En France, plus d’une personne sur dix souffre d’arthrose où le compartiment médial de l’articulation du genou demeure largement affecté. Afin de lutter contre ce fléau qui occasionne des dépenses croissantes dans notre système de santé, l’intégration de traitements non-pharmacologiques et conservateurs dans la prise en charge de cette pathologie est une priorité. De ce fait, les orthèses de décharge pourraient tout à fait répondre à cette nécessité. Malheureusement, au fil des rares prescriptions, force est de constater l’abandon trop rapide de ce type d’appareillage. Majoritairement conçues pour exercer une action mécanique à trois points de pression, les orthèses de décharge sont davantage reconnues pour leur inconfort que pour leurs effets bénéfiques. Etre assis, se tenir debout ou simplement marcher sont autant de situations selon lesquelles l’appareillage devrait être en mesure de s’adapter. Pour autant, les orthèses de décharge exercent, à tort, une seule et même action mécanique continue. Cette dernière est identifiée comme responsable de leur inconfort. Fort de ce constat, ce travail de thèse se penche sur une piste jusqu’alors inexplorée, une action mécanique variable des orthèses de décharge à trois points de pression, garante d’un confort accru dans le but d’améliorer l’alliance thérapeutique. Sur la base de cette idée brevetée, nous verrons à travers ce travail les différentes étapes de validation qui permettent de caractériser un appareillage dynamique, avantageusement comparé aux modèles jusqu’alors proposés. / In France, more than one person out of ten suffers from osteoarthritis, which particularly affects the medial compartment of the knee joint. In order to overcome this issue, which causes increased expenditure in the healthcare system, the integration of non-pharmacological and conservative treatments for the management of this pathology is a priority. As a result, unloader knee braces could fully meet this need. However, few prescriptions and a poor long-term compliance are frequently reported. Usually designed to exert a mechanical action with three-point pressure, unloader knee braces are better known for causing discomfort rather than leading to beneficial effects. Indeed, these braces exert erroneously a continuous mechanical action, which has been identified as responsible for the discomfort. To counteract this problem, equipment should be able to adapt between situations as sitting, standing or walking. Therefore, this thesis focuses on a changeable mechanical action of three-point pressure orthoses, ensuring greater comfort and potentially resulting in improved compliance. According to this idea, this work explores the different stages of validation, which allow to characterize a dynamic unloader knee brace and describe its advantages over the traditional proposed models.

Osteoarthritis is a chronic degenerative joint disease that affects the whole joint, including the articulating surfaces and capsular tissues in and around the joint (Hügle and Geurts 2016). Osteoarthritis currently impacts 27 million Americans (Racine 2015). Two prominent features in osteoarthritis that are correlated with greater pain and reduced function are MRI-identified bone marrow lesions and CT-identified subchondral bone cysts (Kumar et al. 2013). At this time, the relationship between bone marrow lesions and subchondral bone cysts has not been confirmed. Nor has the nature of the tissues associated with these clinical signs been fully characterized, pointing to the need for further research to identify the composition of subchondral bone cysts as these cysts could be a potential target for therapeutic intervention. This study focused on characterizing the tissue content of subchondral bone cysts in osteoarthritic femoral heads. Osteoarthritic femoral heads were collected from male and female patients, ranging in age from 43-72 years old, who underwent total hip replacement. After surgery, the femoral heads were fixed in 4% paraformaldehyde and scanned via micro-computed tomography (MicroCT). The MicroCT images were used to identify regions in each head containing large subchondral bone cysts, the primary compressive bone, and anterior cartilage. These regions were mapped to the actual femoral head and guided the dissection of the femoral head. Samples from each of the regions were decalcified, embedded in paraffin, and cut into 5-micron-thick histological sections which were then mounted onto slides. Each section was stained in Safranin-O/Fast green and hematoxylin and eosin to visualize the tissues present. Immunohistochemistry with anti-CD31 was carried out on selected slides to identify blood vessels. The samples within all three regions of the femoral head were graded histologically for the presence of subchondral bone cysts, whether cartilage was within the cyst region, if the histological section matched its corresponding MicroCT image, if the articular cartilage was fibrillated, the presence of sclerotic bone, the presence of osteophytes, and the presence of blood vessels. It was clear that many of these samples were in later stages of osteoarthritis considering most samples exhibited all of the above characteristics, contained fibrous tissue, and had little normal fatty marrow. Typically, subchondral bone cysts presented beneath fibrillated and degenerated articular cartilage, contained fibrous tissue that was much more intensely vascularized and innervated as compared to normal fatty marrow, and was surrounded by sclerotic trabecular bone. In some cases, osteophytes also formed at the articular surface beneath areas of degenerated cartilage. Some subchondral bone cysts contained cartilage and even smooth muscle cells in addition to fibrous connective tissue. The varied location of the subchondral bone cysts shows the need for further research as to how their etiologies develop. The content of the subchondral bone cysts suggests that areas with disrupted trabeculae become intensely vascularized to allow the influx of inflammatory materials and mesenchymal stem cells to lay down fibrous tissue and thicken the surrounding trabeculae to stabilize the weakened microstructure of the femoral head. By gaining a comprehensive understanding of the pathology of osteoarthritis and of subchondral bone cysts in particular, the progression of the disease can be more firmly established and potential new treatments can be developed.

