O Ministério da Saúde adverte que o Diabetes Mellitus é um problema de saúde pública devido sua alta taxa de prevalência. Estudos demonstram a correlação entre o funcionamento psicodinâmico de pacientes com diabetes mellitus tipo 1 e o controle glicêmico. Considerando que o controle glicêmico adequado minimiza os riscos para a mãe, o feto e o futuro bebê, salienta-se a importância de um atendimento psicoterápico na fase gestacional. Contudo, não existem pesquisas sobre Psicoterapia Breve Operacionalizada (PBO) enquanto técnica terapêutica para este tipo de população. O objetivo da pesquisa foi investigar possibilidades e limites da PBO no atendimento a gestantes portadoras de diabetes mellitus tipo 1 (DM1) com mau controle glicêmico. A metodologia utilizada para a pesquisa foi o clinico-qualitativo. O estudo envolveu quatro gestantes portadoras de DM1 com mau controle glicêmico. As gestantes foram encaminhadas pela Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, local onde as mesmas são atendidas. Foram utilizados como instrumentos: entrevista clínica psicológica; Escala Diagnóstica Adaptativa Operacionalizada; e Psicoterapia Breve Operacionalizada. As gestantes que concordaram em participar assinaram o Termo de Consentimento Livre e Esclarecido que após lido e explicado, foi assinado pela pesquisadora e gestante. Foram realizadas duas ou três entrevistas inicias para o diagnóstico adaptativo operacionalizado e planejamento da PBO. O número de sessões utilizadas para PBO foi definido conforme o diagnóstico adaptativo da gestante e sua situação-problema. As entrevistas e as sessões psicoterápicas tiveram duração de 45 minutos e frequência de uma vez por semana. A análise dos resultados foi realizada através da comparação entre o diagnóstico adaptativo operacionalizado realizado antes e depois da PBO. Foi verificado se ocorreu nas gestantes, durante estes períodos, mudanças adaptativas; além da averiguação das alterações no controle glicêmico, antes e após a PBO. A pesquisa expôs que houve mudanças de grupo adaptativo da qual as gestantes pertenciam. Cecília e Beatriz obtiveram melhora no diagnóstico adaptativo. Por intermédio do acompanhamento da evolução do controle glicêmico, pode-se verificar alterações com o decorrer da PBO: a porcentagem de hipoglicemias e hipoglicemias graves melhoraram; as porcentagens de valores alterados e de hiperglicemias, por sua vez, tiveram piora com o decorrer da gravidez, e, mesmo com a PBO, o rigoroso controle alimentar e insulinoterapia, inclusive em internações, foram dificilmente controlados. Das quatro gestantes estudadas duas tiveram crise adaptativa e as soluções encontradas por elas foram satisfatórias. O que pode restringir o processo psicoterapêutico é a transferência negativa persistente, contudo, ela pode ser trabalhada e minimizada. As possibilidades da PBO no atendimento às gestantes com DM1 encontradas na pesquisa foram: melhorar a eficácia da adaptação; auxiliar as pacientes em crise a solucionarem-na sem a queda da eficácia da adaptação; e, possibilitar as pacientes encontrarem soluções mais adequadas para suas situações-problema / The health ministry adverts that Diabetes Mellitus is a public health concern due to its high prevalence rate. Studies demonstrate the existing relation between the psychodynamic functioning of patients with type 1 diabetes mellitus and the glycemic control. Considering that the adequate glycemic control minimizes risks for the mother, fetus and the future baby, it reinforces the importance of psychotherapeutic treatment during the pregnancy. However, there arent any researches on Operationalized Brief Psychotherapy (OBP) as a therapeutic technique for this kind of population. The aim of the research was to investigate the possibilities and the limits of OBP in the treating of pregnant women with type 1 diabetes mellitus with deficient glycemic control. The methodology used for the research was the clinical-qualitative method. The study involved four pregnant women with DM1 with deficient glycemic control. The women were appointed by the Obstetric Clinic of the Hospital das Clínicas da Faculdade de Medicina from the University of São Paulo, place where they were already being treated. The instruments employed were Psychological Interviews, the Operationalized Adaptive Diagnosis Scale and Operationalized Brief Psychotherapy. The women who agreed to take part in the research signed a consent form that, after read and explained, was then signed by the research agent and the subjects. Two or three initial interviews took place for the Operationalized Adaptive Diagnosis and the planning of the. The number of sessions employed for the OPB was defined in accordance to the adaptive diagnosis of the subject and their problem-situation. The interviews and the psychotherapeutic sessions lasted 45 minutes with the frequency of once a week. The analysis of the results was made through the comparison between the operationalized adaptive diagnosis done before and after the OPB. During these periods, it was verified if there were any adaptive changes in the subjects and, moreover, the analysis of any