Made available in DSpace on 2014-06-11T19:23:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-03-08Bitstream added on 2014-06-13T19:29:41Z : No. of bitstreams: 1 astolphi_rd_me_araca.pdf: 531931 bytes, checksum: 9f2b534f155b8e3b0dc8038c304644f1 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Patologias na cavidade oral podem gerar efeitos deletérios em diversos sistemas do organismo. Nesse sentido, a presença de bactérias nas polpas dentárias pode provocar lesão periapical (LP) e gerar inflamação, culminando na produção de citocinas inflamatórias, como o fator de necrose tumoral-alfa (TNF-α) e a interleucina-6 (IL-6), que podem atingir a circulação sistêmica e causar a resistência insulínica (IR) em órgãos responsivos à insulina. A IR é definida como a diminuição da resposta de tecidos periféricos à ação da insulina, e indivíduos com esta característica são predispostos a desenvolver diabetes mellitus tipo 2 (DM2). Tendo conhecimento de que as citocinas inflamatórias podem gerar alteração no sinal insulínico (SI), tornou-se primordial investigar a possibilidade de um processo inflamatório local, como a LP “per se”, causar IR em indivíduos não diabéticos. Para tanto, foram utilizados ratos Wistar (02 meses de idade), divididos em dois grupos: ratos com LP induzida em primeiro molar superior direito, empregando-se broca em aço carbono dotada de esfera na extremidade com 0,1 mm de diâmetro e ratos-controle (CN). Após 30 dias de indução, realizaram-se os experimentos: 1) coleta de sangue (n=10) e obtenção de plasma para análise das concentrações de glicose, insulina, colesterol total, colesterol HDL (HDL-C), colesterol LDL (LDL-C), colesterol VLDL (VLDL-C), triglicérides, TNF-α e interleucina-6 (IL-6); 2) teste de tolerância à insulina (ITT) para a avaliação da sensibilidade à insulina (n=10); 3) avaliação do grau de fosforilação em tirosina da pp185 (IRS-1/IRS-2) e dos conteúdos de receptor insulínico beta (Rβ) e de substrato do receptor insulínico-1 (IRS-1) em tecido adiposo branco periepididimal, muscular... / Oral cavity’s pathologies may cause deleterious effects in different body systems. The presence of bacteria in dental pulp may cause periapical lesion (PL) and generate inflammation, culminating in the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These cytokines can reach the systemic circulation and may cause insulin resistance (IR) in insulin-responsive tissues. IR is defined as a decreased response of peripheral tissues to insulin action, and individuals with this metabolic state are predisposed to develop type 2 diabetes mellitus (T2DM). Knowing that the inflammatory cytokines may generate alterations in insulin signal, it becomes essential to investigate the possibility of a local inflammatory process as the PL per se cause insulin resistance in non- diabetic individuals. Therefore, the purpose of this study was to determine whether PL can cause changes in the initial phase of insulin signaling and in insulin sensitivity in non-diabetic rats. For this purpose, Wistar rats (two-month-old) were used in the present study. The animals were divided into two groups: 1) group with induced PL in right first upper molars by using a dental handpiece (spot size 0.1 mm); 2) control group (CN). After 30 days post induction, experiments were carried out: 1) blood collection (n = 10) obtaining plasma for glucose, insulin, total cholesterol, HDL cholesterol (HDL-C), triglycerides, LDL cholesterol (LDL-C), VLDL cholesterol (VLDL-C), TNF-α and IL-6 analyses; 2) insulin tolerance test (ITT) for evaluating insulin sensitivity (n = 10); 3) assessment of pp185 (IRS-1 / IRS-2) tyrosine phosphorylation and insulin receptor-beta (Rβ) and insulin receptor substrate-1 (IRS-1) content in periepididymal... (Complete abstract click electronic access below)