Osteoarthritis (OA) is the most common degenerative joint disease, affecting primarily the hip, knee, and hand (Ip 2005). OA of the knee and hip is the 11th highest contributor to global disability (Cross et al. 2014). Hip OA is diagnosed using radiographs, computed tomography (CT), and/or magnetic resonance imaging (MRI). Hip OA affects the whole hip joint, causing pain and reduced range of motion (Altman et al. 1991). The cause of pain in OA is not well understood, but it may be attributed to abnormal growth of blood vessels and nerves in the subchondral bone of the femoral head (Kumar et al. 2013). Quantifying blood vessels and nerves and correlating their presence with diagnostic techniques such as MRI will establish a relationship between femoral head degeneration and pain levels and current diagnostic signs. The aims of this study were: (1) to develop a reproducible histological technique to identify blood vessels and nerves in bone sections; and (2) to apply this protocol to identify blood vessel and nerve characteristics within osteoarthritic femoral heads. Femoral heads were retrieved from 8 OA patients (age range: 40-76; 5 female and 3 male) undergoing total hip replacement surgery. Each sample was evaluated for the presence of subchondral bone cysts using micro-computed tomography (µCT), then regions containing cysts were isolated and dissected for histological processing. Different fixation times in paraformaldehyde (PFA) were tested in three samples to assess the effect of fixation time on binding of the primary antibody to the target. Samples were stained with hematoxylin and eosin to evaluate overall tissue morphology, safarin-O and fast green to visualize the integrity of articular cartilage, anti-CD31 to identify vascular endothelium, and anti-PGP 9.5 to identify peripheral nerve fibers. A protocol was successfully developed to identify CD31-positive blood vessels and PGP 9.5-positive nerves in osteoarthritic femoral heads. The immunohistochemistry protocols for staining with anti-CD31 and anti-PGP 9.5 were optimized for maximum intensity of target staining, minimal background staining, and minimal artefactual tissue folding. Fixation time in PFA was not found to have an effect on quality of staining with anti-CD31. Blood vessels were found in all eight of the samples collected, and peripheral nerves were found in five of the samples. Special attention was paid to regions with fibrous subchondral bone cysts, because these are the most likely type to undergo neurovascular invasion. Out of the five samples with fibrous subchondral bone cysts, blood vessels were identified in all five cyst regions, and peripheral nerves were identified in three cyst regions. Using the protocols developed in this study, blood vessels and nerves were found in osteoarthritic femoral heads. In future, a larger sample set will be used to correlate the nature of blood vessel density and nerves that are found in bone marrow lesions identified on MRI scans obtained before surgery and are associated with bone cysts. This is an important step towards identifying more effective treatments for OA that address the specific underlying causes and the development of non-treatable pain.