alterations in the glycemic control before and after the OPB. The research showed that there were changes in the adaptive group to which the subjects belonged. Cecília and Beatriz had an improvement in the adaptive diagnosis. Through the analysis of the evolution of the glycemic control, it was possible to verify alterations during the OPB: the percentage of both hypoglycemia and severe hypoglycemia showed improvement; however, the percentage of altered rates and of hyperglycemia showed a downturn throughout the pregnancy and, even with the OPB, a strict diet control and insulin therapy, including during admissions, were hardly controlled. From the four pregnant women in the study, two of them had an adaptive crisis and the solution found by them was satisfactory. What can restrict the therapeutic process is the persisting negative transference, however, it can be minimized. The possibilities of the OPB in the treatment of pregnant women with DM1 found with the research were: improving the efficiency of the adaptation, assisting patients in crisis to resolve them without losses in adaptation efficiency and, make patients more able to find more adequate solutions to their problem-situations

Made available in DSpace on 2016-04-27T16:32:23Z (GMT). No. of bitstreams: 1 Paola Sotta Rodrigues.pdf: 598148 bytes, checksum: f7f9493bc306726b4bfd372bb29bc8a9 (MD5) Previous issue date: 2010-10-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The civil rights, among them the right of education for people with deficiency is not a point of agreement actually in Brazil, on the contrary, it is a field of constant tension and divergence. When we face the policies relative to the subject, as well as the discussions that occur in the academic sphere, we realize continuous contradictions that evidence distinct or even antagonistic positions about the principles and the processes for its execution. From this starting point, the present dissertation aims to track, classify and analyze the social demands related to the rights of such population, especially the ones directed to school education, using civil inquests and preparative of civil inquests from the Public Ministry of the State of São Paulo as a source of research and processes. According to it, this is a documental research, which data accomplished in the Public Ministry of the State of São Paulo website (www.mp.sp.gov.br), where there are information about the processes and the public civil actions that entry on it, during the period of 2000 and 2009, where the information were organizes and classified a posteriori in the following categories, that allow us to group and analyze the different demands: education, health, work, transport, life conditions, violation of rights, among others. The main findings were the following: the inconstancy in the quantity of processes, either in quantity or categories by it required; the high influence that the n. 68/2007 Deliberation exerted over the processes, especially in the year of 2007, and the sudden fall in relation to it in the year of 2009 and that the educational requirements were just about the access to school, putting aside the process of school education. Another interesting data is the very little quantity of processes in place in the Comarca of São Paulo, comparing to other much smaller Comarcas. Those findings express a dispersion of demands, revealing the immateriality that those rights assume in the local communities, as well as in the municipal public powers / Os direitos civis, entre eles o da educação das pessoas com deficiência não é um ponto pacífico na atualidade brasileira, pelo contrário, é um campo de constantes tensões e divergências. Ao nos depararmos com as políticas relativas ao assunto, bem como com as discussões que ocorrem no âmbito acadêmico, percebemos contradições constantes que evidenciam posições distintas ou mesmo antagônicas tanto em relação aos princípios, quanto aos processos para sua efetivação. A partir deste ponto de partida, esta dissertação tem o objetivo de rastrear, classificar e analisar as demandas sociais em relação aos direitos dessa população, em especial aqueles voltados à educação escolar, utilizando como fonte de pesquisa os processos, inquéritos civis e preparatórios de inquéritos civis do Ministério Público do Estado de São Paulo. Nesse sentido, esta é uma pesquisa de cunho documental cuja coleta de dados foi realizada no site do Ministério Público do Estado de São Paulo (www.mp.sp.gov.br), onde se encontram informações sobre os processos e ações civis públicas que nele deram entrada, no período entre 2000 e 2009, cujas informações colhidas foram ser organizadas e classificadas a posteriori nas seguintes categorias que permitiram agrupar e analisar as distintas demandas: educação, saúde, trabalho, transporte, trabalho, condições de vida, violação de direitos e outros. Os principais achados foram os seguintes: a inconstância na quantidade de processos, tanto na quantidade, quanto nas categorias por eles exigidas; a alta influência que a Deliberação n. 68/2007 exerceu sobre os processos, especialmente no ano de 2007 e a brusca queda em 2009; as exigências educacionais se resumem ao acesso à escola, ficando secundarizada a escolarização; a baixíssima quantidade de processos instaurados na Comarca de São Paulo, se comparada com Comarcas situadas em municípios muito menores. Estes achados expressam uma dispersão de demandas, reveladoras da pouca importância que esses direitos assumem tanto nas comunidades locais quanto nos poderes públicos municipais

