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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
131

Neparlamentní politické strany v procesu mediální komunikace.Komunikační chování neparlamentních stran v ČR před volbami do PSP ČR v roce 2006 / x

Valentová, Hana January 2011 (has links)
This diploma thesis on the "Non-Parliamentary Political Parties in Media Communication Process. Communication Behaviour of Non-Parliamentary Parties in the Czech Republic prior to the Parliamentary Elections of 2006" suggests that political parties wishing to succeed in the dynamically changing media environment today need to present themselves through the refection of contemporary trends in the development of political communication. Based on the hypothesis that the non-parliamentary (i.e. small) political parties fail to master these principles of media and political communication, which is one (but not the single) reason why they fail to reach spectacular results in elections, this diploma thesis investigates four Czech non-parliamentary political parties participating in the parliamentary elections of 2006. The theoretical part of this diploma thesis introduces the current phenomena of political communication, including the mediatisation and personalisation of politics and the concept of politics as entertainment, with a focus on the examples of professionalization of political communication, political marketing and the importance of public opinion. In the practical part of this diploma thesis, the fundamental definitions are used and the method of semiotic analysis applied to the media...
132

Arqueologia guarani na bacia do rio Santo Anastácio-SP: estudo do sítio Célia Maria / Guarani Archaeology the River Basin Santo Anastácio - SP: Study Site Célia Maria

Pereira, David Lugli Turtera 29 February 2012 (has links)
A pesquisa realizada na área do Sítio Arqueológico Célia Maria, localizado na região da Bacia do Rio Santo Anastácio (afluente da Bacia do Paraná), Estado de São Paulo, demonstrou uma ocupação guarani pré-colonial. A cerâmica foi datada por termoluminescência, situando a ocupação em torno de 450±60 anos atrás. Este trabalho traz dados referentes à cerâmica identificada na área do Sítio Célia Maria, que também apresentou três manchas pretas, lítico polido e possível estrutura de combustão. A partir da análise tecno-tipológica da cerâmica, demonstramos a sequência dos gestos técnicos para a produção dos artefatos, assim como reconstituímos graficamente a forma de vasos, a partir de fragmentos de bordas. Essas reconstituições possibilitaram inferir a forma e a função dos antigos recipientes guarani. Os dados espaciais somados às características dos atributos cerâmicos do Sítio Célia Maria foram confrontados com outras pesquisas disponíveis que versaram sobre a presença dos guarani na Bacia do Paraná e Paranapanema. / The research conducted in the archaeological site area Célia Maria, located in the River Basin Santo Anastácio (tributary of the Paraná Basin), State of São Paulo, demonstrated a precolonial Guarani occupation. The pottery was dated by thermoluminescence, standing occupation around 450±60 years ago. This work has data concerning pottery indentified in Site Célia Maria, who also had three black spots, polished lytic and as possible combustion structure. From the techno-typological ceramics analysis, we demonstrated the gestures sequence to the production of technical artifacts, as well as graphically reconstitute the form of vessels, from fragments of edges. These reconstructions allowed inferring the shape and function of the ancient Guarani containers. The data added to the spatial characteristics of ceramics tributes of Site Célia Maria were compared with other available research that focused on the presence of the Guarani in the Basin of Paraná and Paranapanema.
133

Avaliação in vitro da morfologia e da capacidade de paralisação de lesões incipientes de cárie artificialmente induzidas em dentes decíduos após irradiação com Laser de Er:YAG / In vitro morphological assessment and inhibition of artificial incipient caries lesions after Er:YAG laser irradiation on primary teeth

