Autoimmune diseases such as rheumatoid arthritis (RA) are associated with debilitating chronic inflammation, autoantibody production, articular bone erosions and systemic bone loss. The underlying mechanisms and cell types that initiate these diseases are not fully understood, and current therapies mainly address downstream mechanisms and do not fully halt disease progression in all patients. Moreover, previous studies have largely focused on the role of adaptive immunity in driving these diseases, and less attention has been given to the contribution of innate immune pathways such as DNA sensor signaling pathways in initiating and/or perpetuating autoimmunity and erosive inflammatory arthritis. Detection of microbial nucleic acids by DNA sensors such as endosomal toll-like receptors (TLRs) and cytosolic sensors is an early form of antiviral defense. Upon detection of nucleic acid, TLRs dependent on Unc93B and cytosolic sensors dependent on the adaptor stimulator of interferon genes (STING) orchestrate production of type 1 interferons and pro-inflammatory cytokines to resolve infection. Additionally, the cytosolic DNA sensor absent in melanoma 2 (AIM2), which is not dependent on STING, also recognizes microbial DNA and coordinates the cleavage of pro-IL-1β. Previous studies have largely focused on the role of these DNA sensors in macrophages and dendritic cells in the context of antiviral immunity. In recent years, however, the inappropriate recognition of host nucleic acids by these sensors has been associated with several autoimmune diseases including RA. This dissertation aims to delineate the mechanisms by which DNA sensors contribute to inflammatory arthritis and bone remodeling in the context of a murine model of autoimmunity. In DNase II deficient mice, excessive accrual of undegraded, endogenous DNA leads to robust production of type 1 interferons (IFNs) and proinflammatory cytokines. The high levels of type 1 IFNs result in anemia and embryonic lethality; therefore, the gene for the type 1 IFN receptor (IFNaR) has also been deleted so that the mice survive. DNase II-/- IFNaR-/- double knockout (DKO) mice develop erosive inflammatory arthritis, anti-nuclear antibodies, and splenomegaly not seen in the DNase II+/- IFNaR-/- (Het) control group. To evaluate whether cytosolic or endosomal DNA sensors contribute to the clinical manifestations of DKO mice, genes involved in TLR or cytosolic sensor signaling were deleted on the DKO background. Genetically altered mice include STING/DNaseII/IFNaR TKO (STING TKO), AIM2/DNase II/IFNaR TKO (AIM2 TKO), and Unc93b/DNase II/IFNaR TKO (Unc93 TKO) mice. Our hypothesis was that the STING, AIM2, and/or Unc93 pathways would contribute to the autoimmune manifestations in DNase II deficient mice. Rigorous examination of inflammation in these lines revealed important roles for both the STING and AIM2 pathways in arthritis. Despite the substantial effects of the STING and AIM2 pathways on arthritis, STING TKO and AIM2 TKO mice still exhibited prominent autoantibody production. Interestingly, inflammation persisted in Unc93 TKO mice while autoantibody production to nucleic acids was abrogated. Collectively, these data indicate that innate immune pathways contribute to the initiation/perpetuation of inflammatory arthritis and demonstrate that cytosolic and endosomal pathways play distinct roles in the manifestations of autoimmunity. Moreover, they reveal a previously undescribed role for AIM2 as a sensor of endogenous nucleic acids in inflammatory arthritis. Thus, therapeutics that target the STING and AIM2 pathways may be beneficial for the treatment of inflammatory joint diseases. While the role of hematopoietic cells in driving autoimmunity has been well established, the contribution of stromal elements to disease pathogenesis is less well understood. Therefore, we generated bone marrow chimeras to delineate the contribution of hematopoietic and non-hematopoietic cells to the various autoimmune manifestations in DKO mice. These studies revealed that both donor hematopoietic and host radioresistant cells are required for inflammation in the joint as well as for other features of autoimmunity in DKO mice, including splenomegaly, extramedullary hematopoiesis, and autoantibody production. This data demonstrates that stromal host cells play a major role in DNA-driven autoimmunity. Moreover, these results suggest that targeting not only hematopoietic but also stromal elements may be advantageous in the setting of inflammatory arthritis. In the final chapter of this thesis, a role for innate immune sensor pathways in bone is described. The majority of inflammatory arthritides have been shown to lead to systemic loss of bone. Surprisingly, however, we found that DKO mice accumulate trabecular bone in the long bones over time as well as ectopic bone in the spleens, both sites of robust DNA accrual. Moreover, deficiency of the STING pathway abrogated this bone accumulation. Collectively, these data demonstrate that DNA accrual promotes dysregulated bone remodeling through innate immune sensing pathways. These findings are the first to reveal a role for the STING pathway in bone and may unveil novel targets for the treatment of diseases associated with bone disorders.

