Background and Objective: Smoking is one of the major risk factors for chronic periodontitis. However, the mechanisms involved in tissue degradation due to cigarette smoking are not clear. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) are a system of molecules that regulate bone resorption. The aim of this study was to compare the levels of soluble RANKL (sRANKL), OPG and their relative ratio in GCF among periodontitis patients with varying smoking histories. Material and Methods: GCF samples were collected from 149 periodontitis patients who were never smokers (n=58), former smokers (n=39) and current smokers (n=52). sRANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays. Results: sRANKL, OPG and their relative ratio were not statistically significant among the never smokers, former smokers and current smokers. However, OPG was significantly reduced and subsequently the sRANKL:OPG ratio was significantly increased in the high pack-years group as compared with never smokers. The positive correlation between packyears and sRANKL:OPG ratio was statistically significant even after adjusting for age and current smoking status. Conclusion: Increased lifetime exposure to cigarette smoking above a minimum threshold suppresses OPG production and leads to increased sRANKL:OPG. This may partially explain increased bone loss in smoking-related periodontitis. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352109 / Thesis (D.Clin.Dent.) - University of Adelaide, School of Dentistry, 2009

Includes bibliographies. / 1 v. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / A collection of 27 published journal articles representing work carried out between 1983 and 1995, the major thrust being an extension of the author's PhD studies. Centres on detailed investigations into the nature of proteoglycans in various periodontal compartments and what factors might influence their structure and synthesis. / Thesis (D.D.Sc.)--University of Adelaide, Dept. of Dentistry, 1996

Background and Objective: Smoking is one of the major risk factors for chronic periodontitis. However, the mechanisms involved in tissue degradation due to cigarette smoking are not clear. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) are a system of molecules that regulate bone resorption. The aim of this study was to compare the levels of soluble RANKL (sRANKL), OPG and their relative ratio in GCF among periodontitis patients with varying smoking histories. Material and Methods: GCF samples were collected from 149 periodontitis patients who were never smokers (n=58), former smokers (n=39) and current smokers (n=52). sRANKL and OPG concentrations in GCF were measured by enzyme-linked immunosorbent assays. Results: sRANKL, OPG and their relative ratio were not statistically significant among the never smokers, former smokers and current smokers. However, OPG was significantly reduced and subsequently the sRANKL:OPG ratio was significantly increased in the high pack-years group as compared with never smokers. The positive correlation between packyears and sRANKL:OPG ratio was statistically significant even after adjusting for age and current smoking status. Conclusion: Increased lifetime exposure to cigarette smoking above a minimum threshold suppresses OPG production and leads to increased sRANKL:OPG. This may partially explain increased bone loss in smoking-related periodontitis. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352109 / Thesis (D.Clin.Dent.) - University of Adelaide, School of Dentistry, 2009

Thesis (doctoral)--University of Helsinki, 1979. / "From the Dept. of Periodontology, Institute of Dentistry, University of Helsinki, Finland." Includes bibliographical references (p. 37-42).

Thesis (doctoral)--University of Helsinki, 1979. / "From the Dept. of Periodontology, Institute of Dentistry, University of Helsinki, Finland." Includes bibliographical references (p. 37-42).

Thesis (M.Ch.D.(Periodontology and Oral Medicine))--University of Pretoria, 1999. / Includes abstract in English and Afrikaans. Includes bibliographical references. Also available online.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliographical references.

Thesis (M.S.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 43 pages. Includes Vita. Includes bibliographical references.

