Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 69-79).

Thesis (Ph.D. in Immunology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 91-100). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Dissertation (Ph.D.) -- The University of Texas Southwestern Medical Center at Dallas, 2006. / Embargoed. Vita. Bibliography

Thesis (M.S.)--University of Tennessee Health Science Center, 2008. / Title from title page screen (viewed on February 27, 2009). Research advisor: Terrence L. Geiger, MD, PhD. Document formatted into pages (xi, 74 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 64-74).

The main and most critical function of the immune system is to distinguish between self and non-self and react accordingly. Differentiating self-reactive immune cells as soon as they develop is the phenomenon of tolerance against self-antigens and is a highly regulated process. The development of autoantibodies is a sign of the breakdown of tolerance and may be the harbinger of the onset of an autoimmune disease. It is well-known fact that many systemic autoimmune diseases (AUIDs) first manifest in the oral cavity. If proven that oral infections trigger AUIDs, then improving oral health may be a potential therapeutic strategy to reduce autoimmune disease incidence. Although etiology and pathogenesis of specific AUIDs may vary, presentation in the oral cavity often involves oral lesions manifested at early stages of systemic inflammatory and autoimmune disease. Therefore regular dental and medical checkups may provide an opportunity for clinicians, in particular dentists, to contribute to earlier detection of AUIDs thereby improving long-term treatment options and overall patient prognosis. Mechanisms leading to the onset of autoimmune disease are still being considered. Epidemiological inquires and the increasing numbers of genome-wide association studies have analyzed the breakdown of tolerance and the causes behind autoimmunity. The role of the environment is crucial in the onset of autoimmunity via the breakdown of tolerance; through toll-like receptors that mediate innate immunity which in turn triggers the adaptive autoimmune response, T regulatory cells and Th17 differentiation, through changes in the spleen autoantibody production due to a change in the B cell count, and through self antigen and epigenetic deviations induced by environmental spurs. In spite of many research efforts and the accumulation of innovative data, there are still multiple gaps in knowledge pertaining to this subject matter. The autoimmune process begins with the activation of Tcells by antigen presenting cells (APC) and progresses to CD4+ CD25+ Tcells and forkhead box P3 (Foxp3), which stimulate Th1 and Th2 responses and finally B cell activation, which plays a role in autoimmune development. This paper will review the etiopathogenesis of autoimmune diseases and different cell players as well as transcription factors such as TGF–β, IL–6, IL–10, IL–17, Th–17, T reg cells, B reg cells, Th–1, Th–2, and INF–γ. This paper aims to review published evidence and further explore the etiopathology of individual autoimmune diseases such as Behcet's, Crohn's disease, Sjögren syndrome, systemic lupus erythematosus, and rheumatoid arthritis and the subsequent dental implications and therapeutic management. This review also aims to study the most relevant autoimmune, auto-inflammatory, and systemic chronic inflammatory diseases, as well as mechanisms of autoimmune manifestation with respect to oral health.

