Communications in Soil Science and Plant Analysis 43(5), 745-755.

  6. The role of emotional and behavioral disorders in the development of drug dependence in patients with medication-induced headache (review

    Directory of Open Access Journals (Sweden)

    A. E. Shagbazyan

    2016-01-01

    Full Text Available Medication-induced headache (MIH is a variety of chronic daily headache (HA. MIH belongs to secondary (symptomatic HA, develops as a complication of pre-existing primary cephalgia, and is caused by the overuse of drugs to relieve HA. The role of drug dependence syndrome and behavioral and emotional disorders in the development of MIH, which may be associated with dysfunction of certain brain systems that control these functions, has been recently discussed. The paper reviews the literature dealing with studies of the role of behavioral and emotional disorders and orbitofrontal cortical dysfunction in the development of drug dependence syndrome in patients with MIH. The importance of analyzing these aspects of MIH is determined by the prospects for applying alternative approaches to managing these patients.

  7. Myxobacterial natural products: An under-valued source of products for drug discovery for neurological disorders.

    Science.gov (United States)

    Dehhaghi, Mona; Mohammadipanah, Fatemeh; Guillemin, Gilles J

    2018-03-02

    Age-related disorders impose noticeable financial and emotional burdens on society. This impact is becoming more prevalent with the increasing incidence of neurodegenerative diseases and is causing critical concerns for treatment of patients worldwide. Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neuron disease are the most prevalent and the most expensive to treat neurodegenerative diseases globally. Therefore, exploring effective therapies to overcome these disorders is a necessity. Natural products and their derivatives have increasingly attracted attention in drug discovery programs that have identified microorganisms which produce a large range of metabolites with bioactive properties. Myxobacteria, a group of Gram-negative bacteria with large genome size, produce a wide range of secondary metabolites with significant chemical structures and a variety of biological effects. They are potent natural product producers. In this review paper, we attempt to overview some secondary metabolites synthesized by myxobacteria with neuroprotective activity through known mechanisms including production of polyunsaturated fatty acids, reduction of apoptosis, immunomodulation, stress reduction of endoplasmic reticulum, stabilization of microtubules, enzyme inhibition and serotonin receptor modulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments.

    Science.gov (United States)

    Zhao, Yan-Hong; Zhang, Xue-Fang; Zhao, Yan-Qiu; Bai, Fan; Qin, Fan; Sun, Jing; Dong, Ying

    2017-08-01

    Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein. Imatinib is the first-line treatment of CML; however, many patients are resistant to this drug. In this study, we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments. GSE24946 was downloaded from the GEO database, which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5). Three drug treatment groups were considered for this study: arsenic trioxide (ATO), AMN107, and ATO+AMN107. Each group had one sample at each time point (3, 12, 24, and 48 h). Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened, and their expression patterns were revealed based on Short Time-series Expression Miner (STEM). Then, the functional enrichment analysis of time-series genes in each group was performed using DAVID, and the genes enriched in the top ten functional categories were extracted to detect their expression patterns. Different time-series genes were identified in the three groups, and most of them were enriched in the ribosome and oxidative phosphorylation pathways. Time-series genes in the three treatment groups had different expression patterns and functions. Time-series genes in the ATO group (e.g. CCNA2 and DAB2) were significantly associated with cell adhesion, those in the AMN107 group were related to cellular carbohydrate metabolic process, while those in the ATO+AMN107 group (e.g. AP2M1) were significantly related to cell proliferation and antigen processing. In imatinib-resistant CML cells, ATO could influence genes related to cell adhesion, AMN107 might affect genes involved in cellular carbohydrate metabolism, and the combination therapy might regulate genes involved in cell proliferation.

