The RET receptor tyrosine kinase has essential roles in cell survival, differentiation, and proliferation. Oncogenic activation of RET causes the cancer syndrome multiple endocrine neoplasia type 2 (MEN 2), and is a frequent event in sporadic thyroid carcinomas. Multiple endocrine neoplasia 2B (MEN 2B), a subtype of MEN 2, is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET), however the molecular mechanisms that lead to the disease phenotype are unclear. In this study, we show that the M918T mutation causes a 10 fold increase in ATP binding affinity, and leads to a more stable receptor-ATP complex, relative to the wildtype receptor. We also show that 2B-RET can dimerize and become autophosphorylated in the absence of ligand. Our data suggest that multiple distinct but complementary molecular mechanisms underlie the MEN 2B phenotype and provide potential targets for effective therapeutics for this disease. In the second part of the study, we identified a novel β-catenin-RET kinase signaling pathway which is a critical contributor to the development and metastasis of human thyroid carcinoma. We show that RET binds to, and tyrosine phosphorylates, β-catenin and demonstrate that the interaction between RET and β-catenin can be direct and independent of cytoplasmic kinases, such as SRC. As a result of RET-mediated tyrosine phosphorylation, β-catenin escapes cytosolic downregulation by the APC/Axin/GSK3 complex and accumulates in the nucleus, where it can stimulate β-catenin-specific transcriptional programs in a RET-dependent fashion. We show that downregulation of β-catenin activity decreases RET-mediated cell proliferation, colony formation, and tumour growth in nude mice. Finally, we used a structure guided approach to identify and characterize a novel, non-ATP competitive, RET inhibitor; SW-01. We show that SW-01 provides significant RET inhibition in an in vitro kinase assay using purified RET. Moreover, RET phosphorylation is blocked, or dramatically reduced, in vivo in cells overexpressing active RET. We observe a significant decrease in cell proliferation and colony formation in RET-expressing cells in the presence of SW-01. Together, our data suggest that SW-01 has potential as a novel RET kinase inhibitor with clinical utility. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2008-09-15 16:20:59.976

Resumo: A citricultura é importante para a economia brasileira devido aos recordes de exportações e pela geração de empregos direto e indireto. O sensoriamento remoto é a fonte primária de informações sobre a cobertura do solo em decorrência dos avanços tecnológicos nos sistemas sensores. A incorporação de procedimentos geoestatísticos em estudos ambientais baseado em técnicas de Krigagem tem sido utilizada por profissionais da área de sensoriamento remoto. O objetivo deste trabalho foi comparar a precisão de métodos de classificação de imagens orbitais na determinação de áreas cultivadas com citros, na Mesoregião de Bauru e Araraquara, através de métodos de sensoriamento remoto e geoestatísticos, para a discriminação e quantificação da área plantada. A área de estudo utilizada nesta pesquisa esta localizada na região central do Estado de São Paulo, com uma área de 56.146,78 ha. Foi utilizado o SIG-SPRING para o processamento dos dados. Foram utilizadas as bandas 2, 3 e 4 da imagem digital proveniente do satélite CBERS 2B, câmera CCD (Câmera Imageadora de Alta Resolução) que fornece imagens com uma resolução espacial de 20 metros. A imagem foi de 16/04/2009, nas órbitas/ponto 157/124 e 157/125. No processo de classificação das imagens foram estudados três métodos de classificação, sendo o CLUSTER não-supervisionado, o MAXVER (Máxima Verossimilhança) e a KI (Krigagem Indicativa) supervisionados, além da classificação em tela tida como verdade terrestre. As fidedignidades das classificações foram avaliadas pelo índice Kappa. Pelos resultados obtidos nas classificações de imagem para a discriminação e quantificação de áreas cultivadas com citros pode-se concluir: os classificadores obtiveram melhor qualidade de classificação para as áreas maiores com CITROS;a Krigagem Indicativa unificou as áreas pequenas de CITROS em uma única área... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The citrus industry is important for the Brazilian economy due to record exports and generating direct and indirect jobs. Remote sensing is the primary source of information on land cover as a result of technological advances in sensor systems. The incorporation of geostatistics procedures in environmental studies based on Kriging techniques has been used by professionals in areas of remote sensing. The aim of this study was to compare the accuracy of classification methods in the determination of satellite images of areas cultivated with citrus, Mesoregião in Araraquara, Bauru, and, through methods of remote sensing and geostatistics to discrimination and quantification of the area planted. The study area used in this research is located in the central region of São Paulo, with an area of 56,146.78 ha. It was used the GIS-SPRING for data processing. We used bands 2, 3 and 4 of the digital image from the satellite CBERS 2B, CCD camera (Camera high resolution image) that provides images with a spatial resolution of 20 meters. The image dated of 04/16/2009, the path/row 157/124 and 157/125. In the process of image classification were studied three methods of classification, and unsupervised clustering, the MLC (Maximum Likelihood) and KI (kriging) supervised classification beyond the screen taken as ground truth. The validation of classifications were evaluated by Kappa index. The results obtained of image classification onto discrimination and quantification of citrus areas were: the classifiers had improved quality of classification for wide citrus areas, the Indicative Kriging unified the small citrus areas in a single area, the Indicative Kriging was the classifier that less classified riparian vegetation area such as citrus, the others changed riparian vegetation by citrus. The validation showed that Indicative Kriging was the classifier which had the lower quality rating than... (Complete abstract click electronic access below) / Orientador: Célia Regina Lopes Zimback / Coorientador: Paulo Milton Barbosa Landim / Banca: Julião Soares de Souza Lima / Banca: Sergio Lazaro de Lima / Mestre

Made available in DSpace on 2014-06-11T19:24:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T20:31:55Z : No. of bitstreams: 1 silva_af_me_botfca.pdf: 1495276 bytes, checksum: fb2de316101ec3a42fe84ea5707baf27 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A citricultura é importante para a economia brasileira devido aos recordes de exportações e pela geração de empregos direto e indireto. O sensoriamento remoto é a fonte primária de informações sobre a cobertura do solo em decorrência dos avanços tecnológicos nos sistemas sensores. A incorporação de procedimentos geoestatísticos em estudos ambientais baseado em técnicas de Krigagem tem sido utilizada por profissionais da área de sensoriamento remoto. O objetivo deste trabalho foi comparar a precisão de métodos de classificação de imagens orbitais na determinação de áreas cultivadas com citros, na Mesoregião de Bauru e Araraquara, através de métodos de sensoriamento remoto e geoestatísticos, para a discriminação e quantificação da área plantada. A área de estudo utilizada nesta pesquisa esta localizada na região central do Estado de São Paulo, com uma área de 56.146,78 ha. Foi utilizado o SIG-SPRING para o processamento dos dados. Foram utilizadas as bandas 2, 3 e 4 da imagem digital proveniente do satélite CBERS 2B, câmera CCD (Câmera Imageadora de Alta Resolução) que fornece imagens com uma resolução espacial de 20 metros. A imagem foi de 16/04/2009, nas órbitas/ponto 157/124 e 157/125. No processo de classificação das imagens foram estudados três métodos de classificação, sendo o CLUSTER não-supervisionado, o MAXVER (Máxima Verossimilhança) e a KI (Krigagem Indicativa) supervisionados, além da classificação em tela tida como verdade terrestre. As fidedignidades das classificações foram avaliadas pelo índice Kappa. Pelos resultados obtidos nas classificações de imagem para a discriminação e quantificação de áreas cultivadas com citros pode-se concluir: os classificadores obtiveram melhor qualidade de classificação para as áreas maiores com CITROS;a Krigagem Indicativa unificou as áreas pequenas de CITROS em uma única área... / The citrus industry is important for the Brazilian economy due to record exports and generating direct and indirect jobs. Remote sensing is the primary source of information on land cover as a result of technological advances in sensor systems. The incorporation of geostatistics procedures in environmental studies based on Kriging techniques has been used by professionals in areas of remote sensing. The aim of this study was to compare the accuracy of classification methods in the determination of satellite images of areas cultivated with citrus, Mesoregião in