Contexto: Pacientes com tireoidite autoimune crônica com anticorpos de peroxidase tireoideana (Anti-TPO) podem progredir para hipotireoidismo subclínico e clínico. Estudos anteriores mostraram uma redução no anti-TPO em pacientes com hipotireoidismo que receberam tratamento de reposição de LT4 e suplementação de selênio. Objetivos: Avaliar se a selenometionina (SeMet) reduz o anti-TPO em pacientes anti-TPO positivos eutireoideos tratados com LT4 e melhora a ecogenecidade da tireoide em comparação com grupo de pacientes tratados com placebo. Desenho: Estudo duplo-cego aleatório controlado com placebo. Pacientes e métodos: Um total de 55 pacientes consecutivos com TCA (50 mulheres, 5 homens, idade mediana de 48 anos variando de 20 a 58), 4 tabagistas, 4 anos desde o diagnóstico da doença (mediana), com TSH normal ou levemente elevado, T4L dentro dos níveis normais, anti-TPO maior que 100 U/ml foram aleatoriamente selecionados para receber uma dose diária de 200 ?g de selenometionina (grupo SeMet; n = 28) ou placebo (grupo P; n = 27) por 3 meses. Anticorpos da tireoperoxidase e tireoglobulina (TPO-Ab; TG-Ab), TSH, FT4, T3, T4, proteína C-reativa (PCR), citocinas (IL6, IL10, TNF), glicose sanguínea em jejum, calcitonina, selênio plasmático, concentração de iodo na urina, atividade da peroxidase de glutationa 1 em eritrócitos (GPx1) foram dosados no basal, após 3 e 6 meses de acompanhamento. Polimorfismo do GPx1-Pro198Leu foi avaliado no basal. Foi efetuado ultrassom de tireoide (US) em cada ponto de acompanhamento. Ecogenecidade do tecido foi caracterizada por análise histográfica computadorizada em escala de cinza e expressa como índice de ecogenecidade (EI). A relação entre concentração de Selênio e atividade GPx1 nos eritrócitos foi analisada para cada genótipo. O IE e associações de variáveis clínicas também foram avaliadas. Resultados: Não houve diferenças nas características iniciais (basais) entre o grupo SeMet e P. Selênio plasmático e atividade GPx1 aumentaram no grupo SeMet mas não variaram no grupo P durante a suplementação de SeMet. Anti-TPO, anti-TG, TSH e hormônios tireoidianos não variaram significativamente no grupo P. Anti-TPO no grupo SeMet era de 1009 (176- >3000) no basal, 958 (161- > 3000) aos 3 meses e 768 (65-2821) U/ml aos 6 meses. Neste grupo, as variações em relação ao basal foram de -5% aos 3 meses e -24% aos 6 meses, respectivamente. No grupo P, as mudanças em relação ao basal foram de 1206 (154- >3000), 1404 (231- >3000), 1430 (140- >3000 U/ml), respectivamente (valores médios e limítrofes); +16% aos 3 meses e +18% aos 6 meses, respectivamente. Níveis de TSH, no grupo SeMet, foram de 1,7 (0,8 - 2,5) no basal, 3,0 (1,1 - 6,3) aos 3 meses e 3,2 (1,1 - 6,5) ?U/mL aos 6 meses, no grupo P, os níveis de TSH foram de 1,7 (0,8 - 2,5) no basal, 2,2 (0,6 - 6,8) e 2,5 (0,9 - 5,5) ?U/mL, respectivamente (valores médios e limítrofes). Valores médios da proteína C-reativa foram inferiores a 10mg/L nos dois grupos. O percentual dos genótipos no grupo SeMet eram de 7,1%, 64,3% e 28,6% para Leu/Leu, Pro/Leu e Pro/Pro (o genótipo mais frequente), respectivamente; no grupo P, a distribuição foi 0,0%, 51,9% e 48,1% para Leu/Leu, Pro/Leu e Pro/Pro, respectivamente, comparado com controles normais (11,4%, 39,2% e 49,4% Leu/Leu, Pro/Leu e Pro/Pro respectivamente). O IE exibiu tendência a uma diferença significativa indo de 1,2 no basal para 1,0 aos 3 meses e 1,1 aos 6 meses para o grupo SeMet, respectivamente, enquanto que permaneceu constante (1,2 no basal, 1,2 aos 3 meses e 1,2 aos 6 meses) para o grupo P, respectivamente. Após o período de suplementação, o coeficiente de correlação r = 0,95 (p < 0,001) para Pro/Pro e a tendência foi a mesma que o basal para o grupo Pro/Leu. No grupo SeMet, o IE correlacionou-se positivamente com a velocidade sistólica de pico nas artérias inferiores da tireoide no basal (r = 0,5, p = 0,008) e após o período de suplementação (r = 0,46; p = 0,025). Anti-TG correlacionou-se com valores do fator de necrose tumoral médios no grupo placebo (r = 0,46; p = 0,015). Conclusão: A suplementação por 3 meses aumentou os marcadores do status de selênio. SeMet parece ser eficaz em reduzir a ecogenecidade da tireoide e em