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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.
1

Exploring the relationship between the education and the welfare systems at the municipal level : a case study of Lod Israel

Katz, Chana January 2000 (has links)
No description available.
2

A retrospective analysis of children with and without disabilities attending the Teddy Bear Clinic, Johannesburg

Deroukakis, Marilena 22 October 2010 (has links)
MSc (Med) (Paediatric Neurodevelopment), Faculty of Health Sciences, University of the Witwatersrand / The intersection of two marginalised groups of children, the disabled and the abused, was the focus of this research report. The study examined data from the Teddy Bear Clinic over an eight-year period and detected differences in the prevalence of sexual abuse, physical abuse and neglect of disabled and non-disabled children. The population of disabled-abused were further classified according to age, population group and gender in order to elucidate relationships between variables that might affect prevalence of maltreatment. A summary of the results shows that specific sub-populations of the disabled (the physically, mentally and learning disabled) had prevalence rates peculiar to them. The mentally and physically disabled had increased rates of sexual abuse, whilst the learning disabled had increased prevalence for neglect. Analysis of those children with multiple disabilities revealed no risk for neglect but they were at increased risk for sexual abuse. Disabled children are therefore not a homogeneous group.
3

Onchocerciasis, lymphatic filariasis, soil transmitted helminthiasis, and schistosomiasis: integration and economic evaluation of mass drug administration using ivermectin, albendazole, and praziquantel

Evans, Darin S. January 2013 (has links)
Thesis (Dr.P.H.)--Boston University / The recently classified neglected tropical diseases (NTD), -- onchocerciasis, lymphatic filariasis, schistosomiasis, and soil-transmitted helminthiasis -- are all coendemic in Nigeria. The World Health Organization recommended strategy for addressing these diseases is preventive chemotherapy through annual mass drug administration (MDA) with ivermectin, albendazole, and praziquantel. Integrated delivery of these medicines has become the de facto strategy advocated for in the literature as a means of reducing costs through shared resources. Little empirical evidence, however, exists to support this. This paper explores these diseases and the concept of integration in the context of the global strategies for their control. A literature review was conducted using PubMed to identify articles published containing any of the disease names and costs. Of the 2,028 articles returned, only 14 published between 1998 and 2011 met the criteria for review. All costs were adjusted for inflation. Overall, the mean cost of MDA by any means was 0.83 cents. No data comparing separate MDA to integrated MDA were found. To examine this, a model was created comparing MDA programs with similar distribution strategies and targeting similar diseases. Data from separate articles presenting stand alone MDA were combined to give a mean cost of 0.42 cents to deliver two medicines in two rounds. This was compared with articles showing integrated MDA, which gave a mean cost of 0.25 cents to deliver two medicines in a single round. This suggests a cost savings of 40 percent. To verify this, data from a NTD program in Nigeria that transitioned to integrated MDA was examined in detail. In 2008, eight districts received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round of all three drugs was co-administered. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009). The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870, similar to savings seen in the literature review. Cost savings were attributed largely to transportation and personnel costs. Integrated delivery of medicines is recommended for mature programs targeting these diseases.
4

Gene Expression Analysis Of Upregulated Genes By 20-OH Ecdysone in <em>Brugia malayi</em>

Lazaro, Monica 27 March 2015 (has links)
Brugia malayi is a filarial nematode causing lymphatic filariasis in humans characterized by swelling of the lower extremities. The aim of this study was to conduct a real time PCR (qRT-PCR) to verify gene expression levels of Brugia malayi nematodes treated with 20 hydroxyecdysone. Transcriptome analysis was previously performed resulting in the identification of 44 genes that were upregulated by exposure to 20-hydroxyecdysone. Based on transcriptome results, known GO Terms and functions, four genes and one endogenous housekeeping gene were chosen for validation by RT-PCR. Induced samples showed a mean increase of microfilarie by 2.2 fold. Induced wells exhibited a 2.8 fold increase of pre- microfilarie production. On day two adult females treated with 20-HE displayed 3.8-fold increase of microfilaria production as compared to uninduced controls. Overall, all four genes showed upregulation with treatment of 20-hydroxyecdysone at levels that corresponded to the results obtained from the transcriptome analysis. Findings in this experiment expand on the understanding of the ecdysone response system in Brugia malayi, which could serve as a potential drug target against filarial disease.
5

