ABSTRACT Background: On behalf of the Orthopedic clinic, Västerås, a study has been conducted with focus on comparing the results after conservative and surgical treatment due to complete achillestendon rupture. Aim: To compare results when testing the active and passive range of motion, calf muscle endurance, estimation of pain related to the achillestendon and self-efficacy to be physically active for individuals who have undergone conservative or surgical treatment after complete achillestendon rupture. Method: 14 individuals afflicted by complete achillestendon rupture in 2010 were recruited as a purposive sample. Examination were conducted of: Ankle range of motion with a goniometer, calf muscle endurance through a toe-raise test, estimation of pain intensity related to the achillestendon by VAS and self-efficacy to be physically active through “Exercise self-efficacy scale”. P-value and the median were calculated. Result: The results of ankle range of motion and calf muscle endurance were based on the difference between the injured and the healthy side. When testing active plantarflexion the conservative group had a median of 4 ̊ and the surgical group had a median of 10 ̊. At the toe-raise test the conservative group had a median of 11 toe-raises and the surgical group a median of 7. Through estimation of “Exercise self-efficacy scale” the conservative group had a median of 115 point and the surgical group a median of 94. When testing active dorsiflexion, passive plantarflexion, passive dorsiflexion and estimation of pain related to the achillestendon the median value were 0 for both groups. Conclusion: There was no statistical significance between the groups.   Key words: Achilles tendon, operative, rupture, self efficacy, treatment outcome. / SAMMANFATTNING Bakgrund: På uppdrag av Ortoped kliniken Västerås, har en studie genomförts med fokus på att jämföra resultat efter konservativ respektive operativ behandling i samband med total hälseneruptur. Syfte: Att jämföra resultaten vid test av aktiv och passiv fotledsrörlighet, vadmuskeluthållighet, skattning av smärta relaterat till hälsenan samt self-efficacy för att vara fysiskt aktiv för individer som genomgått konservativ respektive operativ behandling efter total hälseneruptur. Metod: 14 individer som drabbats av total hälseneruptur under 2010 rekryterades enligt ett ändamålsenligt urval. Undersökningar gjordes av fotledsrörlighet med hjälp av goniometer, vadmuskeluthållighet via ett tåhävningstest, skattning av smärtintensitet relaterat till hälsenan via VAS och self-efficacy för att vara fysiskt aktiv via ”Exercise self-efficacy scale”. P-värde och median beräknades. Resultat: Resultaten för fotledsrörligheten och vadmuskeluthålligheten baserade sig på skillnaden mellan frisk och skadad sida. Vid test av aktiv plantarflexion hade den konservativa gruppen en median på 4° och den operativa gruppen en median på 10°. Vid tåhävningstestet hade den konservativa gruppen en median på 11 stycken tåhävningar och den operativa gruppen en median på 7. Vid skattning via ”Exercise self-efficacy scale” hade den konservativa gruppen en median på 115 poäng och den operativa gruppen en median på 94. Vid test av aktiv dorsalflexion, passiv plantarflexion, passiv dorsalflexion samt vid skattning av smärta blev medianvärdet 0 för båda grupperna. Slutsats: Det förelåg ingen statistisk signifikant skillnad mellan grupperna.   Nyckelord: Behandlingsresultat, egen förmåga, hälsena, operationer, ruptur.

Abstract Type I collagen is the main connective tissue protein in vertebrates. The cross-linking and correct organisation of the molecules is crucial for the proper function of the tissue. Traditionally collagen cross-linking has been studied using chemical cross-link analyses. However, this does not distinguish between the collagen types or the location of the cross-link within the molecule. The focus in this work was to study the carboxyterminal telopeptide domain of type I collagen for the differently cross-linked forms. An immunochemical approach was used and a new immunoassay, SP4, was developed for the detection of immaturely cross-linked peptide forms. The differently cross-linked structures were purified and characterised from human bone by using SP4 together with the earlier developed ICTP assay for trivalently cross-linked C-terminal telopeptide form. It was found that the majority of the trivalent cross-links in the C-terminal telopeptide were presently unknown structures, other than pyridinoline. A non-cross-linked form of C-terminal telopeptide of α1-chain of type I collagen was also discovered in bone. The epitope of the ICTP assay was characterised and found to reside in the phenylalanine rich region of the ICTP peptide. MMP-9, but not cathepsin K, mediated breakdown of the collagenous matrix was found to produce a peptide detectable by the ICTP assay. Healthy human Achilles tendon comprises mainly of type I collagen. In ruptured Achilles tendons, an increased type III collagen content was found. Since the synthesis of type III collagen was not increased, it is postulated that the type III collagen must have accumulated over a long period of time indicative of a long-lasting microtraumatic process in the tendon before the total rupture occurred. The ICTP content was increased and the ratio of SP4 to ICTP decreased in calcified stenotic aortic valves suggesting a change in the molecular organisation and cross-linking towards the type found in human bone. The total collagen content was dramatically decreased in the calcified valves. Both in the Achilles tendons and in the aortic valves, the ICTP content was found to decrease with age with a concomitant increase in the variants of the C-terminal telopeptide structures detectable with the SP4 assay, pointing to a change in the molecular organisation of the collagenous matrix in these tissues.