A hallmark of the joint disease osteoarthritis (OA) is the degradation of the articular cartilage in the affected joint, debilitating pain and decreased mobility. At present there are no disease modifying drugs for treatment of osteoarthritis. This represents a significant, unmet medical need as there is a large and increasing prevalence of OA. Using a systems biology approach, we aimed to better understand the pathogenic mechanisms of OA and ultimately aid development of therapeutics. This thesis focuses on the analysis of gene expression data from human OA cartilage obtained at total knee replacement (TKR). This transcriptomics approach gives a genome-wide overview of changes, but can be challenging to interpret. Network-based algorithms provide a framework for the fusion of knowledge so allowing effective interpretation. The PhenomeExpress algorithm was developed as part of this thesis to aid the interpretation of gene expression data. PhenomeExpress uses known disease gene associations to identify relevant dysregulated pathways in the data. PhenomeExpress was further developed into an 'app' for Cytoscape, the widely used network analysis and visualisation platform. To investigate the processes that occur during the degradation of cartilage we examined the gene expression of damaged and intact OA cartilage using RNA-Seq and identified key altered pathways with PhenomeExpress. A regulatory network driven by four transcription factors accounts for a significant proportion of the observed differential expression of damage-associated genes in the PhenomeExpress identified pathways. We further explored the role of the cytokines IL-1 and TNF that have been reported to β drive the progression of OA. Comparison of the expression response of in vitro cytokine-treated explants with the in vivo damage response revealed major differences, providing little evidence for any significant role of IL-1 and TNF as drivers of OA β damage in vivo. Finally, we examined the heterogeneity of OA through analysis of cartilage expression profiles at TKR. Through a network-based clustering method, we found two subgroups of patients on the basis of their gene expression profiles. These subgroups were found to have distinct OA expression perturbations and we identified TGF and S100A8/9 β signalling as potentially explaining the observed differential expression. We developeda RT-qPCR based classifier that allowed classification of new samples into these subgroups so allowing future assessment of the clinical significance of these subgroups. The work presented in this thesis includes a novel, widely-accessible tool for the analysis of disease gene expression data, which we used to give new insights into the pathogenesis of osteoarthritis. We have produced a rich dataset for future research and our analysis of this data has increased our understanding of cartilage damage processes and the heterogeneity of OA.

In total, four experiments were conducted to determine the therapeutic and safety effects of the nutraceutical, turmeric and its active ingredient curcumin on canine and equine. Two studies were conducted on client-owned, moderately arthritic canines, studying the therapeutic and safety effect of curcumin’s anti-inflammatory properties. In Exp. 1, two different dosages, 500 mg, SID of 95% curcumin and 250 mg, BID of 95% liposomal-curcumin, were evaluated in ten moderately arthritic dogs over five months. The dogs in the 95% curcumin group had an overall greater significance in pain reduction by Day 60. Exp. 2, was a follow-up experiment to Exp. 1. In Exp. 2, two different dosages, 500 mg, SID or 100 mg, SID of 95% curcumin, were evaluated in ten moderately arthritic dogs over five months. Findings showed that dogs in the 500 mg, SID group had an overall greater significance in pain reduction by Day 60. Experiment 3 and 4 were a two-part project looking at the anti-microbial and anti-inflammatory properties of turmeric, curcumin, and liposomal-curcumin in cecally-cannulated equine. Exp. 3, was a two-part in vitro study, the first part looked at the anti-microbial effects of turmeric, curcumin, and liposomal-curcumin in reducing opportunistic bacteria found in the equine hindgut, including Streptococcus bovis/equinus complex (SBEC) (P = 0.0056), E. coli K-12 (P = 0.5114), Escherichia coli general (P = 0.1083), Clostridium difficile (P < 0.001), and Clostridium perfringens (P = 0.2439). Treatment D, 95% liposomal-curcumin, numerically reduced the concentration of all five opportunistic strains, and was therefore selected for use in the follow-up in vitro experiment. The second in vitro studied the effects of four different dosages, 15 g, 20 g, 25g, and 30 g of 500 mg/g of 95% liposomal-curcumin at reducing the concentration of SBEC (P < 0.0001), E. coli K-12 (P = 0.0124), E.coli general (P = 0.032), C. difficile (P = 0.5608), and C. perfringens (P = 0.4214). In Exp. 4, 500 mg/g of 95% liposomal-curcumin at 15 g, 25 g, and 35 g, were tested in vivo for anti-inflammatory and anti-microbial therapeutic effects. In total, four experiments were conducted to determine the therapeutic and safety effects of the nutraceutical, turmeric, and its active ingredient curcumin on canines and equines. Two studies were conducted on client-owned, moderately arthritic canines, studying the therapeutic and safety effect of curcumin’s anti-inflammatory properties. In Exp. 1, two different dosages, 500 mg, SID of 95% curcumin and 250 mg, BID of 95% liposomal-curcumin, were evaluated in ten moderately arthritic dogs over five months. The dogs in the 95% curcumin group, overall, had