Livelihoods of Fulani pastoralists and burden of bacterial zoonoses in the Kachia grazing reserve, Nigeria

Ducrotoy, Marie Julie January 2015 (has links)
The work presented focuses on bacterial zoonoses in northern Nigeria, and more specifically on brucellosis in the Kachia grazing reserve (KGR) - rangeland set-aside by the government to sedentarise Fulani pastoralists. The objectives of the study were to 1) undertake demographic and socioeconomic profiling of the KGR community; 2) review the evidence for brucellosis burden in Nigeria; 3) assess the suitability and performance of brucellosis diagnostic tests selected for use; 4) compare burden of brucellosis across different species (animal and human) and determine Brucella species present in KGR; 5) explore social or environmental factors which may promote or prevent brucellosis transmission; 6) make recommendations for brucellosis control in the KGR and Nigeria; 7) explore community perception of disease and determine household expenditure on animal health; 8) critically evaluate the system’s, integrated, disease cluster, ‘One Health’ approach applied in this study. Three surveys comprising animal (cattle, sheep and goat) and human sampling, administration of questionnaires, focus group discussions and key informant interviews were undertaken in March, June and October 2011. A population census was undertaken in June 2011. Comparison of 2010 government census data with June 2011 census data showed that a mass immigration event occurred in April-May 2011 as a result of post-election violence, with cattle and human populations increasing by 75%. Questionnaire and census data demonstrated the diversity and heterogeneity of the Fulani community in terms of wealth status (roughly corresponding to livestock assets), household size and composition and livelihood diversification strategies. While Fulani in grazing reserves were assumed to be sedentary, KGR households were found to practice wide-range dry and wet season transhumance. Cattle productivity parameters and herd dynamics were similar to those reported by other authors for the extensive pastoralist systems in the sub-humid zone. Herd increase over a one-year period was found to be low or negative for most households in this low input, low output system. Brucellosis epidemiology in the KGR involves B. abortus biovar 3a with low individual and moderate cattle herd prevalence and occasional spill-over into small ruminants. No human brucellosis was detected despite over 80% of the KGR population consuming raw milk and engaging in risky behaviours, raising questions about the potential lower virulence of the local biovar. Low infection rates in livestock, disease-reducing intuitive behaviours or immunity may also be at play. The RBT was found to perform well under field conditions, despite poor concordance when applied in different laboratories and under different conditions. Prospects for control/elimination of brucellosis in the KGR are poor, but low animal burden and absence of human disease render vaccination uneconomic. A review of the literature in Nigeria suggests that brucellosis burden is higher in intensive livestock production systems, which should be targeted first. A laissez-faire approach to brucellosis control in the nomadic pastoralist domain may appeal to policy-makers, as interventions in migratory populations are difficult. Brucellosis is perceived by the KGR community as the number three-priority disease, after trypanosomiasis and Fasciola gigantica/clostridial infection and this was reflected in household expenditure on chemotherapeutics and prophylaxis. Finally, the value of the One Health approach is the ability to see the whole picture, including disease impacts in the animal reservoir as well as the human population, without which erroneous epidemiological and economic conclusions may be drawn; for example, presence of brucellosis in the animal reservoir does not necessarily indicate presence of human disease. This work shows that moving from disciplinary silos to a more holistic or system’s approach spanning epidemiology, evaluation of diagnostic and control tools as well as socio-economic, cultural and institutional aspects can lead to more appropriate recommendations for disease control.
6

Public health at the margins : local realities and the control of neglected tropical diseases in Eastern Africa

