O crack, uma droga de abuso constituída principalmente por cocaína, continua sendo um grande problema social e de saúde pública. Apesar de vários estudos em modelos animais com outras formas de cocaína, raros são os relatos sobre os efeitos da exposição pulmonar ao crack em roedores, devido à dificuldade de realizar a exposição dos mesmos à droga, o que seria de grande valia, uma vez que eliminaria variáveis encontradas em usuários, como o uso de outras drogas. Assim, o propósito do presente estudo foi avaliar os efeitos tóxicos, imunotóxicos e ainda, alterações comportamentais de ratos Wistar machos expostos ao crack pela via pulmonar. Inicialmente, foram realizadas determinações de cocaína nas pedras de crack utilizadas e também, a quantidade de crack e tempo de exposição dos animais para obtenção de níveis séricos de cocaína semelhantes àqueles encontrados na literatura, e os dados obtidos foram de: 67% de cocaína no crack e a queima de 250 mg de crack, com exposição dos animais por 10 minutos acarretou em níveis plasmáticos próximos de 170 ng/mL de cocaína. Assim, em cada experimento foram utilizados 30 ratos divididos em 3 grupos iguais, um controle, um experimental e um grupo pair-fed, já que a cocaína promove efeitos anorexígenos que poderiam interferir nas avaliações comportamentais e imunológicas aqui estudadas, e que foram expostos ou não à fumaça resultante de 250 mg de crack, por 10 minutos, duas vezes ao dia, durante 28 dias. Ao final do período experimental, os animais foram submetidos à eutanásia para realização de avaliações bíoquimicas, hematológicas, histopatológicas, análise de órgãos-linfóides, avaliação das respostas imune inata (inflamatória), humoral e a avaliação da reação de hipersensibilidade do tipo IV. Ainda, ao longo do período experimental, estes mesmos animais foram avaliados quanto a possíveis alterações comportamentais e para tal foram utilizados 3 métodos distintos: avaliação cognitiva em labirinto em T, avaliação geral do comportamento em campo aberto e ainda, a avaliação de preferência ou aversão ao odor da droga. A exposição ao crack não resultou em alterações que caracterizem toxicidade em parâmetros clínicos, bioquímicos, hematológicos e histopatológicos; não foram observadas alterações com significado clínico nas avaliações do peso relativo, celularidade, morfometria de órgãos linfoides e fenotipagem de linfócitos esplênicos de ratos expostos à droga. Não houve efeitos imunomodulatórios nas avaliações do burst oxidativo e fagocitose de macrófagos peritoneais e de neutrófilos circulantes, assim como nas avaliações da produção de anticorpos T-dependentes e na reação de hipersensibilidade do tipo IV. Quanto às avaliações comportamentais, os animais expostos à droga apresentaram aumento da atividade locomotora, e uma maior preferência ao odor característico do crack, aparentemente sem prejuízo cognitivo. Em conclusão, a exposição de ratos 2 vezes ao dia, por 28 dias ao crack não promoveu alterações imunotóxicas; por outro lado, comportamentos clássicos da exposição à cocaína foram observados nos animais expostos, evidenciando que o modelo aqui utilizado será de grande utilidade para outros estudos que envolvam drogas de abuso, como possíveis estratégias terapêuticas e o melhor entendimento da toxicocinética de drogas utilizadas pela via pulmonar / Crack cocaine, a drug of abuse that consists mainly of cocaine, remains as a major social and public health problem. Although several studies in animal models with other forms of cocaine, there are few scientific reports on the effects of pulmonary exposure to crack in rodents, this is due to the difficulty of performing their exposure, which would be of great value, since would eliminate variables observed in users, such as the use of other drugs. Initially, the concentration of cocaine in crack samples, as the amount of crack and time of exposure of the animals to obtain serum levels of cocaine similar to those found in the literature were determined, and the data obtained were: 67% of cocaine in crack, and 250 mg of crack, exposing the animals for 10 minutes resulted in plasma levels close to 170 ng/mL of cocaine. Thus, the purpose of this study was to evaluate the toxic effects, immunotoxic and behavioral changes of male Wistar rats exposed to crack cocaine. Thus, in each experiment were used 30 rats divided into three groups, one control, one experimental and one pair-fed, since it is known that cocaine promotes anorexic effects that may interfere with behavioral and immunological assessments that will be studied here, and who were exposed or not to the burning of 250 mg of crack, for 10 minutes, twice daily for 28 days. At the end of the experiment, the animals were euthanized to perform biochemical evaluation, hematological, histopathological, analysis of lymphoid organs, evaluation of innate immune responses (inflammatory), humoral and the assessment of the type IV hypersensitivity reaction. Still, throughout the experimental period, these same animals were evaluated for possible behavioral changes and were used three different methods: cognitive assessment in T-maze, overall assessment on open field behavior and the evaluation of preference or aversion to the odor of the drug. Exposure to crack cocaine, did not result in changes that characterize toxicity in clinical, biochemical, hematological and histopathological parameters; were not observed clinically meaningful changes in the relative weight ratings, cellularity, morphology of lymphoid organs and phenotyping of splenic lymphocytes from rats exposed to the drug. There was no immunomodulatory effect in the evaluations of oxidative burst and phagocytosis of peritoneal macrophages and in circulating neutrophils, and the assessments of the production of T-dependent antibodies and the type IV hypersensitivity reaction. With regard to behavioral assessments, the animals exposed to the drug showed increased locomotor activity, and greater preference to the characteristic odor of crack cocaine, apparently without cognitive impairment. In conclusion, in the exposure model to crack cocaine used here, immunotoxic changes were not evident; by contrast, classic behavior of cocaine exposure were observed in the animals exposed, indicating that the model used herein will be useful for the study of other parameters involving drugs of abuse, in evaluation of therapeutic strategies and a better understanding of drugs toxicokinetics used by the pulmonary route

