O objetivo deste trabalho é apresentar uma nova abordagem para obtenção de configurações para sistemas de distribuição de energia elétrica com o intuito de minimizar o valor de perdas ativas sem violar as restrições operacionais. Para isso, considera-se que os sistemas de distribuição estão operando em regime permanente e que suas fases estão equilibradas e simétricas, podendo o sistema ser representado por um diagrama unifilar. A reconfiguração é feita de forma a redistribuir os fluxos de corrente nas linhas, transferindo cargas entre os alimentadores e melhorando o perfil de tensão ao longo do sistema. O problema de reconfiguração do sistema pode ser formulado como um problema de programação não-linear inteiro misto. Devido à explosão combinatorial inerente a este tipo de problema, a resolução do mesmo por técnicas de otimização clássicas torna-se pouco atraente, dando espaço para técnicas heurísticas e metaheurísticas. Essas outras, mesmo não garantindo o ótimo global, são capazes de encontrar boas soluções em um espaço de tempo relativamente curto. Para a resolução do problema de reconfiguração, utilizou-se uma nova metodologia baseada no comportamento de colônias de formigas em busca de alimento na natureza. Nesta, formigas artificiais (agentes) exploram o meio ambiente (sistema de distribuição) e trocam informações para tentar encontrar a topologia que apresente os menores valores de perdas ativas. Para o cálculo das perdas, este trabalho também apresenta uma nova abordagem para resolução do problema de fluxo de potência (FP) em sistemas de distribuição radial. O fluxo de potência é uma ferramenta básica utilizada pelos centros de controle para determinar os estados e condições operacionais desses sistemas de potência. Basicamente, as metodologias empregadas para o cálculo do fluxo de potência são baseadas nos métodos clássicos de Newton ou Gauss. Mas em sistemas de distribuição de energia, devido a particularidades inerentes a estes, como a alta relação entre resistência e reatância das linhas (r/x) e a operação radial, estes métodos apresentam problemas de convergência e se tornam ineficientes na maioria das vezes. A abordagem consiste na associação dos métodos da função penalidade e de Newton. O mal-condicionamento da matriz Jacobiana de Newton é resolvido pela associação com o método da função penalidade. São apresentados testes realizados em sistemas de 5 barras, 16 barras, 33 barras, 69 barras e 136 barras para avaliar a potencialidade das técnicas propostas. Os resultados são considerados bons ou muito bons quando comparado com as técnicas existentes atualmente. / The objective of this work is to present a novel methodology for obtaining new configurations of the distribution system in order to minimize the active power losses without violating operational constraints. For this, it is considered that any distribution system is operating in a steady state and that it is balanced, therefore it can be represented by a one-line diagram. The reconfiguration is done in order to redistribute de current flows on the distribution power lines, transferring loads among the feeders and improving the voltage profile along the system. Such problem can be formulated as a mixed integer nonlinear programming problem. Due to its inherent combinatorial characteristic and since its solution by classic optimization techniques is not appealing, heuristic and metaheuristic techniques are thus better suited for its solution. Although these latter do not guarantee a global optimum, they are able to find good solutions in a relatively short time. The solution of the reconfiguration problem in this approach makes use of a novel methodology based on ant colony behavior, when these search for victuals in nature. In this technique, the artificial ants (agents) explore the environment (distribution system) and exchange information among them in order to find the topology that provides the smallest active losses. For the active losses calculation, this work also presents a novel approach for the solution of the power flow problem for radial distribution systems. The solution of the power flow problem is used by system operators in order to determine the state and operational conditions of power systems. Basically, the most common techniques used in the power flow solution are based on either Newton\'s or Gauss\' approaches. However, due to particular characteristics of distribution systems such as the high ratio of r/x and the radial topology, these methods present convergence problems and are not efficient in most of the cases. Thus, this novel technique consists in associating Newton\'s and the penalty function approaches. The matter of the ill-conditioned Jacobian matrix in Newton\'s method is overcome with the penalty function method. Some tests performed in different systems are then presented in order to assess the effectiveness of both proposed techniques.