Bardosh, Kevin Louis January 2015 (has links)
Neglected Tropical Diseases (NTDs) are both causes and manifestations of poverty in developing countries. Recent advocacy efforts have increased the profile of NTDs, and led to bold new control and elimination targets set for 2020 by the World Health Organisation. However there are multifaceted challenges in effectively implementing NTD interventions in resource-poor contexts that need to be understood and engaged. While there is a growing call by researchers and international agencies for a science of global health delivery to understand these complexities, the exact nature of this science remains contested. This thesis contributes to these debates by advancing a critical social science perspective on the factors that mediate intervention effectiveness for NTD control. Grounded in a social constructivist approach using mixed methods, it critiques prevailing orthodoxies by unpacking the nature, processes and outcomes of three large-scale NTD prevention programmes in Eastern Africa. Focused on different diseases, these case studies represent different types of intervention approaches: top-down, participatory and public-private partnership. The thesis traces the social, technical and environmental processes that mediate the delivery, adoption and use of particular health technologies, such as pit latrines, insecticides and vaccination. Together, these case studies reveal surprisingly similar reasons for why many interventions do not perform according to expectations. Despite new approaches that claim to overcome stereotypical challenges of top-down planning, narrow technocratic perspectives continue to play a defining role in maintaining disjunctions between global aspirations, local realities and intervention outcomes. New perspectives and changes in orientation are needed that emphasise flexibility, learning and adaptability to local contexts. Towards this end, the thesis outlines a conceptual framework based on a comparative analysis of the case studies that highlights five interrelated domains where effectiveness is determined: geographical/livelihood variation, local agency, incentives, the socio-materiality of technology and planning/governance. I argue that addressing the shortcomings of contemporary interventions requires that programme planners actively engage these domains by seeking to “order complexity.” Greater integration of social science perspectives into the management of NTD programmes would provide significant benefit. In these ways, the thesis contributes to wider debates about the nature of global health interventions and the influence of local contexts in mediating efforts to improve the health and wellbeing of the world’s poor and marginalised.
7

Prevalence of Strongyloides stercoralis infection in adult HIV–positive patients and comparison of specificity and sensitivity of five different methods to detect a current infection in Mwanza Province /Northern Tanzania / Prävelenz einer Strongyloides stercoralis Infektion bei Erwachsenen HIV positiven Patienten und Vergleich von Sensitivität und Spezifität fünf diagnostischer Verfahren in der Provinz Mwanza in Nord Tansania