a greater reduction in pain by Day 60. Exp. 2, was a follow-up experiment to Exp. 1. In Exp. 2, two different dosages, 500 mg, SID or 100 mg, SID of 95% curcumin, were evaluated in ten moderately arthritic dogs over five months. We observed that dogs in the 500 mg, SID group had an overall greater significance in pain reduction by Day 60. Experiment 3 and 4 were conducted as a two-part project looking at the antimicrobial and anti-inflammatory properties of turmeric, curcumin, and liposomal-curcumin. The purpose of these studies were to investigate both form and dose of turmeric and its active ingredient, curcumin, on reducing opportunistic bacteria found in the equine hindgut. The bacterial strains of interest included Streptococcus bovis/equinus complex (SBEC), Escherichia coli K-12, Escherichia coli general, Clostridium difficile, and Clostridium perfringens. Exp. 3, was a two-part in vitro study; the first part looked at the antimicrobial effects of turmeric, curcumin, and liposomal-curcumin (LIPC) on reducing opportunistic bacteria found in the equine hindgut, including SBEC (P = 0.006), E. coli K-12 (P = 0.50), E. coli general (P = 0.11), C. difficile (P < 0.0001), and C. perfringens (P = 0.24). The follow-up in vitro 24 h batch culture examined four different dosages (15 g, 20 g, 25 g, and 30 g) of 500 mg/g of LIPC, at reducing the concentration of opportunistic bacteria. These results were utilized to determine the dosing rate in vivo. Exp. 3, in vitro, evaluated the efficacy of antimicrobial and anti-inflammatory properties of LIPC dosed at 15, 20, 25, and 35 g. These results were utilized to determine the dosing rate in vivo. Exp. 4, in vivo, evaluated the efficacy of antimicrobial and anti-inflammatory properties of LIPC dosed at 15, 25, and 35 g compared to a control. In vivo, LIPC’s antimicrobial properties, at 15 g, significantly decreased (P = 0.02) SBEC compared to other treatments. In addition, C. perfringens tended (P = 0.12) to decrease as LIPC dose increased. Non-significant results in digestion, blood parameters, and range of motion suggest there were no adverse side effects from oral dosing increasing doses of curcumin. Valerate decreased (P = 0.005) linearly as LIPC dose increased. As LIPC dose increased, butyrate and iso-valerate decreased (P ≤ 0.03) linearly. However, acetate tended (P = 0.10) to increase linearly as the dose of LIPC increased. Treatment did not affect (P ≥ 0.19) any of the other individual VFAs measured, but increasing doses of LIPC tended (P = 0.10) to increase total VFA concentrations. Additionally, LIPC tended (P = 0.11) to increase total VFA concentrations when compared to control. In the future, further work should be conducted examining liposomal-curcumin’s antimicrobial properties in canine and anti-inflammatory properties in equine over a longer period of time

<b>Background:</b> Sport is an important form of physical activity and has been shown to have many health benefits. Cricket is a popular sport in the UK and internationally, but little is known about the short- and long-term health effects of a career in elite cricket. This thesis will describe the long-term physical and mental health of former elite cricketers compared to the general population, explore the association of cricket-related factors with their long-term musculoskeletal health, and evaluate the effect of elite fast bowling on the knee cartilage of current elite fast bowlers. <b>Methods:</b> A sample of male former elite English cricketers was recruited for a cross-sectional retrospective questionnaire study of the long-term health of former cricketers. Chronic conditions in the former cricketers were compared to a general population sample and cricket-related factors including playing position and injury were tested for their association with musculoskeletal outcomes. A sample of male and female current elite fast bowlers was recruited for a biomechanics and cross-sectional MRI study of their knee cartilage. The knee cartilage was compared between the bowlers' trailing leg versus the higher loaded leading leg, and was tested for associations with bowling kinematic and kinetic parameters. <b>Results:</b> The former elite cricketers reported a higher prevalence of osteoarthritis, total hip replacement, total knee replacement, anxiety and depression than the general population sample and a lower prevalence of heart problems than the general population. Injury was the only cricket-related factor analysed to be associated with the musculoskeletal outcomes of joint pain, osteoarthritis, and joint replacement in the former cricketers. The current elite fast bowlers did not demonstrate a statistically significant difference between the compartmental knee cartilage volume in the trailing leg versus the higher loaded leading leg. A clinically significantly greater cartilage volume was found in the lateral tibia compartment of the leading leg than the trailing leg. The lateral tibia cartilage of the leading leg was also found to be significantly associated with the knee flexion/extension moment and abduction/adduction moment at leading leg strike of the bowling action. <b>Conclusions:</b> This research identifies risks and benefits of a career in elite cricket, providing targets for prevention and resource provision for chronic conditions in current cricketers and cricketers transitioning out of elite cricket. These results also suggest that cartilage may be sensitive to bowling loads in current elite fast bowlers, providing evidence that increased physical activity and loading is associated with increased cartilage volume.

