Much research in recent years for evidence evaluation in forensic science has focussed on methods for determining the likelihood ratio in various scenarios. One proposition concerning the evidence is put forward by the prosecution and another is put forward by the defence. The likelihood of each of these two propositions is calculated, given the evidence. The likelihood ratio, or value of the evidence, is then given by the ratio of the likelihoods associated with these two propositions. The aim of this research is twofold. Firstly, it is intended to provide methodology for the evaluation of the likelihood ratio for continuous autocorrelated data. The likelihood ratio is evaluated for two such scenarios. The first is when the evidence consists of data which are autocorrelated at lag one. The second, an extension to this, is when the observed evidential data are also believed to be driven by an underlying latent Markov chain. Two models have been developed to take these attributes into account, an autoregressive model of order one and a hidden Markov model, which does not assume independence of adjacent data points conditional on the hidden states. A nonparametric model which does not make a parametric assumption about the data and which accounts for lag one autocorrelation is also developed. The performance of these three models is compared to the performance of a model which assumes independence of the data. The second aim of the research is to develop models to evaluate evidence relating to traces of cocaine on banknotes, as measured by the log peak area of the ion count for cocaine product ion m/z 105, obtained using tandem mass spectrometry. Here, the prosecution proposition is that the banknotes are associated with a person who is involved with criminal activity relating to cocaine and the defence proposition is the converse, which is that the banknotes are associated with a person who is not involved with criminal activity relating to cocaine. Two data sets are available, one of banknotes seized in criminal investigations and associated with crime involving cocaine, and one of banknotes from general circulation. Previous methods for the evaluation of this evidence were concerned with the percentage of banknotes contaminated or assumed independence of measurements of quantities of cocaine on adjacent banknotes. It is known that nearly all banknotes have traces of cocaine on them and it was found that there was autocorrelation within samples of banknotes so thesemethods are not appropriate. The models developed for autocorrelated data are applied to evidence relating to traces of cocaine on banknotes; the results obtained for each of the models are compared using rates of misleading evidence, Tippett plots and scatter plots. It is found that the hiddenMarkov model is the best choice for themodelling of cocaine traces on banknotes because it has the lowest rate of misleading evidence and it also results in likelihood ratios which are large enough to give support to the prosecution proposition for some samples of banknotes seized from crime scenes. Comparison of the results obtained for models which take autocorrelation into account with the results obtained from the model which assumes independence indicate that not accounting for autocorrelation can result in the overstating of the likelihood ratio.

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in the expression of ΔFosB, a member of the Fos family of transcription factors, through activation of neuronal nicotinic receptors. We used mice as a model system to investigate the effects of adolescent nicotine exposure on responses to cocaine, amphetamine, and morphine in adulthood. We found that exposure to nicotine during the early phase of adolescence (postnatal day 28) enhanced cocaine CPP, acute locomotor activity, and locomotor sensitization in adulthood. Our data demonstrate that nicotine priming effects on cocaine are affected by the dose, duration, method of administration, age of exposure, and mouse strain. These data strongly suggest that nicotine intake during adolescence may cross-sensitize the brain to the rewarding effects of cocaine. A follow-up study was undertaken to determine if this enhancement applies to other drugs of abuse. The repeated exposure to 0.5 mg/kg nicotine (subcutaneous) during early adolescence resulted in significant enhancement of amphetamine and morphine preference in a CPP test, but had no effect on the somatic signs of morphine withdrawal. In addition, we investigated the possible neuronal mechanisms underlining enhancements to behavioral responses using both in vivo and in vitro techniques. Our results showed that nicotinic antagonists, with varying subtype selectivity, administered during adolescence prior to nicotine exposure diminished cocaine enhancement in CPP. This suggests that the enhancement of cocaine behavioral responses is mediated by neuronal nicotine receptors (mainly β2* and α7). Finally, studies of ∆FosB revealed significant effects of age and nicotine pre-treatment in nucleus accumbens (NAc), but not in the prefrontal cortex (PFC). Indeed, nicotine pre-treatment was able to significantly increase ∆FosB levels in NAc of early adolescent mice compared to adult mice. This accumulation of ∆FosB persisted for several weeks. Further studies are needed to fully examine the mechanisms of action underlying the observed changes in cocaine rewards.

Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. Furthermore, it activates a neurobiological mechanism that is shared by many drugs of abuse, which will increase susceptibility to their rewarding effects. The work in this thesis contributes to the further understanding of this critical developmental period. Conditioned-place-preference, acute locomotor and locomotor sensitization pardigms were used to examine changes in cocaine sensitivity in adulthood. Testing was performed on adult ICR mice that were exposed to nicotine (0.1 or 0.5 mg/kg, S.C., b.i.d.) or saline during adolescence (postnatal days 28 or 46) or adult (postnatal day 70). Data showed that a 7-day exposure to the higher dose of nicotine (0.5 mg/kg) altered cocaine-induced responses. In contrast, neither 1 day exposure nor a low dose of nicotine (0.1 mg/kg) elicited this effect. A follow-up study was undertaken to determine if this enhancement generally applies to other drugs of abuse. Pre-exposure to 0.5mg/kg nicotine during early adolescence demonstrated significant enhancement to morphine reward, but it failed to increase d-amphetamine preference in a CPP model. Further research will be required in order to more fully examine the mechanisms of action for the observed changes in cocaine rewards. In summary, these findings suggest that early adolescent nicotine exposure leads to changes in cocaine reward and sensitivity during adulthood in both dose and duration matters. Indeed, the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

Thesis advisor: Stephen C. Heinrichs / This study investigated the effects of baclofen, a GABAB agonist, on modulating drug seeking and drug reward in a novel model of reinstatement. To investigate drug seeking, rats were trained to nosepoke for cocaine infusions, given a drug holiday, and under a baclofen pretreatment (0, 0.2, 1, or 5 mg/kg i.p.), were exposed to an odor conditioned discriminative stimulus (DS+) that reinstated cocaine self-administration. To investigate drug reward, an odor reactivity test was used. Rats were tested for changes in odor preference after the acquisition, drug holiday, and reinstatement phases of self-administration behavior were each completed. Pretreatment with the low dose of baclofen (0.2) attenuated cocaine seeking primed by a conditioned DS+. Medium doses (1.0) caused no change in drug seeking. High doses (5.0) caused a reduction in drug seeking, but this was due to motor impairment. No doses of baclofen had any affect on the rewarding properties of cocaine or cocaine-associated stimuli. It can be concluded that GABAB receptors have no role in modulating the rewarding properties of drug rewards or drug-associated stimuli, but instead play a role in modulating drug seeking. In rats that were exposed to a drug in the past, low levels of GABAB receptor activation reduce drug-seeking, while medium to high levels could have reduced dopamine levels to the point that increased drug seeking or motor impairment was seen. / Thesis (BA) — Boston College, 2004. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology. / Discipline: College Honors Program.