O Ministério da Saúde adverte que o Diabetes Mellitus é um problema de saúde pública devido sua alta taxa de prevalência. Estudos demonstram a correlação entre o funcionamento psicodinâmico de pacientes com diabetes mellitus tipo 1 e o controle glicêmico. Considerando que o controle glicêmico adequado minimiza os riscos para a mãe, o feto e o futuro bebê, salienta-se a importância de um atendimento psicoterápico na fase gestacional. Contudo, não existem pesquisas sobre Psicoterapia Breve Operacionalizada (PBO) enquanto técnica terapêutica para este tipo de população. O objetivo da pesquisa foi investigar possibilidades e limites da PBO no atendimento a gestantes portadoras de diabetes mellitus tipo 1 (DM1) com mau controle glicêmico. A metodologia utilizada para a pesquisa foi o clinico-qualitativo. O estudo envolveu quatro gestantes portadoras de DM1 com mau controle glicêmico. As gestantes foram encaminhadas pela Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, local onde as mesmas são atendidas. Foram utilizados como instrumentos: entrevista clínica psicológica; Escala Diagnóstica Adaptativa Operacionalizada; e Psicoterapia Breve Operacionalizada. As gestantes que concordaram em participar assinaram o Termo de Consentimento Livre e Esclarecido que após lido e explicado, foi assinado pela pesquisadora e gestante. Foram realizadas duas ou três entrevistas inicias para o diagnóstico adaptativo operacionalizado e planejamento da PBO. O número de sessões utilizadas para PBO foi definido conforme o diagnóstico adaptativo da gestante e sua situação-problema. As entrevistas e as sessões psicoterápicas tiveram duração de 45 minutos e frequência de uma vez por semana. A análise dos resultados foi realizada através da comparação entre o diagnóstico adaptativo operacionalizado realizado antes e depois da PBO. Foi verificado se ocorreu nas gestantes, durante estes períodos, mudanças adaptativas; além da averiguação das alterações no controle glicêmico, antes e após a PBO. A pesquisa expôs que houve mudanças de grupo adaptativo da qual as gestantes pertenciam. Cecília e Beatriz obtiveram melhora no diagnóstico adaptativo. Por intermédio do acompanhamento da evolução do controle glicêmico, pode-se verificar alterações com o decorrer da PBO: a porcentagem de hipoglicemias e hipoglicemias graves melhoraram; as porcentagens de valores alterados e de hiperglicemias, por sua vez, tiveram piora com o decorrer da gravidez, e, mesmo com a PBO, o rigoroso controle alimentar e insulinoterapia, inclusive em internações, foram dificilmente controlados. Das quatro gestantes estudadas duas tiveram crise adaptativa e as soluções encontradas por elas foram satisfatórias. O que pode restringir o processo psicoterapêutico é a transferência negativa persistente, contudo, ela pode ser trabalhada e minimizada. As possibilidades da PBO no atendimento às gestantes com DM1 encontradas na pesquisa foram: melhorar a eficácia da adaptação; auxiliar as pacientes em crise a solucionarem-na sem a queda da eficácia da adaptação; e, possibilitar as pacientes encontrarem soluções mais adequadas para suas situações-problema / The health ministry adverts that Diabetes Mellitus is a public health concern due to its high prevalence rate. Studies demonstrate the existing relation between the psychodynamic functioning of patients with type 1 diabetes mellitus and the glycemic control. Considering that the adequate glycemic control minimizes risks for the mother, fetus and the future baby, it reinforces the importance of psychotherapeutic treatment during the pregnancy. However, there arent any researches on Operationalized Brief Psychotherapy (OBP) as a therapeutic technique for this kind of population. The aim of the research was to investigate the possibilities and the limits of OBP in the treating of pregnant women with type 1 diabetes mellitus with deficient glycemic control. The methodology used for the research was the clinical-qualitative method. The study involved four pregnant women with DM1 with deficient glycemic control. The women were appointed by the Obstetric Clinic of the Hospital das Clínicas da Faculdade de Medicina from the University of São Paulo, place where they were already being treated. The instruments employed were Psychological Interviews, the Operationalized Adaptive Diagnosis Scale and Operationalized Brief Psychotherapy. The women who agreed to take part in the research signed a consent form that, after read and explained, was then signed by the research agent and the subjects. Two or three initial interviews took place for the Operationalized Adaptive Diagnosis and the planning of the. The number of sessions employed for the OPB was defined in accordance to the adaptive