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;

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Considerando que o colágeno tipo V (Col V) pode ser exposto em processos de remodelamento tecidual, gerando autoimunidade em diversas patologias, postulamos que a administração oral de Col V possa modular a inflamação e remodelamento da sinovite articular experimental, evitando a destruição articular. Neste estudo a artrite foi induzida em ratos Lewis, machos com aproximadamente 250g, por injeção intra-articular de 500 ug de albumina de soro bovino metilada (mBSA) emulsificada em adjuvante de Freund completo (ACF) (10 ul), seguido por reforços intra-articulares de mBSA (500 ug) em solução salina (50 ul), após 7 e 14 dias da primeira injeção (grupo com artrite induzida; AI). Animais sem indução de artrite receberam solução salina (50 ml) por via intra-articular (grupo controle; CT). Após a primeira injeção de mBSA/ACF, a suplementação de Col V bovino (300ul/500ug) foi administrada por via oral nos animais com AI, durante 15 e 30 (AI-ColV15, n=10; AI-ColV30, n=10 ) dias e nos animais CT por 30 (CT-ColV30, n=10) dias. Nossos dados demonstraram que após 15 e 30 dias, a administração oral de Col V levou à diminuição do edema e infiltrado inflamatório severo, conteúdo total de fibras de colágeno, colágeno tipo I, subpopulação de linfócitos, macrófagos, IL-1beta, IL-10 e metaloproteinase 2 no tecido sinovial, e redução IL-1beta, TNFalfa, IL-17 e IL-10 no soro. Ocorreu maior expressão de caspase 9 no tecido sinovial dos animais que receberam o Col V. Pode-se concluir que a suplementação com Col V bovino reduziu a inflamação sinovial e resposta fibrótica independentemente do tempo, possivelmente por aumento da apoptose das células inflamatórias / Whereas type V collagen (Col V) can be exposed in tissue remodeling process, leading to autoimmunity in various pathologies, we postulate that the oral administration Col V can modulate inflammation and remodeling of joint experimental synovitis, preventing joint destruction. In this study, arthritis was induced in Lewis male rats of approximately 250g, by intra-articular injection of 500 ?g serum albumin methylated from bovine serum (mBSA) (500 ug) emulsified in complete Freund\'s adjuvant (CFA) (10 ul), followed by stiffeners intraarticular of mBSA (500 ug) in saline (50 ul) after 7 and 14 days from the first injection (group induced arthritis; AI). Animals received no arthritis induction brine (50 ul) by intraarticular (control group; CT). After the first injection of mBSA / CFA supplementation Col V bovine (300ul / 500ug) was administered orally in animals with AI for 15 and 30 (AI-ColV15, n = 10, I-ColV30, n = 10) days and animals CT per 30 (CT-ColV30, n = 10) days. Our data showed that after 15 and 30 days, oral administration of Col V led to the reduction of edema and severe inflammatory infiltrate, total content of collagen fibers, collagen type I, subpopulation of lymphocytes, macrophages, IL-1beta, IL-10 and metalloproteinase 2 in synovial tissue and reduced the IL-1beta, TNFalfa, and IL-17 IL-10 serum. There increased expression of caspase-9 in the synovial tissue of animals receiving Col V. It can be concluded that supplementation with bovine Col V reduced synovial inflammation and fibrotic response regardless of time, possibly by increased apoptosis of inflammatory cells