A precisão na fabricação de um implante pode ser verificada pelo grau de adaptação na interface implante/componente protético. Uma pobre adaptação permite a infiltração de microrganismos através dessa interface e a colonização dos espaços vazios dos implantes, levando ao surgimento de reações inflamatórias dos tecidos periimplantares e ao insucesso clínico do tratamento. O objetivo deste trabalho foi avaliar, in vitro, a infiltração de uma bactéria, o Staphylococcus aureus, através da interface implante/componente protético, pelo método de cultura bacteriana. Foram utilizados vinte conjuntos de implantes Cone Morse, com os Pilares CM (NEODENT®, Curitiba, Paraná, Brasil), divididos em dois grupos: Grupo A, onde foram avaliados quanto à infiltração bacteriana de fora para dentro dos implantes, e Grupo B, onde foram avaliados quanto à infiltração bacteriana de dentro para fora dos implantes. Foram utilizados também vinte conjuntos de implantes Titamax II Plus, com os Mini Pilares Cônicos II Plus (NEODENT®, Curitiba, Paraná, Brasil), divididos em dois grupos: Grupo C, onde foram avaliados quanto à infiltração bacteriana de fora para dentro dos implantes, e Grupo D, onde foram avaliados quanto à infiltração bacteriana de dentro para fora dos implantes. Na avaliação da infiltração bacteriana de dentro para fora dos implantes, foi feita a inoculação da bactéria na parte interna dos implantes, e estes mergulhados em tubos de ensaio contendo um meio de enriquecimento estéril. Para avaliação da infiltração bacteriana de fora para dentro dos implantes, os conjuntos implantes/componentes foram mergulhados em tubos de ensaio contendo um meio de enriquecimento com cepas da bactéria. Ocorreu infiltração bacteriana em todos os grupos, e não houve diferença estatisticamente significante entre os grupos A e C, nem entre os grupos B e D, em relação à percentagem da passagem do microrganismo na interface implante/componente protético. / The precision in the manufacture of an implant can be determined by the degree of adaptation at the abutment-implant interface. A poor adaptation allows the infiltration of microorganisms through this interface and colonization of empty spaces of the implants, leading to inflammatory reactions and clinical failure of treatment. The aim of the present in-vitro study was to investigate leakage of Staphylococcus aureus through the abutment-implant interface, by the method of bacterial culture. It was used twenty sets of Morse Taper implants with Pillars CM (NEODENTTM, Curitiba, Paraná, Brazil), divided into two groups: Group A, which were evaluated for bacterial infiltration into the inner part of the implants, and Group B, which were evaluated for bacterial infiltration from the inner part of the implants. Were also used twenty sets of Titamax II Plus implants, with the conical Mini Pillars II Plus (NEODENTTM, Curitiba, Paraná, Brazil), divided into two groups: Group C, which were evaluated for bacterial infiltration into the inner part of the implants and Group D, which were evaluated for bacterial infiltration from the inner part of the implants. In the evaluation of bacterial infiltration from the implants, the assemblies had the inner parts inoculated with S. aureus, and each assembly was incubated in BHI broth. For assessment of bacterial leakage into the implants, each assembly was submerged in S. aureus culture in tubes. Bacterial infiltration occurred in all groups, and there was no statistically significant difference between groups A and C, or between groups B and D.

A expansão marítima dos séculos XV e XVI reconfigurou as atividades mercantis na Europa e levou a difusão dos centros de comércio e das fontes de mercadorias em novas praças na Ásia, na América e na África. O trato transcontinental e as finanças, que ganharam complexidade, concretizaram-se nas relações entre as redes de comércio com atuação global. Portugal foi o nascedouro de grande parte dessas redes familiares que se multiplicaram e passaram a ter negócios em todas as frentes do trato colonial. No início do século XVII, os grandes cabedais lusos transferiram-se para Amsterdã e Hamburgo. Famílias cristãs-novas destacaram-se no trato mercantil, entre elas a dos Dias de Milão perseguida e presa pela Inquisição , que reapareceu em Amsterdã e Hamburgo com grande atuação no comércio internacional / The maritime expansion that occurred during the XV and XVI centuries reconfigured the mercantile activities in Europe and led to the dissemination of commercial centers and sources of commodities on new places of Asia, America and Africa. The transcontinental treat and finances gained complexity that substantiated itself in global trade networks. Portugal was the incubator of a great deal of those multiplying family networks that started to have businesses in all fronts of the colonial treat. At the beginning of the XVII century, the great Portuguese estates were transferred to Amsterdam and Hamburg. New-Christian families had significant importance in commercial dealings, among them the Dias de Milão family, persecuted and arrested by the Inquisition that reappeared in Amsterdam and Hamburg with great outwork on international commerce

