MSc (Med), Epidemiology and Biostatistics,University of the Witwatersrand, Faculty of Health Sciences / Introduction In developing countries, diarrhoea is a major cause of morbidity and mortality among children under five years of age. This study aimed to determine the effect of age and HIV infection status on incidence of acute gastroenteritis and to identify risk factors associated with death and prolonged hospitalisation. Methods A secondary data analysis was performed using an existing cohort of children enrolled on a pneumococcal vaccine efficacy study performed in 1998-2005 in Soweto. Results The incidence rate of acute gastroenteritis requiring hospitalisation was 10.13 (CI95% 9.68, 10.58) per 1000 person years. Incidence was highest in those under six months of age, decreased with increasing age, and was 5.42 times (CI95% 4.89, 6.01) higher in those infected with HIV compared to that in HIV-uninfected children. HIV-infected children were more likely to be malnourished, have severe dehydration and have a concomitant diagnosis of lower respiratory tract infection (LRTI). HIV-infected children were four times more likely to die in hospital (OR 3.99 CI95% 2.04, 7.81) and almost twice as likely to be hospitalized > 2 days (OR 1.81 CI95% 1.38, 2.38) compared to HIV-uninfected children. Presence of malnutrition, severe dehydration and a concomitant diagnosis of LRTI were also significant risk factors for death and prolonged hospitalisation. Conclusions Acute gastroenteritis is an important cause of hospitalisation in children under 2 years, especially among HIV-infected children. Prevention and management of severe dehydration, malnutrition, HIV infection and concomitant LRTI need to be targeted to decrease mortality and shorten the duration of hospitalisation in children admitted with acute gastroenteritis.

The Five-Factor Model (FFM) is one of the most dominant and widely acceptedframeworks of personality, however it has been criticised for its primarily Eurocentric individualistic focus on aspects of personality as a result of its development within the English lexicon (McCrae &Terracciano, 2005).The use of imported etic inventories presents an array of difficulties for personality assessment within South Africa, as indigenous and collective personality traits are absent from these measures of personality (Nel, 2008). This study, therefore, aimed to explore the collective dimension of personality using the South African Personality Inventory (SAPI) and the Cross-cultural Personality Assessment Inventory-2 (CPAI-2) in a non-probability convenience sample of 489 South African first-year Psychology students from the University of the Witwatersrand. A quantitative section was conducted to investigate the internal consistency reliability, construct validity and construct biasof the collective dimension of the two instruments. From the results it was evident that both instruments had adequate internal consistency reliability for the scales and subscales of the collective dimensions of personality, but some reliability coefficients were low; particularly for Social Desirability and its sub-clusters, as well as Ren Qing, Discipline and Thrift vs Extravagance. Construct validity for the SAPI was found to be problematic in that the five factor structure proposed by Nel (2008) did not replicate; however a three factor structure was found to be the best fit. Construct validity for the CPAI-2 was found to be good in that the six factor structure of the Interpersonal Relatedness factor proposed by Cheung et al. (2008) was replicated. Evidence for construct bias across gender, race and home language was found in both instruments. Finally a qualitative thematic content analysis of data obtained from two focus groups of 19 first year Psychology students from the original sample was conducted and issues related to a general understanding of personality, the innate existence of personality vs the overt expression of personality, collectivism in personality, a national identity, culture, psychometric testing and social desirability were explored. This study thus contributed to both the local and international context in terms of personality theory and assessment in organisations, as well as theoretically to the etic-emic debate.

