RESUMO
Clinical trials have indicated that a vaccine must be immunogenic in genetically diverse human populations and that immunogenicity and protective efficacy in animal models are two key indices required for the approval of a new vaccine. Additionally, the immune response (immunogenicity) and immunoprotection are dependent on the mouse strain. Therefore, the objective of the present study was to determine the immune response (immunogenicity) and the protective efficacy (behavioral response) in three inbred mouse strains immunized with the M6TT vaccine. Female BALB/c, C57Bl/6, and DBA/2 inbred mice were immunized with the M6-TT vaccine. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used tail-flick testing to evaluate the antinociceptive effects induced by heroin. Additionally, heroin-induced locomotor activity and place preference were evaluated. The M6-TT vaccine was able to generate a specific antibody titer in the three inbred mouse strains evaluated. The antibodies reduced the antinociceptive effect of different doses of heroin. In addition, they decreased the heroin-induced locomotor activity and place preference. These findings suggest that the M6-TT vaccine generates a powerful immunogenic response capable of reducing the antinociceptive and reinforcing effects of heroin in different inbred mouse strains, which supports its possible future use in clinical trials in genetically diverse human populations.
Assuntos
Heroína/imunologia , Morfina/imunologia , Transtornos Relacionados ao Uso de Opioides/terapia , Vacinas/imunologia , Analgésicos Opioides , Animais , Modelos Animais de Doenças , Feminino , Heroína/efeitos adversos , Humanos , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Morfina/efeitos adversos , Nociceptividade , Transtornos Relacionados ao Uso de Opioides/imunologia , Reforço Psicológico , Vacinas/administração & dosagemRESUMO
Outbreaks of wound botulism are rare, but clinicians and health departments should maintain suspicion for signs, symptoms, and risk factors of wound botulism among persons who inject drugs in order to initiate treatment quickly. This report describes an outbreak of three wound botulism cases among persons in two adjacent counties who injected drugs. Provisional information about these cases was previously published in the CDC National Botulism Surveillance Summary. All three cases in this outbreak were laboratory-confirmed, including one case with detection of botulinum toxin type A in a wound culture sample taken 43 days after last possible heroin exposure. Findings highlight the delay in diagnosis which led to prolonged hospitalization and the persistence of botulinum toxin in one patient.
Assuntos
Botulismo , Usuários de Drogas , Abuso de Substâncias por Via Intravenosa , Infecção dos Ferimentos , Botulismo/diagnóstico , Botulismo/epidemiologia , Botulismo/etiologia , Heroína/efeitos adversos , Humanos , New Mexico , Abuso de Substâncias por Via Intravenosa/complicações , Infecção dos Ferimentos/induzido quimicamente , Infecção dos Ferimentos/epidemiologiaRESUMO
Resumo Fundamento Atualmente, o vício em heroína é um problema de saúde preocupante, e as informações sobre os efeitos eletrocardiográficos da heroína são limitadas. Objetivos O objetivo do presente estudo é investigar os efeitos da dependência de heroína em parâmetros eletrocardiográficos. Métodos Um total de 136 indivíduos, incluindo 66 indivíduos que fumam heroína como grupo de estudo e 70 indivíduos saudáveis sem dependência de drogas como grupo de controle, foram incluídos no estudo. Indivíduos que injetam heroína foram excluídos. A avaliação eletrocardiográfica (ECG) dos usuários de heroína foi realizada e comparada com as do grupo controle. Além disso, os ECGs pré e pós-tratamento do grupo usuário de heroína foram comparados. Um valor de p<0,05 foi aceito como estatisticamente