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.

Title: Viscousand elastic properties of soft tissue"in situ" Goals and methods: The aim of this thesis is to measure the viscoelastic properties of human soleus muscle and Achilles tendonin vivo and post mortem in situ. It is a pilot study that uses myotonometry as the method of measurement. Based on the response of connective tissues on deformation made by tip of myotonometer, resp. its viscoelastic properties, curves in graphsare created. Three main described parameters of thecurveare steepness, deflection and its surface area. Main goal of the experiment is to compare properties of different types of tissue and their potential differences while denervated or innervated. Results of this study may help with better understanding of the soft tissues behavior in response to manual therapeutic contact. The study also describes the differences between in vivo and post mortem tissue properties that may be help further studies which use post mortem tissues to predict in vivo behavior. Results: Soft tissues in vivo have higher viscosity. In comparison, post mortem tissues have significantly higher stiffness and energy dissipation than in vivo. Elasticproperties of denervated soft tissue manifest with approx. 7 secondsdelay. Viscoelastic properties of muscle tissueshow changes depending on deeper...

Tendinopatias são distúrbios comuns com uma variedade de tratamentos e terapias e a Laserterapia aparece como uma alternativa no tratamento destas doenças. Nós investigamos os efeitos da irradiação laser no modelo de tendinite induzida por colagenase, em tendões calcâneo de ratos, verificando sua ação em importantes marcadores inflamatórios. Métodos: Foram utilizados ratos machos (Wistar) divididos em grupos: Salina e tendinite tratados com Diclofenado de Sódio ou Laser (1J, 3J ou 6J). A tendinite foi induzida por colagenase (100<font face=\"Symbol\">mg/tendão) sobre o tendão calcâneo que foi removido para análises. Foi verificado a expressão de COX-1, 2, TNF-a, TGF-<font face=\"Symbol\">b, IL-10, MMP-3, 9 e 13 (RT-PCR), a produção de PGE2 (ELISA) e a expressão de NT, COX-2 e NK-1 (Western Blotting). Resultados e discussão: A laserterapia (810nm, 100mW, 3 J), utilizada no tratamento da tendinite induzida por colagenase em tendão calcâneo de ratos, foi eficaz na redução de importantes marcadores inflamatórios, tornando-se uma ferramenta promissora para o tratamento de lesões tendíneas. / Tendinopathy is a common disease with a variety of treatments and therapies. Laser therapy appears as a alternative treatment. We research the effects of the laser irradiation in tendinitis model induced by collagenase injection on Achilles tendon rats, verified its action in important inflammatory markers. Methods: The male rats (Wistar) were used and divided in groups: Saline and tendinitis, treated with Sodium diclofenac or Laser (1J, 3J or 6J). The tendinitis was induced by collagenase (100<font face=\"Symbol\">mg/tendon) on the Achilles tendon which was removed for analyzes. The genic expression for COX-1, 2; TNF-a, TGF-<font face=\"Symbol\">b; IL-10; MMP-3, 9, 13 (RT-PCR); PGE2 production (ELISA kits) and NT, COX-2, NK-1 expression (Western Blotting) was measured. Results and discussion: The Laser therapy (810nm, 100mW, 3 J) used in the treatment of the tendinitis induced by collagenase in Achilles tendon in rats, was effective in the reduction of important inflammatory markers, becoming a promising tool for the treatment of tendon diseases.