L’entreprise publique (ou d’Etat) gère dans la plupart des pays une part importante du patrimoine collectif, c’est ainsi qu’il lui incombe de respecter des critères de gouvernance stricts et rigoureux. Au Maroc, la gouvernance des entreprises publiques occupe de plus en plus une place importante dans les grandes orientations stratégiques, mais aussi l’opinion publique notamment avec les différents événements ayant marqué la région du MENA (le printemps arabe comme exemple).Cependant, devant cette importance, l’inventaire de la littérature empirique ne permet pas d’obtenir une image claire concernant l’impact de la gouvernance sur cette structure. Ce travail vient ainsi clarifier cette place au Maroc en comparaison avec l’Europe, par le biais d’une présentation des différents mécanismes et dispositifs mis en places pour protégé l’intérêt publique et assurer la confiance. Dans l’objectif d’obtenir des réponses plus concluantes concernant l’impact de la gouvernance sur la performance de l’entreprise publique, la thèse présente l’état des lieux des conseils d’administration des entreprises publiques marocaines, afin de tester leur impact sur la performance financière de ces structures, en utilisant des analyses de régression sous forme de données de panel. Nos recherches ont permis de clarifier les effets des organes de contrôle au sein de l’entreprise publique. D’une part, dans le cas marocain l’apport d’informations, de connaissances et de compétences ne constitue pas une vraie source d’influence sur la performance de l’entreprise publique, bien au contraire dans le cas d’administrateur qui exerce ou ayant exercé une activité au sein de la même entreprise, par contre la présence du capital privé peut être source à la fois d’un apport cognitif et disciplinaire. / The State-Owned Enterprise (SOE) operates in most countries a large part of the collective patrimony, thus its responsibility to comply with strict and rigorous governance criteria. In Morocco, the governance of SOE holds increasingly an important place in the major strategic directions, and also in public opinion, particularly with the various events that marked the MENA region (the Arab Spring as an example). However, to this importance, the inventory of the empirical literature does not allow to get a clear picture of the impact of governance on this structure. This work has thus clarified this up in Morocco in comparison with Europe, through a presentation of the various mechanisms and procedures established to protected the public interest and ensure confidence. To obtain more conclusive answers about the impact of governance on the performance of the SOE, this thesis present the inventory of boards of Moroccan strategic SOEs to test their impact on the financial performance of these structures, using regression analyzes in the form of panel data. Our research has helped to clarify the effects of the supervisory organs within the SOE. First, in the Moroccan case the providing information’s, knowledge and skills is not a real source of influence on the performance of the SOE, on the contrary in the case of administrator who is or formerly employed in the same company, by against the presence of private capital can be a source of both cognitive and disciplinary contribution.

A regulação da expressão gênica é vital para todos os organismos se adaptarem rapidamente às mudanças ambientais. Estes mecanismos adaptativos são altamente complexos e a maioria deles não está completamente esclarecida. O fosfato inorgânico (Pi), um nutriente essencial para todos os organismos, é requerido em importantes processos celulares como a biosíntese de ácidos nucléicos e a sinalização metabólica. O sistema de aquisição de Pi no fungo filamentoso Neurospora crassa inclui pelo menos quatro genes regulatórios: nuc-2, preg, pgov e nuc-1. Em condições limitantes de Pi, NUC- 2, uma proteína com domínio de repetição de anquirina, inibe o funcionamento do complexo PREG-PGOV, ativando assim o fator de transcrição NUC-1 e a expressão de genes envolvidos na captação de fosfato, como fosfatases, fosfato permeases e nucleases. Visando entender a funcionalidade do gene nuc-2 na regulação da expressão gênica em resposta aos níveis de Pi exógeno, foram construídas duas bibliotecas de subtração de cDNA entre as linhagens selvagem St.L.74A e nuc-2A de N. crassa, cultivadas em Pilimitante. Obtivemos 52 transcritos induzidos e 16 