Tashima, Adriana Yuri 29 May 2006 (has links)
O objetivo deste estudo in vitro foi avaliar a morfologia e a paralisação da progressão de lesões de cárie artificiais em esmalte após irradiação da superfície com laser de Er:YAG (KaVo Key II). A amostra (120 blocos de esmalte de dentes decíduos), submetida à ciclagem de pH durante 7 dias, foi divida aleatoriamente entre as fases experimentais. Na fase morfológica os espécimes receberam os seguintes tratamentos: controle (C), laser focado (LC), laser desfocado 3mm (L3), laser desfocado 6mm (L6), e foram preparados para microscopia eletrônica de varredura. Para avaliação da efetividade do laser os espécimes foram divididos entre 9 grupos experimentais: controle negativo (CN), controle positivo (CP), laser focado (LC), laser desfocado 3mm (L3), laser desfocado 6mm (L6), aplicação tópica de flúor (F), LC mais flúor (LCF), L3 mais flúor (L3F) e L6 mais flúor (L6F). Os grupos foram submetidos a novo desafio cariogênico (exceto grupo CN) seguido de preparo para microscopia de luz polarizada. Os dados obtidos foram analisados usando os testes estatísticos ANOVA e LSD. Imagens com lupa estereoscópica também foram realizadas e o resultado submetido aos testes estatísticos Qui-quadrado, Exato de Fisher e teste de concordância. A análise visual e morfológica mostrou ablação superficial da lesão de mancha branca irradiada no grupo LC, aumento de porosidade foi visualizado no grupo L3 assim como ausência de alteração morfológica no grupo L6. Os resultados da microscopia de luz polarizada mostraram que a irradiação do laser mais flúor impediu a progressão da cárie, nos grupos LCF, L3F e L6F e reduziu o corpo da lesão no grupo L6F. Pode-se concluir que a associação entre o laser de Er:YAG desfocado 6mm mais aplicação de flúor diminuiu a profundidade da lesão incipiente de cárie sem ocasionar alteração morfológica e que os demais grupos em que a associação entre laser e flúor estava presente foram efetivos na paralisação das lesões. / The aim of this in vitro study was to evaluate the morphological effects of Er:YAG laser (KaVo Key II) irradiation on artificial enamel caries lesions and its ability to arrest the progression of these lesions. The sample (120 enamel blocks from primary teeth) was previously submitted to pH-cycling and then randomly divided into the groups. In the morphological analysis, the specimens were subdivided into 4 groups: control (C), focused laser (LC), defocused laser 3mm (L3), defocused laser 6mm (L6) and then prepared for scanning electron microscopy. To evaluate the effectiveness of the laser on incipient caries lesions, the specimens were divided into 9 groups: negative control (NC), positive control (PC), focused laser (LC), defocused laser 3mm (L3), defocused laser 6mm (L6), topical fluoride application (F), LC and fluoride (LCF), L3 and fluoride (L3F) and L6 and fluoride (L6F). All groups were submitted once again to ph cycling (except NC) and prepared for polarized light microscopy. ANOVA and LSD statistical tests were used. Images were also observed under stereoscopic loupe and were submitted to Chi-square test, Fishers´ exact test and reproducibility assessment. Visual and morphological evaluations showed that superficial ablation was present on the artificial white spot caries lesions in group LC, porosity increase in group L3 and no morphological alteration in group L6. Results under polarized light microscopy showed that laser irradiation and fluoride was able to arrest the caries progression in groups LCF, L3F and L6F and reduce the lesion´s depth in L6F. In conclusion, it was detected that the association of Er:YAG defocused laser 6mm irradiation and fluoride was able to reduce the depth of the artificial incipient caries lesions without producing any morphological alteration and that the association of laser and fluoride was effective in arresting incipient caries lesions.
134

Programa Cultura Viva: do Governo Federal à Prefeitura de São Paulo

Teixeira, Vinicius Ribeiro Alvarez 07 April 2017 (has links)
Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-04-17T10:43:55Z No. of bitstreams: 1 Vinicius Ribeiro Alvarez Teixeira.pdf: 754035 bytes, checksum: 001d08f97d25e696bc8eb09c393f5c24 (MD5) / Made available in DSpace on 2017-04-17T10:43:55Z (GMT). No. of bitstreams: 1 Vinicius Ribeiro Alvarez Teixeira.pdf: 754035 bytes, checksum: 001d08f97d25e696bc8eb09c393f5c24 (MD5) Previous issue date: 2017-04-07 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / The present work discusses the relationship between State and culture, especially regarding to the called popular traditional cultures. Thereby, it also approaches concepts and precepts that in somehow influence the debate and the course of cultural policies, national or international. As a research object, the study emphasizes the analysis of the themes addressed in the Programa Cultura Viva. The study aimed to understand the path of the program from the policy formulation, in the Ministry of Culture, to its implementation by the city of São Paulo / O presente trabalho discute a relação entre Estado e cultura, sobretudo, no que concerne às chamadas culturas tradicionais populares. Dessa maneira, aborda também conceitos e preceitos que de alguma forma influem no debate e no curso das políticas culturais, seja em âmbito nacional ou internacional. Enquanto objeto de pesquisa, o estudo privilegia a análise dos temas que perpassam o Programa Cultura Viva. Buscou-se compreender a trajetória do programa desde a sua formulação, no Ministério da Cultura, até a sua implementação pela Prefeitura de São Paulo
135

