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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.
81

Dengue and development: a critical political ecology

Mulligan, Kate 04 1900 (has links)
<p>Policies for the control of dengue fever often construct the mosquito-borne virus as a disease of poverty, and call for disease control through “development” to meet the needs of poor populations and impoverished or unsanitary spaces. However, exceptions to the narrative of a rich/poor dengue divide persist in non-poor urban environments across the world. One example is Malaysia's new administrative capital city of Putrajaya – a wealthy and centrally planned new city with among the highest rates of dengue in the country.</p> <p>This dissertation drew on theories of ecosocial epidemiology and urban political ecology to investigate and contextualize the geography of dengue and development in Putrajaya. Key informant interviews and critical discourse analysis found that infectious disease control fell well below other urban priorities for the city, and that globally dominant dengue control strategies targeted toward poor populations were inappropriately transferred to Putrajaya's non-poor local environment. A systematic review of the research literature found no clear evidence showing an association between dengue and conditions of poverty. These findings challenge conventional thinking by policy makers about epidemiological transition and the social determinants of health.</p> <p>The dissertation addresses the dearth of research into the world's neglected tropical diseases (NTDs); in particular, gaps in our understanding of the biopolitical and socioecological contexts (sites of urban governance, sites of health policy development and implementation, and sites of academic research) in which policies for NTDs like dengue are determined, enacted and justified. The dissertation further identifies non-poor urban environments – in particular those undergoing rapid development, such as Putrajaya – as key spaces for future geographic and political ecological research related to epidemiological transition, economic development and the social and environmental determinants of health.</p> / Doctor of Philosophy (PhD)
82

Improvement of global access to life-saving medicines : facing the future

Versteynen, Leo January 2010 (has links)
This research, with the main focus on HIV/AIDS, tuberculosis and malaria, was based on data from the literature, and on questionnaire and interview surveys with the main stakeholders: authorities, drug-developers and NGOs/foundations. It revealed the following determinants, which contributed to the occurrence of drug pricing conflicts in Brazil, Thailand and South Africa: governmental constitutional commitments to supply medicines to poor people, the existence of a local pharmaceutical industry capable of producing generic versions of patented medicines and long histories of disease treatment programmes. The research documented the preferred approaches to increase global access to life-saving medicines for the next decade, which were found to be: public-private-partnerships, prevention measures, dedication of >0.5% of GNP to poor countries, and improvement of national healthcare/insurance systems. Those approaches were integrated into a conceptual framework, which could enable country-level organizations to move beyond the conflict mentality via a 'Public-Private-Partnership for gradual Self-Sufficiency and Sustainability Model,' (P3S3). Within this framework, rich countries should invest >0.5% of their GNP to help to alleviate poverty in poor countries. With these funds, national governments should implement programmes to expand implementation of disease prevention measures and improve national - 4 - healthcare/insurance systems and the quality of the medicines involved. Public-private-partnerships should act as 'steering-and-controlling' organizations to guide the process and to minimise corruption. As a positive message to all who currently lack access to these medicines, the thesis author's conclusion is that the use of this model could help to turn the current unsustainable development policies into sustainable ones, and as a consequence, it would contribute to improvements in the quality of life of millions of people in poor countries.
83

Síntese e desenvolvimento de métodos analíticos para o estudo de pró-fármacos dendriméricos potencialmente ativos em doenças negligenciadas / Synthesis and analytical methods development to study dendrimeric prodrugs potentially actives in neglected diseases.

