Rheumatoid arthritis (RA) is a systemic, inflammatory disease, which predominantly affects multiple joints. RA is characterized by swollen joints and peri-articular bone erosion. Conventional RA treatments have shown to reduce inflammation and slow down bone erosion, but repair of bone erosion is limited. Additionally, failure to repair for bone erosion in rheumatoid arthritis (RA) is caused by inadequate osteoblast-mediated bone formation resulting from focal inflammatory environment. Hence, there is immediate need to facilitate greater insight and develop a new therapeutic strategy to aid osteoblast -mediated repair of bone loss in RA. CKIP-1 is an intracellular inhibitor, that can negatively regulate osteoblast lineage cells differentiation and activity. CKIP-1 levels were found to be aberrantly over expressed in bone specimens from RA patients and arthritis mice, which was associated with reduced bone formation and increased disease severity. By genetic approach, overexpressed CKIP-1 in osteoblast exacerbated bone erosion and articular inflammation in CIA mice, whereas deficiency of CKIP-1 in osteoblast alleviates bone erosion in CIA mice. By pharmacological approach, RNA interference-based silencing of osteoblastic CKIP-1 led to bone formation-mediated reparative process at erosive site and reduced articular inflammation in arthritis induced mice. To extend above findings to a more relevant species that more closely resemble humans, we aimed to investigate the role of osteoblastic Casein kinase-2 interacting protein-1 (CKIP-1) in failure to repair bone erosion in non-human primate (NHP) arthritis model in this study. We found that CKIP-1 mRNA expression in osteoblasts of arthritic NHP was significantly suppressed by CKIP-1 siRNA treatment. Moreover, silencing of CKIP-1 in osteoblast of arthritis monkey improved clinical signs such as reduction in arthritis score, joint swelling and increase in body weight. Similarly, suppression of osteoblastic CKIP-1 resulted in better organized bony and articular structure with, fewer bone erosion sites as observed in x ray and micro CT images. Moreover, we found increase in bone mass, bone formation parameters such as BFR/BS and MAR and histological examination revealed attenuation of peri articular bone erosion and intraarticular inflammation in CKIP-1 siRNA treated arthritis monkeys. Taken together, these data strongly suggest that highly expressed osteoblastic CKIP-1 plays an important role in failure to repair articular bone erosion by inhibiting bone formation in RA. Targeting osteoblastic CKIP-1 could serve as a new therapeutic strategy by bone repair augmentation in RA.

No description available.

We examined the nutrient intake of women with rheumatoid arthritis (RA) before and after initiation of treatment with arthritis medication. Results of past (before taking arthritis medication) and present diets of RA subjects were compared to the past and present diets of the non-RA group. Subjects with RA were 19 women with a mean age of 65 ± 9 years who were diagnosed with RA and were receiving arthritis medication on a regular basis. The non-RA subjects were 19 women with a mean age of 57 ± 3 years who were apparently healthy and were not taking any prescription medication. Both groups were interviewed to determine past and present dietary nutrient intake by using the Health Habits and History food frequency questionnaire (FFQ) developed by the National Cancer Institute. Nutrient intake determined from 3-day dietary records and present diet FFQs were comparable. Total energy and fat in the past diets of the RA group were significantly higher (p<0.05) than the past diets of the non-RA group. Within each group there were significant reductions (p<0.05) between the past and present mean dietary intakes of total energy, fat and protein. There were no significant differences between the past and present micronutrient intakes between or within the two groups. However, the micronutrient content of the present diets of the RA group was lower in calcium, iron, thiamin and riboflavin than the non-RA group as measured by the number of subjects who had <67% of the RDA. There was a significant (p<0.05) decrease in the mean daily consumption of the meat, poultry, fish, eggs and bean group in both non-RA and RA groups. There was also a significant (p<0.05) decrease in the mean daily consumption of the fat, oil and sweets group among the RA subjects. RA subjects were taking an average of 3±1 arthritis medications. There were no significant correlations between the number of medications taken by the RA group and their dietary nutrient intake. However, the significant (p<0.05) decline in total energy intake by the RA group could possibly be due to medication side effects. Since present total energy intake was lower in both groups, these results could reflect the general decline in energy intake with advancing age. There were significant (p<0.05) differences between the past and present self-reported weights of the non-RA and RA groups showing a general reduction in weight over time in both groups. Mean body mass indexes (BMI) for RA subjects was higher than the non-RA subjects', possibly reflecting the lower activity level of the RA group. / Graduation date: 1996