  9. Approximate energies and thermal properties of a position-dependent mass charged particle under external magnetic fields

    International Nuclear Information System (INIS)

    Eshghi, M; Mehraban, H; Ikhdair, S M

    2017-01-01

    We solve the Schrödinger equation with a position-dependent mass (PDM) charged particle interacted via the superposition of the Morse-plus-Coulomb potentials and is under the influence of external magnetic and Aharonov–Bohm (AB) flux fields. The nonrelativistic bound state energies together with their wave functions are calculated for two spatially-dependent mass distribution functions. We also study the thermal quantities of such a system. Further, the canonical formalism is used to compute various thermodynamic variables for second choosing mass by using the Gibbs formalism. We give plots for energy states as a function of various physical parameters. The behavior of the internal energy, specific heat, and entropy as functions of temperature and mass density parameter in the inverse-square mass case for different values of magnetic field are shown. (paper)

  10. Growth and magnetic properties dependence of the Co–Cu/Cu films electrodeposited under high magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Franczak, Agnieszka, E-mail: agnieszka.franczak@mtm.kuleuven.be [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); Department of Materials Science (MTM), KU Leuven, Kasteelpark Arenberg 44, 3001 Haverlee (Leuven) (Belgium); Levesque, Alexandra [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); Zabinski, Piotr [Laboratory of Physical Chemistry and Electrochemistry, Faculty of Non-Ferrous Metals, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Li, Donggang [Key Laboratory of Electromagnetic Processing of Materials (Ministry of Education), Northeastern University, 314 Box, 110004 Shenyang (China); Czapkiewicz, Maciej [Department of Electronics, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Kowalik, Remigiusz [Laboratory of Physical Chemistry and Electrochemistry, Faculty of Non-Ferrous Metals, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Bohr, Frédéric [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); and others

    2015-07-15

    The present work is focused on the investigations of magnetic properties dependence on microstructure of Co–Cu/Cu films electrodeposited under superimposed high magnetic field. The experimental results indicate a strong effect of an external magnetic field on the morphology of deposited films, more precisely on the Co:Cu ratio that determines the film growth. It is shown that the Co–Cu/Cu films electrodeposited without superimposed magnetic field consisted of two clearly visible features: compact film with incorporated granular particles. Under a superimposed external high magnetic field the privilege growth of the particles was induced. As a consequence, development of the well-defined branched structure of Co–Cu/Cu film was observed. In contrary, the phase compositional investigations do not reveal any changes in the phase formation during electrodeposition under magnetic field conditions. Thus, it is assumed that a strong growth of Co–Cu/Cu films in (111) direction under magnetic or non-magnetic electrodeposition conditions is related with the growth of Cu (111) plane and embedded into it some of the Co fcc atoms of same (111) orientation, as well as the Co hcp atoms that grows in the (002) direction. This non-equilibrium growth of Co–Cu/Cu films under magnetic deposition conditions affects strongly the magnetic properties of deposited films, revealing that films obtained under magnetic fields higher than 3 T were no more magnetic materials. - Highlights: • Co–Cu/Cu electrodeposits were obtained at elevated temperature under HMFs. • The effects of HMFs on microstructure and magnetic properties were investigated. • Interesting morphological changes due to HMFs has been observed. • Changes in Co:Cu ratio due to HMFs modified the magnetic properties of deposits.

  11. Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

    Science.gov (United States)

    Park, Glen D; Mitchel, Jules T

    2016-06-01

    While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product. © 2016 New York Academy of Sciences.

  12. TRICARE; removal of the prohibition to use addictive drugs in the maintenance treatment of substance dependence in TRICARE beneficiaries. Final rule.

    Science.gov (United States)

    2013-10-22

    The Department of Defense (DoD) is publishing this final rule to remove the exclusion of drug maintenance programs and allow TRICARE coverage of the substitution of a therapeutic drug, with addictive potential, for a drug of addiction when medically necessary and appropriate as part of a comprehensive treatment plan for an individual with substance use dependence. The current regulation prohibits coverage of drug maintenance programs where one addictive substance is substituted for another. The final rule allows TRICARE to cover, as part of otherwise authorized treatment of substance use disorder, utilization of a specific category of psychoactive agent when medically necessary and appropriate. Removal of the exclusion is based on recognition of the accumulated medical evidence supporting the use of certain pharmacotherapies as one component in the continuum of opioid treatment services. Medication assisted treatment, to include drug maintenance involving substitution of a therapeutic drug with addiction potential, for a drug of addiction, is now generally accepted by qualified professionals to be reasonable and adequate as a component in the safe and effective treatment of substance use disorders treatment services, and thus appropriate for inclusion as a component in the TRICARE authorized substance use disorder treatment for beneficiaries.

  13. Elucidating the role of dose in the biopharmaceutics classification of drugs: the concepts of critical dose, effective in vivo solubility, and dose-dependent BCS.