Direct Analysis in Real Time (DART) ionization/mass spectrometry allows for the high throughput analysis of a wide range of materials including but not limited to: solids, liquids, powders, tablets, and plant materials. The ability to detect cocaine was established in a reproducible manner with the use of a DART ionization source (IonSense Inc., Saugus, MA) interfaced to a modified single quadrupole mass spectrometer. Development of a methodology for the detection of cocaine within contrived street quality drug mixtures involved the optimization of the ionization source, sample introduction mechanism, ion guide, and mass analysis parameters. An analytical method was created that utilized ionized helium carrier gas heated to 300°C and an automated sample introduction apparatus consisting of a Linear Rail Enclosure that holds consumable QuickStrip^TM sample cards. Ionized molecules were then fragmented by manipulation of voltage levels within the ion guide to gain more structural information prior to detection by a single quadrupole mass spectrometer. Cocaine was detected by the modified DART/MS analytical platform and gave two peaks within the mass spectrum at m/z 304 and 182. Optimization of in-source fragmentation by manual adjustment of the skimmer focus voltage allowed for the reproducible fragmentation of cocaine and the ability to increase or decrease the amount of fragmentation seen between the two peaks detected for cocaine. With the use of fragmentation, this analytical platform can be classified as a Category A technique as defined by the Scientific Working Group for the Analysis of Seized Drugs. The robust detection of cocaine was demonstrated for reference samples at concentrations as low as 10 ng/μL (50 ng) with high signal abundance greater than ten times the signal to noise ratio. Furthermore, the detection of cocaine at 10 ng/μL was demonstrated for multi component mixtures of up to 14 additional components containing common adulterants and diluents found within street quality samples. In total, 25 common excipients were tested using the same method parameters as optimized for cocaine analysis. Of these 25 excipients tested, five were not detected in positive ion mode (one could be detected in negative ion mode). Of the twenty excipients that could be detected by mass spectrometry, two pairs of excipients (levamisole/tetramisole and creatine/creatinine) could not be differentiated from each other. There were no excipients tested that had equivalent m/z values as those of cocaine. Experimentation into the effects of various excipients at multiple concentrations on the abundance of the two cocaine peaks was performed. Regardless of excipient amount (up to 10 times more concentrated than cocaine) and the number of components (up to 15 total components) the ratio of abundance between the m/z 304 to 182 peaks did not vary greater than 22% relative standard deviation. A match criteria protocol was developed for the ability of an analyst to confirm the presence of cocaine within unknown forensic case samples that have previously tested positive for the presumptive identification of cocaine. The identification of cocaine was based on various factors such as the signal to noise ratio at m/z 304 and 182, the ratio of abundance between those two peaks as well as positive and negative controls. This match criteria protocol was utilized for 25 double blind mock forensic casework samples was performed. Determination for the presence of cocaine within these unknown samples gave an analyst error rate of 0%, with no false positives or false negatives predicted. To further aid human interpretation and identification of compounds within mixtures, the advanced chemometric software, Analyze IQ, was utilized. Development of predictive classification models using a combination of pre-processing steps, principle component analysis and machine learning techniques was achieved. Models were built using 381 unique samples for the purposes of identifying the presence of cocaine within unknown samples. Of all methods available within the Analyze IQ software, the optimization of a model using principle component analysis with support vector machine regression with a radial basis function kernel yielded an initial error rate of 0% for 72 samples tested. Furthermore, of the samples tested against the model, 20 samples were comprised of excipients that were not incorporated into the initial model development process. The inclusion of these samples (10 spiked with cocaine, 10 absent of cocaine), shows that predictive modeling based software can provide an accurate, robust, and evolving approach to the identification of cocaine within sample compositions that have not previously been tested and stored in a database of known reference samples. Predictive modeling has advantages over current mass spectral libraries, which are limited to the identification of pure compounds. To further test the abilities of predictive models, optimized machine learning models were applied to 25 double blind mock forensic casework samples. The predictive modeling error rate was identical to the human interpretation rate for the double blind mock casework samples with a 0% error rate. Using the DART/MS analytical platform, 25 mock forensic casework samples along with positive and negative controls were analyzed and identified for the presence of cocaine within 30 minutes. On the order of 15 to 30 times faster than modern GC/MS and LC/MS methods, the ability to analyze and identify samples faster would allow for an increase in samples being processed on a daily basis and allow for the reduction of case backlogs that currently plague controlled substances sections of forensic science laboratories throughout the United States.