O estudo teve por objetivo avaliar o us o de c ocaína e/ou de crack e suas possíveis relações com os aspectos biológicos, psicológicos e sociais. Trata-se de um estudo do tipo transversal, de ab ordagem quantitativa. O estudo foi desenvolvido no CAPSad de Ribeirão Preto, SP, por meio de uma amostra de conveniência composta por 95 clientes do serviço, sendo 42 (44,2%) usuários de cocaína e 53 (55,8%) de crack. Os instrumentos de coleta de dados foram: Informações sociodemográficas, Escala de Severidade da D ependência de Drogas (SDS), Cocaine Craving Questionnaire-Brief (CCQ-B), Severity Alcohol Dependence Data (SADD), Inventário das Consequências do Beber (DrInC) e o Addiction Severity Índex (ASI6). A análise de dados foi realizada empregando- se os testes t de Student, para amostras independentes, o de correlação de Pearson e S pearman. A amostra foi composta predominantemente por usuários do sexo masculino, adultos, solteiros, cor branca, com baixo nível de escolaridade, religião católica e t rabalhos informais, sem diferença entre os grupos. Não houve diferenças entre usuários de cocaína e de crack para droga de maior uso, idade do primeiro uso, tempo, em anos e dias, de consumo da droga, uso de álcool no padr ão binge (na vida), níveis de gr avidade da dependência do álcool e da f issura. Os usuários de crack apresentaram maiores níveis de s everidade da de pendência da droga, avaliada tanto segundo a escala SDS quanto do ASI6. O uso de drogas e o suporte familiar e social constituíram as áreas mais prejudicadas entre esses usuários (p<=,005). Correlações entre os escores das áreas: uso de drogas (r=0,33, p<,000), psiquiátrica (r=0,27, p.<,007), legal/justiça (r=0,23, p<,024), suporte familiar/social do ASI e os escores do SDS foram baixas e estatisticamente significativas. Encontrou-se ainda uma correlação negativa entre as áreas do ASI-6: uso de dr ogas (r=-,36, p<,000), uso de álcool (r=-0,29, p<,003), legal/justiça (r=-,23, p<,024), e, positiva, entre a área família (r=0,24,p<,005) e o nível de gravidade da fissura. A escala DrInC correlacionou apenas com a área uso do álcool (ASI6). Correlações também foram identificadas entre a maioria das áreas do ASI6; no entanto, foram exceções as áreas família e emprego/financeira. A idade correlacionou com as áreas, uso de drogas (r=- 0,25, p<,014), legal/justiça (r=-0,21, p<,04) de forma negativa; e, positiva entre com a área médica do ASI6 (r=0,43, p<,000). As consequências do beber não se diferenciaram entre os usuários de cocaína e crack. Houve uma correlação positiva entre o escore total do ASI, a SDS e do DrinC, mas contrariamente aos escores do CCQ-B total. A idade correlacionou com as consequencas do beber (DrInC) e com os níveis de gravidade da dependência do álcool (SADD). Pode se concluir que a relação entre o uso de cocaína e/ou crack e os aspectos biológicos, psicológicos e s ociais são complexas e multidimensionais. Assim, avaliar as peculiaridades relacionadas ao uso de cocaína e crack possibilitou identificar elementos cruciais nos aspectos de saúde e sociais que podem contribuir, de maneira mais apropriada, no norteamento e planejamento da assistência com qualidade a essa população. / The aim in this study was to evaluate cocaine and/or crack use and its possible relations with biological, psychological and social aspects. A cross-sectional study with a quantitative approach was undertaken. The research was developed at the CAPSad in Ribeirão Preto, SP, Brazil, using a convenience sample of 95 service clients, 42 (44.2%) of whom were cocaine users and 53 (55.8%) crack users. The data collection instruments were: Sociodemographic information, Severity of Dependence Scale (SDS), Cocaine Craving Questionnaire-Brief (CCQ-B), Severity Alcohol Dependence Data (SADD), Drinker Inventory of Consequences (DrInC) and t he Addiction Severity Index (ASI-6). For data analysis, Student\'s t-test was used, and Pearson and Spearman\'s correlation test for independent samples. The sample predominantly included male, adult, white users with low education levels, Catholic and active in informal work, without any difference between the groups. No differences were found between cocaine and crack users with regard to the most used drug, age of first use, duration of drug consumption, in years and days, binge drinking (in life), severity levels of alcohol dependence and craving. Crack users showed higher severity levels of drug dependence, assessed according to the SDS and ASI6. Drugs use and family and social support were the most impaired areas among these users (p<=.005). Correlations between area scores: drugs use (r=0.33, p<.000), psychiatric (r=0.27, p<.007), legal/justice (r=0.23, p<.024), family/social support on the ASI and SDS scores were low and s tatistically significant. In addition, a neg ative correlation was found between ASI-6 areas: drugs use (r=-.36, p<.000), alcohol use (r=-0.29, p<.003), legal/justice (r=-.23, p<.024), and a positive correlation between the family area (r=0.24,p<.005) and the severity level of the craving. The DrInC scale was only correlated with the alcohol use area (ASI-6). Correlations were also identified among most ASI-6 areas; exceptions were the family and employment/financial areas. Age was negatively correlated with drugs use (r=- 0.25, p<.014), legal/justice (r=-0.21, p<.04), and positively with the medical area of the ASI-6 (r=0.43, p<.000). No distinctions in drinking consequences were found between cocaine and crack users. A positive correlation was found between total ASI score, SDS and DrInC, but opposed to total CCQ-B scores. Age was correlated with drinking consequences (DrInC) and with alcohol dependence severity levels (SADD). In conclusion, the relation between cocaine and/or crack use and biological, psychological and social aspects are complex and multidimensional. Therefore, assessing the peculiarities of cocaine and crack use permitted the identification of crucial elements in health and social aspects, which can contribute more appropriately to guide and plan quality care to this population

Submitted by PPG Psicologia (psicologia-pg@pucrs.br) on 2018-03-21T13:20:05Z No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-04-03T20:11:47Z (GMT) No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) / Made available in DSpace on 2018-04-03T20:22:52Z (GMT). No. of bitstreams: 1 TES_BRENO_SANVICENTE_VIEIRA.pdf: 6222146 bytes, checksum: d1e5e710fc5ec0e52c03bb4ffe92d0f8 (MD5) Previous issue date: 2018-03-07 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / In Brazil, 1.4% of the population reports lifetime use of smoked cocaine (crack). The use of the drug relates to social and economic issues for society and poses serious health problems, including early death. Crack cocaine use disorder (CUD) is the medical condition which refers the pathological use of the drug. CUD relates to several negative outcomes such as higher rates of HIV and HCV infections, familiar problems and crime involvement, in addition to a higher prevalence of concurrent mental disorders. Scientific agendas promote evidence-based studies as a need for better therapeutics. In this regard, some gaps in the field require attention. In this line, distinct factors confer vulnerability for crack cocaine use in males and females: more males use the drug (a 3:1 proportion), but females show a faster transition from initial drug use to CUD. The course of the disease also show differences; females report a higher craving for the drug, while males have more frequent involvement with violent crimes. Thus, scientific commitments highlight a calling for the integration of those biopsychosocial models that consider individual characteristics in addition to those who consider addictive disorders as ?brain diseases.? A more consistent interdisciplinary integration of knowledge from classical theories in combination with advances provided for technologic methods is a promising route. Hence, the aim of this doctoral thesis was to investigate sex differences in crack cocaine users. To address the main objective, the thesis has two studies with groups of participants diagnosed with CUD and hospitalized for drug detoxification. These two groups were one of males (CK-M) and a second of females (CK-F). Study 1 had as its objective to get a picture of sex differences in the psychosocial profile. Study 2 had as its objective the identification of sex differences in brain functioning level. Study 1 had 798 CK-M and 546 CK-F. Results consistently revealed CK-M as having a more severe alcohol use history and higher rates of concurrent alcohol use disorder than CK-F. On the other hand, CK-F showed an earlier crack cocaine use onset, higher drug use severity, and more familiar and work problems along with a higher prevalence for lifetime mental disorders. Particularly, CK-F showed higher rates for trauma and stress. Study 2 had a sample of 80 participants: CK-M (n = 20), CK-F (n = 20), a group of males (HC-M, n = 20), and another of healthy female controls (HC-F, n = 20). Participants did a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The method makes it possible to investigate temporal associations between nonspatially related brain areas by using as a measure fluctuations in the blood oxygen-level dependent (BOLD) level. It