van Eckert, Viviane Roxann January 2020 (has links) (PDF)
S. stercoralis is a helminthic parasite which is common in tropical and subtropical regions. It causes a persistent but often inapparent infection in humans. In the state of a protracted immunosuppression this parasite can cause a life-threatening hyperinfection syndrome. Most often the hyperinfection syndrome was found after prolonged high dose corticosteroid treatment. In HIV-infected individuals high dose corticosteroids are used for the treatment of the immune reconstitution inflammatory syndrome (IRIS) or as adjunct treatment in the treatment of meningeal or pericardial tuberculosis. Case reports from Tanzania demonstrate that Strongyloidiasis is prevalent not only in coastal regions but also in the Lake province of Tanzania. However, data on the local prevalence of S. stercoralis infection based on sensitive techniques are scanty, especially in HIV-infected individuals. The main objective of this study is to provide data on the prevalence of S. stercoralis infections in the adult HIV-infected population attending the Bugando Medical Centre for medical care. Specific objectives of the study are the comparison of the sensitivities and specificities of five different methods in detecting S. stercoralis. Four methods to detect S. stercoralis larvae used stool samples; one method to detect S. stercoralis antibodies required blood samples. The study used the Agar-plate-culture-technique and a modified Harada-Mori-culture-technique for the direct detection of helminthic larvae in the collected faecal samples. In addition, a recently described PCR-assay from faecal specimens and an ELISA for S. stercoralis antibodies have been applied. The Faecal Parasite Concentrator (FPC) stool concentration technique was used for the differential diagnosis of other intestinal helminthic parasites. The results of the study may influence the current treatment guidelines for HIV-infected patients in case that a relevant prevalence of S. stercoralis infection is found. Then, prior to a prolonged iatrogenic immunosuppression -like the high dose corticosteroid treatment for IRIS- a prophylactic anthelminthic treatment capable to eradicate a S. stercoralis infection could be recommendable. The prevalence of a current S. stercoralis infection using the PCR as a gold standard was 5.4%. The Agar plate method showed positive results in 19 out of 278 cases (6.1%), the modified Harada Mori technique in 13 of 278 (4.7%) cases. With PCR as gold standard the sensitivity of the agar plate method was 60%, the positive predictive value 47.4%, the specificity 96.2% and the negative predictive value 97.7 %. The sensitivity of the Harada Mori technique was 36.4%, the positive predictive value 30.7% with a specificity of 96.4% and negative predictive value 97.1%. The modified Harada Mori technique allowed in principal the morphological identification of nematode larvae. Microscopic analysis showed a specificity of 100% and a sensitivity of 46.7%. Antibodies were detected in 45 of 278 cases 16.2% by ELISA, with a sensitivity of 92.9% and a specificity of 87.8%. The findings of this study show that none of the diagnostic tests can be implemented as a routine diagnostic procedure to diagnose a current infection. This leads to the conclusion that it is high time to consider the provision of a prophylactic treatment within patients who are either HIV positive patients who could develop an IRIS after receiving ART, patients with a HTLV-1 infection and the growing number of patients under iatrogenic immunosuppression for various reasons. / S. stercoralis ist ein helmintischer Parasit der Endemisch in den Tropen und Subtropen, vor allem im warmen und feuchtem Milieu vorkommt. Eine Infektion mit S. stercoralis verläuft häufig asymptomatisch, kann aber über Jahre im menschlichen Körper persistieren. Bei immungeschwächten Patienten kann es zu einen Hyperinfektionssyndrom mit hoher Mortalität kommen Häufig kommt es zu einen Hyperinfektionssyndrom nach Einnahme von hoch Dosis Kortikosteroiden. Ca 20% der HIV positiven Patienten, die eine antiretrovirale Therapie beginnen entwickeln ein Immunrekonstitutionssyndrom. Die Therapie der Wahl ist dann u.a. hoch Dosis Kortikosteroide. Laut WHO sind 30-100 Millionen Menschen mit S. stercoralis infiziert. Diese Ungenauigkeit wiederspiegelt den erschwerten Nachweis einer Infektion. Bisher gibt es eine geringe Kenntnis über die Prävalenz von. S. stercoralis Infektionen in Tansania und kaum Daten vom bevölkerungsreichen Westen Tansanias. Die Region Mwanza am Lake Victoria zeigt sich als ein perfektes Milieu für das Vorkommen von S. stercoralis. Bisherige Ergebnisse der durchgeführten diagnostischen Tests weisen nur fragliche Sensitivitäten auf und es existieren keine Daten zur Prävalenz unter HIV positiven Patienten. Zudem wurden noch keine diagnostischen Methoden zur Prävalenzermittlung bei HIV positiven Patienten erprobt. Ziel der Studie ist die Verbesserung der Kenntnisse über Prävalenz von S.stercoralis Infektionen im bevölkerungsreichen Westen Tansanias. Die Analyse von Faktoren die Prävalenz von S. stercoralis beeinflussen, sowie Analyse der Prävalenz unter HIV Patienten mit fünf diagnostischen Testverfahren und Empfehlungen für den Umgang mit HIV Patienten in tropischen Milieu mit S. stercoralis Infektionswahrscheinlichkeit. Mit 278 Serum und Stuhlproben von HIV positiven Patienten wurden folgende Verfahren angewandt. Mit den Stuhlproben, die Modifizierte Harada Mori Methode und Agar Platten Methode am Bugando Medical Center, ein Realtime PCR und die FPC Methode und Mikroskopieren im Missionsärztlichen Institut, Würzburg. Mit den Serumproben erfolgte ein In House ELISA am Bernhard Nocht Institut, Hamburg. Die Prävalenz einer S.stercoralis Infektion in der PCR Methode war 5.4%. Die Agar Platten Methode zeigte positive Ergebnisse in 19 von 278 Fällen (6.1%). Die modifizierte Harada Mori Methode in 13 von 278 Fällen (4.7%). Unter der Annahme der PCR Methode als Goldstandard wies die Agar Platten Methode eine Sensitivität von 60% und Spezifität von 96.2% auf. Die Sensitivität der Harada Mori Methode war 36.4% und Spezifität von 96.4.%.Die FPC Methode zeigte eine Spezifität von 100%, jedoch nur Sensitivität von 46.7%.Das in House ELISA zeigte positive Ergebnisse bei 45 von 278 Patienten (16.2%) mit einer Sensitivität von 92.9%, jedoch nur Spezifität von 87.8%.Diese ungenauen Ergebnisse wiederspiegeln die Schwierigkeit eine S.stercoralis Infektion zu diagnostizieren. Die Ergebnisse zeigen, dass kein Verfahren als Standardverfahren, um eine Infektion zu diagnostizieren, in Nordtansania, implementiert werden kann. Somit kann man zusammenfassend sagen, dass alle Patienten die eine ART beginnen prophylaktisch gegen S. stercoralis behandelt werden sollten. Zumindest die, die eine TBC Koinfektion haben und auf die das Risikoprofil zutrifft.
8