reduzir o anti-TPO (porém não o anti-TG) após 3 meses de intervenção, mas não influencia o TSH ou os hormônios tireoideanos / Context: Autoimmune chronic thyroiditis (ACT) euthyroid subjects with positive thyroid peroxidase antibodies (TPO-Ab) may progress to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease in TPO-Ab in hypothyroid patients receiving LT4 replacement therapy plus selenium supplementation. Objectives: To evaluate in euthyroid TPOAb-positive LT4-treated subjects whether selenometionine (SeMet) decreases TPO-Ab and improves thyroid ecogenicity in comparison with placebo. Design: Randomized, placebo-controlled, double-blind study. Patients and methods: A total of 55 consecutive patients with ACT (50 F, 5 M, age median: 48, range: 20-58 years), 4 smokers, duration of disease (median) 4 years, normal or slightly elevated TSH and FT4 within the normal range, TPO-Ab >= 100 U/mL were randomized to receive 200 ?g selenometionine daily ((group SeMet; n = 28) or placebo (group P; n = 27) for 3 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; TG-Ab), TSH, FT4, T3, T4, C-reactive protein (CRP), cytokines (IL6, IL10, TNF), fasting blood glucose, calcitonin, plasma selenium, urine iodine concentrations, activity of glutathione peroxidase 1 in erythrocytes (GPx1) were estimated at baseline, after 3 and 6 months of follow-up; GPx1-Pro198Leu polymorphism was assessed at baseline. Thyroid ultrasound (US) was performed at each follow-up point. Tissue ecogenicity was characterized by computerized grey-scale histographic analysis and expressed as ecogenicity index (EI). The relationship between Se concentration and GPx1 erytrocyte activity was analysed for each genotype group. EI and clinical variables associations were also evaluated. Results: There were no differences in baseline characteristics between the SeMet group and the P group. During SeMet supplementation, plasma Se and GPx1 activity did not change in the P group, but increased in the SeMet group. TPO-Ab, anti-TG, TSH and thyroid hormones did not change significantly in group P. TPO-Ab in the SeMet group were 1009 (176- >3000) at baseline, 958 (161- >3000) at 3 months and 768 (65-2821) U/mL at 6 months. In this group change from baseline were -5 at 3 months and -24% at 6 months, respectively. In the P group change from baseline were 1206 (154- >3000), 1404 (231- >3000) and 1430 (140- >3000) U/mL, respectively (mean values with range); from baseline were +16 at 3 months and +18% at 6 months, respectively. TSH in the SeMet group were 1.7 (0·8-2·5) at baseline, 3·0 (1·1-6·3) at 3 months and 3.2 (1,1-6,5) uU/mL at 6 months; in the P group were 1·7 (0·8-2·4), 2·2 (0·6-6·8) and 2.5 (0.9-5.5) ?U/mL, respectively (mean values with range). C-reative protein mean level was <10 mg/L in both groups. Genotype proportions in the SeMet group were 7.1, 64.3, and 28,6% for Leu/Leu, Pro/Leu and Pro/Pro (the wild-type genotype), respectively; in the P group were 0.0, 51.9 and 48.1 for Leu/Leu, Pro/Leu and Pro/Pro, respectively compared with normal controls (11.4, 39.2 and 49.4%, Leu/Leu, Pro/Leu and Pro/Pro, respectively). EI exhibited a tendency towards a significant difference from 1.2 at baseline to 1.0 at 3 months and 1.1 at 6 months for the SeMet group, respectively and remained the same (1.2 at baseline, 1.2 at 3 months and 1.2 at 6 months) for the P group, respectively. For the SeMet group there was no significant correlation for Pro/Pro and Pro/Leu genotypes at the baseline. After the supplementation period, the correlation coefficient was r = 0.95 (p < 0.001) for Pro/Pro and the trend was the same as baseline for Pro/Leu. In the Semet group EI correlated positively with systolic peak velocity in the inferior thyroid arteries at baseline (r = 0.50; p = 0.008) and after supplementation period (r = 0,46; p = 0,025). Anti-TG correlated with tumor necrosis factor mean values in the Placebo group at baseline (r = 0,46; p = 0,015). Conclusion: Three months selenometionine supplementation increased markers of selenium status. SeMet seems to be effective in reducing thyroid echogenicity and in reducing TPO-Ab (but not TG-Ab) after 3 months of intervention, but does not influence TSH or thyroid hormones