Este estudo tem como objetivo, descrever a microbiota intestinal de pacientes com retocolite ulcerativa grave, em tratamento clínico, antes e após retocolectomia com anastomose de bolsa ileal ao canal anal. Comparou-se a flora bacteriana do íleo terminal e do reto no pré-operatório com a flora encontrada na bolsa ileal após dois e oito meses do fechamento da ileostomia e com a flora do íleo terminal e do reto de um grupo controle. Observou-se que a Veillonella sp foi a bactéria mais freqüentemente encontrada em todos os grupos. Não houve diferenças significativas entre a flora intestinal do grupo controle e dos pacientes com retocolite ulcerativa / The aim of this study is to describe the intestinal microbiota of patients with severe ulcerative colitis, under clinical treatment, before and after proctocolectomy and ileal pouch-anal anastomosis. Intestinal flora of distal ileum and rectum before surgery was compared with the flora found in ileal pouch after two and eight months after ileostomy closure and with the flora of distal ileum and rectum of controls. Veillonella sp was the most frequent microorganism found in all groups. There were no significant differences between the intestinal microbiota found in controls and in patients with ulcerative colitis

Introdução: Várias são as propostas descritas para tratar farmacologicamente a lesão traumática da medula espinal. A metilprednisolona já foi padronizada para uso clínico. O fator estimulador de colônia de granulócitos (G-CSF) tem sido promissor em estudos experimentais e clínicos. Não há pesquisas quanto ao efeito da associação dos dois fármacos. Objetivo: Avaliar o efeito do tratamento com o fator estimulador de colônia de granulócitos associado a metilprednisolona na lesão medular aguda experimental em ratos. Material e métodos: Foram avaliados 40 ratos Wistar submetidos a lesão medular moderada com o NYU-Impactor. Os animais foram divididos em quatro grupos de 10 ratos. O Grupo Controle não recebeu tratamento; o Grupo G-CSF, foi tratado com G-CSF no momento da lesão e diariamente ao longo dos cinco dias subsequentes; o Grupo Metilprednisolona, com metilprednisolona durante 24 horas; e o Grupo G-CSF/Metilprednisolona, com metilprednisolona durante 24 horas e G-CSF no momento da lesão e ao longo de cinco dias. Os animais foram mantidos vivos durante 42 dias; a avaliação funcional foi realizada com a aplicação da escala funcional de Basso, Beattie e Bresnahan (BBB) nos dias 2, 7, 14, 21, 28, 35 e 42 subsequentes à lesão. A avaliação dos potenciais evocados motores foi realizada no dia 42 e a avaliação histológica da lesão da região da medula espinal lesada, realizada logo após a eutanásia ocorrida no dia 42. Resultados e conclusões: A associação de metilprednisolona e G-CSF no tratamento do traumatismo medular contuso experimental em ratos promoveu melhora neurológica avaliada pela escala BBB superior à melhora promovida pela metilprednisolona e G-CSF quando utilizadas isoladamente. A associação teve também efeito sinérgico que resultou em melhora nos parâmetros histológicos no local da lesão. Não houve diferença entre os grupos quanto à avaliação neurofisiológica / Introduction: There are several proposals to pharmacologically treat traumatic spinal cord injury. Methylprednisolone has already been standardized for clinical use. Granulocyte colony stimulating factor (G-CSF) has been promising in experimental and clinical studies. There is no research on the effect of the association of the two drugs. Objective: to evaluate the effect of combined treatment of the granulocyte colony-stimulating factor (G-CSF) associated with methylprednisolone in experimental acute spinal cord injury in rats. Material and methods: Forty male Wistar rats were submitted to a moderate spinal cord injury with the NYU-Impactor. The animals were divided into four groups of ten rats each. The Control Group was not treated; the G-CSF Group was treated with G-CSF at the time of injury and daily over the next five days; the Methylprednisolone Group was treated with methylprednisolone for 24 hours; the G-CSF/methylprednisolone Group, was treated with methylprednisolone for 24 hours and G-CSF at the time of injury and daily over the next five days. The animals were kept alive for 42 days; Functional evaluation was performed using the Basso, Beattie and Bresnahan (BBB) score on days 2, 7, 14, 21, 28, 35 and 42 following the spinal cord injury. Evaluation of motor evoked potentials was held and histological examination of the lesion of the spinal cord was done immediately after euthanasia on day 42. Results and conclusions: The combination of methylprednisolone and G-CSF in the treatment of experimental spinal cord injury in rats promoted neurological improvement as assessed by BBB scale with greater improvement than with methylprednisolone or G-CSF when used alone. The combination of treatment had also a synergistic effect resulting in improvement in histological parameters at the injury site. There was no difference between groups regarding neurophysiological evaluation

Le corpus de films est constitué par les films amateurs tournés par les coloniaux dans les colonies françaises, Madagascar et le Sénégal. Ce corpus source est enrichi des films contemporains les utilisant. Dans le cadre d'une pratique d'action-recherche, deux films ont été réalisés. En 3 mouvements nous avons essayé de déterminer la valeur des films amateurs coloniaux aujourd’hui. Nous nous sommes appuyés sur l’anthropologie pragmatique et la philosophie de l’ordinaire pour comprendre les enjeux de ces films. Nos enquêtes révèlent que cette absence de valeur correspond à un déni de réalité de la situation coloniale, niant à la fois les injustices et les liens affectifs qui avaient pu être créées principalement entre les enfants de colons et les domestiques. D'où le paradoxe : des films dits "domestiques", les domestiques sont absents. Cette absence est essentielle. Sans les nounous et les boys, ces films sont des no man’s land. De plus, le contexte colonial crée un rapport d'illégitimité voir d'illégalité de ces films. En conclusion nous proposons d'une part une méthode de reconstruction cinématographique qui mette au cœur de son dispositif