is an indirect measure of energy consumption, and by testing those correlations, functional connectivity (FC) can be investigated. Results supported CK-M as having an overall higher intra- and internetwork FC, while CK-F showed an overall lower FC in this regard. Taking both studies, the conclusions of this thesis point toward the existence of sex differences in all biopsychosocial domains. Thus, the interpretation of studies in crack cocaine use, particularly those testing interventions, need to resemble the possible existence of sex differences. Therefore, a hope from studies like this is that sex-specific models for crack cocaine use and CUD emerge and become tested. Similarly, possible interventions, also need to be aware of such backgrounds and consider possible sex differences when developing interventions, researches and public health policies as well. / No Brasil, cerca de 1.4% da popula??o refere j? ter feito uso de coca?na atrav?s de sua forma fumada (crack). O uso da droga gera repercuss?es sociais e econ?micas para a sociedade, al?m de ser um grave problema de sa?de relacionado, inclusive, com a morte precoce. Considerando o Transtorno por Uso de Coca?na (TUC) a manifesta??o patol?gica relacionada ao uso da droga, alguns dos desfechos desfavor?veis incluem: maiores taxas de infec??o por HIV e HCV; problemas judiciais e familiares, al?m maior preval?ncia de transtornos mentais em comorbidade. Iniciativas cient?ficas estimulam que propostas baseadas em evid?ncias sejam realizadas na tentativa de melhores resultados para o tratamento e preven??o do TUC. Neste sentido, maiores aprofundamentos em lacunas do conhecimento na ?rea s?o importantes. Assim, homens e mulheres possuem fatores de vulnerabilidade ao uso da droga distintos: Mais homens usam coca?na (propor??o de 3:1), mas mulheres apresentam uma evolu??o mais r?pida ao TUC ap?s o in?cio do uso. O curso da doen?a tamb?m ? diferente, mulheres sentem mais fissura pela droga, enquanto homens tem mais consequ?ncias relacionadas a crimes violentos. Assim sendo, iniciativas cient?ficas destacam a necessidade de integra??o de modelos biopsicossociais, que levem em conta as caracter?sticas individuais, mas que tamb?m considerem transtornos aditivos ?doen?as do c?rebro?, favorecendo a interdisciplinaridade entre antigas e robustas bases te?ricas e avan?os tecnol?gicos. Neste sentido, o objetivo desta tese foi investigar diferen?as entre homens e mulheres usu?rios de crack. Para tanto, dois estudos foram realizados com grupos de portadores de TUC internados para desintoxica??o do uso de crack, tendo sempre um grupo de homens (TUC-H) e outro de mulheres (TUC-M). No Estudo 1, o objetivo foi tra?ar um claro perfil de diferen?as psicossociais e de gravidade do uso de drogas, enquanto no Estudo 2 o objetivo foi identificar a exist?ncia de diferen?as em um n?vel de funcionamento cerebral. O Estudo 1 teve 798 TUC-H e 546 TUC-M. Resultados identificaram robustas diferen?as, com TUC-H possuindo uma hist?ria mais grave de uso de ?lcool, bem como uma maior preval?ncia para o transtorno por uso de ?lcool. Em contrapartida, TUC-M apresentam uma idade mais precoce do in?cio do uso de crack, maior severidade do uso de drogas em geral, preju?zos mais significativos nas esferas de trabalho e fam?lia, al?m taxas mais altas de preval?ncia de transtornos mentais (em especial transtornos relacionados a trauma e estresse). No Estudo 2, com 80 participantes al?m dos grupos TUC-H (n = 20) e TUC-M (n=20), participaram 20 homens saud?veis e 20 mulheres saud?veis. O m?todo utilizado foi um exame de Resson?ncia Magn?tica funcional (fMRI) em estado de repouso (rs-fMRI). Rs-fMRI permite avaliar associa??es na flutua??o do sinal BOLD (blood oxygen-level dependente, do ingl?s n?vel dependente de oxig?nio no sangue), que ? uma medida indireta de consumo energ?tico, entre ?reas cerebrais anatomicamente distintas, o que ? aceito como um dado de conectividade funcional (CF). Os resultados indicaram que de maneira geral, TUC-H apresentam um aumento na CF entre diferentes redes cerebrais, enquanto TUC-F apresentam redu??o na CF. Com base nos resultados, a tese conclui que homens e mulheres usu?rios de crack apresentam diferen?as em caracter?sticas que permeiam todos os dom?nios biopsicossociais, o que deve ser considerado ao levar em conta interpreta??es de estudos na ?rea e, principalmente, ao planejarem-se poss?veis interven??es no futuro. Portanto, espera-se que modelos sexo-espec?ficos para o uso de coca?na e do TUC sejam formulados, bem como que interven??es, pesquisas e inclusive pol?ticas de sa?de p?blica considerem poss?veis diferen?as em suas fundamenta??es.