reprimidos pela proteína NUC-2. A categorização funcional destas sequências revelou genes envolvidos em diversos processos celulares, como transporte, regulação transcricional, transdução de sinal, metabolismo, síntese protéica e desenvolvimento. Entre os genes modulados negativamente pela proteína NUC-2, foi identificado um gene que codifica a proteína MAK-2 (mitogen-activated protein kinase-2), envolvida em vias de sinalização intracelular. O papel funcional deste gene no monitoramento do Pi extracelular foi avaliado por microarranjos de oligonucleotídeos, comparando as linhagens selvagem e mutante mak-2, cultivadas em baixa concentração de Pi. Foram identificados 4.214 genes regulados pela proteína MAK- 2, dentre eles a ciclina codificada pelo gene preg. Além disto, genes regulados em função da concentração de Pi foram identificados, mostrando o envolvimento de 3.174 transcritos. Os resultados obtidos neste trabalho revelam novos aspectos moleculares envolvidos na adaptação à disponibilidade de Pi extracelular, sugerindo que o gene mak-2 constitui um novo componente da via de sinalização e monitoramento de fosfato em N. crassa. / Gene expression regulation is crucial for all organisms to rapidly adapt to environmental changes. These adaptive mechanisms are highly complex and most of them have not been completely elucidated. The inorganic phosphate (Pi), an essential nutrient for all organisms, is required for important cellular processes, such as nucleic acids biosynthesis and metabolic signaling. The Pi acquisition system in the filamentous fungus Neurospora crassa includes at least four regulatory genes: nuc-2, preg, pgov and nuc-1. Under limiting Pi conditions, NUC-2, an ankyrin-like repeat protein, inhibits the functioning of the PREG-PGOV complex, allowing the activation of the transcription factor NUC-1 and the expression of genes involved in phosphate acquisition, such as phosphatases, phosphate permeases and nucleases. Aiming at a better comprehension of the nuc-2 functionality in gene expression regulation in response to exogenous Pi levels, two cDNA subtraction libraries were constructed comparing N. crassa wild type St.L.74A and nuc-2A strains, grown under Pi starvation. We obtained 52 NUC-2 up- and 16 downregulated genes. Functional categorization of these sequences revealed genes involved in several cellular processes, such as cellular transport, transcriptional regulation, metabolism, protein synthesis and development. Among the NUC-2 negatively modulated genes, we identified the MAK-2 (mitogen-activated protein kinase-2) protein coding gene, involved in the intracellular signaling pathway. The functional role of this gene in the extracellular Pi sensing was evaluated by oligonucleotide microarrays, comparing wild type and mak-2 strains responses under Pi starvation. We identified 4.214 MAK-2 regulated genes, among them the cyclin coding gene, preg. Furthermore, 3.174 genes regulated in response to Pi levels were identified. In a nutshell, the results obtained in this work reveal novel molecular aspects of the adaptation to extracellular Pi availability, suggesting that the mak-2 gene constitutes a novel component of the N. crassa phosphate sensing and signaling pathway.

by Hiu Wong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references. / SUMMARY --- p.1 / INTRODUCTION --- p.4 / LITERATURE REVIEW --- p.8 / Chapter I. --- Nasopharyngeal carcinoma (NPC) --- p.8 / Chapter A. --- Epidemiology of NPC --- p.8 / Chapter B. --- Anatomy of NPC --- p.11 / Chapter C. --- Pathology of NPC --- p.12 / Chapter D. --- Histological classification of NPC --- p.14 / Chapter E. --- Stage classification of NPC --- p.15 / Chapter F. --- Clinical feature of NPC --- p.18 / Chapter G. --- Diagnosis of NPC --- p.19 / Chapter (a) --- Clinical examination / Chapter (b) --- Radiographic examination / Chapter (c) --- Laboratory examination / Chapter (d) --- Biopsy examination / Chapter H. --- Treatment of NPC --- p.21 / Chapter (a) --- Surgery / Chapter (b) --- Chemotherapy / Chapter (c) --- Radiotherapy / Chapter I. --- Prognosis of NPC --- p.23 / Chapter J. --- Etiology of NPC --- p.24 / Chapter (a) --- Dietary factor / Chapter (b) --- Genetic factor / Chapter (c) --- Environmental factor / Chapter (d) --- EBV infection / Chapter (e) --- Others / Chapter II. --- Beta-2 Microglobulin (B2M) --- p.30 / Chapter A. --- Structure and function of B2M --- p.30 / Chapter B. --- Clinical chemistry of B2M --- p.33 / Chapter C. --- B2M and its relationship to immunogenetic system --- p.34 / Chapter D. --- B2M in solid malignancies --- p.35 / Chapter E. --- B2M in hematologic malignancies --- p.36 / Chapter F. --- B2M in non-malignant diseases --- p.38 / Chapter III. --- Epstein - Barr Virus (EBV) --- p.41 / Chapter A. --- Morphology / Chapter B. --- EBV infection --- p.42 / Chapter C. --- EBV and Nasopharyngeal Carcinoma --- p.44 / Chapter D. --- Relationship of EBV to other human disease --- p.46 / Chapter (a) --- The relationship of EBV to IM / Chapter (b) --- The relationship of EBV to BL / Chapter E. --- EBV genome-carrying lymphoid cell lines --- p.50 / Chapter IV. --- TUMOUR ANTIGEN OF SQUEMOUS CELL CARCINOMA --- p.55 / Chapter A. --- The source of TA-4 --- p.55 / Chapter B. --- Characteristics of TA-4 --- p.56 / Chapter C. --- TA-4 in squamous cell carcinoma of uterine cervix --- p.57 / Chapter D. --- TA-4 in other type of squamous cell carcinaoma --- p.58 / MATERIALS AND METHODS / Chapter A. --- Materials --- p.61 / Chapter B. --- Measurement of Beta-2 Microglobulin --- p.63 / Chapter (a) --- Principles / Chapter (b) --- Assay protocol / Chapter (c) --- Reproducibility / Chapter C. --- Detection of EBV antibody titres in human sera --- p.68 / Chapter (a) --- Induction of EA/VCA in Raji/P3HR-1 cell lines / Chapter (b) --- Detection of antibody titres to EA/VCA in human sera / Chapter D. --- Measurement of squamous cell carcinoma associated antigen --- p.75 / RESULTS --- p.79 / Chapter A. --- Diurnal change of serum B2M or TA-4 level --- p.79 / Chapter B. --- The B2M and TA-4 levels in apparently healthy people --- p.81 / Chapter C. --- The usefullness of assay in initial diagnosis and staging --- p.81 / Chapter (a) --- Correlation between serum B2M levels and staging of NPC / Chapter (b) --- Correlation between serum TA-4 levels and staging of NPC / Chapter D. --- Correlation between histological differentiation of NPC and B2M and TA-4 level --- p.91 / Chapter E. --- The usefulness of assay for monitoring the NPC --- p.93 / Chapter (a) --- patients achieved completed remission / Chapter (b) --- patients developed local recurrence / Chapter (c) --- patients developed distant metastases / DISCUSSION --- p.131 / Chapter A. --- Serum B2M in NPC patients --- p.131 / Chapter B. --- Serum TA-4 in NPC ptients --- p.136 / Chapter C. --- EBV antibody titres in NPC patients --- p.137 / Chapter D. --- Conclusion --- p.141 / Chapter E. --- Suggested further study --- p.143 / REFERENCES --- p.146

Afin de mieux connaître les mécanismes moléculaires impliqués dans le cancer du sein, nous avons entrepris l’étude de la fonction du gène suppresseur de tumeur WWOX comprenant le site fragile FRA16D. Nous avons mis en évidence l’association de WWOX avec des composants de la voie de signalisation intracellulaire Wnt/β-caténine : Dvl-2, BCL9 et BCL9-2, ainsi que, l’histone deacetylase 3 (HDAC3). Nous avons défini, pour la première fois, WWOX en tant que nouvel inhibiteur de la voie Wnt/β-caténine. Nos résultats suggèrent que WWOX agit sur cette voie en séquestrant Dvl-2 dans le cytoplasme et en inhibant les activités transcriptionnelles de BCL9 et BCL9-2. En outre, nous avons démontré que HDAC3 est également capable d’inhiber l’activité transcriptionelle de BCL9-2. HDAC3 agirait en recrutant WWOX sur BCL9-2 et cela indépendamment de son activité déacétylase. L’inhibition de la voie Wnt/β-caténine par WWOX suggère que l’inhibition de l’expression de WWOX, souvent observée dans le cancer du sein, pourrait conduire à la suractivation de cette voie et par conséquent à la stimulation de la progression tumorale. En parallèle de ce travail, nous avons étudié l’implication des nouveaux partenaires moléculaires de WWOX que nous avons trouvé dans la carcinogenèse mammaire. Nous avons mis en évidence une surexpression de BCL9, et non pas de BCL9-2, dans les tumeurs du sein, cette surexpression serait due, au moins en partie à des polyploïdies et des amplifications du gène, suggérant un rôle important de BCL9 dans cette pathologie. / In our attempt to better understand the molecular mecanisms in breast carcinogenesis, we studied the role of the tumor suppressor gene WWOX that encompasses the common fragile site FRD16D. We have identified actors of the Wnt/β-catenin pathway as new interactors of WWOX: Dvl-2, BCL9 and BCL9-2 just as HDAC3. We