Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos. / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T17:32:08Z (GMT). No. of bitstreams: 1 CastroSobrinho_JucaraMariade_D.pdf: 1214452 bytes, checksum: db87fc4f5e35e2d9e1091af5b48fc8cf (MD5) Previous issue date: 2012 / Resumo: Objetivo: Analisar a associação entre a coinfecção por papilomavírus humano (HPV), Chlamydia trachomatis (CT), vaginose bacteriana (VB) e resposta inflamatória (RI) com a gravidade da neoplasia cervical. Sujeitos e métodos: Estudo experimental, de corte transversal, realizado em Campinas, São Paulo e em Goiânia, Goiás, Brasil. A casuística incluiu amostras biológicas de 290 mulheres consecutivas submetidas à excisão da zona de transformação (EZT) ou conização. Para o estudo que avaliou a coinfecção entre HPV e CT e a associação com gravidade da neoplasia cervical foram selecionadas 251 (86,6%) mulheres infectadas por HPV de alto risco (HR-HPV). A detecção de HPV foi realizada utilizando os primers PGMY09/11 e a genotipagem através de hibridização reversa em pontos. A detecção da CT foi realizada por polimerase chain reaction (PCR) empregando primers cujo alvo é uma região de plasmídio críptico, gerando um fragmento de aproximadamente 512 pares de base. Para o estudo que avaliou a VB e resposta inflamatória e a associação destas condições com a gravidade da neoplasia cervical foram selecionadas 211 mulheres infectadas por HR-HPV, com esfregaços cervicais disponíveis para as análises. A presença de 20% ou mais de células indicadoras no esfregaço cervical corado pelo método de Papanicolau foi considerada positiva para VB. A resposta inflamatória nos esfregaços cervicais foi avaliada pela contagem do número de neutrófilos. O encontro de 30 ou mais neutrófilos por campo microscópico, observado sob o aumento de 1000x, foi considerado como presença de resposta inflamatória. Resultados: A prevalência de CT em mulheres HPV positivas foi de 15,1% (38/251). Foi observada uma associação significativa em mulheres CT negativas, com 30 anos ou mais, e NIC 2 ou pior diagnóstico, mas esta associação não foi observada em mulheres CT positivas. Infecções por HPV 16 e/ou 18 foram detectadas em 50% das mulheres CT negativas com menos de 29 anos e que apresentavam NIC 2 ou pior diagnóstico, e em 19,5% das mulheres CT negativas com NIC 1 ou não neoplásico. Nestas mulheres, a associação entre HPV 16 e/ou 18 e NIC 2 ou pior diagnóstico foi significativa, mas esta associação não foi observada no grupo CT positivo. Resposta inflamatória e VB foram observadas em 43,5% e 46,2% dos esfregaços cervicais de mulheres com NIC 2. Resposta inflamatória e VB foram observados em 64,2% e 32,6% dos esfregaços cervicais de mulheres com diagnóstico histológico de NIC 3. Nestas mulheres, quando infectadas pelos tipos de HPV 16 e/ou 18, foram observadas resposta inflamatória e VB, respectivamente, em 43,1% e 20% dos casos. Resposta inflamatória apresentou associação estatisticamente significante com NIC 2 ou pior diagnóstico em mulheres infectadas pelos tipos de HPV 16 e/ou 18 (OR= 6,70; 95%IC:2,32-19,31) e por outros tipos de HPV (OR=4,90; 95%IC: 1,86-12,89). Associações significativas foram observadas em mulheres com VB e NIC 2 ou pior diagnóstico, infectadas pelos tipos de HPV 16 e/ou 18 (OR= 3,38; 95% IC :1,07-10,64) e por outros tipos de HPV (OR= 3,38; 95%IC: 1,15-10,01). Conclusões: A infecção por CT detectada por PCR não mostrou associação com o aumento do risco para NIC 2 ou pior diagnóstico em mulheres HPV positivas. Em mulheres CT negativas e com menos de 30 anos de idade, os tipos de HPV 16 e/ou 18 estão associados à NIC 2 ou pior diagnóstico, resultado não observado para as mulheres CT positivas. A VB e resposta inflamatória estão associadas à NIC 2 ou pior diagnóstico em mulheres HR-HPV positivas / Abstract: Objective: To analyze the association between co-infection Human Papillomavirus (HPV) and Chlamydia trachomatis (CT), bacterial vaginosis (BV) and