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1.
Biophys J ; 123(5): 555-571, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38291752

RESUMO

Multiscale models aiming to connect muscle's molecular and cellular function have been difficult to develop, in part due to a lack of self-consistent multiscale data. To address this gap, we measured the force response from single, skinned rabbit psoas muscle fibers to ramp shortenings and step stretches performed on the plateau region of the force-length relationship. We isolated myosin from the same muscles and, under similar conditions, performed single-molecule and ensemble measurements of myosin's ATP-dependent interaction with actin using laser trapping and in vitro motility assays. We fit the fiber data by developing a partial differential equation model that includes thick filament activation, whereby an increase in force on the thick filament pulls myosin out of an inhibited state. The model also includes a series elastic element and a parallel elastic element. This parallel elastic element models a titin-actin interaction proposed to account for the increase in isometric force after stretch (residual force enhancement). By optimizing the model fit to a subset of our fiber measurements, we specified seven unknown parameters. The model then successfully predicted the remainder of our fiber measurements and also our molecular measurements from the laser trap and in vitro motility. The success of the model suggests that our multiscale data are self-consistent and can serve as a testbed for other multiscale models. Moreover, the model captures the decrease in isometric force observed in our muscle fibers after active shortening (force depression), suggesting a molecular mechanism for force depression, whereby a parallel elastic element combines with thick filament activation to decrease the number of cycling cross-bridges.


Assuntos
Actinas , Depressão , Animais , Coelhos , Sarcômeros/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Miosinas , Contração Muscular
2.
Arch Bone Jt Surg ; 11(11): 711-716, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058970

RESUMO

Objectives: The study aimed at discovering the existing differences in lower limb joints' kinematics, and EMG signals of 4 particular muscles of the ankle joint during gait, between normal subjects and patients with bilateral triple arthrodesis. Methods: In this research, a 3D motion analysis system was used and joints' angles were calculated using a MATLAB code, and based on the data collected from markers movements, for patients with bilateral triple arthrodesis and normal subjects. Moreover, the EMG signals of ankle muscles in each subject, and the graphs of mean plus and minus standard deviation of lower limb joint angles and muscles' EMG were calculated by MATLAB. Results: In all patients, an initial ankle eversion and valgus deformity were observed in their knee joints. In addition, for all patients, the maximum knee extension was less than that of the average value of the normal subjects. Furthermore, the results of the electromyography showed that, in all patients, delay occurred in gastrocnemius and soleus muscles in maximum contraction in their EMG signals. Besides, during the early stance phase of gait cycles, the mean value of EMG of peroneus brevis muscle for patients was more than that of normal subjects. Conclusion: Atrophy of four ankle muscles including (soleus, lateral gastrocnemius, tibialis anterior and peroneus brevis), also limitation of joints movement were observed in patients, compared to normal subjects. Based on the results of this work, in order to reduce further musculoskeletal disorders in patients who underwent bilateral triple arthrodesis surgery, there is a serious need to use physiotherapy after the surgery.

3.
J Biomech ; 155: 111659, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37290181

RESUMO

Studies of muscle structure and function can be traced to at least 2,000 years ago. However, the modern era of muscle contraction mechanisms started in the 1950s with the classic works by AF Huxley and HE Huxley, both born in the United Kingdom, but not related and working independently. HE Huxley was the first to suggest that muscle contraction occurred through the sliding of two sets of filamentous structures (actin or thin filaments and myosin or thick filaments). AF Huxley then developed a biologically inspired mathematical model suggesting a possible molecular mechanism of how this sliding of actin and myosin might take place. This model then evolved from a two-state to a multi-state model of myosin-actin interactions, and from one that suggested a linear motor causing the sliding to a rotating motor. This model, the cross-bridge model of muscle contraction, is still widely used in biomechanics, and even the more sophisticated cross-bridge models of today still contain many of the features originally proposed by AF Huxley. In 2002, we discovered a hitherto unknown property of muscle contraction that suggested the involvement of passive structures in active force production, the so-called passive force enhancement. It was quickly revealed that this passive force enhancement was caused by the filamentous protein titin, and the three-filament (actin, myosin, and titin) sarcomere model of muscle contraction evolved. There are many suggestions of how these three proteins interact to cause contraction and produce active force, and one such suggestion is described here, but the molecular details of this proposed mechanism still need careful evaluation.