Araraquara, Bauru, and, through methods of remote sensing and geostatistics to discrimination and quantification of the area planted. The study area used in this research is located in the central region of São Paulo, with an area of 56,146.78 ha. It was used the GIS-SPRING for data processing. We used bands 2, 3 and 4 of the digital image from the satellite CBERS 2B, CCD camera (Camera high resolution image) that provides images with a spatial resolution of 20 meters. The image dated of 04/16/2009, the path/row 157/124 and 157/125. In the process of image classification were studied three methods of classification, and unsupervised clustering, the MLC (Maximum Likelihood) and KI (kriging) supervised classification beyond the screen taken as ground truth. The validation of classifications were evaluated by Kappa index. The results obtained of image classification onto discrimination and quantification of citrus areas were: the classifiers had improved quality of classification for wide citrus areas, the Indicative Kriging unified the small citrus areas in a single area, the Indicative Kriging was the classifier that less classified riparian vegetation area such as citrus, the others changed riparian vegetation by citrus. The validation showed that Indicative Kriging was the classifier which had the lower quality rating than... (Complete abstract click electronic access below)

Förväntat kunskapsbidrag: Matematik 2b är den andra obligatoriska matematikkursen på Samhällsvetenskapsprogrammet och är en av de mest utmanande kurserna på gymnasiet. På det nationella kursprovet i Matematik 2b blir en stor andel av eleverna inte godkända och en mycket liten andel av eleverna får de högsta betygen. Eleverna når inte längre i sin kunskapsutveckling, vilket får konsekvenser både för individerna och för samhället. Vår förhoppning var att kunna bidra med konkreta förslag på hur skolor och speciallärare i matematik kan arbeta förebyggande och därmed hantera Matematik 2b mer framgångsrikt.Syfte och preciserade frågeställningar: Syftet med examensarbetet är att belysa hur elever på Samhällsvetenskapsprogrammet på en gymnasieskola kan nå längre i sin kunskapsutveckling i kursen Matematik 2b.Preciserade frågeställningar:•Vilka utmaningar ser elever, ämneslärare i matematik och skolledare med kursen Matematik 2b?•Vad menar elever, ämneslärare i matematik och skolledare möjliggör att eleverna, i kursen Matematik 2b, når längre i sin kunskapsutveckling?Teori: Den teoretiska utgångspunkten för arbetet var systemteori och ekologisk systemteori med Bronfenbrenners utvecklingsekologiska modell. Tillämpar skolor ett systemiskt perspektiv och därmed ser till helheter gynnar det deras förebyggande arbete. Med Bronfenbrenners modell kan skolans komplexa verklighet synliggöras och analyseras. Elevers lärande och utveckling är beroende av det sammanhang som de befinner sig i.Metod: Studien har en kvalitativ ansats. För att fånga olika uppfattningar om Matematik 2b genomfördes en fokusgruppsintervju med fyra matematiklärare samt enskilda intervjuer med elva elever och en skolledare. Det insamlade materialet koncentrerades för att få fram det väsentliga som därefter kategoriserades under olika teman.Resultat: Studien pekar på att utmaningarna med Matematik 2b är mångfasetterade. Det framkom att det bl.a. kan handla om förkunskaper, förväntningar, motivation, organisation, stödverksamhet och styrdokument. Om problemet är mångfasetterat bör lösningen vara detsamma, ”endast variation kan möta variation”. Ett gediget förebyggande arbete i matematikkursen som föregår Matematik 2b, utmaningar för alla elever, bra studiestrategier, genomtänkt återkoppling, ömsesidigt förtroende mellan lärare och elev och lämplig schemaläggning är några av de möjliga framgångsfaktorerna som identifierades i studien.Implikationer: Ett förebyggande arbete på alla nivåer, både i skolan (individ-, grupp- och skolnivå) och utanför skolan (kommunal- och nationell nivå) kan möjliggöra att elever når längre i sin kunskapsutveckling i Matematik 2b. En viktig pusselbit, för att skolor ska kunna hantera Matematik 2b mer framgångsrikt, kan vara en verksam speciallärare i matematik. Speciallärare kan initiera och leda utvecklingsarbete i matematik, handleda matematiklärare, vara bollplank till skolledning, bistå matematiklärare med undervisningsmaterial, lyfta fram framgångsrika studiestrategier, utforma och ansvara för stödundervisning, verka för att lärare erbjuder elever struktur och samverka med speciallärare i matematik på andra skolor.

