Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Made available in DSpace on 2015-03-26T13:47:25Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1265748 bytes, checksum: 6ec2ab64f2ffff7c785ba2692dabdda0 (MD5) Previous issue date: 2013-11-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This dissertation was carried out in two subprojects, with the first being entitled Clinical and biomechanical analyzes of the common calcaneal tendon of Wistar rats underwent laser therapy associate or not to eccentric exercise , and the second Histomorphometric analysis of the common calcaneal tendon of Wistar rats treated with laser therapy and eccentric exercise . The first subproject aimed to evaluate the effect of low-level laser therapy associated to eccentric exercise (downhill walking) on tendinopathy of the common calcaneal tendon of Wistar rats, by clinical and biomechanical analyzes, while the second subproject, by means of histopathological and morphometrical analyzes. Sixty-three adult male rats were randomly distributed into the following groups: L (laser), E (eccentric exercise), LE (laser and eccentric exercise), R (rest), CT (contralateral tendon) and H (healthy tendon). The last two groups were present only in the first subproject. Unilateral tendinopathy with induced lesion was done by transversal compression followed by scarification of the tendon fibers, except in animals of group H. The treatments laser therapy (904 nm/3 J/cm2) and, or eccentric exercise (downhill walking; 12 m/min; 50 min/day; 15o inclination treadmill) began 24 h after surgery and remained for 20 days. The animals were submitted to physical evaluation (painful sensitivity and locomotion capacity examination) every three days, with euthanasia performed 3, 7, 14, and 21 days after lesion induction, except in the animals submitted to clinical and biomechanical analyzes, with this procedure being conducted only on day 21. During euthanasia, a macroscopic evaluation of the lesion site was carried out and the transversal diameter of the tendon was measured (analayzed only the first subproject). Sequentially, 18 tendons (from 15 rats) were collected and frozen at -20oC until biomechanical test, on which the characteristics maximum load (N), stress at ultimate tension (MPa) and maximum extension (mm) were analyzed. For the histomorphometric analysis, the following characteristics were studied: hemorrhage, fibrinous tissue adhesions, epitendon thickening, organization and amount of collagen fibers and blood vessels, inflammatory infiltrate and fibroblasts, as well as collagens (type I and III) and connective tissue organization. Local edema was observed on the xi first 72 h postoperative, but no pain was detected under physical examination. The macroscopic evaluation performed in the first subproject rats showed no increase in the transversal diameter of the tendons, and no presence of fibrous adhesions. However, this last characteristic was observed in an animal in the rest group, and in another in the laser therapy group, during the one week evaluation in the second subproject. In clinical and biomechanical analyzes, the group submitted to the eccentric exercise presented the lowest (p=0.0000) locomotion capacity among the injured animals (including those in the rest group), while in second subproject, such result was presented by the group underwent to rest (p=0.0008). No difference occured between groups, even when considering healthy and collateral tendons, in the evaluated biomechanical characteristics maximum load (p=0.4379), stress at ultimate tension (p=0.4605) and maximum extension (p=0.3820). However, it was observed among injured tendon, that the LE group required greater load and strain to rupture. No difference was found among groups, or between times in the characteristics hemorrhage, formation of fibrinous adhesion, organization of collagen fibers and connective tissue organization. Considering the groups, regardless of time, it was observed that eccentric exercise caused epitendon thickening (p=0.0204), which was lower in the group submitted to laser therapy. Histological analysis showed difference (p=0.0032) in the number of inflammatory cells along time, being observed in greater amount only in exercised group. This result was confirmed by morphometric analysis, which demonstrated that there was significant interaction (group x time) in this caracteristic, where the eccentric exercise increased (p=0.0014) the inflammatory infiltrate over time (3 and 21 days), however, when associate with laser teraphy, there was reduction the inflammatory reaction. On the other hand, the combination of the treatments led to a greater angiogenesis in morphometric (p=0.0000) and histological (p=0.0006) analyzes, compared to the other groups, while the application of low-level laser alone reduced this characteristic along time. Animals kept at rest presented the lowest (p=0.0000) amount of fibroblasts in morphometric analysis. However, in the histological evaluation significant interaction (group x time) (p=0.0024) was observed. Greater amount fibroblast was observed in groups E, L and LE, the 7 th , 14 th and 21 st days, respectively. The animals who received laser and were exercised showed higher (p=0.0000) amount of collagen fibers along time. The use of low-level laser at the dose of 3 J and wavelength of 904 nm, associated to walking treadmill eccentric exercise began 24 h after surgically-induced tendinopathy in Wistar rats does not result in biomechanically xii tendon as resistant or elastic as a healthy tendon. On the other hand, the combination of treatments shows the advantage of increasing the amount of collagen fibers, reduce fibrinous adhesion and inflammatory infiltrate. However, the application of laser therapy alone is adequate for angiogenesis and tendon thickening prevention. Keywords: Achilles tendon; histomorphometrical and biomechanical analyzes of tendon, physical activity, therapy with laser. / A dissertação foi desenvolvida em dois subprojetos, sendo o primeiro intitulado Análises clínica e biomecânica do tendão calcanear comuns de ratos Wistar submetido à laserterapia associada ou não a exercício excêntrico , e o segundo Análise histomorfometrica do tendão calcanear comum de ratos Wistar tratado com laserterapia e exercício excêntrico . O primeiro subprojeto teve como objetivo avaliar o efeito da terapia com laser de baixa potência associada a exercício excêntrico (caminhada em declive) na tendinopatia do tendão calcanear comum de ratos Wistar, mediante análises clínica e biomecânica, enquanto no segundo por meio de análises histopatológica e morfométrica. Foram utilizados 63 ratos machos, adultos, que foram distribuídos aleatoriamente nos grupos L (laser), E (exercício excêntrico), LE (laser e exercício excêntrico), R (repouso), CL (tendão contralateral) e S (tendão sadio). Os últimos dois grupos existiram apenas no primeiro subprojeto. Tendinopatia unilateral com lesão induzida foi realizada mediante compressão transversal seguida por escarificações das fibras dos tendões, exceto nos animais do grupo S. Os tratamentos laserterapia (904 nm/3 J/cm2) e/ou exercício excêntrico (caminhada em declive; 12 m/min; 50 min/dia; esteira com 15o de inclinação) iniciaram 24 h após cirurgia e permaneceram por 20 dias. Os animais foram submetidos à avaliação física (sensibilidade dolorosa e exame da capacidade motora) a cada três dias, com eutanásia sendo realizadas 3, 7, 14 e 21 dias após indução de tendinopatia, exceto nos animais submetidos às análises clínica e biomecânica, cujo procedimento foi realizado apenas aos 21 dias. Durante a eutanásia foi realizada avaliação macroscópica do local da lesão e o diâmetro transversal do tendão foi mensurado (analisado apenas no primeiro subprojeto). Na sequência, 18 tendões (provenientes de 15 ratos) foram obtidos e congelados a -20oC até o momento do teste biomecânico, onde foram analisadas as características carga máxima (N), tensão na carga (MPa) e extensão máxima (mm). Para a análise histomorfométrica as seguintes características foram estudadas: hemorragia, aderência tecidual fibrinosa, espessamento do epitendão, organização e quantidade das fibras colágenas e dos vasos sanguíneos, infiltrado inflamatório e fibroblastos, assim como colágenos (tipo I e III) e viii organização do tecido conjuntivo. Edema local foi observado nas primeiras 72 h do pós- operatório, mas não foi constatado dor durante exame físico. Não houve aumento no diâmetro transversal dos tendões nem presença de aderência fibrosa na avaliação macroscópica realizada nos ratos do primeiro subprojeto. Entretanto, essa última característica foi observada em um animal deixado em repouso e outro submetido à laserterapia na avaliação realizada com uma semana no segundo subprojeto. Nas análises clínica e biomecânica, o grupo submetido a exercício excêntrico apresentou menor (p=0,0000) capacidade de locomoção entre os animais lesionados (incluindo os do grupo em repouso), já no segundo subprojeto foram os ratos mantidos em repouso (p=0,0008). Não houve diferença entre grupos, inclusive considerando-se os tendões sadios e contralaterais, nas características biomecânicas carga máxima (p=0,4379), tensão na carga (p=0,4605) e extensão máxima (p=0,3820) avaliadas. Entretanto, foi observado entre os tendões lesionados, que os do grupo LE necessitaram maior carga e tensão para se romperem. Não houve diferença entre grupos nem entre tempos nas características hemorragia, formação de aderência fibrinosa, organização das fibras colágenas e organização do tecido conjuntivo. Considerando os grupos, independentemente do tempo, foi observado que o exercício excêntrico acarretou espessamento do epitendão (p=0,0204), que foi menor no grupo submetido à laserterapia. A análise histológica apresentou diferença (p=0,0032) na quantidade de células inflamatórias ao longo do tempo, sendo observado em maior quantidade no grupo apenas exercitado. Esse resultado foi confirmado pela análise morfométrica, que demonstrou haver interação significativa (grupos x tempo) nessa característica, onde o exercício excêntrico aumentou (p=0,0014) o infiltrado inflamatório ao longo do tempo (3 e 21 dias), porém, quando associado à laserterapia, ocorreu redução do reação inflamatória. Por outro