Paes, Lorena Cristine 11 November 2016 (has links)
Doenças infecciosas parasitárias consideradas negligenciadas representam um grande problema de saúde pública em muitos países e regiões. Os fármacos disponíveis na terapêutica são, em geral, tóxicos e de eficácia discutível. Portanto, a descoberta e o planejamento de novos quimioterápicos são extremamente necessários. Neste contexto, os pró-fármacos dendriméricos podem ser úteis. Porém, é necessário esforço adicional para viabilizar os custos, simplificar as estratégias de síntese e investigar os comportamentos de liberação. Ademais, é importante a melhoria dos métodos analíticos, dos métodos de purificação e identificação dos produtos de síntese, para a determinação das propriedades físico-químicas e atividade biológica, visando à efetiva aplicação desta tecnologia. Face ao exposto, o objetivo deste trabalho foi estudar a identidade, pureza e liberação de dois potenciais pró-fármacos dendriméricos, baseados em 3- hidroxiflavona, planejados para serem ativos em doença de Chagas e leishmaniose. O primeiro, estruturalmente, contendo inositol como núcleo e ramos constituídos por éster da 3- hidroxiflavona com ácido málico e o segundo, estruturalmente contendo o dendrímero PAMAM-G0 (poliamidoamina de geração inicial) como transportador e ácido succínico como espaçante. Desenvolveram-se métodos adequados à determinação da 3-hidroxiflavona por HPLC-UV (Cromatografia líquida de alto desempenho, com detecção no ultravioleta) e MEKC (Cromatografia eletrocinética micelar). Comparando-se esses métodos, o método por HPLC foi mais sensível, preciso e exato na quantificação da 3-hidroflavona, enquanto o método por eletroforese capilar foi mais rápido e de menor custo. O éster da 3-hidroxiflavona com o ácido málico mostrou-se instável em soluções orgânicas, aquosas em diferentes pH e nas condições reacionais de diversas estratégias de síntese avaliadas, o que impediu a obtenção do dendrímero baseado em inositol como núcleo conforme proposto. Já o dendrímero PAMAM-G0 funcionalizado com 3-hidroxiflavona foi sintetizado, purificado e caracterizado com sucesso. Não se observou liberação da 3-hidroxiflavona a partir desse dendrímero em solução gástrica simulada (pH 1,2) e a mesma foi lenta em soluções tampão com pH entre 5,0 e 8,5, a 37,0 ºC. Ensaios de atividade biológica do PAMAM-G0-SUC-3-OH-FLAV em amastigotas de Trypanosoma cruzi, cepas Y(Curitiba) e Y(SS), comparativamente ao benznidazol e ao nifurtimox, mostraram atividade moderada e baixa seletividade. / Infectious parasitoses considered neglected diseases represent a great health problem for many countries and areas. Drugs available in the therapeutics are, generally, toxics and do not have good efficacy. So, the discovery and design of new chemotherapeutic agents are extremely needed. In this context, dendrimeric prodrugs may be useful. However, additional effort is required to make the costs accessible, to simplify the synthetic strategies and to investigate the behavior of cleavage. The improvement of analytical methods, purification methods and identification of synthetic products, in order to determine the physicochemical properties and bioactivity aiming to effectively implement this technology, is also required. Based on foregoing considerations, the objective of this work was to study the identity, purity and drug release of two potential dendrimeric prodrugs, based on 3-hydroxyflavone, designed to be active in leishmaniasis and Chagas disease. The first structurally contains myo-inositol as the core and branches consisting of esters from 3-hydroxyflavone with malic acid. The second structurally contains PAMAM-G0 dendrimer (initial generation polyamidoamine) as carrier and succinic acid as spacer. Suitable analytical methods for determining 3-hydroxyflavone by HPLC-UV (High Performance Liquid Chromatography) and MEKC (Micellar Electrokinetic Chromatography) have been developed. Comparing these methods, HPLC method showed more sensitivity, precision and accuracy in the quantification of 3-hydroxyflavone, while the capillary electrophoresis method was faster and less expensive. The ester of 3-hydroxyflavone with malic acid showed to be unstable in organic and aqueous solutions, at different pH and at reaction conditions of synthetic strategies evaluated, which prevented the obtaining of dendrimer based on mio-isositol as core. Notwithstanding, PAMAM-G0 dendrimer funcionalized with 3- hydroxyflavone was synthesized, purified and characterized successfully. There were no 3- hydroxyflavone releases from this dendrimer in simulated gastric fluid (pH 1.2) and a slow release was observed in buffer solutions with pH between 5.0 and 8.5, at 37.0 ºC. Submitted to biological assays in amastigotes of two strains of T. cruzi, Y(Curitiba) and Y(SS), compared to benznidazole e nifurtimox, PAMAM-G0-SUCC-3-OH-FLAV showed moderated activity and low selectivity index.
84