Abstract The Achilles tendon is the largest tendon in the human body and is affected by many diseases and is vulnerable to many forms of damage due to the heavy loads it must bear. Rupture of the Achilles tendon has become more common in recent times, with an almost four-fold increase in prevalence from 1979–1990 to 1991–2000 and a peak incidence of 19 ruptures per 100 000 of population in 1999 in our epidemiological assessment. The incidences of major complications, re-rupture and deep infection, increased along with primary ruptures, peaking in 1999. The results after successful primary repair are good in over 90% of cases, as we have shown in a randomized study and in a review of the literature, and the result after re-rupture is still good in about 70% of cases, but achieving good performance after deep infection is a highly random matter. Our retrospective survey did not identify any good results, but the deep infection cases in our randomized study showed good performance due to prompt action taken for their treatment. The best method for treating a ruptured Achilles tendon has been under debate for almost 100 years, with surgery and conservative methods advocated to equal extents. We have advocated surgical treatment as the primary choice and conservative treatment is given for selected high risk patients, for example patients with diabetes, skin problems, systemic use of corticosteroids or severe other illness. The type of surgery technique is not a straightforward choice, either, and various forms of open surgery and percutaneous techniques exist. We compared an end-to-end simple suture with the same suture augmented with one central gastrocnemius turn-over flap in a randomized series of 60 patients and found no differences with respect to subjective complaints, calf muscle strength or tendon elongation with time. The end-to-end technique is simpler and is therefore justified as the primary method of choice for the surgical repair of fresh complete Achilles tendon ruptures. The tissue composition has been shown to alter not only with time but also after repeated tearing of the tendon collagen fibres. A normal tendon is mainly composed of type I collagen, but the rupture areas express more type III collagen, which is thinner and withstands loads less effectively. Type III collagen accumulates slowly in the tendon, since its production does not increase very much, a situation that is indicative of microtrauma. Crosslinking of the fibres is important for collagen matrix properties, and we found that there is a change in the quality of crosslinking with age and that this may have role in the observed changes in tendon stiffness, as also noted in other studies. We also studied the appearance of tenascin-C at the rupture site in the Achilles tendon and at two other sites in the same tendon, but found no difference in its expression. It has been proposed that tenascin-C may take part in the tendon’s reaction to loading, but its exact function remains unknown.