No contexto analítico forense, questões relacionadas à estabilidade química dos compostos a serem avaliados podem acarretar desvios analíticos consideráveis, o que pode gerar conclusões equivocadas a respeito da composição da amostra. Dessa forma, diante das estratégias para conservação da composição química em amostras biológicas atualmente disponíveis, buscou-se, com o presente trabalho, avaliar a aplicabilidade da técnica de DBS (Dried Blood Spot) para o contexto forense, uma vez que vem sendo sugerido que esta técnica promove maior estabilidade química e, ainda, não interfere na composição da amostra, dentre outras vantagens. Assim, no presente estudo foi avaliada a estabilidade da cocaína, éster metilecgonina, benzoilecgonina, clonazepam, diazepam e alprazolam em amostras de sangue total post mortem aplicadas ou não em DBS, para que se pudesse comparar os resultados obtidos, e, então, verificar a viabilidade do acondicionamento das amostras em cada uma dessas matrizes. Concomitantemente, foi avaliado o impacto da temperatura sobre a estabilidade química dessas substâncias nas diferentes matrizes. Para alcançar o objetivo final, foram desenvolvidas e validadas metodologias analíticas por LC/MS-MS, segundo parâmetros sugeridos em guias de validação internacionais. Posteriormente, foram incubadas amostras contendo concentrações conhecidas das substâncias de interesse em DBS e em sangue total, as quais foram acondicionadas em diversas temperaturas e analisadas em diferentes intervalos de tempo. Os dados obtidos para estudo de estabilidade da cocaína e metabólitos sugerem que, apesar das amostras de sangue total acondicionadas em freezer não apresentarem redução na concentração acima de 20%, de maneira geral, amostras de DBS promoveram maior estabilidade química aos compostos monitorados. O estudo sugere, ainda, que a temperatura apresenta grande impacto sobre a estabilidade desses compostos, em consonância com outros estudos publicados na literatura. Já os dados de estudo de estabilidade obtidos para os benzodiazepínicos selecionados apresentaram maior uniformidade que os dados obtidos para cocaína e metabólitos. Assim, para todas as condições avaliadas, ou seja, para as duas diferentes matrizes e para as diferentes temperaturas, foi observado que os compostos, de maneira geral, não apresentaram queda na concentração acima de 20% durante o período de estudo. A análise estatística indica não haver, em termos gerais, diferença significativa entre as diferentes formas de acondicionamento. Por fim, o estudo realizado mostra a compatibilidade da técnica de DBS com aplicações forenses, e, em alguns casos, sugere qualidade técnica superior em relação àanálise em sangue total, já que é capaz de manter a estabilidade de compostos considerados instáveis em meio aquoso. / In the forensic context, instability of chemical compounds may result in considerable analytical errors that could lead to inaccurate conclusions regarding the composition of the sample. Thus, given the available chemical composition conservation strategies for biological samples, this work aims to assess the applicability of the DBS (Dried Blood Spot) technique to the forensic context, considering that this approach improves the chemical stability, and does not interfere with the composition of the sample. Therefore, this study investigated the chemical stability of cocaine, methylecgonine ester, benzoylecgonine, diazepam and alprazolam in post mortem whole blood samples. The DBS method was used for the processing of part of the samples, in order to compare results, and then evaluate the storage conditions on the viability of each blood matrix (whole blood in relation to DBS). Concurrently, the effects of temperature on the stability of those chemical substances were also evaluated. Analytical methodologies based on LC/MS-MS were developed and validated, according to parameters suggested by international guidelines. Afterward, samples containing known concentrations of the analytes were incubated in two distinct matrices (DBS and whole blood) at several temperatures, and were analyzed at different time intervals. Although whole blood samples stored in freezer do not present concentration decay above 20 per cent, results suggest that DBS samples promoted greater chemical stability of the compounds of interest. Furthermore, temperature appears to affect greatly the stability of those analytes, consonant with previous studies. Regarding the stability study data obtained for the selected benzodiazepines, they presented greater uniformity than the data obtained for cocaine and metabolites. Therefore, considering all the described conditions, i.e., the two distinct matrices and the different temperatures, the compounds of interest did not present a decrease in concentration above 20 per cent during the study period. The statistical analysis indicate that there is no significant differences between the deployed storage methods. Thus, further studies, with a greater number of samples, are recommended in order to corroborate the statistical findings for the benzodiazepine compounds presented in this study. This study shows the compatibility of the DBS technique with forensic applications, and, in some cases, suggests its superior technical quality in relation to the whole blood analysis, since it preserves the chemical stability of compounds.