Assuntos
Actinas , Contração Muscular , Conectina/metabolismo , Actinas/metabolismo , Contração Muscular/fisiologia , Sarcômeros/fisiologia , Miosinas/metabolismo
4.
Dev Med Child Neurol ; 65(12): 1639-1645, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37198748

RESUMO

AIM: To determine the dose-response relationship of collagenase Clostridium histolyticum (CCH) on collagen content and the change in muscle fiber bundle stiffness after ex vivo treatment of adductor longus biopsies with CCH in children with cerebral palsy (CP). METHOD: Biopsy samples of adductor longus from children with CP (classified in Gross Motor Function Classification System levels IV and V) were treated with 0 U/mL, 200 U/mL, 350 U/mL, or 500 U/mL CCH; percentage collagen reduction was measured to determine the dose-response. Peak and steady-state stresses were determined at 1%, 2.5%, 5%, and 7.5% strain increments; Young's modulus was calculated. RESULTS: Eleven patients were enrolled (nine males, two females, mean age at surgery 6 years 5 months; range: 2-16 years). A linear CCH dose-response relationship was determined. Peak and steady-state stress generation increased linearly at 5.9/2.3mN/mm2 , 12.4/5.3mN/mm2 , 22.2/9.7mN/mm2 , and 33.3/15.5mN/mm2 at each percentage strain increment respectively. After CCH treatment, peak and steady-state stress generation decreased to 3.2/1.2mN/mm2 , 6.5/2.9mN/mm2 , 12.2/5.7mN/mm2 , and 15.4/7.7mN/mm2 respectively (p < 0.004). Young's modulus decreased from 205 kPa to 100 kPa after CCH (p = 0.003). INTERPRETATION: This preclinical ex vivo study provides proof of concept for the use of collagenase to decrease muscle stiffness in individuals with CP.


Assuntos
Paralisia Cerebral , Masculino , Criança , Feminino , Humanos , Colagenase Microbiana/uso terapêutico , Músculo Esquelético , Colágeno , Fibras Musculares Esqueléticas , Resultado do Tratamento
5.
Front Sports Act Living ; 4: 853701, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35434617

RESUMO

A retrospective analysis of routine countermovement jump (CMJ) testing, a coupled eccentric-concentric (stretch-shorten-cycle: SSC) movement, was performed in female elite alpine skiers with anterior cruciate ligament (ACL) reconstruction (ACLR) and without ACLR. A total of 567 tests obtained from the daily training environment were analyzed in 41 elite female athletes (non-injured control: n = 30, ACLR: n = 17), including n = 6 athletes with pre-injury data, between 16 and 32 years of age from alpine ski racing (n = 32) and skier cross (n = 9). Bilateral CMJ testing was conducted on a dual force plate system, and the limb-specific vertical ground reaction force (Fz) was analyzed to obtain the net eccentric deceleration impulse (Ecc), lower limb stiffness (Stiff), maximal vertical jump height (JH), peak external mechanical power (PP) exerted on the body center of mass (BCM), modified-reactive-strength-index (RSImod), and the loss in BCM velocity during the final phase of the takeoff Δ(Vmax-Vtakeoff). Eccentric and concentric phase-specific between-limb asymmetry indexes (AIs) were also calculated. Additive mixed effects models (AMMs) were used to compare the age-dependent and post-injury time course change between groups. The mean values for non-injured controls >25 years of age were used as a comparative benchmark for recovery given the absence of pre-injury data. Net eccentric deceleration impulse increased and Δ(Vmax-Vtakeoff) decreased with age for the non-injured control group (p < 0.001) while between-limb AI (mean ± SD) fell between 1 ± 5% for the concentric phase and 3 ± 7% for the eccentric deceleration phase. Between-limb asymmetry became smaller in ACLR skiers with time-from-surgery to reach non-injured control values by 2 years, but SSC function, such as JH and PP, remained depressed up to 5 years post-surgery (p < 0.01), indicating impairments in SSC function. This highlights the importance of evaluating SSC performance capacity alongside vertical jump force-time asymmetries in female ACLR alpine skiers.