Orientador: Doris Hissako Sumida / Coorientador: Luciano Tavares Ângelo Cintra / Banca: Maria Aparecida Visconti / Banca: Marília Afonso Rabelo Buzalaf / Resumo: Patologias na cavidade oral podem gerar efeitos deletérios em diversos sistemas do organismo. Nesse sentido, a presença de bactérias nas polpas dentárias pode provocar lesão periapical (LP) e gerar inflamação, culminando na produção de citocinas inflamatórias, como o fator de necrose tumoral-alfa (TNF-α) e a interleucina-6 (IL-6), que podem atingir a circulação sistêmica e causar a resistência insulínica (IR) em órgãos responsivos à insulina. A IR é definida como a diminuição da resposta de tecidos periféricos à ação da insulina, e indivíduos com esta característica são predispostos a desenvolver diabetes mellitus tipo 2 (DM2). Tendo conhecimento de que as citocinas inflamatórias podem gerar alteração no sinal insulínico (SI), tornou-se primordial investigar a possibilidade de um processo inflamatório local, como a LP "per se", causar IR em indivíduos não diabéticos. Para tanto, foram utilizados ratos Wistar (02 meses de idade), divididos em dois grupos: ratos com LP induzida em primeiro molar superior direito, empregando-se broca em aço carbono dotada de esfera na extremidade com 0,1 mm de diâmetro e ratos-controle (CN). Após 30 dias de indução, realizaram-se os experimentos: 1) coleta de sangue (n=10) e obtenção de plasma para análise das concentrações de glicose, insulina, colesterol total, colesterol HDL (HDL-C), colesterol LDL (LDL-C), colesterol VLDL (VLDL-C), triglicérides, TNF-α e interleucina-6 (IL-6); 2) teste de tolerância à insulina (ITT) para a avaliação da sensibilidade à insulina (n=10); 3) avaliação do grau de fosforilação em tirosina da pp185 (IRS-1/IRS-2) e dos conteúdos de receptor insulínico beta (Rβ) e de substrato do receptor insulínico-1 (IRS-1) em tecido adiposo branco periepididimal, muscular... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Oral cavity's pathologies may cause deleterious effects in different body systems. The presence of bacteria in dental pulp may cause periapical lesion (PL) and generate inflammation, culminating in the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These cytokines can reach the systemic circulation and may cause insulin resistance (IR) in insulin-responsive tissues. IR is defined as a decreased response of peripheral tissues to insulin action, and individuals with this metabolic state are predisposed to develop type 2 diabetes mellitus (T2DM). Knowing that the inflammatory cytokines may generate alterations in insulin signal, it becomes essential to investigate the possibility of a local inflammatory process as the PL "per se" cause insulin resistance in non- diabetic individuals. Therefore, the purpose of this study was to determine whether PL can cause changes in the initial phase of insulin signaling and in insulin sensitivity in non-diabetic rats. For this purpose, Wistar rats (two-month-old) were used in the present study. The animals were divided into two groups: 1) group with induced PL in right first upper molars by using a dental handpiece (spot size 0.1 mm); 2) control group (CN). After 30 days post induction, experiments were carried out: 1) blood collection (n = 10) obtaining plasma for glucose, insulin, total cholesterol, HDL cholesterol (HDL-C), triglycerides, LDL cholesterol (LDL-C), VLDL cholesterol (VLDL-C), TNF-α and IL-6 analyses; 2) insulin tolerance test (ITT) for evaluating insulin sensitivity (n = 10); 3) assessment of pp185 (IRS-1 / IRS-2) tyrosine phosphorylation and insulin receptor-beta (Rβ) and insulin receptor substrate-1 (IRS-1) content in periepididymal... (Complete abstract click electronic access below) / Mestre