A alta prevalência de uso de cocaína, e o alarmante número de apreensões do entorpecente, trazem à tona a necessidade de se explorar novas formas de combate ao tráfico. A investigação dos componentes presentes nas amostras apreendidas tem sido bastante explorada, pois. para chegar ao consumidor final, a cocaína \"de rua\", além das etapas básicas de obtenção, muitas vezes é também submetida às etapas de adição de diluentes e de adulterantes. Sabendo-se que o maior número de laudos expedidos pelo Núcleo de Perícias Criminalísticas de Araçatuba é atribuído a exames relacionados com entorpecentes, e que para a cidade não há estudo a cerca dos componentes das amostras apreendidas de cocaína e suas referências geográficas, o presente trabalho teve por objetivo investigar os adulterantes presentes em 92 amostras de cocaína apreendidas na região de Araçatuba, no período de 2014 a 2015 empregando o método de extração líquido-líquido e análise por Cromatografia em fase Gasosa utilizando detector de Espectrometria de massas. Como resultado foram identificados, em ordem decrescente de recorrência, os adulterantes: cafeína, lidocaína, fenacetina, levamisol, carisoprodol, aminopirina, benzocaína metotrimeprazina e cloridrato de cetamina. Também foram identificados outros alcaloides como éster de metilecgonidina, cinamoilcocaínas e norcocaína. A maior parte das amostras analisadas demonstrou-se adulterada e em mais de 78% das amostras foi detectado o éster de metilecgonidina, substância formada a partir da pirólise, ou degradação térmica da cocaína. Foram elaborados mapas georreferenciados baseados nos sítios das apreensões, em que se pode visualizar que as mesmas ocorreram nas regiões periféricas das cidades abordadas, demonstrando a presença de três principais núcleos de densidade de apreensões, localizados na cidade de Araçatuba / The high prevalence of cocaine use, and its alarming number of seizures, shows the need to explore new tools for drug trafficking combat. Investigations about components presents in drug seized samples has been high explored, mainly because drug dealers used to add compounds on street cocaine, like diluents and adulterants. Knowing that the highest number of reports made on Núcleo de Perícias Criminalísticas de Araçatuba are related to narcotics, and that for this city there is no study about the components of the cocaine seized samples and its geographic references, the present work had the aim of investigating the adulterants present in 92 cocaine samples seized in the region of Araçatuba, from 2014 to 2015, using the method of liquid-liquid extraction and analysis by Gas Chromatography Mass Spectrometry. As a result, the adulterants identified: were caffeine, followed by lidocaine, phenacetin, levamisole, carisoprodol, aminopyrine, benzocaine methotrimeprazine and ketamine. Other alkaloids have also been identified as ecgonidine methy ester, cinnamoylcocaine and norcocaine. Most of the analyzed samples were adulterated and in more than 78% of them showed the presence of ecgonidine methyl ester, a compound formed from the cocaine pyrolysis, or thermal degradation. Georeferenced maps were made based on the seizure geographic coordinates, where it can be seen that they occurred in the peripheral regions of the cities, and the presence of three main seizure density areas, located in the city of Araçatuba.

A fase da adolescência difere da adulta em parâmetros comportamentais e neurológicos. A proteína de ligação responsiva ao AMPc (CREB) é um fator de transcrição regulado por três vias principais: PKA, CaMK e ERK, as quais apresentam atividade alterada em resposta à cocaína. Neste trabalho, foram avaliadas as atividades dessas vias, bem como os níveis de um de seus genes alvo (prodinorfina), do inibidor endógeno de CRE (Icer) e da proteína ativadora de CREB (CBP) em resposta à administração de cocaína, além dos comportamentos induzidos pelo psicoestimulante. Os adolescentes apresentaram maior sensibilização psicomotora, atividade exploratória e comportamento tipo ansiedade em comparação aos adultos. Os adolescentes exibiram aumento da atividade da via da PKA e da expressão de Icer, CBP e Pdyn; os adultos apresentaram diminuição de CaMKs, GluR1 e Icer. Essas diferentes respostas neuroadaptativas podem ajudar na compreensão dos mecanismos ontogênicos envolvidos na dependência. / The adolescence differs from adulthood in behavioral and neurochemichal aspects. The cAMP responsive binding protein (CREB) is a transcription factor regulated by three main pathways in the mesolimbic-dopaminergic circuit: PKA, CaMK and ERK, which are modulated by cocaine. This study evaluated the activity of these pathways, as well as the levels of one of its main target genes (prodynorphin), endogenous CRE inhibitor (Icer) and CREB binding protein (CBP) in response to cocaine administration, besides the behaviors induced by the psychostimulant. Adolescents presented greater locomotor activation, psychomotor sensitization, exploratory activity and anxiety-like behavior compared to adults. Adolescents exhibited increased PKA pathway activity and expression of Icer, CBP, and Pdyn; adults showed decreased levels of CaMKs, GluR1 and Icer. These different neuroadaptive responses may help understanding the ontogenic mechanisms involved in addiction.