Leucoencefalopatia com substância branca evanescente é uma doença geneticamente determinada, causada por mutação no gene do eIF2B. A idade varia do período pré-natal até idade adulta, as manifestações geralmente são desencadeadas por trauma ou infecção. Os sintomas são variáveis, incluem ataxia cerebelar, espasticidade e relativa preservação cognitiva. Os achados de ressonância magnética (RM) são típicos e caracterizam-se por extenso comprometimento da substância branca. Estudamos 10 pacientes, com evolução súbita ou progressiva dos primeiros sintomas, entre 1 a 12 anos de idade. Ataxia e espasticidade estavam presentes em todos os pacientes e funções cognitivas relativamente preservadas. A clínica associada à RM, que demonstrava comprometimento difuso da substância branca, permitiu o diagnóstico / Leukoencephalopathy with vanishing white matter is an inherited disorder caused by mutation in one of five subunits of eIF2B gene. Age of onset varies from prenatal to adulthood and manifestations are commonly triggered by trauma or infection. Symptoms are variable and include cerebellar ataxia and spasticity, with relative sparing of cognitive function. Magnetic resonance imaging (MRI) findings are typically characterized by widespread white matter abnormality. We studied 10 patients, with sudden or slowly progressive symptoms starting between 1-12 years of age. Ataxia and spasticity were present in all patients, and cognitive functions were relatively preserved. MRI studies demonstrated diffuse white matter abnormalities which, combined with clinical findings, allow diagnosis

La pollution atmosphérique constitue de nos jours un enjeu sociétal majeur, tant pour ses conséquences néfastes sur la santé humaine que sur l'environnement. L'objectif général de ce présent travail était de déterminer le niveau de la pollution atmosphérique dakaroise, extérieure et intérieure, et d'évaluer son impact sanitaire au sein de la population urbaine. Les particules fines (PM₂.₅) et une fraction plus grossière (PM>₂.₅) échantillonnées sur un site urbain de Dakar (HLM), caractérisées par de fortes émissions du trafic routier, ont été comparées aux particules échantillonnées dans une zone rurale, Toubab Dialaw, située à environ 40 kms de Dakar. Les caractéristiques physicochimiques des échantillons ont révélé que les particules différaient par leurs propriétés physiques (surface) et chimiques (en termes de CHN, métaux, ions, paraffines, COV et HAP) de 65 à 75 % plus élevées dans les échantillons urbains. Selon les différentes sources et les différentes propriétés physiques et chimiques, la réponse inflammatoire (TNF-α, IL-1β, IL-6, IL-8) et les dommages oxydatifs (protéines carbonylées totales et 8-OHdG) se sont révélés plus importants dans les cellules bronchiques BEAS-2B exposées aux particules urbaines. La campagne de mesure de la qualité de l'air a montré que l'intérieur du bus était plus pollué en PM₁₀, CO, CO₂ et NO que le marché et les sites intérieurs urbains et ruraux. La comparaison de la qualité de l'air entre les sites intérieurs et extérieurs a révélé que, particulièrement dans les zones urbaines, la qualité de l'air intérieur pouvait être moins bonne que celle des sites extérieurs correspondants. Le suivi de l'exposition individuelle aux polluants a montré que les ménagères de la zone urbaine et rurale étaient plus exposées que les professionnels à la pollution de l'air, confirmant les observations précédentes d'un niveau d'exposition potentiellement plus élevé des polluants dans l'environnement intérieur. Cependant, il convient de tenir compte du niveau d'exposition des commerçants et des conducteurs d'autobus résultant de l'échappement du trafic avec des véhicules souvent anciens, mal entretenus et non contrôlés, en raison des niveaux élevés de polluants gazeux rapportés ici. / Air pollution is nowadays a major societal challenge, as much for its harmful consequences on human health as on the environment. The general objective of this work was to determine the level of Dakar air pollution, outdoor and indoor, and to assess its health impact in the urban population. Fine particles (PM₂.₅) and a coarser fraction (PM>₂.