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Goliati, Tiyamike Harold. "Desafios dos profissionais de saúde do Malaui sob a política neoliberl = migração e falta de enfermeiros no setor público de saúde do Malaui 1993-2008." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/285958.
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Previous issue date: 2010<br>Resumo: A falta de enfermeiras do setor público de saúde de Malaui está afetando a habilidade das enfermeiras remanescentes para executarem seus deveres eficientemente. Essa escassez tem sido exacerbada pela existência de migração de enfermeiras e outros profissionais ligados à saúde. A deterioração do setor público de saúde combinada ao ambiente pobre de trabalho e salários reais em queda repele a migração de enfermeiras do setor público de saúde do país para organizações privadas e países desenvolvidos ao perceberem que têm uma boa remuneração e um ambiente de trabalho ideal para seus funcionários. A implementação de políticas neoliberais no país contribuiu com o declínio dos gastos sociais com a saúde e com outros serviços sociais que tem uma implicação direta no desenvolvimento social. Metodologia: A pesquisa visou entender a migração e a falta de enfermeiras no setor público de saúde no contexto de desafios contemporâneos para os profissionais de saúde em Malaui sob as políticas neoliberais. Ele empregou uma abordagem mista de desenho. Os dados foram analisados usando o pacote de estatísticas para ciências sociais (SPSS) versão 15.0 para Windows. Dados qualitativos foram feitos por análise de conteúdo e então, analisados posteriormente pelo SPSS. Resultados: As enfermeiras de Malaui encontram desafios multilaterais. Eles incluem baixos salários, baixos benefícios de aposentadoria, acomodação inadequada, nenhum acesso aos empréstimos do governo para enfermeiras de cabeceira, recursos/enfermeiras insuficientes, a sobrecarga de trabalho, as condições precárias de trabalho, as escassas oportunidades de treinamento, ambiente inseguro de trabalho. Conclusão: A situação, no entanto, está mudando lentamente devido ao crescente comprometimento do governo com relação ao setor de saúde, juntamente com medidas Keynesianas na economia. O desgaste das enfermeiras tem estado sob uma tendência descendente; as saídas de enfermeiras de instituições de treinamento têm aumentado; indicadores econômicos e sociais têm sido positivos; e o pacote de remuneração, as condições de trabalho e o ambiente de trabalho têm melhorado. Salários em termos reais têm subido em uma tentativa de reverter os salários reais em queda que balançaram o Mercado de trabalho desde que as políticas neoliberais encontraram seu espaço na política de Malaui<br>Abstract: Shortage of nurses in Malawian public health sector is affecting the ability of the remaining nurses to discharge their duties effectively. This scarcity has been exacerbated by existence of migration of nurses and other health-care personnel. Deterioration of the public health sector combined with the poor working environment and decreasing real wages repel the out-migration of nurses from the country?s public health sector to private organisations and developed countries perceived to have good remuneration package and ideal working environment for their employees. The implementation of neoliberal policies in the country contributed to decreasing social spending for health and other social services that have a direct implication on social development. Methodology: The research was aimed at understanding the migration and shortage of nurses in the public health sector in the context of contemporary challenges for health-care professionals in Malawi under neoliberal policies. It employed a mixed design approach. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 15.0 for Windows. Qualitative data were done by content analysis and then analysed further by SPSS. Results: Malawian nurses face multilayered challenges. These include, low salaries, low retirement benefits, Inadequate accommodation, No access to Government loans for bedside nurses, insufficient resources/nurses, Work overload, Poor working conditions, scarce training opportunities, unsafe working environment. Conclusion: the situation, however, is slightly changing due to increased government commitment towards health sector coupled with Keynesian measures in the economy. Nurses? attrition has been on a downward trend; outputs of nurses from training institutions have been rising; social and economic indicators have been positive; and remuneration package, working conditions and working environment have been improving. Salaries in real terms have been rising in an attempt to reverse the decreasing real wages that rocked the labour market since neoliberal policies found its space in the Malawian policymaking<br>Mestrado<br>Economia Social e do Trabalho<br>Mestre em Desenvolvimento Econômico
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Fisher, Sarah Marie. "The Design and Evaluation of a Durable and Cost-Effective Handle for the LifePump™." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu155537322622029.
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McNamee, Cameron. "The hunger trap ganyu labor and agricultural output in Malawi /." CONNECT TO ELECTRONIC THESIS, 2007. http://dspace.wrlc.org/handle/1961/4263.
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Thorold, Alan Peter Hereward. "The Yao Muslims : religion and social change in southern Malawi." Thesis, University of Cambridge, 1995. https://www.repository.cam.ac.uk/handle/1810/226813.
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The African Muslim minority in Malawi has been identified with one particular linguistic group, the Yao. The dissertation begins with the problem of their conversion and adherence to Islam in the face of seemingly adverse circumstances. In exploring-solutions to this problem the emergence of a Yao identity is outlined and the politics of conversion are described. The narrative then moves on to the transformations of the Yao Muslims in the hundred years since their conversion. A model of religious change is developed that attempts to account for both the dynamics of change and the contemporary situation of Islam in southern Malawi. The Yao Muslims are shown to be divided into three competing and sometimes hostile factions that are termed the Sufis, the sukuti or 'quietist' movement and the new reformists. The appearance of these movements and their interaction with one another is described in relation to the questions of identity and religious practice. The model proposes a three phase scheme of Islamic change (appropriation and accommodation followed by internal reform and then the new reformist movement) that is defined in part by the relationship of the Yao Muslims to writing and the Book. It is suggested that a certain logic of transformation is endogenous to Islam as a religion of the Book and that the scripturalist tendencies of the reformist movement give it an advantage over the followers of Sufi practices, especially in the context of modern systems of communication and education. The general approach is that of an historical anthropology, linking notions of structured change to anthropological concerns with ritual and practice. The analysis concludes by raising questions about the nature of religious change in the context of an increasingly volatile world system and the place of the anthropology of religion in the understanding of modernity.
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Quinn, Ann-Lise. "Working on the Protestant ethic : life in a Presbyterian community in Malawi." Thesis, University of Cambridge, 1993. https://www.repository.cam.ac.uk/handle/1810/272568.
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Kamwamba-Mtethiwa, Jean Tiyamika. "Sustainable irrigation development : the adoption of small-scale pumped irrigation in Malawi." Thesis, Cranfield University, 2016. http://dspace.lib.cranfield.ac.uk/handle/1826/10005.
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There has been an increased interest on small-scale pumped irrigation (SSPI) in Sub Saharan Africa (SSA), however little is known on the adoption processes behind this technology. Moreover, the conditions for successful SSPI adoption remain largely unexplored. This research aims to achieve a deeper understanding of the present adoption processes to inform future policy. The thesis was framed around the diffusion of innovations model (Rogers 2003), using the systematic review methodology and field surveys. Interviews involving 212 farmers and 25 other stakeholders were conducted between 2013 and 2014 within 3 districts in Malawi. The responses were analysed using descriptive statistics and content analysis. The systematic review revealed that evidence relating to pump performance in SSA was limited, lacked standards and confined within particular regions. The field surveys identified that four different pumped systems have been adopted by farmers in Malawi; group treadle, individual treadle, group motorized and individual motorized. Farmers generally prefer individually managed pumps that are easy to operate and fit in with their existing farming practices. Adoption is driven either by the attributes of self-motivated farmers or by incentives such as free or subsidized pumps. While adoption by self-motivated farmers is consistent with Rogers (2003) model, adoption due to incentives shows differences. The research proposes a modification to the Rogers (2003) model and revised definition of success in SSPI adoption, leading to a new framework showing pathways of success. This framework identifies the routes taken by farmers who successfully adopt or discontinue using pumps. Incentive farmers are typically the poorer; these need continued external support to survive the learning curve. For self-motivated farmers, their higher socio-economic status supports successful adoption. To ensure sustainability, SSPI promoters need to offer continued support to incentive farmers and/or reduce barriers to accessing the pumps for self-motivated farmers.
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Chidanti-Malunga, Joseph Fred. "Wetland farming and small-scale informal irrigation in Malawi : the case of Shire Valley." Thesis, Cranfield University, 2009. http://dspace.lib.cranfield.ac.uk/handle/1826/4457.
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Historically, Malawi has depended on rain-fed agricultural systems. It is reported that the frequent droughts and unreliable rainfall since early 1990s have caused many small-scale farmers to turn to the wetlands as alternative sites for crop production. There they use low-cost farming methods and various forms of ‘informal’ irrigation. This study, to better understand the water management practices and the socioeconomic characteristics of the wetland farmers, was carried out in the Shire Valley, at the southern tip of Malawi. This covers about 600,000ha and supports around 250,000 farming families. More than half is wetland, characterized by a network of small streams, rivers, and swamps, and a mosaic of many very small farms separated by bush. Phase I mainly documented the agriculture technologies and socioeconomic characteristics of wetland farming and small-scale informal irrigation systems. 200 farmers and other key informants were interviewed. Phase II aimed to define and measure the benefits of the current systems. The major farming systems groups were identified using cluster analysis and focus group discussions were carried out with 7 to 10 members of each. The results were assessed using gross margin analysis. The results show that flood recession agriculture, river diversion and treadle pumps were the commonest water management technologies among the farmers interviewed. Most preferred flood recession and river diversion to treadle pump, citing capital requirements and running costs as major obstacles. However, the government and NGOs were promoting treadle pump technology (mostly) and river diversion, but not recession agriculture. Motorized pumps, introduced under various schemes, were no longer in use due to farmers’ inability to meet fuel costs and repairs. Farmer access to land was largely under the control of individual farmers who pass on ownership to their children under traditional custom. This finding is contrary to the documented land policy which describes chiefs as custodians of the land. Many farmers viewed group farming as a surrender of their land ownership rights. However, team work was seen to be common in river diversion technologies where a committee was usually chosen to manage a main canal traversing several farms. Even under these circumstances, farmers still preferred to manage their plots individually. The economic analysis showed low farmer-benefits, except where flood recession agriculture was used to grow sweet potatoes, although this receives no attention from government or NGOs. Among the problems were the farmers’ inability to afford inputs, promotion of unsuitable technologies, and government controlled market prices. The study found that the increased wetland use was partly a livelihood diversification strategy linked to droughts and the worsening of the economic situations caused by structural adjustments in the early 1990s. This study encourages government or NGOs to promote the technologies that are acceptable to the farmers and seen to benefit them under the local socioeconomic conditions. Locally, these include flood recession agriculture and small river diversions. Reducing production costs and increasing yields through more efficient water use and improved extension services should be encouraged, and subsidizing input costs and freeing market prices would also help.
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Ahn, Tyler. "Children of Malawi the impact of agricultural technology on educational attainment and child labor hours /." CONNECT TO ELECTRONIC THESIS, 2007. http://dspace.wrlc.org/handle/1961/4174.
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Putter, C. "Unfolding tragedies : the impact of a mother's death on her kin and community : an ethnography from Southern Malawi." Thesis, Queen Margaret University, 2003. https://eresearch.qmu.ac.uk/handle/20.500.12289/7474.