Desenvolvimento de metodologias analíticas para avaliação de cálcio, ferro e zinco ligados a proteínas de tecido hepático de Tilápia do Nilo(Oreochromis Niloticus ) /

Lima, Paula Monteiro de, 1983. January 2010 (has links)
Orientador: Pedro de Magalhães Padilha / Banca: Paulo Roberto Ramos / Banca: Lincoln Carlos de Oliveira / Resumo: No presente trabalho foi feito uma análise qualitativa de cálcio, ferro e zinco em spots de proteínas de amostras de tecido hepático de tilápia do Nilo (Oreochromis niloticus) por Fluorescência de Raios-X de Radiação Síncroton, após a separação das proteínas por Eletroforese Bidimensional em Gel de Poliacrilamida (2D-PAGE). Os espectros de fluorescência obtidos indicaram a presença de cálcio, ferro e zinco em doze, seis e oito spots protéicos das amostras de fígado, respectivamente. Os íons metálicos detectados nas amostras estão distribuídas principalmente em proteínas de massa molar menor que 45 kDa e com pI na faixa de 4,5 a 9,0. Além do cálcio, ferro e zinco foram detectados a presença de enxofre e fósforo, elementos não metálicos, que podem ser constituintes da estrutura das proteínas. As concentrações de cálcio, ferro e zinco ligados às proteínas foram determinadas por FAAS após a mineralização ácida dos spots protéicos, encontrando-se concentrações na faixa de 1,08 a 5,80 mg g-1, 2,02 a 8,03 mm g-1 e 1,60 a 8,55 mg g-1, respectivamente / Abstract: An investigation was made into calcium, iron and zinc in protein spots in samples of Nile tilapia (Oreochromis niloticus) liver tissue obtained after protein separation by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and subsequent qualitative and quantitative evaluation by synchrotron radiation X-ray fluorescence (SRXRF) and graphite furnace atomic absorption spectrometry (FAAS). An analysis of the fluorescence spectra indicated the presence of calcium, iron and zinc in twelve, six and eight liver protein spots, respectively. The metal ions found were distributed mainly in proteins with a molar mass of less than 40.00 kDa and more than 12.00 kDa, with pI in the range of 4.70 to 9.40. The only exception was a spot presenting protein with a molar mass of 10.10 kDa. In addition to calcium, iron and zinc, sulfur and phosphorus - which are non-metals that may be part of the protein structure, were also detected. After microwave-assisted acid mineralization of the proteins spots, a FAAS estimation of the concentration of calcium, iron and zinc bound to these proteins indicated a range of 1.08 to 5.80 mg g-1, 2.02 to 8.03 mg g-1 e 1.60 to 8.55 mg g-1, respectively / Mestre
136

Sinergismo entre eventos clim?ticos extremos, desmatamento e aumento da suscetibilidade a inc?ndios florestais no Estado do Acre / Synergism between extreme weather events, deforestation and increased susceptibility and risk of forest fires in Acre state

