Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-18T12:02:52Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE DOUTORADO COM CORREÇOES.pdf: 10540720 bytes, checksum: f145a8c9fdeee7916351a8189dd086ab (MD5) / Made available in DSpace on 2016-07-18T12:02:52Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE DOUTORADO COM CORREÇOES.pdf: 10540720 bytes, checksum: f145a8c9fdeee7916351a8189dd086ab (MD5) Previous issue date: 2015-08-25 / FACEPE / A doença de Chagas, causada pelo Trypanosoma cruzi, constitui-se um dos maiores problemas de saúde pública em países do cone sul das Américas, pela sua vasta distribuição, altos índices de prevalência e gravidade de evolução. Embora o nifurtimox ainda seja utilizado em alguns países, o único fármaco atualmente disponível para a quimioterapia anti-Chagásica no Brasil é o benznidazol. No entanto, é ineficaz frente ao estágio crônico da doença e seu uso está associado à incidência de efeitos colaterais graves, o que torna imprescindível a busca por novos fármacos anti-T. cruzi. Para o desenvolvimento de um tratamento farmacológico apropriado, é necessária a descoberta de novos alvos terapêuticos no parasito, entre os quais se destaca a cruzaína, uma cisteína protease essencial à sua sobrevivência. As tiossemicarbazonas constituem uma classe de compostos bastante examinada devido a sua versatilidade química e ampla gama de atividades farmacológicas, com destaque para sua potencial atividade inibitória frente à enzima cruzaína. Com base nisso, foi planejada a síntese de uma série de 32 inéditas aril-tiossemicarbazonas (38a-l; 39a-t) através da o–alquilação de fenóis com 2-haloacetofenonas em meio básico, seguida pela condensação entre as acetofenonas e tiossemicarbazidas em meio ácido. A elucidação estrutural foi realizada por RMN 1H, RMN 13C, IV; a pureza foi determinada por análise elementar e a estrutura cristalográfica caracterizada pela difração de raios-X. A avaliação antiparasitária foi determinada frente às formas epimastigota, amastigota e tripomastigota do T. cruzi, ao passo que a citotoxicidade contra células hospedeiras foi avaliada em esplenócitos e fibroblastos. Ademais, analisou-se o processo de morte celular induzido pelos compostos, bem como a inibição causada por eles sobre a enzima cruzaína. A rota sintética empregada forneceu as aril-tiossemicarbazonas (38a-l; 39a-t) com rendimento e pureza aceitáveis. A análise de RMN indicou a presença de isômeros, de tal maneira que a estrutura cristalográfica obtida revelou a geometria e a configuração dos compostos obtidos. Já a avaliação da atividade antiparasitária, revelou que a maioria dos compostos exibiu atividade superior ao benznidazol contra as formas extracelulares do T. cruzi, com destaque para os compostos 39a e 39c, que mostraram atividade antiparasitária ampla e seletiva. O composto 39c, por sua vez, foi o mais seletivo contra as formas extracelulares do parasita e não apresentou citotoxicidade sobre esplenócitos de camundongo em altas concentrações. Por outro lado, estas aril-tiossemicarbazonas demonstraram, de um modo geral, baixa seletividade frente à forma amastigota do parasito. Além disso, 14 dos compostos testados inibiram a cruzaína com percentuais de inibição superiores a 70%, denotando que as alterações na conformação molecular e planaridade das tiossemicarbazonas aumentaram a afinidade pelo sítio de ligação da enzima. As tiossemicarbazonas 39i e 39n revelaram-se potentes inibidores, comparáveis ao composto de referência, K11777. Por último, foi observado que o tratamento baseado nestas tiossemicarbazonas causou morte celular de tripomastigotas por necrose. Enfim, o planejamento estrutural efetuado permitiu compreender aspectos químicos e relações estrutura-atividades de novas aril-tiossemicarbazonas. Consequentemente, isto resultou na triagem e identificação de inéditas aril-tiossemicarbazonas dotadas de atividade anti-T. cruzi de amplo espectro de ação, que afetam a ação da cruzaína e subsequentemente levam a morte celular por necrose. / Chagas disease, caused by Trypanosoma cruzi, it constitutes one of the major public health