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In examining the specific impact of a mother's death on her surviving family and community, the thesis highlights the social devastation resulting from such an event. Crucially, it argues that the increased frequency of maternal death associated with the HIV/AIDS epidemic, and the associated increase in numbers of orphaned children, have the potential to provoke full-scale destruction of traditional kinship structures and coping mechanisms. The study contributes to a gendered study of death and the resultant coping mechanisms as well as emphasizing the importance of sibling bonds in Malawian kinship. Furthermore, it provides an analysis of the current trends relating to orphan care, and suggests how these goals could be improved within the specific cultural context. The findings are based on 14 months of in situ fieldwork, during which time a totla of 78 interviews were conducted with 66 individuals, 46 of whom are case studies. Further interviews were conducted with hospital personnel, workers with orphans, and teachers, i.e. those in positions to provide social commentary. Nudist N4 software was used for data management of the interview transcripts and fieldnotes, and facilitated access to the coded data as analysis proceeded. An historical understanding of Malawi's cultural context is outlined in the introductory chapter and the entire discussion is grounded within this context. More detailed anthropological data is provided in the chapter on kinship, which emphasizes the importance of maternal kin in looking after orphans subsequent to a mother's death. Chapters on HIV and death outline how communities are besieged by illnesses surrounding HIV-infection, and how the increased death rates associated with HIV have undermined the traditional bereavement processes, and, hence, the associated coping mechanisms. The thesis concludes with a discussion of the kinds of orphan care currently available in Malawi, followed by recommendations on how the needs of orphans could better be met by development initiatives that are more suited to working with community-based organizations.
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Marandet, Elodie. "Governing through freedom, ruling at a distance : neoliberal governmentality and the new aid architecture in the AIDS response in Malawi." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/7657.
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In this thesis, I critically analyse power relations between donors and the government of Malawi (GoM) under the new aid architecture and argue that this new configuration represents a shift away from domination, with donors attempting to impose policies, and towards more subtle interactions, through which donors seek to transform the GoM into a self-disciplined, entrepreneurial, neoliberal subject by shaping its aspirations and promoting specific norms of conduct, ‘truths’ and policy-related techniques. The research focuses on funding for AIDS and draws on forty interviews with representatives from the GoM, donors and civil society, conducted in Malawi 2008, as well as discursive analysis of secondary sources. I use Foucault’s concept of governmentality, a form of productive power focused on the care of the population and working through individuals’ subjectivities, and extend it to the relation between donors and the GoM. I show that the agency of the GoM is both elicited by the principle of country ownership, and re-worked through the increased involvement of donors in the policy sphere. I explore how these interactions are legitimised by a discourse that presents donors and the GoM as equals, while casting the GoM as technically deficient and requiring donors’ intervention. I analyse how donors instrumentalise dialogue with the GoM to instil an ethos of self-responsibility.I also investigate how AIDS funding has been made reliant on public financial management reforms, which re-code social domains according to an economic logic, by subordinating government activities to macroeconomic imperatives and creating new undemocratic accountabilities based on market rationalities. I argue that by restructuring the GoM according to this neoliberal rationality, the new aid architecture has programmatic effects, allowing donors to rule at a distance. I also examine avenues for resistance, particularly the potential residing in the intrinsic contradictions of this rationality.
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Smith, Benjamin Wellard. "Rock art in south-central Africa : a study based on the pictographs of Dedza District, Malawi and Kasama District, Zambia." Thesis, University of Cambridge, 1995. https://www.repository.cam.ac.uk/handle/1810/283703.
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Uny, Isabelle. "Weighing the options for delivery care in rural Malawi : community actors' perceptions of the 2007 policy guidelines and redefined traditional birth attendants' roles." Thesis, Queen Margaret University, 2017. https://eresearch.qmu.ac.uk/handle/20.500.12289/7469.
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Despite significant recent improvements, maternal mortality remains high in Malawi. To address this, the Government prioritised strategies promoting skilled birth attendance. However, in a country where 80% of the population resides in rural areas, there are tremendous barriers to institutional deliveries. Historically rural women have been supported in childbirth by Traditional Birth Attendants (TBAs), and by skilled birth attendants (SBAs) at the health facility. In the past, TBAs were trained to help bridge the gaps in provision and accessibility of care but in the 1990’s, the WHO recommended halting their training because it was perceived as ineffective for maternal mortality reduction. In 2007, the Government of Malawi issued Community Guidelines to promote skilled birth attendance and banned TBA utilization for routine deliveries. This grounded theory qualitative study used interviews and focus groups to explore community actors’ perceptions of the 2007 Policy Guidelines and their implementation, and how the Policy affected the decisions and actions of rural women regarding their delivery care. Findings from this study indicate that although all actors may agree that delivering at facilities is safest when complications occur, this does not necessarily ensure their compliance. Women, men and TBAs particularly, perceived the Policy as prescriptive. Furthermore, the implementation of the policy aggravated some of the barriers women already faced. Issues of disrespectful and neglectful care at facilities also partly led women towards non-compliance. Furthermore, a view from the ground demonstrated that the Policy had led to a rupture of linkages between TBAs and SBAs, which have had a detrimental effect on the continuum of care. This study helps fill an important gap in research concerning maternal health policy implementation analysis in LICs, by focusing on the perceptions of those at the receiving end of policy change, and on their needs, and aspirations.
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Gama, Elvis Sitithana Mpakati. "The implications of contracting out health care provision to private not-for-profit health care providers : the case of service level agreements in Malawi." Thesis, Queen Margaret University, 2013. https://eresearch.qmu.ac.uk/handle/20.500.12289/7457.
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Background: The Malawi government in 2002 embarked on an innovative health care financing mechanism called Service Level Agreement (SLA) with Christian Health Association of Malawi (CHAM) institutions that are located in areas where people with low incomes reside. The rationale of SLA was to increase access, equity and quality of health care services as well as to reduce the financial burden of health expenditure faced by poor and rural communities. This thesis evaluates the implications of SLA contracting out mechanism on access, utilization and financial risk protection, and determines factors that might have affected the performance of SLAs in relation to their objectives. Methods: The study adopted a triangulation approach using qualitative and quantitative methods and case studies to investigate the implications of contracting out in Malawi. Data sources included documentary review, in-depth, semi-structured interviews and questionnaire survey. The principal agent model guided the conceptual framework of the study. Results: We find positive impact on overall access to health care services, qualitative evidence of perverse incentives for both parties to the contracting out programme and that some intended beneficiaries are still exposed to financial risk. Conclusion: An important conclusion of this study is that contracting out has succeeded in improving access to maternal and child health care as well as provided financial risk protection associated with out of pocket expenditure. However, despite this improvement in access and reduction in financial risk, we observe little evidence of meaningful improvement in quality and efficiency, perhaps because SLA focused on demand side factors, and paid little attention to supply factors: resources, materials and infrastructure continued to be inadequate.
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Kachale, Blessings. "Elderly carers : the experiences of the elderly caring for orphans and vulnerable children in the context of the HIV/Aids epidemic in Chiradzuru district, Malawi." Thesis, Queen Margaret University, 2015. https://eresearch.qmu.ac.uk/handle/20.500.12289/7464.
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PURPOSE: This qualitative study explores the day-to-day care experiences and livelihoods challenges of the elderly carers of orphan and vulnerable children (OVCs) in rural Chiradzuru district in Malawi. The study aims to highlight the impact of AIDS mortality on Elderly Households’ livelihood assets. METHOD: Using case study approach data was collected from 43 cases comprised of 23 individuals and 3 Focus Groups. The main study participants were elderly-headed households caring for OVCs. Data was collected and the evidence converged using the Sustainable Livelihood Framework (SLF) to analyse findings. FINDINGS: The main ten study participants were between the ages 55-90+ caring for thirty-eight OVCs; seven of whom were single females caring for OVCs aged between 2-16 years old-some of them caring for second generation of orphans(great grandchildren). Although this is crisis-led fostering, most of the elderly have accepted the responsibility regardless of their capabilities. This highlights the value of family based care in these families. Six of the ten elderly carers had lost a significant number of assets to AIDS sickness and death of family members. A few had given up their wage earning livelihoods to care for OVCs while for the very old (71-90) their physical old-age disabilities affected pursuance of livelihoods impacting their food security and acquisition of basic needs. There was mutual reciprocity between the OVCs and their carers to pursue livelihoods which increased household resilience. Conclusion: The elderly in Chiradzuru need social security support so that they must not give up care of their children to alternative care arrangements which can contribute to trauma on OVCs.
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Jimmy-Gama, Dixon. "An assessment of the capacity of faculty-based youth friendly reproductive health services to promote sexual and reproductive health among unmarried adolescents : evidence from rural Malawi." Thesis, Queen Margaret University, 2009. https://eresearch.qmu.ac.uk/handle/20.500.12289/7456.
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Despite the recognition of the influence of cultural norms on adolescent sexual behaviours in most societies (Kaler 2004; Chege 2005), less attention has been paid to the link between social norms and effectiveness of health facilities to promote adolescent sexual and reproductive health (ASRH). This thesis therefore examines the capacity of facilitybased youth-friendly reproductive health services (YFRHS) to promote ASRH in rural Malawian societies where culture strongly influences adolescent sexual behaviours. The study employs a social constructionist epistemology and a social interactionism theory to understand the capacity of YFRHS in ASRH promotion in rural Malawi. Qualitative and quantitative data were collected using a sequential exploratory design. Semi-structured in-depth interviews, participant observations, client exit interviews, survey, focus group discussions and review of health strategic and service utilisation documents/records were conducted. The results were generated by triangulating both qualitative and quantitative data. The findings of the study illuminate how social norms related to social identities influence adolescent sexual behaviours and ASRH promotion. An exploration of the cultural context reveals a major disjuncture between an ideal norm - no premarital sex - and a modelled norm where unmarried adolescents are expected to engage in unsafe sex. It also shows the conflicts between the cultural and scientific models of ASRH promotion. Structural gender asymmetry that emphasises subservience in females and hegemonic masculinity also reduces adolescents’ rights and agency in SRH promotion. The health providers are cultural agents. They manage diverse roles both as ‘moral guardians’ and as ‘health promoters’ in a way that limits their effectiveness as health promoters. The thesis concludes that the way facility-based YFRHS is implemented has limited impact on SRH promotion among unmarried adolescents of rural Malawi. The study recommends that appropriate health promotion interventions based on conscientisationoriented empowerment theories directed at adolescents, community and health workers should be used in ASRH promotion in societies with strong cultural influence on sexual behaviours.
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Malkawi, Bashar H. [Verfasser]. "Jordan and the World Trading System / Bashar H. Malkawi." München : GRIN Verlag, 2018. http://d-nb.info/1175287652/34.
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DUDENKO, PASCAL ALEXANDRE. "Prothese totale de hanche pour coxopathie pagetique : a propos de 23 observations." Lille 2, 1988. http://www.theses.fr/1988LIL2M013.
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PAPI, JEAN-ALAIN. "Contribution a l'etude de l'echotomographie dans le depistage de la maladie luxante de la hanche." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20161.
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GAUDUCHON, THIERRY. "Traitement de la coxopathie pagetique par prothese totale de hanche : a propos de 19 observations." Lyon 1, 1991. http://www.theses.fr/1991LYO1M166.
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Gaillard, Catherine. "Coxopathies pagetiques : a partir de 27 observations." Limoges, 1988. http://www.theses.fr/1988LIMO0197.