Tostes, Juliana de Oliveira 29 February 2016 (has links)
Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2016-10-25T11:21:37Z No. of bitstreams: 1 2016 - Juliana de Oliveira Tostes.pdf: 4618564 bytes, checksum: 951350c8676b3f82092fedfc3a9e0f79 (MD5) / Made available in DSpace on 2016-10-25T11:21:37Z (GMT). No. of bitstreams: 1 2016 - Juliana de Oliveira Tostes.pdf: 4618564 bytes, checksum: 951350c8676b3f82092fedfc3a9e0f79 (MD5) Previous issue date: 2016-02-29 / This research analyzes the temporal and spatial variables that can affect the distribution and frequency of hot spots in the state of Acre. Given the scarcity of regular spatial information and long time series for the study area, it was initially carried out a validation between air temperature and precipitation data in Global Grid Precipitation Climatology Centre (GPCC), University of Delaware (UDEL) and Global Historical Climatology Network (GHCN) with data from five Weather Stations Mainstream (EMC) to Acre and region, through an analysis of precision and accuracy of the data. Regarding precipitation, it was found that both the GPCC UDEL represented as the average variability significantly throughout the series. In relation to the air temperature standards, although the accuracy of GHCN and UDEL was low, it was satisfactory accuracy according to statistical methods. Assuming that the extreme weather events increase susceptibility to forest fires, then it was carried out an analysis of the influence of climate variability modes in generating categorized scenarios dry or wet years, based on the Standardized Precipitation Index (SPI) and Harmonic and Spectral (AHE). It was found that the AHE is not able to identify the intensity of the events, but was satisfactory in the signal cycles identifying the anomaly, i.e., whether the abnormality SPI was positive or negative. It was found that the Atlantic signal had greater influence on the precipitation of the Pacific. For the regions that correspond to Groups 1, 2 and 3 there was an inverse pattern for precipitation in relation to ENSO compared to the North and East Amazon. Thus, it identified negative precipitation anomalies during La Ni?a and El Ni?o events during positive events for the dry and rainy seasons. For the area corresponding to the effect Group 4 was otherwise. The natural climate variability patterns identified in this study may contribute to the establishment of strategies for prevention and adaptation to extreme events. Finally, in Chapter 3 was carried out an analysis of the spatial and temporal patterns of the fire in Acre, through a discussion of various climatic, environmental and anthropogenic variables that contribute to its occurrence. Thus, through the Random Forest algorithm were generated susceptibility maps that estimated the probability of fires and burned in the state. . It was found that although drought triggers an increase in the number of hot spots, its spatial pattern is more related to human factors such as the proximity areas already cleared. / A presente pesquisa analisa as vari?veis temporais e espaciais que podem afetar a distribui??o e frequ?ncia dos focos de calor no estado do Acre. Diante da escassez de dados regularmente espacializados e com longa s?rie temporal para a ?rea de estudo, inicialmente foi realizada uma valida??o entre os dados de temperatura do ar e precipita??o em grade do Global Precipitation Climatology Centre (GPCC), Universidade de Delaware (UDEL) e Global Historical Climatology Network (GHCN) com dados de cinco Esta??es Meteorol?gicas Convencionais (EMC) para o Acre e regi?o, atrav?s de uma an?lise da precis?o e exatid?o dos dados. Em rela??o ? precipita??o, verificou-se que tanto o GPCC quanto da UDEL representaram significativamente as variabilidades m?dias ao longo da s?rie. Em rela??o aos padr?es da temperatura do ar, embora a precis?o do GHCN e da UDEL tenha sido baixa, a exatid?o foi satisfat?ria segundo os m?todos estat?sticos. Partindo do pressuposto que os eventos clim?ticos extremos aumentam a suscetibilidade a inc?ndios florestais, em seguida foi realizada uma an?lise da influ?ncia dos modos de variabilidade clim?tica na gera??o de cen?rios categorizados de anos secos ou ?midos, baseado no ?ndice de Precipita??o Padronizado (SPI) e na An?lise Harm?nica e Espectral (AHE). Verificou-se que a AHE n?o foi capaz de identificar a intensidade dos eventos, mas mostrou-se satisfat?ria na identifica??o dos ciclos de sinal da anomalia, ou seja, se anomalia do SPI foi positiva ou negativa. Verificou-se que o sinal do Atl?ntico teve maior influ?ncia sobre a precipita??o do que o Pac?fico. Para as regi?es que correspondem os Grupos 1, 2 e 3 observou-se um padr?o inverso para a precipita??o em rela??o ao ENOS, quando comparado com a Amaz?nia Norte e Oriental. Assim, foram identificadas anomalias negativas de precipita??o durante eventos de La Ni?a e positivas durante eventos de El Ni?o para as esta??es seca e chuvosa. Para a regi?o que corresponde ao Grupo 4 o efeito foi contr?rio. Os padr?es de variabilidade natural do clima identificados nesse trabalho podem contribuir para o estabelecimento de estrat?gias de preven??o e adapta??o aos eventos extremos. Finalmente, no Cap?tulo 3 foi realizada uma an?lise sobre o padr?o espacial e temporal do fogo no Acre, atrav?s de uma discuss?o sobre diversas vari?veis clim?ticas, ambientais e antr?picas que contribuem para a sua ocorr?ncia. Assim, por meio do algoritmo Random Forest foram gerados mapas de suscetibilidade que estimaram a probabilidade de ocorr?ncia de inc?ndios e queimadas no estado. Verificou-se que, embora a estiagem propicie um aumento do n?mero de focos de calor, o seu padr?o espacial est? mais relacionado a fatores antr?picos, tais como a proximidade de ?reas j? desmatadas.
137