diagnosis of the subject and their problem-situation. The interviews and the psychotherapeutic sessions lasted 45 minutes with the frequency of once a week. The analysis of the results was made through the comparison between the operationalized adaptive diagnosis done before and after the OPB. During these periods, it was verified if there were any adaptive changes in the subjects and, moreover, the analysis of any alterations in the glycemic control before and after the OPB. The research showed that there were changes in the adaptive group to which the subjects belonged. Cecília and Beatriz had an improvement in the adaptive diagnosis. Through the analysis of the evolution of the glycemic control, it was possible to verify alterations during the OPB: the percentage of both hypoglycemia and severe hypoglycemia showed improvement; however, the percentage of altered rates and of hyperglycemia showed a downturn throughout the pregnancy and, even with the OPB, a strict diet control and insulin therapy, including during admissions, were hardly controlled. From the four pregnant women in the study, two of them had an adaptive crisis and the solution found by them was satisfactory. What can restrict the therapeutic process is the persisting negative transference, however, it can be minimized. The possibilities of the OPB in the treatment of pregnant women with DM1 found with the research were: improving the efficiency of the adaptation, assisting patients in crisis to resolve them without losses in adaptation efficiency and, make patients more able to find more adequate solutions to their problem-situations

SEISMIC STRENGTHENING OF A MID-RISE REINFORCED CONCRETE FRAME USING CFRPs: AN APPLICATION FROM REAL LIFE Tan, Mustafa T&uuml / mer M.S., Department Of Civil Engineering Supervisor: Prof. Dr. G&uuml / ney &Ouml / zcebe Co-Supervisor: Assoc. Prof. Dr. BariS Binici May 2009, 162 pages FRP retrofitting allows the utilization of brick infill walls as lateral load resisting elements. This practical retrofit scheme is a strong alternative to strengthen low to mid-rise deficient reinforced concrete (RC) structures in Turkey. The advantages of the FRP applications, to name a few, are the speed of construction and elimination of the need for building evacuation during construction. In this retrofit scheme, infill walls are adopted to the existing frame system by using FRP tension ties anchored the boundary frame using FRP dowels. Results of experiments have previously shown that FRP strengthened infill walls can enhance lateral load carrying capacity and reduce damage by limiting interstory drift deformations. In previous, analytical studies, a detailed mathematical model and a simplified version of the model for compression struts and tension ties was proposed and verified by comparing model estimations with test results. In this study, an existing 9-storey deficient RC building located in Antakya was chosen to design and apply a hybrid strengthening scheme with FRPs and reduced number of shear walls. Linear elastic analysis procedure was utilized (force based assessment technique) along with the rules of Mode Superposition Method for the reftrofit design. FRP retrofit scheme was employed using the simplified model and design was conducted such that life safety performance criterion is satisfied employing elastic spectrum with 10% probability of exceedance in 50 years according to the Turkish Earthquake Code 2007. Further analytical studies are performed by using Modal Pushover and Nonlinear Time-History Analyses. At the end of these nonlinear analyses, performance check is performed according to Turkish Earthquake Code 2007, using the strains resulting from the sum of yield and plastic rotations at demand in the critical sections. CFRP retrofitting works started at October 2008 and finished at December 2008 for the building mentioned in this study. Eccentric reinforced concrete shearwall installation is still being undertaken. All construction business is carried out without evacuation of the building occupants. This project is one of the first examples of its kind in Turkey. Keywords: CFRP, Carbon Fiber Reinforced Polymers, Masonry Infill Walls, Reinforced Concrete Infill Walls, Mid-Rise Deficient Structures, Turkish Earthquake Code 2007, Modal Pushover Analysis, Nonlinear Time History Analysis, Linear Elastic Building Assessment

