22 resultados para Drug of abuse
Resumo:
Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.
Resumo:
Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.
Resumo:
Background HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Methods Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Results Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. Conclusions These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression.
Resumo:
Approximately 200 million people, 5% aged 15-64 worldwide are illicit drug or substance abusers (World Drug Report, 2006). Between 2002 and 2005, an average of 8.2% of 12 year olds and older in the Miami, Fort Lauderdale metropolitan areas used illicit drugs (SAMHSA, 2007). Eight percent of pregnant women, aged 15 to 25, were more likely to have used illicit drugs during pregnancy than pregnant women aged 26 to 44. Alcohol use was 9.8% and cigarette use was 18% for pregnant women aged 15 to 44 (SAMHSA, 2005). Approximately a quarter of annual birth defects are attributed to the exposure of drugs or substance abuse in utero (General Accounting Office, 1991). Physical, psychological and emotional challenges may be present for the illicit drug/substance abuse (ID/SA) mother and infant placing them at a disadvantage early in their relationship (Shonkoff & Marshall, 1990). Mothers with low self efficacy have insecurely attached infants (Donovan, Leavitt, & Walsh, 1987). As the ID/SA mother struggles with wanting to be a good parent, education is needed to help her care for her infant. In this experimental study residential rehabilitating ID/SA mothers peer taught infant massage. Massage builds bonding/attachment between mother and infant (Reese & Storm, 2008) and peer teaching is effective because participants have faced similar challenges and speak the same language (Boud, Cohen, & Sampson 2001). Quantitative data were collected using the General Self-Efficacy and Maternal Attachment Inventory-Revised Scale before and after the 4-week intervention program. A reported result of this study was that empowering ID/SA mothers increased their self-efficacy, which in turn allowed the mothers to tackle challenges encountered and created feelings of being a fit mother to their infants. This research contributes to the existing database promoting evidence-based practice in drug rehabilitation centers. Healthcare personnel, such as nurse educators and maternal-child health practitioners, can develop programs in drug rehabilitation centers that cultivate an environment where the ID/SA rehabilitating mothers can peer teach each other, while creating a support system. Using infant massage as a therapeutic tool can develop a healthy infant and nurture a more positive relationship between mother and infant.
Resumo:
Approximately 200 million people, 5% aged 15-64 worldwide are illicit drug or substance abusers (World Drug Report, 2006). Between 2002 and 2005, an average of 8.2% of 12 year olds and older in the Miami, Fort Lauderdale metropolitan areas used illicit drugs (SAMHSA, 2007). Eight percent of pregnant women, aged 15 to 25, were more likely to have used illicit drugs during pregnancy than pregnant women aged 26 to 44. Alcohol use was 9.8% and cigarette use was 18% for pregnant women aged 15 to 44 (SAMHSA, 2005). Approximately a quarter of annual birth defects are attributed to the exposure of drugs or substance abuse in utero (General Accounting Office, 1991). Physical, psychological and emotional challenges may be present for the illicit drug/substance abuse (ID/SA) mother and infant placing them at a disadvantage early in their relationship (Shonkoff & Marshall, 1990). Mothers with low self efficacy have insecurely attached infants (Donovan, Leavitt, & Walsh, 1987). As the ID/SA mother struggles with wanting to be a good parent, education is needed to help her care for her infant. In this experimental study residential rehabilitating ID/SA mothers peer taught infant massage. Massage builds bonding/attachment between mother and infant (Reese & Storm, 2008) and peer teaching is effective because participants have faced similar challenges and speak the same language (Boud, Cohen, & Sampson 2001). Quantitative data were collected using the General Self-Efficacy and Maternal Attachment Inventory-Revised Scale before and after the 4-week intervention program. A reported result of this study was that empowering ID/SA mothers increased their self-efficacy, which in turn allowed the mothers to tackle challenges encountered and created feelings of being a fit mother to their infants. This research contributes to the existing database promoting evidence-based practice in drug rehabilitation centers. Healthcare personnel, such as nurse educators and maternal-child health practitioners, can develop programs in drug rehabilitation centers that cultivate an environment where the ID/SA rehabilitating mothers can peer teach each other, while creating a support system. Using infant massage as a therapeutic tool can develop a healthy infant and nurture a more positive relationship between mother and infant.
Resumo:
Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p<0.01) at 6 months, but not 3 months, post-intervention. Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.
Resumo:
Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.
Resumo:
Despite widespread recognition of the problem of adolescent alcohol and other drug (AOD) abuse, research on its most common treatment modality, group work, is lacking. This research gap is alarming given that outcomes range from positive to potentially iatrogenic. This study sought to identify change mechanisms and/or treatment factors that are observable within group treatment sessions and that may predict AOD use outcomes. This NIH (F31 DA 020233-01A1) study evaluated 108, 10-19 year olds and the 19 school-based treatment groups to which they were previously assigned (R01 AA10246; PI: Wagner). Associations between motivational interviewing (MI) based change talk variables, group leader MI skills, and alcohol and marijuana use outcomes up to 12-months following treatment were evaluated. Treatment session audio recordings and transcripts (1R21AA015679-01; PI: Macgowan) were coded using a new discourse analysis coding scheme for measuring group member change talk (Amrhein, 2003). Therapist MI skills were similarly measured using the Motivational Interviewing Treatment Integrity instrument. Group member responses to commitment predicted group marijuana use at the 1-month follow up. Also, group leader empathy was significantly associated with group commitment for marijuana use at the middle and ending stages of treatment. Both of the above process measures were applied in a group setting for the first time. Building upon MI and social learning theory principles, group commitment and group member responses to commitment are new observable, in-session, process constructs that may predict positive and negative adolescent group treatment outcomes. These constructs, as well as the discourse analysis method and instruments used to measure them, raise many possibilities for future group work process research and practice.