Background: Previously research shows that people treated conservatively can have reduced foot function after Achilles tendon rupture. However, there are few qualitative studies in the subject, so this essay is written to provide a deeper understanding of how these people feel about their foot function one to two years after the injury. Purpose: Investigate how people perceive their foot function after conservative treatment one to two year after Achilles tendon rupture and if they have an avoidance behavior in their everyday lives. Method: Four people who suffered from Achilles tendon rupture participated in this qualitative study. The study was conducted with semi-structured interviews, which in turn were processed using qualitative content analysis. Results: The perceived foot function is today varied in terms of mobility, strength and pain according to the participants. They feel difference in their everyday life in comparison with before the injury. It appears that participants have avoidance behavior when it comes to the situation of injury. They expressed that the time course of development of foot function from the time of injury until today has been long-lasting but most of the participants mentions that there is still development of the foot function. Conclusion: The participants experience reduced foot function in varying degrees, who affect them in their everyday life, in situations including walking and staircase- walking. For this reason is it difficult to draw a collective conclusion of the participants experienced foot function. However, the situations where the injury occurred are avoided by the participants because of fear of getting a new rupture. Development of foot function is continuing, but is perceived as slow by many participants and they are not satisfied with this. / Bakgrund: Forskning visar att konservativ behandling kan ge nedsatt fotfunktion efter hälseneruptur. Få kvalitativa studier finns inom ämnet, därmed bör denna studie skrivas för att ge djupare förståelse för hur dessa personer upplever sin fotfunktion. Syfte: Undersöka hur personer som behandlats konservativt upplever sin fotfunktion ett till två år efter en hälseneruptur samt om de upplever sig ha ett undvikande beteende i vardagen.   Metod: Fyra personer som ådragit sig hälseneruptur medverkade i denna kvalitativa studie. Semistrukturerade intervjuer genomfördes och bearbetades med hjälp av kvalitativ innehållsanalys. Resultat: Upplevd fotfunktion är varierande gällande rörlighet, styrka och smärta. Deltagarna upplever skillnad i vardagen jämfört med innan skadan. Deltagarna har undvikande beteende gällande skadesituationen. Tidsförloppet gällande förändringen av fotfunktion från skadetillfället tills i dag har varit långdraget men de flesta upplever att utveckling fortfarande sker. Slutsats: Nedsatt fotfunktion upplevs i varierande grad, vilket påverkar i vardagen vid exempelvis gång och trappgång. Detta gör det svårt att dra någon gemensam slutsats gällande deltagarnas fotfunktion. Samtliga har dock någon form av undvikande beteende gällande aktiviteten som utfördes vid skadetillfället, på grund av oro och rädsla för ny skada. Fotfunktionens förändring upplevs som långsam vilket gör flera deltagare missnöjda.

Orientador: Edson Rosa Pimentel / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T11:50:11Z (GMT). No. of bitstreams: 1 Guerra_FlaviaDaRe_D.pdf: 2578763 bytes, checksum: 4d00d5fa99bb0b97be32b1a4af7e825a (MD5) Previous issue date: 2013 / Resumo: O tendão calcanear é o tendão mais acometido por ruptura, particularmente em atividades esportivas. O processo de cicatrização resulta em uma matriz extracelular (MEC) menos organizada o que reduz sua resistência à tensão e torna-o mais susceptível à recorrência de lesões. A terapia com o laser de baixa potência (LBP) tem se mostrado efetiva, porém existem resultados contraditórios com relação a seus protocolos. Propusemos-nos a avaliar os efeitos de diferentes terapias com o LBP em tendão calcanear parcialmente seccionado. Para tal foram utilizados ratos Wistar machos adultos, distribuídos em 7 grupos experimentais: G1- Tendão intacto; G2-Tendão seccionado; G3- lesão + LBP (4J/cm2-contínuo); G4- lesão + LBP (4J/cm2-20 Hz); G5- Tendão seccionado; G6- lesão + LBP (4J/cm2-contínuo); G7- lesão + LBP (4J/cm2-20 Hz até o 7º dia e 2 KHz do 8º ao 14º dia). G2, G3 e G4 foram eutanaziados no 8º dia após lesão, e G5, G6 e G7 no 15º dia. Foram realizadas as dosagens de proteínas não-colagênicas (PNC), glicosaminoglicanos (GAG) e hidroxiprolina (HOPro), além de eletroforese em gel de agarose, zimografia para MMP-2 e -9 e western blotting (WB) para colágeno I e III. O estudo estrutural foi feito por meio de lâminas coradas em hematoxilina-eosina (HE) e azul de toluidina (AT) além de análise e medidas de birrefringência por meio de microscopia de polarização. A análise funcional foi realizada por meio do Catwalk. Com relação à HOPro houve um decréscimo significativo em todos os grupos quando comparados ao G1, exceto G7. A dosagem de GAG revelou um aumento em todos os grupos exceto G5 e o gel de agarose mostrou um aumento no conteúdo de dermatan sulfado em todos os grupos transeccionados, sendo menos expressivo em G4 e G7. Nos cortes corados com AT os grupos transeccionados apresentaram maior metacromasia, em especial os grupos tratados. WB para colágeno I mostrou um aumento em G4 e G7. Quanto ao colágeno III G4 apresentou valores maiores quando comparado a G2. A zimografia para MMP-2 indicou maiores valores em G4 e G7. A MMP-9 aumentou em G3 e G4. A análise de birrefringência revelou acentuada desorganização em todos os grupos, com melhora significativa em G7. Os resultados do catwalk apontaram que, após a cirurgia os grupos que receberam o laser pulsado conseguiram apoiar melhor a pata quando comparado aos demais grupos. Nossos resultados mostram que o LBP contínuo e pulsado tem efeitos diferentes sobre o processo de reparo do tendão. O LBP pulsado