problems in southern cone countries of the Americas for its wide distribution, high rates of prevalence and severity of evolution. Although nifurtimox is still used in some countries, the only drug currently available for anti-chagasic chemotherapy in Brazil is benznidazole. However, it is ineffective against the chronic stage of the disease and is associated with serious side effects, which makes it essential to search for new drugs anti-T. cruzi. For developing an appropriate drug treatment, the discovery of new therapeutic targets in the parasite is necessary, among which stands out the cruzain, a cysteine protease essential for their survival. The thiosemicarbazones are a class of compounds quite examined due to its chemical versatility and wide range of pharmacological activities, highlighting its potential inhibitory activity against the enzyme cruzain. Based on this, it was planned synthesis of a series of novel 32 aryl-thiosemicarbazones (38a-l, 39a-t) by o-alkylation of phenols with 2-haloacetofenonas in basic medium, followed by condensation between acetophenone and thiosemicarbazides in acidic medium. The structural elucidation was performed by 1H NMR, 13C NMR, IR; purity was determined by elemental analysis and the crystal structure characterized by X-ray diffraction. The evaluation antiparasitic was given front of the epimastigote, amastigote and trypomastigote forms of T. cruzi, while the cytotoxicity was evaluated against host cells in splenocytes and fibroblasts. Furthermore, it was examined whether the cell death induced by the compounds, as well as inhibition caused by them on the enzyme cruzain. The employed synthetic route provided the aryl thiosemicarbazones (38a-l, 39a-t) with acceptable yield and purity. NMR analysis indicated the presence of isomers, such that the crystal structure obtained showed the geometry and configuration of the compounds obtained. Since the evaluation of antiparasitic activity, revealed that most of the compounds exhibited superior activity to benznidazole against extracellular forms of T. cruzi, especially the compounds 39a and 39c, which showed broad and selective antiparasitic activity. Compound 39c, in turn, was the most selective against extracellular forms of the parasite and showed no cytotoxicity against mouse splenocytes in high concentrations. On the other hand, these aryl thiosemicarbazones shown, generally, low selectivity towards the amastigote form of the parasite. Furthermore, 14 of the tested compounds inhibited cruzain with inhibition percentage higher than 70%, indicating that the changes in molecular conformation and planarity of thiosemicarbazones increased affinity for the enzyme binding site. The thiosemicarbazones 39i and 39n have proved to be potent inhibitors comparable to the reference compound, K11777. Finally, it was observed that treatment based on these thiosemicarbazones caused cell death of trypomastigotes by a necrotic pathway. In the end, the structural planning made possible understand chemical aspects and structure-activity relationships of new aryl thiosemicarbazones. Consequently, this resulted in the screening and identification of inedited aryl thiosemicarbazones endowed with antiparasitic activity of broad spectrum of action, affecting the action of cruzain and subsequently leading to cell death by necrosis.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-12T11:58:21Z No. of bitstreams: 2 Dissertação - Anália Cirqueira Milhomem - 2017.pdf: 1969169 bytes, checksum: 990bb0603cc940e039264e7209f95907 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-12T11:58:37Z (GMT) No. of bitstreams: 2 Dissertação - Anália Cirqueira Milhomem - 2017.pdf: 1969169 bytes, checksum: 990bb0603cc940e039264e7209f95907 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-04-12T11:58:37Z (GMT). No. of bitstreams: 2 Dissertação - Anália Cirqueira Milhomem - 2017.pdf: 1969169 bytes, checksum: 990bb0603cc940e039264e7209f95907 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-15 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Neurocysticercosis (NCC) is one of the diseases