Considerando que o colágeno tipo V (Col V) pode ser exposto em processos de remodelamento tecidual, gerando autoimunidade em diversas patologias, postulamos que a administração oral de Col V possa modular a inflamação e remodelamento da sinovite articular experimental, evitando a destruição articular. Neste estudo a artrite foi induzida em ratos Lewis, machos com aproximadamente 250g, por injeção intra-articular de 500 ug de albumina de soro bovino metilada (mBSA) emulsificada em adjuvante de Freund completo (ACF) (10 ul), seguido por reforços intra-articulares de mBSA (500 ug) em solução salina (50 ul), após 7 e 14 dias da primeira injeção (grupo com artrite induzida; AI). Animais sem indução de artrite receberam solução salina (50 ml) por via intra-articular (grupo controle; CT). Após a primeira injeção de mBSA/ACF, a suplementação de Col V bovino (300ul/500ug) foi administrada por via oral nos animais com AI, durante 15 e 30 (AI-ColV15, n=10; AI-ColV30, n=10 ) dias e nos animais CT por 30 (CT-ColV30, n=10) dias. Nossos dados demonstraram que após 15 e 30 dias, a administração oral de Col V levou à diminuição do edema e infiltrado inflamatório severo, conteúdo total de fibras de colágeno, colágeno tipo I, subpopulação de linfócitos, macrófagos, IL-1beta, IL-10 e metaloproteinase 2 no tecido sinovial, e redução IL-1beta, TNFalfa, IL-17 e IL-10 no soro. Ocorreu maior expressão de caspase 9 no tecido sinovial dos animais que receberam o Col V. Pode-se concluir que a suplementação com Col V bovino reduziu a inflamação sinovial e resposta fibrótica independentemente do tempo, possivelmente por aumento da apoptose das células inflamatórias / Whereas type V collagen (Col V) can be exposed in tissue remodeling process, leading to autoimmunity in various pathologies, we postulate that the oral administration Col V can modulate inflammation and remodeling of joint experimental synovitis, preventing joint destruction. In this study, arthritis was induced in Lewis male rats of approximately 250g, by intra-articular injection of 500 ?g serum albumin methylated from bovine serum (mBSA) (500 ug) emulsified in complete Freund\'s adjuvant (CFA) (10 ul), followed by stiffeners intraarticular of mBSA (500 ug) in saline (50 ul) after 7 and 14 days from the first injection (group induced arthritis; AI). Animals received no arthritis induction brine (50 ul) by intraarticular (control group; CT). After the first injection of mBSA / CFA supplementation Col V bovine (300ul / 500ug) was administered orally in animals with AI for 15 and 30 (AI-ColV15, n = 10, I-ColV30, n = 10) days and animals CT per 30 (CT-ColV30, n = 10) days. Our data showed that after 15 and 30 days, oral administration of Col V led to the reduction of edema and severe inflammatory infiltrate, total content of collagen fibers, collagen type I, subpopulation of lymphocytes, macrophages, IL-1beta, IL-10 and metalloproteinase 2 in synovial tissue and reduced the IL-1beta, TNFalfa, and IL-17 IL-10 serum. There increased expression of caspase-9 in the synovial tissue of animals receiving Col V. It can be concluded that supplementation with bovine Col V reduced synovial inflammation and fibrotic response regardless of time, possibly by increased apoptosis of inflammatory cells