O abuso da cocaína representa atualmente um dos grandes problemas mundiais de saúde pública. A utilização de análises toxicológicas para verificar a exposição à cocaína é de grande interesse social pois possibilita que medidas de prevenção e controle sejam adotadas. Um dos indicadores biológicos da exposição à cocaína é a benzoilecgonina pois é o principal produto de biotransformação encontrado na urina. Entretanto, as propriedades físico-químicas da benzoilecgonina dificultam sua análise por técnicas cromatográficas empregadas em Laboratórios de Toxicologia. Extrações líquido-líquido não fornecem bons índices de recuperação e há a necessidade de derivação da benzoilecgonina para posterior análise por cromatografia em fase gasosa. No trabalho, a aplicação de extração em fase sólida seguida da conversão de benzoilecgonina em cocaína com diazometano possibilitou a padronização do método, utilizando as técnicas de cromatografia em fase gasosa associada à espectrometria de massa, cromatografia em fase gasosa com detector de nitrogênio-fósforo e cromatografia em camada delgada de alta eficiência. Amostras provenientes de usuários de cocaína foram submetidas ao método padronizado e em todas foi possível a detecção de cocaína pelas técnicas cromatográficas utilizadas. / Cocaine abuse is now representing one of the greatest world public health problem. Great social interests have been generated with the using of toxicological analyses with the aim of detecting cocaine exposure to adopt prevention and control measures. Benzoylecgonine, the main metabolite found in urine, is one of the biological markers of cocaine exposure. However, its physical-chemical properties make the chromatographic analyses of this substance a difficult task. Liquid-liquid extraction of this analyte from biological sample does not provide good recovery and the derivatization of benzoyleconine for further detection by gas chromatography is a need. In this study, the application of solid phase extraction followed by benzoylecgonine conversion into cocaine with diazomethane made the standardization of the method possible. The following techniques were used: gas chromatography/ mass spectrometry (GC/MS), gas chromatography/ nitrogen-phosphorous detection (GC/NPD) and high performance thin-Iayer chromatography (HPTLC). Samples collected from cocaine abusers were submitted to the standardized extraction and derivatization techniques. Cocaine was detected in ali samples when chromatography was applied.