Les mammifères femelles naissent avec un très grand nombre de follicules ovariens primordiaux (104-106); par contre, la grande majorité (99%) de ces follicules n’atteignent jamais la maturité et subissent l’atrésie, principalement par l’apoptose des cellules de la granulosa. Notre laboratoire a démontré que les hyaluronidases des mammifères induisent l’apoptose des cellules de la granulosa et sont impliquées dans l’atrésie des follicules mais que cet effet apoptotique ne serait pas dû à leur activité enzymatique. Notre modèle propose que les hyaluronidases aient un rôle dans les follicules non destinés à ovuler. Le but de la présente étude est d’évaluer la folliculogénèse et la fertilité des souris déficientes de ces enzymes. Les résultats montrent que la délétion de Hyal-3 ne semble pas affecter la fonction ovarienne des souris mais qu’il pourrait y avoir un effet compensatoire par Hyal-1 chez les souris déficientes de Hyal-3 étant donné que son expression est augmentée chez ces souris. La délétion de Hyal-1 a pour effet d’augmenter le nombre des follicules primordiaux, primaires et secondaires, particulièrement chez les souris de bas âge, et de diminuer le niveau d’apoptose des cellules de la granulosa. Afin d’évaluer la fonction de Hyal-1, -2 et -3 sans effet compensatoire entre elles, nous avons voulu créer une souris déficiente des ces 3 hyaluronidases spécifiquement dans les gonades en utilisant le système Cre/loxP. Un vecteur contenant la séquence Cre sous le contrôle du promoteur de Inhibin-α, qui conduit l’expression des gènes en aval chez les cellules somatiques des gonades, a été construit avec succès. En conclusion, cette étude nous révèle que Hyal-3 ne semble pas affecter la fonction ovarienne mais que la délétion de Hyal-1 augmente la folliculogénèse et diminue l’apoptose des cellules de la granulosa. / Female mammals are born with a large number of ovarian primordial follicles, though the vast majority of these never reach the preovulatory stage and undergo atresia, mainly through granulosa cell apoptosis. Our laboratory has established that mammalian hyaluronidases induce apoptosis of ovarian granulosa cells and that they are involved in follicular atresia but that their apoptotic effect is not due to their enzymatic activity. Our model suggests that mammalian hyaluronidases might have a role in follicles not destined to ovulate. The aim of this study was to evaluate the folliculogenesis and fertility of mice devoid of these enzymes. Our results showed that Hyal-3 KO mice have normal folliculogenesis, which could be explained by a compensatory effect of Hyal-1 since its expression is upregulated in these mice. In contrast, Hyal-1 KO mice had increased numbers of primordial, primary and secondary follicles, particularly in young mice, and lower levels of granulosa cell apoptosis. In order to investigate the effect of the three hyaluronidases, Hyal-1, -2 and -3, without a compensatory effect by one another, we decided to create a transgenic mouse deficient in all these three hyaluronidases but only in the gonads by using the Cre/loxP system. We successfully created a plasmid containing the Cre sequence under the control of Inhibin-α promoter, which conducts gene expression in somatic cells of the gonads. In conclusion, the present work demonstrates that Hyal-3 does not have any effect on ovarian function, but that deletion of Hyal-1 in mice promotes increased folliculogenesis and lowers granulosa cell apoptosis.

Emerging energy storage applications are driving the demand for Li-ion battery positive electrode materials with higher energy densities and lower costs. The recent production of complete pseudo-ternary phase diagrams of the Li-Mn-Ni-O system generated using combinatorial methods has provided a greater understanding of the impact of initial composition, synthesis temperature, and cooling rate on the phases that form in the final materials. This thesis focuses on the synthesis and characterization of gram-scale positive electrode materials in the Li-Mn-Ni-O system. Structural analysis of these samples has resulted in the production of partial pseudo-ternary phase diagrams focusing on the positive electrode materials region of the Li-Mn-Ni-O system at 800°C and 900°C in air for both quenched and slow cooled compositions. These bulk-scale diagrams support the observations of the combinatorial diagrams, and show similar layered and cubic structures contained within several single- and multi-phase regions. The phases that form at each composition are shown to be dependent on both the reaction temperature and cooling rate used during synthesis. The electrochemical characterization of two composition series near Li2MnO3, one quenched and one slow cooled, is presented. The quenched compositions exhibited reversible cycling at 4.4 V, voltage plateaus and small increases in capacity above 4.6 V, and large first cycle irreversible capacity losses at 4.8 V. In the slow cooled series, all but one composition exhibited initial capacities below 100 mAh/g which began to continually increase with cycling, with several compositions exhibiting capacity increases of 300% over 150 cycles at 4.9 V. In both series, analysis of the voltage and differential capacity plots indicated that significant structure rearrangements are taking place in these materials during extended cycling, the possible origins of which are discussed. Finally, high precision coulometry studies of one Li-deficient and two Li-rich single-phase layered compositions are discussed. These materials exhibit minimal oxidation of simple carbonate-based electrolyte when cycled to high potential, with the Li-deficient composition producing less electrolyte oxidation at 4.6 V vs. Li/Li+ than commercial Li[Ni1/3Mn1/3Co1/3]O2 at 4.2 V. The inherent inertness of this composition may make it suitable for use as a thin protective layer in a core-shell particle.