Introdução: O uso do crack constitui-se um dos maiores problemas de saúde pública na atua-lidade. O crack apresenta-se como uma nova forma de uso da cocaína, com padrão de uso cada vez mais intenso e compulsivo, ocasionando inúmeras intercorrências e implicações sociais e a saúde, levando o usuário a busca de tratamento. Objetivo: Conhecer a trajetória de tratamento do usuário de Crack em serviço ambulatorial de Atenção Psicossocial – CAPSAD III, através das narrativas sobre o consumo e busca por serviço especializado na rede pública de saúde. Método: Estudo qualitativo de uma amostra intencional de doze usuários de crack, sendo oito homens e quatro mulheres, em tratamento no CAPS ad III no município de João Pessoa/PB. Os dados foram explorados utilizando-se a técnica de análise de conteúdo. Instrumentos: Foi uti-lizada como instrumento de investigação, entrevista semiestruturada individual para a coleta dos dados sociodemográficos e das narrativas sobre o uso do crack e busca por tratamento. Foram aplicados o Questionário da Trajetória do Usuário de Crack/QTTUC e a Escala de Re-caída para usuários de crack – ERUC, porém os dados serão analisados e publicados em artigos posteriormente. Resultados: Os achados apontam dificuldades de acesso aos serviços especi-alizados, ocorrendo mais de uma tentativa para conseguir tratamento na rede pública de saúde e observa-se que os serviços da atenção básica e rede hospitalar, ainda não se encontram pre-parados para atendimento as demandas oriundas dos usuários de crack. Além da relevância do tratamento ambulatorial, evidencia-se a necessidade de serviços da assistência social para reta-guarda aos usuários em situação de extrema vulnerabilidade social. Conclusão: Os resultados sugerem a implementação de programas que possam facilitar o acesso de usuários de crack aos serviços do Sistema único de Saúde- SUS, qua / Background: Today, crack addiction is one of the major public health issues. Crack is as a new way of cocaine use, with intense and compulsive brains and body effects, resulting in a huge social complications, as well as health implications, leading to seek treatment. Aims: Under-stand the trajectory of crack addicted while in treatment at clinic of Psychosocial Care – CAPS AD III, through narratives about consumption and seeking for specialized doctors from public 8 health system care. Method: Qualitative study; convenience sample of 12 crack addicted, 8 men and 4 women, undergoing treatment at CAPS ad in the city of João Pessoa / PB. We review the data through content analysis technique. Instruments: We made a semi-structured inter-view for each subject for demographic data collection, as well as we collected narratives about the consumption of crack and treatment. We applied questionnaire of crack User trajec-tory/QTTUC and Crack Use Relapse Scale (CURS), but the data will be analyzed and published later. Results: These findings indicate that accessing specialized services is a tough pathway. Usually, the health public consumer must go there more than one time to be attend. In addition, the public health system still have not enough structure to attend demands from crack users. Be-sides the relevance of clinic treatment, it is highlighted that social services is essential for users supporting. Conclusion: The results suggest that is mandatory develop and execute programs that would facilitate crack users access to the Public Health System. To sum up, increase quality actions at different levels of health care and improve the relapse prevention process is central to crack users avoid relapses while in treatment.

Made available in DSpace on 2016-03-22T17:26:36Z (GMT). No. of bitstreams: 1 Dissert Rogerio Goncalves do Amaral.pdf: 234851 bytes, checksum: da3c002d659e5f365e9fe87b5421f59e (MD5) Previous issue date: 2011-06-22 / Objectives: Evaluate the profile and patterns of consumption of crack cocaine users who were hospitalized in Pelotas, Southern Brazil. Also, it was estimated the time to become addict, since the moment crack cocaine was used by the first time. . Methods: Cross-sectional study of 162 patients with the help of a structured questionnaire evaluating socio-demographic characteristics, strategies used to obtain the drug, ways of access to the drug, and criminal history. ICD-10 criteria were used to estimate the time between first use and addiction. Results: Most patients were young men (82,1%) with low literacy level and low income. The main strategy to obtain the drug was stealing, assaulting and drug traffic. The access to drugs was considered very easy (49,4%) or easy (42%) by most of the addicts, and 86% were able to obtain the drug in less than 30 minutes. After two months of having used crack for the first time, 44% were addicts, and this proportion increased to 73% with six months of use and 87% after one year. Conclusions: Crack cocaine is very easy to