Made available in DSpace on 2014-06-11T19:25:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-16Bitstream added on 2014-06-13T19:12:38Z : No. of bitstreams: 1 figueiredoneto_em_me_botfm.pdf: 437501 bytes, checksum: 9465339e4a387fbb504707f548414dc6 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A osteoartrose é uma desordem caracterizada por mecanismos degradativos que acomete principalmente as articulações dos quadris, joelhos, mãos e coluna vertebral. Indivíduos sintomáticos podem manifestar dor de características mecânicas, rigidez e diminuição ou perda da função articular. A atividade física e a qualidade de vida (QV) nesses pacientes podem estar diminuídas. O objetivo deste trabalho foi quantificar e qualificar a qualidade de vida e a atividade física de pacientes com osteoartrose atendidos no ambulatório de reumatologia da Faculdade de Medicina de Botucatu – UNESP. Os sujeitos deste estudo foram os pacientes do ambulatório de reumatologia com diagnóstico de osteoartrose dos quais colhidos dados epidemiológicos e características da doença. O método utilizado foi a avaliação através dos questionários Medical Outcomes Study 36 Short-Form Health Survey (SF-36), Índice Western Ontario and McMaster Universities (WOMAC) e Australian/Canadian (AUSCAN) Osteoarthritis Hand Index para avaliação da qualidade de vida e o International Physical Activity Questionnaire (IPAQ) para avaliar as atividades físicas. Foi utilizada também a Escala Visual Analógica para mensurar a dor. Os resultados obtidos foram a inclusão de 100 pacientes, 92 (92%) mulheres, média de idade 59,9 ± 9,4 (40-85) anos. Dez (10%) pacientes apresentavam uma articulação acometida, 69 (69%) duas e 21 (21%) três ou mais. O acometimento de joelhos e mãos representaram 66 (66%) dos casos e 91 (91%) apresentavam pelo menos a mão e mais alguma articulação de carga. A avaliação pelo SF-36 mostrou que os maiores escores foram obtidos nos domínios AS, AE e EGS, com médias de, respectivamente, 71,5 ± 31,9, 71,3 ± 44,2 e 64,1 ± 26,3. O valor médio do escore WOMAC foi de 27,1 ± 18,9. A média do AUSCAN-D foi... / Osteoarthritis is a disorder characterized by degeneratives mechanisms that affects mainly hips, knees, hands and spine. Symptomatic individuals can manifest mechanical pain, stiffness and decrease or loss of joint function. Physical activity and quality of life in these patients can be reduced The aim of this study was to quantify and qualify the quality of life and physical activity in patients with osteoarthritis followed in the rheumatology outclinic of Botucatu Medical School - UNESP. Patients were included and their epidemiological data and characteristics of disease were recorded. The method used were the questionnaires Medical Outcomes Study Short-Form 36 Health Survey (SF-36), Western Ontario McMaster Universities Index (WOMAC) and Australian / Canadian (AUSCAN) Osteoarthritis Hand Index for assessing the quality of life and the International Physical Activity Questionnaire (IPAQ) to assess the physical activities. Visual Analogue Scale were used to measure pain. As results, hundred patients, 92 (92%) women, average age 59.9 ± 9.4 (40-85) years were included. Ten (10%) had one joint affected, 69 (69%) two and 21 (21%) three or more. The involvement of knees and hands represented 66 (66%) of the cases and 91 (91%) had at least a hand and some load articulations. SF-36 in higher scores were observed in the AS, AE and EGS domains, with averages of, respectively, 71.5 ± 31.9, 71.3 ± 44.2 and 64.1 ± 26.3. The mean WOMAC score was 27.1 ± 18.9. The average AUSCAN-D was 2.8 ± 2.9, the AUSCAN-R of 3.3 ± 3.2 and AUSCAN-F was 2.9 ± 2.7. The IPAQ showed that 62 patients (70%) were considered active or very active and 30 (30%) sedentary or insufficiently active. The subjective evaluation of the intensity of joint pain that presented by the EVA average of 55.1 ± 30 mm. In conclusion, patients with OA are active individuals when evaluated by IPAQ, most ...(Complete abstract click electronic access below)