significativo. Resultados A frequência cardíaca (77,2±12,8 versus 71,4±11,2; p=0,02) foi maior no grupo usuário de heroína em comparação com o grupo controle. Os intervalos QT (341,50±25,80 versus 379,11±45,23; p=0,01), QTc (385,12±29,11 versus 411,3±51,70; p<0,01) e o intervalo do pico ao fim da onda T (Tpe) (65,41±10,82 versus 73,3±10,13; p<0,01) foram significativamente menores no grupo usuário de heroína. Nenhuma diferença foi observada entre os grupos com respeito às razões Tpe/QT e Tpe/QTc. Na análise de subgrupo do grupo usuário de heroína, os intervalos QT (356,81±37,49 versus 381,18±40,03; p<0,01) e QTc (382,06±26,41 versus 396,06±29,80; p<0,01) foram significativamente mais curtos no período pré-tratamento. Conclusão O vício em heroína afeta significativamente os intervalos de tempo QT, QTc e Tpe. Os efeitos de arritmia desses parâmetros já são conhecidos. Os parâmetros eletrocardiográficos desses indivíduos merecem mais atenção. (Arq Bras Cardiol. 2020; 115(6):1135-1141)
Abstract Background Heroin addiction is currently a significant health problem, and information on the electrocardiographic effects of heroin is limited. Objetivo The aim of the present study is to investigate effects of heroin addiction on electrocardiographic parameters. Methods A total of 136 individuals, including 66 individuals who smoke heroin as the study group and 70 healthy individuals with no drug addiction as the control group, were included in the study. Individuals who inject heroin were excluded. Electrocardiographic (ECG) evaluation of those using heroin was performed and compared with those of the control group. In addition, pre-treatment and post-treatment ECG of the heroin group were compared. A p-value of <0.05 was accepted as statistically significant. Results Heart rate (77.2±12.8 versus 71.4±11.2; p=0.02) were found to be higher in the heroin group compared to the control group. QT (341.50±25.80 versus 379.11±45.23; p=0.01), QTc intervals (385.12±29.11 versus 411.3±51.70; p<0.01), and T peak to end time (Tpe) (65.41±10.82 versus 73.3±10.13; p<0.01) were significantly shorter in the heroin group. No difference was observed between the groups with regard to Tpe/QT and Tpe/QTc ratios. In the subgroup analysis of the heroin group, QT (356.81±37.49 versus 381.18±40.03; p<0.01) and QTc (382.06±26.41 versus 396.06±29.80; p<0.01) intervals were significantly shorter in the pre-treatment period. Conclusion Heroin addiction significantly affects the QT, QTc, and Tpe time intervals. The arrhythmia effects of these parameters are well known. More attention to the electrocardiographic parameters of these individuals should be given. (Arq Bras Cardiol. 2020; 115(6):1135-1141)
Assuntos
Humanos , Heroína/efeitos adversos , Eletrocardiografia , Arritmias Cardíacas , Frequência CardíacaRESUMO
We studied mechanisms driving gender differences in HIV incidence among 651 women and men who inject drugs (PWID) in Tijuana, Mexico, hypothesizing that sex work will mediate the association between female gender and HIV incidence. Of 43 HIV seroconversions occurring between 2011 and 2018, 8.8% were among females and 5.2% among males. HIV incidence density was significantly higher among females versus males (1.75 per 100 person years [PY], 95% CI 1.16-2.66, vs. 0.95 per 100 PY, 95% CI 0.62-1.47). Factors significantly associated with HIV seroconversion were: sex work (adjusted hazard ratio [aHR] = 2.25, 95% CI 1.05-4.80); methamphetamine injection (aHR = 2.30, 95% CI 1.12-4.73); and methamphetamine and heroin co-injection in the past six months (aHR = 2.26, 95% CI 1.23-4.15). In mediation analyses, sex work mediated a substantial proportion (84.3%) of the association between female gender and HIV incidence. Interventions should target female PWID who engage in sex work to reduce gender-related disparities in HIV incidence.