Estudos in vitro e in vivo da atividade leishmanicida de novos derivados sintéticos / Studies in vitro and in vivo of the leishmanicidal activity of noval sintetic derivatives

Queiroz, Aline Cavalcanti de 26 February 2015 (has links)
The arsenal of drugs available for treating Leishmania infections is limited and presents high toxicity. Therefore, new, effective, and less toxic leishmaniasis treatments are still needed. In this work, two series of derivatives, containing a semicarbazone or hydrazide-N- acylhydrazone scaffolds was designed and synthetized as protease inhibitors. From these series, derivatives LASSBio 1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 highlighted, showing in vitro and in vivo leishmanicidal activities. Thus, these derivatives presented a potent leishmanicidal activity against amastigotes of L. major (IC50 of 1.5 µΜ to LASSBio 1483, 8.5 µΜ to LASSBio 1705 and 1.,9 µΜ to LASSBio 1707) , L. amazonensis (IC50 of 3.5 µΜ to LASSBio 1483 and 84.0 µΜ to LASSBio 1736), L. braziliensis (IC50 of 31.7 µΜ to LASSBio 1483, 8.0 µΜ to LASSBio 1705 and 5.3 µΜ to LASSBio 1736) and L. chagasi (IC50 of 53.3 µΜ to LASSBio 1707 and 57,6 µΜ to LASSBio 1736). Also, the leishmanicidal activity of derivatives LASSBio-1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 were mediated via induction of apoptosis as evidenced by externalization of phospholipids, despolarization of mitochondrial membrane and elevation of activation of caspases. The ultrastructural morphological effects against the parasite of LASSBio 1483 and LASSBio 1736 against L. chagasi promastigotes were also verified. The treatment of L. amazonensis -infected BALB/c mice with derivatives LASSBio 1483 (effect of 30.5% and 33.3% in infected ear, by p.o and i.p., respectively), LASSBio 1705 1483 (effect of 58.5% in infected ear and 61.1% in lymph node, i.p.), LASSBio 1707 (effect of 56.5% in lymph node, i.p.) and LASSBio 1736 (effect of 53.6% in infected ear, i.p.)or the treatment of L. chagasi - infected hamsters with LASSBio 1707 (effect of 53.6, i.p.)and LASSBio 1736 (effect of 46.0%, i.p.) led to a significant reduction of parasite burden when compared to controls that received PBS. The treatment with these derivatives did not result in hepatic or renal toxicity in these animals models of leishmaniasis. These data make LASSBio 1483, LASSBio 1705, LASSBio 1707 and LASSBio 1736 new lead-candidates against cutaneous and visceral leishmaniasis. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O arsenal de fármacos disponíveis para o tratamento das infecções por Leishmania spp. é limitada e de elevada toxicidade. Portanto, novos tratamentos, eficazes e menos tóxicos para leishmaniose ainda são necessários. Neste trabalho, duas séries de derivados contendo as subunidades semicarbazona ou hidrazida-N-acilhidrazona foram desenhados e sintetizados como inibidores de proteases. A partir destas séries, os derivados LASSBio 1483, LASSBio 1705, LASSBio 1707 e LASSBio 1736 se destacaram, mostrando atividade leishmanicida in vitro e in vivo . Assim, esses derivados apresentaram atividade leishmanicida potente contra amastigotas de L. major (CI 50 de 1,5 µΜ para LASSBio 1483, 8,5 µΜ para LASSBio 1705 e 15,9 µΜ para LASSBio 1707) , L. amazonensis (CI 50 de 3,5 µΜ para LASSBio 1483 e 84,0 µΜ para LASSBio 1736) , L. braziliensis (CI 50 de 31,7 µΜ para LASSBio 1483, 8,0 µΜ para LASSBio 1705 e 5,3 µΜ para LASSBio 1736) e L. chagasi (CI 50 de 53,3 µΜ para LASSBio 1707 e 57,6 µΜ para LASSBio 1736). Além disso, a atividade leishmanicida dos derivados LASSBio 1483, LASSBio 1705, LASSBio1707 e LASSBio 1736 foi mediada via indução de apoptose como evidenciado pela externalização de fosfolipídeos de membrana, despolarização da membrana mitocondrial e ativação de caspases. Os efeitos morfológicos ultra-estruturais de LASSBio 1483 e LASSBio 1736 em promastigotas de L. chagasi também foram verificados. O tratamento de camundongos BALB/c infectados por L. amazonensis com os derivados LASSBio 1483 (efeito de 30,5% e 33,3% na orelha infectada, por v.o. e i.p., respectivamente), LASSBio 1705 (efeito de 58,1% na orelha infectada e de 61,1% no linfonodo, i.p.) , LASSBio 1707 (efeito de 56,5% no linfonodo, i.p.) e LASSBio 1736 (efeito de 38,8% na orelha infectada , i.p.) ou o tratamento de hamsters infectados por L. chagasi com LASSBio 1707 (efeito de 53,6%, i.p.) e LASSBio 1736 (efeito de 46,0%, i.p.), na dose de 30 µmols/kg/dia, levaram a uma redução significativa da carga parasitária quando comparados aos controles que receberam PBS. O tratamento com estes derivados não resultaram em toxicidade hepática ou renal nestes modelos animais de leishmaniose. Estes dados fazem de LASSBio-1483, LASSBio-1705, LASSBio-1707 e LASSBio-1736 novos candidatos a protótipos a fármacos contra leishmaniose cutânea e visceral
85