Wong Hei Lui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 192-226). / Abstracts in English and Chinese. / Publications Based On The Work In This Thesis --- p.i / Abstract --- p.ii / Acknowledgements --- p.vii / Abbreviations --- p.viii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Normal joint --- p.1 / Chapter 1.11 --- Biology of joint --- p.1 / Chapter 1.12 --- Structure of synovial joint --- p.1 / Chapter 1.13 --- Components of the mature synovial joint --- p.3 / Chapter 1.131 --- Articular cartilage --- p.3 / Chapter 1.1311 --- Water --- p.4 / Chapter 1.1312 --- Cartilage matrix --- p.4 / Chapter 1.1313 --- Chondrocyte --- p.5 / Chapter 1.132 --- Synovium --- p.5 / Chapter 1.1321 --- Synovium vasculature --- p.6 / Chapter 1.1322 --- Synovial blood flow --- p.7 / Chapter 1.133 --- Synovial fluid --- p.8 / Chapter 1.134 --- Bone --- p.9 / Chapter 1.2 --- Pathological processes of arthritis --- p.11 / Chapter 1.21 --- Activation of immune cells in arthritis --- p.11 / Chapter 1.22 --- Synovial proliferation --- p.13 / Chapter 1.221 --- Synovial lining cell activation --- p.13 / Chapter 1.222 --- Pannus invasion --- p.14 / Chapter 1.23 --- Cartilage and bone degradation --- p.14 / Chapter 1.231 --- Depletion of proteoglycan (GAG) --- p.15 / Chapter 1.232 --- Collagen denature --- p.15 / Chapter 1.3 --- Tachykinins (TKs) --- p.17 / Chapter 1.31 --- History --- p.17 / Chapter 1.32 --- "Synthesis, storage and release of TKs" --- p.17 / Chapter 1.33 --- Tachykinin receptors --- p.18 / Chapter 1.331 --- Characterization of NK1 receptor --- p.19 / Chapter 1.332 --- Characterization of NK2 receptor --- p.19 / Chapter 1.333 --- Characterization of NK3 receptor --- p.20 / Chapter 1.34 --- Effector systems of TKs --- p.21 / Chapter 1.35 --- Termination of TK signals --- p.21 / Chapter 1.351 --- Enzymatic breakdown --- p.21 / Chapter 1.352 --- Receptor desensitization --- p.22 / Chapter 1.353 --- Receptor endocytosis --- p.22 / Chapter 1.36 --- TK receptor antagonists --- p.23 / Chapter 1.361 --- Selective NK1 receptor antagonists --- p.23 / Chapter 1.362 --- Selective NK2 receptor antagonists --- p.24 / Chapter 1.363 --- Selective NK3 receptor antagonists --- p.25 / Chapter 1.4 --- Roles of tachykinins in arthritis --- p.28 / Chapter 1.41 --- Correlation between tachykinins and joint inflammation --- p.28 / Chapter 1.42 --- Roles of tachykinins in immune cell activation --- p.30 / Chapter 1.43 --- Roles of tachykinins in synovial proliferation --- p.31 / Chapter 1.44 --- Roles of tachykinins in cartilage degradation --- p.32 / Chapter 1.5 --- Animal model of arthritis --- p.33 / Chapter 1.51 --- Instability model --- p.33 / Chapter 1.52 --- Immobilization model --- p.34 / Chapter 1.53 --- Noxious agent-induced model --- p.34 / Chapter 1.531 --- Collagen-induced erosive arthritis --- p.34 / Chapter 1.532 --- Cartilage oligometric matrix protein-induced arthritis --- p.35 / Chapter 1.533 --- Oil-induced arthritis --- p.35 / Chapter 1.534 --- Streptococcal cell wall-induced arthritis --- p.35 / Chapter 1.535 --- Adjuvant-induced arthritis --- p.36 / Chapter 1.536 --- Pristane-induced arthritis --- p.36 / Chapter 1.6 --- Current anti-arthritic therapies --- p.39 / Chapter 1.61 --- Non steroid anti-inflammatory drugs --- p.39 / Chapter 1.62 --- Glucocorticoid --- p.44 / Chapter 1.63 --- Second-line treatment --- p.46 / Chapter 1.631 --- Sulfasalazine --- p.46 / Chapter 1.632 --- Gold salts --- p.47 / Chapter 1 633 --- D-penicillamine --- p.48 / Chapter 1.634 --- Antimalarial --- p.49 / Chapter 1 .635 --- Methotrexate --- p.51 / Chapter 1.64 --- New trends for treatment of arthritis --- p.53 / Chapter 1.641 --- Anti-cytokine therapy --- p.53 / Chapter 1.642 --- Anti-angiogenesis therapy --- p.54 / Chapter 1.7 --- Aims of study --- p.57 / Chapter Chapter 2 --- Material and drugs --- p.62 / Chapter Chapter 3 --- Methodology --- p.62 / Chapter 3.1 --- Animals used and anaesthetization --- p.62 / Chapter 3.2 --- Measurement of plasma protein extravasation --- p.63 / Chapter 3.3 --- Measurement of knee joint sizes --- p.64 / Chapter 3.4 --- Measurement of knee joint blood flow --- p.65 / Chapter 3.5 --- Measurement of histological changes --- p.65 / Chapter 3.51 --- Dissection and fixation --- p.65 / Chapter 3.52 --- Decalcification --- p.66 / Chapter 3.53 --- Processing --- p.66 / Chapter 3.54 --- Embedding --- p.67 / Chapter 3.55 --- Sectioning --- p.67 / Chapter 3.56 --- Staining --- p.69 / Chapter 3.6 --- Data analysis --- p.69 / Chapter 3.61 --- Scoring systems --- p.72 / Chapter Chapter 4 --- A model of monoarthritis in rats --- p.72 / Chapter 4.1 --- Introduction --- p.72 / Chapter 4.2 --- Method --- p.73 / Chapter 4.3 --- Results --- p.73 / Chapter 4.31 --- Lewis rats --- p.73 / Chapter 4.32 --- Sprague-Dawley (SD) rats --- p.74 / Chapter 4.33 --- Comparison of FCA-induced changes in Lewis and SD rats --- p.74 / Chapter 4.34 --- Histological studies on arthritic SD rats --- p.75 / Chapter 4.4 --- Discussion --- p.93 / Chapter 4.5 --- Conclusions --- p.95 / Chapter Chapter 5 --- Effect of Substance P on adjuvant-induced arthritis --- p.96 / Chapter 5.1 --- Introduction --- p.96 / Chapter 5.2 --- Method --- p.98 / Chapter 5.3 --- Results --- p.99 / Chapter 5.31 --- Evans blue extravasation --- p.99 / Chapter 5.32 --- Joint size --- p.100 / Chapter 5.33 --- Knee joint blood flow --- p.101 / Chapter 5.34 --- Histology results --- p.102 / Chapter 5.341 --- Infiltration of immune cells in synovial tissue --- p.102 / Chapter 5.342 --- Synovial tissue proliferation --- p.102 / Chapter 5.343 --- Cartilage degradation --- p.103 / Chapter 5.344 --- Bone degradation --- p.103 / Chapter 5.4 --- Discussion --- p.120 / Chapter 5.5 --- Conclusions --- p.125 / Chapter Chapter 6 --- Effects of tachykinin receptor antagonists on FCA-induced arthritis / Chapter 6.1 --- Introduction --- p.126 / Chapter 6.2 --- Method --- p.128 / Chapter 6. 21 --- Intravenous NK1 receptor antagonists on FCA-induced arthritis --- p.128 / Chapter 6. 22 --- Intraperitoneal TK receptor antagonists on FCA-induced arthritis --- p.128 / Chapter 6.3 --- Results --- p.129 / Chapter 6.31 --- Intravenous NK1 227}0اreceptor antagonists on FCA-induced arthritis Evans blue extravasation and joint swelling --- p.129 / Chapter 6.32 --- Intraperitoneal tachykinin receptor antagonists on FCA- induced arthritis Evans blue extravasation and joint swelling --- p.129 / Chapter 6.33 --- Intraperitoneal tachykinin receptor antagonists on FCA- induced immune cell accumulation --- p.130 / Chapter 6.34 --- Intraperitoneal tachykinin receptor antagonists on FCA- induced synovial tissue proliferation --- p.131 / Chapter 6.35 --- Intraperitoneal tachykinin receptor antagonists on FCA- induced cartilage degration and bone erosion --- p.131 / Chapter 6.4 --- Discussion --- p.159 / Chapter 6.5 --- Conclusions --- p.162 / Chapter Chapter 7 --- Individual and combined effects of dexamethasone and TK receptor antagonists on FCA-induced arthritis --- p.163 / Chapter 7.1 --- Introduction --- p.163 / Chapter 7.2 --- Method --- p.166 / Chapter 7.3 --- Results --- p.167 / Chapter 7.31 --- Evans blue extravasation --- p.167 / Chapter 7.32 --- Knee joint size --- p.167 / Chapter 7.33 --- Body weight --- p.168 / Chapter 7.34 --- Cellular infiltration --- p.168 / Chapter 7.35 --- Synovial tissue proliferation --- p.168 / Chapter 7.36 --- Cartilage degradation --- p.169 / Chapter 7.4 --- Discussion --- p.184 / Chapter 7.5 --- Conclusions --- p.187 / Chapter Chapter 8 --- General discussions and conclusions --- p.188 / References --- p.192