show, for the first time, that WWOX is an inhibitor of the Wnt/β-catenin pathway. Our results suggest that WWOX binds Dvl-2 in the cytoplasm and inhibits BCL9 and BCL9-2’s transcriptionnal activities. Moreover, we have shown that HDAC3 inhibits as well the transcriptional activity of BCL9-2 by recruiting it on WWOX. We then demonstrated that HDAC3 acts independently of its deacetylase activity. The inhibition of the Wnt/b-catenin pathway by WWOX suggests that the down expression of WWOX, frequently found in breast tumors, could trigger the over activation of the Wnt/β-catenin pathway and therefore a tumor progression. In parallel, we have studied the implication of the newly identified molecular partners of WWOX in the mammary carcinogenesis. We have identified an overexpression of BCL9, but not BCL9-2, in a large serie of invasive breast tumors, this overexpression is due, at least in part to polyploidy and gene amplification, suggesting BCL9 plays an important role in this pathology.

Dans cette thèse, nous étudions les effets des Nouvelles Aides à la Vente et à l’Achat (NAVA) sur le comportement du consommateur. La littérature existante sur ces effets met en exergue des manquements qui justifient les trois propositions de recherche développées, impliquant des variables affectives, motivationnelles et cognitives. Trois premières études exploratoires qualitatives confortent et précisent ces propositions de recherche tandis que deux autres proposent une taxinomie des NAVA basée sur leurs caractéristiques intrinsèques. Deux séries d’hypothèses de recherche sont ensuite proposées. La première concerne l’effet direct d’une NAVA récréative sur l’attitude et le comportement du consommateur, alors que la seconde concerne le mécanisme enclenché en présence d’un tel outil. La phase empirique confirmatoire comprenant trois études quantitatives permet de tester ces hypothèses. Les résultats montrent que la présence (vs. l’absence) d’une NAVA génère (1) plus de réactions affectives positives et moins de réactions affectives négatives, (2) plus de curiosité spécifique envers le produit, (3) plus de confiance envers le site, moins de risque perçu et (4) plus d’intention de fréquenter et d’acheter en magasin. L’expertise en nouvelles technologies et le besoin de toucher modèrent certains de ces effets. La curiosité spécifique est médiatrice des effets des réactions affectives positives, de la confiance et du risque perçu sur le comportement. La discussion de ces résultats et leurs contributions sont exposées dans le dernier chapitre. Enfin, dans une synthèse générale, les limites et voies de recherche de ce travail sont présentées. / In this dissertation, we study the effects of Interactive Consumer Decision Aids (ICDA) on consumer attitudes and behavior. Through the analysis of the literature on the effects of ICDA, we highlight priority research areas. From the review, we make three research propositions concerning the effects of ICDA on the affective, motivational and cognitive dimensions of consumer attitudes. Three exploratory qualitative studies strengthen and clarify these research propositions. Two further exploratory studies lead to the proposal of a taxonomy, based on the intrinsic characteristics of ICDA. Two sets of research hypotheses are then offered. The first set of hypotheses concerns the direct effect of the presence of a recreational ICDA on attitudes and behavior, while the second set concerns the mechanism activated in the presence of such a tool. The confirmatory steps, including three empirical quantitative studies (of which two were pre-tests) allow us to test these hypotheses. The results show that the presence (vs. absence) of an ICDA generates (1) more positive and less negative affective reactions, (2) more specific curiosity about the product, (3) higher trust in the website, less perceived risk and (4) more intent to patronize and purchase. Some of the effects are found to be moderated by the consumer’s expertise about new technologies and by the need to touch. The results also show that the specific curiosity about the product and about the ICDA mediate the effects of positive affective reactions, trust and perceived risk on the behavioral intention variables. The discussion of these results and of their implications is outlined in the last chapter. Finally, the limits of the work and suggestions for further research are presented.