Foram estimados custos diretos de diferentes opções de tratamento para artrite reumatóide com base em dados de eficácia obtidos por revisão de literatura. O modelo analítico de tomada de decisão para o tratamento e desfechos durante um período de 48 meses baseado no modelo de Markov foi fundamentado em protocolos clínicos recomendados pela Sociedade Brasileira de Reumatologia, com esquemas alternativos para cinco ciclos de tratamento durante o período de quatro anos. O paciente pode permanecer em algumas das etapas ou migrar entre elas, de acordo com a resposta à terapia. Foram analisados custos diretos (medicamentos, materiais médico-hospitalares e exames laboratoriais). As doses dos medicamentos e o monitoramento foram baseados no Consenso Brasileiro para o Diagnóstico e Tratamento da Artrite Reumatóide, considerando-se o peso médio do paciente de 70 kg. Na comparação entre o custo das cinco etapas de tratamento os resultados mostram que a etapa que usa o medicamento infliximabe tem um custo superior às outras, este causado pelo preço de aquisição do medicamento. O custo do monitoramento tem impacto nas etapas que utilizam os medicamentos com preço de aquisição menor. O ciclo com a menor razão custo/efetividade foi o 1 (respondedor ao MTX). Aquele que usa o biológico desde o início do tratamento é responsável pela maior razão de custo/efetividade. A variação do custo entre os outros ciclos não foi muito grande, mas todas devem ser consideradas quando da escolha do prescritor. Estes resultados se mostraram robustos com a análise de sensibilidade. / The costs of the different rheumatoid arthritis therapy options were estimated and they were compared by cos/efficacy reason, through the development of an analytical model for a 48-month period. For the calculation of these costs, it was developed an analytical decision model based on the Markov Analysis, where five different therapy stages were elaborated based on clinical protocols recommended by the Brazilian Society of Rheumatology, and then five therapy cycles, where patients may continue in some of those stages or shift between them according to the therapy response, for a time horizon of 4 years. Only direct costs with drugs, medical-hospital materials for drug administration and laboratory examinations required for the patient monitoring because of the use of some drugs, were comprised in the analyzed data. The doses of drugs and the monitoring were based on the Brazilian Consensus for the Diagnosis and Treatment of Rheumatoid Arthritis, considering the average patient weight of 70 kg. When comparing the cost of the five treatment stages, the results show that the stage in which the infleximabe drug is used has a cost higher than that of the other stages and that the impact is caused by the drug acquisition price. The monitoring cost impacts the stages that employ drugs with smaller acquisition price. The cost-effectiveness cycle was the number 1 (good response with MTX). When we use de biologic in the beginning, it is responsible for the higher cost-effectiveness reason. The cost variation between cycles 2, 3 and 4 was smaller, but they have to be considered for the decision maker. The sensitivity analysis confirm this results.

No description available.

Bibliography: leaves 172-185. / xii, 185 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the induction of heat shock protein (HSP) by some of the anti-inflammatory agents and antirheumatic agents used in the management of rheumatoid arthritis. Presents HSP induction in peripheral white blood cells cultured in vitro. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1995?

Copy of author's previously published article. / Bibliography: leaves 189-219. / ix, 219, [69] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Explores pathways by which therapeutic agents may affect the inflammatory reaction in rheumatoid arthritis and confirms and expands observation on anti-rheumatic agents that are capable of regulating the activity as well as the expression and production of a variety of inflammatory mediators related to tissue destruction in the inflamed joint. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1997