atuou sobre o processo inflamatório possibilitando que o animal apoiasse melhor a pata ao caminhar e promoveu a síntese e organização do colágeno. Desta maneira acreditamos que este protocolo de tratamento pode ser adaptado para o uso em clínicas de reabilitação de maneira a acelerar o reparo e melhorar as características morfológicas, bioquímicas e funcionais deste tendão / Abstract: The Achilles tendon has a high incidence of rupture, particularly in sports activities. The healing process leads to a disorganized extracellular matrix (ECM) which reduces its tensile strength and lead to a high rate of injury recurrence. Low level laser therapy (LLLT) has been effective, but there are conflicting results regarding their protocols. Our purpose was to evaluate the effects of different therapies with LLLT in partially tenotomized Achilles tendon. Adult male Wistar rats were divided into 7 groups: G1 ? intact; G2 ? injured; G3 ? injured + LLL (4 J/cm2 continuous); G4 ? injured + LLL (4 J/cm2 ? 20 Hz); G5 ? injured; G6 ? injured + LLL (4 J/cm2 continuous); and G7 ? injured + LLL (4 J/cm2 ? 20 Hz until the 7th day and 2 kHz from 8?14 days). G2, G3 and G4 were euthanized 8 days after injury, and G5, G6 and G7 were euthanized on the 15th day. Quantification of non-collagenous protein (NCP), glycosaminoglycans (GAG) and hydroxyproline (HOPro) was performed, in addition to electrophoresis on agarose gel, zymography for MMP-2 and -9, western blotting (WB) for collagen types I and III. The structural analysis was done by hematoxylin-eosin (HE) and toluidine blue (TB) staines with in addition to birefringence measurements and analysis by polarization microscopy. Functional analysis was performed using the gait assessment of the animals in the Catwalk. Regarding HOPro there was a significant decrease in all groups when compared to the G1, except G7. The dosage of GAG showed an increase in all groups except G5 and agarose gel showed an increase in the content of dermatan sulfat in all transected groups, being less expressive in G4 and G7. In sections stained with TB the tenotomized groups showed metachromasia, particularly the treated groups. WB for collagen I showed an increase in G4 and G7. In G4 collagen III showed higher values when compared to G2. The zymography for MMPs-2 showed higher values for G4 and G7. MMP-9 increased in G3 and G4. Analysis of birefringence showed marked disorganization in all groups, with a significant improvement in G7. The catwalk results showed that after surgery, G4 had better results when compared to other groups. Our results show that the continuous and pulsed LLLT has different effects on the process of tendon repair. Pulsed laser acted on the inflammatory process improving the gait and promoting collagen synthesis and organization. Thus we believe that this treatment protocol can be adapted for use in rehabilitation clinics in order to accelerate the repair and enhance the morphological, biochemical and functional characteristics of the tendon / Doutorado / Anatomia / Doutora em Biologia Celular e Estrutural

Abstract The purposes of the present research were to compare the outcome after Achilles tendon rupture repair in two postoperative regimens, to compare Achilles tendon elongation in two postoperative treatment methods, to compare the effects of two postoperative methods on motor performance aspects such as simple reaction time, choice reaction time, speed of movement, foot tapping speed and coordination, to test the mechanical properties of the recently developed poly-L/D-lactide (PLDLA) sutures and Maxon® sutures when implanted in the Achilles tendons of rabbits, and to study the histological tissue reactions and biodegradation of these sutures under the same conditions. Isokinetic calf muscle strength scores at the last control check-up were excellent in 56% of the patients in the early motion group, good in 32%, fair in 8%, and poor in 4%, whereas the scores in the cast group were excellent in 29% of cases, good in 50% and fair in 21%. The ankle performance scores were excellent or good in 88% of the patients in the early motion group, fair in 4% and poor in 8%, whereas the scores in the cast group were excellent or good in 92% of cases and fair in 8%. No significant differences were seen between the two groups at 3 months and at the last control checkups with regard to pain, stiffness, subjective calf muscle weakness, footwear restrictions, range of ankle motion, isokinetic calf muscle strength or overall outcome. The complications included 1 re-rupture in the early motion group and 1 deep infection and 2 re-ruptures in the cast group. AT elongation occurred in both groups, but was somewhat less marked in the early motion group. The AT elongation curves rose at first and then fell slowly in both groups. The patients who had less AT elongation achieved a better clinical outcome. AT elongation did not correlate significantly with age, body mass index or isokinetic peak torques. The recovery of motor performance functions such as simple reaction time, choice reaction time, speed of movement, foot tapping speed and coordination did not depend on the two postoperative regimens. The motor functions of the operated leg had obviously recovered to the level of the non-operated leg 12 weeks after the operation. Sutures made of PLDLA were used successfully for Achilles tendon repair in rabbits. There was no significant difference between the in vitro and in vivo tensile strength retention of the sutures. By comparison with Maxon®, PLDLA was found to have a lower initial tensile strength but more prolonged strength retention. The breaking strength values of the Achilles tendons repaired with sutures of these types were not significantly different at 6 weeks. Intratendinous PLDLA sutures formed a thinner fibrous capsule during the 12-week follow-up period than did Maxon® sutures of the same diameter. The suture materials had not been totally absorbed by 12 weeks.