    Science.gov (United States)

    Charkoftaki, Georgia; Dokoumetzidis, Aristides; Valsami, Georgia; Macheras, Panos

    2012-11-01

    To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose for the various classes of BCS and the marginal cases in between classes. Simulations based on the mathematical model of F versus dose produced patterns of a constant F throughout a wide range of doses for drugs of Classes I, II and III, justifying biowaiver claim. For Classes I and III the pattern of a constant F stops at a critical dose Dose(cr) after which the amount of drug absorbed, is independent from the dose. For doses higher than Dose(cr), Class I drugs become Class II and Class III drugs become Class IV. Dose(cr) was used to define an in vivo effective solubility as S(eff) = Dose(cr)/250 ml. Literature data were used to support our simulation results. A new biopharmaceutic classification of drugs is proposed, based on F, separating drugs into three regions, taking into account the dose, and Dose(cr), while the regions for claiming biowaiver are clearly defined.

  14. Inventory model with cash flow oriented and time-dependent holding cost under permissible delay in payments

    Directory of Open Access Journals (Sweden)

    Tripathi R.P.

    2013-01-01

    Full Text Available This study develops an inventory model for determining an optimal ordering policy for non-deteriorating items and time-dependent holding cost with delayed payments permitted by the supplier under inflation and time-discounting. The discounted cash flows approach is applied to study the problem analysis. Mathematical models have been derived under two different situations i.e. case I: The permissible delay period is less than cycle time for settling the account and case II: The permissible delay period is greater than or equal to cycle time for settling the account. An algorithm is used to obtain minimum total present value of the costs over the time horizon H. Finally, numerical example and sensitivity analysis demonstrate the applicability of the proposed model. The main purpose of this paper is to investigate the optimal cycle time and optimal payment time for an item so that annual total relevant cost is minimized.

  15. Segmental-dependent membrane permeability along the intestine following oral drug administration: Evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat.

    Science.gov (United States)

    Dahan, Arik; West, Brady T; Amidon, Gordon L

    2009-02-15

    In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following oral drug administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar P(eff) values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower P(eff) in the distal parts. Similar P(eff) values for all drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.

  16. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  17. Novel near-infrared BiFC systems from a bacterial phytochrome for imaging protein interactions and drug evaluation under physiological conditions.

    Science.gov (United States)

    Chen, Minghai; Li, Wei; Zhang, Zhiping; Liu, Sanying; Zhang, Xiaowei; Zhang, Xian-En; Cui, Zongqiang

    2015-04-01

    Monitoring protein-protein interactions (PPIs) in live subjects is critical for understanding these fundamental biological processes. Bimolecular fluorescence complementation (BiFC) provides a good technique for imaging PPIs; however, a BiFC system with a long wavelength remains to be pursued for in vivo imaging. Here, we conducted systematic screening of split reporters from a bacterial phytochrome-based, near-infrared fluorescent protein (iRFP). Several new near-infrared phytochrome BiFC systems were built based on selected split sites including the amino acids residues 97/98, 99/100, 122/123, and 123/124. These new near-infrared BiFC systems from a bacterial phytochrome were verified as powerful tools for imaging PPIs under physiological conditions in live cells and in live mice. The interaction between HIV-1 integrase (IN) and cellular cofactor protein Lens epithelium-derived growth factor (LEDGF/p75) was visualized in live cells using the newly constructed iRFP BiFC system because of its important roles in HIV-1 integration and replication. Because the HIV IN-LEDGF/p75 interaction is an attractive anti-HIV target, drug evaluation assays to inhibit the HIV IN-LEDGF/p75 interaction were also performed using the newly constructed BiFC system. The results showed that compound 6 and carbidopa inhibit the HIV IN-LEDGF/p75 interaction in a dose-dependent manner under physiological conditions in the BiFC assays. This study provides novel near-infrared BiFC systems for imaging protein interactions under physiological conditions and provides guidance for splitting other bacterial phytochrome-like proteins to construct BiFC systems. The study also provides a new method for drug evaluation in live cells based on iRFP BiFC systems and supplies some new information regarding candidate drugs for anti-HIV therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Drug Stroop: Mechanisms of response to computerized cognitive behavioral therapy for cocaine dependence in a randomized clinical trial.