neglected by the World Health Organization (WHO), and the parasitic infection that most affects the Central Nervous System (CNS) throughout the world. Thus, it is necessary to deepen the knowledge regarding its immunopathogenesis and physiopathology in order to elucidate mechanisms by which NCC causes tissue injury in infected patients. With the advent of this necessity the search for ways to facilitate the experimental study of this disease has arisen, and today, the use of the cysticercus species of Taenia crassiceps is well diffused in the scientific environment. The objective of this work was to describe the general pathological processes and the profile of systemic and in situ cytokines in C57BL / 6 mice after intracranial inoculation of viable cysticerci of T. crassiceps. Three experimental groups were used: healthy control, surgical control and infected group. After 90 days of infection, mice were euthanized and histopathological analysis of the brain, spleen cell culture, homogenate production and ELISA for IL-4, IL10 and IFN-γ were performed. The histopathological analysis of the encephalus allowed to verify the presence of cysticercus in the lateral ventricles or in the extraparenchymal region, presence of mononuclear inflammatory infiltrate (MN) around the parasite, microgliosis and meningitis. The analysis of the systemic and in situ immune profiles of the infected mice showed a predominance of Th2-type response, with high IL-4 concentration, low IFN-γ and IL-10 levels modulating the two responses, but mainly Th1. The in situ cytokine dosage was similar between the experimental groups, which leads us to conclude that the cysticercus exerts immunomodulation for its survival, in addition to which it also benefits from the cerebral immunoprivilege. In conclusion, correlating the immune and histological aspects described after the analysis, we can suggest that T. crassiceps cysticercosis infection in C57BL / 6 mice triggers an inflammatory response, a predominance of Th2 type profile with MN inflammatory infiltrate presence, Meningitis and microgliosis. / A neurocisticercose (NCC) é uma das doenças negligenciadas pela Organização Mundial de Saúde (OMS), e a infecção parasitária que mais acomete o Sistema Nervoso Central (SNC) em todo o mundo. Dessa forma, faz-se necessário aprofundar os conhecimentos quanto a sua imunopatogênese e fisiopatologia com o intuito de elucidar mecanismos pelos quais a NCC provoca lesão tecidual nos pacientes infectados. Com o advento desta necessidade a busca por formas de facilitar o estudo experimental desta doença surgiram, e hoje, a utilização da espécie de cisticercos de Taenia crassiceps está bem difundida no meio científico. O objetivo deste trabalho foi descrever os processos patológicos gerais e o perfil de citocinas sistêmicas e in situ em camundongos C57BL/6, após inoculação intracraniana de cisticercos viáveis de T. crassiceps. Para isso foram utilizados três grupos experimentais: controle saudável, controle cirúrgico e grupo infectado. Após 90 dias de infecção foi realizada eutanásia dos camundongos e posteriormente foi realizada análise histopatológica dos encéfalos, cultura de células do baço, produção de homogenato e ELISA para dosagem de IL-4, IL10 e IFN-γ. A análise histopatológica dos encéfalos permitiu comprovar a presença do cisticerco, nos ventrículos laterais ou na região extraparenquimal, presença de infiltrado inflamatório mononuclear (MN) ao redor do parasito, microgliose e meningite discretas. As análises dos perfis imunes sistêmico e in situ dos camundongos infectados não apresentou diferenças estatisticamente significativas entre os grupos analisados, o que nos fazer deduzir que o cisticerco exerce imunomodulação buscando sua sobrevivência, além do que se beneficia também do imunoprivilégio cerebral. Em conclusão, correlacionando os aspectos imunes e histológicos descritos após as análises realizadas, podemos sugerir que a infecção por cisticercos de T. crassiceps em camundongos C57BL/6, desencadeia resposta inflamatória com a presença infiltrado inflamatório MN, meningite e microgliose.