Avaliação in vitro da morfologia e da capacidade de paralisação de lesões incipientes de cárie artificialmente induzidas em dentes decíduos após irradiação com Laser de Er:YAG / In vitro morphological assessment and inhibition of artificial incipient caries lesions after Er:YAG laser irradiation on primary teeth

Adriana Yuri Tashima 29 May 2006 (has links)
O objetivo deste estudo in vitro foi avaliar a morfologia e a paralisação da progressão de lesões de cárie artificiais em esmalte após irradiação da superfície com laser de Er:YAG (KaVo Key II). A amostra (120 blocos de esmalte de dentes decíduos), submetida à ciclagem de pH durante 7 dias, foi divida aleatoriamente entre as fases experimentais. Na fase morfológica os espécimes receberam os seguintes tratamentos: controle (C), laser focado (LC), laser desfocado 3mm (L3), laser desfocado 6mm (L6), e foram preparados para microscopia eletrônica de varredura. Para avaliação da efetividade do laser os espécimes foram divididos entre 9 grupos experimentais: controle negativo (CN), controle positivo (CP), laser focado (LC), laser desfocado 3mm (L3), laser desfocado 6mm (L6), aplicação tópica de flúor (F), LC mais flúor (LCF), L3 mais flúor (L3F) e L6 mais flúor (L6F). Os grupos foram submetidos a novo desafio cariogênico (exceto grupo CN) seguido de preparo para microscopia de luz polarizada. Os dados obtidos foram analisados usando os testes estatísticos ANOVA e LSD. Imagens com lupa estereoscópica também foram realizadas e o resultado submetido aos testes estatísticos Qui-quadrado, Exato de Fisher e teste de concordância. A análise visual e morfológica mostrou ablação superficial da lesão de mancha branca irradiada no grupo LC, aumento de porosidade foi visualizado no grupo L3 assim como ausência de alteração morfológica no grupo L6. Os resultados da microscopia de luz polarizada mostraram que a irradiação do laser mais flúor impediu a progressão da cárie, nos grupos LCF, L3F e L6F e reduziu o corpo da lesão no grupo L6F. Pode-se concluir que a associação entre o laser de Er:YAG desfocado 6mm mais aplicação de flúor diminuiu a profundidade da lesão incipiente de cárie sem ocasionar alteração morfológica e que os demais grupos em que a associação entre laser e flúor estava presente foram efetivos na paralisação das lesões. / The aim of this in vitro study was to evaluate the morphological effects of Er:YAG laser (KaVo Key II) irradiation on artificial enamel caries lesions and its ability to arrest the progression of these lesions. The sample (120 enamel blocks from primary teeth) was previously submitted to pH-cycling and then randomly divided into the groups. In the morphological analysis, the specimens were subdivided into 4 groups: control (C), focused laser (LC), defocused laser 3mm (L3), defocused laser 6mm (L6) and then prepared for scanning electron microscopy. To evaluate the effectiveness of the laser on incipient caries lesions, the specimens were divided into 9 groups: negative control (NC), positive control (PC), focused laser (LC), defocused laser 3mm (L3), defocused laser 6mm (L6), topical fluoride application (F), LC and fluoride (LCF), L3 and fluoride (L3F) and L6 and fluoride (L6F). All groups were submitted once again to ph cycling (except NC) and prepared for polarized light microscopy. ANOVA and LSD statistical tests were used. Images were also observed under stereoscopic loupe and were submitted to Chi-square test, Fishers´ exact test and reproducibility assessment. Visual and morphological evaluations showed that superficial ablation was present on the artificial white spot caries lesions in group LC, porosity increase in group L3 and no morphological alteration in group L6. Results under polarized light microscopy showed that laser irradiation and fluoride was able to arrest the caries progression in groups LCF, L3F and L6F and reduce the lesion´s depth in L6F. In conclusion, it was detected that the association of Er:YAG defocused laser 6mm irradiation and fluoride was able to reduce the depth of the artificial incipient caries lesions without producing any morphological alteration and that the association of laser and fluoride was effective in arresting incipient caries lesions.
138

Modélisation et estimation du trafic intracellulaire par tomographie de réseaux et microscopie de fluorescence