Saúde pública, inovação farmacêutica e propriedade intelectual: o desenvolvimento de um novo medicamento contra a malária no Brasil / Public Health, pharmaceutical innovation and intelectual property: the development of a new medicine against malaria in Brazil

Koichi Kameda de Figueiredo Carvalho 06 September 2012 (has links)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Esta dissertação tem como objetivo estudar a relação entre propriedade intelectual, inovação e saúde pública, com foco na análise do consórcio farmacêutico para desenvolvimento do medicamento combinação em dose fixa artesunato-mefloquina (ASMQ) contra a malária. A concepção dessa iniciativa se insere num momento histórico, final dos anos 1990 e início dos anos 2000, em que estudos apontaram a insuficiência da pesquisa e desenvolvimento para as doenças negligenciadas. Na época, o cenário da malária era particularmente preocupante, dada a disseminação de resistência aos medicamentos disponíveis e à falta de perspectiva do lançamento de novos produtos contra a doença. Para proteger a última classe de antimaláricos eficazes, a saber,os derivados a base de artemisinina, uma estratégia encontrada foi a do recurso à terapia combinada a base de artemisinina (artemisinin based combination therapy ACT). Contudo, dos 4 ACTs recomendados pela OMS em 2001, apenas 1 se encontrava disponível no mercado. O projeto FACT foi então criado, em 2002, com o propósito de desenvolver dois novos ACTs artesunato-mefloquina e artesunato-amodiaquina. O consórcio do ASMQ, por suas especificidades, em particular a produção de inovação por um laboratório público do Sul e a circulação Sul-Sul de conhecimentos e tecnologias , o tornam de interesse para estudos nos campos da bioética e da saúde pública; tendo sido, por isso, escolhido como objeto desta dissertação. O estudo se apoiou em pesquisa bibliográfica, de fundamental relevância para a compreensão dos problemas de acesso e de disponibilidade de novos produtos para doenças negligenciadas, decorrentes de um modelo de inovação farmacêutica sustentado em patentes. De forma complementar, foram feitos: i) trabalho de observação durante a 65a Assembleia Mundial da Saúde, da Organização Mundial da Saúdem, evento de importância para os debates sobre propriedade intelectual e interesse público; e ii) entrevistas com integrantes de equipes das duas principais instituições participantes do consórcio FACT (Farmanguinhos/Fiocruz e DNDi). / This thesis aims to study the relationship between intellectual property, innovation and public health, considering the case of the consortium for the development of the fixed-dose combination artesunate-mefloquine (ASMQ) for the treatment of malaria. The genesis of this initiative is part of a historical moment (late 1990s and early 2000s), when studies highlighted the crisis on R&D for neglected diseases. At that time, the scenario of malaria was particularly worrying, given the spread of drug resistance and also the fact that there was no expectation for launching new antimalarials in the market. A strategy was then developed to protect the last class of effective antimalarials (artemisinin derivatives) by establishment of the artemisin-based combination therapies (ACTs). Nevertheless, only one of the four ACTs recommended by WHO in 2001 was available. The FACT project was then created in 2002 with the purpose of developing two new ACTs - artesunate-mefloquine and artesunateamodiaquine. The ASMQ Consortium, due to its specific features (production of an innovation by a public laboratory located in the South and South-South knowledge circulation), may interest the studies in the fields of Bioethics and Public Health, and was chosen to integrate this thesis. Besides the analysis of specialized literature, which was of fundamental importance for understanding the problems of access and availability that arises from the current model of innovation adopted by the pharmaceutical industry, an observation work was conducted during the 65th World Health Assembly, World Health Organization, held in Geneva during May 2012, which was of valuable importance for the debates regarding intellectual property and public interest. Also we conducted interviews with actors belonging to the two institutions participants of the consortium FACT (Farmanguinhos / Fiocruz and DNDi) in order to better understand the initiative.
86