A presente investigação constitui um estudo de caso sobre a tripanossomíase americana, conhecida como doença de Chagas, em seus aspectos epistemológicos e sociais, articulados através da análise de diferentes valores envolvidos nas pesquisas sobre essa enfermidade. Na elaboração de uma biografia procuramos enfatizar dois aspectos dessa patologia. Por um lado, que a tripanossomíase americana pode ser interpretada como um agente histórico, na medida em que a identidade dessa entidade nosológica não pode ser dissociada de sua caracterização científica e social, tampouco reduzida a apenas uma dessas dimensões. Por outro lado, colocar a doença como protagonista dessa história nos permite evidenciar de que modo o predomínio da narrativa das instituições médicas e científicas legitimou a invisibilização da perspectiva das pessoas afetadas por essa patologia. A primeira parte da tese está centrada sobre a faceta científica e médica da doença, a qual permitiu que a nova patologia humana fosse estabelecida como um fato. Com relação aos aspectos sociais da doença, estes são focalizados na segunda parte da tese, onde examinamos as ideias envolvidas nas representações dos trópicos e das populações rurais como sinônimos de atraso. / The present investigation is a case study of American trypanosomiasis, known as Chagas disease, in its epistemological and social aspects, articulated through an analysis of the different values involved in research on this disease. In the elaboration of a biography, we aim to emphasize two aspects of this pathology. On the one hand, American trypanosomiasis can be interpreted as a historical agent, to the extent that the identity of this nosological entity cannot be dissociated from its scientific and social characterization, nor can it be reduced to just one of these dimensions. On the other hand, to put the disease as the protagonist of this history allows us to show the ways in which the predominance of medical and scientific institutions narrative has legitimated the invisibility of the perspectives of the ones affected by this pathology. The first part of this thesis is centered on the scientific and medical facet of the disease, which allowed the new human pathology to be established as a fact. The social aspects of the disease will be focalized in the second part of the thesis, where we examine the ideas involved in representations of the tropics and of rural populations as synonyms of backwardness.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-02T12:28:43Z No. of bitstreams: 1 thaismirandamoreira.pdf: 1261834 bytes, checksum: ba7c70f75855686a0f9fbb9027cac67e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-02T16:27:19Z (GMT) No. of bitstreams: 1 thaismirandamoreira.pdf: 1261834 bytes, checksum: ba7c70f75855686a0f9fbb9027cac67e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-02T16:27:44Z (GMT) No. of bitstreams: 1 thaismirandamoreira.pdf: 1261834 bytes, checksum: ba7c70f75855686a0f9fbb9027cac67e (MD5) / Made available in DSpace on 2017-06-02T16:27:44Z (GMT). No. of bitstreams: 1 thaismirandamoreira.pdf: 1261834 bytes, checksum: ba7c70f75855686a0f9fbb9027cac67e (MD5) Previous issue date: 2016-03-21 / Esta pesquisa tem por objetivo avaliar por meio da análise de pedidos de patentes no Instituto Nacional de Propriedade Industrial (INPI) a ineficácia da Lei de Propriedade Industrial (Lei n° 9.279/96) no que concerne ao estímulo de investimentos em pesquisa e desenvolvimento (P&D) de medicamentos para doenças negligenciadas, bem como evidenciar como os doentes negligenciados influenciam no processo de desenvolvimento de inovações na área. Pretendese discutir a legalidade e a legitimidade de patentes farmacêuticas por meio de uma metodologia pautada na teoria da luta por reconhecimento de Axel Honneth atrelada à ideia de “viver plenamente a lei” de Zenon Bankowski. Isso se realiza por meio da coleta de dados e da construção de tabelas que verificam o atual panorama dos depósitos de patentes ligados à Dengue, bem como pela interpretação desses dados pela lente da teoria do direito como identidade usando o método da análise de conteúdo por traços de significação. Além dos dados coletados a partir dos pedidos de patentes depositados no INPI, utilizam-se dados oficiais do governo brasileiro, bem como dados da Organização Mundial da Saúde (OMS) e de organizações humanitárias a Médicos Sem Fronteiras (MSF) e a Drugs for Neglected Diseases initiative (DNDi). O cruzamento desses dados auxilia o processo de inferências relacionadas ao investimento em