A Cannabis sativa L., conhecida popularmente no Brasil como maconha, tem sido apontada como a droga de uso ilícito de maior consumo no mundo contemporâneo. As análises toxicológicas utilizadas para verificar o seu uso vem ganhando cada vez maior importância em diversos ambientes de trabalho, desportivos, prisões, clínicas para tratamento de farmacodependência, centros de emergência toxicológica, enfermarias de psiquiatria, entre outros. A presença de canabinóides na urina indica o uso de produtos derivados da planta Cannabis. A maioria dos estudos encontrados na literatura especializada se refere ao perfil de eliminação do 11-nor-&#916 9-THC-COOH, principal produto de biotransformação do &#916 9-THC, que, dependendo da sensibilidade e especificidade da técnica analítica utilizada, poderá ser detectado a longo prazo na urina. Uma constante preocupação é determinar o período de detecção, ou seja, o tempo transcorrido desde a interrupção do uso da droga até a obtenção do primeiro resultado negativo na urina. Este trabalho teve como objetivo investigar o período de detecção de canabinóides urinários em uma população usuária de Cannabis, residentes em uma clínica de tratamento, pela técnica de imunofluorescência polarizada, considerando 50 ng/mL como valor de referência. Foi avaliada a influência do padrão de uso da droga no período de detecção de canabinóides. Entre os pacientes estudados, o período de detecção foi de grande variação: de 33 a 498 horas. Não houve correlação estatística relevante entre o período de detecção e as variáveis freqüência de uso, tempo total de utilização e quantidade de cigarros utilizada na última exposição. / The marijuana, one of the products originated from the Cannabis sativa L., is the illicit used drug of major consume in the world. The toxicological analysis to verify the use of the drug are increasing importance in several workplaces drug-testing programs, sportive, prisions, drug treatment and rehabilitation clinics, emergency toxicology departments and other. The cannabinoids in urine indicates the exposition of products originated from the Cannabis. An important concern is to determine the detection times of cannabinoids in urine i.e. the time from the use of the drug until the first negative result. Most of the studies in the speciallized literature report the elimination profile of the 11-nor-9-carboxy- &#916 9-tetrahydrocannabinol (THCCOOH), which the primary cannabinoid metabolite. According to those studies, the urinary cannabinoids detection times can be made for a long time depending on the sensibility and accuracy of the methods used. The purpose of this work was estudy the detection time of the urinary cannabinoids in the marijuana users population after drug abstaining, by FPIA, using a 50ng/mL cutoff. The pattern in drug use influence on the urinary cannabinoids detection times was evaluated. The detection time in the studied population ranged from 33 to 498 hours. The statistic correlation between the detection time and the drug use pattern was not significant (p&#8804 0,05).

Dans cette thèse, nous construisons un modèle épidémiologique de la dissémina- tion de normes juridiques. L’objectif est d’expliquer la transmission de normes juridiques américaines régissant les tests de dépistages pour drogues au travail vers le Canada ainsi que la propagation subséquente de ces normes à travers la jurisprudence canadienne. La propagation des normes régissant les tests de dépistages pour drogues au travail sert donc à la fois de point de départ pour une réflexion théorique sur la transmission de normes juridiques et pour une étude de cas empirique. Nous partons de la prémisse que les explications du changement juridique, telles celle de la transplantation et celle de l’harmonisation, sont essentiellement métaphoriques. Ces métaphores explicatives fonctionnent en invitant des comparaisons entre les domaines connus et inconnus. Quand ce processus de comparaison est systématisé, la métaphore devient un modèle. Dans la thèse, nous appliquons cette procédure de systématisation afin de transformer la métaphore de la propagation virale en modèle épidémiologique. Après une revue de la littérature sur les épidémies sociales, nous décrivons les éléments pertinents de la théorie épidémiologique pour, ensuite, les transposer au domaine juridique. Le modèle est alors opérationnalisé en l’appliquant à une base de données composée de la jurisprudence pertinente (n=187). Les résultats soutiennent les hypothèses du modèle. 90 % des décisions qui citent les sources américaines sont infectées selon les critères du modèle, alors que seulement 64 % des décisions qui ne citent pas de sources américaines sont infectées. Cela soutient l’hypothèse d’une épidémie dite de « réservoir commun ». Nous avons également démontré une corrélation positive entre la référence à ces décisions et l’état d’infection! : 87 % des décisions qui citent des décisions qui réfèrent aux sources américaines sont infectées, alors que le taux d’infection parmi la population restante est de seulement 53 %. Les résultats semblables ont été obtenus pour les décisions de troisième génération. Cela soutient l’hypothèse selon laquelle il y a eu propagation à travers la jurisprudence suite aux contacts initiaux avec le réservoir commun. Des corrélations positives ont aussi été démontrées entre l’état d’infection et l’appartenance à l’une ou l’autre de sous-populations particulières qui seraient, par hypothèse, des points d’infection. En conclusion de la thèse, nous avançons que c’est