Saúde pública, inovação farmacêutica e propriedade intelectual: o desenvolvimento de um novo medicamento contra a malária no Brasil / Public Health, pharmaceutical innovation and intelectual property: the development of a new medicine against malaria in Brazil

Koichi Kameda de Figueiredo Carvalho 06 September 2012 (has links)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Esta dissertação tem como objetivo estudar a relação entre propriedade intelectual, inovação e saúde pública, com foco na análise do consórcio farmacêutico para desenvolvimento do medicamento combinação em dose fixa artesunato-mefloquina (ASMQ) contra a malária. A concepção dessa iniciativa se insere num momento histórico, final dos anos 1990 e início dos anos 2000, em que estudos apontaram a insuficiência da pesquisa e desenvolvimento para as doenças negligenciadas. Na época, o cenário da malária era particularmente preocupante, dada a disseminação de resistência aos medicamentos disponíveis e à falta de perspectiva do lançamento de novos produtos contra a doença. Para proteger a última classe de antimaláricos eficazes, a saber,os derivados a base de artemisinina, uma estratégia encontrada foi a do recurso à terapia combinada a base de artemisinina (artemisinin based combination therapy ACT). Contudo, dos 4 ACTs recomendados pela OMS em 2001, apenas 1 se encontrava disponível no mercado. O projeto FACT foi então criado, em 2002, com o propósito de desenvolver dois novos ACTs artesunato-mefloquina e artesunato-amodiaquina. O consórcio do ASMQ, por suas especificidades, em particular a produção de inovação por um laboratório público do Sul e a circulação Sul-Sul de conhecimentos e tecnologias , o tornam de interesse para estudos nos campos da bioética e da saúde pública; tendo sido, por isso, escolhido como objeto desta dissertação. O estudo se apoiou em pesquisa bibliográfica, de fundamental relevância para a compreensão dos problemas de acesso e de disponibilidade de novos produtos para doenças negligenciadas, decorrentes de um modelo de inovação farmacêutica sustentado em patentes. De forma complementar, foram feitos: i) trabalho de observação durante a 65a Assembleia Mundial da Saúde, da Organização Mundial da Saúdem, evento de importância para os debates sobre propriedade intelectual e interesse público; e ii) entrevistas com integrantes de equipes das duas principais instituições participantes do consórcio FACT (Farmanguinhos/Fiocruz e DNDi). / This thesis aims to study the relationship between intellectual property, innovation and public health, considering the case of the consortium for the development of the fixed-dose combination artesunate-mefloquine (ASMQ) for the treatment of malaria. The genesis of this initiative is part of a historical moment (late 1990s and early 2000s), when studies highlighted the crisis on R&D for neglected diseases. At that time, the scenario of malaria was particularly worrying, given the spread of drug resistance and also the fact that there was no expectation for launching new antimalarials in the market. A strategy was then developed to protect the last class of effective antimalarials (artemisinin derivatives) by establishment of the artemisin-based combination therapies (ACTs). Nevertheless, only one of the four ACTs recommended by WHO in 2001 was available. The FACT project was then created in 2002 with the purpose of developing two new ACTs - artesunate-mefloquine and artesunateamodiaquine. The ASMQ Consortium, due to its specific features (production of an innovation by a public laboratory located in the South and South-South knowledge circulation), may interest the studies in the fields of Bioethics and Public Health, and was chosen to integrate this thesis. Besides the analysis of specialized literature, which was of fundamental importance for understanding the problems of access and availability that arises from the current model of innovation adopted by the pharmaceutical industry, an observation work was conducted during the 65th World Health Assembly, World Health Organization, held in Geneva during May 2012, which was of valuable importance for the debates regarding intellectual property and public interest. Also we conducted interviews with actors belonging to the two institutions participants of the consortium FACT (Farmanguinhos / Fiocruz and DNDi) in order to better understand the initiative.
87