Objetivo: No atual trabalho propomo-nos a avaliar morfometricamente possíveis alterações na reparação óssea alveolar pós-exodontia de ratos tratados com Meloxicam, um anti-inflamatório inibidor preferencial da cicloxigenase 2 (COX-2) e correlacionar com a expressão temporal da COX-2 e do fator de transcrição 2 com domínio Runt (Runx-2) associada com a diferenciação de células da linhagem osteoblástica. Material e Métodos: A exodontia do incisivo superior direito foi realizada em 120 ratos Wistar, divididos em grupo controle (n = 60) - animais tratados com injeção intraperitoneal de 0,1 ml de solução salina 0,9% diariamente e grupo tratado (n = 60) animais tratados com injeção de Meloxicam na dose de 3mg/kg de massa corporal, diariamente, ambos durante 7 dias. O volume total do alvéolo (VtA) e do tecido ósseo (VtO), o número de células imunomarcadas/mm² (Nm) para COX-2 e Runx-2 e a expressão protéica por Western blotting (WB) da COX-2 e RUNX-2 foram avaliados nos períodos 3, 7, 10, 14, 21 e 30 dias póscirurgias. Resultados: No grupo tratado o VtA manteve-se constante até os 21 dias, enquanto que no controle foi 0,272 vezes menor em relação aos 3 dias decorrente da maior atividade osteoclástica. Porém, aos 14 dias, no grupo tratado o VtO foi 0,337 vezes menor em relação ao controle decorrente da inibição parcial da transmigração de células inflamatórias responsáveis pela degradação do coágulo e da angiogênese, ocasionando um retardo na formação dos tecidos de granulação/conjuntivo, na diferenciação das células osteoblásticas e na formação/remodelação do tecido ósseo, e consequentemente no reparo ósseo alveolar. A imunomarcação para COX-2 foi observada em diversos tipos celulares, como fibroblastos, células endoteliais, células inflamatórias, osteoblastos e osteócitos. O Nm para COX-2 não apresentou diferenças estatísticas significantes entre os grupos no intervalo de 3 e 21 dias pós-cirurgia, enquanto que, a expressão protéica pelo WB foi em média 0,232 vezes menor no grupo tratado em relação ao controle. Por outro lado, a imunomarcação para Runx-2 foi mais expressiva em osteoblastos e osteócitos e raramente em fibroblastos. O Nm para Runx-2 no grupo tratado durante todo período experimental foi em média 0,256 vezes menor em relação ao controle, sendo o mesmo observado para a expressão protéica pelo WB. Conclusão: Dentro dos limites da atual pesquisa, a aplicação do Meloxicam por um curto período de tempo atrasa temporariamente o processo inicial de reparo ósseo alveolar diminuindo a expressão das proteínas COX-2 e RUNX-2. / Objective: To evaluate morphometrically possible changes in post-extraction alveolar bone healing in rats treated with Meloxicam, a selective anti-inflammatory inhibitor of cyclooxygenase (COX-2) and to correlate it with the temporal expression of COX-2 and transcription factor 2 with Runt domain (Runx-2) associated with differentiation of osteoblastic lineage cells. Material and Methods: The extraction of the right upper incisor was made in 120 male Wistar rats, divided into control group (n=60) - animals treated with an intraperitoneal injection of 0,1 ml of 0,9% NaCl solution daily for 7 days and the treated group (n=60) - animals treated with injection of 3mg/kg of body weight of Meloxicam 0.9% NaCl solution daily for 7 days. The total alveolar volume (VtA), total bone tissue volume (VtO), number of immunohistochemically positive cells/mm² (Nm) for COX-2 and RUNX-2 and the Western blotting (WB) COX-2 and RUNX-2 protein expressions were evaluated after 3, 7, 10, 14, 21 and 30 days after the surgeries. Results: In the treated group the VtA remained constant until the 21st day, while in the control group at the same day the value was 0,272 times lower compared to the 3 days period, due to the higher osteoclastic activity. However, at 14 days the VtO was 0,337 times lower in the treated group compared to the control due to the partial inhibition of the transmigration of inflammatory cells responsible for the degradation of the clot and angiogenesis, causing a delay in the formation of granulation/connective tissues, differentiation of osteoblastic cells and in bone tissue formation/remodeling, and consequently in the alveolar bone repair. The immunostaining for COX-2 was observed in various cell types, such as fibroblasts, endothelial cells, inflammatory cells, osteoblasts and osteocytes. The Nm for COX-2 showed no statistical differences between groups from the 3rd to the 21st day, while the WB protein expression was on average 0,232 times lower in the treated group compared to the control. On the other hand, the immunostaining for Runx-2 was more expressive in osteoblasts and osteocytes and rarely in fibroblasts. The Nm for Runx-2 on the treated group was, during the whole experimental period, on average 0,256 times smaller than in the control. The same difference was observed in the protein expression by WB. Conclusion: Within the limits of the present study, its was concluded that the application of Meloxicam daily for 7 days causes a temporary delay in the alveolar bone repair decreasing the expression of proteins COX-2 and RUNX-2.

Made available in DSpace on 2018-08-01T23:25:58Z (GMT). No. of bitstreams: 1 tese_10204_Artigo Mestradro Nathália - Defesa 01.08 (1) (1).pdf: 7254929 bytes, checksum: 36eb94c32d1fc4c52933a3189e3caba0 (MD5) Previous issue date: 2016-08-19 / À medida que o processo de odontogênese avança, dando início à deposição de tecidos mineralizados da coroa, ocorre de forma paralela o processo de erupção dentária, que permite ao dente atravessar as barreiras teciduais que o circundam até que ele possa emergir na cavidade oral. Esse processo envolve a degradação da lâmina própria e a reabsorção da parte superior da cripta óssea que envolve o dente por ação de metaloproteinases (MMPs).O objetivo desta pesquisa foi identificar a expressão de MMP-2 em germes dentários de molares de ratos e nos tecidos circunjacentes ao longo do processo eruptivo. A detecção de MMP-2 foi realizada por imuno-histoquímica em 24 amostras de animais com idades entre 04 a 16 dias. A expressão de MMP-2 foi bservada no tecido ósseo basal e apical e em regiões do germe dentário: papila dentária, ameloblastos, odontoblastos, retículo estrelado efolículo dentário. Os esultados desta pesquisa indicam que a forte expressão de MMP-2 em ameloblastos e odontoblastos pode indicar um papel dessa enzima nos processos de síntese, mineralização e maturação dos tecidos mineralizados do dente. Por outro lado, a expressão de MMP-2 no folículo dentário e osso ao redor do germe podem indicar a participação de MMP-2 nos processos de remodelação óssea necessários para o prosseguimento do processo de erupção dentária.