les trois acteurs liés aux films amateurs : les filmeurs, les filmés, les personnes dans le Hors champs. D'autre part nous proposons la création d'un institut des films amateurs coloniaux reposant sur des principes établis par un éthique de l'archivistique audiovisuelle et qui permettrait aux anciens colonisés de se réapproprier les images spoliées de leur propre passé à une époque où il y avait un monopole des moyens de production audiovisuelle. Cela répondrait à une justice mémorielle, audiovisuelle et affective. / The films corpus is made by amateur films shot by colonials in the French colonies, Madagascar and Senegal. This source corpus is enriched by contemporary films using these amateur films and films from the colonial era. As part of a practice of action research, two films were made. In 3 movements we tried to determine the value colonial home movies may have today. We relied on the pragmatic anthropology and ordinary philosophy to understand the issues of these films. The starting assumption was that these films had been abandoned, they had no more value as a result of a colonial state denied by settlers. Our historical and sociological surveys show that this lack of value is a denial of reality of the colonial situation, denying both injustice and emotional ties that had been created mainly between the settler children and servants. Hence the paradox of films called "domestic" is that domestics are absent. This lack is essential. Without nannies and boys, these films are a no man's land. Moreover, the colonial context creates a report view illegitimacy illegality of these films. In conclusion we propose firstly a cinematic reconstruction method that puts the heart of its system linked to the three actors amateur films: the filmmakers, the filmed people and those in the fields Out. Secondly we propose the creation of an institute of colonial amateur films based on principles established by an ethic of audiovisual archiving that allow former colonized to reclaim the images of their own past at a time when there was a monopoly of audiovisual means of production. This would respond to a memorial, audiovisual and emotional justice.

A precisão na fabricação de um implante pode ser verificada pelo grau de adaptação na interface implante/componente protético. Uma pobre adaptação permite a infiltração de microrganismos através dessa interface e a colonização dos espaços vazios dos implantes, levando ao surgimento de reações inflamatórias dos tecidos periimplantares e ao insucesso clínico do tratamento. O objetivo deste trabalho foi avaliar, in vitro, a infiltração de uma bactéria, o Staphylococcus aureus, através da interface implante/componente protético, pelo método de cultura bacteriana. Foram utilizados vinte conjuntos de implantes Cone Morse, com os Pilares CM (NEODENT®, Curitiba, Paraná, Brasil), divididos em dois grupos: Grupo A, onde foram avaliados quanto à infiltração bacteriana de fora para dentro dos implantes, e Grupo B, onde foram avaliados quanto à infiltração bacteriana de dentro para fora dos implantes. Foram utilizados também vinte conjuntos de implantes Titamax II Plus, com os Mini Pilares Cônicos II Plus (NEODENT®, Curitiba, Paraná, Brasil), divididos em dois grupos: Grupo C, onde foram avaliados quanto à infiltração bacteriana de fora para dentro dos implantes, e Grupo D, onde foram avaliados quanto à infiltração bacteriana de dentro para fora dos implantes. Na avaliação da infiltração bacteriana de dentro para fora dos implantes, foi feita a inoculação da bactéria na parte interna dos implantes, e estes mergulhados em tubos de ensaio contendo um meio de enriquecimento estéril. Para avaliação da infiltração bacteriana de fora para dentro dos implantes, os conjuntos implantes/componentes foram mergulhados em tubos de ensaio contendo um meio de enriquecimento com cepas da bactéria. Ocorreu infiltração bacteriana em todos os grupos, e não houve diferença estatisticamente significante entre os grupos A e C, nem entre os grupos B e D, em relação à percentagem da passagem do microrganismo na interface implante/componente protético. / The precision in the manufacture of an implant can be determined by the degree of adaptation at the abutment-implant interface. A poor adaptation allows the infiltration of microorganisms through this interface and colonization of empty spaces of the implants, leading to inflammatory reactions and clinical failure of treatment. The aim of the present in-vitro study was to investigate leakage of Staphylococcus aureus through the abutment-implant interface, by the method of bacterial culture. It was used twenty sets of Morse Taper implants with Pillars CM (NEODENTTM, Curitiba, Paraná, Brazil), divided into two groups: Group A, which were evaluated for bacterial infiltration into the inner part of the implants, and Group B, which were evaluated for bacterial infiltration from the inner part of the implants. Were also used twenty sets of Titamax II Plus implants, with the conical Mini Pillars II Plus (NEODENTTM, Curitiba, Paraná, Brazil), divided into two groups: Group C, which were evaluated for bacterial infiltration into the inner part of the implants and Group D, which were evaluated for bacterial infiltration from the inner part of the implants. In the evaluation of bacterial infiltration from the implants, the assemblies had the inner parts inoculated with S. aureus, and each assembly was incubated in BHI broth. For assessment of bacterial leakage into the implants, each assembly was submerged in S. aureus culture in tubes. Bacterial infiltration occurred in all groups, and there was no statistically significant difference between groups A and C, or between groups B and D.