    Science.gov (United States)

    DeVito, Elise E; Kiluk, Brian D; Nich, Charla; Mouratidis, Maria; Carroll, Kathleen M

    2018-02-01

    Poor performance on Drug Stroop tasks, which could indicate attentional bias to drug-related cues, craving, poor cognitive control (including poor response inhibition), has been associated with substance use severity, treatment retention and substance use treatment outcomes. Cognitive Behavioral Therapy (CBT) focuses on training in appraisal and coping strategies, including strategies to minimize the negative impact of triggers and coping with drug-cue-induced craving. One mechanism of action of CBT may be the strengthening of cognitive control processes and reduction of attentional bias to drug-related stimuli. Methadone-maintained individuals with cocaine-use disorders, participating in a randomized controlled trial of treatment as usual (TAU) versus TAU plus access to computer-based CBT (CBT4CBT), completed a computerized Drug Stroop task at pre- and post-treatment. Analyses determined whether attentional bias toward drug-related stimuli changed differentially by treatment group or cocaine use outcomes across the treatment period and whether engagement in components of CBT4CBT or TAU treatment related to changes in attentional bias toward drug-related stimuli at post- versus pre-treatment. Participants achieving a longer duration of cocaine abstinence during treatment (3+ weeks) showed greater reductions in Drug Stroop Effect than those with shorter maximum continuous abstinence. Reductions in Drug Stroop Effect across treatment were associated with greater engagement with CBT4CBT-specific treatment components, but not TAU-specific treatment components. Reduction in attentional bias to drug-related cues and craving and/or improved executive cognitive control and response inhibition may contribute to the mechanism of action of CBT4CBT. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Systematic evaluation of "compliance" to prescribed treatment medications and "abstinence" from psychoactive drug abuse in chemical dependence programs: data from the comprehensive analysis of reported drugs.

    Science.gov (United States)

    Blum, Kenneth; Han, David; Femino, John; Smith, David E; Saunders, Scott; Simpatico, Thomas; Schoenthaler, Stephen J; Oscar-Berman, Marlene; Gold, Mark S

    2014-01-01

    This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across "levels of care" in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD) data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens) were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; Pabuse detected in either the first or last urine samples (abstinence). Moreover, in 2010, 16.9% of the patients (n = 57) were abstinent at first but not at last urine (deteriorating abstinence), the percentage dropped to 13.3% (n = 174) in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511) representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10-8) of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10-16) was found. Being cognizant of the trend toward drug urine testing being linked to medical necessity eliminating abusive screening, the interpretation of these valuable results require further intensive investigation.

  20. Three-Level Supply Chain Coordination under Disruptions Based on Revenue-Sharing Contract with Price Dependent Demand

    Directory of Open Access Journals (Sweden)

    Qinghua Pang

    2014-01-01

    Full Text Available Considering the market demand is stochastic and dependent on price, this paper shows that the revenue-sharing contract could coordinate a three-level supply chain consisting of one manufacturer, one distributor, and one retailer under normal environment. However, the original revenue-sharing contract cannot coordinate the supply chain under disruptions in circumstances of certain incidents leading to significant changes in market demand and causing additional deviation costs. To solve the problem, this essay introduces two improved forms of revenue-sharing contract: a mixed contract form based on a quantity discount policy and a pure form, which are characterized by antidisruption ability. The model of improved revenue-sharing contract is optimized when the market demand is in the additive form or in the multiplicative form with price dependent demand. Formulas are given to calculate the optimal contract parameters. Finally, this essay demonstrates the accuracy of the model of improved revenue-sharing contract with the help of numerical examples.

  1. Electromechanical behavior of polyaniline/poly (vinyl alcohol) blend films under static, dynamic and time-dependent strains

    International Nuclear Information System (INIS)