Neglecting the Essentials: Addressing Barriers to Accessing Off-Patent Essential Medicines for Neglected Diseases in Canada

Houston, Adam Rainis 09 September 2022 (has links)
In Canada, less than half of the drugs that the World Health Organization classifies as Essential Medicines for the treatment of Neglected Diseases like Chagas disease, drug-resistant tuberculosis, echinococcosis, leishmaniasis, leprosy, malaria and sleeping sickness are formally available, even as collectively hundreds of patients require access to them each year. Essential Medicines, according to the WHO, are those “intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford”. Nevertheless, many of these Essential Medicines, like the conditions they treat, are neglected by pharmaceutical companies and governments alike in low-burden, high-income countries like Canada. The result is a reversal of the usual access to medicines narrative around novel, patented medicines unavailable in low-income countries; these are old, off-patent Essential Medicines, many of which have become widely available in low and middle-income countries yet increasingly difficult to access in many high-income countries. Their absence from countries like Canada is not due to their lack of medical utility – many of them are recognized domestically as the standard of care – but their lack of commercial value. Unfortunately, Canada’s regulatory system is premised upon keeping unsafe, ineffective or poor-quality drugs out, not bringing Essential Medicines in. As a result, these drugs must be accessed through ill-fitting mechanisms like Canada’s Special Access Programme (SAP). Other high-income countries face similar access challenges, though they may manifest in different ways; in the United States for instance, drugs that have disappeared from the Canadian market or simply never been introduced in the first place have instead had de facto monopolies unscrupulously exploited. In turn, as the COVID-19 pandemic has served to underscore, access to these Essential Medicines for Neglected Diseases is an issue that cannot be solved solely at the domestic level. Essential Medicines that threaten to disappear before the diseases they treat do also serve to highlight broader issues of domestic and international concern, from drug shortages to antimicrobial resistance. This thesis provides an in-depth exploration of the problem, and offers guidance on what Canada in particular can do about improving access to medicines, especially those for Neglected Diseases that have been largely absent from the Canadian pharmaceutical agenda.
9

Discriminação de organismos do gênero Leishmania por análises de perfis de dissociação em alta resolução (HRM - High Resolution Melting) / Discrimination of organisms from the Leishmania genus by High Resolution Melting analysis (HRM)