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LE, TOURNEUR LETAN CORINNE. "Evaluation de la prevention de la maladie thromboembolique dans un service d'orthopedie : etude de 100 malades apres prothese de hanche." Rennes 1, 1993. http://www.theses.fr/1993REN1M076.
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GACON, THIERRY. "Indications de la prothese totale de hanche dans la maladie de paget : a propos de 22 cas (de la clinique orthopedique du parc lyon, du chr de besancon et du chu de lyon)." Lyon 1, 1993. http://www.theses.fr/1993LYO1M131.
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CESSOU-VIENNE, ANNE. "Manifestations osteo-articulaires de la maladie de gaucher a partir d'une observation personnelle et d'une revue de la litterature." Lyon 1, 1990. http://www.theses.fr/1990LYO1M059.
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Boubel, Jacques. "Etude d'une famille présentant sur cinq générations une association CMT et luxation congénitale de la hanche." Montpellier 1, 2000. http://www.theses.fr/2000MON11138.
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TOURLAN, JEAN-MARC. "Le traitement de la maladie luxante de hanche par le harnais de pavlik : a propos de 140 cas." Lyon 1, 1988. http://www.theses.fr/1988LYO1M103.
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Winzenrieth, Renaud. "Caractérisation et modélisation de la hanche chez l'enfant par IRM : application à la maladie de Legg-Calvé-Perthes." Compiègne, 2004. http://www.theses.fr/2004COMP1545.
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La maladie de Legg-Calvé-Perthes touche un grand nombre d'enfants, principalement des garçons. Cette maladie résulte d'une absence de vascularisation de l'épiphyse fémorale et se définit comme une ischémie vasculaire provoquant d'importants problèmes biomécaniques. C'est dans ce contexte clinique que s'inscrit ce travail concernant la caractérisation et la modélisation de la hanche, de manière à mieux connaître l'aspect de l'articulation aux différents stades de la maladie et à pouvoir trouver des facteurs objectifs donnant une classification prospective de la maladie. Pour cela, deux approches complémentaires ont été abordées: une approche biomécanique modélisant l'articulation et évaluant les rapports de forces mécaniques appliquées sur cette articulation; et une approche par traitement d'images, permettant l'obtention de la géométrie de l'articulation, la quantification biomécanique des différents tissus articulaires et la vascularisation de la tête fémorale<br>Legg-Calvé-Perthes disease is defined as an idiopathic avascular necrosis of the femoral epiphysis leading to biomechanical disorders. It affects a number of children, more frequently boys. It is in this clinical context that our study characterizes and models the hip. This study has been performed to better understand the various stages of the disease and the objective factors to identify the prospective classification of the disease. For this, two complementary approaches were elaborated: a biomechanical approach modelling the articulation and evaluating the applied mechanical stress; and an image processing approach, allowing to obtain the joint geometry, the biomechanical characterization of the joint tissues and the vascularization of the femoral head
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Kany, Jean. "Interet de la triple osteotomie pelvienne dans les formes graves de la maladie de legg-perthes-calve : etude de son influence sur la morphologie du cotyle." Toulouse 3, 1994. http://www.theses.fr/1994TOU31530.
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Proumen, Gérard. "Evaluation d'une héparine de bas poids moléculaire : l'enoxaparine dans la prévention de la maladie thrombo-embolique lors de la chirurgie de la hanche : étude rétrospective à partir de 237 observations." Montpellier 1, 1990. http://www.theses.fr/1990MON11056.
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LACHMANN, ROLLAND. "Maladie luxante et dysplasie de la hanche chez le nouveau-ne et le nourrisson : interet du harnais de pavlik." Saint-Etienne, 1988. http://www.theses.fr/1988STET6024.
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Gachard, Nathalie. "Etude moléculaire des lymphomes B indolents : exemple des lymphomes de la zone marginale et de la maladie de Waldenström." Limoges, 2012. http://aurore.unilim.fr/theses/nxfile/default/69545d39-f061-48b4-8ff3-5f185f51be2c/blobholder:0/2012LIMO310I.pdf.
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Le locus des chaînes lourdes des immunoglobulines est une structure génétique complexe qui subit de nombreux remaniements géniques au cours de la maturation B mais aussi au cours des modèles tumoraux que sont les lymphomes B. Les lymphomes de la zone marginale (MZL) comportent 3 sous-types selon le territoire infiltré : les lymphomes spléniques de la zone marginale (SMZL), les lymphomes ganglionnaires de la zone marginale (NMZL) et les lymphomes des tissus lymphoïdes liés aux muqueuses ou lymphomes de MALT (Mucosa-Associated Lymphoid Tissue). Les MZL partagent parfois des caractéristiques communes avec le lymphome lymphoplasmocytaire/maladie de Waldenström (LPL/WM). Notre travail a consisté en l’étude du réarrangement génique de la chaîne lourde de l’immunoglobuline des MZL et du LPL/WM. Dans un premier temps, nous avons réalisé une analyse génétique sur des prélèvements médullaires de 11 cas de SMZL et 14 cas de LPL/WM. Le répertoire IGHV, les profils mutationnels et l’analyse des HCDR3 ont prouvé qu’il s’agissait de deux maladies distinctes provenant de deux compartiments cellulaires ayant des expositions à l’antigène différentes Dans un deuxième temps, nous avons effectué une comparaison des profils IGHV et une recherche de la mutation MYD88 L265P pour 92 ZML et 31 cas LPL/WM, à partir de matériel tumoral issu du territoire initial d’infiltration. Nous avons montré que les SMZL, NMZL et LPL/WM sont des entités distinctes ayant des histoires d’exposition antigénique différentes et que la mutation L265P de MYD88 est fortement associée au diagnostic de LPL/WM. Nous avons mis en évidence des critères génétiques IGHV spécifiques pour chacun d’entre eux. Enfin, nous proposons des clés diagnostiques non ambiguës pour ces lymphomes. Nous discutons l’hypothèse d’une stimulation antigénique chronique dans la survenue de ces lymphomes dans un modèle d’infection chronique en rapport étroit avec le contexte auto-immun ainsi que l’origine cellulaire des SMZL, NMZL et LPL/WM. Les perspectives de ce travail sont d’étudier les voies de signalisation impliquées dans la physiopathologie de ces lymphomes<br>The immunoglobulin heavy chain locus (IgH) is a complex genetic structure that undergoes many genetic recombinations during B cell maturation and B cell lymphomas. Marginal zone lymphomas (MZL) are B cell neoplasms with common morphologic and pathogenic features. Three distinct subtypes are described, based on the primary infiltrated organ: splenic MZL (SMZL), nodal MZL (NMZ and extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma). MZLs share common characteristics with lymphoplasmacytic lymphoma (LPL). Here, we analysed the IGHV gene repertoire consisting in determination of IGHV usage, somatic mutation pattern, distribution of mutations and analysis of VDJ junction. We, first, compared 11 cases of SMZL and 14 cases of LPL/WM on homogeneous material consisting of infiltrated bone marrow trephine biopsies. In a second step, we performed a retrospective analysis of IGHV gene sequences and identified the occurrence of MYD88 L265P mutations from MZLs and 31 LPL/WMs from tumor material of initial infiltration. We highlighted specific genetic criteria for SMZL, NMZL and LPL/WM. Altogether, we showed that SMZLs, NMZLs, and LPL/WM are distinct entities with different antigen exposure histories and that the MYD88 L265P mutation is nearly restricted to LPL/WMs. We evidenced the specific features of the IGVH gene repertoire of each of these three entities. We also proposed unambiguous diagnosis keys for these lymphomas. We discuss the hypothesis role a continuous antigenic stimulation as a important player in the occurrence of these tumours. We also discuss their relationship with autoimmunity and speculate on their normal counterpart. Future directions of this work would be to focus on the NF-kappa B signaling pathways involved in the emergence of the clonal transformed B cells
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Costa, Fausto Guimarães. "Prospecção de inibidores para a enzima malato sintase do Paracoccidioides brasiliensis: uma avaliação por triagem virtual e dinâmica molecular." Universidade Federal de Goiás, 2015. http://repositorio.bc.ufg.br/tede/handle/tede/4841.
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Previous issue date: 2015-04-16<br>Paracoccidioidomycose<br>A Paracoccidioidomicose...
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Grosset, Jean-François. "Propriétés neuromusculaires des fléchisseurs plantaires d'enfant prépubère : Evolution avec l'âge et étude de cas d'enfants alités atteints d'ostéochondrite primitive de hanche." Compiègne, 2005. http://www.theses.fr/2005COMP1562.
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Cette étude fut menée afin d'explorer les propriétés neuromécaniques des muscles extenseurs de la cheville chez l'enfant prépubère entre 7 et Il ans. Ceci a été permis par le développement, chez l'enfant, de techniques permettant d'analyser, par électromyographie de surface, les modalités d'activation du muscle strié squelettique en conditions réflexes ou volontaires et de mesurer les propriétés mécaniques (contractilité et élasticité) du triceps sural. Cette étude avait donc pour objectif de dresser un bilan des propriétés neuromécaniques chez des enfants prépubères et d'établir des relations entre les paramètres mesurés et l'âge des enfants. Ces relations devaient ensuite servir de référence pour évaluer l'atteinte des propriétés neuromécaniques chez des enfants hospitalisés pour ostéochondrite primitive de hanche et nécessitant une longue période d'alitement. Chez les enfants sains, cette étude a ainsi permis de montrer une amélioration des propriétés contractiles et des capacités d'activation volontaire du triceps sural avec l'âge, ainsi qu'une augmentation, avec l'âge, de la raideur musculo-articulaire en condition active et passive. Des corrélations entre les changements des réflexes à l'étirement musculaire, mécaniquement induits, et les propriétés élastiques musculo-articulaires ont alors pu être mises en évidence au cours de la croissance. Pour les quatre enfants prépubères hospitalisés, la comparaison avec les données obtenues chez les enfants sains nous a permis de mettre en évidence une détérioration des propriétés contractiles ainsi que des capacités d'activation, une plus faible raideur musculo-articulaire en condition passive, un indice de raideur musculo-articulaire plus important en condition active, et des réflexes mécaniquement induits plus importants. RESUN Ce travail a ainsi démontré la faisabilité de la mise en œuvre d'un tel protocole expérimental 1 pour une population d'enfants prépubères sains ou pathologiques et a également permis de caractériser les propriétés neuromécaniques pour ces 2 populations d'enfants<br>This study was undertaken in order to explore the neuromecanical properties of the ankle plantar flexor muscles in prepubertal children aged from 7 to 11 years. This was allowed by the development, for child, of techniques making it possible to analyze, by surface electromyography, the activation modalities of the skeletal striated muscle in reflexes or voluntary conditions and to measure the mechanical properties (contractility and elasticity) of the triceps surae. This study aimed thus to draw up an assessment of the neuromecanical properties in prepubertal children and to establish relations between the measured parameters and the age of the children. These relations were then used as reference to evaluate the attack of the neuromecanical properties in hospitalized children for osteonecrosis of the hip and requiring a long period of confinement to bed. For the healthy children, this study made it possible to show an improvement of the contractile properties and the voluntary activation capacities of the triceps surae with the age, as well as an increase, with the age, of the musculo-articular stiffness in active and passive condition. Correlations between the changes of the stretch reflexes, mechanically induced, and the musculo-articular elastic properties could then be highlighted during the growth. For the four hospitalized prepubertal children, the comparison with the data obtained for the healthy children enabled us to highlight a deterioration of the contractile properties as well as the activation capacities, a lower musculo-articular stiffness in passive condition, an index of musculo-articular stiffness more important in active condition, and reflexes mechanically induced more important. Thus this work demonstrated the feasibility of the implementation of such an experimental mAI protocol for a population of healthy or pathological prepubertal children and also made it possible to characterize the neuromecanical properties for these 2 populations of children
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Koudra, Fahamia. "Maladie hémolytique du nouveau-né." Acfas-Sudbury, 2004. https://zone.biblio.laurentian.ca/dspace/handle/10219/59.