    Akhilesan, S; Lakshmana Rao, C; Varughese, S

    2014-01-01

    We report on the experimentally observed electrical conductivity enhancement in polyaniline/poly (vinyl alcohol) blend films under uniaxial tensile loading. Polyaniline (PANI) is an intrinsically conducting polymer, which does not form stretchable free-standing films easily and hence its electromechanical characterization is a challenge. Blending of PANI with other insulating polymers is a good choice to overcome the processability problem. We report the electromechanical response of solution blended and HCl doped PANI/PVA blends subjected to uniaxial, static, dynamic and time-dependent tensile loading. The demonstrated viscoelastic and morphological contributions of the component polymers to the electrical conductivity behavior in these blends could lead to interesting applications in strain sensors and flexible electronics. The reversibility of the electromechanical response under dynamic strain is found to increase in blends with higher PANI content. Time-dependent conductivity studies during mechanical stress relaxation reveal that variations in the micro-domain ordering and the relative relaxation rate of the individual polymer phases can give rise to interesting electrical conductivity changes in PANI blends. From morphological and electrical conductivity studies, we show that PANI undergoes primary and secondary agglomeration behavior in these blends that contributes to the changes in conductivity behavior during the deformation. A 3D variable range hopping (VRH) process, which uses a deformable core and shell concept based on blend morphology analysis, is used to explain the experimentally observed electromechanical behavior. (papers)

  2. The predictive validity of the Drinking-Related Cognitions Scale in alcohol-dependent patients under abstinence-oriented treatment

    Directory of Open Access Journals (Sweden)

    Sawayama Toru

    2012-05-01

    Full Text Available Abstract Background Cognitive factors associated with drinking behavior such as positive alcohol expectancies, self-efficacy, perception of impaired control over drinking and perception of drinking problems are considered to have a significant influence on treatment effects and outcome in alcohol-dependent patients. However, the development of a rating scale on lack of perception or denial of drinking problems and impaired control over drinking has not been substantial, even though these are important factors in patients under abstinence-oriented treatment as well as participants in self-help groups such as Alcoholics Anonymous (AA. The Drinking-Related Cognitions Scale (DRCS is a new self-reported rating scale developed to briefly measure cognitive factors associated with drinking behavior in alcohol-dependent patients under abstinence-oriented treatment, including positive alcohol expectancies, abstinence self-efficacy, perception of impaired control over drinking, and perception of drinking problems. Here, we conducted a prospective cohort study to explore the predictive validity of DRCS. Methods Participants in this study were 175 middle-aged and elderly Japanese male patients who met the DSM-IV Diagnostic Criteria for Alcohol Dependence. DRCS scores were recorded before and after the inpatient abstinence-oriented treatment program, and treatment outcome was evaluated one year after discharge. Results Of the 175 participants, 30 were not available for follow-up; thus the number of subjects for analysis in this study was 145. When the total DRCS score and subscale scores were compared before and after inpatient treatment, a significant increase was seen for both scores. Both the total DRCS score and each subscale score were significantly related to total abstinence, percentage of abstinent days, and the first drinking occasion during the one-year post-treatment period. Therefore, good treatment outcome was significantly predicted by low

  3. Ex vivo permeability experiments in excised rat intestinal tissue and in vitro solubility measurements in aspirated human intestinal fluids support age-dependent oral drug absorption.

    Science.gov (United States)

    Annaert, Pieter; Brouwers, Joachim; Bijnens, Ann; Lammert, Frank; Tack, Jan; Augustijns, Patrick

    2010-01-31

    The possible influence of advanced age on intestinal drug absorption was investigated by determining the effects of aging on (i) solubility of model drugs in human intestinal fluids (HIF) obtained from two age groups (18-25 years; 62-72 years); and (ii) transepithelial permeation of model drugs across intestinal tissue excised from young, adult and old rats. Average equilibrium solubility values for 10 poorly soluble compounds in HIF aspirated from both age groups showed high interindividual variability, but did not reveal significant differences. Characterization of the HIF from both age groups demonstrated comparable pH profiles, while concentrations of individual bile salts showed pronounced variability between individuals, however without statistical differences between age groups. Transepithelial permeation of the transcellular probe metoprolol was significantly increased in old rats (38 weeks) compared to the younger age groups, while the modulatory role of P-glycoprotein in transepithelial talinolol transport was observed in adult and old rats but not in young rats. In conclusion, age-dependent permeability of intestinal tissue (rather than age-dependent luminal drug solubility) may contribute to altered intestinal drug absorption in older patients compared to young adults. Copyright 2009 Elsevier B.V. All rights reserved.

  4. [The forecast of illicit drug use in adolescents with addictive behavior: personality traits and the level of genetic risk of substance dependence.