Abstract The Achilles tendon is the strongest and largest of human tendons, and its proper function is essential for normal gait. Most acute Achilles tendon injuries occur during sports, particularly in ball games. The purposes of this study were (1) to examine the incidence of total Achilles tendon rupture (ATR) over a 33-year period in the city of Oulu and to investigate its changes with respect to age, sex, and injury mechanism. (2) to compare ≥10-year outcomes of two postoperative regimens after ATR repair: early weightbearing with early mobilization versus early weightbearing with early immobilization in tension, (3) to compare clinical outcome and calf muscle strength recovery after conservative treatment or open surgical repair of acute ATR, followed by identical accelerated rehabilitation programs. The overall incidence per 100 000 person years increased from 2.1 in 1979 to 21.5 in 2011. The incidence increased in all age groups. The incidence of sports-related ruptures increased during the second 11-year period, whereas the incidence of non-sports-related ruptures increased steadily over the entire study period. Early mobilization and immobilization in tension after ATR repair resulted in similar clinical outcomes and isokinetic strengths. Regardless of patient satisfaction with the operative treatment, calf muscle strength did not recover normally, even at the 10-year follow-up. Surgery and conservative treatment of acute ATR resulted in similar Achilles tendon performance score after 18 months, but surgery restored calf muscle strength earlier. Surgery also resulted in better health-related quality of life in the domains of physical functioning and bodily pain. Conservative treatment with a functional protocol is recommended for a large majority of patients. However, patients with high physical expectations could still benefit from operative treatment. In conclusion, the incidence of ATR is rising, postoperative immobilization and early mobilization result in similar long-term results in terms of the Achilles tendon performance score and calf muscle function, and conservative treatment with a functional protocol is the preferred treatment for the majority of patients. / Tiivistelmä Akillesjänne on ihmisen suurin ja vahvin jänne ja sen kunnollinen toiminta on edellytys normaalille kävelylle. Suurin osa akillesjänteen repeämistä syntyy urheilussa, erityisesti pallopeleissä. Ensimmäisessä osatyössä oli tarkoitus selvittää täydellisten akillesjänteen repeämien esiintyvyys Oulussa 33 vuoden aikana ja selvittää potilaiden ikä ja sukupuoli sekä vammamekanismi. Toisessa osatyössä vertailtiin akillesjänteen repeämän hoitotuloksia 11 vuotta vamman jälkeen. Tässä tutkimuksessa verrattiin kahta erilaista leikkauksen jälkeistä hoitomenetelmää; toisessa sallittiin varhainen varaaminen ja nilkan liikuttelu kun taas toisessa sallittiin varhainen varaaminen, mutta nilkka kipsattiin ojennukseen. Kolmannessa osatyössä vertailtiin tuloksia leikattujen ja ilman leikkausta hoidettujen potilaiden välillä. Molemmat ryhmät hoidettiin samanlaisella irrotettavalla varaamisen sallivalla lastalla. Akillesjänteen repeämien esiintyvyys oli 2.1/100 000 vuonna 1979 ja nousi vuoteen 2011 mennessä 21.5/100 000:een ja nousua oli kaikissa ikäryhmissä. Urheiluun liittyvät repeämät lisääntyivät erityisesti jakson keskimmäisen 11-vuotis jakson aikana kun taas urheiluun liittymättömät repeämät lisääntyivät koko seurantajakson ajan. Vertailtaessa kahta erilaista leikkauksen jälkeistä hoitomenetelmää todettiin ettei potilaiden välillä ollut eroa kliinisissä mittareissa tai voimissa 11 vuotta vamman jälkeen. Vaikka potilastyytyväisyys oli hyvä ei pohkeen voima palautunut normaaliksi edes 11 vuotta vamman jälkeen. Vertailtaessa leikkauksella ja ilman leikkausta hoidettuja potilaita ei myöskään todettu eroja kliinisissä mittareissa, mutta kirurgisella hoidolla voima palautui hiukan nopeammin ja ero myös säilyi 18 kuukautta vammasta. Myös elämänlaatumittarilla mitattuna leikkauksella hoidetut olivat kivun ja fyysisen toiminnan osalta tyytyväisempiä. Suurimmalle osalle potilaista konservatiivinen hoito sopii erinomaisesti, mutta jotkut fyysisesti aktiiviset potilaat hyötynevät leikkaushoidosta.