Orientador: Paola Castro Moraes / Coorientador: Luis Gustavo Gosuen Gonçalves Dias / Banca: Geórgia Modé Magalhães / Banca: Annelise Carla Camplesi dos Santos / Resumo: Devido ao aumento da expectativa de vida dos animais e ocrescente número de pessoas, a osteoartrite (OA), também conhecida como artrose,surge como uma das afecções mais relevantes na medicina veterinária e humana. Diversos tratamentos são utilizados e propostos, porém não há ainda consenso sobre a melhor terapia. Objetivou-se investigar e comparar a eficácia do Laser de baixaintensidade e o ultrassom terapêutico em conjunto com plasma rico em plaquetas(PRP), no tratamento da osteoartrite induzida em joelhos de ratos. Foram utilizados72 ratos distribuídos aleatoriamente em nove grupos de oito animais: Grupo Controle(GC), Grupo solução fisiológica (GCF), Grupo osteoartrite 21 dias (GOA21), Grupoosteoartrite 42 dias (GOA42), Grupo osteoartrite e Laser (GOALa), Grupo osteoartritee Ultrassom terapêutico (GOAUS), Grupo osteoartrite e PRP (GOAPrp), Grupoosteoartrite, PRP e Laser (GOAPrpLa) e Grupo osteoartrite, PRP e ultrassomterapêutico (GOAPrpUS). Foi realizada infiltração intra-articular de papaína 4% ecisteína 0,03M e, 21 dias após a indução, iniciou-se tratamento por três semanas comlaser, ultrassom e/ou PRP. Foram realizadas avaliações perimétricas, termográficas,macro e microscópicas. Os resultados mostraram interação significativa entre osgrupos em relação ao tempo para as avaliações perimétricas e termográficas,comprovando que a termografia foi eficaz para avaliar o comportamento da inflamaçãoarticular. Não foram observadas alterações macrosc... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Due to increasing life expectancy of animals and the growing number of people, osteoarthritis (OA), also known as arthrosis, appears as one of themost important diseases in veterinary and human medicine. Several treatments areuse and proposed, but there is no consensus about the best therapy. This study aimedto investigate and compare the efficacy of Low-level laser therapy and therapeuticultrasound in conjunction with platelet-rich plasma (PRP) in the treatment ofosteoarthritis induced in rats' knees. Randomly were used 72 mice divided into ninegroups of eight animals: Control Group (CG), group saline (GCF), Group osteoarthritis21 days (GOA21), Group osteoarthritis 42 days (GOA42), Group osteoarthritis andLaser (GOALa), Group osteoarthritis and therapeutic Ultrasound (GOAUS),osteoarthritis and PRP Group (GOAPrp), osteoarthritis Group, PRP and Laser(GOAPrpLa) and Group osteoarthritis, PRP and therapeutic ultrasound (GOAPrpUS).It was performed intra-articular infiltration of papain and cysteine 0.03M 4% and 21days after the induction started three weeks treatment with laser, ultrasound and / orPRP. Evaluations were performed perimeter, thermographic, macro and microscopic.A significant interaction between the groups with respect to time to the perimeter andthermographic ratings, proving that thermography was effective to evaluate thebehavior of articular inflammation. Macroscopic changes were observe in the articularcartilage in any animal, a ... (Complete abstract click electronic access below) / Mestre

Orientador: João Batista de Miranda / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T13:23:10Z (GMT). No. of bitstreams: 1 Zorzi_AlessandroRozim_M.pdf: 2318090 bytes, checksum: 67428e73d40fe1ff0a25f4c17e78e4f8 (MD5) Previous issue date: 2010 / Resumo: Introdução: A técnica de abertura de cunha medial apresenta vantagens em relação às outras de osteotomia valgizante da tíbia, o que a tem tornado muito popular. Sua desvantagem é a criação de uma falha óssea na tíbia proximal, o que poderia possibilitar perda de correção ou retardo de consolidação. O uso de enxerto ósseo autólogo da crista ilíaca tem sido preconizado para diminuir o risco destas complicações. Entretanto, nenhum estudo clínico comparou a evolução clínica entre pacientes com e sem o uso do enxerto ósseo. Hipótese: Não há necessidade de enxerto ósseo na osteotomia de abertura medial, fixada com placa-calço igual ou menor que 12,5 mm. Desenho do estudo: Estudo clínico controlado, duplo-cego, randomizado. Métodos: Foram realizadas 46 osteotomias entre Abril de 2007 e Novembro de 2008. As