Com o objetivo de analisar a influência do fenômeno de congelamento e o tempo de criopreservação sobre as propriedades biomecânicas de tendões, os autores estudaram 40 tendões de Aquiles obtidos de 20 cadáveres humanos. De cada cadáver foram retirados dois tendões, sendo que um foi testado a fresco e o contralateral congelado a - 85o C, durante um período de seis ou 12 semanas. Os corpos de prova foram submetidos a ensaios de tração, com análise de suas propriedades biomecânicas. Os resultados foram comparados estatisticamente pelo método de "t-student", com índice de significância de 0,05, não havendo diferença significativa entre os grupos "congelado" e "a fresco" / For the purpose of analyzing the influence of the freezing phenomenon and cryopreservation time over the biomechanical properties of tendons, the authors studied 40 Achilles tendons from 20 human cadavers. Each cadaver had two tendons removed, one of which was tested whilst fresh and its contralateral whilst frozen at - 85o C, for a period of six or 12 weeks. The trial items were submitted to tensile testing in order to analyze their biomechanical properties. The results were compared statistically using the T-Student method, with a significance ratio of 0.05, there being no significant difference between the 'frozen' group and the 'fresh' group

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

INTRODUÇÃO: Este estudo tem como objetivo comparar os achados biomecânicos e anatomopatológicos de um modelo animal inédito de tendinopatia do tendão do calcâneo, induzido por injeções seriadas de baixa dose da enzima colagenase bacteriana, com o modelo mais comumente utilizado na literatura, induzido por injeção única de maior dose da enzima, e com os controles. A hipótese é que a utilização de injeções seriadas resultaria em alterações tendíneas mais progressivas e duradouras, similar à doença nos humanos. MÉTODOS: Quarenta e cinco (N=45) coelhos foram randomizados em três diferentes grupos de estudo (A, B e Controles). Animais do Grupo A (n=18) foram submetidos a três injeções seriadas de baixa dose de colagenase (0,1mg), em ambos os tendões do calcâneo, separadas por intervalo de duas semanas. Animais do Grupo B (n=18) foram injetados com dose única de maior dose (0,3mg). Já no Grupo Controle, animais (n=9) foram injetados bilateralmente com três doses seriadas de solução fisiológica 0,9%. Após a última injeção, foi realizada eutanásia do mesmo número de animais dos Grupos A e B (n=6), com 10 semanas (Subgrupos A1 e B1), 12 semanas (Subgrupos A2 e B2) e 16 semanas (Subgrupos A3 e B3). Todos os animais do Grupo controle foram eutanasiados após 16 semanas. Alterações anatomopatológicas, pelo escore de Bonar, e biomecânicas foram comparadas entre os grupos e dentro de cada grupo, para os diferentes momentos de eutanásia. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Após 16 semanas, o escore anatomopatológico de Bonar foi significativamente maior para ambos os Grupos A (11,8±2,28) e B (5,6±2,51), quando comparados aos controles (2±0,76). Os valores para o grupo A também diferiram do Grupo B (p < 0,001). Para os desfechos biomecânicos, os grupos diferiram quanto à área de secção transversa do tendão (p=0,003), módulo de elasticidade (p=0,024), e tensões no limite da elasticidade (p=0,020) e na resistência máxima (p=0,022), com piores resultados encontrados nos animais do Grupo A. Na semana 12, também houve diferença entre os Grupos A e B para o escore anatomopatológico de Bonar (p=0,028) e para a tensão no limite da elasticidade(p=0,013), novamente com piores resultados no Grupo A. Já na 10a semana, foram os coelhos do Grupo B que demonstraram alterações mais pronunciadas quando comparados aos do Grupo A, com diferença significativa no Escore de Bonar (p=0,033), área de secção transversa do tendão (p=0,038), rigidez (p=0,048), módulo de elasticidade (p=0,024), força, tensão, energia e densidade de energia no limite da elasticidade (p=0,008, p=0,020, p=0,047 e p=0,0015, respectivamente) além de força e tensão no limite da resistência máxima (p=0,004 e p=0,008, respectivamente). A comparação dos desfechos dentro de cada grupo, entre os diferentes subgrupos, apresentou diferenças significativas no escore de Bonar em ambos os grupos A (p=0,012) e B (p < 0,001). Parâmetros biomecânicos não diferiram entre os subgrupos do Grupo A. Já os subgrupos do grupo B apresentaram diferenças na área de secção transversa do tendão (p=0,011), módulo de elasticidade (p=0,024), tensão no limite da elasticidade (p=0,023) e da resistência máxima (p=0,031), assim como na a densidade de energia no limite da elasticidade (p=0,017), com resultados mais pronunciados no subgrupo B1. CONCLUSÃO: O modelo animal de tendinopatia do tendão