Bakgrund: Vid diagnostik av käkbenslesioner skickas ibland en remiss till röntgenspecialist för ett utlåtande. Röntgenspecialisten ger en eller flera tentativa diagnoser vilka kan underlätta vid beslut om behandling. Efter behandlingen skickas en biopsi till patolog för att erhålla en patologanatomisk diagnos. Syftet med denna studie är att 1) utreda hur väl tentativa röntgenologiska diagnoser överensstämmer med patologanatomiska diagnoser av käkbenslesioner och 2) utvärdera hur ofta röntgenutlåtanden kan leda till felaktig behandling av käkbenslesioner.Material och metod: Röntgenutlåtanden och motsvarande patologanatomiska diagnoser jämfördes retrospektivt under en tioårsperiod för nio vanliga käkbenslesioner. För varje käkbenslesion räknades antalet korrekta respektive inkorrekta röntgenologiska diagnoser som erhållits. Utöver detta jämfördes även den förväntade behandlingen av varje tentativ röntgendiagnos med den förväntade behandlingen av den korrekta patologanatomiska diagnosen. Utifrån detta gjordes sedan en bedömning av huruvida röntgenutlåtandet kunde leda till underbehandling, korrekt behandling eller överbehandling. Resultat: Röntgendiagnoserna överensstämde med de patologanatomiska diagnoserna i 191 av 394 fall (48%). Därutöver gav 61 röntgenutlåtanden (16%) den korrekta diagnosen tillsammans med en eller flera inkorrekta diagnoser. 142 utlåtanden (36%) gav endast en eller flera inkorrekta diagnoser. Drygt en fjärdedel av alla röntgenutlåtanden bedömdes kunna leda till felaktig behandling. Konklusion: Resultaten indikerar en anmärkningsvärd diskrepans mellan de tentativa röntgendiagnoserna och de patologanatomiska diagnoserna av de undersökta käkbenslesionerna. När röntgenspecialisten ger fler än en tentativ diagnos finns en ökad risk för överbehandling vilket kan leda till onödigt lidande för patienten samt en ökad kostnad för både patienten och samhället. Baserat på dessa resultat bör röntgenspecialisternas rutiner för hur många tentativa diagnoser de anger i sina röntgenutlåtanden ses över. / Background: When diagnosing jaw lesions, a referral may be sent to a radiologist for a radiographic report. The radiologist offers one or several tentative diagnoses, which help form the basis for treatment. After treatment a biopsy is sent to a pathologist for a pathoanatomical diagnosis. The aim of this study is to 1) determine the correspondence between tentative radiographic diagnoses and pathoanatomical diagnoses of jaw lesions and 2) evaluate how frequently radiographic reports may lead to incorrect treatment of jaw lesions. Materials and methods: Radiographic reports and pathoanatomical diagnoses of nine common jaw lesions were compared retrospectively over a ten-year period. The numbers of correct and incorrect tentative radiographic diagnoses were counted for each lesion. In addition, the expected treatments of the tentative radiographic diagnoses were compared with the expected treatments of the correct pathoanatomical diagnoses. Each report was then categorized as leading to undertreatment, correct treatment or overtreatment.Results: The radiographic reports corresponded with the pathoanatomical diagnoses in 191 out of 394 cases (48%). In addition, 61 radiographic reports (16%) stated the correct diagnosis along with one or several incorrect diagnoses. 142 reports (36%) only stated one or several incorrect diagnoses. Just over a quarter of the radiographic reports were deemed to lead to incorrect treatment. Conclusion: The results indicate a remarkable discrepancy between tentative radiographic diagnoses and pathoanatomical diagnoses for the studied jaw lesions. There is a tendency towards overtreatment when more than one tentative diagnosis is stated in the radiographic reports. Overtreatment may lead to unnecessary suffering for the patient and financial loss for both the patient and society. Based on these results, radiologists should review their practice of stating several tentative diagnoses in their reports.