Η HDL είναι ένα μείγμα λιποπρωτεϊνικών σωματιδίων υψηλής πυκνότητας, που ανάλογα με τη σύσταση τους σε λιπίδια μπορούν να είναι δισκοειδή ή σφαιρικά. Η κύρια αθηροπροστατευτική δράση της HDL, οφείλεται στο γεγονός ότι η συγκεκριμένη λιποπρωτεΐνη συλλέγει την περίσσεια χοληστερόλης από τους περιφερικούς ιστούς και τη μεταφέρει στο ήπαρ όπου καταβολίζεται. Επιπλέον, έχει αντιφλεγμονώδη και αντιοξειδωτική δράση. Η κύρια πρωτεΐνη της HDL είναι η απολιποπρωτεΐνη Α-Ι (apoA-I). Ωστόσο, πρόσφατα αποδείχθηκε ότι σε πειραματόζωα με έλλειψη στην apoA-I και κατά συνέπεια στην κλασσική HDL, η απολιποπρωτεΐνη Ε (apoE) αλληλεπιδρά με τον μεταφορέα λιπιδίων ABCA1 προάγοντας την de novo σύνθεση HDL σωματιδίων. Στην παρούσα μελέτη, στόχος ήταν η εύρεση της περιοχής της apoE που είναι υπεύθυνη για την λειτουργική αλληλεπίδραση με τον ABCA1 για το σχηματισμό HDL. Για το σκοπό αυτό, ανασυνδυασμένοι αδενοϊοί που εξέφραζαν καρβοξυ-τελικές συντετμημένες μορφές της apoE4 (AdGFP-E4[1-259], AdGFP-E4[1-229], AdGFP-E4[1-202], AdGFP-E4[1-185]), χορηγήθηκαν σε ποντίκια με έλλειψη στην ApoA-I σε δόση 8x108 pfu και πέντε μέρες μετά τη μόλυνση δείγματα πλάσματος αναλύθηκαν για το σχηματισμό HDL. Κλασματοποίηση των λιποπρωτεϊνών του πλάσματος με υπερφυγοκέντρηση σε διαβάθμιση πυκνότητας καθώς και FPLC χρωματογραφία αποκάλυψε ότι όλες οι συντετμημένες μορφές της apoE4 προάγουν το σχηματισμό HDL. Ανάλυση ηλεκτρονικής μικροσκοπίας με αρνητική χρώση των HDL κλασμάτων, επιβεβαίωσε ότι όλες οι συντετμημένες μορφές της apoE4 είναι ικανές να προάγουν το σχηματισμό σωματιδίων με διάμετρο στην περιοχή της HDL. Τα δεδομένα αυτά οδηγούν στο συμπέρασμα ότι η αμινοτελική περιοχή της apoE που εκτείνεται από τα αμινοξέα 1 έως 185 αρκεί για το σχηματισμό HDL σωματιδίων in vivo. Αυτά τα ευρήματα, ανοίγουν το δρόμο στην έρευνα για το σχεδιασμό βιολογικών φαρμάκων με βάση την apoE για τη θεραπεία της δυσλιπιδαιμίας, της αθηροσκλήρωσης και της στεφανιαίας νόσου. / HDL is a mixture of high density lipoprotein particles that depending on the lipid composition may be discoidal or spherical. The main atheroprotective property of HDL is reverse cholesterol transport, a process that unloads excess cholesterol from peripheral tissues and transports it to the liver for catabolism. HDL has also anti-inflammatory and antioxidant properties. The main protein of HDL is apolipoprotein A-I (apoA-I). However, recently it was shown that in the absence of apoA-I and consequently classical HDL, apolipoprotein E (apoE) interacts functionally with the lipid transporter ABCA1, promoting the de novo synthesis of HDL-like particles. The present study focused on the identification of the domain of apoE that is responsible for the functional interaction with ABCA1 and the formation of apoE-containing HDL. Recombinant attenuated adenoviruses expressing carboxy-terminal truncated forms of apoE4 (apoE4[1-259], apoE4[1-229], apoE4[1-202], and apoE4[1-185]) were administered to apoA-I-deficient mice at a low dose of 8x108 pfu and five days post-infection plasma samples were isolated and analyzed for HDL formation. Fractionation of plasma lipoproteins of the infected mice by density gradient ultracentrifugation and FPLC revealed that all forms were capable of promoting HDL formation. Negative staining electron microscopy analysis of the HDL density fractions confirmed that all C-terminal truncated forms of apoE4 promoted the formation of particles with diameters in the HDL region. Taken together, these data establish that the aminoterminal 1 to 185 region of apoE suffices for the formation of HDL particles in vivo. These findings may have important ramifications in the design of apoE-based biological drugs for the treatment of dyslipidemia, atherosclerosis and coronary heart disease.