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Ferreira, Isadora Tassinari 1988. "Avaliação da capacidade funcional do timo em camundongos experimentalmente infectados com 'Plasmodium berghei' NK65." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316947.
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Orientador: Liana Maria Cardoso Verinaud<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-27T11:12:10Z (GMT). No. of bitstreams: 1
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Previous issue date: 2015<br>Resumo: O Resumo poderá ser visualizado no texto completo da tese digital<br>Abstract: The Abstract is available with the full electronic digital document<br>Mestrado<br>Imunologia<br>Mestra em Genética e Biologia Molecular
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Silva, Neto Benedito Rodrigues da. "Perfil transcricional e proteômico de Paracoccidioides em resposta à itraconazol e anfotericina B e identificação de compostos com potencial antifúngico." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3642.
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Previous issue date: 2013-05-02<br>Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq<br>The thermally dimorphic fungal pathogen Paracoccidioides is the agent of
paracoccidioidomycosis. This disease is characterized by a granulomatous inflammation
with clinical forms ranging from a benign localized infection to a disseminated one. The
triazole drugs are broad-spectrum antifungal agents and are currently used to treat
infections caused by various pathogenic yeast and molds. The mechanism of action of
azoles has been elucidated in some fungi, although little is known in Paracoccidioides.
Here we aim to investigate the mechanism of action of itraconazole on Paracoccidioides
by using Representational Difference Analysis from Paracoccidioides yeast cells grown
in the absence and presence of itraconazole for 1 and 2 h. Among the Paracoccidioides
genes up-regulated by itraconazole were those mainly involved in cellular transport,
metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6,
ERG3, ERG5 and ERG25 were up-regulated when evaluated in a timely manner. In vivo
infection experiment in mice corroborated in vitro results. The glyoxylate cycle and its
key enzymes isocitrate lyase and malate synthase (MLS) play a crucial role in the
pathogenicity and virulence of various fungi such as the human pathogens. Here, we
describe a study conducted to develop rational ligands as candidates to inhibit receptor
PbMLS. The important step in the search for ligands for this receptor based on structural
homology, molecular docking and molecular dynamics involving scanning virtual
(virtual screening) through the program AutoDock Vina. Identified from the database of
natural compounds (ZINC data bank) potential candidate ligands to inhibit the activity of
PbMLS when compared to the original binder. This process led us to monoterpene indole
alkaloids of the genus Palicourea (Rubiaceae) comprises about 230 species from shrubs
and small trees distributed mainly in tropical regions. From the molecular docking fifteen
compounds were tested as to its effectiveness in inhibiting the activity of PbMLS. The
specific activity of PbMLS was affected by the compounds. Four indol alkaloids showed
ability to reduce the enzyme activity. Since PbMLS is a linked surface protein that
behaves as an anchorless adhesin, and PbICL is here described as adhesin, we also
investigated if those compounds inhibit the adhesion of the protein to extracellular. Twodimensional
gel electrophoresis we used to investigate the proteins expressed
differentially during treatment with itraconazole and amphotericin B. Gels of three
independent biological replicates were digitalized and the images were analyzed using
the ImageMaster 2D Platinum 6.0 software (GE Healthcare). Spot intensities were
normalized and the statistics analyses were estimated by one-way ANOVA. The spots of
interest were excised, in-gel digested with trypsin, and the peptides were then analyzed
by MS and/or MS/MS and and sequenced. The results obtained here should assist in
understanding the mode of action of drugs in Paracoccidioides, and outline studies
identifying compounds with antifungal activity.<br>O fungo patógeno termodimórfico Paracoccidioides é o agente da
paracoccidioidomicose. Esta doença é caracterizada por uma inflamação granulomatosa
onde as formas clínicas vão da infecção localizada benigna a uma uma disseminada. As
drogas triazólicas são antifúngicos de amplo espectro e são usadas atualmente para tratar
infecções causadas por vários fungos patogênicos e fungos. O mecanismo de ação dos
azólicos foi elucidado em alguns fungos, embora pouco se sabe em Paracoccidioides.
Aqui, em primeiro lugar pretendemos investigar o mecanismo de ação do itraconazol em
Paracoccidioides usando análise de diferença representacional de Paracoccidioides
células de levedura crescidas na ausência e na presença de itraconazol por 1 e 2 horas.
Entre os genes Paracoccidioides up-regulados pelo itraconazol foram os envolvidos,
principalmente no transporte celular, metabolismo/energia, transcrição, defesa e
virulência. ERG11, ERG6, ERG3, ERG5 e ERG25 foram regulados quando avaliados de
forma temporal. Experimentos de infecção em camundongos corroborou resultados in
vitro. O ciclo do glioxilato e suas enzimas chave isocitrato liase (ICL) e malato sintetase
(MLS) desempenham um papel fundamental na patogenicidade e virulência de vários
fungos, assim como patogênese em humanos. Neste trabalho, descrevemos um estudo
realizado para desenvolver ligantes racionais como candidatos pra inibir o receptor
PbMLS. Apresentamos um passo importante na busca de ligantes para este receptor
baseando-se em homologia de estruturas, dinâmica molecular e acoplamento molecular
envolvendo varredura virtual (virtual screening) por meio do programa AutoDock Vina.
Identificamos a partir de banco de compostos naturais (data bank ZINC) potenciais
ligantes candidatos a inibir a atividade de PbMLS quando comparados ao ligante
original. Este processo nos conduziu aos alcalóides indólicos monoterpênicos do gênero
Palicourea (Rubiaceae) que compreende cerca de 230 espécies entre arbustos e pequenas
árvores distribuídas, principalmente, nas regiões tropicais.A partir da ancoragem
molecular quinze compostos foram testados quanto à sua eficácia na inibição da atividade
de PbMLS. A atividade específica de PbMLS foi afetado pelos compostos. Quatro
alcalóides indólico mostraram capacidade de reduzir a atividade da enzima. Desde que
PbMLS é uma proteína associada à superfície que se comporta como uma adesina
ancorada também foi investigado se os compostos inibem a adesão da proteína às
matrizes extracelulares. O processo de eletroforese em gel bidimensional foi utilizado
para investigar as proteínas diferencialmente expressas durante o tratamento com
itraconazol e anfotericina B. Gel de três réplicas biológicas independentes foram
digitalizadas e as imagens foram analisadas usando o software 6.0 Platinum 2D
ImageMaster (GE Healthcare). Intensidades dos spots foram normalizados e foram
estimadas as análises estatísticas por ANOVA one-way. Os spots de interesse foram
excisadas do gel digerida com tripsina e os péptidos foram analisados por MS e / ou MS /
MS e sequenciados. Os resultados obtidos aqui devem ajudar na compreensão do
mecanismo de ação de drogas em Paracoccidioides, e delinear estudos de identificação
de compostos com atividade antifúngica.
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Crawford, Oliver. "The political thought of Tan Malaka." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/287945.
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In the course of a fairly brief lifetime, lasting only a little over fifty years (1897-1949), Tan Malaka was variously a schoolteacher, the chair of the Indonesian Communist Party (PKI), a Comintern agent, a political exile, and a revolutionary leader. He travelled the world, living for spells in the Netherlands, Germany, Russia, China, the Philippines, Singapore, and Thailand. Tan Malaka's colourful life and political career have attracted comment from historians, but there has not yet been an in-depth treatment of his ideas, even though he produced a large corpus of writings and was acknowledged to be among the foremost political intellects of his generation in Indonesia. This thesis is an analysis and contextualization of Tan Malaka's political thought. It places his writings within a series of contemporary debates: on the nature of the Indonesian past and the country's potential for revolution; on imperialism and the post-colonial future of Asia; on the relationship between Islam, capitalism, and Communism; on the reformation of Indonesian thinking; and on the appropriate strategy and goals for the Indonesian revolution. These debates, and Tan Malaka's interventions within them, reveal that Indonesia during the 'national awakening' period (1900-50) was the scene of great intellectual innovation, where foreign and indigenous concepts were fused, adapted and reworked. Tan Malaka's writings provide a particularly vivid example of this, combining as they do the concepts and language of Marxism, Islamic morality, and Minangkabau custom, sometimes in tension, in other places flowing together without apparent strain. Tan Malaka was not unique in this respect, as the thesis shows, which suggests that late- colonial Indonesia provides promising terrain for the 'global turn' in intellectual history, that seeks to understand the circulation, interaction and transformation of ideas across national and cultural boundaries, especially in the non-Western world.
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Krugner, Fernando. "Niveis dos receptores soluveis de transferrina e graus de maturidade dos reticulocitos na talassemia alfa+." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313387.
