Thesis (doctoral)--Karolinska Institutet, Stockholm, 1988. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1988. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Titre de l'écran-titre (visionné le 13 juillet 2023) / Ce projet porte sur l'impact de l'hyperglycémie sur la sécrétion de cytokines pro-inflammatoires et de métalloprotéinases matricielles par les cellules gingivales à la suite d'une stimulation de la réponse inflammatoire par des biofilms sous-gingivaux dysbiotiques. La maladie parodontale est une maladie inflammatoire induite par l'infiltration de bactéries parodontopathogènes et conduit à la destruction irréversible de l'ensemble des tissus de soutien de la dent. Celle-ci induit une inflammation qui joue un rôle important dans le développement d'une dysbiose du microbiome sous-gingival. Il a été suggéré qu'une dysbiose du microbiome sous-gingival augmentait le risque de parodontite chez des patients diabétiques à cause d'une inhibition de leurs réponses immunitaires et métaboliques. Cependant, l'impact de l'hyperglycémie sur la régulation de la réponse inflammatoire gingivale est peu connu et la modulation de cette réponse est peu étudiée. Nous avançons l'hypothèse qu'un environnement hyperglycémique peut affecter les interactions hôte-microbiome et par conséquent influencer la réponse inflammatoire d'un patient atteint de parodontite. Pour cela nous avons étudié la réponse inflammatoire d'un modèle de co-culture de fibroblastes gingivaux et de macrophages stimulés par des échantillons de plaque dentaire provenant d'individus sains ou atteints de parodontite, et ce, en présence de concentrations normales ou élevées de glucose. Le profil de sécrétion de cytokines pro-inflammatoires et métalloprotéinases matricielles a été par la suite analysé. Nous avons observé une augmentation significative des niveaux de sécrétions de plusieurs cytokines reflétant l'impact de l'environnement hyperglycémique sur la modulation de l'inflammation. Les résultats que nous avons obtenus permettront éventuellement de planifier des traitements parodontaux personnalisés et adaptés, ainsi que de développer des stratégies de prévention individualisées pour mieux contrôler le développement et la progression de la maladie parodontale chez les patients diabétiques.

O aumento gengival à uma condiÃÃo bucal cuja origem à atribuÃda à interaÃÃo de mÃltiplos fatores, dentre eles susceptibilidade genÃtica, influÃncia de hormÃnios na puberdade e na gravidez, uso de medicamentos como Ãs fenitoÃna, ciclosporina, diltiazen e anfetamina, aÃÃo das citocinas prÃ-inflamatÃrias como o TNF-α, e atà causas neoplÃsicas. Embora o acÃmulo excessivo da placa dentÃria e a inflamaÃÃo crÃnica gengival, tambÃm, estejam relacionados como provÃveis fatores predisponentes ao aumento gengival, à controverso se a inflamaÃÃo prÃ-existente estimula o crescimento gengival por dificultar a higienizaÃÃo dentÃria, ocasiona o acÃmulo da placa bacteriana e conseqÃente processo inflamatÃrio, predispondo o indivÃduo à destrutiva doenÃa do periodonto. Desta forma, o presente estudo teve o objetivo de avaliar se a gengivite està presente em todos os pacientes com aumento gengival, e se a evoluÃÃo do processo inflamatÃrio responde satisfatoriamente ao tratamento com a clorexidina. Quatorze pacientes portadores de crescimento gengival, que se submeteram voluntariamente ao tratamento cirÃrgico, aceitaram em participar do estudo. As primeiras biÃpsias gengivais foram obtidas dos pacientes, antes da realizaÃÃo da gengivectomia, para estudo do processo inflamatÃrio gengival pelos exames histolÃgico (H&E) e para a avaliaÃÃo da composiÃÃo das cÃlulas mononucleares da inflamaÃÃo, pelo mÃtodo imunohistoquÃmico de Peroxidase-Anti-Peroxidase (PAP), utilizando anticorpos monoclonais para os marcadores celulares CD43 (linfÃcitos T), CD20 (cÃlulas B) e CD68 (macrÃfagos). Em seguida os pacientes foram instruidos a realizar bochechos com clorexidina a 0,12% (sem Ãlcool), 30 min