853 resultados para Alcohol Drug Interaction.
Resumo:
An uptake system was developed using Caco-2 cell monolayers and the dipeptide, glycyl-[3H]L-proline, as a probe compound. Glycyl-[3H]L-proline uptake was via the di-/tripeptide transport system (DTS) and, exhibited concentration-, pH- and temperature-dependency. Dipeptides inhibited uptake of the probe, and the design of the system allowed competitors to be ranked against one another with respect to affinity for the transporter. The structural features required to ensure or increase interaction with the DTS were defined by studying the effect of a series of glycyl-L-proline and angiotensin-converting enzyme (ACE)-inhibitor (SQ-29852) analogues on the uptake of the probe. The SQ-29852 structure was divided into six domains (A-F) and competitors were grouped into series depending on structural variations within specific regions. Domain A was found to prefer a hydrophobic function, such as a phenyl group, and was intolerant to positive charges and H+ -acceptors and donors. SQ-29852 analogues were more tolerant of substitutions in the C domain, compared to glycyl-L-proline analogues, suggesting that interactions along the length of the SQ-29852 molecule may override the effects of substitutions in the C domain. SQ-29852 analogues showed a preference for a positive function, such as an amine group in this region, but dipeptide structures favoured an uncharged substitution. Lipophilic substituents in domain D increased affinity of SQ-29852 analogues with the DTS. A similar effect was observed for ACE-NEP inhibitor analogues. Domain E, corresponding to the carboxyl group was found to be tolerant of esterification for SQ-29852 analogues but not for dipeptides. Structural features which may increase interaction for one series of compounds, may not have the same effect for another series, indicating that the presence of multiple recognition sites on a molecule may override the deleterious effect of anyone change. Modifying current, poorly absorbed peptidomimetic structures to fit the proposed hypothetical model may improve oral bioavailability by increasing affinity for the DTS. The stereochemical preference of the transporter was explored using four series of compounds (SQ-29852, lysylproline, alanylproline and alanylalanine enantiomers). The L, L stereochemistry was the preferred conformation for all four series, agreeing with previous studies. However, D, D enantiomers were shown in some cases to be substrates for the DTS, although exhibiting a lower affinity than their L, L counterparts. All the ACE-inhibitors and β-lactam antibiotics investigated, produced a degree of inhibition of the probe, and thus show some affinity for the DTS. This contrasts with previous reports that found several ACE inhibitors to be absorbed via a passive process, thus suggesting that compounds are capable of binding to the transporter site and inhibiting the probe without being translocated into the cell. This was also shown to be the case for oligodeoxynucleotide conjugated to a lipophilic group (vitamin E), and highlights the possibility that other orally administered drug candidates may exert non-specific effects on the DTS and possibly have a nutritional impact. Molecular modelling of selected ACE-NEP inhibitors revealed that the three carbonyl functions can be oriented in a similar direction, and this conformation was found to exist in a local energy-minimised state, indicating that the carbonyls may possibly be involved in hydrogen-bond formation with the binding site of the DTS.
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Zinc is essential for the activity of thymulin, a thymic hormone involved in T-lymphocyte differentiation and activation. Zinc deficiency is widespread in populations with HIV infection, and HIV+ drug users are particularly susceptible to zinc deficiency and immune suppression. This dissertation explored the relationship of zinc-bound active thymulin to plasma zinc, CD4+ and CD8+ cell count, the CD4+/CD8+ ratio, and drug use in HIV-infected drug users. Zinc-bound active thymulin was assessed in plasma of HIV+ drug users who were participating in a 30 month zinc supplementation trial. Plasma from 80 participants at the 12 month visit, and 40 of these same participants, randomly selected, at the baseline visit were assessed for zinc-bound active thymulin levels using a modification of the rosette inhibition assay. Thymulin activity was directly associated with CD4+ cell count (β = 0.127, p = 0.002) and inversely associated with cocaine use (β = −0.908, p = 0.026; R2 = 0.188, p = 0.019) independent of HIV viral load, age, gender and antiretroviral use. An increase in thymulin activity was 1.4 times more likely when CD4+ cell count increased (OR = 1.402, 95%CI: 1.006–1.956), independent of change in viral load, antiretroviral use, and age. Participants who used cocaine consistently, were 7.6 times less likely to have an increase in thymulin activity (OR = 0.133, 95%CI: 0.017–1.061). There was a direct correlation between change in plasma zinc and change in zinc-bound active thymulin (r = 0.243, p = 0.13). Analysis of CD4+ cell count decline in 222 participants in the zinc supplementation trial across the 30 months showed that both crack cocaine use and heavy alcohol use accelerated CD4+ cell count decline. Thymulin activity is directly associated with HIV disease progression, measured by CD4+ cell count, and is depressed with cocaine use independent of antiretroviral use and HIV viral load. Cocaine and heavy alcohol accelerate CD4+ cell count decline. The effect of cocaine on thymic output requires further evaluation as a mechanism for the association of cocaine use with faster HIV disease progression.