seulement après avoir construit un modèle et d’avoir constaté ses limites que nous pouvons vraiment comprendre le rôle des métaphores et des modèles dans l’explication de phénomènes juridiques. / In this thesis, I construct an epidemiological model to explain the transmission of legal norms governing drug testing in the workplace from the United States to Canada and their subsequent spread across the jurisprudence. Employment drug testing norms thus serve as both the starting point for a reflection on how norms spread and a case study for the empirical testing of a theoretical model. I begin with the premise that many explanations of legal change – such as transplant and harmonization – are grounded in metaphors, and then argue that such metaphors work by inviting the hearer to make comparisons between the familiar and the unfamiliar. When this process of comparison is systematized, the metaphor becomes a model. This process of systematization is applied; extending a viral metaphor into an epidemiological model. After reviewing the literature on social epidemics, I set out those aspects of epidemiological theory that may be profitably transposed to the domain of law. I then operationalize the model by applying it to a dataset composed of tribunal decisions (n=187) using computer assisted text analysis. The results support the hypotheses generated by the model. 90% of decisions that cited American sources met the model’s criteria for infection, compared to only 64% of those that didn’t cite American sources. This supports the hypothesis of a common reservoir epidemic. Citation to those infected decisions was also positively correlated to infection: 87% of the citing population was infected, compared to only 53% of the remaining population that cited neither an American source nor one of the infected decisions that cited an American source. Similar results were obtained for third generation decisions. This supports the hypothesis of a serial-transfer epidemic subsequent to contact with the reservoir. Positive correlation to infection was also demonstrated for particular sub-populations hypothesized to be act as points of infection and to a hypothesized vector. In the conclusion, I argue that it is only after we have gone through the process of constructing a model and seen the strengths and limits of its application, that we have access to the full scope of the insights into the role of metaphors and models in the explanation of legal phenomena.

A Cannabis sativa L., conhecida popularmente no Brasil como maconha, tem sido apontada como a droga de uso ilícito de maior consumo no mundo contemporâneo. As análises toxicológicas utilizadas para verificar o seu uso vem ganhando cada vez maior importância em diversos ambientes de trabalho, desportivos, prisões, clínicas para tratamento de farmacodependência, centros de emergência toxicológica, enfermarias de psiquiatria, entre outros. A presença de canabinóides na urina indica o uso de produtos derivados da planta Cannabis. A maioria dos estudos encontrados na literatura especializada se refere ao perfil de eliminação do 11-nor-&#916 9-THC-COOH, principal produto de biotransformação do &#916 9-THC, que, dependendo da sensibilidade e especificidade da técnica analítica utilizada, poderá ser detectado a longo prazo na urina. Uma constante preocupação é determinar o período de detecção, ou seja, o tempo transcorrido desde a interrupção do uso da droga até a obtenção do primeiro resultado negativo na urina. Este trabalho teve como objetivo investigar o período de detecção de canabinóides urinários em uma população usuária de Cannabis, residentes em uma clínica de tratamento, pela técnica de imunofluorescência polarizada, considerando 50 ng/mL como valor de referência. Foi avaliada a influência do padrão de uso da droga no período de detecção de canabinóides. Entre os pacientes estudados, o período de detecção foi de grande variação: de 33 a 498 horas. Não houve correlação estatística relevante entre o período de detecção e as variáveis freqüência de uso, tempo total de utilização e quantidade de cigarros utilizada na última exposição. / The marijuana, one of the products originated from the Cannabis sativa L., is the illicit used drug of major consume in the world. The toxicological analysis to verify the use of the drug are increasing importance in several workplaces drug-testing programs, sportive, prisions, drug treatment and rehabilitation clinics, emergency toxicology departments and other. The cannabinoids in urine indicates the exposition of products originated from the Cannabis. An important concern is to determine the detection times of cannabinoids in urine i.e. the time from the use of the drug until the first negative result. Most of the studies in the speciallized literature report the elimination profile of the 11-nor-9-carboxy- &#916 9-tetrahydrocannabinol (THCCOOH), which the primary cannabinoid metabolite. According to those studies, the urinary cannabinoids detection times can be made for a long time depending on the sensibility and accuracy of the methods used. The purpose of this work was estudy the detection time of the urinary cannabinoids in the marijuana users population after drug abstaining, by FPIA, using a 50ng/mL cutoff. The pattern in drug use influence on the urinary cannabinoids detection times was evaluated. The detection time in the studied population ranged from 33 to 498 hours. The statistic correlation between the detection time and the drug use pattern was not significant (p&#8804 0,05).