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.

Ruptura do tendão calcâneo é uma das lesões tendíneas mais frequentes. Embora a maioria dos trabalhos sugira que o exercício seja benéfico na cicatrização tendínea, não há consenso sobre o efeito do antiinflamatório neste contexto. Trabalhos experimentais tentam reproduzir lesão aguda deste tendão, em diferentes espécies animais. Neste estudo, descrevemos uma técnica de tenotomia completa do tendão calcâneo direito em ratos e, em seguida, avaliamos os efeitos do uso do antiinflamatório e do exercício aeróbico, isoladamente e em combinação, sobre a proliferação celular e o perfil biomecânico do tendão calcâneo, durante o processo de cicatrização após tenotomia. Estudo experimental com 156 ratos machos adultos, da raça Wistar, com idade média de 3 meses e peso médio de 300g. Após anestesia com tiopental e com auxílio da microscopia de luz, foi realizada incisão longitudinal posterior de cinco milímetros, em direção proximal, a partir da tuberosidade posterior do calcâneo da pata direita do rato. Foi feito corte transversal do tendão calcâneo, a sete milímetros da tuberosidade do calcâneo, com preservação do tendão plantar. Utilizamos as técnicas de Hematoxilina e Eosina, Picrosirius-red e Resorcina-fucsina de Weigert para avaliação da cicatrização tendínea e das fibras dos sistemas colágeno e elástico. Após a tenotomia, metade dos animais receberam tenoxicam intramuscular por 7 dias e no 8o dia iniciou-se protocolo de exercício em esteira na metade de cada grupo. Os ratos foram divididos aleatoriamente em 4 grupos de tratamento: A sem antiinflamatório E sem exercício (controle); B com antiinflamatório E com exercício; C sem antiinflamatório E com exercício; D com antiinflamatório E sem exercício. Os animais foram eutanasiados com 1, 2, 4 e 8 semanas após a tenotomia, para avaliação histológica pelo PCNA, e biomecânica através do teste de resistência à tração e da medida do ciclo locomotor. Foram realizados análise de variância, teste de Kruskal-Wallis e o método de Bonferroni, no programa R Project, versão 2.11.1. O tempo cirúrgico médio foi de 1 minuto e 24 segundos, sem complicações observadas até a 8a semana pós-operatória. Observamos proliferação celular e fibrilogênese com duas semanas, e diminuição da celularidade e das fibras elásticas na 8a semana, além de mudanças na organização estrutural do sistema colágeno. Encontramos pico da imunomarcação com PCNA na 2a semana em todos os grupos, exceto no grupo A, cujo pico aconteceu com 1 semana da tenotomia. Evidenciamos resistência à tração significativamente maior (p=0,02) nos ratos submetidos ao exercício, 8 semanas após ruptura. Nos grupos com antiinflamatório, observamos um ciclo locomotor mais estável durante todo o tempo avaliado. Consideramos a técnica cirúrgica experimental de tenotomia completa do tendão calcâneo, realizada com auxílio da microscopia de luz e preservação do tendão plantar, simples, rápida, com sinais de cicatrização tendínea normal e de fácil reprodução em ratos. O exercício aeróbico, iniciado precocemente após tenotomia completa do tendão calcâneo, é significativamente benéfico na sua recuperação biomecânica e o uso combinado com antiinflamatório confere maior estabilidade na marcha, o que pode proteger contra rerruptura tendínea em ratos / Achilles tendon rupture is one of the most frequent tendon injuries. Although most studies have shown the benefits of exercise on tendon regeneration, controversy still exists concerning non-steroidal antinflammatory drug (NSAID) effects in this context. Several experimental models have been used for the study of Achilles tendon injury. In this study, we describe the surgical technique of right Achilles tenotomy in rats and subsequently evaluate the effects of NSAID and aerobic exercise, in an isolated fashion and combined, on cell proliferation and biomechanical aspects of the Achilles tendon after tenotomy. Experimental study with 156 male Wistar rats with an average age of 3 months and with average weight of 300g. Surgical procedures were performed under light microscopy, after anesthesia with thiopental. A five millimeters posterior longitudinal incision was created, proximally directed, starting five millimeters proximal to the posterior calcaneal