Submitted by DAYANE DE ALMEIDA BRANDÃO null (dayaneabrandao@hotmail.com) on 2016-05-16T01:24:28Z No. of bitstreams: 1 Dayane de Almeida Brandão-FINAL.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-05-17T14:19:23Z (GMT) No. of bitstreams: 1 brandao_da_me_arafo.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) / Made available in DSpace on 2016-05-17T14:19:23Z (GMT). No. of bitstreams: 1 brandao_da_me_arafo.pdf: 3147709 bytes, checksum: 4a2e64ad8796eb690412408acd162ec3 (MD5) Previous issue date: 2016-03-18 / Curcumin é um polifenol amarelo extraído do rizoma de uma planta tropical, do tipo herbácea. Possui ações anti-inflamatória, antioxidante, antiangiogênica, imunomodulatória, citotóxica, antimicrobiana e antiapoptótica. A aplicação terapêutica do curcumin vem sendo avaliada em modelos pré-clínicos e estudos de várias doenças. As limitações da eficácia do curcumin in vivo são atribuídas à sua má solubilidade em veículos aquosos e baixa taxa de absorção no trato gastrointestinal. O objetivo desse trabalho foi avaliar o efeito dose-resposta do composto sintético análogo ao curcumin (CMC2.24) em diferentes doses (1 mg, 3 mg, 10 mg, 30 mg) sobre o processo inflamatório e osteoclastogênese em modelo de doença periodontal in vivo e in vitro, para analisar qual é a dose mínima necessária para que o composto tenha o efeito biológico. A doença periodontal foi induzida em ratos por meio de injeção de 30 µg de LPS de Escherichia coli, realizadas 3x/semana durante 4 semanas. Os controles receberam injeções do mesmo volume do veículo de diluição do LPS (PBS). A administração de CMC2.24 (1, 3, 10 e 30mg/kg) foi feita por via intragástrica (gavagem oral) diariamente, durante 29 dias (um dia antes da primeira injeção de LPS/PBS). A expressão de fosfatase ácido tartarato resistente (TRAP), indicativa de diferenciação osteoclástica, foi avaliada por meio de imunohistoquímica, a proporção de células inflamatórias, em cortes corados com H/E, por estereometria, a presença de citocinas através do PCR em tecido gengival e a reabsorção óssea por análise de coloração por azul de metileno e microtomografia computadorizada. Nos experimentos in vitro, macrófagos foram estimulados com microrganismos e tratados com CMC2.24 em concentração de 1, 3, 10 e 30 µM. A expressão gênica foi avaliada através de PCR e ELISA, enquanto fagocitose e quantificação de espécies reativas de oxigênio foram avaliadas por atividade fagocitária e produção de ROS, respectivamente. De acordo com os resultados, CMC2.24 reduziu significativamente o infiltrado inflamatório. Além disso, CMC diminuiu significativamente a quantidade de células TRAP positiva a partir de 3 mg/kg e a perda óssea alveolar, a partir de 1 mg/kg. In vitro, experimentos utilizando macrófagos demonstraram que o CMC inibe a produção de TNF e IL-10 após estímulos microbianos. Além disso, CMC2.24 também inibiu atividade fagocitária e estimulou a produção de ROS. CMC2.24 em diferentes doses demonstrou potencial terapêutico para aplicação em doença periodontal, devido à inibição da resposta inflamatória e também foi efetivo na redução da reabsorção óssea inflamatória. / Curcumin is a yellowish polyphenol extracted from the rizome of a herbaceous tropical plant. It has multiple biological activities described, including anti-inflammatory, antioxidant, antiangiogenic, immunomodulatory, cytotoxic, antimicrobial and pro- and antiapoptotic activities. Its therapeutic application is actively evaluated in preclinical models and clinical studies of various diseases. In vivo use of curcumin is limited by its pharmacodynamic propereties, such as poor solubility in aqueous vehicles, low absorption rate in the gastrointestinal tract and short half-life in the peripheral circulation. The aim of this study was to evaluate the dose-response effect of a synthetic compound that is structurally to natural curcumin (CMC2.24) in a model of experimental periodontal disease that mimics the host-microbial interaction and the resultant inflammation and bone resorption that are hallmarks of this conditions in humans. Periodontal disease was induced in mice by injection of 30 ug LPS of Escherichia coli, carried out 3x / week for 4 weeks. Controls received injections of the same volume of vehicle (PBS). Administration of CMC2.24 (1, 3, 10 and 30mg / kg) was performed daily (starting the day before the first LPS/PBS injection) by oral gavage (1, 3, 10 and 30 mg/Kg) during the whole experimental period. Immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP) was used to identify osteoclasts in the area of interest; the inflammatory infiltrate was assessed by stereometric/morphological analysis in H/E-stained sections; expression of candidate inflammatory cytokines in the gingival tissue determined by RT-PCR and the extent of inflammatory bone resorption quantitated macroscopic analysis of the area of exposed root surface and also by computed microtomography. In in vitro experiments, murine macrophages were stimulated with periodontal diseaseassociated microorganisms in the presence and absence of CMC2.24 (1, 3, 10 and 30 uM). Gene expression was assessed by RT-PCR and ELISA; phagocytic activity was studied by immunocytofluorescence and production of reactive oxygen species was determined by a biochemical assay using a ROS-substrate that emit fluorescence upon cleavage. In vivo, administration of CMC2.24 significantly reduced the inflammatory infiltrate, and the number of osteoclasts starting at the 3 mg/Kg dosage; whereas inflammatory bone resorption was significantly inhibited already at the 1 mg/Kg dosage. In vitro, pre-treatment of macrophages with CMC2.24 markedly inhibited the production of TNF and IL-10 after microbial stimuli. CMC2.24 also inhibited phagocytic activity and stimulated production of ROS. We conclude that CMC2.24 at low doses (3 mg/Kg) has therapeutic potential for application in periodontal disease, due to inhibition of microbial-related inflammation.