Síntese e desenvolvimento de métodos analíticos para o estudo de pró-fármacos dendriméricos potencialmente ativos em doenças negligenciadas / Synthesis and analytical methods development to study dendrimeric prodrugs potentially actives in neglected diseases.

Lorena Cristine Paes 11 November 2016 (has links)
Doenças infecciosas parasitárias consideradas negligenciadas representam um grande problema de saúde pública em muitos países e regiões. Os fármacos disponíveis na terapêutica são, em geral, tóxicos e de eficácia discutível. Portanto, a descoberta e o planejamento de novos quimioterápicos são extremamente necessários. Neste contexto, os pró-fármacos dendriméricos podem ser úteis. Porém, é necessário esforço adicional para viabilizar os custos, simplificar as estratégias de síntese e investigar os comportamentos de liberação. Ademais, é importante a melhoria dos métodos analíticos, dos métodos de purificação e identificação dos produtos de síntese, para a determinação das propriedades físico-químicas e atividade biológica, visando à efetiva aplicação desta tecnologia. Face ao exposto, o objetivo deste trabalho foi estudar a identidade, pureza e liberação de dois potenciais pró-fármacos dendriméricos, baseados em 3- hidroxiflavona, planejados para serem ativos em doença de Chagas e leishmaniose. O primeiro, estruturalmente, contendo inositol como núcleo e ramos constituídos por éster da 3- hidroxiflavona com ácido málico e o segundo, estruturalmente contendo o dendrímero PAMAM-G0 (poliamidoamina de geração inicial) como transportador e ácido succínico como espaçante. Desenvolveram-se métodos adequados à determinação da 3-hidroxiflavona por HPLC-UV (Cromatografia líquida de alto desempenho, com detecção no ultravioleta) e MEKC (Cromatografia eletrocinética micelar). Comparando-se esses métodos, o método por HPLC foi mais sensível, preciso e exato na quantificação da 3-hidroflavona, enquanto o método por eletroforese capilar foi mais rápido e de menor custo. O éster da 3-hidroxiflavona com o ácido málico mostrou-se instável em soluções orgânicas, aquosas em diferentes pH e nas condições reacionais de diversas estratégias de síntese avaliadas, o que impediu a obtenção do dendrímero baseado em inositol como núcleo conforme proposto. Já o dendrímero PAMAM-G0 funcionalizado com 3-hidroxiflavona foi sintetizado, purificado e caracterizado com sucesso. Não se observou liberação da 3-hidroxiflavona a partir desse dendrímero em solução gástrica simulada (pH 1,2) e a mesma foi lenta em soluções tampão com pH entre 5,0 e 8,5, a 37,0 ºC. Ensaios de atividade biológica do PAMAM-G0-SUC-3-OH-FLAV em amastigotas de Trypanosoma cruzi, cepas Y(Curitiba) e Y(SS), comparativamente ao benznidazol e ao nifurtimox, mostraram atividade moderada e baixa seletividade. / Infectious parasitoses considered neglected diseases represent a great health problem for many countries and areas. Drugs available in the therapeutics are, generally, toxics and do not have good efficacy. So, the discovery and design of new chemotherapeutic agents are extremely needed. In this context, dendrimeric prodrugs may be useful. However, additional effort is required to make the costs accessible, to simplify the synthetic strategies and to investigate the behavior of cleavage. The improvement of analytical methods, purification methods and identification of synthetic products, in order to determine the physicochemical properties and bioactivity aiming to effectively implement this technology, is also required. Based on foregoing considerations, the objective of this work was to study the identity, purity and drug release of two potential dendrimeric prodrugs, based on 3-hydroxyflavone, designed to be active in leishmaniasis and Chagas disease. The first structurally contains myo-inositol as the core and branches consisting of esters from 3-hydroxyflavone with malic acid. The second structurally contains PAMAM-G0 dendrimer (initial generation polyamidoamine) as carrier and succinic acid as spacer. Suitable analytical methods for determining 3-hydroxyflavone by HPLC-UV (High Performance Liquid Chromatography) and MEKC (Micellar Electrokinetic Chromatography) have been developed. Comparing these methods, HPLC method showed more sensitivity, precision and accuracy in the quantification of 3-hydroxyflavone, while the capillary electrophoresis method was faster and less expensive. The ester of 3-hydroxyflavone with malic acid showed to be unstable in organic and aqueous solutions, at different pH and at reaction conditions of synthetic strategies evaluated, which prevented the obtaining of dendrimer based on mio-isositol as core. Notwithstanding, PAMAM-G0 dendrimer funcionalized with 3- hydroxyflavone was synthesized, purified and characterized successfully. There were no 3- hydroxyflavone releases from this dendrimer in simulated gastric fluid (pH 1.2) and a slow release was observed in buffer solutions with pH between 5.0 and 8.5, at 37.0 ºC. Submitted to biological assays in amastigotes of two strains of T. cruzi, Y(Curitiba) and Y(SS), compared to benznidazole e nifurtimox, PAMAM-G0-SUCC-3-OH-FLAV showed moderated activity and low selectivity index.
88

