Submitted by Mariana De Almeida Lourenço (maalmeida1@terra.com.br) on 2019-01-29T12:04:26Z No. of bitstreams: 1 TESE_Mariana_Almeida_FINAL.pdf: 3376155 bytes, checksum: 3ab5bd7934378b17e0fc5c3b3bdc4cb9 (MD5) / Rejected by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br), reason: Prezada Mariana, O documento enviado para a coleção Campus Unesp Rio Claro foi recusado pelo(s) seguinte(s) motivo(s): - Ficha catalográfica: Note que abaixo do quadrado conta o Instituto errado. Está Biblioteca da Faculdade de Ciências Farmacêuticas, Araraquara. Necessário refazer no site e corrigir o campus. Agradecemos a compreensão e aguardamos o envio do novo arquivo. Atenciosamente, Biblioteca Campus Rio Claro Repositório Institucional UNESP https://repositorio.unesp.br on 2019-01-29T18:30:27Z (GMT) / Submitted by Mariana De Almeida Lourenço (maalmeida1@terra.com.br) on 2019-01-30T11:47:23Z No. of bitstreams: 1 TESE_Mariana_Almeida_Lourenco.pdf: 3376137 bytes, checksum: b295dd19c611a8e8c01700329ec22a7f (MD5) / Approved for entry into archive by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br) on 2019-01-30T12:50:36Z (GMT) No. of bitstreams: 1 lourenço_ma_dr_rcla.pdf: 3179228 bytes, checksum: 9affa4b46e866d3534005db21feb3961 (MD5) / Made available in DSpace on 2019-01-30T12:50:36Z (GMT). No. of bitstreams: 1 lourenço_ma_dr_rcla.pdf: 3179228 bytes, checksum: 9affa4b46e866d3534005db21feb3961 (MD5) Previous issue date: 2018-12-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A articulação do joelho é frequentemente acometida por sinovite em pacientes com artrite reumatoide (AR). Esse processo inflamatório provoca um reflexo de inibição muscular artrogênica e consequente diminuição de força nos extensores de joelho, além de dor, edema e prejuízos funcionais. A infiltração intra-articular (IIA) com hexacetonide de triancinolona (HT) tem se mostrado eficaz no controle do acometimento articular em pacientes com AR. O objetivo geral do presente estudo foi analisar os efeitos da infiltração intra-articular em mulheres com AR de HT ou solução salina em parâmetros como força muscular de extensores de joelho, dor, edema, funcionalidade e amplitude de movimento. Vinte e uma mulheres com AR foram randomizadas aleatoriamente para receber 3ml de HT (GI) ou de solução salina (GC) no joelho, com avaliações feitas em 4 momentos: imediatamente antes a IIA, após 2, 6 e 12 semanas. Foram aplicados questionários para funcionalidade (WOMAC, Lequesne, HAQ), escala visual analógica para dor ao repouso e ao movimento, circumetria, teste de força de extensores de joelho, biofotogrametria para amplitude de movimento e os testes físicos Timed Up And Go (TUG) e Teste de Sentar e Levantar. Na análise estatística foi realizado teste de normalidade de Shapiro-Wilk, Teste de Levene para homogeneidade dos grupos, análise de variância (ANOVA) mista com medidas repetidas para comparação intra e inter grupos, correlação de Pearson e regressão linear com significância de P< 0,05. Foi observado diminuição da dor ao repouso e ao movimento, redução do edema e melhora da funcionalidade no grupo que recebeu o medicamento, porém não houve diferença significativa entre os grupos com relação à força muscular e amplitude de movimento. O presente estudo mostrou que, embora não haja diferença na força muscular e amplitude de movimento, a eficácia da IIA com HT em joelho parece ser superior na melhora da dor, edema e funcionalidade quando comparada a solução salina em mulheres com AR. / The knee joint is often affected by synovitis in rheumatoid arthritis (RA) patients. This inflammatory process causes a reflex of arthrogenic muscle inhibition and consequent decrease of strength in the knee extensors, pain, swelling and functional impairment. Intra-articular infiltration (IIA) with triamcinolone hexacetonide (HT) has been shown to be effective in controlling joint involvement in RA patients. The general objective of the present study was to analyze the effects of intraarticular infiltration in RA women´s knee with HT or saline solution in parameters such as knee extensors muscle strength, pain, swelling, functionality and range of motion. Twenty-one RA women were randomly assigned to receive 3ml of TH (GI) or saline solution (GC) in the knee, with assessments made in 4 moments: immediately before the IIA, after 2, 6 and 12 weeks. Functional questionnaires (WOMAC, Lequesne, HAQ), visual analogue scale for pain, circummetry, knee extensor strength test, biophotogrammetry for range of motion and the physical test Timed Up And Go (TUG). Statistical analysis was performed using the Shapiro-Wilk normality test, Levene test for homogeneity of groups, mixed analysis of variance (ANOVA) with repeated measures for intra and inter group comparison, Pearson's correlation and linear regression with significance of P <0,05. Decreased pain at rest and movement, reduction of swelling and improvement of functionality in the group receiving the medication were observed, but there was no significant difference between the groups in relation to muscle strength and range of motion. The present study showed that, although there is no difference in muscle strength and range of motion, the effectiveness of IIA with HT in knee appears to be superior in improving joint inflammation and functionality when compared to saline solution in RA women.