Assuntos
Infecções por HIV/epidemiologia , Heroína/efeitos adversos , Metanfetamina/efeitos adversos , Trabalho Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Feminino , Infecções por HIV/diagnóstico , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Heroin addiction is currently a significant health problem, and information on the electrocardiographic effects of heroin is limited. OBJETIVO: The aim of the present study is to investigate effects of heroin addiction on electrocardiographic parameters. METHODS: A total of 136 individuals, including 66 individuals who smoke heroin as the study group and 70 healthy individuals with no drug addiction as the control group, were included in the study. Individuals who inject heroin were excluded. Electrocardiographic (ECG) evaluation of those using heroin was performed and compared with those of the control group. In addition, pre-treatment and post-treatment ECG of the heroin group were compared. A p-value of <0.05 was accepted as statistically significant. RESULTS: Heart rate (77.2±12.8 versus 71.4±11.2; p=0.02) were found to be higher in the heroin group compared to the control group. QT (341.50±25.80 versus 379.11±45.23; p=0.01), QTc intervals (385.12±29.11 versus 411.3±51.70; p<0.01), and T peak to end time (Tpe) (65.41±10.82 versus 73.3±10.13; p<0.01) were significantly shorter in the heroin group. No difference was observed between the groups with regard to Tpe/QT and Tpe/QTc ratios. In the subgroup analysis of the heroin group, QT (356.81±37.49 versus 381.18±40.03; p<0.01) and QTc (382.06±26.41 versus 396.06±29.80; p<0.01) intervals were significantly shorter in the pre-treatment period. CONCLUSION: Heroin addiction significantly affects the QT, QTc, and Tpe time intervals. The arrhythmia effects of these parameters are well known. More attention to the electrocardiographic parameters of these individuals should be given. (Arq Bras Cardiol. 2020; 115(6):1135-1141).
FUNDAMENTO: Atualmente, o vício em heroína é um problema de saúde preocupante, e as informações sobre os efeitos eletrocardiográficos da heroína são limitadas. OBJETIVOS: O objetivo do presente estudo é investigar os efeitos da dependência de heroína em parâmetros eletrocardiográficos. MÉTODOS: Um total de 136 indivíduos, incluindo 66 indivíduos que fumam heroína como grupo de estudo e 70 indivíduos saudáveis sem dependência de drogas como grupo de controle, foram incluídos no estudo. Indivíduos que injetam heroína foram excluídos. A avaliação eletrocardiográfica (ECG) dos usuários de heroína foi realizada e comparada com as do grupo controle. Além disso, os ECGs pré e pós-tratamento do grupo usuário de heroína foram comparados. Um valor de p<0,05 foi aceito como estatisticamente significativo. RESULTADOS: A frequência cardíaca (77,2±12,8 versus 71,4±11,2; p=0,02) foi maior no grupo usuário de heroína em comparação com o grupo controle. Os intervalos QT (341,50±25,80 versus 379,11±45,23; p=0,01), QTc (385,12±29,11 versus 411,3±51,70; p<0,01) e o intervalo do pico ao fim da onda T (Tpe) (65,41±10,82 versus 73,3±10,13; p<0,01) foram significativamente menores no grupo usuário de heroína. Nenhuma diferença foi observada entre os grupos com respeito às razões Tpe/QT e Tpe/QTc. Na análise de subgrupo do grupo usuário de heroína, os intervalos QT (356,81±37,49 versus 381,18±40,03; p<0,01) e QTc (382,06±26,41 versus 396,06±29,80; p<0,01) foram significativamente mais curtos no período pré-tratamento. CONCLUSÃO: O vício em heroína afeta significativamente os intervalos de tempo QT, QTc e Tpe. Os efeitos de arritmia desses parâmetros já são conhecidos. Os parâmetros eletrocardiográficos desses indivíduos merecem mais atenção. (Arq Bras Cardiol. 2020; 115(6):1135-1141).