Violence is a dreadful phenomenon spread throughout the world, resulting in unfortunate events that can ultimately cause death. It is known that some countries play a much worrying role in this scenario than others. Brazil is one of them. The present study has focused on identifying the use of cocaine within 105 postmortem cases arriving at the Institute of Legal Medicine of São Paulo (IML-SP) through analytic toxicological methods and latter applying genetic testing to see whether the presence of certain single nucleotide polymorphisms (SNPs) is more predominant within users rather than non-users, which would help to better understand one\'s susceptibility to abuse the drug. Both blood and hair samples have been analysed through ultra-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) in order to distinguish between recent or chronic cocaine use among violent individuals whose violence has ultimately leaded to their death. Two dilute-and-shoot methods have been validated and used for this purpose, and the final residue was analysed through the UPLC-ESIMS/ MS system. From the 105 postmortem cases, a rather high proportion of cocaine and its metabolites was found. A chronic use of the drug was denoted in 53% of the cases, which were positive for cocaine and benzoylecgonine, followed by 43% for norcocaine, 40% for cocaethylene and 13% for anhydroecgonine methyl ester, in hair. As for blood, reflecting the use of cocaine prior to death, 51% of the cases have shown to be positive for benzoylecgonine, followed by 41% for cocaine, 23% for cocaethylene and 20% for norcocaine. These findings suggest a probable association between the use of the drug and risky/violent behaviours. Genetic wise, a significant difference has been observed for SNP rs4263329 from the BCHE gene in its dominant model, with higher frequencies of the genotypes A/G and G/G seen in cocaine users rather than non-users (OR=8.91; 95%CI=1.58-50.21; &#961;=0.01). Likewise, also SNP rs6280 from the DRD3> gene presented a significant association in both its additive and dominant model, suggesting that the C allele may be playing a role in cocaine use as both genotypes T/C and C/C were significantly more frequent in users than non-users. This association was not lost when adjusted for covariants using logistic regression (OR=4.96; 95%CI=1.07; &#961;=0.04). Finally, a statistically significant association (&#961; = 0.003) was also encountered among individuals with both A/G and G/G genotypes within SNP rs4263329 and the use of cocaine HCl (f(A/G+G/G)=44.7%) versus crack-cocaine (f(A/G+G/G)=7.7%) and nonusers (f(A/G+G/G)=16.2%). In conclusion, this study has found significant associations within two SNPs related to cocaine use, however, due to several inherent limitations, these must be confirmed by further studies with a higher number of subjects and within a more controlled setting. Definite assumptions may not be made at this point and future researches are to be conducted. / A violência é um fenômeno aterrador espalhado por todo o mundo, resultando em eventos que podem, em última instância, causar a morte. Sabe-se que, em alguns países esse cenário é mais preocupante que em outros. O Brasil é um deles. O presente estudo teve como objetivo identificar o uso de cocaína em 105 casos postmortem provenientes do Instituto de Medicina Legal de São Paulo (IML-SP) por meio de métodos toxicológicos analíticos e posterior aplicação de testes genéticos para verificar se a presença de determinados polimorfismos de nucleotídeo único (SNPs) é mais predominante dentro dos usuários do que dos não usuários, o que explicaria uma possível suscetibilidade de um indivíduo ao abuso da droga. Amostras de sangue e cabelo foram analisadas através de cromatografia líquida de ultra-eficiência acoplada a espectrometria de massas e ionização por electrospray (UPLC-ESI-MS/MS) para distinguir entre uso recente ou crônico de cocaína entre indivíduos violentos cuja violência levou à sua morte. Para tal, dois métodos de extração baseados na técnica de \"dilute-and-shoot\" foram validados e utilizados para esse fim, e o resíduo final foi analisado através de um sistema UPLC-ESI-MS/MS. Dos 105 casos postmortem, foi encontrada uma proporção significativa de cocaína e seus produtos de biotransformação. O uso crônico da droga foi denotado em 53% dos casos, sendo estes positivos para cocaína e benzoilecgonina, seguidos de 43% para norcocaína, 40% para cocaetileno e 13% para anidroecgonina metil éster, no cabelo. Quanto ao sangue, refletindo o uso de cocaína antes da