lado, a associação dos tratamentos ocasionou maior angiogênese, nas análises morfométrica (p=0,0000) e histológica (p=0,0006), quando comparado com os demais grupos, enquanto a aplicação isolada do laser de baixa potência reduziu essa característica ao longo do tempo. Os animais mantidos em repouso foram os que apresentaram menor (p=0,0000) quantidade de fibroblastos na análise morfométrica. Já na avaliação histológica, houve interação significativa (grupo x tempo) (p=0,0024). Maior quantidade de fibroblastos foi observada nos grupos E, L e LE, nos 7 o , 14 o e 21 o dias, respectivamente. Os animais que receberam laser e foram exercitados apresentaram maior (p=0,0000) quantidade de fibras colágenas ao longo do tempo. A utilização do laser de baixa potência na dose de 3 J e comprimento de onda de ix 904 nm, associada ao exercício excêntrico caminhada em esteira, iniciados 24 h após tendinopatia induzida cirurgicamente em ratos Wistar não resulta em um tendão biomecanicamente tão resistente ou elástico quanto o tendão saudável. Por outro lado, a combinação dos tratamentos possui a vantagem de aumentar a quantidade de fibras colágenas, reduz a aderência fibrinosa e infiltrado inflamatório. Já a aplicação isolada da laserterapia é adequada para angiogênese e para evitar o espessamento do tendão. Palavras-chave: tendão de Aquiles; análise histomorfometria e biomecâmica do tendão, atividade física, terapia a laser.

INTRODUÇÃO: A disfunção do tendão tibial posterior (DTTP), principal causa de pé plano adquirido no adulto, é mais frequente em indivíduos do gênero feminino e apresenta pico de incidência na sexta década de vida. Diversos fatores de risco - intrínsecos e extrínsecos - e condições sistêmicas associadas são descritas na literatura. A predisposição genética resultante da maior expressão de genes relacionados ao metabolismo hormonal, principalmente do estrogênio, pode desempenhar influência na fisiopatogenia dessa lesão em associação aos fatores comportamentais e endógenos. OBJETIVO: Analisar a frequência de polimorfismos nos genes dos receptores de estrogênio (RE) dos tipos alfa (RE1) e beta (RE2), em pacientes na pós-menopausa com diagnóstico de tendinopatia do tendão do músculo tibial posterior e em pacientes assintomáticas. CASUÍSTICAS e MÉTODOS: Foram incluídas 202 pacientes do gênero feminino (N=202), com idade superior a 40 anos, divididas em 2 grupos (n=101), de casos e controles. Foram definidos como casos pacientes na pós-menopausa com diagnóstico de DTTP, realizado por meio dos exames clínico e de imagem (RM), e, como controles, pacientes com as mesmas características epidemiológicas, assintomáticas, que apresentavam exames clínico e de imagem normais para a avaliação do tendão tibial posterior. Células epiteliais da mucosa bucal das pacientes incluídas no estudo foram coletadas por meio de bochecho com solução glicosada para extração e análise do RESULTADOS: Pacientes portadoras do genótipo xx do SNP XbaI apresentaram risco estimado 2,38 vezes maior (p = 0,029) de desenvolver a DTTP quando comparadas às portadoras dos genótipos selvagem ou heterozigoto. Já a distribuição dos genótipos dos SNP PvuII e AluI não apresentou associação com o desenvolvimento da doença. ADN genômico. Os SNP dos genes dos RE1 (XbaI e PvuII) e RE2 (AluI) foram avaliados com base em PCR-RFLP. CONCLUSÃO: O presente estudo demonstra que pacientes com polimorfismo XbaI do RE1 apresentam maior risco de desenvolvimento da disfunção do tendão tibial posterior / INTRODUCTION: Posterior tibial tendon dysfunction (PTTD), the most common cause of flatfoot deformity in adults, is more frequent in the female gender with peak incidence in the sixth decade of life. Multiple risk factors - intrinsic and extrinsic - and associated systemic conditions have been described in the literature. Genetic predisposition secondary to hyperexpression of genes related to hormonal metabolism, particularly the estrogens, may play a role in the pathogenesis of this disease acting in association with behavioral and endogenous risk factors. OBJECTIVE: The aim of this study was to analyze the frequency of polymorphisms of the estrogen receptors (ER) alpha (ER1) and beta (ER2) in postmenopausal women with PTTD when compared to asymptomatic control patients. METHODS: 202 female patients over the age of 40 were included in the study (N = 202). They were then divided into 2 different groups (n = 101): cases and controls. We defined as cases postmenopausal women with symptomatic PTTD, diagnosed by clinical and MRI examinations. Females with similar epidemiology, but clinically asymptomatic and with normal MRI evaluation for the posterior tibial tendon were defined as controls. Oral mucosa epithelial cells were collected from the patients and genomic DNA was extracted from the samples. The SNPs for the ER1 (XbaI and PvuII) and ER2 (AluI) genes were assessed by PCR-RFLP. RESULTS: Patients with SNP Xbal genotype xx had 2.38 higher estimated risk (p = 0,029) in developing PTTD, when compared to patients with the other genotypes. No associations were found for the SNP PvuII and AluI. CONCLUSION: The present study demonstrates that patients with the Xbal single nucleotide polymorphism of estrogen receptor 1 gene have higher risk of developing posterior tibial tendon dysfunction