<p>Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage damage and loss in the joints that affects approximately 27 million adults in the US. Tissue that is damaged by OA is a major health concern since cartilage tissue has a limited ability to self-repair due to the lack of vasculature in cartilage and low cell content. Tissue engineering efforts aim towards the development of cartilage repair strategies that mimic articular cartilage and are able to halt the progression of the disease as well as restore cartilage to its normal function.</p><p>This study harnesses the biological activity of collagen type II, present in articular cartilage, and the superior mechanical properties of collagen type I by characterizing gels made of collagen type I and II blends (1:0, 3:1, 1:1, 1:3, and 0:1). The collagen blend hydrogels were able to incorporate both types of collagen and retain chondroitin sulfate (CS) and hyaluronic acid (HA). Cryoscanning electron microscopy images showed that the 3:1 ratio of collagen type I to type II gels had a lower void space percentage (36.4%) than the 1:1 gels (46.5%) and the complex modulus was larger for the 3:1 gels (G*=5.0 Pa) compared to the 1:1 gels (G*=1.2 Pa). The 3:1 blend consistently formed gels with superior mechanical properties compared to the other blends and has the potential to be implemented as a scaffold for articular cartilage engineering.</p> <p>Following the work done to characterize the collagen scaffolds, we studied whether an aggrecan mimic, CS-GAHb, composed of CS and HA binding peptides, GAH, and not its separate components, is able to prevent glycosaminoglycan (GAG) and collagen release when incorporated into chondrocyte-embedded collagen gels. Bovine chondrocytes were cultured and embedded in collagen type I scaffolds with CS, GAH, CS and GAH, or CS-GAHb molecules. Gels composed of 3:1 collagen type I and II with CS or CS-GAHb were also studied. The results obtained showed CS-GAHb is able to decrease GAG and collagen release and increase GAG retention in the gels. CS-GAHb also stimulated cytokine production during the initial days of scaffold culture. However, the addition of CS-GAHb into the chondrocyte-embedded collagen scaffolds did not affect ECM protein expression in the gels. The incorporation of collagen type II into the collagen type I scaffolds did not significantly affect GAG and cytokine production and ECM protein synthesis, but did increase collagen release. The results suggest the complex interaction between CS-GAHb, the chondrocytes, and the gel matrix make these scaffolds promising constructs for articular cartilage repair.</p> <p>Finally, we used Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, to determine if high frequency ultrasound can ensure intra-articular injections of the aggrecan mimic are accurately positioned in the knee joint. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. We assessed our ability to visualize important anatomical landmarks, the needle, and anatomical changes due to the injection. From the ultrasound images, we were able to visualize clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. The results demonstrate this image-guided technique can be used to visualize the location of an intra-articular injection in the joints of guinea pigs and we are able to effectively inject the aggrecan mimic into knee joints.</p><p>All of the work presented here suggests that the addition of the aggrecan mimic to collagen I and collagen I and II scaffolds has shown that this type of construct could be useful for treating cartilage damage in the future.</p>