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Brincar(es) na infância: possibilidades no contexto da doença falciforme e da hemofiliaOliveira, Luciana da Silva de 20 August 2010 (has links)
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Previous issue date: 2010-08-20 / O presente estudo investigou como o brincar se faz presente no cotidiano de crianças portadoras de doença falciforme e de crianças portadoras de hemofilia. Trata-se de sujeitos que possuem uma doença crônica no sangue, com a qual terão de conviver ao longo de toda a vida. Devido a isso, demandam cautela quando à prática de atividades extenuantes. A fim de responder minha questão, decidi realizar uma triangulação envolvendo entrevistas com as mães, desenhos com as crianças e observação do contexto escolar em que estão inseridas. Os achados foram analisados na perspectiva do paradigma indiciário na linha de Ginzburg, compreendendo que cada dado se constitui como peculiar. Como respaldo teórico, busquei as contribuições de dois grandes autores: Winnicott e Vigotski. O primeiro foi médico pediatra e, ao imbricar-se no mundo da psicanálise, buscou compreender questões diversas da natureza humana, dentre as quais o brincar. Com base em suas contribuições, desvelei, junto à maternagem suficientemente boa, o contexto familiar da doença, bem como a relação do brincar com a saúde. Com Vigotski, na linha do materialismo histórico-dialético, busquei compreender os aspectos do brincar no espaço da vida, entre as pessoas e as instituições que medeiam as relações construídas socialmente. É esse autor quem me auxilia a dialogar com as crianças e a compreender tanto as possibilidades do brincar, como o contexto escolar dos sujeitos pesquisados. Os achados me levaram a concluir que, apesar de demandar certos cuidados para a manutenção do bem estar do sujeito, a doença falciforme e a hemofilia não impedem que a criança tenha qualidade de vida e que o brincar, mesmo nas ocasiões mais delicadas, em que os sintomas se agravam, não apenas pode ser exercido e explorado, como contribui para a promoção da saúde. / The playing act was investigated by this study in its meaning to the children’s daily with falciform and hemophilie diseases. We are talking about subjects who has a blood chronic disease that will last during their entire lives. Because of that, they need more care when tiresome activities practices are done. To turn possible answer our question, we decide to carry out a triangling among mother’ interviews, drawings with children and observation of the school context in which they are put in. The findings were analysed in the Ginzburg indicering paradigm perspetive understanding each record as a peculiar one. By theoretical supporting, we have the Winnicott and Vigotski contributions. Winnicott was a pediatrician doctor who immersing himself in psychoanalysis, sought understand different questions about human nature, inluding playing act. Based in his contributions, we can reveal together with a good mothering the familiar and context disease and a relation between playing act and health. With Vigotski and his historic-dialetic materialism, we seek to understand the playing act aspects in the life space between people and institutions that mediate relations socially constructed. This author helps us to talk with children and to understand as the playing act possibilities as the school context of the researched subjetcts. The findings lead us to conclude that falciform and hemophilie diseases don’t hinder child to have a good quality life, in spite of the care that must be spend to garantie the person well-being. The playing act, even in the difficult occasions when the symptoms are intensified, can be carried out and explored.
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Hépatocytes différenciés à partir de cellules souches pluripotentes induites : modèle pour la thérapie cellulaire et génique autologue de l'hémophilie B et modèle préclinique chez le primate / Hepatocytes differentiated from induced pluripotent stem cells : model for autologous cell and gene therapy of hemophilia B and preclinical model in primateLuce, Eléanor 15 December 2017 (has links)
Ce projet de thèse vise à modéliser puis à apporter la preuve de concept d’une thérapie cellulaire et génique autologue de maladies héréditaires du foie par la transplantation d’hépatocytes différenciés à partir des cellules souches pluripotentes induites (iPSC) spécifiques du patient, une fois celles-ci corrigées du défaut génétique. L’hémophilie B (HB) est une maladie héréditaire causée par une mutation du gène F9, codant le facteur IX (FIX) de la coagulation synthétisé dans le foie par les hépatocytes. Des fibroblastes d’un patient porteur de la « mutation royale » ont été reprogrammés en iPSC puis différenciés en hépatocytes. L’étude de l’ARNm du F9 par séquençage haut débit a confirmé la présence d’un site d’épissage anormal codant une protéine tronquée. D’autres iPSC ont été obtenues à partir des cellules d’un second patient HB exprimant un FIX inactif. Après insertion ciblée d’une cassette thérapeutique codant le FIX dans un site génomique sûr à l’aide d’endonucléases artificielles (CRISPR/Cas9), nous avons différencié les iPSC corrigées et non corrigées en hépatocytes (respectivement corr-HB-Heps et HB-Heps) et confirmé une expression plus importante de l’ARNm du F9 et de la protéine FIX dans les corr-HB-Heps. En revanche, nous n’avons pas détecté d’activité du FIX transgénique sans doute à cause d’une différenciation incomplète des hépatocytes. Nous avons alors développé un protocole de différenciation en sphéroïdes permettant une différenciation plus efficace confirmée aux niveaux ARN et protéine FIX. L’analyse de l’activité du FIX produit nous permettra de valider la correction in vitro avant de la valider in vivo en transplantant les corr-HB-Heps dans un modèle de souris F9KO. Finalement, la dernière partie de ce travail a consisté à développer un protocole de différenciation d’iPSC de singe en hépatocytes en vue d’une transplantation autologue dans le foie de l’animal donneur pour valider la faisabilité et la sécurité de cette approche chez le gros animal. / This PhD project aims to model and to bring a proof of concept for autologous cell/gene therapy of inherited liver diseases by transplanting hepatocytes differentiated from patient-specific induced pluripotent stem cells (iPSCs), after correction of the genetic defect. Hemophilia B (HB) is an inherited disease caused by a mutation in the F9 gene encoding clotting factor IX (FIX), synthesized in the liver by hepatocytes. Fibroblasts of a patient with the "royal mutation" were reprogrammed in iPSCs then differentiated into hepatocytes. The study of the F9 mRNA by high-throughput sequencing confirmed the presence of an abnormal splice site leading to a truncated protein explaining hemophilia. Other iPSCs were obtained and characterized from the cells of a second HB patient expressing an inactive FIX. By targeting in these iPSCs the insertion of a therapeutic cassette encoding FIX into a safe harbor site using artificial endonucleases (CRISPR/Cas9), we differentiated the corrected and non-corrected iPSC into hepatocytes. Quantitative analyzes confirmed a higher expression of F9 mRNA and FIX protein in the corrected clones. In contrast, we did not detect transgenic FIX activity due to a lack of post-translational modifications necessary for FIX activity. We then developed a protocol of differentiation in spheroids quantitatively more efficient to produce FIX. Detection of FIX activity will validate our in vitro approach before validation in vivo by transplanting the corrected hepatocytes in a F9KO mouse model. Finally, the last part of this work consisted in the development of a differentiation protocol of nonhuman primate iPSCs into hepatocytes for autologous transplantation into the liver of the donor animal in order to validate the feasibility and the safety of such an approach in the large animal
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