apÃs a escovaÃÃo durante 30 segundos, por dez dias, pela manhà e noite. SubseqÃentemente, biÃpsias gengivais foram obtidas do tecido gengival removido durante o tratamento cirÃrgico, para novas avaliaÃÃes histolÃgica e imunohistoquÃmicas. Os resultados obtidos foram os seguintes: i) todos os pacientes com aumento gengival apresentaram o processo inflamatÃrio gengival em evoluÃÃo, num grau histolÃgico de intensidade variando de 1 a 3; ii) o processo inflamatÃrio revelou a presenÃa de cÃlulas T (5,7  2,07 por 6 campos microscÃpicos), cÃlulas B (9,0  4,64) e macrÃfagos (62,6  16,44); e iii) o tratamento com a clorexidina resultou numa reduÃÃo histolÃgica da inflamaÃÃo em 59% dos pacientes, mas nÃo alterou o quadro em quatro pacientes (29%), enquanto que dois pacientes (14%) apresentaram um aumento do processo inflamatÃrio. ApÃs tratamento com a clorexidina, evidenciou-se uma reduÃÃo de ordem 40% dos macrÃfagos no tecido gengival (40,5  9,15; p=0.05), com uma moderada alteraÃÃo dos valores das cÃlulas T (8,25  1,71) e B (12,75  6,99), revelando uma diminuÃda participaÃÃo dos macrÃfagos no processo inflamatÃrio, e a possÃvel ativaÃÃo das defesas pelos linfÃcitos. Essas observaÃÃes sugerem que ao aumento gengival parece estar associada com a gengivite, e o tratamento com a clorexidina, em forma de bochechos diÃrios, pode ser eficaz na reduÃÃo do processo inflamatÃrio, na maioria dos pacientes. / Gingival hyperplasia is an oral condition whose origin is attributed to the interaction of multiple factors: among them, genetic susceptibility; hormonal influences during puberty and pregnancy; therapy with drugs as varied as phenontoin, cyclosporine, diltiazen and anphetamines; action of proinflammatory cytokines, as TNF-α; and even neoplastic causes. Although excessive accumulation of dental plaque and chronic gingivitis have been included among predisposing factors for gingival hyperplasia, it is not yet known if preexisting gingivitis stimulates the gingival growth, or the hypertrophy promotes, due to the difficulties in dental hygiene, the accumulation of bacterial plaque and the consequent gingivitis, predisposing the individual to destructive periodontal disease. This study had the objective of evaluating if gingivitis is present in all gingival hyperplasia patients, and if the inflammation process responds satisfactorily to chlorhexidine treatment. Fourteen patients who were to undergo voluntary surgical treatment for gingival hyperplasia consented to participate in the study. The initial gingival biopsies were obtained from the patients before they underwent gingivectomy, to evaluate the inflammatory process by histology (H&E), and immunohistochemistry by Peroxidase-Anti-Peroxidase (PAP) method, utilizing monoclonal antibodies to cell markers CD43 (T cells), CD20 (B cells) and CD68 (macrophages). The patients were subsequently induced to perform mouthrinses 30 minutes after dental higiene, with 0.12% chlorhexidine for 30s during 10 days. Biopsies were then obtained from the gingival tissue removed by gingivectomy, for fresh histology and PAP evaluations. The results were as follows: i) all the patients with hyperplasia had ginigival inflammation in evolution, of histological grades 1 to 3; ii) the inflammatory process revealed presence of T cells (5.7  2.07 per 6 microscopic fields), B cells (9.0Â4.64), and macrophages (62.6 16.44); iii) chlorhexidine treatment resulted histological reduction of inflammation, with a 40% decrease in macrophages (40.5  9.15; p=0.05), and a moderate rise in T (8.25 1.71) and B (12.75  6.99) cells in the gingival tissue, revealing a decreased participation of macrophages, and possibly an increased engagement of lymphocytes in defenses. These observations suggest that there is a definite association between gingival hyperplasia and gingivitis, and that mouthrinses of chlorhexidine can be effective in diminishing the severity of gingival inflammation, in a majority (59%) of individuals.