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-08-15T12:53:28Z No. of bitstreams: 1 danieljorgesallesdefreitas.pdf: 1825968 bytes, checksum: 13910bdcb0a17f0ed07f3bb10c54361a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-15T12:59:19Z (GMT) No. of bitstreams: 1 danieljorgesallesdefreitas.pdf: 1825968 bytes, checksum: 13910bdcb0a17f0ed07f3bb10c54361a (MD5) / Made available in DSpace on 2017-08-15T12:59:19Z (GMT). No. of bitstreams: 1 danieljorgesallesdefreitas.pdf: 1825968 bytes, checksum: 13910bdcb0a17f0ed07f3bb10c54361a (MD5) Previous issue date: 2017-07-23 / A realização de testes químicos no ambiente de trabalho para identificar o uso de drogas lícitas e ilícitas pelos funcionários é uma prática instituída em muitas empresas de grande porte no Brasil. Esse trabalho aborda o tema sociologicamente e discute questões relacionadas aos testes a partir de pesquisa de inspiração etnográfica realizada dentro de uma empresa mantém um programa de testagem em seus funcionários. Buscando contextualizar o tema no debate sobre as formas de controle social na sociedade contemporânea. Recorre-se à genealogia de poder de Foucault para se construir um referencial analítico que permite descrever os testes de drogas no ambiente de trabalho como práticas de vigilância representativas de um arranjo de poder governamental biopolítico, mecanismos cujos efeitos de poder voltam-se menos para o disciplinamento dos indivíduos do que para a fabricação de tipos específicos de liberdade e a administração das condutas dos sujeitos livres por meio de técnicas atuariais e classificação social. Adotando uma abordagem interpretativa com o objetivo de compreender como os próprios funcionários atribuem sentido aos testes de drogas, a pesquisa empírica enseja uma análise dos valores e significados sociais articulados por tais práticas. Ao final a pesquisa permite delinear algumas novas tendências no controle social contemporâneo, que se apresenta de formas muito mais difusas e descentralizadas, bem como depreender os discursos e os sentidos simbólicos que o legitimam e sustentam. Além disso, o trabalho também pretende contribuir com a questão metodológica apresentando algumas discussões sobre perspectivas e abordagens para pesquisas empíricas sobre a vigilância. Ao compreender como os indivíduos percebem e lidam com essas novas formas de controle social, esse trabalho pretende colaborar com os esforços para se entender melhor a sociedade contemporânea e alguns de seus processos sociais mais desafiadores – como transformações nas concepções de liberdade, responsabilidade individual e segurança. / Workplace drug testing is a common practice in large companies in Brazil. In this work this practice is approached sociologically and questions related to the tests are debated from an ethnographic research held within a specific company that maintains a regular drug testing program on its employees. To contextualize the theme in the debate about forms of social control in contemporary society, Foucault's genealogy of power is used, constructing an analytical framework that allow to describe the workplace drug testing as a surveillance practice representative of the biopolitical governmental power arrangement, a mechanism whose power effects are less focused on disciplining individuals than on fabricate specific types of freedom and on the management of the conduct of free subjects through actuarial techniques and social classification. By adopting an interpretive approach to understand how employees themselves give meaning to the workplace drug testing, empirical research provides an analysis of the values and social meanings articulated by such practices. At the end it is possible to delineate some new tendencies in contemporary social control, which presents itself in much more diffuse and decentralized ways, as well as to understand some discourses and symbolic meanings that legitimize and sustain it. In addition, the paper also aims to contribute to the methodological issue by presenting some discussions on perspectives and approaches to empirical research on surveillance. By understanding how individuals perceive and deal with these new forms of social control, this work seeks to collaborate with efforts to better understand contemporary society and some of its more challenging social processes - such as changes in conceptions of freedom, individual responsibility, and security.