morte, 51% dos casos mostraram-se positivos para benzoilecgonina, seguido de 41% para cocaína, 23% para cocaetileno e 20% para norcocaína. Esses dados corroboram a hipótese provável da relação entre o uso da droga e comportamentos de risco/violentos. Quanto à genética, uma diferença significativa foi observada para o SNP rs4263329 do gene BCHE em seu modelo dominante, com maiores frequências dos genótipos A/G e G/G vistos em usuários de cocaína ao contrário de não usuários (OR=8,91; 95%IC=1,58-50,21; &#961;=0,01). Da mesma forma, também o SNP rs6280 do gene DRD3 apresentou uma associação significativa tanto no seu modelo aditivo quanto dominante, sugerindo que o alelo C pode estar desempenhando um papel no uso de cocaína, pois ambos os genótipos T/C e C/C foram significativamente mais frequentes nos usuários do que não usuários. Essa associação não foi perdida quando ajustada para co-variáveis usando regressão logística (OR=4,96; 95%IC=1,07; &#961;=0,04). Finalmente, uma associação estatisticamente significativa (&#961;=0,003) também foi encontrada entre indivíduos com ambos os genótipos A/G e G/G dentro do SNP rs4263329 e o uso de cocaína HCl (f(A/G + G/G)=44,7%) versus crack (f(A/G + G/G)=7,7%) e não usuários (f(A/G + G/G)=16,2%). Em conclusão, este estudo encontrou associações significativas em dois SNPs relacionados ao uso de cocaína, no entanto, devido a várias limitações inerentes, estas devem ser confirmadas por mais estudos com um maior número de indivíduos e dentro de um cenário mais controlado. Hipóteses definitivas não poderão ser feitas neste momento e futuras pesquisas devem ser conduzidas.

O uso indiscriminado de substâncias psicoativas por motoristas e suas conseqüências no trânsito têm sido objeto de grande preocupação por parte de especialistas e da sociedade em geral. O Código de Trânsito Brasileiro de 1997 determina como infração gravíssima \"dirigir sob a influência de álcool, em nível superior a seis decigramas por litro de sangue, ou de qualquer substância entorpecente ou que determine dependência física ou psíquica\". Desta forma, o presente trabalho teve como intuito investigar a utilização da saliva como espécime biológico para verificar o uso de álcool e drogas (anfetamina, metanfetamina, cocaína e maconha) por motoristas no trânsito. Para alcançar esse objetivo, um método foi desenvolvido e validado para determinação seriada desses analitos em uma única alíquota de saliva, utilizando a técnica de headspace e a microextração em fase sólida (SPME). Amostras coletadas aleatoriamente de motoristas de caminhão (n=561) que trafegavam em rodovias de São Paulo foram submetidas ao método proposto. Do total de amostras de saliva analisadas, 17 (3,0%) apresentaram resultado positivo, sendo 8 para etanol, 4 para anfetamina, 2 para cocaína, 2 para tetraidrocanabinol (THC) e 1 para cocaína e THC. A pesquisa retrata de forma pioneira no Brasil a utilização da saliva como possível amostra biológica para monitorar motoristas que estariam dirigindo sob a influência de drogas. / The consequences of car accidents in the traffic when psychoactive drugs are abused by professional drivers are of great concern of specialists in the subject as well as of the general population. For the Brazilian Traffic Code of 1997 to drive under the influence of alcohol, with blood leveI superior to six decigrams per liter, or any other psychoactive drug which causes physical or psychic dependence is considered an infraction in which the transgressor is subject to heavy penalties. The objective of this work was to investigate the possibilities of using saliva as biological samples to screen the use of alcohol and drugs (amphetamine, methamphetamine, cocaine and marijuana) by traffic drivers. In order to achieve this aim, a method was developed and validated for the serial determination of those analites in a single aliquot of a saliva sample. Gas-chromatographic/ headspace for the determination of alcohol and solid phase microextraction (SPME) for the determination of the other drugs were used in the analyses. Samples collected at random from truck drivers (n=561) in public roads in the city of São Paulo were analyzed by the proposed method. The obtained results were: 17 (3.0%) of all analyzed saliva samples were found to be positive, being 8 for ethanol, 4 for amphetamine, 2 for cocaine, 2 for tetrahydrocannabinol (THC) and 1 for cocaine and THC simultaneously. This study pioneered in Brazil the use of saliva as a very convenient biological sample to screen individuaIs driving under the influence of drugs