Resumo: A tendinose calcificante do músculo supra-espinhoso é pouco conhecida em cães. Sua apresentação e relevância clínicas, bem como os padrões epidemiológicos, permanecem obscuros nesta espécie. Neste estudo, objetivou-se a descrição clínico-epidemiólogica da afecção e dos padrões radiográficos e ultrasonográficos das lesões. Para tal, foi realizado levantamento retrospectivo em 2164 cães submetidos à avaliação radiográfica dos ombros, atendidos na Clínica Cirúrgica de pequenos animais da Universidade de Giessen, Alemanha, no período compreendido entre janeiro de 1996 a julho de 2006. Alterações radiográficas compatíves com tendinose calcificante do supra-espinhoso foram observadas em 144 cães. Observouse, dentro da população estudada, que 93% dos cães era de raças de grande porte, especialmente Rottweilers, concentrados na faixa de 4 a 7,9 anos e machos. As lesões foram diagnosticadas unilateralmente em mais de 80% dos cães, sendo que 70% apresentavam sinais clínicos. A maioria destes cães (75%) era portadora de outra afecção ortopédica, destacando-se a fragmentação do processo coronóide medial da ulna, dificultando a confirmação da tendinose como causa da manifestação clínica. Adicionalmente, foram revisadas imagens radiográficas de 138 ombros acometidos pela afecção e ultra-sonográficas de 21 ombros, a fim de se detalhar os padrões de imagem existentes. As lesões observadas por meio de radiografia foram classificadas em cinco graus. Na maioria dos cães sintomáticos, não portadores de outra afecção ortopédica, as lesões foram classificadas como de graus 3 e 4 à radiografia e mostraram-se como áreas hiperecóicas com sombreamento acústico à ultra-sonografia. A avaliação ultrasonográfica permitiu acessar o parênquima tendíneo com detalhes e a presença de hipoecogenicidade circundante à área calcificada foi sugestiva de processo inflamatório. / Abstract: Supraspinatus calcifying tendinosis is a relatively unknown disorder in dogs. Its clinical presentation, relevance and epidemiological pattern remain unclear. In the present study, we aimed its clinical-epidemiological, radiological and sonographic description performing a retrospective study in dogs presented to the Small Animal Surgery Clinics of the Giessen University, Germany, between January 1996 and July 2006. In 2164 dogs which shoulders were submitted to radiographies, 144 presented lesions compatible to supraspinatus calcifying tendinosis. It was observed that 93% were large breed dogs, specially Rottweilers, male, aging between 4 and 7,9 years old. The calcifying lesions were unilateral in 80% of the cases; 70% of the dogs showed clinical symptoms however, a great amount (75%) of them presented also some other orthopedic abnormality, speccially ulnae fragmented coronoid process, which was considered the clinical signs cause. Additionally, 138 shoulder radiographies and 21 shoulder sonographies were reviewed and their findings described. A radiological classification system in five degrees was proposed, according to the lesion appearance. In the major part of the symptomatic dogs, not affected by other orthopedic abnormality, the lesions were radiologically classified in degree 3 and 4 and showed a dense distal shadowing by sonographic evaluation. Sonography also allowed tendon parenchyma evaluation, providing tissue details. The presence of hypoechoic area surrounding the calcific lesion was sugestive of infflamatory process. / Orientador: João Guilherme Padilha Filho / Coorientador: Martin Kramer / Banca: Júlio Carlos Canola / Banca: Paola Castro de Moraes / Banca: Naida Cristina Borges / Banca: Fernando de Biasi / Doutor

Orientador: Edson Rosa Pimentel / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T15:25:06Z (GMT). No. of bitstreams: 1 Vieira_CristianoPedrozo_D.pdf: 3245048 bytes, checksum: 0556c35183a4503cef8427390d086781 (MD5) Previous issue date: 2015 / Resumo: Nutrição terapêutica é a administração de alguns nutrientes, em doses maiores que as necessidades alimentares diárias que podem prevenir deficiências orgânicas e atuar como agentes farmacológicos. A glicina apresenta amplos efeitos benéficos em processos inflamatórios e tumorais. O Chá verde feito de folhas e brotos da planta Camellia sinensis, é a segunda bebida mais consumida em todo mundo. O interesse econômico e social tem ganhado espaço no mercado e atualmente seu consumo faz parte da rotina diária de muitas pessoas que utilizam essa bebida como uma finalidade terapêutica. O Chá verde possui propriedades antimutagênicas, antidiabéticos, antiinflamatórias, antioxidante, antimicrobial e hipocolesterolêmica. A tendinite é reconhecidamente um problema clínico que motiva a comunidade científica a buscar tratamentos que auxiliem no restabelecimento das propriedades funcionais dos tendões. O presente estudo investigou o efeito do chá verde e ou da ração rica em glicina após 7 e 21 dias da indução da tendinite com colagenase. Ensaios bioquímicos, moleculares, morfológicos e biomecânicos foram