No description available.

Investigar a eficácia da lama negra brasileira como tratamento para inflamação em modelos experimentais de artrite. O efeito antiinflamatório de aplicações de lama foi comparado ao tratamento com água aquecida e ausência de tratamento em modelos experimentais de artrite e osteoartrite induzidas em coelhos e em ratos, visando parâmetros inflamatórios e cartilagem. O tratamento com lama melhorou a infiltração de leucócitos e exerceu um efeito protetor parcial na sinóvia e cartilagem. Nossos resultados sugerem que a lama brasileira apresenta efeito antiinflamatório e pode ser útil como um método complementar ao tratamento de pacientes com doenças articulares crônicas / Investigate the effectiveness of a Brazilian black mud as treatment for inflammation in experimental models of arthritis. Effects of mud applications was compared with warm water and no treatment in experimental models of arthritis and osteoarthritis induced in rabbits and in rats, regarding inflammatory parameters and cartilage. Treatment with mud impaired leukocyte infiltration which was followed by a partial protective effect on synovium and cartilage. Our results show that Brazilian mud presents an anti-inflammatory effect and can be useful as a complementary approach to treat patients with chronicle articular diseases

Investigar a eficácia da lama negra brasileira como tratamento para inflamação em modelos experimentais de artrite. O efeito antiinflamatório de aplicações de lama foi comparado ao tratamento com água aquecida e ausência de tratamento em modelos experimentais de artrite e osteoartrite induzidas em coelhos e em ratos, visando parâmetros inflamatórios e cartilagem. O tratamento com lama melhorou a infiltração de leucócitos e exerceu um efeito protetor parcial na sinóvia e cartilagem. Nossos resultados sugerem que a lama brasileira apresenta efeito antiinflamatório e pode ser útil como um método complementar ao tratamento de pacientes com doenças articulares crônicas / Investigate the effectiveness of a Brazilian black mud as treatment for inflammation in experimental models of arthritis. Effects of mud applications was compared with warm water and no treatment in experimental models of arthritis and osteoarthritis induced in rabbits and in rats, regarding inflammatory parameters and cartilage. Treatment with mud impaired leukocyte infiltration which was followed by a partial protective effect on synovium and cartilage. Our results show that Brazilian mud presents an anti-inflammatory effect and can be useful as a complementary approach to treat patients with chronicle articular diseases

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 5 uppsatser.

Ngan, Kit Shan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 176-187). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

<p>The overall aim was to improve the knowledge and understanding of eating habits of older men with somatic diseases, and the men's perceptions about managing food-related habits, such as grocery shopping and cooking. A total of 67 men between 64 and 89 years of age were visited in their homes on two occasions with 1-2 weeks in between. The participants were diagnosed with one of the three diseases Parkinson’s disease, rheumatoid arthritis, or stroke. A food survey, with repeated 24-h recall, was used to assess food intake and meal patterns. Interviews with 18 participants were conducted with open-ended questions. The interviews were further analysed with a thematic framework approach.The findings showed that eating events were distributed over a 24-h period.Further, co-living men had a significantly larger number of eating events over the day (p=0.001). No differences in daily energy intake were observed between co-living and single-living men. Co-living men’s hot eating events were compared with those of single-living men more often cooked from fresh ingredients (p=0.001), including a greater mix of vegetables/roots (p=0.003).Thematic analysis revealed three different approaches to food-related activities(FRA), namely ‘Cooking as a pleasure’, describing joy in cooking; ‘Cooking as a need’, indicating no habits or skills in cooking; and ‘Food is served’, that is, being served meals by a partner. The men's approaches to FRA were affected in particular by gender-related roles, but also by changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence. Further adaptive strategies were used among the men in attempts to maintain continuity and independence in FRA. In conclusion, single-living older men, especially those with activity limitations, were identified as being a vulnerable group from a nutritional perspective. Further, health care efforts in promoting FRA should preferably be individualised with respect to the older man’s approach to these activities.</p>

The overall aim was to improve the knowledge and understanding of eating habits of older men with somatic diseases, and the men's perceptions about managing food-related habits, such as grocery shopping and cooking. A total of 67 men between 64 and 89 years of age were visited in their homes on two occasions with 1-2 weeks in between. The participants were diagnosed with one of the three diseases Parkinson’s disease, rheumatoid arthritis, or stroke. A food survey, with repeated 24-h recall, was used to assess food intake and meal patterns. Interviews with 18 participants were conducted with open-ended questions. The interviews were further analysed with a thematic framework approach.The findings showed that eating events were distributed over a 24-h period.Further, co-living men had a significantly larger number of eating events over the day (p=0.001). No differences in daily energy intake were observed between co-living and single-living men. Co-living men’s hot eating events were compared with those of single-living men more often cooked from fresh ingredients (p=0.001), including a greater mix of vegetables/roots (p=0.003).Thematic analysis revealed three different approaches to food-related activities(FRA), namely ‘Cooking as a pleasure’, describing joy in cooking; ‘Cooking as a need’, indicating no habits or skills in cooking; and ‘Food is served’, that is, being served meals by a partner. The men's approaches to FRA were affected in particular by gender-related roles, but also by changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence. Further adaptive strategies were used among the men in attempts to maintain continuity and independence in FRA. In conclusion, single-living older men, especially those with activity limitations, were identified as being a vulnerable group from a nutritional perspective. Further, health care efforts in promoting FRA should preferably be individualised with respect to the older man’s approach to these activities.