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Orientadores: Maria de Fatima Sonati, Helena Z. W. Grotto<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-03T22:50:17Z (GMT). No. of bitstreams: 1
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Previous issue date: 2004<br>Resumo: Objetivo. Foi sugerido que, o aumento do número de células vermelhas (RBC) mais jovens na circulação em crianças a+-talassêmicas poderiam estar correlacionados com as altas freqüências do alelo a+-talassêmico em regiões endêmicas de malária. A avaliação dos reticulócitos (RET) nessa condição, contudo, não tem sido realizada até o presente momento. Nosso objetivo foi determinar a contagem de RET circulantes e suas frações de maturidade, além do Receptor solúvel de Transferrina (sTfR) e dos níveis de eritropoietina sérica (s-Epo), em heterozigotos da talassemia a+ da região Sudeste do Brasil, área não sujeita à ação da malária. Material e Métodos. Foram estudados 121 portadores de talassemia a+ (-a3.7/aa) (T) e 249 controles normais (aa/aa) (C), sub-classificados de acordo com as seguintes faixas etárias:1-5 anos (T=27;C=41), 6-10 (T=18;C=42), 11-15 (T=16;C=44), 16-20 (T=20;C=42) e maior de 20 (T=40;C=80), todos com níveis normais de Ferritina (FER). A análise dos RET foi feita utilizando citometria de fluxo, a determinação dos níveis de sTfR e s-Epo por imunonefelometria e quimioluminescência, respectivamente. Resultados. Não houve nenhuma diferença estatística entre T e C na avaliação dos RET [porcentagens e valores absolutos, p=0,2643 e 0,5421; nas frações de maturidade (alta, média e baixa), (p=0,2579, 0,2196 e 0,4192); e no Índice de Maturidade RET (RMI), p=0,2471, respectivamente], tão quanto nos níveis de s-Epo (p=0,5711). Os níveis de sTfR foram significativamente mais altos em T (p=0,0001) nos sub-grupos de 1-5 anos e maior de 20 (p=0,0082 e 0,0436, respectivamente). Conclusões. Embora os níveis de sTfR tenham sido mais altos, não foi observado qualquer alteração no número e maturação dos RET, nesses a+-talassêmicos aqui analisados, uma região livre de malária. Os resultados são compatíveis com uma eritropoiese compensatória<br>Abstract: Background and Objective. It has been suggested that an increased number of young circulating red blood cells (RBC) in a+-thalassemic children could be related to the high frequencies of the a+-thalassemic allele in malaria endemic areas. Reticulocyte (RET) evaluation in this condition, however, has not been performed so far. Our objective was to determine the RET number and maturation degree, in addition to the soluble transferrin receptor (sTfR) and serum erythropoietin (s-Epo) levels, in a+-thalassemia heterozygotes from Southeastern Brazil, an area not subjected to malaria. Design and Methods. We studied 121 a+-thalassemia carriers (-a3.7/aa) (T) and 249 normal controls (aa/aa) (C), sub-classified according to age [1-5 years (T=27;C=41), 6-10 (T=18;C=42), 11-15 (T=16;C=44), 16-20 (T=20;C=42) and over 20 (T=40;C=80)], all of them with normal ferritin levels. RET analyzes were performed by flow cytometry and the sTfR and s-Epo levels determined by immunonephelometry and chemiluminescence, respectively. Results. There was no statistical difference between T and C regarding the RET evaluation [percentages and absolute values, p=0.2643 and 0.5421; high, medium and low maturation degree, p=0.2579, 0.2196 and 0.4192; RET Maturity Index (RMI), p=0.2471, respectively], as well as the s-Epo levels (p=0.5711). The sTfR concentrations were higher in T (p=0.0001), reaching statistical significance in the 1-5 and over 20 subgroups (p=0.0082 and 0.0436, respectively). Interpretation and Conclusions. Although the higher sTfR levels, we could not observe any alteration in RET number and maturation in the a+-thalassemic population analyzed here, a region free from malaria. These results are compatible with a compensatory erythopoiesis<br>Mestrado<br>Ciencias Biomedicas<br>Mestre em Ciências Médicas
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Leow, Rachel. "Language, nation, and the state in the decolonisation of Malaya, c.1920-1965." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/252253.
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Sanchez, Bruno Antonio Marinho. "Plasmódios transfectados com a proteína de fluorescência verde (GFP) para ensaios de quimioterapia experimental." reponame:Repositório Institucional da FIOCRUZ, 2007. https://www.arca.fiocruz.br/handle/icict/4036.
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Previous issue date: 2007<br>A resistência do Plasmodium falciparum aos principais antimaláricos ainda é o principalproblema no controle da malária humana. [...] Parasitos da malária transfectadoscom a Proteína de Fluorescência Verde (GFP) têm sido produzidos em sistema detransformação estável. Isso permite utilizar a fluorescência como um marcador paraidentificar os parasitos. Assim, buscou-se neste estudo determinar o uso potencial deparasitas da malária murina (P. berghei) e da malária humana (P.falciparum)transfectados com a GFP para os ensaios de quimioterapia experimental. Para osexperimentos in vivo, utilizou-se a cepa GFP-P. berghei que apresenta um geneexógeno de fluorescência verde e resistência à pirimetamina (Sultan et al. 1999).Camundongos suíço-albinos ou BALB/c foram infectados com a cepa GFP-P. bergheiou a cepa não transformada (NK65), por via intraperitoneal. Excluindo as drogas commecanismo de ação similar ao da pirimetamina, os resultados iniciais demonstraram quea susceptibilidade a diferentes classes de antimaláricos foi semelhante entre a cepa GFPP.berghei e a cepa P. berghei NK65. Demonstrou-se ainda que a virulência in vivo dacepa GFP-P. berghei foi similar a da cepa não transformada. A próxima etapa foivalidar a cepa GFP-P. berghei em um ensaio fluorimétrico para avaliar drogasantimaláricas. Para tal, os animais foram infectados com a cepa GFP-P. berghei,tratados com antimaláricos convencionais, e as parasitemias avaliadas pela citometria defluxo ou pelo método convencional de microscopia óptica. A parasitemia determinadapela citometria de fluxo se correlacionou com aquela determinada pela microscopiaóptica. Assim, os resultados permitiram concluir que a cepa GFP-P. berghei foiadequada para a triagem de drogas in vivo podendo substituir a técnica convencional demicroscopia óptica. [...] A cepa GFP-P.falciparum foi mantida emcultivo contínuo e as parasitemias das culturas foram analisadas, em paralelo, porcitometria de fluxo e microscopia óptica. Os resultados obtidos in vitro tambémdemonstraram que a quantificação da parasitemia obtida por citometria de fluxo eraespecífica. Finalmente, em ensaios quimioterápicos in vitro, utilizando antimaláricosconvencionais, o método fluorimétrico foi similar ao da hipoxantina tritiada. [...] O modelo descrito neste trabalho podefuncionar como uma importante ferramenta para acelerar o processo dedesenvolvimento de novas drogas para o tratamento da malária
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Dias, Roberta Costa. "Uma contribuição ao estudo da malária no Estado de Roraima e sua associação com a precipitação pluviométrica no período, 1985-1996." reponame:Repositório Institucional da FIOCRUZ, 2003. https://www.arca.fiocruz.br/handle/icict/4507.
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Previous issue date: 2003<br>Introdução: A malária é uma doença parasitária provocada por protozoários do gênero Plasmodium. (...) Baseado na importância da malária em Roraima (...) o objetivo deste trabalho foi analisar uma base de dados secundária para tentar contribuir com o estudo da problemática da transmissão da malária nesse Estado. Metodologia: Fez-se a análise histórica de uma base de dados de malária e outra de precipitação pluviométrica para o período de 1985 a 1996. Foram calculados os índices parasitários anuais e mensais (IPA e IPM, respectivamente). Utilizou-se os dados das leituras diárias da precipitação de 20 estações pluviométricas.Foram utilizados vários programas para a realização das análises: Surfer para gerar dados interpolados para a variável precipitação, com uso do método kriging; Arcview para elaboração de mapas; Spring para a realização da análise espacial e obtenção do índice de Moran; e, SAS para a análise estatística utilizando PROC GLM e as médias foram obtidas por LSMEANS. Resultados e conclusões: Em Roraima, a malária se apresenta com valores médios a altos no Estado de Roraima durante todo o período de estudo. A análise dos dados antes e depois da divisão municipal sugere que a malária possui transmissão focal e que os dados sobre essa doença devem ser obtidos, de preferência, por localidade. Dessa forma, os planejamentos de controle não se dispersariam em uma grande área e sim sobre as áreas que realmente tem relevância e assim diminuir a incidência e a prevalência da doença.A observação de que o uso de uma defasagem de um a dois meses é a ideal para verificar os possíveis períodos de transmissão da malária associados com a precipitação (=0,0001), sugerindo que essa análise provavelmente deva ser feita utilizando-se de períodos de tempo menores como semanas e até mesmo dias para determinar com maior precisão qual é a defasagem real entre a precipitação e a transmissão da doença em Roraima. Com relação aos dados de precipitação, pode-se afirmar que o uso do interpolador para inferir dados de chuva das estações pluviométricas para todo o município é possível de ser efetuado, visto que os valores originais de cada estação coincidem com a sua localização no mapa interpolado. De acordo com isso, estudos futuros que visem a elaboração de modelos explicativos para o mecanismo de transmissão da malária em Roraima, devem levar em consideração os outros fatores de risco para a transmissão da doença e não unicamente a precipitação pluviométrica.
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Leite, Juliana Almeida 1984. "Desenvolvimento de vacinas contra plasmodium spp. baseadas em antígenos de fase sanguínea = Development of vaccines based on plasmodiumspp. blood stage antigens." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316722.
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Orientador: Fabio Trindade Maranhão Costa<br>Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-23T23:10:56Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013<br>Resumo: O resumo poderá ser visualizado no texto completo da tese digital<br>Abstract: The complete abstract is available with the full electronic document.<br>Doutorado<br>Imunologia<br>Doutora em Genética e Biologia Molecular
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Valencia, Ayala edward. "Patrones de recurrencia y resistencia asociadas a la variabilidad genética de plasmodium vivax durante la malaria." Master's thesis, Lima, 2012. http://cybertesis.unmsm.edu.pe/handle/cybertesis/3501.
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Plasmodium vivax agente etiológico de la malaria, exhibe una gran variabilidad genética durante episodios recurrentes de la enfermedad. Esta recurrencia es informada como de baja prevalencia asociada con la malaria asintomática. Así mismo los episodios recurrentes (reinfecciones o relapsos) a menudo pueden ser confundidos por resistencia a fármacos como la cloroquina. Por lo tanto el objetivo principal de este estudio fue relacionar los patrones de recurrencia y la resistencia con la variabilidad genética de P. vivax. En este estudio se evaluaron las muestras secuenciales de individuos provenientes de una región endémica del Perú (Mazán-Iquitos), diagnosticados previamente con malaria, por microscopía, durante seguimientos activos y sometidos a un régimen de tratamiento estándar con cloroquina. La genotipificación realizada en base al gen pvmsp3-α, utilizando el Nested PCR y la digestión enzimática, permitió identificar una alta variabilidad genética de P. vivax, a partir de la cual, se identificaron los patrones de recurrencia, establecidos como relapsos, a partir de estadios latentes o hipnozoitos homólogos (con haplotipos idénticos) y reinfecciones (con haplotipos diferentes). Los rangos de tiempo permitieron una identificación más precisa, observándose mayores frecuencias de relapsos por hipnozoitos homólogos antes de los 90 días post-primera evaluación y mayores frecuencias de reinfecciones después de este periodo. Así mismo las recurrencias en el primer periodo de tiempo, por haplotipos diferentes, pueden deberse también a hipnozoitos heterólogos. Complementando el estudio, el análisis de secuenciamiento del gen pvmdr1, permitió identificar SNPs, codificantes de mutaciones no sinónimas, relacionadas con resistencia a cloroquina. Estos SNPs, a través del software U-Melt (análisis in sílico), presentaron variaciones en las temperaturas de fusión. Finalmente los resultados de cuantificación relativa con qPCR Real Time no mostraron diferencias significativas en el número de copias del gen pvmdr1.
Palabras clave: Cloroquina, Genotipificación, Haplotipos, Hipnozoito, Malaria Asintomática, Recurrencia, Variabilidad.<br>--- Plasmodium vivax etiologic agent of malaria has a large genetic variability during recurrent episodes of the disease. This recurrence is reported as low prevalence associated with asymptomatic malaria. Also recurrent episodes (reinfection or relapse) can often be mistaken for drug resistance as chloroquine. Therefore the main objective of this study was to correlate the patterns of recurrence and resistance to the genetic variability of P. vivax. In this study, we evaluated the sequential samples of individuals from an endemic region of Peru (Mazán-Iquitos), previously diagnosed with malaria microscopy during active follows and subjected to a standard treatment regimen with chloroquine. Genotyping based on the pvmsp3-α gene, using Nested PCR and enzymatic digestion, identified high genetic variability of P. vivax, from which were identified recurrence patterns established as relapse, from latent stages or homologous hypnozoites (with identical haplotypes) and reinfections (with different haplotypes). The time ranges allow more accurate identification, with higher frequency of relapses by homologous hypnozoites before 90 days post-first evaluation and higher frequencies of reinfection after this period. Also recurrences in the first period of time, for different haplotypes may also be due to heterologous hypnozoites. Complementing the study, the sequencing analysis of the gene pvmdr1, identified SNPs, encoding nonsynonymous mutations related to resistance to chloroquine. These SNPs, through U-Melt software (in sílico analysis), showed variations in the melting temperatures. Finally the results of relative cuantification with Real Time qPCR no showed significant differences in copy number of the pvmdr1 gene.