This thesis deals with the influence of the newly synthesized drug on the electrical activity of the isolated heart of rat. Part of the thesis is a theoretical analysis of the use laboratory animals in experiments and ethical aspects related to the use of laboratory animals. There is also an analysis of drug testing, test substances, electrocardiography and methods used to detect and measure ECG signal. The two algorithms used for the QT interval are automated. The QT interval is the main indicator of cardiotoxicity and is considered to be the gold standard in evaluating the effect of the drug. In the practical part the ECG records obtained at the Faculty of Medicine at Masaryk University in Brno are processed. These records are dimmed manually and automatically. The manual dimming was consulted with a specialist in cardiography and statistically processed. Statistical processing served to compare with the results of the automatic ECG measurement. The algorithm is used to automate the measurement, and the results are compared with the reference points obtained from cardiology experts and manual measurement results. This work serves as a pilot study for the development and testing of a new active substance.

Animal testing is still the common method to test the efficacy of new drugs, but tissue engineered in vitro models are becoming more acceptable for replacing and reducing animal testing in anti-cancer drug screening by developing in vitro three-dimensional (3D) tumour models for anti-cancer drug testing. In this study, three-dimensional (3D) culture methods were developed to mimic the tumour microenvironment. 3D culturing is to seed, maintain and expand cultured cells in three-dimensional space, in contrast to the traditional two-dimensional (2D) method in which the cells attach to the bottom of culture containers as monolayers. To mimic the intercellular interplay for tumour study, cell co-culture was applied. In this thesis, perfusion culture showed a better homeostasis for 3D tumour model growth over 17 days, with a more controllable working platform and a more reliable response-dose correlation for data interpretation. In the Matrigel sandwich system, the co-culture of breast cancer cells and endothelial cells demonstrated the morphology featuring a vascular network and tumour structures, with the thickness of the three-dimensional structure around 100µm and tubule length 200-400 µm, and maintained for 10 days. The comparisons studies between Matrigel sandwich and other methods suggest that though not fully characterised, Matrigel is still a valuable scaffold choice for developing co-culture 3D tumour model. Finally, the combination of perfusion and co-culture showed the potential of applying this model in angiogenesis assay, with a drug response profile combining cell viability and morphology to mimic in vivo tumour physiology.

Indiana University-Purdue University Indianapolis (IUPUI) / Human induced pluripotent stem (iPS) cells have the unique ability to differentiate into 200 or so somatic cell types that make up the adult human being. The use of human iPS cells to study development and disease is a highly exciting and interdependent field that holds great promise in understanding and elucidating mechanisms behind cellular differentiation with future applications in drug screening and cell replacement studies for complex and currently incurable cellular degenerative disorders. The recent advent of iPS cell technology allows for the generation of patient-specific cell lines that enable us to model the progression of a disease phenotype in a human in vitro model. Differentiation of iPS cells toward the affected cell type provides an unlimited source of diseased cells for examination, and to further study the developmental progression of the disease in vitro, also called the “disease-in-a-dish” model. In this study, efforts were undertaken to recapitulate the differentiation of distinct retinal cell affected in two highly prevalent retinal diseases, Usher syndrome and glaucoma. Using a line of Type III Usher Syndrome patient derived iPS cells efforts were undertaken to develop such an approach as an effective in vitro model for studies of Usher Syndrome, the most commonly inherited disorder affecting both vision and hearing. Using existing lines of iPS cells, studies were also aimed at differentiation and characterization of the more complex retinal cell types, retinal ganglion cells (RGCs) and astrocytes, the cell types affected in glaucoma, a severe neurodegenerative disease of the retina leading to eventual irreversible blindness. Using a previously described protocol, the iPS cells were directed to differentiate toward a retinal fate through a step-wise process that proceeds through all of the major stages of neuroretinal development. The differentiation process was monitored for a period of 70 days for the differentiation of retinal cell types and 150 days for astrocyte development. The different stages of differentiation and the individually derived somatic cell types were characterized by the expression of developmentally associated transcription factors specific to each cell type. Further approaches were undertaken to characterize the morphological differences between RGCs and other neuroretinal cell types derived in the process. The results of this study successfully demonstrated that Usher syndrome patient derived iPS cells differentiated to the affected photoreceptors of Usher syndrome along with other mature retinal cell types, chronologically analogous to the development of the cell types in a mature human retina. This study also established a robust method for the in vitro derivation of RGCs and astrocytes from human iPS cells and provided novel methodologies and evidence to characterize these individual somatic cell types. Overall, this study provides a unique insight into the application of human pluripotent stem cell biology by establishing a novel platform for future studies of in vitro disease modeling of the retinal degenerative diseases: Usher syndrome and glaucoma. In downstream applications of this study, the disease relevant cell types derived from human iPS cells can be used as tools to further study disease progression, drug screening and cell replacement strategies.