Thesis (Ph.D. in Biostatistics) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 53-56). Online version available via ProQuest Digital Dissertations.

Orientador: João Roberto Gonçalves / Banca: Miriam Ayko Nakane Matsumoto / Banca: Ary dos Santos Pinto / Resumo: Dois artigos foram redigidos e utilizados para a avaliação dos objetivos apresentados. Objetivo: Capítulo 1: Avaliar as alterações e estabilidade do espaço aéreo faringeano, das estruturas esqueléticas e dentárias após avanço e rotação antihorária do complexo maxilo-mandibular associado a próteses totais de ATM em pacientes portadores de artrite reumatóide. Capítulo 2: Avaliar as alterações das estruturas esqueléticas, dentárias e a estabilidade da técnica da condiloplastia, reposicionamento do disco articular e cirurgia ortognática como tratamento integral do paciente portador de osteocondroma condilar. Material e Método: Capítulo 1: Foram avaliadas telerradiografias laterais de dezessete pacientes (14 gên.feminino, 3 gên. masculino) portadores de artrite reumatóide, com 14 a 56 anos de idade (média de 25,4 anos) selecionados consecutivamente. Todos os pacientes foram submetidos ao avanço mandibular e reconstrução das ATMs com prótese total de ATM (TMJ Concepts); e cirurgia ortognática com rotação anti-horária do complexo maxilo-mandibular simultaneamente. A média de acompanhamento do pósoperatório em longo prazo foi de 27 meses após a cirurgia. As telerradiografias da amostra foram tomadas em 3 tempos (pré-operatório imediato-T1, pós-operatório imediato- T2 e pós-operatório em longo prazo- T3) e avaliadas por meio da análise cefalométrica. Capítulo 2: Foram analisadas telerradiografias laterais de quinze pacientes (12 gên.feminino, 3 gên. masculino), com 13 a 56 anos de idade (média de 32,3 anos), portadores de osteocondroma condilar ativo unilateral consecutivamente tratados. Os pacientes foram submetidos à condiloplastia, reposicionamento do disco articular e cirurgia ortognática simultânea. O acompanhamento pós-cirúrgico foi de 19 meses em média. As telerradiografias foram tomadas em três intervalos: pré-cirúrgico (T1)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Two scientific papers have been drafted and will be used for the evaluation of the goals presented. Objective: Chapter 1: Evaluate surgical changes and stability of the narrowest retroglossal airway space, dental and skeletal structures after rotation of maxillomandibular complex counter-clockwise and mandibular advancement associated with total joint TMJ prosthetics replacements in patients with rheumatoid arthritis. Chapter 2: Evaluate surgical changes and stability of conservative condylectomy and articular disc repositioning as the surgical management of patients with mandibular condylar osteochondroma. Material and Method: Chapter 1: Lateral cephalometric radiographs of seventeen patients (14 females, 3 males), with average age of 25.4 years (age 14- 56) selected consecutively with rheumatoid arthritis were evaluated. All patients underwent TMJ reconstruction and mandibular advancement with TMJ Concepts custom made total joint prostheses and maxillomandibular counter-clockwise rotation at the same operation. Average post surgical follow-up was 27 months. Each patient's lateral radiographs measurements were cephalometric evaluated immediate before surgery-T1, immediate post surgery-T2 and long-term-follow-up-T3. Chapter 2: Lateral cephalometric radiographs of fifteen patients (12 females and 3 males), average age of 32.3 years (range, 13 to 56 years), with unilateral active osteochondroma of the mandibular condyle were analyzed. All patients underwent conservative condylectomy, recontouring of the remaining condylar neck stump and articular disc repositioning and indicated orthognathic surgical procedures. Average post surgical follow-up was 19 months. Each patient's lateral cephalograms were traced, digitized and measured at 3 time intervals (presurgery-T1, immediate post surgery-T2 and long-term follow-up-T3). Results: Chapter 1: Immediate after surgery the oclusal plane angle... (Complete abstract click electronic access below) / Mestre