Biogeographical patterns of African trypanosomoses for improved planning and implementation of field interventions

Cecchi, Giuliano 29 November 2011 (has links)
Spatially-explicit information is essential for planning and implementing interventions against vector-borne diseases. This is also true for African trypanosomoses, a group of diseases of both humans and animals caused by protozoa of the Genus Trypanosoma, and transmitted by tsetse flies (Genus Glossina).<p>In this thesis the knowledge gaps and the requirements for an evidence-based decision making in the field of tsetse and trypanosomoses are identified, with a focus on georeferenced data and Geographic Information Systems (GIS). Datasets, tools and analyses are presented that aim to fill some of the identified knowledge gaps.<p>For the human form of the disease, also known as sleeping sickness, case detection and treatment are the mainstay of control, so that accurate knowledge of the geographic distribution of infections is paramount. In this study, an Atlas was developed that provides village-level information on the reported occurrence of sleeping sickness. The geodatabase underpinning the Atlas also includes the results of active screening activities, even when no cases were detected. The Atlas enables epidemiological maps to be generated at a range of scales, from local to global, thus providing evidence for strategic and technical decision making.<p>In the field of animal trypanosomosis control, also known as nagana, much emphasis has recently been placed on the vector. Accurate delineation of tsetse habitat appears as an essential component of ongoing and upcoming interventions against tsetse. The present study focused on land cover datasets and tsetse habitat. The suitability for tsetse of standardized land cover classes was explored at continental, regional and national level, using a combination of inductive and deductive approaches. The land cover classes most suitable for tsetse were identified and described, and tailored datasets were derived.<p>The suite of datasets, methodologies and tools presented in this thesis provides evidence for informed planning and implementation of interventions against African trypanosomoses at a range of spatial scales. / Doctorat en Sciences agronomiques et ingénierie biologique / info:eu-repo/semantics/nonPublished
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A Natural Product and High-Throughput Screening Synthetic Approach Towards the Discovery of Antileishmanial Agents