pesquisa e desenvolvimento de produtos, fármacos e vacinas para o controle e erradicação de doenças que afetam pessoas negligenciadas. São analisados o número de pedidos de patentes depositados por ano, o perfil dos produtos depositados, a origem do investimento em pesquisa e desenvolvimento dos produtos objetos dos pedidos, bem como dois depósitos específicos que podem culminar no desenvolvimento de vacinas contra a dengue. Por fim, a partir dessa estratégia metodologia conclui-se genericamente pela necessidade de revisão dos diplomas legais que tratam sobre Propriedade Intelectual ou, até mesmo, pela superação do sistema patentário a fim reverter o quadro de colonização do direito à saúde pela lógica mercadológica que reina hoje. / This research’s main objective is to assess, by the analysis of patent deposits in Brazil’s National Institute of Industrial Property (INPI), the efficacy of Brazilian Industrial Property Law (Federal law n. 9.279/96) in stimulating Research and Development (R&D) investment on neglected diseases’ medicine, as well as evaluate how neglected patients affect the R&D processes in the area. The legality and the legitimacy of pharmaceutical patents are investigated based on a methodological approach influenced by Axel Honneth’s idea of “struggle for recognition” and Zenon Bankowski’s theory of “living lawfully”. In order to assess the field chosen, the research is carried out focusing on data analysis of patent deposits concerning dengue fever, studied with help of Honneth’s methodological lenses by content analysis through signification traits identification. In addition to the patent deposits in the INPI data collected, official governmental indicators, as well as those from World Health Organization (OMS), Doctors Without Borders (MSF), and Drugs for Neglected Diseases Initiative (DNDi) were used. The crossing of these data allows the establishment of strong inferences related to R&D investment on pharmaceuticals and vaccines towards the control and eradication of diseases that target neglected people. To do so, I analyze the number of patent deposits per year, the profile of the deposited products, the origin of the R&D investment in such products, as well as two specific deposits that can originate the development of vaccines to prevent dengue fever. Lastly, with help of these methodological references and tools I conclude, in broader terms, that there is a great need of reviewing the current laws on Intellectual Property or even that is time to overcome the entire patent-based system in order to reverse the submission of the right to health solely to a market-oriented rationality.

Les histones désacétylases (HDACs) sont les principales cibles des médicaments épigénétiques anticancéreux actuellement approuvés par la FDA. Les HDACs jouent aussi un rôle important dans l'homéostasie des pathogènes eucaryotes. Par conséquent, une stratégie pour lutter contre les maladies négligées causées par ces pathogènes est de modifier les médicaments épigénétiques actuellement approuvés qui ciblent les HDACs. HDAC8 de Schistosoma mansoni (smHDAC8) est une cible médicamenteuse valable pour traiter la schistosomiase, deuxième maladie négligée mortelle après le paludisme. Les différences structurales entre les poches catalytiques des HDAC8 humaine et smHDAC8 ont permis la conception d'inhibiteurs sélectifs des schistosomes qui se lient dans une poche sélective unique à HDAC8. Ce travail de thèse montre comment cibler sélectivement des isoformes HDAC l'aide de structures à résolution atomique, et ouvre la porte à l'étude du mode d'action de HDAC8 au niveau fondamental. / Histone deacetylases (HDACs) are the major targets of currently FDA-approved anti-cancer epigenetic drugs. HDACs also play an important role in the homeostasis of eukaryotic pathogens. Hence, a strategy to tackle neglected diseases caused by these pathogens is to modify currently approved epigenetic drugs targeting HDACs. HDAC8 from Schistosoma mansoni (smHDAC8) was shown to be a valid drug target to treat schistosomiasis, second deadliest tropical disease after malaria. Structural differences between human HDAC8 and smHDAC8 catalytic pocket enabled the design of schistosome-selective inhibitors that bind in a HDAC8 selective pocket, which is unique to HDAC8 among the highly conserved HDAC isozymes. This thesis work shows how to target selectively related isoforms with the help of atomic resolution structures, and opens the door to the investigation of the mode of action of HDAC8 at the fundamental level.