Ce travail a consisté à élaborer un biomatériau hybride constitué d’un tissu de fibres de carbone (TFC) revêtu de phosphates de calcium (CaP) déposés par un procédé de sono-électrodéposition et à étudier l’influence des paramètres expérimentaux sur la composition chimique, la microtexture et la structure des revêtements phosphocalciques, ainsi que la biocompatibilité in vitro du biomatériau hybride. La densité de courant s’est avérée être un paramètre important. Pour de fortes densités de courant (≥ 100 mA/g), un régime d’électrolyse rapide de l’eau entraîne la formation d’un dépôt aciculaire d’hydroxyapatite déficitaire en calcium (CaD-HAP) carbonatée avec la présence éventuelle d’une phase de calcite. Pour de faibles densités de courant (≤ 50 mA/g), un régime d’électrolyse lent de l’eau entraîne la formation d’un dépôt plaquettaire de CaD-HAP carbonatée issu de l’hydrolyse in situ du phosphate octocalcique plaquettaire préalablement précipité. Pour l’ensemble des dépôts, les particules sont constituées d’un coeur de CaD-HAP carbonatée de structure ordonnée et d’une surface hydratée de CaD-HAP carbonatée de structure désordonnée qui résulte de l’existence d’une zone de sursaturation lors de la précipitation des CaP. La sono-électrodéposition se révèle être un procédé versatile capable d’orienter la synthèse des phases de CaP, avec pour une faible densité de courant appliquée l’obtention d’un dépôt biomimétique comparable à la partie minérale du tissu osseux obtenue par le processus d’ostéogénèse naturelle. Des tests de viabilité in vitro réalisés avec des ostéoblastes humains primaires ont montré que la nanoporosité et le caractère hydrophile des TFC n’impactent pas la biocompatibilité et que les paramètres tels que le précurseur des fibres, l’ensimage et/ou la forme lobée des fibres semblent favoriser l’adhésion et la prolifération des cellules. / This work is focused on the synthesis of a novel hybrid biomaterial made of carbon fibers cloth (CFC)/ calcium phosphates (CaP) using the sono-electrochemical technique and the study of the influence of experimental parameters on the chemical composition, microtexture and structure of CaP deposits and on in vitro biocompatibility. Current density is shown to be a crucial parameter. Specifically, at high current densities ((≥ 100 mA/g), the fast water electrolysis rate leads to a needle-like deposit consisting in a major phase of carbonated calcium deficient hydroxyapatite (CaD-HAP) mixed with a calcium carbonate phase. At low current densities (≤ 50 mA/g), the slow water electrolysis rate generates a plate-like carbonated CaD-HAP phase, coming from the in situ hydrolysis of a former octacalcium phosphate phase. Whatever the experimental conditions, particles of the deposits consists in a carbonated CaD-HAP core showing an ordered structure, surrounded by a hydrated and disordered carbonated CaD-HAP surface layer which results of the formation of oversaturated domains during CaP precipitation. Sono-electrodeposition is shown to be a versatile process able to control the nature of CaP phases. Especially, at low current density a biomimetic CaP deposit is obtained, similar to the mineral part of bones produced during natural osteogenesis. In vitro biologic tests using primary human osteoblasts showed that the nano-porosity and hydrophilicity of the carbon fibers do not affect the biocompatibility and that fiber precursor, sizing and lobe shaped fibers seems to favor adhesion and proliferation of human cells.

No presente trabalho, foram processados compósitos de polietileno de alta densidade (PEAD) com hidroxiapatita deficiente de cálcio (HA), com o objetivo de obter materiais com melhores propriedades mecânicas e bioatividade. A adição da HA deficiente de cálcio proporcionou um aumento no módulo de elasticidade (maior rigidez), menor resistência ao impacto e decréscimo do grau de cristalinidade do PEAD, proporcionando uma maior bioatividade ao material. A análise térmica exploratória (sistema não isotérmico) foi realizada por meio da técnica de calorimetria exploratória diferencial (DSC) e foram avaliados os teores de fosfato de cálcio e a velocidade de rotação da rosca no processamento dos materiais. No estudo da cristalização não-isotérmica observou-se uma diminuição da temperatura de cristalização com o aumento da taxa de resfriamento para todos os materiais sintetizados. A energia de ativação (Ea) da cristalização dos materiais foi avaliada por meio dos métodos Kissinger e Ozawa. A amostra com 5% de HA deficiente de cálcio e velocidade de processamento de 200 rpm foi a que apresentou menor valor de energia de ativação, 262 kJ/mol, menor desvio da linearidade e a que mais se assemelhou à matriz de PEAD sem HA. O teor de hidroxiapatita deficiente de cálcio não favorece o processo de cristalização devido à alta energia de ativação determinada pelos métodos descritos. Provavelmente, a velocidade de rotação, favorece a dispersão da carga na matriz de PEAD, dificultando o processo de cristalização. Na aplicação do método de Osawa-Avrami, os coeficientes de correlação indicaram perda na correlação linear. Estas perdas podem estar associadas a uma pequena percentagem de cristalização secundária e/ou à escolha das temperaturas utilizadas para determinar a velocidade de cristalização. Na determinação dos parâmetros pelo método de Mo, as menores percentagens de cristalização apresentaram um grande desvio da linearidade, com coeficiente de correlação bem menor que 1 e com o aumento da percentagem de cristalização, o desvio da linearidade diminui, ficando próximo de 1. Os resultados obtidos mostraram que o modelo de Mo e de Osawa-Avrami não foram capazes de definir o comportamento cinético dos materiais produzidos neste trabalho. / In this work, composites of high density polyethylene HDPE with calciumdeficient hydroxyapatite were synthesized in order to obtain materials with good mechanical properties and bioactivity. The addition of calcium-deficient hydroxyapatite resulted in an increase in elastic modulus (high rigidity), lower impact resistance and lower HDPE crystallinity degree, promoting, in these materials, a higher bioactivity. Scanning thermal analysis (non-isothermal system) was carried out by differential scanning calorimetry (DSC), and it was evaluated the calcium phosphate content added and the screw speed in the processing. In non-isothermal crystallization studies it was observed a decrease in crystallization temperature as the cooling rate was increased for all produced materials. The activation energy of crystallization was evaluated by Kissinger and Ozawa methods. The sample with 5 wt.% of calcium-deficient hydroxyapatite and processed at 200 rpm screw speed showed the lower value of activation energy (262 kJ/mol) and the lower deviation from linearity. Calcium-deficient hydroxyapatite does not promote the crystallization process due to the high activation energy determined by the described methods. Probably the screw speed promotes the dispersion of the filler in the HDPE matrix and hinders the crystallization process. Correlation coefficients in Osawa-Avrami method indicated loss in the linear correlation. These losses might be associated with a small percentage of secundary crystallization and/or the temperatures chosen to determine the crystallization rate. The parameters obteined from Mo method, the lower percentages of crystallization showed a great deviation from linearity, with correlation coefficient much smaller than 1, when increasing the percentage of crystallization, the deviation from linearity decreases, getting closer to 1.The results of Mo and Osawa-Avrami models were not able to set the kinetic behavior of the materials produced in this study.