Keywords: Chloroquine, Genotyping, Haplotypes, Hipnozoite, Recurrence, Asymptomatic Malaria, Variability.
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Francke, Pedro. "Impacto económico de la malaria en el Perú." Economía, 2012. http://repositorio.pucp.edu.pe/index/handle/123456789/117551.
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Malaria is one of the more important public health problems in Peru and the world.Besides the human costs, that are the most important, malaria has an economic impact. Thispaper estimates the cost that malaria has for the peruvian society in 119.5 million of Soles in1998, equal to 1.5 per cent of the total health expenditures. Because these costs are principallyborned by the families, that try to recuperate them by additional work efforts, they are not wellperceived by the society and the disease is subvalorated in public policies.<br>La malaria es uno de los principales problemas de salud pública en el Perú y en el mundo.Además de los costos humanos, que son los más importantes, la malaria tiene también un impactoeconómico. El presente trabajo estima el costo que tiene la malaria para la sociedad peruana en119.5 millones de nuevos soles para el año 1998, lo que equivale al 1.5 por ciento del gasto total ensalud. Debido a que los principales costos de malaria son aquellos que se generan sobre las familias,que tienden a recuperarlos mediante un mayor esfuerzo familiar, ellos no son adecuadamentepercibidos por la sociedad, lo que favorece la subvaluación de la importancia de la enfermedad.
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Machado, Daniela Rodriguez de Assis. "Malaria experimental por Plasmodium chabaudi chabaudi linhagem CR em camundongo NOD/Uni ("Non-obese diabetic")." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317831.
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Previous issue date: 2008<br>Resumo: A malária é uma parasitose que mata mais de um milhão de pessoas por ano. No Brasil, 99% dos casos ocorrem na Amazônia Legal. O Plasmodium chabaudi chabaudi CR, não letal, representa a malária experimental de autocontrole. A hipoglicemia é uma característica comum da malária causada pelo P. falciparum e também está presente na malária murina. O diabetes tipo 1 é uma doença auto-imune órgão-específica que tem como conseqüência a destruição das células ß produtoras de insulina, nas ilhotas de Langerhans. Alguns trabalhos observaram que a infecção de camundongos com o estágio sangüíneo de P. chabaudi induziu uma hipoglicemia em camundongos normais e normalizou a hiperglicemia em camundongos moderadamente diabéticos por indução pela streptozotocina (STZ). No camundongo NOD ("non-obese diabetic"), o diabetes é determinado geneticamente e simula o desenvolvimento do diabetes tipo 1. O presente trabalho se propõe avaliar a influência do diabetes mellitus tipo 1 na infecção experimental por Plasmodium chabaudi chabaudi, linhagem CR, em camundongos fêmeos NOD/Uni, com diferentes graus de diabetes (diabetes moderada e diabetes severa). Camundongos fêmeos livres de patógenos específicos (SPF) da linhagem NOD/Uni com oito a 42 semanas de idade foram infectados via intraperitoneal com 1x107 eritrócitos parasitados pelo Plasmodium chabaudi chabaudi CR. A glicemia foi determinada pela deposição de sangue coletado diretamente da cauda do animal em fita reativa do aparelho Roche Accu-Chek Active® em dias alternados. A parasitemia foi expressa em percentagem de hemácias parasitadas mediante observação de esfregaço sangüíneo corado com May-Grünwald e Giemsa. Os camundongos NOD/Uni foram classificados segundo o grau de diabetes em moderada (300 a 500 mg/dL) e severa (>500 mg/dL). Foi observada redução da glicemia a partir do quinto dia de infecção nos camundongos NOD/Uni, em geral no pico da infecção. Esta redução não ocorreu nos camundongos NOD/Uni sem infecção e nos camundongos da linhagem BALB/c/Uni infectados pelo Plasmodium chabaudi chabaudi CR. As principais lesões renais observadas foram edema, necrose e infiltração glomerular, descamação e dilatação dos túbulos contorcidos e espessamento da membrana basal glomerular. Os camundongos da linhagem NOD/Uni infectados pelo Plasmodium chabaudi chabaudi CR apresentaram maior sobrevida em relação aos camundongos sem infecção. A redução da glicemia parece estar relacionada a diversos fatores dentre eles, a influência das proteínas de membrana GPIs (glycosylphosphatidylinositols) e o equilíbrio entre a resposta dos linfócitos Th1/Th2.<br>Abstract: Plasmodium chabaudi chabaudi CR in Non-Obese Diabetic (NOD) mice Malaria is a parasitic disease that kills more than one million people worldwide each year. In Brazil, the 99% of the cases occur in the northern States that encompass the Amazon Basin. Plasmodium chabaudi chabaudi is an important experimental model for several aspects of malaria research, including parasite biology and immunology. It is recognized as a developmental analog to human infection by Plasmodium falciparum. The non-lethal Plasmodium chabaudi chabaudi CR strain represents the experimental autocontrol disease. Hypoglycemia is a common symptom of P. falciparum malaria and also occurs in murine malaria. The Type 1 diabetes is an organ-specific autoimmune disease that destroys the insulin-producing ß cells of the Islets of Langerhans. In non-obese diabetic (NOD) mice, diabetes is genetically determined and also develops type 1 diabetes. The present work evaluated type 1 diabetes mellitus during experimental infection by Plasmodium chabaudi chabaudi CR strain in female NOD mice with moderate and severe diabetes. Eight to 42 week-old female specific pathogens free (SPF) NOD/Uni mice were inoculated with red blood cells parasitized sample containing the total of 1x107 Plasmodium chabaudi chabaudi CR by intraperitoneal injection. Routine measurement of blood glucose in NOD/Uni mice was performed every other day for 11 days post-infection. Glycemia was quantified using Roche Accu-Chek Active kits with blood collected from the tail of each animal. The parasitemia was expressed as percent of infected erythrocytes counted by microscopy analysis of tail blood films stained with Giemsa. The animals were classified according to their degree of diabetes into two groups: moderate diabetes (300 to 500 mg/dL) and severe diabetes (>500 mg/dL). The control group was composed of animals of the BALB/c/Uni strain. The natural death of NOD/Uni mice was recorded for both infected and healthy animals. Glycemia decreased at the height of parasitemia around the fifth day of infection. The diabetic infected animals presented higher survival after the onset of diabetes when compared with non-infected control. The main renal lesions found were glomerular edema, glomerular necrosis, cell infiltration, tubular atrophy and expansion of the glomerular basement membrane. The decrease of blood glycemia remains incompletely understood and it seems to be related to GPIs (glycosylphosphatidylinositols) proteins and the balance between Th1/Th2 responses.<br>Mestrado<br>Parasitologia<br>Mestre em Parasitologia
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Rodrigues, Flávia Guimarães. "Obtenção e caracterização molecular de mosquitos Aedes fluviatilis transgênicos para o bloqueio da malária aviária." reponame:Repositório Institucional da FIOCRUZ, 2007. https://www.arca.fiocruz.br/handle/icict/4026.
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Previous issue date: 2007<br>[...] Teve como objetivo estudar duas moléculas antiparasíticas (gomesina e fosfolipase A2 (PLA2m)) como candidatas à expressão em mosquitos. O peptídeo antimicrobiano gomesina da aranha Acanthoscurria gomesiana, foi capaz de inibir o desenvolvimento das formas sanguíneas das cepas W2 e 3D7-GFP de P. falciparum, com valores de IC50 de 75,8 e86,6 (...). Anteriormente, experimentos in vitro, mostraram que aenzima fosfolipase A2 (PLA2) isolada do veneno de abelha apresentou ação inibitória sobre o desenvolvimento de P. falciparum e P. gallinaceum, mas apresentou efeitos deletérios em mosquitos transgênicos, quando na sua forma ativa. Neste trabalho, expressamos em bactérias e purificamos uma forma mutante da proteína (PLA2m). Na concentração de 0,1(...) a proteína recombinante foi capaz de reduzir em até 79 por cento o número de oocistosde P. gallinaceum em mosquitos Aedes fluviatilis, quando adicionada ao sangue de aves domésticas (Gallus gallus domesticus) infectadas. Para a geração de mosquitostransgênicos utilizamos o promotor da proteína 1 da matriz peritrófica de An. gambiae (AgPer1) para dirigir a expressão do gene da PLA2m. A construção do gene híbrido(AgPer1/PLA2m) foi inserida no elemento de transposição piggyBac, que contém como marcador, o gene da proteína verde fluorescente melhorada (EGFP). Pela microinjeção de770 embriões, foram formadas 15 famílias e, após a seleção de cerca de 22.000 larvas foram obtidas quatro linhagens transgênicas, representando uma eficiência na transformação de 27 por cento. A expressão do EGFP foi observada no tubo neural e olhos de larva, pupa e adulto. Utilizando iniciadores específicos, confirmamos, pela PCR, a presença dos genes EGFP (700pb) e PLA2m (500bp). A produção do RNAm da PLA2m foi específicano intestino de fêmeas, não variando após a alimentação sanguínea. Por microscopia confocal detectamos a presença da proteína PLA2m no intestino dos mosquitostransgênicos. Além disso, ensaios de bloqueio ao parasita mostraram redução significativa do desenvolvimento de oocistos de P. gallinaceum, de 17,5 a 68,5 por cento, nas quatro linhagens transgênicas. Este estudo mostra a importância de moléculas efetoras e da geração demosquitos transgênicos como estratégia alternativa de controle da malária, bem como, uma ferramenta para estudos de interação parasita/ vetor invertebrado
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Carvalho, Arlindo Vicente de Assunção. "Estratégias de controle da malária em São Tomé e Príncipe: 1946-2002." reponame:Repositório Institucional da FIOCRUZ, 2005. https://www.arca.fiocruz.br/handle/icict/5198.