O carcinoma colorretal é um dos tumores malignos mais freqüentes no mundo ocidental. Sua incidência varia mundialmente; nos Estados Unidos (EUA), é o terceiro câncer mais comum entre os homens e o segundo entre as mulheres, sendo a segunda causa de morte por câncer, ficando atrás apenas do tumor de pulmão. No Brasil é a quarta neoplasia mais freqüente em homens e a segunda em mulheres na região sul. Os principais indicadores prognósticos do adenocarcinoma colorretal incluem a diferenciação histológica, profundidade de invasão e ocorrência de metástases. Recentemente, têm sido realizados diversos estudos em biologia molecular objetivando a identificação de novos parâmetros prognósticos. Dentre eles, os fatores que regulam o ciclo celular, influenciam no crescimento e no mecanismo de apoptose têm demonstrado resultados promissores. Os avanços da biologia molecular permitiram demonstrar a carcinogênese como uma série de alterações progressivas e particulares em cada neoplasia. Embora algumas alterações já estejam bem estabelecidas, outras ainda necessitam ser melhor avaliadas e ter assim sua importância determinada. Entre os muitos componentes desse ciclo tem-se destacado como objeto de interesse a proteína ciclooxigenase-2 (COX-2) por seu aparecimento freqüente nas neoplasias colorretais bem como pelos resultados promissores dos estudos com seus inibidores na profilaxia e tratamento das neoplasias colorretais. A ciclooxigenase é uma enzima fundamental na síntese de eicosanóides como as prostaglandinas PGE2 e PGD2 a partir do ácido araquidônico. Foi isolada pela primeira vez por Hemler em 1976. Trata-se de um homodímero (complexo formado por duas moléculas) que possui um peso molecular de 71 Kd. A expressão da COX-2 pode ocorrer em uma variedade de tipos celulares e tecidos especializados onde desempenha funções biológicas específicas, tais como reprodução, imunidade, fisiologia renal, reabsorção óssea e secreção pancreática. Freqüentemente encontrada em várias neoplasias, tem como prováveis formas de ação a formação de prostaglandinas e o estímulo das mesmas em mecanismos de angiogênese, crescimento celular, adesão e diferenciação. O objetivo deste estudo é avaliar a prevalência da proteína COX-2 nas neoplasias colorretais e sua relação com parâmetros patológicos prognósticos para o câncer colorretal. Foram avaliadas 65 lesões neoplásicas colorretais através de imunoistoquímica para a presença de COX-2. Também analisaram-se fatores patológicos prognósticos e estagiamento das lesões. A COX-2 expressou-se positivamente em 27% dos adenomas tubulares, 40% dos adenomas vilosos e 70% dos carcinomas. Diferença estatisticamente significante foi obtida na expressão da COX-2 entre adenomas e carcinomas, porém não houve significância nas demais variáveis estudadas. Concluiu-se que a expressão da COX-2 variou progressivamente com a progressão da lesão neoplásica, mas não influenciou os parâmetros patológicos de mau prognóstico. / the western world. Its occurrence varies worldwide, and in the USA colorectal cancer is the third most common manifestation of cancer among men and the second among women. In the south region of Brazil, colorectal cancer is ranked fourth among men and second among women as the most frequent neoplasia. Prognosis includes mainly the investigation of tumor histology, extent of invasion, and metastases. Several molecular biology studies have been recently conducted to identify novel prognostic parameters, including cell cycle regulating factors that modify growth and apoptosis. These parameters have shown great promise to therapeutic approach in colorectal carcinoma. Advancements in molecular biology have shown that carcinogenesis comprises a series of progressive, specific alterations for different neoplasias. Although some alterations have been steadily characterized, others are still demanding more research to determine their actual role. Among many elements involved in carcinogenic process, expression of cyclooxygenase-2 (COX-2) has raised considerable interest due to the frequency of enzyme occurrence in colorectal neoplasias and the promising results obtained with COX-2 inhibitors in prophylaxis and treatment of the disease. COX-2 plays a fundamental role in the synthesis of eicosanoids as prostaglandins PGE2 and PGD2, starting from arachidonic acid. COX-2 is a 71-kD homodimer (a complex formed by two molecules), and was first isolated by Hemler in 1976. COX-2 is expressed in a variety of cell types and purpose-specific tissues, with particular biological functions such as reproduction, immunoresponse, kidney physiology, bone reabsorption and pancreatic secretion Often detected in various neoplasias, COX-2 is supposed to act by forming prostaglandins and by stimulating prostaglandin action in angiogenesis, cell growth, adhesion and differentiation. This study aimed at evaluating COX-2 prevalence in colorectal neoplasias, and to establish the relationship with pathologic prognostic parameters for colorectal cancer. Sixty-five neoplastic lesions were immunohistochemically evaluated for COX-2 expression according to lesion stages. COX-2 was positively expressed in 27% of the tubular adenomas, in 40% of the villous adenomas, and in 70% of the carcinomas analyzed. A statistically significant difference was observed for COX-2 expression between adenomas and carcinomas p=0.002, but no such significance was seen among the other variables investigated. COX-2 expression was therefore understood to vary progressively with the neoplasia stage, yet with no established influence on pathologic parameters for poor prognosis.