osteotomias foram divididas aleatoriamente por um programa de computador em dois grupos de 23 joelhos cada. No grupo A, foi usado enxerto autólogo da crista ilíaca para preencher o espaço. No grupo B, o espaço foi deixado sem preenchimento. O enxerto foi coletado nos dois grupos, para garantir o mascaramento tanto dos pacientes quanto dos avaliadores. Avaliações clínicas foram realizadas a cada duas semanas até que sinais clínicos de consolidação estivessem presentes. Resultados: As varáveis demográficas foram similares nos dois grupos. A média de tempo para consolidação no grupo A foi de 12,4 semanas (IC 11,2 - 13,6), e no grupo B foi de 13,7 semanas (IC 12,5-14,9), sem diferença estatística (p=0,130). Perda de correção ocorreu em um paciente no grupo A (4,35%) e em dois pacientes no grupo B (8,7%). Conclusão: Nesta amostra, o tempo de consolidação das osteotomias foi similar nos grupos com e sem enxerto ósseo / Abstract: Background: Medial opening-wedge has gained popularity among other techniques of high tibial osteotomy with many advantages. The disadvantage of this method is the creation of a gap, with the possibility of collapse or delayed bone healing, and the need to harvest iliac crest bone graft. The filling of the gap is recommended, but no reports have compared grafted and ungrafted osteotomies. Hypothesis: There is no need for graft to achieve bone union in medial opening-wedge high tibial osteotomy when 12,5 mm or less spacer plate is used. Study design: Double-blinded randomized controlled clinical trial. Methods: Forty-six opening-wedge high tibial osteotomies were carried out. They were randomly divided by software in two groups of 23 knees: group A filled with autologous bone graft and group B unfilled. Bone graft was taken in all cases to ensure blindness of patients and investigators. Clinical evaluations were performed each two weeks until signs of bone union were achieved. Results: Demographic variables were similar in both groups. Mean time to bone union in group A was 12.4 weeks (CI 11.2-13.6) and in group B was 13.7 weeks (CI 12.5-14.9), without significant difference (p=0.130). Signals of loosening of screws occurred in one patient (4,35%) in group A, against two patients (8,7%) in group B. Conclusion: In this series both groups achieved bone union in similar times / Mestrado / Cirurgia / Mestre em Cirurgia

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A viscossuplementaÃÃo à uma tÃcnica terapÃutica utilizada no tratamento de osteoartrite, a qual busca substituir o lÃquido sinovial (lubrificante das articulaÃÃes) por soluÃÃes viscoelÃsticas de derivados do Ãcido hialurÃnico com propriedades reolÃgicas melhores que a deste lÃquido. Este tratamento à caro e comercialmente sà se utilizada o Ãcido hialurÃnico. O estudo de outros polissacarÃdeos, tais como a goma guar e a quitina, para aplicaÃÃo em viscossuplementaÃÃo, aumenta a possibilidade de substituir o Ãcido hialurÃnico por outros de fontes mais abundantes e viÃveis. A goma guar (GGNP) foi purificada por vÃrios mÃtodos com a finalidade de reduzir contaminantes, como polissacarÃdeos (que nÃo galactomanana) e principalmente proteÃnas. O mÃtodo de maior eficiÃncia na reduÃÃo destes contaminantes foi o mÃtodo fÃsico+Fehling, resultando em uma guar (GGFISFEH) com 96% de galactomanana e 0% de proteÃnas. A goma comercial (GGNP) e a purificada (GGFISFEH) foram reticuladas com glutaraldeÃdo para originar hidrogÃis fluidos de alta viscosidade. O aumento da viscosidade do polissacarÃdeo com o tempo de reaÃÃo de reticulaÃÃo à gradativo e pode ser interrompido no momento em que se obtÃm um hidrogel fluido, por diÃlise contra Ãgua. Os hidrogÃis obtidos tem viscosidade quarenta vezes (GelGGNP) e oitocentas vezes (GelGGFISFEH) a viscosidade das soluÃÃes iniciais das gomas. A goma guar purificada (GGFISFEH) foi modificada por reaÃÃo de oxidaÃÃo com reagente TEMPO e por reaÃÃo de sulfataÃÃo, com a finalidade de introduzir grupos carboxilato e sulfato, assemelhando a estrutura desta ao Ãcido hialurÃnico e ao condroitim sulfato. As reaÃÃes foram eficientes na modificaÃÃo, resultando em grau de substituiÃÃo (GS) de 0,36 