inflammatory response with the severity of the cervical neoplasia. Subjects and methods: This is cross-sectional experimental study carried through in Campinas, São Paulo and in Goiânia, Goiás, Brazil. The casuistic included 290 consecutive women submitted a the Excision of the Transformation Zone or conization due CIN 2 and CIN 3. For the study that evaluated the association between HPV and CT and severity of cervical neoplasia were selected 251 women who were infected with high-risk HPV (HR-HPV). HPV detection .was performed by PCR using primers PGMY09/11 and genotyping by reverse lineblot hybridization assay. The detection of CT was performed by PCR. For the study that evaluated the association between BV and inflammatory response with the severity of cervical neoplasia were selected 211 women infected with HR-HPV with cervical smears available for analysis. The presence of 20% or more clue cells in cervical smears stained by the Papanicolaou method was considered positive for VB. Inflammatory response was assessed by counting the number of neutrophils. The finding of 30 or more neutrophils per field observed under 1000x magnification was taken as presence of inflammatory response. Results: The prevalence of CT in HPV positive women was 15.1% (38/251). Significant association was observed between women with 30 years or older and CIN 2 or worse diagnosis for those CT negative, but this association was not observed for those CT positive. HPV 16 and/or HPV 18 were detected in 50% of the women ? 29 years age with CIN 2 or worse diagnosis who were CT negative, and in 19.5% for those women with CIN 1 or no neoplastic in histological diagnostic. In these women the association between HPV 16 and/or 18 and CIN 2 or worse diagnosis was significative, but this association also was not observed considering the CT positive group. Inflammatory response and BV were observed in 5.5% and 16.7% of cervical smear of women with no neoplastic diagnosis and were observed in 22.9% and 12.5% of cervical smears of women with CIN 1 in histological diagnosis. Inflammatory response and BV were observed in 43.5% and 46.2% of cervical smears of women with CIN 2 in histological diagnosis. The BV prevalence was higher in cervical smears of women infected by the types 16 and/or 18 (25.6%) and inflammatory response was more observed in cervical smears of women infected by other HPV types (25.6%). Inflammatory response and BV were observed in 64.2% and 32.6% of cervical smears of women with CIN 3 in histological diagnosis and were more observed in cervical smears of women infected types 16 and/or 18 representing respectively 43.1% and 20.0% of cases. Inflammatory response and BV were more observed in cervical smears of women infected types 16 and/or 18 in women with invasive carcinoma, representing 27.2% and 18.2% of cases respectively. Inflammatory response was significantly associated with CIN 2 or worse diagnosis in women infeted by HPV16 and/or HPV 18 (OR= 6.70; 95%CI : 2.32-19.31) and HPV other types than HPV16 and/or18 (OR=4.90; 95%CI: 1.86-12.89). Significant associations with BV and CIN 2 or worse diagnosis were observed in women infected by HPV 16 and/or 18 (OR= 3.38; 95%C1:07-10.64) and HPV types other than HPV16 and/or 18 (OR=3.38; 95%CI: 1.15-10.01). Conclusions: CT infection detected by PCR, does not increase the risk for CIN 2 or worse diagnosis in HPV positive women. HPV 16 and/or HPV 18 types in young women are associated with CIN 2 or worse diagnosis, but without obvious association with CT. BV and inflammatory response are associated with CIN 2 or worse diagnosis in women HR-HPV positives women / Doutorado / Ciencias Biomedicas / Doutora em Tocoginecologia

AIMS: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. MATERIALS & METHODS: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition, tyrosine phosphorylation events were investigated. RESULTS & CONCLUSION: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic.