    Science.gov (United States)

    Yakovlev, A N; Brodyansky, V M; Schurina, A V; Romashkin, R A; Kibitov, A O

    2016-01-01

    To clarify the psychological mechanism underlying the genetic risk of substance addiction at the first stage of drug use by adolescents. Genetic risk was evaluated by genotyping of 5 polymorphisms of the dopaminergic system genes (dopamine receptor D2 and D4 genes and tyrosine hydroxylase gene). Psychological testing was performed using the Russian version of Temperament and Character Inventory (TCI-125). Seventy-five adolescents, aged 14-17 years, (girls 32%), who misused alcohol, including 22 adolescents using drugs, were examined. The level of genetic risk was directly correlated with the probability of drug use by boys, for girls the correlation was not confirmed. The increase of the level of genetic risk for boys was correlated with the increase on the scale «Self-directedness» of TCI-125 that may reflect a probable tendency to replacement of negative information, feeling of illusory wellbeing. The findings clarify the direction of measures for the prevention of drug use.

  5. Effects of cross-anisotropy and stress-dependency of pavement layers on pavement responses under dynamic truck loading

    Directory of Open Access Journals (Sweden)

    Rafiqul A. Tarefder

    2016-06-01

    Full Text Available Previous studies by the authors have determined pavement responses under dynamic loading considering cross-anisotropy in one layer only, either the cross-anisotropic viscoelastic asphalt concrete (AC layer or the cross-anisotropic stress-dependent base layer, but not both. This study evaluates pavement stress–strain responses considering cross-anisotropy in all layers, i.e. AC, base and subbase, using finite element modeling (FEM technique. An instrumented pavement section on Interstate I-40 near Albuquerque, New Mexico was used in ABAQUS framework as model geometry. Field asphalt cores were collected and tested in the laboratory to determine the cross-anisotropy (n-values defined by horizontal to vertical modulus ratio, and other viscoelastic parameters as inputs of the model incorporated through user defined material interface (UMAT functionality in ABAQUS. Field base and subbase materials were also collected and tested in the laboratory to determine stress-dependent nonlinear elastic model parameters, as inputs of the model, again incorporated through UMAT. The model validation task was carried out using field-measured deflections and strain values under falling weight deflectometer (FWD loads at the instrumented section. The validated model was then subjected to an actual truck loading for studying cross-anisotropic effects. It was observed that horizontal tensile strain at the bottom of the AC layer and vertical strains in all layers decreased with an increase in n-value of the asphalt layer, from n < 1 (anisotropy to n=1 (isotropy. This indicates that the increase in horizontal modulus caused the decrease in layer strains. It was also observed that if the base and subbase layers were considered stress-dependent instead of linear elastic unbound layers, the horizontal tensile strain at the bottom of the asphalt layer increased and vertical strains on top of the base and subbase also increased.

  6. [Abuse, dependence and intoxication of substances].

    Science.gov (United States)

    Wada, Kiyoshi

    2015-09-01

    As for substance-related disorders, there were several differences between ICD-10 and DSM-IV, however, the concept of "dependence" had been essential for both criteria. DSM-5 published in 2013 had erased dependence. This confuses us. It is important to recognize dependence again. "Abuse" is the self-intake behavior of drug against the social norms. Repeated abuse results in dependence. Dependence is a state of loss of control against drug use due to craving. Abuse can produce "acute intoxication", and repeated abuse under dependence can produce "chronic intoxication". It is important to understand abuse, dependence and "intoxication" based on their relationship from the point of time course.

  7. Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Xin-Yan Pei

    Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

  8. Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

    Science.gov (United States)

    Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

    2014-01-01

    The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

  9. [The manual "Problematic use and dependence of prescipted drugs" in daily routine care - a study among participants in a training to qualify in "primary addiction treatment"].

    Science.gov (United States)

    Ulbricht, S; Gross, B; Kunstmann, W; Meyer, C; John, U

    2011-12-01

    To strengthen the position of physicians regarding problematic use and dependence of prescripted drugs a manual was issued by the German Medical Association in 2007.  A study among participants in a training to qualify in "primary addiction treatment" was conducted. The utilisation of the manual, its relevance for routine care and self-estimated changes in drug prescription were examined. All 542 participants in training courses between 1.9.2008 and 31.12.2009 were asked about participation in a survey 12 weeks later. A number of 267 took part in this investigation. A proportion of 60,7 % among GPs that received the manual dealt with them beyond the training course. From 178 physicians, who confirmed the provision of drug prescription, a number of 56 stated changes in their drug prescription. A higher probabilty for changes in drug prescription was given in case of a high percentage of new informations that could be culled from the manual. The interest for the manual beyond the training course and the amount of self-estimated changes in drug prescription should encourage to use this within training measures in a systematic way. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France.