₅) sampled at an urban site in Dakar (HLM), characterized by high road traffic emissions, were compared with particles sampled at a rural area, Toubab Dialaw located about 40 km from Dakar. The physicochemical characteristics of samples revealed that PMs differ for their physical (surface area) and chemical properties (in terms of CHN, metals, ions, paraffins, VOCs and PAHs) that were 65 to 75 % higher in urban samples. In accordance with the different sources and different physical and chemical properties, the inflammatory response (TNF-α, IL-1β, IL-6, IL-8) and the oxidative damage (total carbonylated proteins and 8-OHdG) were found higher in bronchial BEAS-2B cells exposed to urban PMs. The air quality measurement campaign showed that the bus interior was more polluted with PM₁₀, CO, CO₂ and NO than the market and the urban and rural indoor sites. The comparison of air quality between indoor and outdoor sites revealed that, particularly in urban areas, indoor air quality may be worse than the corresponding outdoor one. Monitoring individual exposure to pollutants showed that housewives in urban and rural sites were more exposed than professionals to air pollution, confirming previous observations of potential higher individual exposure level to pollutants in indoor environment. However, exposure level of traders and bus drivers that would result from the exhaust of traffic with often old, poorly maintained and uncontrolled vehicles has to be taken into consideration due the higher levels of gaseous pollutants here reported.

Submitted by Priscila Nascimento (pnascimento@icict.fiocruz.br) on 2012-11-26T11:51:30Z No. of bitstreams: 1 luciana-de-santos-almeida.pdf: 1492447 bytes, checksum: fb4ac7dc61ce8aa49ecd3124c10c4ec4 (MD5) / Made available in DSpace on 2012-11-26T11:51:30Z (GMT). No. of bitstreams: 1 luciana-de-santos-almeida.pdf: 1492447 bytes, checksum: fb4ac7dc61ce8aa49ecd3124c10c4ec4 (MD5) Previous issue date: 2009 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. / A Era da Engenharia Genética ou Biotecnologia Moderna, que teve início nos anos 1970, encontra diversas aplicações em vários segmentos de atividades, dentre eles a saúde e alimentos. Na área de saúde têm -se o destaque para a indústria de biofármacos, que tem tido um crescimento acelerado nos últimos anos, pelo fato desses novos medicamentos serem voltados para a terapêutica de doenças que aflige uma parcela considerável da população mundial. Como exemplo pode-se citar o interferon alfa 2b humano recombinante, que faz parte do Programa de Medicamentos de Dispensação Excepcional do Ministério da Saúde, e está incluído no Protocolo Clínico para Hepatite C. Como forma de atender à demanda da população brasileira quanto às necessidades desse biofármaco, Bio-Manguinhos assinou em 2004 um Contrato de Transferência de Tecnologia como o Centro de Engenharia Genética e Biotecnologia de Cuba (CIGB), com o propósito de nacionalizar a produção do referido medicamento. Este trabalho teve como objetivo realizar uma pesquisa qualitativa para elencar os Requerimentos Fundamentais para Transferência, Registro Sanitário, Estabelecimento e Parâmetros de Estabilidade de Bancos de Células de E. coli que expressa o interferon alfa 2b humano recombinante. Foi elaborado um questionário, que serviu como fonte de coleta de dados, que foi enviado por e-mail a diversas Agências Regulatórias e pesquisadores da academia científica. Esse questionário teve como objetivo elencar os principais testes/requisitos que os Bancos de Células devem apresentar. O índice geral de retorno dos questionários foi igual a 39,3%, sendo que o índice de respostas dos pesquisadores foi igual a 62,5% e das Agências Regulatórias igual a 8,3%. O índice de marcação dos itens ficou em torno de 80% e ficou estabelecido que aqueles itens que tiveram um índice maior que 50% seriam os requerimentos indispensáveis a serem descritos. Não foi possível validar o trabalho pelo índice de retorno dos questionários por parte das Agências Regulatórias. Porém, acredita-se que aquilo que foi descrito pode servir como um passo inicial na elaboração de uma norma específica relativa ao Controle de Banco de Células de procariotos, pois representa a opinião de experientes pesquisadores da comunidade científica. E ainda contribuir nos requisitos específicos que serão futuramente estabelecidos pela ANVISA, relativos ao registro de um produto biogenérico/biossimilar. / The Age of Genetic Engineering and Modern Biotechnology, which began in the 1970s, has had several applications in various business activities, among of which are health and food. In health area the emphasis has been on the biopharmaceutical industry that has had a rapid growth in recent years, because these new drugs are aimed towards the therapy of diseases that afflict a significant part of the world’s population. As an example, it can be mentioned the recombinant human interferon-alpha 2b, which is part of the Drugs of Exceptional