Resumo:
Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^
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Abuse of drugs and alcohol in the workplace has reached epidemic proportions in the hotel industry. The authors review considerations for drug testing and discuss drug and alcohol testing methods and the manner in which an effective policy should be developed.
Resumo:
Maltreatment experienced in childhood or adolescence is a known risk factor for later problem alcohol and/or other drug (AOD) use (Bailey & McCloskey, 2005; Shin, Edwards, Heeren, 2009). A growing body of empirical work has found significant associations between adolescent girls’ AOD use and maltreatment experiences. However, questions remain as to how this relation unfolds with African-American and Hispanic adolescent girls. Guided by four relational models that have been proposed in the literature, this study examined the links between maltreatment, trauma symptoms, and alcohol and/or other drug (AOD) problems in a sample of 170 African-American and Hispanic adolescent girls who were participants in a school-based AOD use intervention. Results of this study revealed that maltreatment experiences (physical and emotional abuse) were positively related to trauma symptoms, which were positively related to AOD problem severity, alcohol abuse, alcohol dependency, drug abuse, and drug dependency. Perceived discrimination moderated this relation between sexual abuse and trauma symptoms, such that more perceived discrimination resulted in a stronger effect of sexual abuse on trauma symptoms. Ethnic identity moderated the relation between sexual abuse and AOD problem severity, such that ethnic identity demonstrated protective properties in the relation between sexual abuse and AOD problem severity. My research adds to extant knowledge on the relation between maltreatment and AOD use in adolescent girls and suggests the importance of developing interventions targeting maltreatment and AOD use concurrently.
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:
Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. ^ A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p^
Resumo:
Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth.
Resumo:
Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p
Resumo:
Maltreatment experienced in childhood or adolescence is a known risk factor for later problem alcohol and/or other drug (AOD) use (Bailey & McCloskey, 2005; Shin, Edwards, Heeren, 2009). A growing body of empirical work has found significant associations between adolescent girls’ AOD use and maltreatment experiences. However, questions remain as to how this relation unfolds with African-American and Hispanic adolescent girls. Guided by four relational models that have been proposed in the literature, this study examined the links between maltreatment, trauma symptoms, and alcohol and/or other drug (AOD) problems in a sample of 170 African-American and Hispanic adolescent girls who were participants in a school-based AOD use intervention. Results of this study revealed that maltreatment experiences (physical and emotional abuse) were positively related to trauma symptoms, which were positively related to AOD problem severity, alcohol abuse, alcohol dependency, drug abuse, and drug dependency. Perceived discrimination moderated this relation between sexual abuse and trauma symptoms, such that more perceived discrimination resulted in a stronger effect of sexual abuse on trauma symptoms. Ethnic identity moderated the relation between sexual abuse and AOD problem severity, such that ethnic identity demonstrated protective properties in the relation between sexual abuse and AOD problem severity. My research adds to extant knowledge on the relation between maltreatment and AOD use in adolescent girls and suggests the importance of developing interventions targeting maltreatment and AOD use concurrently.
Resumo:
The United Nations Office of Drug Control (UNODC) published ‘International Standards on Drug Use Prevention’ in 2013. The Standards were developed through a systematic assessment of the international evidence on prevention and they provide a summary of the available scientific evidence. The briefing provides a summary of the UNODC prevention standards and gives corresponding examples of relevant UK guidelines,programmes and interventions currently available in England. Its aim is to help people who commission, develop and implement prevention strategies and interventions to translate the standards into the English operating landscape. It also aims to support local authority commissioners to develop their prevention strategies and implement them in line with evidence.
Resumo:
Poster presented at the 44th ESCP Symposium on Clinical Pharmacy. Lisbon, 28-30 October 2015
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.