Foram estimados custos diretos de diferentes opções de tratamento para artrite reumatóide com base em dados de eficácia obtidos por revisão de literatura. O modelo analítico de tomada de decisão para o tratamento e desfechos durante um período de 48 meses baseado no modelo de Markov foi fundamentado em protocolos clínicos recomendados pela Sociedade Brasileira de Reumatologia, com esquemas alternativos para cinco ciclos de tratamento durante o período de quatro anos. O paciente pode permanecer em algumas das etapas ou migrar entre elas, de acordo com a resposta à terapia. Foram analisados custos diretos (medicamentos, materiais médico-hospitalares e exames laboratoriais). As doses dos medicamentos e o monitoramento foram baseados no Consenso Brasileiro para o Diagnóstico e Tratamento da Artrite Reumatóide, considerando-se o peso médio do paciente de 70 kg. Na comparação entre o custo das cinco etapas de tratamento os resultados mostram que a etapa que usa o medicamento infliximabe tem um custo superior às outras, este causado pelo preço de aquisição do medicamento. O custo do monitoramento tem impacto nas etapas que utilizam os medicamentos com preço de aquisição menor. O ciclo com a menor razão custo/efetividade foi o 1 (respondedor ao MTX). Aquele que usa o biológico desde o início do tratamento é responsável pela maior razão de custo/efetividade. A variação do custo entre os outros ciclos não foi muito grande, mas todas devem ser consideradas quando da escolha do prescritor. Estes resultados se mostraram robustos com a análise de sensibilidade. / The costs of the different rheumatoid arthritis therapy options were estimated and they were compared by cos/efficacy reason, through the development of an analytical model for a 48-month period. For the calculation of these costs, it was developed an analytical decision model based on the Markov Analysis, where five different therapy stages were elaborated based on clinical protocols recommended by the Brazilian Society of Rheumatology, and then five therapy cycles, where patients may continue in some of those stages or shift between them according to the therapy response, for a time horizon of 4 years. Only direct costs with drugs, medical-hospital materials for drug administration and laboratory examinations required for the patient monitoring because of the use of some drugs, were comprised in the analyzed data. The doses of drugs and the monitoring were based on the Brazilian Consensus for the Diagnosis and Treatment of Rheumatoid Arthritis, considering the average patient weight of 70 kg. When comparing the cost of the five treatment stages, the results show that the stage in which the infleximabe drug is used has a cost higher than that of the other stages and that the impact is caused by the drug acquisition price. The monitoring cost impacts the stages that employ drugs with smaller acquisition price. The cost-effectiveness cycle was the number 1 (good response with MTX). When we use de biologic in the beginning, it is responsible for the higher cost-effectiveness reason. The cost variation between cycles 2, 3 and 4 was smaller, but they have to be considered for the decision maker. The sensitivity analysis confirm this results.

Ketoprofen is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of ketoprofen can cause gastric irritation and adverse renal effects. Transdermal delivery of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug concentrations at the site of administration. The release of ketoprofen from proprietary gel products from three different countries was evaluated by comparing the in vitro release profiles. Twenty extemporaneously prepared ketoprofen gel formulations using Carbopol® polymers were manufactured. The effect of polymer, drug concentration, pH and solvent systems on the in vitro release of ketoprofen from these formulations were investigated. The gels were evaluated for drug content and pH. The release of the drug from all the formulations obeyed the Higuchi principle. Two static FDA approved diffusion cells, namely the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell, were compared by measuring the in vitro release rate of ketoprofen from all the gel formulations through a synthetic silicone membrane. High-performance liquid chromatography and ultraviolet spectrophotometric analytical techniques were both used for the analysis of ketoprofen. The validated methods were employed for the determination of ketoprofen in the sample solutions taken from the receptor fluid. Two of the three proprietary products registered under the same manufacturing license exhibited similar results whereas the third product differed significantly. Among the variables investigated, the vehicle pH and solvent composition were found have the most significant effect on the in vitro release of ketoprofen from Carbopol® polymers. The different grades of Carbopol® polymers showed statistically significantly different release kinetics with respect to lag time. When evaluating the proprietary products, both the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell were deemed adequate although higher profiles were generally obtained from the European Pharmacopoeia diffusion cells. Smoother diffusion profiles were obtained from samples analysed by high-performance liquid chromatography than by ultraviolet spectrophotometry in both diffusion cells. Sample solutions taken from Franz diffusion cells and analysed by ultraviolet spectrophotometry also produced smooth diffusion profiles. Erratic and higher diffusion profiles were observed with samples taken from the European Pharmacopoeia diffusion cell and analysed by ultraviolet spectrophotometry. The choice of diffusion cells and analytical procedure in product development must be weighed against the relatively poor reproducibility as observed with the European Pharmacopoeia diffusion cell.

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.