Pecot, Thierry 15 March 2010 (has links) (PDF)
Cette thèse traite de l'analyse et de la simulation du trafic vésiculaire sur des séquences d'images de microscopie de fluorescence. À contre-courant des approches habituelles exploitant un suivi individuel des vésicules, nous avons développé une approche globale (tomographie de réseaux) inspirée de travaux antérieurs sur l'analyse du trafic routier et l'analyse du trafic sur des réseaux de télécommunications. Cette approche repose sur l'utilisation de comptages locaux de vésicules couplés à une procédure de routage qui permettent d'estimer les trajectoires globales des vésicules sur l'ensemble d'une séquence d'images. Contrairement aux précédentes applications de la tomographie de réseaux, les comptages et le routage sont également des inconnues du problème. Afin de mesurer les comptages locaux de vésicules, nous avons développé une méthode de séparation des composantes “objet” et “fond” dans des séquences de microscopie de fluorescence. Cette méthode exploite un terme de détection non local reposant sur la similarité entre motifs de l'image et utilise la composante “fond” estimée comme “référence” pour améliorer la détection des vésicules. Par ailleurs, la procédure de routage dépend des données observées. Dans le cas de l'estimation du trafic, le routage est établi à partir du comptage des vésicules ; dans le cas de simulations, le routage est contrôlé par l'utilisateur. La génération de séquences synthétiques a permis d'évaluer quantitativement la méthode d'estimation du trafic vésiculaire. Cette méthode a égale- ment été évaluée sur des séquences d'images réelles de microscopie dans le cadre d'une étude précise sur le transport membranaire et le trafic vésiculaire régulé par des isoformes de la protéine Rab6.
139

Development of Field-adapted Analytical Methods for the Determination of New Antimalarial Drugs in Biological Fluids

Lindegårdh, Niklas January 2003 (has links)
<p>This thesis deals with the development of analytical methods for the determination of new antimalarial drugs in biological fluids. The goal was to develop methods that facilitate clinical studies performed in the field, such as capillary blood sampling onto sampling paper.</p><p>Methods for the determination of atovaquone (ATQ) in plasma, whole blood and capillary blood applied onto sampling paper were developed and validated. </p><p>Automated solid-phase extraction (SPE) and liquid chromatography (LC) with UV absorbance detection was used to quantify ATQ. Venous blood contained higher levels of ATQ than capillary blood after a single dose of Malarone (ATQ + proguanil).</p><p>Ion-pairing LC was used to separate amodiaquine (AQ), chloroquine (CQ) and their metabolites on a CN-column. A method for quantification of AQ, CQ and their metabolites in capillary blood applied onto sampling paper was developed and validated. Perchloric acid and acetonitrile were used to facilitate the extraction of the analytes from the sampling paper. The liquid extract was further cleaned by SPE.</p><p>Methods for the determination of piperaquine (PQ) in plasma and whole blood using SPE and LC were developed and validated. Addition of trichloroacetic acid (TCA) to the samples prior to injection into the LC-system significantly enhanced the efficiency for the PQ peak. Serum and whole blood contained higher levels (about 300 nM) of PQ than plasma (about 200 nM) after a single oral dose of 340 mg PQ. This indicates that PQ may be taken up in the leucocytes and thrombocytes.</p>
140

Development of Field-adapted Analytical Methods for the Determination of New Antimalarial Drugs in Biological Fluids

Lindegårdh, Niklas January 2003 (has links)
This thesis deals with the development of analytical methods for the determination of new antimalarial drugs in biological fluids. The goal was to develop methods that facilitate clinical studies performed in the field, such as capillary blood sampling onto sampling paper. Methods for the determination of atovaquone (ATQ) in plasma, whole blood and capillary blood applied onto sampling paper were developed and validated. Automated solid-phase extraction (SPE) and liquid chromatography (LC) with UV absorbance detection was used to quantify ATQ. Venous blood contained higher levels of ATQ than capillary blood after a single dose of Malarone (ATQ + proguanil). Ion-pairing LC was used to separate amodiaquine (AQ), chloroquine (CQ) and their metabolites on a CN-column. A method for quantification of AQ, CQ and their metabolites in capillary blood applied onto sampling paper was developed and validated. Perchloric acid and acetonitrile were used to facilitate the extraction of the analytes from the sampling paper. The liquid extract was further cleaned by SPE. Methods for the determination of piperaquine (PQ) in plasma and whole blood using SPE and LC were developed and validated. Addition of trichloroacetic acid (TCA) to the samples prior to injection into the LC-system significantly enhanced the efficiency for the PQ peak. Serum and whole blood contained higher levels (about 300 nM) of PQ than plasma (about 200 nM) after a single oral dose of 340 mg PQ. This indicates that PQ may be taken up in the leucocytes and thrombocytes.

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