tuberosity. A complete tenotomy of the Achilles tendon was performed, seven millimeters away from the calcaneal tuberosity. The plantaris tendon was preserved. We used Hematoxilin and Eosin, Picrosirius-red and Weigerts Resorcin-fucsin to observe general tendon healing, especially regarding collagen and elastic fibers. After tenotomy, half of the rats received an intramuscular injection of tenoxican for 7 days and exercise was initiated on the 8th day for half the animals of each group. Rats were randomly divided into four treatment groups: A) no NSAID and no exercise; B) NSAID plus exercise; C) no NSAID, with exercise; D) NSAID and no exercise. Animals were sacrificed at 1, 2, 4 and 8 weeks after the tenotomy and cell proliferation was evaluated by immunohistochemistry for PCNA, biomechanical evaluation was performed with ultimate load and gait cycle analysis was also carried out. We used the test of analysis of variance, the Kruskal-Wallis test and also, Bonferroni method, in the R Project program 2.11.1. The mean operative time was one minute and 24 seconds, without complications observed until the 8th postoperative week. Histological studies showed cellular proliferation and fibrilogenesis at two weeks, with decreased amounts of cellularity and elastic fibers at the 8th week, besides changes in structural organization of collagen fibers. The highest intensity of PCNA immunostaining was found at 2 weeks in all groups except for group A (control) that had the highest intensity at 1 week. Animals submitted to exercise had significantly higher (P = 0.02) ultimate loads at 8 weeks after injury. The animals that received NSAID presented with a more stable gait cycle. The surgical technique described for complete Achilles tenotomy, under light microscopy and sparing the plantaris tendon, is simple and quick, shows signs of normal healing process, and it is easily reproducible in rats. Aerobic exercise, initiated early after a complete Achilles tendon tenotomy, was beneficial to the biomechanical aspects of the tendon during regeneration and the combined use of NSAID improved the gaits characteristics, which could be protective against reruptures

Ruptura do tendão calcâneo é uma das lesões tendíneas mais frequentes. Embora a maioria dos trabalhos sugira que o exercício seja benéfico na cicatrização tendínea, não há consenso sobre o efeito do antiinflamatório neste contexto. Trabalhos experimentais tentam reproduzir lesão aguda deste tendão, em diferentes espécies animais. Neste estudo, descrevemos uma técnica de tenotomia completa do tendão calcâneo direito em ratos e, em seguida, avaliamos os efeitos do uso do antiinflamatório e do exercício aeróbico, isoladamente e em combinação, sobre a proliferação celular e o perfil biomecânico do tendão calcâneo, durante o processo de cicatrização após tenotomia. Estudo experimental com 156 ratos machos adultos, da raça Wistar, com idade média de 3 meses e peso médio de 300g. Após anestesia com tiopental e com auxílio da microscopia de luz, foi realizada incisão longitudinal posterior de cinco milímetros, em direção proximal, a partir da tuberosidade posterior do calcâneo da pata direita do rato. Foi feito corte transversal do tendão calcâneo, a sete milímetros da tuberosidade do calcâneo, com preservação do tendão plantar. Utilizamos as técnicas de Hematoxilina e Eosina, Picrosirius-red e Resorcina-fucsina de Weigert para avaliação da cicatrização tendínea e das fibras dos sistemas colágeno e elástico. Após a tenotomia, metade dos animais receberam tenoxicam intramuscular por 7 dias e no 8o dia iniciou-se protocolo de exercício em esteira na metade de cada grupo. Os ratos foram divididos aleatoriamente em 4 grupos de tratamento: A sem antiinflamatório E sem exercício (controle); B com antiinflamatório E com exercício; C sem antiinflamatório E com exercício; D com antiinflamatório E sem exercício. Os animais foram eutanasiados com 1, 2, 4 e 8 semanas após a tenotomia, para avaliação histológica pelo PCNA, e biomecânica através do teste de resistência à tração e da medida do ciclo locomotor. Foram realizados análise de variância, teste de Kruskal-Wallis e o método de Bonferroni, no programa R Project, versão 2.11.1. O tempo cirúrgico médio foi de 1 minuto e 24 segundos, sem complicações