obtain and it leads to addiction in a short period of time. As it is widely used, and criminal acts are commonly used for its achievement, crack cocaine is an important reason for the increase of violence in urban societies / Objetivos: Estudar o perfil e padrões de consumo de pacientes internados por uso de crack, e estimar o tempo para se tornar dependente após experimentar crack pela primeira vez. Métodos: Estudo transversal com 162 pacientes internados para desintoxicação em um hospital psiquiátrico em Pelotas, Rio Grande do Sul. Utilizou-se um questionário para avaliar características sociodemográficas, estratégias usadas para adquirir crack, acesso à droga e história penitenciária criminal. Os critérios da CID-10 para síndrome de dependência foram usados para estimar o tempo em que o paciente se tornou dependente após experimentar a primeira pedra de crack. Resultados: A maioria dos pacientes era homens jovens (82,1%), com baixa escolaridade e renda. A principal estratégia ilegal para conseguir crack foi furtar, seguida por assaltos e tráfico de drogas. O acesso à droga foi considerado muito fácil (49,4%) ou fácil (42%) pela maioria dos usuários, sendo que 86% tinham acesso ao crack em menos de 30 minutos. Dois meses após experimentarem a primeira pedra de crack, 44% já se tornaram dependentes, e esta proporção aumentou para 73% aos seis meses e 87% com um ano. Conclusões: O crack é uma substância com acesso muito fácil que leva a dependência em período muito curto e com um impacto importante no aumento da violência na sociedade

A fase da adolescência difere da fase adulta em parâmetros comportamentais e neuroquímicos. Alterações do fator de transcrição CREB, da neurotrofina BDNF e seu receptor TrkB têm sido encontradas no circuito dopaminérgico-mesolímbico com o uso de cocaína. Este estudo avalia os efeitos da administração de cocaína em camundongos adolescentes e adultos na sensibilização psicomotora, no comportamento tipo ansiedade, nos níveis protéicos de CREB/pCREB, BDNF e TrkB e na expressão gênica de BDNF e TrkB no córtex pré-frontal (CPF) e hipocampo desses animais. Os adolescentes mostraram-se mais suscetíveis aos efeitos da droga, com maior ativação locomotora, maior efeito de condicionamento ao ambiente, maior nível de ansiedade induzido pela droga e alterações neuroquímicas distintas dos adultos (diminuição dos níveis de CREB com o tratamento repetido e aumento na abstinência em CPF e hipocampo; aumento de RNAm de BDNF após tratamento agudo, repetido e abstinência em CPF e diminuição no hipocampo), sugerindo maior vulnerabilidade desse grupo no desenvolvimento da dependência. / The adolescence differs from adulthood in behavioral and neurochemichal aspects. Changes in the activity of the transcriptional factor CREB, neurotrofin BDNF and its receptor TrkB have been found in the mesolimbic-dopaminergic circuitry following the use of cocaine. This study evaluates the effects of cocaine administration in adolescent and adult mice in the locomotor sensitization and in the anxiety-like behavior. The study also accesses the protein levels of CREB/pCREB, BDNF and TrkB, and gene expression of BDNF and TrkB in the prefrontal cortex and hippocampus of these animals. In a general way, adolescents were more susceptible to drug effects, with increased levels of locomotor activity, environmental conditioning, anxiety-like behavior and greater neurochemichal alterations, suggesting an increased risk in the development of drug dependence.

No mundo os acidentes de trânsito são responsáveis pela morte de aproximadamente 1,2 milhão de pessoas por ano. No Brasil, em 2014, foram mais de 44 mil óbitos no trânsito. O uso de substâncias psicoativas na direção é considerado um importante fator contribuinte para a ocorrência destes acidentes. Além do álcool, as drogas ilícitas mais utilizadas em nosso país são a anfetamina, a cocaína e a cannabis. As anfetaminas e a cocaína são utilizadas por motoristas de caminhão, que consomem para se manterem acordados por muitas horas e estão propensos a dormir ao volante. Portanto, há necessidade de conhecer o problema para que as autoridades competentes possam implementar políticas públicas relacionadas ao uso de drogas por motoristas e assim, minimizar os acidentes de trânsito no Brasil. Objetivo: Avaliar a prevalência do uso de substâncias psicoativas (anfetaminas, cocaína e cannabis) entre motoristas de caminhão que trafegavam em rodovias do Estado de São Paulo, através de análises toxicológicas em urina e correlacionar com dados sociodemográficos e ocupacionais. Métodos: Trata-se de estudo observacional do tipo transversal e a coleta dos dados foi realizada entre os anos de 2008 e 2012. Participaram do estudo 1.316 motoristas que, após assinarem o termo de consentimento livre e esclarecido e responderem a um questionário sobre dados sociodemográficos e ocupacionais, forneceram uma amostra de