para a goma oxidada (GGOXID) e 0,60 para a sulfatada (GGSULF). AnÃlises de RMN de 13C e 1H indicam que a sulfataÃÃo ocorreu no C6 da galactose e a oxidaÃÃo no C6 da manose. A quitina foi carboximetilada para originar um polieletrÃlito solÃvel em Ãgua e com grupo acetil glicosamina semelhante ao do Ãcido hialurÃnico. Esta reaÃÃo foi testada em vÃrias condiÃÃes reacionais, resultando em GS diferentes. O melhor rendimento foi de 92% com um GS de 0,53. Os testes farmacolÃgicos foram realizados em ratos Wistar. Avaliou-se o efeito per si na cavidade articular de GGNP e GGFISFEH, ambas em soluÃÃo e gel. A GGNP causou incapacitaÃÃo e influxo celular dosedependente, efeito nÃo demonstrado por GGFISFEH. A incapacitaÃÃo articular foi maior com a administraÃÃo do GelGGNP. Avaliou-se tambÃm, o efeito terapÃutico da GGFISFEH em soluÃÃo e gel, e Hilano G-F20 em osteoartrite induzida pelo modelo de transecÃÃo do ligamento cruzado anterior. A inibiÃÃo da incapacitaÃÃo articular obtida pelo gel ou pela soluÃÃo de guar foram absolutamente semelhantes ao resultado obtido com o Hilano G-F 20. A goma guar apresenta potencial como agente viscossuplementador. / The viscosupplementation is a therapeutic technique used in the osteoarthritis treatment, in which the sinovial fluid (lubricant of the ligaments) is replaced by viscoelastic solutions derived from hyaluronic acid with rheological properties better than the starting material. This treatment is expensive and commercially, only hialuronic acid is used. The research of other polysaccharides such as the guar gum and chitin, for the application on viscosupplementation, increases the possibility of substituting the hyaluronic acid with other from more abundant sources and more viable. The guar gum (GGNP) was purified through various methods with the aim to reduce contaminants, such as polysaccharides (but not galactomannan) and most importantly, proteins. The method with best efficiency in the reduction of these contaminants was the physic+Fehling method, resulting in a guar (GGFISFEH) with 96% of galactomannan and 0% of proteins. The commercial gum (GGNP) and the purified (GGFISFEH) were crosslinked with glutaraldehyde to originate fluids hydrogel of high viscosity. The increase in viscosity of the polysaccharides with the increase of the crosslinking reaction time is gradual and can be interrupted at the moment a hydrogel fluid is obtained through dialysis against water. The hydrogels obtained have viscosity forty times (GelGGNP) and eight hundred times (GelGGFISFEH) than the initial viscosities of the gums. The purified guar gum (GGFISFEH) was modified through oxidative reaction with a TEMPO reagent and through a sulfatation reaction, with the aim of introducing carboxylated and sulphate groups, making their structure similar to the one from the hyaluronic acid and the chondroitin sulfate. The reactions were efficient in the modification, resulting in degree of substitution (DS) of 0.36 for the oxidated gum (GGOXID) and 0.60 for the sulfated gum(GGSULF). 13C and 1H NMR analyses indicated that the sulfatation occurred in C6 of galactose and the oxidation on C6 of mannose The chitin was carboxylated to form a water soluble polyeletrolite and with a group of acetyl glucosamine similar to the hyaluronic acid. This reaction was tested in various conditions, resulting in different DS. The best yield was of 92% with a DS of 0.53. The pharmacological tests were conducted on rats Wistar. The effect, per si, in the articulate cavity of GGNP and GFISFEH, both in solution and gel was also studied. The GGNP caused incapacitation and dosage-dependant cell influx, an effect not demonstrated by GGFISFEH. The articular incapacitation was greater with the administration of GelGGNP. It was also evaluated the therapeutic effect of GGFISFEH in solution and gel, and Hilano G-F20 in osteoarthritis induced by the transection of the anterior cruciate ligament. The inhibition of the articular incapacitation obtained through gel or through the guar solution were entirely similar to the results obtained with the Hilano G-F20. The guar gum presents potential as a viscosuplemented agent.