calcâneo induzida por injeções seriadas de colagenase apresentou alterações anatomopatológicas e biomecânicas mais avançadas na 16a semana, de caráter progressivo e duradouro, similar à doença dos humanos. Tal modelo experimental pode representar uma melhor opção na indução da tendinopatia do tendão do calcâneo, possibilitando a realização de estudos promissores no futuro / INTRODUCTION: This study aims to compare the biomechanical and histological findings of a new animal model of Achilles tendinopathy induced by serial low-dose injections of bacterial collagenase with the most commonly used high-dose single injection and to controls. The hypothesis of the study is that consecutive low-dose injections of collagenase would result in more progressive and long-lasting tendinopathic findings, reproducing better the disease in humans. METHODS: Forty-five (N=45) rabbits were randomly divided into three groups (A, B and Control). Animals in Group A (n=18) underwent three serial low-dose (0,1mg) injections of bacterial type I collagenase in both Achilles tendons, separated by a two-week interval. Animals in Group B (n=18) underwent bilateral single high dose injection (0,3mg) of the same enzyme. In the Control Group, animals (n=9) were injected bilaterally with three consecutive doses of saline solution, separated by a two-week interval. Following the last injection, the same number of rabbits from Groups A and B (n=6) were euthanized after 10 weeks (Subgroups A1 and B1), 12 weeks (Subgroups A2 and B2), and 16 weeks (Subgroups A3 and B3). Animals in the Control Group were all euthanized after 16 weeks. Histological findings, using the Bonar tendinopathy score, and biomechanical properties of the Achilles tendons were compared between the groups and inside each the group, in the different time-points of euthanasia. Findings at 16 weeks were considered primary outcomes. P-values < 0,05 were considered significant. RESULTS: After 16 weeks, the Bonar score was significantly increased for both Groups A (11,8±2,28) and B (5,6±2,51), when compared to controls (2±0,76). Group A has also differed from Group B (p < 0,001). Regarding biomechanical findings, groups differed in cross-sectional area of the Achilles tendon (p=0,003), Young\'s modulus (p=0,024), Yield stress (p=0,020) and ultimate tensile strength (p=0,022), with the worst results in animals from Group A. At 12 weeks, comparison between Groups A and B have shown significant differences for Bonar score (p=0,028) and Yield stress (p=0,013), again with worse results in Group A. Conversely, at 10 weeks, rabbits in Group B showed worse results when compared to Group A, with significant differences in the Bonar score (p=0,033), cross sectional area of the tendon (p=0,038), stiffness (p=0,048), Young\'s modulus (p=0,024), Yield tension (0,008), Yield stress (p=0,020), energy Yield (p=0,047), ultimate tension (p=0,004), ultimate stress (p=0,008) and yield strain energy density (p=0,015). The comparison of outcomes inside each group, in the different time-points of follow-up, demonstrated significant differences in the Bonar score for Group A (p=0,012) and Group B (p < 0,001). Regarding biomechanical properties, Group A showed no differences between the subgroups for any of the parameters evaluated. Subgroups in Group B differed for cross-sectional area of the tendon (p=0,011), Young\'s modulus (p=0,024), Yield stress (p=0,023), ultimate stress (p=0,031) and yield strain energy density (p=0,017), with worst results in the earliest follow-up (Subgroup B1). CONCLUSIONS: The animal model of Achilles tendinopathy induced by consecutive injections of collagenase showed worse histological and biomechanical properties after 16 weeks, demonstrating more progressive and long lasting tendinopathic findings, reproducing better the disease in humans. This novel experimental model can represent a better option to induce Achilles tendinopathy, allowing promising future research on the subject

INTRODUÇÃO: Este estudo tem como objetivo comparar os achados biomecânicos e anatomopatológicos de um modelo animal inédito de tendinopatia do tendão do calcâneo, induzido por injeções seriadas de baixa dose da enzima colagenase bacteriana, com o modelo mais comumente utilizado na literatura, induzido por injeção única de maior dose da enzima, e com os controles. A hipótese é que a utilização de injeções seriadas resultaria em alterações tendíneas mais progressivas e duradouras, similar à doença nos humanos. MÉTODOS: Quarenta e cinco (N=45) coelhos foram randomizados em três diferentes grupos de estudo (A, B e Controles). Animais do Grupo A (n=18) foram submetidos a três injeções seriadas de baixa dose de colagenase (0,1mg), em ambos os tendões do calcâneo, separadas por intervalo de duas semanas. Animais do Grupo B (n=18) foram injetados com dose única de maior dose (0,3mg). Já no Grupo Controle, animais (n=9) foram injetados bilateralmente com três doses seriadas de solução fisiológica 0,9%. Após a última injeção, foi realizada eutanásia do mesmo número de animais dos Grupos A e B (n=6), com 10 semanas (Subgrupos A1 e B1), 12 semanas (Subgrupos A2 e B2) e 16 semanas (Subgrupos A3 e B3). Todos os animais do Grupo controle foram eutanasiados após 16 semanas. Alterações anatomopatológicas, pelo escore de Bonar, e biomecânicas foram comparadas entre os grupos e dentro de cada grupo, para os diferentes momentos de eutanásia. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Após 16 semanas, o escore anatomopatológico de Bonar foi significativamente maior para ambos os Grupos A (11,8±2,28) e B (5,6±2,51), quando comparados aos controles (2±0,76). Os valores para o grupo A também diferiram do Grupo B (p < 0,001). Para os desfechos biomecânicos, os grupos diferiram quanto à área de secção transversa do tendão (p=0,003), módulo de elasticidade (p=0,024), e tensões no limite da elasticidade (p=0,020) e na resistência máxima (p=0,022), com piores resultados encontrados nos animais do Grupo A. Na semana 12, também houve diferença entre os Grupos A e B para o escore anatomopatológico de Bonar (p=0,028) e para a tensão no limite da elasticidade(p=0,013), novamente com piores resultados no Grupo A. Já na 10a semana, foram os coelhos do Grupo B que demonstraram alterações mais pronunciadas quando comparados aos do Grupo A, com diferença significativa no Escore de Bonar (p=0,033), área de secção transversa do tendão (p=0,038), rigidez (p=0,048), módulo de elasticidade (p=0,024), força, tensão, energia e densidade de energia no limite da elasticidade (p=0,008, p=0,020, p=0,047 e p=0,0015, respectivamente) além de força e tensão no limite da resistência máxima (p=0,004 e p=0,008, respectivamente). A comparação dos desfechos dentro de cada grupo, entre os diferentes subgrupos, apresentou diferenças significativas no escore de Bonar em ambos os grupos A (p=0,012) e B (p < 0,001). Parâmetros biomecânicos não diferiram entre os subgrupos do Grupo A. Já os subgrupos do grupo B apresentaram diferenças na área de secção transversa do tendão (p=0,011), módulo de elasticidade (p=0,024), tensão no limite da elasticidade (p=0,023) e da resistência máxima (p=0,031), assim como na a densidade de energia no limite da elasticidade (p=0,017), com resultados mais pronunciados no subgrupo B1. CONCLUSÃO: O modelo animal de tendinopatia do tendão calcâneo induzida por injeções seriadas de colagenase apresentou alterações anatomopatológicas e biomecânicas mais avançadas na 16a semana, de caráter progressivo e duradouro, similar à doença dos humanos. Tal modelo experimental pode representar uma melhor opção na indução da tendinopatia do tendão do calcâneo, possibilitando a realização de estudos promissores no futuro / INTRODUCTION: This study aims to compare the biomechanical and histological findings of a new animal model of Achilles tendinopathy induced by serial low-dose injections of bacterial collagenase with the most commonly used high-dose single injection and to controls. The hypothesis of the study is that consecutive low-dose injections of collagenase would result in more progressive and long-lasting tendinopathic findings, reproducing better the disease in humans. METHODS: Forty-five (N=45) rabbits were randomly divided into three groups (A, B and Control). Animals in Group A (n=18) underwent three serial low-dose (0,1mg) injections of bacterial type I collagenase in both Achilles tendons, separated by a two-week interval. Animals in Group B (n=18) underwent bilateral single high dose injection (0,3mg) of the same enzyme. In the Control Group, animals (n=9) were injected bilaterally with three consecutive doses of saline solution, separated by a two-week interval. Following the last injection, the same number of rabbits from Groups A and B (n=6) were euthanized after 10 weeks (Subgroups A1 and B1), 12 weeks (Subgroups A2 and B2), and 16 weeks (Subgroups A3 and B3). Animals in the Control Group were all euthanized after 16 weeks. Histological findings, using the Bonar tendinopathy score, and biomechanical properties of the Achilles tendons were compared between the groups and inside each the group, in the different time-points of euthanasia. Findings at 16 weeks were considered primary outcomes. P-values < 0,05 were considered significant. RESULTS: After 16 weeks, the Bonar score was significantly increased for both Groups A (11,8±2,28) and B (5,6±2,51), when compared to controls (2±0,76). Group A has also differed from Group B (p < 0,001). Regarding