Tshwane is a city that is expanding eastwards. In the process, valuable cultural and ecological landscapes are being neglected. These unique landscapes, which contain critical environmental assets, could be made attractive to the general public and thus should be protected wherever possible. The expansion of the city is inevitable. While cities need to accommodate more people, they should also provide socially and culturally enriching outdoor spaces. This study uses landscape architecture and regenerative theory to suggest ways of making post-industrial sites productive again. The Hazeldean dairy; a site of cultural significance, environmental assets and physical charm, is in danger of becoming a deteriorating and forgotten landscape. The hypothesis argues that that by adapting to current social, economic and sustainable requirements, a new and living landscape can be created. This would prevent Hazeldean from becoming a characterless buffer between surrounding property developments. The design interventions proposed for the Hazeldean farm should enhance its historical and ecological value and attract visitors to the property for many different reasons, throughout the year. Ultimately, Hazeldean should endure as a physical and socially valuable asset within the rapidly expanding city of Tshwane. / Dissertation ML(Prof)--University of Pretoria, 2014 / Architecture / ML(Prof) / Unrestricted

Orientador: Giuseppina Pace Pereira Lima / Resumo: As plantas alimentícias negligenciadas como a Pereskia grandifolia Hawer e Talinum paniculatum (Jacq.) Gaertn são definidas por possuírem uma ou mais partes, ou produtos, que podem ser utilizados na alimentação. Entretanto, o consumo destas espécies não é comum e tão pouco são divulgadas informações sobre o preparo e a importância nutricional. O cozimento, além de facilitar a palatabilidade dos vegetais, pode aumentar a biodisponibilidade dos compostos bioativos. Essas hortaliças são consumidas, geralmente, após o processamento térmico, que diminuem os fatores antinutricionais presentes quando in natura. Desta forma, o objetivo deste estudo foi avaliar o efeito do cozimento em fervura, vapor e micro-ondas em diferentes tempos, com relação ao conteúdo de poli(fenois) e carotenoides, bem como a atividade antioxidante total em P. grandifolia e T. paniculatum. Os resultados contribuíram para a caracterização de compostos fenólicos e carotenoides em folhas de P. grandifolia e T. paniculatum, os quais possuem uma série de benefícios para a saúde humana. Estes compostos variam conforme a espécie analisada e o processamento térmico empregado, podendo aumentar o valor nutricional e funcional do alimento, sendo essas espécies importantes fontes de compostos bioativos, que podem auxiliar o organismo humano a combater os radicais livres. / Abstract: Neglected food plants such as a Pereskia grandifolia Hawer and Talinum paniculatum (Jacq.) Gaertn are defined by contain one or more parts, or products, that can be used in feeding. However, the consumption of these species is not common and there is few information about the culinary preparation and nutritional importance. Besides, cooking, can to facilitated the palatability of the vegetables, may increase the bioavailability of the bioactive compounds. These vegetables are usually consumed after thermal processing because there is a decrease in antinutritional factors. Thus, the objective of this study was to evaluate the effect of boiling, microwave and steam cooking at different times, about the content of polyphenols and carotenoids, as well as a total antioxidant activity in P. grandifolia and T. paniculatum. The results contributed to the characterization of phenolic compounds and carotenoids in P. grandifolia and T. paniculatum leaves, which have a series of benefits for human health. These compounds vary according to the species analyzed and the thermal processing employed, and may increase the nutritional and functional value of the food. These species are an important sources of these bioactive compounds, which can help the human organism fight against the free radicals. / Mestre

Magister Artium (Development Studies) - MA(DVS) / It is well established that the modern global food system is highly unsustainable, distorted by industrialisation and corporate consolidation, with negative repercussions on the environment and biodiversity as well as human health. Innovative approaches are necessary to push food systems to be more sustainable, equitable, and healthy for all people regardless of income and wealth. In the Cape Town area, the food system is failing to adequately nourish the poor, while climate change poses increasing challenges to the region’s agricultural system. Conceptualising food systems as complex adaptive social ecological systems and utilising the Multilevel Perspective (MLP) framework, this thesis looks at the burgeoning economy in neglected and underutilised species (NUS) in the Cape Town area as a potential innovation that could make the local food system more socially and ecologically resilient. Though at present NUS are only marginally included in the local food system and policy debates, they are increasingly appearing in the food service industry, driven by international gastronomic trends. They hold potential as climate resilient, nutritionally dense, and socially and culturally significant foods in the region, but also carry ecological and social risks. This thesis critically examines the fledgling NUS economy in the Cape Town area, using participant observation and semistructured interviews to unpack its primary motivations and challenges, and ultimately contributes towards a better understanding of the NUS economy as it develops locally. This research shows that the main risks associated with NUS are negative ecological repercussions, privatisation of the NUS economy, and the reproduction and further entrenchment of unequal power dynamics in the region. In order to mitigate these risks and actualise the related benefits associated with NUS, engagement with the ecological, social, and political context of NUS needs to be significantly deepened. This is particularly true for those working in food service, who appear to be driving the NUS economy, and will require education around sustainability and TEK as well as a foregrounding of power-awareness.