No presente trabalho, foram processados compósitos de polietileno de alta densidade (PEAD) com hidroxiapatita deficiente de cálcio (HA), com o objetivo de obter materiais com melhores propriedades mecânicas e bioatividade. A adição da HA deficiente de cálcio proporcionou um aumento no módulo de elasticidade (maior rigidez), menor resistência ao impacto e decréscimo do grau de cristalinidade do PEAD, proporcionando uma maior bioatividade ao material. A análise térmica exploratória (sistema não isotérmico) foi realizada por meio da técnica de calorimetria exploratória diferencial (DSC) e foram avaliados os teores de fosfato de cálcio e a velocidade de rotação da rosca no processamento dos materiais. No estudo da cristalização não-isotérmica observou-se uma diminuição da temperatura de cristalização com o aumento da taxa de resfriamento para todos os materiais sintetizados. A energia de ativação (Ea) da cristalização dos materiais foi avaliada por meio dos métodos Kissinger e Ozawa. A amostra com 5% de HA deficiente de cálcio e velocidade de processamento de 200 rpm foi a que apresentou menor valor de energia de ativação, 262 kJ/mol, menor desvio da linearidade e a que mais se assemelhou à matriz de PEAD sem HA. O teor de hidroxiapatita deficiente de cálcio não favorece o processo de cristalização devido à alta energia de ativação determinada pelos métodos descritos. Provavelmente, a velocidade de rotação, favorece a dispersão da carga na matriz de PEAD, dificultando o processo de cristalização. Na aplicação do método de Osawa-Avrami, os coeficientes de correlação indicaram perda na correlação linear. Estas perdas podem estar associadas a uma pequena percentagem de cristalização secundária e/ou à escolha das temperaturas utilizadas para determinar a velocidade de cristalização. Na determinação dos parâmetros pelo método de Mo, as menores percentagens de cristalização apresentaram um grande desvio da linearidade, com coeficiente de correlação bem menor que 1 e com o aumento da percentagem de cristalização, o desvio da linearidade diminui, ficando próximo de 1. Os resultados obtidos mostraram que o modelo de Mo e de Osawa-Avrami não foram capazes de definir o comportamento cinético dos materiais produzidos neste trabalho. / In this work, composites of high density polyethylene HDPE with calciumdeficient hydroxyapatite were synthesized in order to obtain materials with good mechanical properties and bioactivity. The addition of calcium-deficient hydroxyapatite resulted in an increase in elastic modulus (high rigidity), lower impact resistance and lower HDPE crystallinity degree, promoting, in these materials, a higher bioactivity. Scanning thermal analysis (non-isothermal system) was carried out by differential scanning calorimetry (DSC), and it was evaluated the calcium phosphate content added and the screw speed in the processing. In non-isothermal crystallization studies it was observed a decrease in crystallization temperature as the cooling rate was increased for all produced materials. The activation energy of crystallization was evaluated by Kissinger and Ozawa methods. The sample with 5 wt.% of calcium-deficient hydroxyapatite and processed at 200 rpm screw speed showed the lower value of activation energy (262 kJ/mol) and the lower deviation from linearity. Calcium-deficient hydroxyapatite does not promote the crystallization process due to the high activation energy determined by the described methods. Probably the screw speed promotes the dispersion of the filler in the HDPE matrix and hinders the crystallization process. Correlation coefficients in Osawa-Avrami method indicated loss in the linear correlation. These losses might be associated with a small percentage of secundary crystallization and/or the temperatures chosen to determine the crystallization rate. The parameters obteined from Mo method, the lower percentages of crystallization showed a great deviation from linearity, with correlation coefficient much smaller than 1, when increasing the percentage of crystallization, the deviation from linearity decreases, getting closer to 1.The results of Mo and Osawa-Avrami models were not able to set the kinetic behavior of the materials produced in this study.