Assuntos
Eletrocardiografia , Heroína , Arritmias Cardíacas , Frequência Cardíaca , Heroína/efeitos adversos , HumanosRESUMO
INTRODUCTION: Recent reports from a variety of sources indicate that heroin use among Ecuadorian adolescents is on the rise. In order to design effective prevention and intervention programs, research is needed that quantifies use and assesses risk and protective factors associated with use. METHODS: This study analyzed the National Survey of Drug Use, a nationally representative survey of 50,145 adolescents (49.6% female; M age = 14.92 years, SD = 1.74) conducted in Ecuador in 2015. RESULTS: Overall, 2.3% of the sample reported lifetime heroin use. Logistic regression analysis revealed that higher lifetime heroin use was associated with lifetime use of alcohol (Adj OR = .71 CI[.58, .86]), marijuana (Adj OR = 3.79 CI[3.17, 4.52]), and hard drugs (Adj OR = 16.33 CI[13.89, 19.21]), as well as with greater perceived access to heroin (Adj OR = 2.13 CI[1.93, 2.36]) and repeating more school grades (Adj OR = 1.66 CI[1.37, 2.01]). Higher levels of parental involvement (Adj OR = .95 CI[.91, .99]) were associated with a reduced risk of use. Risk and protective factors operated similarly across age and gender. CONCLUSION: These data suggest that targeting substance use early in adolescence, focusing on school engagement, enhancing parenting skills, and improving family climate may be important approaches to curbing heroin use among Ecuadorian teens. The relative absence of age and gender differences in patterns of risk and protection suggest that a universal prevention approach versus a targeted approach may be most effective.
Assuntos
Heroína/efeitos adversos , Adolescente , Equador , Feminino , Humanos , Masculino , Fatores de Proteção , Fatores de RiscoRESUMO
Addiction to illicit substances or medicines is influenced by cultural, religious, ethnic factors as well as local availability. The purpose of this study was to evaluate the profile of drug users and characteristics of the psychoactive substances used in French overseas territories, using data from the OPPIDUM survey. OPPIDUM is an annual, nationwide, multicentric, cross-sectional study based on specialized care centres that included subjects presenting a drug addiction or under opiate maintenance treatment. The current study includes data from the 2012 and 2013 surveys and focuses on patients included by drug addiction centres located in French overseas departments and territories: French Pacific Ocean (French Polynesia, New Caledonia), French Americas (Guadeloupe, Saint Martin, French Guiana) and Reunion Island. Data from metropolitan France (2013 survey) were included as reference. Two hundred and forty-five patients were included. The sex ratio was 3.7 for the Pacific Ocean, 3.5 for the French Americas and 3.3 for Reunion Island. Cannabis was consumed in all the territories, from 50.8% in Reunion Island to 81.7% in Pacific Ocean. Cocaine was most frequently consumed in the French Americas (61%), mainly in the 'freebase' form (91%), whereas 6.5% of cocaine users in metropolitan France did so. Problematic use of medicines was most frequent in Reunion Island. Heroin seems rarely used in all overseas territories. This study highlights the complexity of substances used in French overseas territories, which often differ from that in mainland France. The relative difference between different areas provides valuable information for future investigations and possible interventions.
Assuntos
Cocaína/administração & dosagem , Heroína/administração & dosagem , Drogas Ilícitas , Psicotrópicos/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Cocaína/efeitos adversos , Feminino , França/epidemiologia , Guiana Francesa/epidemiologia , Guadalupe/epidemiologia , Heroína/efeitos adversos , Humanos , Masculino , Martinica/epidemiologia , Nova Caledônia/epidemiologia , Polinésia/epidemiologia , Psicotrópicos/efeitos adversos , Reunião/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Adulto JovemRESUMO
ABSTRACT Heroin is known to enhance catabolism and inhibit anabolism of purine nucleotides, leading to purine nucleotide deficiencies in rat brains. Here, we determined the effect of exogenous purine nucleotide administration on purine nucleotide metabolism in the brains of heroin-dependent rats. Heroin was administrated in increasing doses for 9 consecutive days to induce addiction, and the biochemical changes associated with heroin and purine nucleotide administration were compared among the treated groups. HPLC was performed to detect the absolute concentrations of purine nucleotides in the rat brain cortices. The enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the treated rat cortices were analyzed, and qRT-PCR was performed to determine the relative expression of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT), and adenosine kinase (AK). Heroin increased the enzymatic activity of ADA and XO, and up-regulated the transcription of ADA and XO. Alternatively, heroin decreased the transcription of AK, APRT, and HGPRT in the rat cortices. Furthermore, purine nucleotide administration alleviated the effect of heroin on purine nucleotide content, activity of essential purine nucleotide metabolic enzymes, and transcript levels of these genes. Our findings therefore represent a novel, putative approach to the treatment of heroin addiction.