A tarefa de planejamento de trajetórias de robôs móveis autônomos consiste em determinar objetivos intermediários para que um robô seja capaz de partir de sua localização inicial e alcançar seu objetivo final. Além do planejamento, é importante definir um método de controle da navegação (seguimento da trajetória) do robô para que ele seja capaz de realizar seu trajeto de forma segura. Este projeto propõe uma abordagem híbrida para planejamento exploratório e execução de trajetórias de robôs móveis autônomos em ambientes indoor. Para o planejamento de trajetória, foram investigados algoritmos de busca em espaço de estados, dando ênfase ao uso de algoritmos evolutivos e algoritmos de otimização por colônia de formigas para a descoberta e otimização da trajetória. O controle da navegação é realizado por meio de comportamentos locais reativos, baseado na exploração e uso de mapas topológicos, os quais permitem uma maior flexibilidade em termos de definição da localização da posição do robô móvel e sobre os detalhes do mapa do ambiente (mapas com informações aproximadas e não métricos). Assim, foi proposto e desenvolvido um método robusto capaz de planejar, mapear e explorar um caminho ótimo ou quase ótimo para que o robô possa navegar e alcançar seu objetivo de forma segura, com pouca informação prévia do ambiente ou mesmo sobre sua localização. Além disso, o robô pode reagir a ambientes com alterações dinâmicas em sua estrutura, considerando por exemplo, elementos dinâmicos como portas que possam ser abertas ou fechadas e passagens que são obstruídas. Por fim, foram realizados diversos testes e simulações a fim de validar o método proposto, com a avaliação da qualidade das soluções encontradas e comparação com outras abordagens tradicionais de planejamento de trajetórias (algoritmos A* e D*). / The task of planning path for autonomous mobile robots consists in determine intermediary goals in order to allow a robot be able to leave its initial location and reach its final goal. Besides the planning, it is important to define a method of navigation control (the trajectory following) of the robot for it be able to do its path safely. This project proposes a hybrid approach to path planning and execution of an autonomous mobile robot in indoor environments. For the path planning, search algorithms in state space have been investigated, with emphasis in evolutionary algorithms and ant colony optimization algorithms for the trajectory search and optimization. The navigation control is done by local reactive behaviors, based on topological maps, which allow more flexibility concerning localization definition of position of the mobile robot and about the details of the environment map (maps with approximate information and not metric). Thus, a robust method able to plan an optimum or almost optimum path for the robot to reach its goal safely has been proposed, with little previous information of the environment. Furthermore, the robot can react to dynamic elements in the environment structure, concerning, for example, dynamic elements such as doors that can be opened or closed and ways that are blocked. Finally, several tests and simulations has been carried out to validate the proposed method, with evaluation of the solutions quality and comparison with others traditional approaches for the path planning task (A* and D* algorithms).

Mobilização inadequada de células progenitoras hematopoéticas (CPH) tem sido observada em 10 - 30% dos pacientes submetidos a transplante de medula óssea (TMO) autogênico para tratamento de doenças onco-hematológicas. Os fatores relacionados com má resposta à mobilização ainda não estão totalmente estabelecidos. Apresentamos uma análise retrospectiva de pacientes submetidos à TMO autogênico com o objetivo de identificar variáveis associadas com resposta ruim ao regime de mobilização utilizado. Casuística e Métodos: Fizeram parte desta análise 307 pacientes com diferentes diagnósticos, tratados com TMO autogênico em uma única Instituição, no período de Abril de 2001 a Abril de 2007. Todos os pacientes incluídos no estudo foram submetidos a um único regime de mobilização baseado na administração de ciclofosfamida (dose total de 60-120 mg/kg de peso IV) e fator estimulador de colônias de granulócitos (G-CSF) (dose diária de 6 - 17 ug/(kg de peso)/dia SC). O sucesso na resposta ao regime de mobilização foi definido quando um número maior ou igual a 2,0x10 (6) células CD34 + /(kg de peso) foi coletado do sangue periférico com até três procedimentos de leucaférese. Resultados: Dos pacientes analisados, 260 apresentaram sucesso na mobilização (84,7%). Nestes pacientes, um número mediano de 3,67 (2,0 - 46,0) células CD34+ /(kg de peso) foi coletado por paciente com um número mediano de 1 (1-3) procedimento de