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Previous issue date: 2005<br>O presente trabalho analisa as estratégias de controle da malária em São Tomé e Príncipe, de 1946 aos dias atuais buscando identificar os limites e potencialidades para viabilizar e manter uma situação de controle sustentado ou erradicação. Características geográficas sócio- econômicas e conjunturais fazem de São Tomé e Príncipe um espaço endêmico, propício à produção e transmissão da malária.De acordo com este estudo, no período colonial recente, a redução dos níveis de endemicidade esteve sempre vinculada ao grau de eficácia das estratégias e a sustenilidade das ações desenvolvidas. Estratégias baseadas na dedetização e na cloroquinazação produziram resultados mais relevantes reduzindo a mortalidade e o nível de endemicidade de hiper-holoendêmico para mesoendêmico.O mesmo estudo revela que após a independência, a implementação de estratégias de erradicação baseadas na pulverização intradomiciliar de DDT e na busca ativa e tratamento de casos tiveram resultados encorajadores. Porém, ambientes institucionais vulneráveis, ações não sustentadas no tempo, mudança no comportamento epidemiológico do vetor, resistência ao inseticida empregue, diminuição da sensibilidade do parasita à cloroquina, não foram capazes de propiciar um controle efetivo nem uma atuação sobre as condições ambientais, impedindo a circulação de parasitos e consequentemente a transmissão da doença. A transmissão da malária colocada em equilíbrio instável antes de se conseguir a interrupção da transmissão, influenciou, de forma negativa a receptividade levando a morbidade e a mortalidade a se instalarem em patamares mais altos.O recrudescimento revelou-se desastroso abrindo caminhos à novas vulnerabilidades. A malária continua sendo a primeira causa de morte e de morbidade em São Tomé e Príncipe. Mobiliza custos enormes com o tratamento e proteção e constitui um sério bloqueio ao progresso econômico do país. Considerando as forças e as fraquezas identificadas no decorrer deste estudo, as particularidades geográfico-ambientais, a complexidade dos fatores epidemiológicos e sócio-econômicos assim como os elementos técnicos em que se baseiam a estratégia mundial, o trabalho discute as estratégias que poderiam viabilizar um controle com sucesso.
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Andrade, Bruno de Bezerril. "Identificação de potenciais determinantes imunológicos de gravidade na malária humana." reponame:Repositório Institucional da FIOCRUZ, 2010. https://www.arca.fiocruz.br/handle/icict/4136.
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Bruno de Bezerril Andrade - 2010.pdf: 74164438 bytes, checksum: a1cccf3d1f924ff7710fc4a73a190f0a (MD5)<br>Universidade Federal da Bahia. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil<br>A malária é considerada uma das mais importantes doenças infecciosas do mxmdo. Esta doença é causada por diversas espécies do protozoário Plasmodium sp., principalmente o Plasmodium falciparum e o Plasmodium vivax, transmitido por mosquitos do gênero Anopheles. Apesar dos esforços governamentais e privados para o desenvolvimento de estratégias para o controle da doença, o panorama atual da malária está piorando, muito em razão do aparecimento de cepas de parasitas resistentes aos medicamentos. Os casos fatais são relatados principalmente na Áfiica e são causados pelo Plasmodium falciparum. Apesar de ser menos letal, a malária causada pelo Plasmodium vivax é mais amplamente distribuída e pode apresentar também alta morbidade e mortalidade. Na maioria das áreas endêmicas, estudos têm identificado vários fatores relacionados à imunidade clínica ou susceptibilidade aos parasitas. Assim, pelo menos quanto à malária causada pelo Plasmodium falciparum, idade, polimorfismos genéticos e exposição repetida ao parasita são considerados importantes determinantes da evolução da doença. Infelizmente, pouco tem sido feito na identificação de fatores preditores consistentes que poderiam ser usados para avaliação clínica. Este quadro é ainda pior para malária causada pelo Plasmodium vivax, provavelmente porque muitos pesquisadores consideram que é uma doença benigna. Além disso, como a maioria do conhecimento atual sobre a patogênese da malária não ajudou a reduzir a ocorrência da infecção e suas complicações, novas abordagens são necessárias para superar este cenário desfavorável. Esta Tese reúne um conjunto de seis manuscritos que visam identificar potenciais determinantes da gravidade da malária em uma área endêmica da Amazônia Ocidental Brasileira. Em primeiro lugar, um método preciso e eficaz para o diagnóstico da malária foi rastreado através da comparação de vários testes, incluindo um software baseado em redes neurais artificiais. O ensaio molecular mostrou-se o mais eficiente para o diagnóstico da malária sintomáticos e assintomáticos. Além disso, a utilização racional de um teste rápido para diagnóstico da malária pode ser promissora em áreas onde há dificuldade na formação continuada dos técnicos diagnósticos. A rede neural artificial indicou que o balanço de citocinas é um forte determinante do quadro clínico. Em outro estudo, uso de sorologia para mensuração de anticorpos IgG contra o sonicado de glândula salivar do vetor Anopheles darlingi mostrou-se útil para a avaliação da exposição ao Plasmodium vivax e também para estimar a imunidade clínica á malária. Em um terceiro estudo com foco na identificação de outros fatores relacionados à imunidade clínica, a exposição natural ao vírus da hepatite B mostrou-se associada à redução da gravidade clínica da malária causada tanto pelo Plasmodium vivax quanto pelo Plasmodium falciparum. No que diz respeito exclusivamente à malária vivax, os casos graves apresentaram uma intensa e desregulada resposta inflamatoria sistêmica. Nestes pacientes, a enzima antioxidante superóxido dismutase-1 surgiu como um excelente marcador da gravidade e mostrou-se envolvida na patogênese da doença grave, na qual há uma liberação de grandes quantidades de heme livre. Em conjunto, os manuscritos desta tese adicionam importantes informações no entendimento dos mecanismos determinantes da gravidade da malária, extremamente<br>Malaria is considered one of the most important infectious diseases that ever threaten the world. This disease is caused mainly by the infection with Plasmodium falciparum or Plasmodium vivax transmitted by Anopheles mosquitoes. Despite governmental and private efforts for the development of key strategies for the disease control, the actual panorama of the Plasmodium infection is getting worse due to the emergence of drug resistMt parasite strains. The lethal cases are reported mostly in Africa and are caused by Plasmodium falciparum. Albeit being less lethal, Plasmodium vivax infections are more widely distributed can cause high morbidity and eventually death. In most endemic areas, studies have indentified a number of factors related to clinical immunity or susceptibility to the parasites. Thus, at least regarding the falciparum malaria, age, genetic polymorphisms and repeated exposure to Plasmodium are considered most important determinants of the disease outcome. Unfortunately, little has been made in the screening of reliable predicting factors that could be ultimately used for clinical evaluations. This landscape is even worse for vivax malaria, probably because many researches consider it as a benign disease. Moreover, as most of the current knowledge about the malaria pathogenesis did not truly help to relieve the disease burden, new insights are necessary to overcome this unfavorable scenario. This thesis brings together a set of six manuscripts that aim to identify potential determinants of the disease severity linked to the immunopathogenesis in an endemic area from the western Brazilian Amazon. First, a precise and effective method for malaria diagnosis was screening by comparing multiple tests, including a software based of artificial neural networks. The molecular assay showed to be the most efficient for the diagnosis of symptomatic and asymptomatic malaria. In addition, the rational use of a rapid test for the diagnosis of malaria may be promising in areas where there is difficulty in continued training of technical human resources. The artificial neural network indicated that the cytokine balance is a strong determinant of the clinical presentation. In another study, the use of serology for measuring IgG antibodies against the sonicate salivary gland of Anopheles darlingi vector is a promising marker of exposure to Plasmodium vivax and can also estimate the clinical immunity. Intriguingly, the natural exposure to the hepatitis B virus appeared as an important factor associated with reduced clinical severity for both vivax and falciparum malaria. Concerning solely the vivax malaria, severe cases have an intense and unregulated inflammatory response. In these patients, the antioxidant enzyme superoxide dismutase-1 has emerged as an excellent marker of severity and was involved in the pathogenesis of the severe disease in which there is a release of large amounts of free heme. Together, the manuscripts of this thesis add important information in understanding the mechanisms that determine the severity of malaria.
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Francelin, Carolina 1985. "Efeito da infecção experimental com Plasmodium berghei NK65 sobre o timo = níveis elevados de apoptose e saída prematura de timócitos CD4+CD8+." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316399.
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Previous issue date: 2011<br>Resumo: O timo é um órgão linfóide primário, responsável pela diferenciação, maturação e desenvolvimento dos linfócitos T (ou timócitos, enquanto no timo). Este órgão apresenta complexa arquitetura tímica composta por elementos celulares e solúveis responsáveis pela migração dos precursores de linfócito T do espaço perivascular para a região cortical e subseqüente migração para a região medular. A trajetória do timócitos pelos microambientes tímicos permite que estas células recebam estímulos que os tornam linfócitos maduros, simples positivos TCD4+ ou TCD8+, prontos para migrar para os órgãos linfóides secundários. Durante a maturação, timócitos que são auto-reativos ou anérgicos são eliminados pelo processo de morte celular programada. Entretanto, a desregulação da apoptose nos linfócitos pode acarretar no desenvolvimento de doenças auto-imunes, tumores e imunodeficiências. Estudos em modelos murinos de atrofia tímica relatam que em diversas infecções parasitárias, virais, helmínticas, bacterianas e fúngicas e até mesmo em distúrbio metabólico como a diabetes experimental o timo é um órgão alvo. Nestes modelos, foi observado intenso acometimento tímico com involução do órgão acompanha por desarranjo da arquitetura tímica e depleção de todas as subpopulações de timócitos. Em estudos anteriores, observamos profundas alterações no timo durante a infecção experimental com Plasmodium berghei que incluíam severa atrofia no décimo quarto dia após inoculação do parasita, alterações histológicas, perda da delimitação cortico-medular, redução de todas sub-populações de timócitos e a presença intra-tímica do parasita. No presente trabalho avaliamos se a grande perda de timócitos observada no timo de animais infectados pelo Plasmodium berghei NK65 é devido a um aumento da ocorrência de apoptose, e/ou necrose, ou se é devida à saída prematura destas células para a periferia.A avaliação de morte celular na população de timócitos total revelou aumento no número de células Anexina-V+/PI- em animais infectados quando comparados aos controles.Ainda, a análise da apoptose em timos atróficos, no pico da parasitemia, revelou aumento de núcleos apoptóticos nas regiões cortical e medular tímica bem como aumento no número de linfócitos (CD4+, DP e DN) Anexina-V positivos. Alteração na expressão de genes pró-apoptóticos no timo de animais infectados quando comparado ao controle, sugerindo a participação de vias de ativação extrínsecas especificas da apoptose, também foram observadas. Embora 90% dos timócitos de animais infectados sejam Anexina-V positivos, as alterações na expressão dos elementos de matriz extracelular, relatadas anteriormente pelo nosso grupo, sugere também a exportação precoce destas células para a periferia do sistema imune. Nossos resultados apontam para um aumento de linfócitos imaturos (DP e DN) nos linfonodos mesentéricos de animais infectados, um indicativo de que parte dos timócitos imaturos sai do timo antes de completarem seu amadurecimento. Em conjunto, nossos dados mostram que as alterações estruturais e de componentes solúveis do timo durante a infecção com Plasmodium berghei NK65 podem favorecer tanto a deleção, por apoptose, de timócitos corticais como também a migração precoce de células imaturas para a periferia do sistema imune. O acometimento tímico na atrofia tímica induzida pelo Plasmodium berghei NK65 revela que durante uma infecção o timo sofre influências de diversos fatores que provocam profundas alterações nas subpopulações linfocitárias. Também, é possível que as alterações observadas em nosso modelo prejudique a resposta imune periférica contra o parasita contribuindo para o agravamento da doença e que a presença de timócitos prematuros nos linfonodos favoreça o desenvolvimento de doenças auto-imunes<br>Abstract: The thymus is the primary lymphoid organ responsible for the differentiation, maturation and development of T lymphocytes (or thymocytes, as in the thymus).This organ presents a complex architecture composed by soluble and cellular elements that support the migration of lymphocyte precursors from space perivascular to the cortical region, and then their migration toward the medullar area. The trajectory of thymocytes by thymic microenvironments allows these cells to receive stimuli that make them mature into CD4+ or CD8+ T cells, which leave the thymus to populate peripheral lymphoid organs. Studies using murine models of thymic atrophy have reported that thymus is a target organ in several parasitic, viral, helminthic, bacterial and fungal infections. In these models, one can observe intense thymic involution accompanying by disruption of thymic architecture and depletion of all thymocyte subpopulations. In a previous study, our laboratory has demonstrated profound changes in the thymus during experimental infection with Plasmodium berghei, the causative agent of Malaria. Such alterations comprised severe atrophy, histopathological changes with loss of cortical-medullary delimitation, and reduction of all thymocytes sub-populations. In addition, the presence of parasites inside the thymus was detected for the first time. In another study using the same experimental model, we have demonstrated that Plasmodium-infected animals present changes in the expression of extracellular matrix elements and chemokine protein families, which are important molecules for the dynamic thymocyte migration within the thymus. In this study we evaluate whether the acute thymic atrophy observed in Plasmodium berghei-infected animals is correlated with increased apoptotic levels of thymocytes, or with their premature emigration to the periphery. Our data showed profound histological alterations, which included a very large number of cells showing nuclear condensation and karyorrhectic changes surrounded by histiocytes suggesting increased levels of apoptosis. This was confirmed by immunohistochemistry and flow cytometry techniques. Also, increased expression of proapoptotic genes was observed in the thymus of infected animals when compared with controls, suggesting the involvement of the extrinsic, or receptor-iniciated, pathway of apoptosis. Although the rate of apoptosis in the thymus from infected animals is much higher than the controls, the hypothesis that a premature emigration of thymic cells to the peripheral lymphoid organs may also account for the severe atrophy observed during Plasmodium infection could not be ruled out. In fact, we have found a consistent fraction of immature cells, mainly double-negative and double-positive thymocytes, in mesenteric lymph nodes of infected animals. Although this result serves as an evidence of premature emigration of non-mature thymocytes, the precise mechanism by which this process occurs is not clear until now. No significant differences were found in the spleen. Taken together, our data show that thymic alterations observed during Plasmodium berghei infection can favour both the deletion of thymocyte subpopulation by apoptosis and the early emigration of immature cells to the periphery of the system immune. As a consequence, an altered peripheral immune response to the parasite can be expected. Our findings provide relevant information concerning the immune involvement in malaria infection. Moreover, the murine model described here could be useful for mechanist studies of acute thymic atrophy<br>Mestrado<br>Imunologia<br>Mestre em Genética e Biologia Molecular
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Thomé, Rodolfo 1987. "Efeito da infecção por Plasmodium berghei sobre a encefalomielite autoimune experimental." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316389.