desenvolvidos. Além disso, tenócitos em cultura foram tratados com glicina após inflamação induzida por TNF-?. Nossos ensaios in vivo mostraram altas concentrações de hidroxiprolina e glicosaminoglicanos no grupo glicina e chá em 21 dias de tratamento. Nos ensaios biomecânicos os grupos chá verde e dieta de glicina em 21 dias suportaram maiores cargas biomecânicas antes da ruptura. Além disso, uma melhor organização das fibras de colágeno foi observada no grupo chá verde em 7 dias. Análises bioquímicas e moleculares da junção miotendínosa mostraram que a inflamação instalada na região osteotendinea pode provocar alterações significativas nesse local. Marcantes alterações foram notadas nas metaloproteínases (MMP) tais como MMP-2, MMP-8 e MMP-9 em animais com tendinite tratados ou não com chá verde e glicina. No estudo in vitro, tenócitos extraídos a partir de tendão de Aquiles foram tratados com TNF-?, seguindo ou não de tratamento com glicina em meio de cultura. Antes e após 24 horas da inflamação foi adicionado glicina. Tenócitos inflamados e tratados com glicina mostraram expressão de colágeno tipo I próxima aos grupos tratados com glicina previamente e depois da inflamação quando comparado ao grupo controle. Todos os grupos tratados com glicina mostraram menor expressão de MMP-2. A atividade da MMP-9 foi alta apenas no grupo tratado com glicina em 48 horas. A concentração de ácido urônico foi menor no grupo tratado com glicina 24 horas após a inflamação. No ensaio de migração celular, resultados em 24 horas de tratamento foram similares ao grupo controle. Em geral, tanto a glicina quanto o chá verde influenciam na síntese dos componentes do tendão, melhoram a organizaçao das fibras colagênicas, aumentam a resistência a cargas do tendão inflamado e consequentemente aceleram o processo de remodelamento após indução da tendinite. Além disso, o tratamento com glicina em cultura de tenócitos mostrou uma reorganização eficiente da matriz extracelular, corroborando com os resultados encontrados in vivo / Abstract: Therapeutic nutrition is the administration of some nutrients, in higher doses than those recommended for the daily food needs that can prevent dysfunctions and act as pharmacological agents. Glycine has large beneficial effects in inflammatory and tumor processes. Green tea made from leaves and buds of the Camellia sinensis plant, is the second most consumed beverage in the world. The economic and social interest has gained space in the market and currently its consumption is part of the daily routine of many people who use this drink as a therapeutic purpose. Green tea has antimutagenic, antidiabetic, anti-inflammatory, antioxidant, antimicrobial and hypocholesterolemic properties. Tendinitis is recognized as a clinical problem that motivates the scientific community to investigate treatments that help in restoring the functional properties of tendons. The present study investigated the effect of green tea and/or diet rich in glycine after 7 and 21 days of tendinitis collagenase-induced. Biochemical, molecular, morphological and biomechanical tests were developed. Furthermore, tenocytes in culture were treated with glycine after inflammation induced by TNF-?. Our tests in vivo showed high concentrations of hydroxyproline and glycosaminoglycans in glycine and green tea group in 21 days of treatment. In biomechanical assay, green tea and glycine diet groups in 21 days showed a high biomechanical loads bore before rupture. In addition, better organization of collagen fibers was observed in green tea group in 7 days. Biochemical and molecular analyzes of myotendinous junction showed that the inflammation installed in osteotendinious region can cause significant change in that region. Remarkable changes were noted in metalloproteinases (MMP) such as MMP-2, MMP-8 and MMP-9 in animals with tendinitis treated with or without glycine and green tea. In the in vitro study, tenocytes from Achilles tendon were treated with TNF-?, or not following treatment with glycine in the culture medium. Before and 24 hours after inflammation was added glycine. Tenocytes inflamed and treated with glycine showed expression of collagen type I close to the treated groups with glycine previously and after the inflammation when compared to the control group. All treated groups showed less glycine MMP-2 expression. The activity of MMP-9 was high only in the group treated with glycine for 48 hours. In the cell migration assay results in 24 hours of treatment were similar to the control group. In general, both glycine and green tea influenced the synthesis of the tendon components, improve the organization of the collagenous fibers, increase the load resistance of the inflamed tendon and consequently accelerate the remodeling process after inducing tendinitis. In addition, the treatment with glycine in tenocytes culture showed efficient reorganization of the extracellular matrix, confirming the results found in vivo / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