Resumo:
New designer drugs are constantly emerging onto the illicit drug market and it is often difficult to validate and maintaincomprehensive analytical methods for accurate detection of these compounds. Generally, toxicology laboratories utilize a screening method, such as immunoassay, for the presumptive identification of drugs of abuse. When a positive result occurs, confirmatory methods, such as gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), are required for more sensitive and specific analyses. In recent years, the need to study the activities of these compounds in screening assays as well as to develop confirmatory techniques to detect them in biological specimens has been recognized. Severe intoxications and fatalities have been encountered with emerging designer drugs, presenting analytical challenges for detection and identification of such novel compounds. The first major task of this research was to evaluate the performance of commercially available immunoassays to determine if designer drugs were cross-reactive. The second major task was to develop and validate a confirmatory method, using LC-MS, to identify and quantify these designer drugs in biological specimens.^ Cross-reactivity towards the cathinone derivatives was found to be minimal. Several other phenethylamines demonstrated cross-reactivity at low concentrations, but results were consistent with those published by the assay manufacturer or as reported in the literature. Current immunoassay-based screening methods may not be ideal for presumptively identifying most designer drugs, including the "bath salts." For this reason, an LC-MS based confirmatory method was developed for 32 compounds, including eight cathinone derivatives, with limits of quantification in the range of 1-10 ng/mL. The method was fully validated for selectivity, matrix effects, stability, recovery, precision, and accuracy. In order to compare the screening and confirmatory techniques, several human specimens were analyzed to demonstrate the importance of using a specific analytical method, such as LC-MS, to detect designer drugs in serum as immunoassays lack cross-reactivity with the novel compounds. Overall, minimal cross-reactivity was observed, highlighting the conclusion that these presumptive screens cannot detect many of the designer drugs and that a confirmatory technique, such as the LC-MS, is required for the comprehensive forensic toxicological analysis of designer drugs.^
Resumo:
The purpose of this study was to determine which factors predicted maladaptive outcomes in sexually abused children. Key factors were aggregated into four categories: abuse characteristics risk factors, individual-level risk factors, family disruption risk factors, and social disruption risk factors. It was hypothesized that (a) individual-level risk factors (e.g., school performance, child alcohol/substance abuse) and (b) abuse characteristics risk factors (e.g., longer duration/frequency of abuse, use of force/threats of force, intrafamilial abuse) would predict higher levels of trauma symptoms. Furthermore, it was hypothesized that (a) family disruption risk factors (e.g., family alcohol/substance use, family psychopathology) and (b) social disruption risk factors (e.g., parental divorce, homelessness, witnessing homicide or violence) would moderate the impact of prior sexual abuse and predict higher levels of trauma symptoms. ^ The participants were 110 female children (5 to 18 years old) presenting for treatment for sexual abuse at a community agency (The Journey Institute) in Miami, Florida. This study conducted a retrospective analysis of an archival data set collected over a three-year period (1998–2001). The measures completed upon intake included The Journey Psychosocial Assessment and The Trauma Symptom Checklist for Children (TSCC; Briere, 1996). Using Pearson correlations and hierarchical multiple regression analysis, this study found that abuse characteristics risk factors and individual-level risk factors were predictive of maladaptive outcomes in this sample of sexually abused girls. However, no moderating effects were found for family disruption risk factors or social disruption risk factors. Therefore, the results of these analyses provided support for the contention that abuse characteristics and individual-level risk factors were appropriate targets for treatment for sexually abused girls. Moreover, limitations of this study, implications for treatment, and directions for future research were discussed. ^
Resumo:
Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.