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Previous issue date: 2014<br>Resumo: A malária permanece como a maior doença infecciosa do mundo, sendo que metade da população mundial se encontra em risco de ser infectada. A destruição do agente causador, protozoários do gênero Plasmodium, é essencial para a resolução da moléstia e é mediada pela atuação coordenada entre linfócitos T e B. Foi noticiado a presença de auto-anticorpos em pacientes portadores de malária, e em alguns casos o agravamento de doenças autoimunes como o lúpus e, possivelmente, a esclerose múltipla. Estudos conduzidos em nosso laboratório demonstraram que a infecção por P. berghei NK65 em camundongos promoveu atrofia do timo e subsequente migração de células T CD4+CD8+ (DP) para órgãos linfoides secundários. Tendo em vista que o timo é o órgão linfoide primário responsável pela maturação e desenvolvimento de linfócitos T, desempenhando um papel primordial em gerar a tolerância central, o presente estudo teve por objetivo investigar o efeito da infecção por P. berghei sobre a evolução clínica da Encefalomielite Autoimune Experimental (EAE) e também sobre o perfil de ativação de células dendríticas. Os resultados obtidos mostraram que camundongos curados da malária apresentaram quadro clínico exacerbado de EAE quando comparados com animais que não entraram em contato com o plasmódio. A piora no quadro clínico de EAE se associou com a migração precoce de células T-DP para o Sistema Nervoso Central (SNC) e pela produção de citocinas inflamatórias por tais células. Camundongos resistentes a EAE desenvolveram a doença após a infecção por plasmódio, indicando que a atrofia tímica induzida pela infecção é capaz de alterar a susceptibilidade ao desenvolvimento de doenças autoimunes. Por outro lado, o tratamento de células dendríticas (DCs) com extratos derivados do plasmódio modificou seu estado de maturação/ativação para um perfil tolerogênico. A transferência adotiva de células dendríticas moduladas com extratos de plasmódio foi capaz de reduzir a EAE, bem como a neuro-inflamação do SNC pela supressão da resposta imune celular a neuro-antígenos. Tomados em conjunto, os resultados obtidos neste estudo mostram que a infecção por Plasmodium berghei NK65 promove alterações significativas no sistema imune que auxiliam na exacerbação da neuro-inflamação autoimune. Por outro lado, a utilização de extratos do plasmódio pode se tornar uma alternativa inovadora na modulação da inflamação por meio da transferência adotiva de células dendríticas tornadas tolerogênicas com tais extratos<br>Abstract: Malaria remains as the most frequent infectious disease in the world, where half of the world population is at risk. Destruction of the causative agent, protozoan of the Plasmodium gender, is essential for the resolution of the disease and this is mediated by the coordinated action of both T and B lymphocytes. It has been demonstrated that malaria-bearing patients possess auto-antibodies, e in some cases, the worsening of autoimmune diseases such as lupus and multiple sclerosis. Studies, conducted by our group, have shown that P. berghei NK65 infection promoted thymic atrophy and the subsequent migration of CD4+CD8+ (DP) T cells towards the peripheral immune system. Since the thymus is the primary lymphoid organ responsible for the generation and maturation of T cells, playing a major role in the shaping of T cells repertoire, the present study aimed to investigate the influence of P. berghei infection in the clinical course of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model for multiple sclerosis, and also over the maturation/activation status of dendritic cells. Results showed that malaria-cured mice developed a more severe EAE clinical course compared with control mice. The worsening in EAE score was related to the migration of DP-T cells towards the Central Nervous System (CNS), where these cells produced high amounts of inflammatory cytokines. Interestingly, EAE-resistant BALB/c mice developed the disease after plasmodia infection, indicating that the thymic atrophy induced by the infection is able to alter the susceptibility to autoimmune diseases. On the other hand, treatment of dendritic cells (DCs) with P.berghei extracts (PbX) modified their activation/maturation status towards a tolerogenic profile. The adoptive transfer of DC-PbX was able to suppress the development of EAE, as well as neuro-inflammation, through the reduction in cellular immune responses towards neuro-antigens. Taken together, the results collected in this study show that Plasmodium berghei NK65 infection promotes significant alterations in the immune system that aid the development of autoimmune neuro-inflammation. On the other hand, the use of plasmodia extracts may become an interesting approach to modulate inflammation through the adoptive transfer of tolerogenic dendritic cells<br>Doutorado<br>Imunologia<br>Doutor em Genetica e Biologia Molecular
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Motta, Fabiana Martins Batista. "A malaria experimental por Plasmodium chabaudi chabaudi em camundongo SCID." [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317908.
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Previous issue date: 2003<br>Resumo: As células NK secretam as citoquinas INF-gama e TNF-alfa ¿ moléculas associadas com a resposta imune mediada por células do tipo Th1 ¿ em resposta a infecção por Plasmodium e ainda respondem à indução pela IL-12, conseguindo enfim, diminuir a mortalidade por P. chabaudi. Apesar de estudos comprovarem que as células NK e suas citoquinas têm papel importante no controle imunológico da malária, sabe-se que fatores genéticos representam um dos maiores determinantes de resistência do hospedeiro para infecção da malária. Para testar o papel das células NK na resposta imune contra malária, foram adotados dois modelos animais: a linhagem C.B-17 SCID/SCID, devido à ausência de células T e B, e camundongos C57BL/6 KO para interferon gama , que apresentam o gene para interferon gama bloqueado. Nesse trabalho, a capacidade dos animais SCID e KO para interferon gama
controlarem a infecção foi avaliada comparando-se a parasitemia entre eles; Foram adotadas , como controle, as linhagens imunocompetentes BALB/c/Uni e C57BL/6/Uni. Esses animais foram infectados intraperitonealmente com 106 eritrócitos parasitados com P. chabaudi da linhagem CR e tiveram sua parasitemia medida em intervalos pré-determinados por várias semanas. Tanto os animais SCID quanto os animais KO, mantiveram altos picos de parasitemia, mesmo durante a fase crônica da infecção. Os camundongos imunocompetentes controlaram a infecção. Os resultados indicam que as células NK colaboram no controle da infecção, diminuindo a parasitemia, porém a imunidade ao P. chabaudi não depende somente da produção de interferon gama, podendo estar relacionada também a fatores genéticos. A malária compromete o rim, não só pela deposição de imunocomplexos, pois os mundongos C.B17 SCID/SCID/Uni desprovidos de imunoglobulinas também desenvolveram patologias renais: descamação das células tubulares, trombose e necrose glomerular, observadas também em camundongos C57BL/6 KO. As alterações renais em C57BL/6 foram mínimas, possivelmente em função do genótipo resistente desta linhagem<br>Abstract: The NK cells secrete the citoquinas INF-gamma and TNF-alpha - molecules associated with the immune protective mediated by cells of the type Th1 - in response to infection for Plasmodium. Instead the induction of these cells with IL- 12 helps to reduce the mortality by P. chabaudi. Although studies was related the NK cells and its citoquinas play a important role in the control of the malaria, it is known that the genetic factors represent one of the largest determinant of resistance by host infected by Plasmodium sp. For testing the malaria immunity by NK cells, we have used two animal models: the C.B-17 SCID/SCID because their absence of T and B cells and the C57BL/6 animals which are deprived for interferon-gamma gene. In this research, the capacity of both to control the infection was evaluated comparing the parasitaemia among them, using the immunocompetent BALB/c/Uni
like a control animal. They were infected intraperitoneally with a dose of 106 parasited red blood cells and the parasitaemia was determined in established intervals for several weeks.
So the animals SCID as the animals KO have maintained high parasitemia during chronic phase of the infection. The immunocompetents mice have decreased the parasitemia level , controlling the infection. It could be concluded that the NK cells collaborate to the malaria immunity reducing the parasitaemia; however the data indicating they don't act alone and the resistance against the P. chabaudi could be also a genetic factor. The malaria affects the kidney, not only for the immunocomplex deposition, because the mice C.B17 SCID/SCID/Uni unprovided immunoglobulins also developed renal pathologies: tubular cells exfoliation, thrombosis and necrosis in the glomerulus, also observed in C57BL/6 KO Interferon-gamma animals. It was not observed kidney alterations in C57BL/6 probably because resistant genotype<br>Mestrado<br>Parasitologia<br>Mestre em Parasitologia