Zampieri, Ricardo Andrade 17 May 2019 (has links)
Leishmanioses são doenças classificadas pela Organização Mundial da Saúde (OMS) como negligenciadas, o que as caracterizam como aquelas que prevalecem em condições de pobreza e representam significativo entrave ao desenvolvimento por contribuírem para desigualdade. Cerca de 350 milhões de pessoas vivem sob o risco de infecção em 98 países da África, Eurásia e Américas. Acometem o homem e outros animais sob um espectro clínico amplo, que varia de discretas lesões, de cura espontânea, a quadros de comprometimento sistêmico, potencialmente fatais. A manutenção do ciclo de transmissão está inserida em um sistema biológico complexo, com a participação de mais de 20 espécies de Leishmania e uma grande variedade de reservatórios e vetores, e o diagnóstico está entre as estratégias empregadas para o controle dessas doenças. A precisa identificação das espécies envolvidas no ciclo de transmissão permite a geração de dados importantes para mapeamentos ecoepidemiológicos e para o delineamento de estratégias terapêuticas e de controle. O material genético do parasita como alvo de detecção e identificação desses organismos é descrito na literatura científica em trabalhos que abordam diversas estratégias metodológicas. Entre as técnicas mais recentes estão as análises de dissociação em alta resolução (HRM- High Resolution Melting), descrita como uma estratégia eficiente para a discriminação de polimorfismos em fragmentos específicos de DNA gerados por PCR (Polymerase Chain Reaction). O presente trabalho teve como principal objetivo padronizar um protocolo de detecção e identificação de Leishmania capaz de discriminar o maior número possível de espécies com base em polimorfismos do gene hsp70, utilizando HRM como ferramenta metodológica. Sequências nucleotídicas de hsp70 disponíveis em banco de dados e obtidas no laboratório foram analisadas in silico e regiões polimórficas foram delimitadas. Das regiões delimitadas, três foram escolhidas por conterem polimorfismos que geraram fragmentos cujas temperaturas de dissociação simuladas são distintas entre espécies ou grupo de espécies. A exploração de perfis de dissociação dos três amplicons de hsp70 obtidos por PCR em tempo real revelou diferenças que permitiram a discriminação das espécies de Leishmania responsáveis por doenças nas Américas, África e Eurásia. Os testes foram padronizados com a utilização de DNA de cepas-referência de Leishmania e então aplicados a amostras de DNA obtidas de amostras clínicas, de campo ou experimentais, como isolados, biópsias humanas frescas ou fixadas, flebotomíneos e cães naturalmente infectados e camundongos experimentalmente infectados. Os resultados obtidos por HRM foram comparados aos obtidos previamente por outras metodologias como PCR convencional, RFLP (Restriction Fragment Length Polymorphism) ou sequenciamento, com confirmação da identidade do parasita nas amostras testadas. O protocolo descrito é relativamente barato, tecnicamente simples, passível de automatização, podendo ser uma alternativa para a detecção e identificação de Leishmania em amostras, em estudos diagnósticos e ecoepidemiológicos. / According to the World Health Organization (WHO), the leishmaniases are classified as neglected diseases, since they are related to poverty and contribute to inequality. Approximately 350 million people are at risk of infection in 98 countries in Africa, Eurasia and Americas. They affect humans and other animals that, depending on the species, causes a wide spectrum of clinical manifestations, that range from discrete lesions of spontaneous healing to potentially fatal systemic disease. The maintenance of the transmission cycle is part of a complex biological system, in which there is the participation of more than 20 species of Leishmania and a large variety of reservoirs and vectors. Diagnosis is important for early control of the disease. A precise identification of the species involved in the transmission cycle allows the generation of important data for eco-epidemiological mapping and for therapeutic measures and control strategies. Several genes have been used as diagnostic targets and several molecular strategies have been used in diagnosis. High resolution melting (HRM) analysis is among the most recent techniques and it is described as an efficient strategy for discriminating polymorphisms in specific DNA fragments generated by PCR (Polymerase Chain Reaction). The main objective of this work was to standardize a protocol for detection and identification of Leishmania spp, capable of discriminating the largest possible number of species based on hsp70 gene polymorphisms through HRM methodological tool. Available nucleotide sequences of hsp70 in databases as well as the ones obtained in the laboratory were analyzed in silico and polymorphic regions were delimited. Three regions were chosen since they contained polymorphisms that generated distinct simulated dissociation temperatures among species or group of species. The analysis of dissociation profiles of the three amplicons of hsp70 obtained by real-time PCR revealed differences that allowed the discrimination of Leishmania species responsible for diseases in the Americas, Africa and Eurasia. The tests were standardized using DNA from Leishmania reference strains and then applied to DNA samples obtained from clinical or from field samples, such as isolates, fresh or fixed human biopsies, phlebotomines and dogs naturally infected, and experimentally infected mice. The results obtained by HRM were compared to those obtained previously by other methodologies such as conventional PCR, RFLP (Restriction Fragment Length Polymorphism) or sequencing, confirming the parasite identity in the samples tested. The described protocol is relatively inexpensive, technically simple, potentially automated, and may be an alternative for the detection and identification of Leishmania in biological samples, in diagnostic and eco-epidemiological studies.
10