Made available in DSpace on 2014-12-17T15:32:20Z (GMT). No. of bitstreams: 1 AnaLDLA_DISSERT.pdf: 3287914 bytes, checksum: 244a318f2c60d05b41aef3b1d3d6d2a0 (MD5) Previous issue date: 2012-02-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Periapical lesions are chronic inflammatory conditions of periradicular tissues considered direct consequences of infectious diseases resulting from pulp necrosis and subsequent progression to periapical region. The participation of the immune response and bone resorption in the formation of these lesions has been investigated, so that different cell types and cytokines have been identified as contributors to this process. In this perspective, this study aimed to evaluate the immunohistochemical expression of IL-17, TGF-?1 and FoxP3 in periapical granulomas (PGs), radicular cysts (RCs) and residual radicular cysts (RRCs), seeking a better understanding of the etiopathogenesis these periapicopatias. To this end, we selected 20 cases of GPs, 20 CRs and 10 RRCs to undergo morphological analysis and immunohistochemistry for biomarkers above, the latter being performed quantitatively using scores and average percentages of immunostaining for the analysis of IL-17 and TGF- ?1, while for the FoxP3 were counted only the positive lymphocytes. The results showed statistically significant differences between TGF-?1 and FoxP3 imunoexpressions, in relation to the periapical lesions studied (p = 0.002, p <0.001, respectively) but not between IL-17 and these (p = 0.355). Furthermore, the analysis of lymphocytes FoxP3-positive revealed significant statistical differences in that refers to the intensity of inflammatory infiltrate (p = 0.003) and also regarding thickness of the epithelial lining (p = 0.009). Finally, it was observed in the case of PGs, strong positive correlation between the amount of FoxP3- positive lymphocytes and the immunohistochemical expression of TGF-?1 (r = 0.755, p<0.001), as well as moderate positive correlation between IL-17 and TGF-?1 imunoexpressions (r = 0.503, p = 0.024). Thus, we can conclude that interactions between Th17 and Treg cells seem to be established at the site of injury, suggesting the involvement of both pro-inflammatory and immunoregulatory cytokines in the pathogenesis of periapical lesions / Les?es periapicais cr?nicas s?o condi??es inflamat?rias dos tecidos perirradiculares consideradas sequelas diretas de processos infecciosos resultantes da necrose pulpar e consequente progress?o para a regi?o periapical. A participa??o da resposta imunol?gica e da reabsor??o ?ssea na forma??o destas les?es tem sido bastante investigada, de modo que diversos tipos celulares e citocinas foram apontados como colaboradores deste processo. Nesta perspectiva, o presente estudo objetivou avaliar a express?o imuno-histoqu?mica da IL- 17, TGF-?1 e FoxP3 em granulomas periapicais (GPs), cistos radiculares (CRs) e cistos radiculares residuais (CRRs), buscando um melhor entendimento sobre a etiopatog?nese destas periapicopatias. Para tanto, foram selecionados 20 casos de GPs, 20 de CRs e 10 de CRRs para serem submetidos ? an?lise morfol?gica e imuno-histoqu?mica para os biomarcadores supracitados, sendo esta ?ltima realizada quantitativamente atrav?s de escores e percentuais m?dios de imunomarca??o para a an?lise da IL-17 e do TGF-?1, enquanto que para o FoxP3 foram contados apenas os linf?citos positivos. Os resultados demonstraram diferen?as estatisticamente significativas entre as imunoexpress?es do TGF-?1 e do FoxP3 em rela??o as les?es periapicais pesquisadas (p = 0,002; p < 0,001, respectivamente), mas n?o entre a IL-17 e estas (p = 0,355). Al?m disso, a an?lise dos linf?citos FoxP3-positivos revelou diferen?as estat?sticas significativas no que se refere ? intensidade do infiltrado inflamat?rio (p = 0,003) e tamb?m quanto ? espessura do revestimento epitelial (p = 0,009). Por fim, observou-se nos casos de GPs, forte correla??o positiva entre a quantidade de linf?citos FoxP3-positivos e a imunoexpress?o do TGF-?1 (r = 0,755; p < 0,001), assim como moderada correla??o positiva entre as imunoexpress?es da IL-17 e do TGF-?1 (r = 0,503; p = 0,024). Destarte, pode-se concluir que intera??es entre c?lulas Th17 e Treg parecem ser estabelecidas no local da agress?o, sugerindo a participa??o de citocinas tanto pr?inflamat?rias como imunorregulat?rias na patogenia das les?es periapicais