Dispensation Program of the Ministry of Health, also is it in the Clinical Protocol for Hepatitis C. In order to meet the demand of the Brazilian population for this drug, in 2004, Bio-Manguinhos signed an Agreement on Technology Transfer with the Center for Genetic and Biotechnology Engineering of Cuba (CIGB), so that this medicine could be produced at national level. This study aimed at doing a qualitative research to list the Fundamental Requirements for Transfer, Registration, Establishment and Stability Parameters of Banks of E. coli Cells expressing recombinant human interferon-alpha 2b. A questionnaire was compiled for data collection. It was sent by e-mail to a number of regulatory agencies and researchers of the scientific academy. This questionnaire aimed at listing the main tests / requirements that banks must submit Cells. The overall rate of return of questionnaires was 39.3%, and the rate of responses from researchers was 62.5% and from regulatory agencies was 8.3 %. The rate of items marked was around 80%, then it was agreed that those items that had a rate higher than 50% would be the essential requirements to be described. The work was not validated due to the low rate of return of questionnaires from the Regulatory Agencies. However, it is believed that what was described can serve as the first step in developing a specific standard relating to control the Banks of Prokaryotes Cells, since it represents the expertise opinion of researchers in the scientific community. Yet, it contributes to the specific requirements that shall eventually be established by ANVISA for the registration of a biogeneric / biosimilar product.

Leucoencefalopatia com substância branca evanescente é uma doença geneticamente determinada, causada por mutação no gene do eIF2B. A idade varia do período pré-natal até idade adulta, as manifestações geralmente são desencadeadas por trauma ou infecção. Os sintomas são variáveis, incluem ataxia cerebelar, espasticidade e relativa preservação cognitiva. Os achados de ressonância magnética (RM) são típicos e caracterizam-se por extenso comprometimento da substância branca. Estudamos 10 pacientes, com evolução súbita ou progressiva dos primeiros sintomas, entre 1 a 12 anos de idade. Ataxia e espasticidade estavam presentes em todos os pacientes e funções cognitivas relativamente preservadas. A clínica associada à RM, que demonstrava comprometimento difuso da substância branca, permitiu o diagnóstico / Leukoencephalopathy with vanishing white matter is an inherited disorder caused by mutation in one of five subunits of eIF2B gene. Age of onset varies from prenatal to adulthood and manifestations are commonly triggered by trauma or infection. Symptoms are variable and include cerebellar ataxia and spasticity, with relative sparing of cognitive function. Magnetic resonance imaging (MRI) findings are typically characterized by widespread white matter abnormality. We studied 10 patients, with sudden or slowly progressive symptoms starting between 1-12 years of age. Ataxia and spasticity were present in all patients, and cognitive functions were relatively preserved. MRI studies demonstrated diffuse white matter abnormalities which, combined with clinical findings, allow diagnosis

The main aim of this work was to use traditional mercury electrodes for the development of voltammetric methods of determination of organic xenobiotics and for the electrochemical study of the interaction between double-stranded deoxyribonucleic acid (DNA) and these compounds. In relation to my previous research work (conducted in the framework of my diploma thesis), firstly, 4-nitrobiphenyl (4-NBP), the suspected carcinogen, was studied. Interaction of DNA with 4-NBP was studied using differential pulse voltammetry (DPV), cyclic voltammetry (CV), and chronocoulometry at a hanging mercury drop electrode (HMDE), and using CV and alternating current voltammetry at a DNA modified HMDE. Using CV, the reduction mechanism was investigated. The interaction of DNA with 4-aminobiphenyl (4-ABP), a metabolite of 4-NBP, and 4-NBP reduction intermediates was studied. It was found that the interaction of DNA with 4-NBP or 4-ABP results in a formation of a DNA aggregate with these analytes. The second studied analyte was methyl violet 2B (MV). For determination of MV in a buffered solution were used: direct current tast polarography and differential pulse polarography at a dropping mercury electrode, and direct current voltammetry, DPV, and differential pulse adsorptive stripping voltammetry (DPAdSV) at HMDE. The...

