Orientadores: Marcio Zaffalon Casati, Antonio Wilson Sallum / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T19:00:36Z (GMT). No. of bitstreams: 1 Gurgel_BrunoCesardeVasconcelos_D.pdf: 2894613 bytes, checksum: b68eb32e96e2245f94ae9bfdc771987e (MD5) Previous issue date: 2005 / Resumo: O objetivo do presente estudo foi avaliar histometricamente o reparo ósseo obtido após a utilização do plasmarico em plaquetas (PRP) e/ou de membranas não reabsorvíveis no tratamentode defeitos ósseos peri-implantares, do tipo deiscência, criados cirurgicamente em cães. Foram utilizados 1O cães adultos, machos, sem raça definida, nos quais os pré-molares inferiores (P2,P3, P4)e o primeiro molar foram extraídos. Após 3 meses das extrações, os leitosparaos implantes foram criados e posteriormente 2 deiscências ósseas vestibulares bilaterais, sendo então inseridos 4 implantes dentais de titânio. As deiscências foram designadas aleatoriamente às seguintes modalidades terapêuticas: 1) controle; 2) ROG; 3)PRP;4) PRP + ROG. Após 3 meses do tratamento, os animais foram sacrificados e os blocos contendo os implantes e tecidos duros adjacentes processados para secções não descalcificadas. Na análise histométrica, os parâmetros avaliados foram o contato osso-implante, a área de preenchimento ósseo dentro das roscas, a área e a densidade de tecido ósseo formado na região fora das roscas. Análise deVariância foi utilizada para a análise estatística dos dados (p<O,O5). Os resultados demonstraram diferenças estatísticas significativas para todos os parâmetros analisados em favor dos grupos tratados commembrana (p<O,O5), no entanto, não foram observadas diferenças quando o PRP foi utilizado (p>O,O5). Dentro dos limites do presente estudo, pôde-se concluir ue o PRP não exerce efeitos adicionais no reparo ósseo e que a ROG promove uma maior formação óssea ao redor dos implantes dentais / Abstract: The aim of the present study was to evaluate, histometrically, the bone healing after utilizing the platelet-rich plasma (PRP) and/ornon-resorbable membranes on the treatment of peri-implant bone defects, deiscense type, surgically created in dogs. Ten mongrel male adult dogswere used; in which the threel ow premolars (P2,P3,P4) and the first molar were extracted. Three months after dental extraction, dental implants sites were created and lately two bilater albuccal bone dehiscence, in which four titanium dental implants were inserted. Dehiscences werer and omly assignedfor the following treatment: 1) contrai; 2) GBR;3) PRP; 4) PRP+ GBR. After 3 months, animais were sacrificed; dental implants and adjacent hard tissues were pracessed for undecalcified sections. At histometrical analysis,the parameter se valuated were bone-implant contact, bone filling area into threads, bone tissue area and bone density formed out the threads. Variance Analysis was utilized for statistical analysis of the data (p<O,O5). There sults demonstrated statically significant differences for ali parameters toward membrane treated graups (p<O,O5), although, differences were not observed when PRP was utilized( p>O,O5). Within the limits of the present study, it was concluded that PRP do not exert additional effects on bone healing and that guided bone regeneration provides increased bone formation araund dental implants / Doutorado / Periodontia / Doutor em Clínica Odontológica

Many polypeptide growth factors act by binding to cell surface receptors that have intrinsic tyrosine kinase activity. Binding of these growth factors to their cognate receptors results in the initiation of mitogenic signals which then get transduced to the interior of the cell. A critical target for extracellular signals is the nucleus. A plethora of recent evidence indicates that extracellular signals can affect nuclear gene expression by modulating transcription factor activity. In this study, I have determined that the transactivation domain of c-Myc (protein product of the c-myc proto-oncogene) is a direct target of mitogen-activated signaling pathways involving protein kinases. Further, my study demonstrates that transactivation of gene expression by c-Myc is regulated as a function of the cell cycle. c-Myc is a sequence-specific DNA binding protein that forms leucine zipper complexes and can act as a transcription factor. Although, significant progress has been made in understanding the cellular properties of c-Myc, the precise molecular mechanism of c-Myc function in oncogenesis and in normal cell growth is not known. I have focused my attention on the property of c-Myc to function as a sequence-specific transcription factor. In my studies, I have employed a fusion protein strategy, where the transactivation domain of the transcription factor c-Myc is fused to the DNA binding domain and nuclear localization signal of the yeast transcription factor GAL4. This fusion protein was expressed together with a plasmid consisting of specific GAL4 binding sites cloned upstream of a minimal E1b promoter and a reporter gene. The activity of the c-Myc transactivation domain was measured as reporter gene activity in cell extracts. This experimental approach enabled me to directly monitor the activity of the c-Myc transactivation domain. Results listed in Chapter II demonstrate that the transactivation domain of c-Myc at Ser-62 is a target of regulation by mitogen-stimulated signaling pathways. Furthermore, I have determined that a mitogen activated protein kinase, p41mapk, can phosphorylate the c-Myc transactivation domain at Ser-62. Phosphorylation at this site results in a marked increase in transactivation of gene expression. A point mutation at the MAP kinase phosphorylation site (Ser-62) causes a decrease in transactivation. c-Myc expression is altered in many types of cancer cells, strongly implicating c-myc as a critical gene in cell growth control. The molecular mechanisms by which c-Myc regulates cellular proliferation are not understood. For instance, it is not clear where in the cell cycle c-Myc functions and what regulates its activity. In exponentially growing cells, the expression levels of c-Myc remain unchanged as the cells progress through the cell cycle. The function of c-Myc may therefore be regulated by a mechanism involving a post-translational modification, such as phosphorylation. Results described in chapter IV demonstrate that the level of c-Myc mediated transactivation oscillates as cells progress through the cell cycle and was greatly increased during the S to G2/M transition. Furthermore, mutation of the phosphorylation site Ser-62 in the c-Myc transactivation domain diminishes this effect, suggesting a functional role for this phosphorylation site in the cell cycle-specific regulation of c-Myc activity. Taken together, my dissertation study reveals a molecular mechanism for the regulation of nuclear gene expression in response to mitogenic stimuli.