Scaduto, Ryan 04 May 2021 (has links)
No description available.
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“Jag offrar mig själv för att kunna försvara mitt område eller mina grabbar” : en studie om den socioekonomiska eftersattheten och dess koppling till gatuvåldet bland unga män i Sverige / “I sacrifice myself in order to be able to defend my area or my boys” : a study about the neglected socioeconomic areas and their connection to street vio men in Sweden

Atilgan, Aslihan, Said, Nadia January 2022 (has links)
This study focuses on examining whether there is a link between crime/street violence and socioeconomically disadvantaged/neglected areas. The study was executed on the basis of professionals' perspective on the issue. The study analyzes young men but the result is based on empirical data from interviews with the professionals who are or have been in touch with young men whose lifestyle is characterized by criminality. The interviewees are professionals in different fields such as social services, leisure activities, politics, defector activities etcetera. Therefore, the study is similar to a casestudy. Our study is conducted with the help of semi-structured interviews since we have chosen a qualitative research method with an abductive approach. The results show that the connection between the issues surrounding street violence and the socioeconomically neglected areas is strong. The stigma around the area and the lack of meaningful leisure leads to risk factors for the young men, in terms of education with fewer resources, overcrowding in their homes, poverty and exclusion in society. These factors in turn lead individually or collectively to the young men being attracted to a lifestyle that is characterized by crime, violence, drug trafficking and so on. Labeling theory was a highly current theory which most of the interviewees pointed out. Bothstigma and labeling of people who live in the neglected areas can cause street violence. This in turn causes fragile social ties in society. Developmental psychopathology is another theory that helped us answer the results in this study. The collected data shows how development differs from one individual to the other, how one person who in general lives under the same circumstances manages to stay away from criminality while another individual doesn't. The conclusion that was drawn from this study, among others, is that a root cause of street violenceis the neglecting of these areas. There is a necessity for more resources and dedicated workers in school, workers in extracurricular functions and other adults that work in close connection to the young men. / Denna studie fokuserar på att undersöka om det finns en koppling mellan kriminalitet och socioekonomiskt eftersatta/utsatta områden. Detta undersöks med avstamp i de yrkesverksammas perspektiv på problematiken. Studien undersöker unga män men resultatet baseras på empirin från intervjuer med yrkesverksamma som är eller har varit i kontakt med unga män vars livsstil präglas av kriminalitet. Intervjupersonerna är yrkesverksamma inom olika fält såsom Socialtjänsten, fritidsverksamheter, politik, avhopparverksamhet med mera. I och med detta liknas undersökningen en fallstudie. Studien genomförs med hjälp av semistrukturerade intervjuer då vi valt en kvalitativ forskningsmetod med en abduktiv ansats. Resultatet visar att kopplingen mellan problematiken kring gatuvåldet och de socioekonomiskt eftersatta områdena är stark. Stigman kring områdena och avsaknaden av en meningsfull fritid orsakar riskfaktorer för unga män i form av bland annat bristfällig skolgång med få resurser, trångboddhet, fattigdom och utanförskap. Dessa faktorer leder i sin tur individuellt eller kollektivt till att unga mändras till en livsstil som präglas av bland annat kriminalitet, våld och droghandel med bristande tillit för de vuxna och ansvariga. Stämplingsteorin kom att bli en högst aktuell teori som merparten av intervjupersonerna beskrev. Både stigmatisering och stämpling av de människor som är bosatta i de eftersatta områdena kan komma att bli en direkt följd av gatuvåld i förhållande till den socioekonomiska eftersattheten. Detta i sin tur orsakar sköra sociala band i samhället. Utvecklingspsykopatologi var en annan teori som hjälpte oss besvara resultatet i studien. Empirin visade på hur utvecklingen skiljer sig från individ till individ när vissa av unga männen som levt under i princip samma förutsättningar lyckas undvika att hamna i en kriminell livsstil, medan andra inte lyckas undvika det. Studiens slutsatser påvisar bland annat att en grundorsak till gatuvåldet är den socioekonomiska eftersattheten. Det finns ett behov av starkare resurser och engagerad personal i skola, fritidsgårdar och andra platser där unga män vistas då dessa faktorer är avgörande för deras uppväxt och framtid.

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