La pollution atmosphérique particulaire constitue un facteur de risque majeur pour la santé humaine. En dépit des nombreuses études réalisées, les mécanismes d'action sous-jacents à l'exposition aux particules et responsables des effets physiopathologiques observés restent encore mal connus. Notre travail a consisté en la collecte d'aérosols particulaires sur 2 sites urbains (Fann et Faidherbe) dans la ville de Dakar (Sénégal) et un site rural (Ngaparou). Les sites urbains sont caractérisés par un trafic automobile dense avec le site de Fann présentant une circulation majoritaire de véhicules de transport en commun alors qu'à Faidherbe le trafic est constitué en majorité de véhicules particuliers. la caractérisation physico-chimique des trois échantillons particulaires a montré une granulométrie fine (96% < 2,5 μm), donc capables de pénétrer profondément dans les poumons, des surfaces spécifiques comprises entre 8 et 13m²/g pouvant adsorber à leur surfaces des substances potentiellement toxiques. Leur composition chimique, riche en éléments inorganiques et organiques, démontre la diversité de leur sources (naturelle et anthropique). Après évaluation de leur cytotoxicité dans les cellules épithéliales bronchiques humaines (BEAS-2B), nous avons montré la capacité de ces aérosols particulaires à induire l'activation métabolique de leur fraction organique par l'induction de l'expression génique des enzymes de métabolisation CYP1A1, 1B1 et NQO1. Nous n'avons pas observé de réponse significative dans le processus d'altération oxydative via la péroxydation lipidique (MDA) et le statut du glutathion (GSSG/GSH). En revanche nous avons montré l'implication de ces aérosols particulaires dans le développement de la réponse inflammatoire par l'expression et la sécrétion significative de cytokines TNF-α, IL-1β, IL-6 et IL-8. / Airborne Particulate Matter (PM) is an important risk factor for human health. In spite of the numerous studies that have been carried out, the underlying mechanisms of action involved in particulate matter physiopathological effects are still unclear. In this work, PM samples were collected in two urban sites (Fann and Faidherbe) in Dakar (Senegal) and in a rural site (Ngaparou). The two urban sites mainly differ in the type of motor vehicles circulating in the area : most of the traffic is made of buses in Fann, whereas they are absent from Faidherbe. The physical characterization of the three samples showed their fine size distribution (96% < 2,5 μm), with surface areas ranging from 8 to 13m²/g. Collected PM were then able to reach deep lung, and to adsorb potentially toxic substances. Their chemical composition, rich in inorganic and organic compounds demonstrated the diversity of emission sources. After assessing their cytotoxicity in human epithelial bronchial cells (BEAS-2B), we showed that these PM could induce gene expression of metabolizing enzymes CYP1A1, 1B1 and NQO1, and therefore the metabolic activation of their organic fraction. No significant response to oxidative damage through lipid peroxidation (MDA) or glutathione status modification (GSSG/GSH) was observed after cells exposure to particulate matter. However, this exposure induced an inflammatory response by a significant increase in expression and secretion of cytokines TNF-α, IL-1β, IL-6 and IL-8.