leucaférese. O insucesso na mobilização foi observado em 47 pacientes (15,3%): 24 (7,8%) que foram submetidos à coleta de CPH de sangue periférico, porém não coletaram número maior ou igual 2,0x10 (6) células CD34+/(kg de peso) com pelo menos três procedimentos de leucaférese; e, 23 (7,5%) foram submetidos à coleta de CPH por punção da medula óssea, por não terem atingido número mínimo de 10 células CD34+/mm3 no sangue periférico para realização de leucaférese. De acordo com análise univariada, os fatores associados com o insucesso foram: diagnóstico (P < 0,0001), tempo de doença (P < 0,0001), número prévio de ciclos de quimioterapia (P = 0,0001), exposição prévia a agentes alquilantes (P = 0.0003) e a mitoxantrone (P = 0,0006), contagem de plaquetas pré-mobilização <150.000/mm3 (P = 0,0006) e intervalo entre o início da mobilização e o pico de células CD 34+ no sangue periférico (P < 0,0001). Idade, sexo, atividade da doença e envolvimento medular ao início da mobilização, tratamento prévio com radioterapia e exposição a análogos da platina não mostraram correlação significativa na resposta à mobilização. Após análise multivariada, as variáveis que permaneceram associadas com insucesso na mobilização foram: diagnóstico (P = 0,0232), número prévio de ciclos da quimioterapia (P = 0,0167), tratamento prévio com mitoxantrone (P = 0,0285) e contagem de plaquetas pré-mobilização < 150.000/mm3 (P = 0,0423). Conclusão: A carga cumulativa de quimioterapia administrada, exposição prévia à mitoxantrone, contagem de plaquetas pré-mobilização e diagnóstico foram os fatores independentes relacionados com a falha na resposta à mobilização. Os achados obtidos podem auxiliar no reconhecimento de pacientes de risco para resposta ruim à mobilização e permitir um planejamento alternativo ou mais agressivo no regime de mobilização para este grupo de pacientes. / Inadequate stem cells mobilization is seen in 10-30% of patients undergoing autotransplantation for hematologic malignancies. Factors affecting peripheral blood progenitor cell (PBSC) mobilization have not been clearly established. We retrospectively reviewed the data of patients treated by autologous bone marrow transplantation (BMT) with the aim to identify factors associated with poor PBSC mobilization. Design and Methods: We evaluated 307 patients with different diagnoses, submitted to autologous BMT between April 2001 and April 2007. PBSC were collected following mobilization with cyclophosphamide (60-120 mg/kg of weight IV) and granulocyte-colony stimulating factor (G-CSF) (dose of 6-17 ug/kg of weight/day SC). Success in mobilization was defined when > ou = a 2,0x10(6) CD34+ cells/(kg weight) could be collected from the peripheral blood with a maximum of three leukapheresis procedures. Clinical and laboratory parameters at the time of mobilization were analyzed for correlations with the number of CD34+ cells collected. Results: Two hundred and sixty patients (84.7%) presented success in mobilization. In this group, a median of 3.67 (2.0-46.0) CD34+ cells/(kg weight) was collected per patient in a median of 1(1-3) leukapheresis procedure. Poor response to mobilization was observed in 47 patients (15.3%): 24 (7.8%) were submitted to PBSC collection but didn\'t collected at least 2.0 x 106 CD34+ cells/(kg weight) with three leukapheresis procedures and 23 (7.5%) didn\'t reach an absolute number count of 10 CD34+ cells/mm3 in the peripheral blood to start collection by leukapheresis. In univariate analysis poorer PBSC mobilization was associated with diagnosis (Pp < 0.0001), time interval from the diagnosis to mobilization (P < 0.0001), number of cycles of previous chemotherapy (P = 0.0001), previous treatment with alkylating agents (P = 0.0003) and mitoxantrone (P = 0.0006), platelet count <150.000/mm3 before mobilization (P = 0.0006) and interval between mobilization and peak of CD34+ cells in peripheral blood (P < 0.0001). No significant correlation was found with age, gender, disease status, marrow involvement at mobilization, prior radiation therapy and exposition to platin analogues. In the stepwise regression model, diagnosis (P = 0.0232), number of cycles of previous chemotherapy (P = 0.0167), previous treatment with mitoxantrone (P = 0.0285) and platelet count <150.000/mm3 before mobilization (P = 0.0423) were found to be independent negative predictive factors for CD34+ cells mobilization. Conclusion: Cumulative load of chemotherapy, exposition to Mitoxantrone, platelet count just prior to mobilization and diagnosis were independent factors related to poor progenitor cells mobilization. These results could help in the previously recognition of patients at risk for poor or no response to mobilization and allow to plan an alternative or more aggressive regimen for this group of patients.