Made available in DSpace on 2014-06-11T19:33:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-03-12Bitstream added on 2014-06-13T20:05:23Z : No. of bitstreams: 1 bastos_as_dr_arafo.pdf: 971405 bytes, checksum: a74b6a8b306a24bb6ac6bb99a6d39a6f (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo teve por objetivo avaliar os níveis locais e sistêmicos de peroxidação lipídica (LPO) e sua correlação com o perfil de marcadores inflamatórios, locais e sistêmicos em com Diabetes mellitus (DM) tipo 2, dislipidemia e periodontite crônica, comparando-os a indivíduos sem diabetes. Além disso, buscou-se propor um método validado para avaliar o malondiadeído (MDA) no fluido sulcular gengival de sítios saudáveis e doentes. A amostra foi constituída de 120 pacientes com doença periodontal crônica divididos em 4 grupos: Grupo1 (DM descompensado); Grupo2 (DM compensado); Grupo3 (sem diabetes com dislipidemia); Grupo 4 (sistemicamente saudável). Toda a amostra foi submetida a exame periodontal completo, exame físico e avaliação laboratorial para verificação da glicemia de jejum, hemoglobina glicada (HbA1c), insulina, proteína C-reativa e perfil lipídico. O exame periodontal consistiu na avaliação do índice de placa visível, do índice de sangramento marginal, da posição da margem gengival, da profundidade de sondagem, do sangramento à sondagem e do nível clínico de inserção. Para todos os grupos foram coletadas amostras de fluido sulcular gengival (FSG) (4 sítios sem periodontite e 4 sítios com periodontite) e de sangue para obtenção do plasma sanguíneo. Os níveis de peroxidação lipídica representados pelo MDA, avaliado por HPLC, e pelo LDL oxidado (LDLox), avaliado por ELISA, foram quantificados no fluido sulcular gengival e no plasma. Foram avaliadas ainda as citocinas (IL)-1, -2, - 4, -5, -6, -7, -8, -10, -12, -13 e fator de necrose tumoral α (TNF-α) no FSG e no plasma. Foi possível determinar e validar o método de avaliação no fluido sulcular gengival, com alta precisão, sendo que os coeficientes... / The aim of this study is to evaluate the levels of the lipid peroxidation and its correlation with systemic and local inflammatory markers profile in patients with type 2 diabetes mellitus (DM2) dyslipidemia and chronic periodontitis compared to systemically healthy patients. We also aimed to quantify a specific product of the lipid peroxidation process, malondialdehyde (MDA), in gingival crevicular fluid and to describe the validation of this method in this matrix using HPLC. The study sample comprised 120 patients divided into four groups with 30 patients in each group: group 1- diabetes with poor metabolic control with dyslipidemia, group 2- diabetes with good metabolic control, group 3- without diabetes with dyslipidemia and group 4- systemically healthy. All the subjects will go through a complete periodontal examination and physical and laboratory evaluation in order to verify fasting plasma glucose, glycated hemoglobin (HbA1c), lipid profile, insulin and high sensitivity C-reactive protein. Periodontal examination will consist of visible plaque index, gingival bleeding index, bleeding on probing, probing depth (PD) and clinical attachment levels (CAL). Plasma and samples of gingival crevicular fluid (GCF) will be collected in 4 sites without periodontal disease and 4 sites with periodontal disease. The lipid peroxidation levels, evaluated by oxidized LDL (ox LDL) and MDA were measured in GCF and in plasma. Inflammatory cytokines, (IL)-1, -2, -4, -5, -6, -7, -8, -10, -12, -13 and tumor necrosis factor-alpha α (TNF-α) were also evaluated in plasma and GCF. It was possible to validate a HPLC-based method to identify and quantify the MDA in GCF with sensitivity, precision, and accuracy even in small concentrations as observed in healthy... (Complete abstract click electronic access below)