Tuberculostáticos potenciais planejados com base na estrutura de maltosiltransferase (GlgE) de mycobacterium tuberculosis. Estudo da síntese por meio de micro-ondas / Potential antituberculosis designed based on the structure of maltosiltransferase (GlgE) of mycobacterium tuberculosis. Study of microwave synthesis.

Fonseca, Guilherme Dutra de Moraes Marques da 15 April 2016 (has links)
A tuberculose (TB) é uma doença infectocontagiosa, causada por micobactérias do complexo Mycobacterium, principalmente, o M. tuberculosis. Praticamente extinta em países desenvolvidos, antigamente denominados Países de Primeiro Mundo, a tuberculose voltou a ter foco mundial dada a sua crescente taxa de incidência e mortalidade. Segundo a Organização Mundial de Saúde, a TB, hoje, figura como principal causa de morte por doenças infectocontagiosas em todo mundo, com a incidência de 8,6 milhões de novos casos ao ano e cerca de 1,5 milhões de mortes. O principal desafio no tratamento da tuberculose é a multirresistência de M. tuberculosis frente aos fármacos disponíveis. Sendo assim, a busca de novos fármacos antituberculose e o estudo de novos alvos são necessários para superar essa situação. Frente à necessidade de exploração de novos alvos e ante a indicação da maltosiltransferase (GlgE) como novo alvo potencialmente promissor contra M. tuberculosis, este projeto pretendeu viabilizar a síntese de análogos da glicose (análoga do substrato natural da GlgE, a maltose 1-fosfato) por meio de rotas sintéticas que fazem uso do micro-ondas. Essas rotas sintéticas seguem os princípios da click chemistry, que são reações químicas modulares, cujas condições reacionais são simples e resultam em produtos de fácil purificação. O presente trabalho também visou à comparação entre o método convencional de síntese de triazóis e aquele que utiliza o micro-ondas, no que se refere aos os tempos de reação, às condições reacionais e aos rendimentos com derivados sintetizados no Laboratório de Planejamento e Síntese de Quimioterápicos Potencialmente Ativos em Doenças Negligenciadas (LAPEN). Entretanto, não obteve-se sucesso na etapa final da rota sintética, a glicosilação. Nos demais métodos sintéticos o micro-ondas mostrou-se uma valiosa ferramenta para obtenção dos compostos triazólicos. / Tuberculosis (TB) is a contagious infectious disease caused by the Mycobacterium complex, mainly by M. tuberculosis. Practically extinct in developed countries, formerly called First World countries, tuberculosis has returned to global focus given its growing incidence rate and mortality. According to the World Health Organization, TB today stands as the main cause of death from infectious diseases worldwide, with the incidence of 8.6 million new cases per year and about 1.5 million deaths. The main challenge in the treatment of TB is multidrug resistance of M. tuberculosis to available drugs. Thus, the search for new anti-tuberculosis drugs and the study of new targets are needed to overcome this situation. Faced with the need to explore new targets and at the indication of maltosiltransferase (GlgE) as a new potentially promising target against M. tuberculosis, this project intended to enable the synthesis of glucose analog (analog of the natural substrate of GlgE, maltose 1- phosphate ) by synthetic routes that make use of microwaves. These synthetic routes follow the principles of click chemistry, which are modular chemical reactions whose conditions are simple and result in easy purification products. This study also aimed to compare the conventional method of triazoles synthesis and the one which uses microwaves in relation to the reaction time, the reaction conditions and yields derivative synthesized in Laboratory of Design and Synthesis of Chemotherapeutic Agents Potentially Active in Neglected Diseases (LAPEN). However, no success was obtained in the final of the synthetic route stage glycosylation. In the other synthetic methods the microwave proved to be a valuable tool for obtaining the triazole compounds.

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