by Lee Juon Kiu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 139-152). / Abstracts in English and Chinese. / Thesis committee --- p.i / Statement --- p.ii / Acknowledgements --- p.iii / Abstract --- p.v / Table of contents --- p.ix / List of figures --- p.xv / List of tables --- p.xvii / List of graphs --- p.xviii / List of abbreviations --- p.xix / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter Chapter 2: --- Literature Review --- p.4 / Chapter 2.1 --- Human granulocyte colony-stimulating factor (hG-CSF) --- p.4 / Chapter 2.1.1 --- Physiological roles --- p.4 / Chapter 2.1.2 --- Molecular properties --- p.8 / Chapter 2.1.3 --- Biochemical properties --- p.9 / Chapter 2.1.4 --- Comparison to G-CSF of other specie --- p.10 / Chapter 2.1.5 --- Clinical application --- p.11 / Chapter 2.1.6 --- Economic value --- p.13 / Chapter 2.2 --- Expression systems producing recombinant hG-CSF --- p.15 / Chapter 2.2.1 --- Bacteria --- p.15 / Chapter 2.2.2 --- Yeasts --- p.17 / Chapter 2.2.3 --- Animal cell lines --- p.18 / Chapter 2.2.4 --- Transgenic animals --- p.19 / Chapter 2.2.5 --- Transgenic plants --- p.20 / Chapter 2.3 --- Plant as bioreactors --- p.21 / Chapter 2.3.1 --- Characteristics of using plant as bioreactors --- p.22 / Chapter 2.3.2 --- Transgenic plants producing hematopoietic growth factors --- p.24 / Chapter 2.3.2.1 --- Granulocyte-macrophage colony-stimulating factor (GM-CSF) --- p.24 / Chapter 2.3.2.2 --- Erythropoietin (Epo) --- p.26 / Chapter 2.3.3 --- Arabidopsis and tobacco as model plants --- p.27 / Chapter 2.3.3.1 --- Arabidopsis --- p.28 / Chapter 2.3.3.2 --- Tobacco --- p.28 / Chapter 2.3.4 --- Phaseolin and its regulatory sequences --- p.29 / Chapter 2.4 --- Plant transformation methods --- p.31 / Chapter 2.4.1 --- Agrobacterium-mediated transformation --- p.31 / Chapter 2.4.1.1 --- Tissue culture methods --- p.31 / Chapter 2.4.1.2 --- Non-tissue culture (In planta) methods --- p.32 / Chapter 2.4.2 --- Direct DNA uptake transformation --- p.33 / Chapter 2.4.2.1 --- Chemical methods --- p.33 / Chapter 2.4.2.2 --- Electrical methods --- p.34 / Chapter 2.4.2.3 --- Physical methods --- p.34 / Chapter Chapter 3: --- Materials and Methods --- p.36 / Chapter 3.1 --- Introduction --- p.36 / Chapter 3.2 --- Chemicals --- p.37 / Chapter 3.3 --- Bacterial strains --- p.37 / Chapter 3.4 --- Chimeric gene construction --- p.37 / Chapter 3.4.1 --- Cloning of pTZ/Phas/His/EK/hG-CSF --- p.41 / Chapter 3.4.2 --- Cloning of pBK/Phas/SP/His/EK/hG-CSF --- p.44 / Chapter 3.4.3 --- Cloning of pBK/Phas/SP/hG-CSF --- p.47 / Chapter 3.4.4 --- Confirmation of sequence fidelity of chimeric genes --- p.50 / Chapter 3.4.5 --- Cloning of chimeric genes into Agrobacterium binary vector --- p.51 / Chapter 3.5 --- Expression in Arabidopsis --- p.52 / Chapter 3.5.1 --- Agrobacterium GV3101/pMP90 transformation --- p.52 / Chapter 3.5.2 --- Arabidopsis transformation --- p.53 / Chapter 3.5.2.1 --- Plant materials --- p.53 / Chapter 3.5.2.2 --- Vacuum infiltration --- p.54 / Chapter 3.5.3 --- Screening of successful R1 transformants --- p.55 / Chapter 3.5.4 --- Screening of hemizygous and homozygous transgenic Arabidopsis --- p.56 / Chapter 3.5.5 --- GUS assay --- p.57 / Chapter 3.5.6 --- Genomic DNA extraction --- p.57 / Chapter 3.5.7 --- Southern blot analysis --- p.58 / Chapter 3.5.8 --- Total RNA extraction from developing siliques --- p.59 / Chapter 3.5.9 --- Northern blot analysis --- p.60 / Chapter 3.5.10 --- Protein extraction and Tricine SDS-PAGE --- p.61 / Chapter 3.5.11 --- Western blot analysis --- p.62 / Chapter 