Tang, Shing Tung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 114-126). / Abstracts in English and Chinese; some appendixes in Chinese. / Chapter Chapter 1: --- Introduction --- p.1 / Chapter Chapter 2: --- Background --- p.5 / HPV Vaccination and Cervical Cancer --- p.5 / Overview of HPV Vaccination in the West and Asia --- p.6 / Chapter Chapter 3: --- Literature Review --- p.9 / Applying the Theory of Planned Behavior in Vaccination Context --- p.9 / Effects of Mass and Interpersonal Communication --- p.22 / Relationship between Mass and Interpersonal Communication --- p.33 / Differential Effects of Mass and Interpersonal Communication --- p.39 / Chapter Chapter 4: --- Methodology --- p.45 / Participants and Procedure --- p.45 / Measures --- p.49 / Chapter Chapter 5: --- Results --- p.54 / Model Fit and Adjustments --- p.54 / Testing the Alternative Model --- p.56 / Evaluating Individual and Contextual Predictors --- p.59 / Examining the Context-to-intention Pathways --- p.60 / Summary of Findings --- p.61 / Chapter Chapter 6: --- Discussion --- p.63 / Comparing the Proposed and Alternative Model --- p.63 / Evaluating the TPB in Vaccination Context --- p.65 / Evaluating Mass and Interpersonal Communication as Contextual Predictors --- p.73 / Further Exploration on the Differential Effects --- p.76 / Theoretical Contributions and Practical Implications --- p.80 / Chapter Chapter 7: --- Limitations and Directions for Future Research --- p.85 / Limitations --- p.85 / Directions for Future Research --- p.90 / Chapter Chapter 8: --- Conclusion --- p.93 / Appendix --- p.96 / References --- p.114

Submitted by Gilvan Almeida (gilvan.almeida@icict.fiocruz.br) on 2016-09-26T14:06:06Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) / Approved for entry into archive by Barata Manoel (msbarata@coc.fiocruz.br) on 2016-10-20T13:18:24Z (GMT) No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) / Made available in DSpace on 2016-10-20T13:18:24Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Casa de Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. / Este estudo trata das ações médicas para prevenção do câncer do colo do útero no Brasil durante o período de 1936 a 1970. O câncer do colo do útero foi incorporado à agenda médica brasileira na década de 1940, a partir do desenvolvimento de ferramentas de diagnóstico precoce e da organização de instituições. Nosso objetivo neste trabalho é analisar o processo de incorporação da doença na medicina brasileira, impulsionado pela introdução e difusão das tecnologias de diagnóstico, no escopo de institucionalização da cancerologia como sub campo da nossa medicina. O Instituto de Ginecologia (IG), no Rio de Janeiro, sob chefia do médico Arnaldo de Moraes, foi o centro de difusão e ensino da colposcopia e da citologia no Brasil. Nossa hipótese de pesquisa é que a colposcopia foi a impulsionadora da formação e organização das instituições de controle do câncer do colodo útero no Brasil em meados do século XX, sendo utilizada de forma conjunta com a citologia até os anos 1960. A organização de ações sobre a doença e as discussões entre os especialistas conduziram à formação de uma rede de prevenção, construída a partir de publicações especializadas, associações profissionais, iniciativas para formação de pessoal e intercâmbio científico. Fizeram parte desta rede o Instituto de Ginecologia, o Hospital de Ginecologia da Faculdade de Medicina de Minas Gerais e o Hospital Aristides Maltez na Bahia. Ambos, com suas peculiaridades, se constituíram como espaços de controle da doença em suas regiões e de institucionalização de um modelo específico de ação que se afirmou no país até a década de 1970. / This study is about the medical actions for cervical cancer prevention in Brasil, from 1936 to 1970. Cervical cancer was incorporated into the medical Brazilian agenda in the 1940s, with the development of early detection tools and the institutions organization. Our objective in this paper is to analyze the disease incorporation on the Brazilian medicine, through the introduction and diffusion of diagnosis technologies, in the scope of cancerology institutionalization as a medicine sub field. The Instituto de Ginecologia (IG), in Rio de Janeiro, under leadership of physician Arnaldo de Moraes, was the learning and dissemination center of colposcopy and cytology in Brazil. Our research hypothesis is that colposcopy was the promoter of the formation and organization of the institutions to cervical cancer control in Brazil in the mid-twentieth century, being used, at the same time, with cytology until the 1960s. The organization of actions about the disease and the discussions among experts led to the formation of a prevention network that was constructed by specialized publications, professional associations, initiatives for personnel training and scientific exchange. The Instituto de Ginecologia, the Hospital de Ginecologia of Minas Gerais and the Hospital Aristides Maltez in Bahia were part of this network. All of them, with their peculiarities, had been constituted as spaces to disease control in their regions and institutionalization of a particular model of action, that was affirmed in the country until the 1970s.