    Science.gov (United States)

    Orriols, Ludivine; Gaillard, Julia; Lapeyre-Mestre, Maryse; Roussin, Anne

    2009-01-01

    Drugs that can be obtained without a medical prescription in community pharmacies are used to treat minor pathologies that can easily be diagnosed by the patient. Some of these drugs contain psychoactive substances with a potential for abuse and dependence. However, there is a lack of data concerning their problematic use in a wide population. To explore the feasibility of a pharmacoepidemiological method to investigate misuse, non-medical use, abuse and dependence on drugs used for self-medication. This cross-sectional pilot study, conducted during a 2-month period (from 15 January to 15 March 2007), was based on the participation of community pharmacies in the Midi-Pyrénées region of France to collect patient data. Patients requesting one drug from a list of available drugs used for self-medication and containing psychoactive substances (codeine in analgesics, pseudoephedrine, dextromethorphan and histamine H(1) receptor antagonists [antihistamines]) were included in the study. A control group was set up that consisted of patients requesting antacid drugs. The pharmacy staff proposed to the patients that they filled in an anonymous questionnaire. The questionnaire was designed to investigate patterns of drug use and the harmful consequences of overuse (abuse). In addition, questions on lack of control over drug use were adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for evaluation of dependence. Thirty-two percent (n = 74) of the solicited pharmacies participated in the survey. Only 4.8% of the solicited patients (n = 817) refused to complete the questionnaire distributed by the pharmacy staff. The questionnaire was completed inside the pharmacy by 53.3% of the patients. The other patients took the questionnaire away from the pharmacy and 31.7% of them returned it in a prepaid envelope. The patient participation rate was 64.9%, and was higher for the psychoactive substance groups than the control group

  11. 78 FR 72901 - Draft Guidance; Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal...

    Science.gov (United States)

    2013-12-04

    ... 503A are met. The conditions of section 503A of the FD&C Act included restrictions on the advertising or promotion of the compounding of any particular drug, class of drug, or type of drug, and the... the Drug Quality and Security Act to remove the unconstitutional advertising, promotion, and...

  12. Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

    Science.gov (United States)

    Suarez-Sharp, Sandra; Delvadia, Poonam R; Dorantes, Angelica; Duan, John; Externbrink, Anna; Gao, Zongming; Ghosh, Tapash; Miksinski, Sarah Pope; Seo, Paul

    2016-05-01

    Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.

  13. Sperm retrieval in anejaculatory diabetic men who failed in drug treatment and penile vibratory stimulation during blood sugar under control.

    Science.gov (United States)

    Lu, S; Cui, Y; Li, X; Zhang, H; Hu, J; Liu, J; Chen, Z-J

    2014-05-01

    Ejaculatory dysfunction is an uncommon cause of male infertility. The aim of this study was to explore non-invasive methods for sperm retrieval in anejaculatory diabetic men who failed in drug treatment and penile vibratory stimulation during blood sugar under control. Among 21 anejaculatory diabetic men who had failed in drug treatment and penile vibratory stimulation, sperm was collected by retrograde ejaculation in 10 patients (group A), and in eight patients, sperm was collected by prostatic massage (group B). We compared the outcome of subsequent assisted reproductive treatment between the two groups; the rate of fertility in group A and in group B was 78.3% and 66.6% respectively, and the rate of good embryo was 56.6% and 48.8% respectively. Eight singleton pregnancies were achieved in the 18 anejaculatory diabetic men, 5 in group A and 3 in group B, the rate of pregnancy between the two groups was 50% and 37.5% respectively. There was no significant difference in the rate of fertility, good embryo rate and pregnancy outcome between the two groups. © 2013 Blackwell Verlag GmbH.

  14. Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells.