biomechanical findings, groups differed in cross-sectional area of the Achilles tendon (p=0,003), Young\'s modulus (p=0,024), Yield stress (p=0,020) and ultimate tensile strength (p=0,022), with the worst results in animals from Group A. At 12 weeks, comparison between Groups A and B have shown significant differences for Bonar score (p=0,028) and Yield stress (p=0,013), again with worse results in Group A. Conversely, at 10 weeks, rabbits in Group B showed worse results when compared to Group A, with significant differences in the Bonar score (p=0,033), cross sectional area of the tendon (p=0,038), stiffness (p=0,048), Young\'s modulus (p=0,024), Yield tension (0,008), Yield stress (p=0,020), energy Yield (p=0,047), ultimate tension (p=0,004), ultimate stress (p=0,008) and yield strain energy density (p=0,015). The comparison of outcomes inside each group, in the different time-points of follow-up, demonstrated significant differences in the Bonar score for Group A (p=0,012) and Group B (p < 0,001). Regarding biomechanical properties, Group A showed no differences between the subgroups for any of the parameters evaluated. Subgroups in Group B differed for cross-sectional area of the tendon (p=0,011), Young\'s modulus (p=0,024), Yield stress (p=0,023), ultimate stress (p=0,031) and yield strain energy density (p=0,017), with worst results in the earliest follow-up (Subgroup B1). CONCLUSIONS: The animal model of Achilles tendinopathy induced by consecutive injections of collagenase showed worse histological and biomechanical properties after 16 weeks, demonstrating more progressive and long lasting tendinopathic findings, reproducing better the disease in humans. This novel experimental model can represent a better option to induce Achilles tendinopathy, allowing promising future research on the subject

Matrix metalloproteinases (MMPs), such as collagenases, are a family of enzymes capable of degrading most constituents of the extracellular matrix. MMPs are thought to be involved in the aetiopathogenesis of tendon rupture. Additionally, failure of healing has in some instances been associated with elevated levels of MMPs. We have studied (a) the effects of the MMP-inhibitor doxycycline on healing of tendons and intestines in experimental models and (b) systemic levels of MMPs and their endogenous inhibitors (TIMPs) in patients with tendon rupture. In the first study, systemic doxycycline treatment lead to weakened rat Achilles tendons during healing after injury. Subsequently, systemic doxycycline was shown to improve biomechanical properties of tendon suture fixation in the rat Achilles tendon. Sutures were also coated with doxycycline, leading to similar improvement in mechanical strength of the suture construct during healing. In the third study, doxycycline-coated sutures improved the strength of healing intestinal anastomoses in an experimental model. Finally, we showed that patients with a history of Achilles tendon rupture had elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In addition, MMP-7 correlated inversely to mechanical strength of the tendon during healing. In conclusion, MMP-inhibitors can be administered systemically and locally to manipulate healing of tendons and intestines. Generalised alterations in the MMP-TIMP system may be involved in the pathogenesis of Achilles tendon rupture and associated with differences in outcome of healing.

Made available in DSpace on 2016-06-02T20:19:19Z (GMT). No. of bitstreams: 1 DissACBS.pdf: 10545595 bytes, checksum: 079933a164ff065ae11e54e43ae5200a (MD5) Previous issue date: 2004-12-20 / The purpose of this study was to analyze the 660 nm GaAlAs laser effect with 10 mW and 40 mW, during 10 seconds, on angiogenesis process and repair quality after partial lesion of Achilles tendon in rats. It was used 104 male rats, that 96 rats had been submitted to lesion by a falling of 186 g from a height of 20 cm, above the right tendon. These rats had been randomly divided in 3 groups, treated in 3 (n = 32), 5 (n = 32) and 7 (n = 32) days, respectively. Each of these groups was divided again into 4 subgroups, which were submitted to laser with mean output of 10 mW (n = 8) and 40 mW (n = 8), a sham treatment (n = 8), and a group with no treatment (n = 8). The analyzes were made by vessels count that have been previous prepared with nanquim ink and by a semiqualitative analyze of polynuclear cells presence, mononuclear cells presence, collagen organization and neovascularization. A fourth group with 8 animals was established as control, without lesion and used as reference for qualitative analyze. The comparison of the groups made evident that the animals submitted to laser showed more vessels number than the control groups (p<0,05) and the 40 mW subgroup showed better vascularization than the others after 3 days of irradiation. (p<0,01). The semiqualitative analyze showed statistical difference (p<0,05) when considering collagen organization and neovascularization in the comparison between the 10 mW, 40 mW and control. Qualitatively, the groups treated with laser showed better repair aspect. The results permit us to conclude that Low Level Laser Therapy with 660 nm promoted an increase of the blood vessels number and better repair quality and the mean output of 40 mW had begun the neovascularization precocious, showing significant difference after 3 days of application. / A proposta desse estudo foi analisar os efeitos do laser AsGaAl, de 660 nm, com 10 mW e 40 mW de potência de saída, aplicado durante 10 segundos, no processo de angiogênese e qualidade de reparo após lesão parcial do tendão calcâneo de ratos. Foram utilizados 104 ratos machos, sendo que 96 foram submetidos à lesão com a queda de um peso de 186 gramas na altura de 20 cm sobre o tendão direito. Estes foram divididos aleatoriamente em 3 grupos, tratados em 3 (n = 32), 5 (n = 32) e 7 (n = 32) dias, respectivamente. Cada um desses grupos foi ainda dividido em 4 subgrupos, submetidos ao laser com potência de saída de 10 mW (n = 8) e 40 mW (n = 8), grupo placebo (n = 8) e grupo sem tratamento (n = 8). As análises foram feitas através da contagem dos vasos que foram previamente corados com tinta nanquim e por meio de uma análise semiqualitativa da presença de células polimorfonucleares, mononucleares, organização de colágeno e neovascularização. Um quarto grupo com 8 animais foi estabelecido como controle padrão, sem lesão que foi utilizado como referência para a análise qualitativa. A comparação dos grupos evidenciou que os animais irradiados mostraram maior número de vasos do que os grupos controle (p<0,05) e o subgrupo de 40 mW apresentou melhor vascularização que os demais após 3 dias de irradiação (p<0,01). A análise semiqualitativa evidenciou diferença estatística (p<0,05) quando foi considerada a organização de colágeno e a neovascularização na comparação entre os grupos 10 mW e 40 mW com os controle. Qualitativamente os grupos tratados com laser apresentaram melhor aspecto do reparo. Os resultados nos permitem concluir que a terapia laser de baixa intensidade, com comprimento de onda de 660 nm promoveu aumento na neovascularização e melhora na qualidade de reparo e a potência de saída de 40 mW iniciou a neovascularização precocemente, mostrando diferença significativa após 3 dias de aplicação.

Tendinopatias são distúrbios comuns com uma variedade de tratamentos e terapias e a Laserterapia aparece como uma alternativa no tratamento destas doenças. Nós investigamos os efeitos da irradiação laser no modelo de tendinite induzida por colagenase, em tendões calcâneo de ratos, verificando sua ação em importantes marcadores inflamatórios. Métodos: Foram utilizados ratos machos (Wistar) divididos em grupos: Salina e tendinite tratados com Diclofenado de Sódio ou Laser (1J, 3J ou 6J). A tendinite foi induzida por colagenase (100<font face=\"Symbol\">mg/tendão) sobre o tendão calcâneo que foi removido para análises. Foi verificado a expressão de COX-1, 2, TNF-a, TGF-<font face=\"Symbol\">b, IL-10, MMP-3, 9 e 13 (RT-PCR), a produção de PGE2 (ELISA) e a expressão de NT, COX-2 e NK-1 (Western Blotting). Resultados e discussão: A laserterapia (810nm, 100mW, 3 J), utilizada no tratamento da tendinite induzida por colagenase em tendão calcâneo de ratos, foi eficaz na redução de importantes marcadores inflamatórios, tornando-se uma ferramenta promissora para o tratamento de lesões tendíneas. / Tendinopathy is a common disease with a variety of treatments and therapies. Laser therapy appears as a alternative treatment. We research the effects of the laser irradiation in tendinitis model induced by collagenase injection on Achilles tendon rats, verified its action in important inflammatory markers. Methods: The male rats (Wistar) were used and divided in groups: Saline and tendinitis, treated with Sodium diclofenac or Laser (1J, 3J or 6J). The tendinitis was induced by collagenase (100<font face=\"Symbol\">mg/tendon) on the Achilles tendon which was removed for analyzes. The genic expression for COX-1, 2; TNF-a, TGF-<font face=\"Symbol\">b; IL-10; MMP-3, 9, 13 (RT-PCR); PGE2 production (ELISA kits) and NT, COX-2, NK-1 expression (Western Blotting) was measured. Results and discussion: The Laser therapy (810nm, 100mW, 3 J) used in the treatment of the tendinitis induced by collagenase in Achilles tendon in rats, was effective in the reduction of important inflammatory markers, becoming a promising tool for the treatment of tendon diseases.