Diplomová práce Účinky rázové vlny v léčbě tendinopatie Achillovy šlachy 1 Abstract This thesis focuses on the observation of the effects of low-energetic focused extracorporeal shock wave therapy (ESWT) in the treatment of Achilles tendinopathy. The theoretical part summarizes the current knowledge of anatomical, histological, kinesiological and biomechanical aspects of Achilles tendon (AT), as well as pathological processes, which can be described as Achilles tendinopathy, their differential diagnosis and treatment options. Last but not least, we present up-to-date information on the physical principles and biological effects of ESWT, not only in the treatment of AT diseases. The main goal of our research was to determine the effectiveness of low-energetic focused ESWT in the treatment of Achilles tendinopathy in comparison to the placebo group. The subject of observation was not only changes in clinical manifestations, but also possible changes in the morphology of AT using ultrasonography (USG). Methods: A total of 20 patients with symptomatic Achilles tendinopathy was included in the study, while only 18 of them completed the entire program, and therefore only the results of these patients were evaluated. They were randomly divided into two groups in 1:1 ratio. Group A was treated by ESWT with...

Degenerative disorders of the rotator cuff tendons account for nearly 75% of all shoulder pain, causing considerable pain and morbidity. Given the strong correlation between age and tendinopathy, and unprecedented population aging, these disorders will become increasingly prevalent. Improved understanding of tendon degeneration will guide the development of future diagnostic and treatments, and is therefore urgently needed. However, the aetiology and pathology of rotator cuff tendinopathy remain unclear. The complicated mechanical environment of the rotator cuff is hypothesised to influence the susceptibility of the tendons to degeneration and tearing. Studies have reported biological adaptations in torn cuff tendons indicative of increased compressive loading within the tendon. The material adaptations of healthy and degenerative cuff tendons are largely unreported but will provide further insight into the role of the mechanical environment in rotator cuff aetiology and pathology. This thesis examined the material adaptations of healthy and diseased tendons to explore the role of mechanical loading in rotator cuff pathology. The material adaptations of healthy animal tendons, and healthy and delaminated human cadaveric rotator cuff tendons, in response to different loading environments were characterised. The effects of age, tears, steroid injection and subacromial decompression surgery on the structural adaptations of human cuff tendons were also studied, as was the effect of tendon cell proliferation on the mechanical properties and degradation behaviour of collagen scaffolds. Loading environment significantly affected the structural adaptations of healthy tendons. Regions exposed to compressive and shear strains exhibited thinner fibres, shorter crimp lengths and thinner, less aligned fibrils compared with regions exposed to tensile strains alone. In healthy rotator cuff tendons, the inhomogeneous loading environment produced topographically inhomogeneous structural adaptations. The tendons of a delaminated rotator cuff exhibited less topographical variation in properties and thinner, less aligned fibrils compared with healthy cuff tendons. Torn cuff tendons exhibited thinner fibrils and shorter crimp lengths compared with control samples. These adaptations were identifiable early in the disease progression, and neither steroid injection nor subacromial decompression surgery significantly influenced these adaptations at seven weeks post‐treatment. Significant correlations between decreasing dimensions and increasing tear size were found when age was included as a confounding factor, reflecting the importance of age and tear size in determining the material properties of tendons. Tendon cell proliferation influenced the mechanical properties and degradation behaviour of the collagen scaffolds, emphasising the integral role of cells in the functional adaptation of biological materials. These results demonstrate the effect of mechanical environment on the material adaptations of tendons. They also indicate the importance of the complicated mechanical environment experienced by the rotator cuff tendons in predisposing the tendons to degeneration and tearing. The observed material adaptations of degenerative and torn tendons suggest that rotator cuff pathology is associated with increased levels of compressive and/or shear strains within the tendon. These changes begin early in the disease progression and neither steroid injection nor sub‐acromial decompression surgery are capable of reversing the changes in the timeframe investigated. These findings highlight the urgent clinical need for pre‐rupture diagnostic techniques for the detection of early pathological changes in the rotator cuff. They also emphasize the requirement for new intervention strategies that restore the healthy mechanical environment and reverse early pathological adaptations in order to prevent catastrophic failure of the tendons.