    Science.gov (United States)

    Li, Mingchuan; Wang, Yong Xing; Luo, Yong; Zhao, Jiahui; Li, Qing; Zhang, Jiao; Jiang, Yongguang

    2016-07-01

    Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death. Hypoxia is an environmental stimulus that plays an important role in the development and cancer progression especially for solid tumors. The key regulator under hypoxic conditions is stabilized hypoxia-inducible factor (HIF)-1α. In the present study, immune-fluorescent staining, siRNAs, qRT-PC, immunoblotting, cell migration and invasion assays were carried out to test typical epithelial to mesenchymal transition under hypoxia and the key regulators of this process in PC3, a human prostate cancer cell line. Our data demonstrated that hypoxia induces diverse molecular, phenotypic and functional changes in prostate cancer cells that are consistent with EMT. We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency. The induced hypoxia could be blocked by HIF-1α gene silencing and reoxygenation of EMT in prostate cancer cells, hypoxia partially reversed accompanied by a process of mesenchymal-epithelial reverting transition (MErT). EMT might be induced by activation of HIF-1α-dependent cell signaling in hypoxic prostate cancer cells.

  15. Systematic evaluation of "compliance" to prescribed treatment medications and "abstinence" from psychoactive drug abuse in chemical dependence programs: data from the comprehensive analysis of reported drugs.

    Directory of Open Access Journals (Sweden)

    Kenneth Blum

    Full Text Available This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across "levels of care" in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; P<.001 had every treatment medication found in both first and last urine specimens (compliance. In addition, 39.2% of the patients (n = 1143; P<.001 had no substance of abuse detected in either the first or last urine samples (abstinence. Moreover, in 2010, 16.9% of the patients (n = 57 were abstinent at first but not at last urine (deteriorating abstinence, the percentage dropped to 13.3% (n = 174 in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511 representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10-8 of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10-16 was found. Being cognizant of the trend toward drug urine testing being linked

  16. Social Representations Used by the Parents of Mexican Adolescent Drug Users under Treatment to Explain Their Children's Drug Use: Gender Differences in Parental Narratives

    Science.gov (United States)

    Nuno-Gutierrez, Bertha Lidia; Alvarez-Nemegyei, Jose; Rodriguez-Cerda, Oscar

    2008-01-01

    The aim of this study was to explore the social representations used by the parents of adolescent drug users to explain the onset of drug use. Differences in explanations between the parents of male and female adolescents were also explored. Sixty parents who accompanied their children to four rehabilitation centers in 2004 completed two…

  17. Efficacy of a group-based multimedia HIV prevention intervention for drug-involved women under community supervision: project WORTH.

    Science.gov (United States)

    El-Bassel, Nabila; Gilbert, Louisa; Goddard-Eckrich, Dawn; Chang, Mingway; Wu, Elwin; Hunt, Tim; Epperson, Matt; Shaw, Stacey A; Rowe, Jessica; Almonte, Maria; Witte, Susan

    2014-01-01

    This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision. We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to Health) among drug-involved women under community supervision. We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention (traditional WORTH); (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH. Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners. Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts (β = 0.10; 95% CI = 0.02-0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI = 0.57-0.90). The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system. Clinical

  18. Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Netikova, J.; Hola, J.; Znojil, V.; Vacha, J.

    1995-01-01

    The authors have recently demonstrated that a combined administration of dipyridamole and adenosine monophosphate to mice induces radioprotective effects in terms of postirradiation hematopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation. It was shown that administration of the drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma radiation enhances hematopoietic recovery and survival of mice exposed to an additional 'top-up' dose of 3.5 Gy. Furthermore, it was ascertained that administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, the present results suggest a more protective role of mechanisms stimulating hematopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation techniques. (author) 1 tab., 1 fig., 25 refs

  19. Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Zhuo-Xin Cheng

    Full Text Available Epithelial to mesenchymal transition (EMT induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.

  20. An EOQ model of time quadratic and inventory dependent demand for deteriorated items with partially backlogged shortages under trade credit

    Science.gov (United States)

    Singh, Pushpinder; Mishra, Nitin Kumar; Singh, Vikramjeet; Saxena, Seema

    2017-07-01

    In this paper a single buyer, single supplier inventory model with time quadratic and stock dependent demand for a finite planning horizon has been studied. Single deteriorating item which suffers shortage, with partial backlogging and some lost sales is considered. Model is divided into two scenarios, one with non permissible delay in payment and other with permissible delay in payment. Latter is called, centralized system, where supplier offers trade credit to retailer. In the centralized system cost saving is shared amongst the two. The objective is to study the difference in minimum costs borne by retailer and supplier, under two scenarios including the above mentioned parameters. To obtain optimal solut