3.5.12 --- Functional analysis --- p.63 / Chapter 3.5.12.1 --- Culture ofNFS-60 cells --- p.64 / Chapter 3.5.12.2 --- MTT assay --- p.65 / Chapter 3.6 --- Expression in tobacco --- p.67 / Chapter 3.6.1 --- Agrobacterium LBA4404/pAL4404 transformation --- p.67 / Chapter 3.6.2 --- Tobacco transformation --- p.68 / Chapter 3.6.2.1 --- Plant materials --- p.68 / Chapter 3.6.2.2 --- Tobacco transformation using leaf-disc technique --- p.68 / Chapter 3.6.3 --- Regeneration of transgenic tobacco --- p.69 / Chapter 3.6.4 --- GUS assay --- p.70 / Chapter 3.6.5 --- Genomic DNA extraction --- p.70 / Chapter 3.6.6 --- Southern blot analysis --- p.70 / Chapter 3.6.7 --- Total RNA extraction from immature seeds --- p.70 / Chapter 3.6.8 --- Northern blot analysis --- p.71 / Chapter 3.6.9 --- Protein extraction and Tricine SDS-PAGE --- p.71 / Chapter 3.6.10 --- Western blot analysis --- p.71 / Chapter 3.6.11 --- Functional analysis --- p.71 / Chapter 3.6.11.1 --- Culture of NFS-60 cells --- p.72 / Chapter 3.6.11.2 --- MTT assay --- p.72 / Chapter Chapter 4: --- Results --- p.73 / Chapter 4.1 --- Chimeric gene construction --- p.73 / Chapter 4.1.1 --- Cloning of pTZ/Phas/His/EK/hG-CSF --- p.73 / Chapter 4.1.2 --- Cloning of pBK/Phas/SP/His/EK/hG-CSF --- p.75 / Chapter 4.1.3 --- Cloning of pBK/Phas/SP/hG-CSF --- p.77 / Chapter 4.1.4 --- Cloning of chimeric genes into Agrobacterium binary vector --- p.79 / Chapter 4.2 --- Expression in Arabidopsis --- p.81 / Chapter 4.2.1 --- Agrobacterium GV3101/pMP90 transformation --- p.81 / Chapter 4.2.2 --- Arabidopsis transformation and screening of R1 transformants --- p.83 / Chapter 4.2.3 --- Screening of hemizygous transgenic R1 Arabidopsis --- p.84 / Chapter 4.2.4 --- Screening of homozygous transgenic R2 Arabidopsis --- p.86 / Chapter 4.2.5 --- GUS assay --- p.88 / Chapter 4.2.6 --- Genomic DNA extraction --- p.89 / Chapter 4.2.7 --- Southern blot analysis --- p.91 / Chapter 4.2.8 --- Total RNA extraction from developing siliques --- p.93 / Chapter 4.2.9 --- Northern blot analysis --- p.94 / Chapter 4.2.10 --- Protein extraction and Tricine SDS-PAGE --- p.96 / Chapter 4.2.11 --- Western blot analysis --- p.99 / Chapter 4.2.12 --- Functional analysis --- p.103 / Chapter 4.3 --- Expression in tobacco --- p.108 / Chapter 4.3.1 --- Agrobacterium LBA4404/pAL4404 transformation --- p.108 / Chapter 4.3.2 --- Tobacco transformation and regeneration of transformants --- p.109 / Chapter 4.3.3 --- GUS assay --- p.111 / Chapter 4.3.4 --- Genomic DNA extraction --- p.112 / Chapter 4.3.5 --- Southern blot analysis --- p.114 / Chapter 4.3.6 --- Total RNA extraction from immature seeds --- p.116 / Chapter 4.3.7 --- Northern blot analysis --- p.116 / Chapter 4.3.8 --- Protein extraction and Tricine SDS-PAGE --- p.118 / Chapter 4.3.9 --- Western blot analysis --- p.120 / Chapter 4.3.10 --- Functional analysis --- p.123 / Chapter Chapter 5: --- Discussion --- p.126 / Chapter 5.1 --- Introduction --- p.126 / Chapter 5.2 --- Successful in producing biologically active rhG-CSF from transgenic plants --- p.128 / Chapter 5.2.1 --- Production level --- p.129 / Chapter 5.2.2 --- O-glycosylation --- p.130 / Chapter 5.2.3 --- Phaseolin signal peptide --- p.131 / Chapter 5.2.4 --- Functional analysis --- p.131 / Chapter 5.3 --- Comparison of the productivity of other expression systems producing rhG-CSF --- p.132 / Chapter 5.4 --- Comparison of the productivity of plants producing different human proteins --- p.135 / Chapter 5.5 --- Future perspectives --- p.137 / Chapter Chapter 6: --- Conclusion --- p.138 / References --- p.139