Made available in DSpace on 2011-05-04T12:36:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2010 / O estudo teve por objetivo analisar as questões levantadas na literatura sobre a associação entre o HPV e o câncer do colo uterino e suas implicações para a política de controle da doença. Buscou-se correlacionar esta discussão com antigas polêmicas entre modelos teóricos divergentes sobre etiologia e as medidas de controle por eles prescritas. Trata-se de uma revisão de artigos científicos com abordagem histórica/conceitual acerca das mudanças recentes no conhecimento científico relacionado à etiologia do câncer do colo do útero. A análise do estudo se deu mediante um diálogo entre o discurso produzido pela epidemiologia e pela biologia molecular sobre a gênese do câncer do colo uterino e a reflexão que vem sendo realizada pela Saúde Pública, tendo como eixo temático a crítica ao modelo ainda hegemônico a respeito da etiologia das doenças, focada na especificidade causal e, de acordo com esta, na generalização de intervenções para prevenção e controle. O caso da relação etiológica entre o HPV e o câncer do colo uterino ilustra bem as características e os limites deste modelo, hegemônico desde o final do século XIX. Apesar dos avanços obtidos na compreensão sobre a etiologia das doenças, a lógica das estratégias de controle não tem acompanhado tais avanços. Ainda que as pesquisas sobre a etiologia deste câncer assinalem haver uma complexa rede de interações entre o agente viral e a célula do colo uterino, o modelo hegemônico insiste em privilegiar uma medida específica de intervenção para o controle do câncer, a vacina contra os tipos de HPV de alto-risco. A comprovação do papel de um agente infeccioso na carcinogênese do colo uterino reforça a fragilidade dos limites teóricos que diferenciam os conceitos de doenças transmissíveis e não transmissíveis. Neste contexto, o desenvolvimento da biologia molecular abre novos caminhos e possibilidades de interpretação do fenômeno patológico, aproximando-se da perspectiva daqueles que há muito tempo já buscaram compreendê-lo em uma referência de maior complexidade. A Saúde Pública e a Epidemiologia estiveram na vanguarda de uma postura racional mais ampla sobre a etiologia das doenças, quando aliaram o conhecimento biológico disponível a aspectos sociais e culturais. Os desafios atuais demandam o esforço de integrar a biologia molecular a outros níveis de determinação das doenças, como forma de aprofundar a compreensão dos vínculos complexos entre eles e de buscar alternativas apropriadas de intervenção. / The study aimed to examine the issues raised in the literature on the association between HPV and cervical cancer and its implications for the politics of disease control. We attempted to correlate this discussion with old controversies between different theoretical models about etiology and control measures prescribed by them. This is a review of scientific articles with historical/conceptual approach about recent changes in scientific knowledge related to the etiology of cervical cancer. The study analysis was made by a dialogue between the discourse of the epidemiology and molecular biology about genesis of cervical cancer and the reflection that is being conducted by Public Health, with its central theme the critique of hegemonic still model on the etiology disease, focusing on causal specificity and, according to this, on the generalization of interventions for prevention and control. The case of the etiologic relationship between HPV and cervical cancer illustrates the characteristics and limits of this model, hegemonic since the late nineteenth century. Despite advances in understanding the etiology of diseases, the logic of control strategies has not accompanied these advances. Although research on the etiology of this cancer points that there is a complex network of interactions between the viral agent and the cell of the cervix, the hegemonic model insists on emphasizing a specific measure of intervention for the control of cancer, the vaccine against HPV types high-risk. The evidence of role of an infectious agent in carcinogenesis of the cervix increases the fragility of the theoretical limits that differentiate the concepts of communicable and non-communicable diseases. In this context, the development of molecular biology opens new avenues and possibilities for interpretation of pathological phenomenon, approaching from the perspective of those who long have sought to understand it on a reference of greater complexity. The Public Health and Epidemiology were in the vanguard of rational stance broader on the etiology of disease, when they allied the biological knowledge available with to social and cultural aspects. The current challenges require the effort for integrate the molecular biology with others levels of determine of diseases as a way to deepen understanding of the complex links between them and to seek suitable alternatives for intervention.