observadas até a 8a semana pós-operatória. Observamos proliferação celular e fibrilogênese com duas semanas, e diminuição da celularidade e das fibras elásticas na 8a semana, além de mudanças na organização estrutural do sistema colágeno. Encontramos pico da imunomarcação com PCNA na 2a semana em todos os grupos, exceto no grupo A, cujo pico aconteceu com 1 semana da tenotomia. Evidenciamos resistência à tração significativamente maior (p=0,02) nos ratos submetidos ao exercício, 8 semanas após ruptura. Nos grupos com antiinflamatório, observamos um ciclo locomotor mais estável durante todo o tempo avaliado. Consideramos a técnica cirúrgica experimental de tenotomia completa do tendão calcâneo, realizada com auxílio da microscopia de luz e preservação do tendão plantar, simples, rápida, com sinais de cicatrização tendínea normal e de fácil reprodução em ratos. O exercício aeróbico, iniciado precocemente após tenotomia completa do tendão calcâneo, é significativamente benéfico na sua recuperação biomecânica e o uso combinado com antiinflamatório confere maior estabilidade na marcha, o que pode proteger contra rerruptura tendínea em ratos / Achilles tendon rupture is one of the most frequent tendon injuries. Although most studies have shown the benefits of exercise on tendon regeneration, controversy still exists concerning non-steroidal antinflammatory drug (NSAID) effects in this context. Several experimental models have been used for the study of Achilles tendon injury. In this study, we describe the surgical technique of right Achilles tenotomy in rats and subsequently evaluate the effects of NSAID and aerobic exercise, in an isolated fashion and combined, on cell proliferation and biomechanical aspects of the Achilles tendon after tenotomy. Experimental study with 156 male Wistar rats with an average age of 3 months and with average weight of 300g. Surgical procedures were performed under light microscopy, after anesthesia with thiopental. A five millimeters posterior longitudinal incision was created, proximally directed, starting five millimeters proximal to the posterior calcaneal tuberosity. A complete tenotomy of the Achilles tendon was performed, seven millimeters away from the calcaneal tuberosity. The plantaris tendon was preserved. We used Hematoxilin and Eosin, Picrosirius-red and Weigerts Resorcin-fucsin to observe general tendon healing, especially regarding collagen and elastic fibers. After tenotomy, half of the rats received an intramuscular injection of tenoxican for 7 days and exercise was initiated on the 8th day for half the animals of each group. Rats were randomly divided into four treatment groups: A) no NSAID and no exercise; B) NSAID plus exercise; C) no NSAID, with exercise; D) NSAID and no exercise. Animals were sacrificed at 1, 2, 4 and 8 weeks after the tenotomy and cell proliferation was evaluated by immunohistochemistry for PCNA, biomechanical evaluation was performed with ultimate load and gait cycle analysis was also carried out. We used the test of analysis of variance, the Kruskal-Wallis test and also, Bonferroni method, in the R Project program 2.11.1. The mean operative time was one minute and 24 seconds, without complications observed until the 8th postoperative week. Histological studies showed cellular proliferation and fibrilogenesis at two weeks, with decreased amounts of cellularity and elastic fibers at the 8th week, besides changes in structural organization of collagen fibers. The highest intensity of PCNA immunostaining was found at 2 weeks in all groups except for group A (control) that had the highest intensity at 1 week. Animals submitted to exercise had significantly higher (P = 0.02) ultimate loads at 8 weeks after injury. The animals that received NSAID presented with a more stable gait cycle. The surgical technique described for complete Achilles tenotomy, under light microscopy and sparing the plantaris tendon, is simple and quick, shows signs of normal healing process, and it is easily reproducible in rats. Aerobic exercise, initiated early after a complete Achilles tendon tenotomy, was beneficial to the biomechanical aspects of the tendon during regeneration and the combined use of NSAID improved the gaits characteristics, which could be protective against reruptures