urina. Essas amostras foram analisadas por imunoensaio e por cromatografia em fase gasosa acoplada à espectrometria de massas. Resultados: Das amostras coletadas, 7,8% (n=103) apresentaram resultados positivos para uma ou mais drogas pesquisadas e/ou seus metabólitos, dos quais 3,4% foram resultados positivos para anfetamina, 2,8% para cocaína e 1,1% para cannabis. O 0,5% restante correspondeu aos casos com mais de uma droga. Com exceção do ano de 2008, as três drogas pesquisadas foram encontradas em todos os anos da pesquisa. Os resultados das análises toxicológicas se distribuíram de formas distintas de acordo com algumas variáveis: a idade, o tempo de profissão e o estado civil estiveram associados com o uso de drogas, enquanto o vínculo empregatício, a etnia e a escolaridade não apresentaram associação. Em relação à viagem, estiveram associados ao consumo de drogas a distância e o tempo de descanso noturno. O descanso diurno, o tempo total e o viajado, as horas de direção sem descanso, o número de ocupantes e o tipo de carga não apresentaram correlações significativas com o uso de drogas. Também não houve associação estatisticamente significante entre o consumo de drogas e doenças como hipertensão arterial, diabetes mellitus e estresse, nem com a prática de atividades físicas. Por outro lado, essa associação foi encontrada com o consumo de álcool, referido pelos caminhoneiros. Conclusão: os resultados indicam o uso de substâncias psicoativas por caminhoneiros e que este uso está associado com a idade, o tempo de profissão e o estado civil, assim como com a distância percorrida e o tempo de descanso noturno / Traffic accidents are responsible for approximately 1.2 million deaths per year worldwide. In Brazil, there were more than 44,000 traffic-related deaths in 2014. The use of psychoactive substances while driving is considered a major contributing factor to the occurrence of these accidents. In addition to alcohol, the most used illicit drugs in our country are amphetamines, cocaine and cannabis. Amphetamines and cocaine are commonly used by truck drivers to stay awake for several hours because they are likely to sleep while driving. Therefore, it is necessary to understand better this problem in order to help authorities implement public policies related to drug use by drivers and thus minimize traffic accidents in Brazil. Objective: To evaluate the prevalence of psychoactive substance (amphetamines, cocaine and cannabis) use among truck drivers in the highways of the State of Sao Paulo by toxicological analysis in urine and to correlate it with sociodemographic and occupational data. Methods: This is an observational cross-sectional study in which data collection was carried out between 2008 and 2012. This study included 1,316 drivers who provided a urine sample after signing a consent form and answering to a questionnaire with sociodemographic and occupational data. The urine samples were analyzed by immunoassay and gas chromatography-mass spectrometry. Results: Of the total samples collected, 7.8% (n = 103) were positive for one or more tested drugs and/or its metabolites, with 3.4% positive for amphetamine, 2.8% for cocaine and 1.1% for cannabis. The remaining 0.5% corresponded to cases with more than one drug. The three drugs were found during most of the study period, except in 2008. Toxicological findings were distributed differently according to some variables: age, employment period and marital status were associated with drug use, while the employment type, ethnicity and education were not. Travel length and night rest period were also associated with drug use. Daytime rest period, travel length period, driving time without rest, number of occupants and freight content did not correlate significantly with drug use. In addition, there was no statistically significant association between consumption of drugs and diseases (such as hypertension, diabetes and stress) or physical activity. However, the association between alcohol use (reported by truck drivers) and drug use was found. Conclusion: The results indicate that the use of psychoactive substances by truck drivers is common and this use is associated with age, employment period and marital status, as well as distance traveled and night rest period