Resumo:
Globally, approximately 208 million people aged 15 and older used illicit drugs at least once in the last 12 months; 2 billion consumed alcohol and tobacco consumption affected 25% (World Drug Report, 2008). In the United States, 20.1 million (8.0%) people aged 12 and older were illicit drug users, 129 million (51.6%) abused alcohol and 70.9 million (28.4%) used tobacco (SAMHSA/OAS, 2008).Usually considered a problem specific to men (Lynch, 2002), 5.2% of pregnant women aged 15 to 44 are also illicit drug and substance abusers (SAMHSA/OAS, 2007). During pregnancy, illicit drugs and substance abuse (ID/SA) can significantly affect a woman and her infant contributing to developmental and communication delays for the infant and influencing parenting abilities (Budden, 1996; March of Dimes, 2006b; Rossetti, 2000). Feelings of guilt and shame and stressful experiences influence approaches to parenting (Ashley, Marsden, & Brady, 2003; Brazelton, & Greenspan, 2000; Ehrmin, 2000; Johnson, & Rosen, 1990; Kelley, 1998; Rossetti, 2000; Velez et al., 2004; Zickler, 1999). Parenthood is an expanded role that can be a trying time for those lacking a sense of self-efficacy and creates a high vulnerability to stress (Bandura, 1994). Residential treatment programs for ID/SA mothers and their children provide an excellent opportunity for effective interventions (Finkelstein, 1994; Social Care Institute for Excellence, 2005). This experimental study evaluated whether teaching American Sign Language (ASL) to mothers living with their infants/children at an ID/SA residential treatment program increased the mothers’ self-efficacy and decreased their anxiety. Quantitative data were collected using the General Self-Efficacy Scale and the State-Trait Anxiety Inventory showing there was both a significant increase in self efficacy and decrease in anxiety for the mothers. This research adds to the knowledge base concerning ID/SA mothers’ caring for their infants/children. By providing a simple low cost program, easily incorporated into existing rehabilitation curricula, the study helps educators and healthcare providers better understand the needs of the ID/SA mothers. This study supports Bandura’s theory that parents who are secure in their efficacy can navigate through the various phases of their child’s development and are less vulnerable to stress (Bandura, 1994).
Resumo:
Globally, approximately 208 million people aged 15 and older used illicit drugs at least once in the last 12 months; 2 billion consumed alcohol and tobacco consumption affected 25% (World Drug Report, 2008). In the United States, 20.1 million (8.0%) people aged 12 and older were illicit drug users, 129 million (51.6%) abused alcohol and 70.9 million (28.4%) used tobacco (SAMHSA/OAS, 2008).Usually considered a problem specific to men (Lynch, 2002), 5.2% of pregnant women aged 15 to 44 are also illicit drug and substance abusers (SAMHSA/OAS, 2007). During pregnancy, illicit drugs and substance abuse (ID/SA) can significantly affect a woman and her infant contributing to developmental and communication delays for the infant and influencing parenting abilities (Budden, 1996; March of Dimes, 2006b; Rossetti, 2000). Feelings of guilt and shame and stressful experiences influence approaches to parenting (Ashley, Marsden, & Brady, 2003; Brazelton, & Greenspan, 2000; Ehrmin, 2000; Johnson, & Rosen, 1990; Kelley, 1998; Rossetti, 2000; Velez et al., 2004; Zickler, 1999). Parenthood is an expanded role that can be a trying time for those lacking a sense of self-efficacy and creates a high vulnerability to stress (Bandura, 1994). Residential treatment programs for ID/SA mothers and their children provide an excellent opportunity for effective interventions (Finkelstein, 1994; Social Care Institute for Excellence, 2005). This experimental study evaluated whether teaching American Sign Language (ASL) to mothers living with their infants/children at an ID/SA residential treatment program increased the mothers’ self-efficacy and decreased their anxiety. Quantitative data were collected using the General Self-Efficacy Scale and the State-Trait Anxiety Inventory showing there was both a significant increase in self efficacy and decrease in anxiety for the mothers. This research adds to the knowledge base concerning ID/SA mothers’ caring for their infants/children. By providing a simple low cost program, easily incorporated into existing rehabilitation curricula, the study helps educators and healthcare providers better understand the needs of the ID/SA mothers. This study supports Bandura’s theory that parents who are secure in their efficacy can navigate through the various phases of their child’s development and are less vulnerable to stress (Bandura, 1994).
Resumo:
The purpose of the research is to study the relationship between international drug interdiction policies and domestic politics in fragile democracies, and to demonstrate how international drug control policies and the use of force fit the rhetoric of war, are legitimized by the principles of a just war, but may also cause collateral damage and negative unintended consequences. The method used is a case study of the Dominican Republic. The research has found that international drug control regimes, primarily led by the U.S. and narrowly focused on interdiction, have influenced an increasingly militarized approach to domestic law enforcement in the Dominican Republic. The collateral damage caused by militarized enforcement comes in the form of negative perceptions of citizen security, loss of respect for the rule of law and due process, and low levels of civil society development. The drug war has exposed the need for significant reform of the institutions charged with carrying out enforcement, the police force and the judicial system in particular. The dissertation concludes that the extent of drug trafficking in the Dominican Republic is beyond the scope of domestic reform efforts alone, but that the programs implemented do show some potential for future success. The dissertation also concludes that the framework of warfare is not the most appropriate for the international problems of drug traffic and abuse. A broader, multipronged approach should be considered by world policy makers in order to address all conditions that allow drugs to flourish without infringing upon democratic and civil rights in the process.
Resumo:
No hospitality organizations are immune from the negative effects of substance abuse in the workplace. Ownters and managers must confront the problem head on and, in order to accomplish this, they must be in possession of the facts regarding the problem, and regarding options for dealing with the problem in the most appropriate manner for their individual organizations. The authors include an assessment of this problem as well as a summary review of procedures for positive management of a potentially negative situation.