Tendon injury prevalence in both athletic and occupational settings is on the increase. Tendon healing properties are poor, despite the complex biological process triggered by the injury, which makes those injuries incapacitating for months. A significant proportion of these injuries remain difficult to treat, and many patients suffer from decreased performance and longstanding sequelae. While mechanical stabilization has been a hallmark of tendon surgical management, orthobiologics are playing an increasing role in optimizing tendon healing. Platelet rich Plasma (PRP), which is a volume of autologous plasma having platelet concentration above baseline, has been suggested as an accelerant orthobiological agent rich in supraphysiological concentration of growth factors. However, strong evidence of its mode of action and of its clinical efficacy is lacking. The purpose of this thesis is to identify the role of PRP in tendon regeneration in in-vitro and clinical studies. Firstly, the viability and biological components of clinically-prepared PRP were studied in novel experiments. This PRP was used in linked in-vitro studies to investigate the possible mechanism of PRP effect on the injured Achilles tendon cells and tissues. Cell count, viability, proliferation and DNA content were studied. The clinical application of PRP in Achilles tendon rupture was assessed in a randomised clinical pilot study using a combination of PROMs, objective outcome measures and a novel imaging modality called functional ultrasound elastography. This non-invasive technique was developed in a healthy-tendons volunteer study and its feasibility in ruptured tendons was assessed in the pilot trial. In another unique study, the immunohistochemical response to PRP was assessed in biopsies taken under US guidance at week 6 and compared to control to explore the possible mechanism of PRP effects. The findings confirmed that PRP is a viable activatable autologous blood product rich in growth factors. The results also confirmed that leukocytes and platelets are present in very high concentration with reversal of lymphocyte neutrophil ratio. Elastography volunteer study confirmed that FUSE is feasible using clinically applicable ultrasound scan. The improved algorithm allowed visualisation of localised strain within the studied tissues. The clinical application of PRP in Achilles tendon rupture revealed positive efficacy signal that PRP led to faster healing, improved pain and earlier restoration of function. However, the findings of this pilot trial were indicative and not confirmative. Immunohistochemistry analysis showed that PRP enhanced the maturity of the healing tendon tissues by promoting better collagen I deposition, improved Collagen III/Collagen I ratio, reduced cellularity, better vascular structure and higher GAGs content when compared with control. The finding may explain the clinical improvement observed in these patients at week 6 onwards. Linked in-vitro studies showed that autologous PRP with its cellular components, which include platelets, leukocytes and erythrocytes, has the ability to stimulate tendon cell migration to the injury site and stimulate proliferation in the injured human tendon. Additionally, it may maintain tissue viability in the hypoxic environment that follows tendon injury. Promoting migration and proliferation of cells and maintain tissue viability may play an important role to accelerate tendon healing. The findings of this project has informed the design of a phase II large multi-centre randomised controlled trial and helped secure major funding from the National Institute of Health Research (NIHR). This trial will set the scene for PRP use in tendon treatment.

OBJETIVO: Avaliar características clínicas, componente vertical da força de reação do solo e função muscular de flexores plantares e dorsais do tornozelo em corredores com e sem tendinopatia de calcâneo, e em indivíduos não corredores. MÉTODOS: Setenta e dois indivíduos (42H: 30M, idade 37,3 ±9,9 anos) foram divididos em três grupos: grupo tendinopatia de calcâneo (GTC, n= 24), grupo de corredores controle (GCC, n=24), e grupo de não corredores (GNC, n=24), sendo que em cada grupo ambos os tornozelos foram avaliados. A AOFAS ankle-hindfoot score, parâmetros da força de reação do solo e dados isocinéticos foram avaliados usando plataformas de força e dinamômetro isocinético. RESULTADOS: A AOFAS ankle-hindfoot score foi significativamente menor no GTC. A FRS foi igual entre os grupos, porém o impulso vertical inicial foi maior no GTC que GCC e GNC. Não houve diferenças para o impulso total. O GTC demonstrou menor trabalho total na velocidade 120º/s que GCC. Não houve diferenças para as outras variáveis isocinéticas entre GTC e GCC, apenas em relação ao GNC. CONCLUSÃO: Os corredores com tendinopatia de calcâneo têm maior impacto no momento de aterrissagem, menor resistência muscular dos flexores plantares e maior comprometimento clínico e funcional. A associação do maior impulso e menor resistência pode ser um fator predisponente e mantenedor para lesão no tendão calcâneo / OBJECTIVE: To evaluate the clinical characteristics, vertical component of the ground reaction force and muscle function of plantar flexors and dorsiflexors of the ankle in runners with and without Achilles tendinopathy and in non-runners. METHODS: Seventy-two subjects (42 M: 30W, 37.3±9.9 years old) were divided into three groups: Achilles Tendinopathy Group (GTC, n=24), Runners Control Group (GCC, n=24) and Non-Runners Group (GNC, n=24), in which both ankles were evaluated in each group. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, parameters of ground reaction force, and isokinetic data were evaluated by means of force platforms and isokinetic dynamometer. RESULTS: The AOFAS ankle-hindfoot score was significantly lower in the GTC. The GRF was similar between the groups; however, the initial vertical impulse was higher in the GTC than in the GCC and GNC. There were no differences regarding the total impulse. The GTC presented lower total work in the 120º/s speed than the GCC. There were no differences regarding the other isokinetic variables between the GTC and GCC, only regarding the GNC. CONCLUSION: Runners with Achilles tendinopathy show higher impact at the moment of landing, lower muscle endurance of plantar flexors and higher clinical and functional damage. The association between higher impulse and lower endurance could be a predisposing and maintaining factor for Achilles tendon

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-12-01Bitstream added on 2014-06-13T20:21:58Z : No. of bitstreams: 1 mestieri_mla_dr_jabo.pdf: 2694352 bytes, checksum: 4e6a0aa7574c83896fbcf276fbb312ff (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A tendinose calcificante do músculo supra-espinhoso é pouco conhecida em cães. Sua apresentação e relevância clínicas, bem como os padrões epidemiológicos, permanecem obscuros nesta espécie. Neste estudo, objetivou-se a descrição clínico-epidemiólogica da afecção e dos padrões radiográficos e ultrasonográficos das lesões. Para tal, foi realizado levantamento retrospectivo em 2164 cães submetidos à avaliação radiográfica dos ombros, atendidos na Clínica Cirúrgica de pequenos animais da Universidade de Giessen, Alemanha, no período compreendido entre janeiro de 1996 a julho de 2006. Alterações radiográficas compatíves com tendinose calcificante do supra-espinhoso foram observadas em 144 cães. Observouse, dentro da população estudada, que 93% dos cães era de raças de grande porte, especialmente Rottweilers, concentrados na faixa de 4 a 7,9 anos e machos. As lesões foram diagnosticadas unilateralmente em mais de 80% dos cães, sendo que 70% apresentavam sinais clínicos. A maioria destes cães (75%) era portadora de outra afecção ortopédica, destacando-se a fragmentação do processo coronóide medial da ulna, dificultando a confirmação da tendinose como causa da manifestação clínica. Adicionalmente, foram revisadas imagens radiográficas de 138 ombros acometidos pela afecção e ultra-sonográficas de 21 ombros, a fim de se detalhar os padrões de imagem existentes. As lesões observadas por meio de radiografia foram classificadas em cinco graus. Na maioria dos cães sintomáticos, não portadores de outra afecção ortopédica, as lesões foram classificadas como de graus 3 e 4 à radiografia e mostraram-se como áreas hiperecóicas com sombreamento acústico à ultra-sonografia. A avaliação ultrasonográfica permitiu acessar o parênquima tendíneo com detalhes e a presença de hipoecogenicidade circundante à área calcificada foi sugestiva de processo inflamatório. / Supraspinatus calcifying tendinosis is a relatively unknown disorder in dogs. Its clinical presentation, relevance and epidemiological pattern remain unclear. In the present study, we aimed its clinical-epidemiological, radiological and sonographic description performing a retrospective study in dogs presented to the Small Animal Surgery Clinics of the Giessen University, Germany, between January 1996 and July 2006. In 2164 dogs which shoulders were submitted to radiographies, 144 presented lesions compatible to supraspinatus calcifying tendinosis. It was observed that 93% were large breed dogs, specially Rottweilers, male, aging between 4 and 7,9 years old. The calcifying lesions were unilateral in 80% of the cases; 70% of the dogs showed clinical symptoms however, a great amount (75%) of them presented also some other orthopedic abnormality, speccially ulnae fragmented coronoid process, which was considered the clinical signs cause. Additionally, 138 shoulder radiographies and 21 shoulder sonographies were reviewed and their findings described. A radiological classification system in five degrees was proposed, according to the lesion appearance. In the major part of the symptomatic dogs, not affected by other orthopedic abnormality, the lesions were radiologically classified in degree 3 and 4 and showed a dense distal shadowing by sonographic evaluation. Sonography also allowed tendon parenchyma evaluation, providing tissue details. The presence of hypoechoic area surrounding the calcific lesion was sugestive of infflamatory process.