by Choi, Heung Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 79-95). / Acknowledgement --- p.iv / Abstract --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Cocaine --- p.1 / Chapter 1.1.1 --- History --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.2 / Chapter 1.1.3 --- Pharmacology --- p.3 / Chapter 1.2 --- Maternal Cocaine Abuse --- p.5 / Chapter 1.2.1 --- Human Studies --- p.5 / Chapter 1.2.1.1 --- Prevalence --- p.5 / Chapter 1.2.1.2 --- Effects of Cocaine on the Developing Fetus --- p.7 / Chapter 1.2.1.2.1 --- Fetal Mortality --- p.8 / Chapter 1.2.1.2.2 --- Placental Abruption --- p.9 / Chapter 1.2.1.2.3 --- Premature Birth --- p.9 / Chapter 1.2.1.2.4 --- Neonatal Effects --- p.10 / Chapter 1.2.1.3 --- Congenital Abnormalities --- p.11 / Chapter 1.2.1.3.1 --- Cardiovascular Abnormality --- p.11 / Chapter 1.2.1.3.2 --- Genitourinary Tract Malformation --- p.12 / Chapter 1.2.1.3.3 --- Gastrointestinal Abnormality --- p.12 / Chapter 1.2.1.3.4 --- Respiratory Disorders --- p.13 / Chapter 1.2.1.3.5 --- Visual and Hearing Disorders --- p.14 / Chapter 1.2.1.3.6 --- CNS and Behavioural Abnormalities --- p.15 / Chapter 1.2.2 --- Animal Studies --- p.17 / Chapter 1.2.2.1 --- "Routes of Administration, Dosage and Tissue Distribution " --- p.18 / Chapter 1.2.2.2 --- Maternal and Offspring Effects --- p.21 / Chapter 1.2.2.2.1 --- Fetal and Maternal Mortality --- p.22 / Chapter 1.2.2.2.2 --- Gestational Length --- p.22 / Chapter 1.2.2.2.3 --- Maternal Weight Gain and Fetal Weight --- p.23 / Chapter 1.2.2.2.4 --- Little Size --- p.24 / Chapter 1.2.2.3 --- Congenital Abnormalities --- p.24 / Chapter 1.2.2.4 --- Behavioral Changes --- p.26 / Chapter 1.2.2.5 --- Neurochemical Changes --- p.28 / Chapter 1.2.2.5.1 --- Glucose Metabolism --- p.28 / Chapter 1.2.2.5.2 --- Dopamine Transporter --- p.29 / Chapter 1.2.2.5.3 --- Dopamine D1 Receptor --- p.29 / Chapter 1.2.2.5.4 --- Dopamine D2 Receptor --- p.30 / Chapter 1.2.2.5.5 --- Tyrosine Hydroxylase --- p.30 / Chapter 1.2.2.5.6 --- Other Changes --- p.31 / Chapter 1.3 --- The Aim of the Study --- p.31 / Chapter CHAPTER II --- MATERIALS AND METHODS / Chapter 2.1 --- Administration of Cocaine --- p.34 / Chapter 2.2 --- Biochemical Studies --- p.35 / Chapter 2.2.1 --- Receptor Binding Assays --- p.36 / Chapter 2.2.1.1 --- Dopamine Transporter --- p.37 / Chapter 2.2.1.1.1 --- Specific Binding Assay and Scatchard Analysis --- p.37 / Chapter 2.2.1.2 --- Dopamine D1 Receptor --- p.38 / Chapter 2.2.1.2.1 --- Association Curve --- p.38 / Chapter 2.2.1.2.2 --- Competition Assay --- p.39 / Chapter 2.2.1.2.3 --- Specific Binding Assay and Scatchard Analysis --- p.39 / Chapter 2.2.1.3 --- Dopamine D2 Receptor --- p.39 / Chapter 2.2.1.3.1 --- Association Curve --- p.40 / Chapter 2.2.1.3.2 --- Competition Assay --- p.40 / Chapter 2.2.1.3.3 --- Specific Binding Assay and Scatchard Analysis --- p.40 / Chapter 2.2.1.4 --- Assay for Residual Cocaine in Maternal Brain --- p.41 / Chapter 2.3 --- Statistics --- p.42 / Chapter 2.4 --- Morphological Studies --- p.42 / Chapter 2.4.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.42 / Chapter 2.5 --- Molecular Genetic Studies --- p.44 / Chapter 2.5.1 --- Material for DNA Insert --- p.44 / Chapter 2.5.1.1 --- "Dopamine Transporter, D2 receptor and β-actin cDNA Probe " --- p.44 / Chapter 2.5.2 --- Preparation for DNA Insert --- p.45 / Chapter 2.5.2.1 --- Competent Cells and Transformation of Plasmid --- p.45 / Chapter 2.5.2.2 --- Growth Transformed Bacteria and Isolation of DNA --- p.46 / Chapter 2.5.2.3 --- Purification of cDNA by Geneclean® II Kit --- p.47 / Chapter 2.5.3 --- Isolation of Total mRNA From Tissue --- p.47 / Chapter 2.5.4 --- Northern Blot Analysis --- p.48 / Chapter 2.5.4.1 --- Analysis of Northern Blots --- p.50 / Chapter 2.5.5 --- In Situ Hybridization --- p.50 / Chapter 2.5.5.1 --- Tissue Preparation --- p.50 / Chapter 2.5.5.2 --- Preparation of Dopamine Transporter Ribroprobe …… --- p.50 / Chapter 2.5.5.3 --- In Situ Hybridization Histochemistry --- p.51 / Chapter CHAPTER III --- RESULTS / Chapter 3.1 --- "Litter Size, Birth Weight and Maternal Weight Gain " --- p.53 / Chapter 3.2 --- Biochemical Studies --- p.53 / Chapter 3.2.1 --- Specific Binding --- p.53 / Chapter 3.2.2 --- Dopamine Transporter - Scatchard Analysis --- p.54 / Chapter 3.2.3 --- Dopamine Receptor --- p.55 / Chapter 3.2.3.1 --- Association Curve --- p.56 / Chapter 3.2.3.2 --- Competitive Curve --- p.57 / Chapter 3.2.3.3 --- Scatchard Analysis --- p.57 / Chapter 3.2.4 --- Dopamine D2 Receptor --- p.59 / Chapter 3.2.4.1 --- Association Curve --- p.59 / Chapter 3.2.4.2 --- Competitive Curve --- p.59 / Chapter 3.2.4.3 --- Scatchard Analysis --- p.59 / Chapter 3.2.5 --- Residual Cocaine Assay in Maternal Brain --- p.61 / Chapter 3.2.5.1 --- Specific Binding --- p.61 / Chapter 3.2.5.1.1 --- Dopamine Transporter --- p.61 / Chapter 3.3.5.1.2 --- Dopamine D1 Receptor --- p.62 / Chapter 3.3.5.1.3 --- Dopamine D2 Receptor --- p.62 / Chapter 3.3 --- Morphological Studies --- p.62 / Chapter 3.3.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.62 / Chapter 3.4 --- Molecular Genetic Studies --- p.63 / Chapter 3.4.1 --- Northern Blot Analysis --- p.63 / Chapter 3.4.1.1 --- Dopamine Transporter --- p.63 / Chapter 3.4.1.2 --- Dopamine D2 Receptor --- p.64 / Chapter 3.4.2 --- In Situ Hybridization --- p.64 / Chapter CHAPTER IV --- DISCUSSION AND CONCLUSION / Chapter 4.1 --- Discussion --- p.65 / Chapter 4.2 --- Conclusion --- p.77 / References --- p.79 / Publications --- p.95