Neglected tropical diseases are parasitic and bacterial diseases mainly prevalent in developing countries affecting people living in poverty. The World Health Organization’s human rights-based approach emphasizes the “prevention, control, elimination and eradication of neglected tropical diseases” through the use of preventative chemotherapy, such as the mass administration of deworming drugs to improve people’s health.This research paper will take a deeper look at how WHO has been communicating NTDs to make them less ‘neglected’ and how the NTD discourse has been shaping development organizations’ action. In addition, it aims to investigate how successful mass deworming has really been in terms of the recent debate.This study is using a combination of a discourse analysis and qualitative interviews in order to investigate how the NTD discourse and recent initiatives by international organizations have contributed to making NTDs less neglected. It deconstructs representations of the ‘Other’ – the superiority of the ‘West’ over the ‘Rest’ – in relation to the NTD discourse and its inherent power structures. Discourses are analyzed to identify power relations between governments, development organizations, pharmaceutical industries, and recipients of deworming drugs as part of Kenya’s 2013 deworming campaign.The results showed that the NTD discourse has helped raise awareness for NTDs. NTDs and their debilitating effect on populations have been better and more widely communicated, making them less ‘neglected’. WHO and other development organizations’ actions have contributed to making NTDs more visible and have given NTDs higher priority on the global health agenda. Findings from this research study revealed that the ongoing debate has not had a negative impact on international funding. More research and development of a vaccine against NTDs is needed to find more ways to tackle these devastating diseases.

Dengue is a major public health problem that affects tens of millions of people annually in tropical and sub-tropical countries. This acute viral infection happens to be severe and even life threatening but there is still no available drug or vaccine. Previous studies have noted early higher viral burden in patients who develop more severe symptoms suggesting that administration of a potent and safe antiviral may prevent progression to severe dengue. To verify this hypothesis, we have conducted the first RCT directed towards reducing the viral burden in vivo by administrating chloroquine (CQ), a cheap and well-tolerated drug that inhibits DENV in vitro with concentrations achievable in vivo, to 307 Vietnamese adults with suspected dengue (257 of them were laboratory-confirmed cases). Unfortunately, we did not see an effect of CQ on the duration of infection. However in patients treated with CQ, we observed a trend towards a lower incidence of severe forms. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. In addition, we have explored the relationships between clinical features, antibody responses and virological markers in these patients. We found that the early magnitude of viremia is positively associated with disease severity and there are serotype dependent differences in infection kinetics. We found as well that DENV was cleared faster and earlier in patients with secondary infections. To complete this study, we have also evaluated 2 rapid lateral flow tests for the diagnosis of dengue in a panel of plasma samples from 245 RT-PCR confirmed dengue patients and 47 with other febrile illnesses. Our data suggest that the NS1 test component of these tests are highly specific and have similar levels of sensitivity (~60%). Both NS1 assays were significantly more sensitive for primary than secondary dengue. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. All these findings are of major importance for further anti-viral drug testing.