6.
J Orthop Res ; 40(12): 2803-2812, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35194823

RESUMO

A retrospective analysis of longitudinally collected athlete monitoring data was conducted to generate a model of neuromuscular recovery after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Neuromuscular testing data including countermovement jump (CMJ) force-time asymmetries and knee extensor strength (maximum voluntary contractionext ) asymmetries (between-limb asymmetry index-AI) were obtained from athletes with ACLR using semitendinosus (ST) autograft (n = 29; AI measurements: n = 494), bone patellar tendon bone autograft (n = 5; AI measurements: n = 88) and noninjured controls (n = 178; AI measurements: n = 3188). Explosive strength measured as the rate of torque development was also calculated. CMJ force-time asymmetries were measured over discrete movement phases (eccentric deceleration phase, concentric phase). Separate additive mixed effects models (additive mixed effects model [AMM]) were fit for each AI with a main effect for the surgical technique and a smooth term for the time since surgery (days). The models explained between 43% and 91% of the deviance in neuromuscular recovery after ACLR. The mean time course was generated from the AMM. Comparative neuromuscular recovery profiles of an athlete with an accelerated progression and an athlete with a delayed progression after a serious multiligament injury were generated. Clinical Significance: This paper provides a new perspective on the utility of longitudinal athlete monitoring including routine testing to develop models of neuromuscular recovery after ACLR that can be used to characterize individual progression throughout rehabilitation.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Músculos Isquiossurais , Humanos , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/reabilitação , Estudos Retrospectivos , Atletas , Força Muscular
7.
Eur J Appl Physiol ; 121(7): 1849-1858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33709206

RESUMO

PURPOSE: Knee flexor electromechanical delay (EMD) has been proposed as a contributing factor to non-contact anterior cruciate ligament (ACL) injury risk and the semitendinosus (ST) autograft technique has been shown to impair knee flexor torque at large angles of knee flexion. The purpose of this study was to analyse the effects of ACL reconstruction (ACLR) using the ST tendon autograft technique on knee flexor EMD across the knee flexion range of motion, in athletes who had returned to competition. METHODS: Athletes with ACLR (n = 8 females, n = 3 males, 1.7 ± 0.5 years post-surgery) and non-injured control athletes (n = 6 females, n = 4 males) performed rapid maximal voluntary contractions of isometric knee flexion and extension at 30°, 50°, 70°, 90°,and 105° of knee flexion. Electrical activity of the ST, biceps femoris (BF), vastus lateralis, and vastus medialis was recorded using surface electromyography. RESULTS: No change in EMD for the knee flexors or extensors was observed across joint angles. Greater EMD was found only for the BF in the ACLR limb of injured athletes compared to the contralateral limb (P < 0.05). In post-hoc analysis, evidence of ST tendon regrowth was noted for only 2/11 athletes. CONCLUSION: While the EMD-joint angle relationship appeared to be unaffected by ST tendon harvest for ACLR, the absence of ST tendon regrowth should be considered. Despite return to competition, greater BF EMD was found, which may impair knee joint stabilization capacity by delaying the transfer time of muscle tension to the tibia after ST autograft.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Músculos Isquiossurais/fisiologia , Músculos Isquiossurais/cirurgia , Tendões dos Músculos Isquiotibiais/transplante , Volta ao Esporte , Transferência Tendinosa/métodos , Autoenxertos , Estudos de Casos e Controles , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular/fisiologia , Adulto Jovem
8.
J Orthop Res ; 39(12): 2556-2567, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580730

RESUMO

Concurrent osteoarthritic (OA) manifestations in bone and cartilage are poorly known. To shed light on this issue, this study aims to investigate changes in subchondral bone and articular cartilage at two time points after anterior cruciate ligament transection (ACLT) in a rabbit model. 2 (N = 16) and 8 (N = 10) weeks after ACLT, the subchondral bone structure, cartilage thickness, Osteoarthritis Research Society International (OARSI) score, fixed charged density (FCD), and collagen orientation angle were analyzed. OA related changes were evaluated by comparing the ACLT to the contralateral (C-L) and control knees. Already 2 weeks after ACLT, higher trabecular number in the medial femoral condyle and femoral groove, greater OARSI score in the femoral condyles, and thinner trabeculae in the lateral tibial plateau and femoral groove were observed in ACLT compared to C-L knees. Only minor changes of cartilage collagen orientation in the femoral condyles and femoral groove and smaller FCD in the femoral condyles, medial tibial plateau, femoral groove and patella were observed. 8 weeks post-ACLT, the surgical knees had thinner subchondral plate and trabeculae, and smaller trabecular bone volume fraction in most of the knee locations. OARSI score was greater in the femoral condyle and lateral tibial plateau cartilage. FCD loss was progressive only in the femoral condyle, femoral groove, and patellar cartilage, and minor changes of cartilage collagen orientation angle were present in the femoral condyles, femoral groove, and lateral tibial plateau. We conclude that ACLT induces progressive subchondral bone loss, during which proteoglycan loss occurs followed by their partly recovery, as indicated by FCD results.


Assuntos
Cartilagem Articular , Fraturas Intra-Articulares , Osteoartrite , Animais , Ligamento Cruzado Anterior/cirurgia , Modelos Animais de Doenças , Epífises , Osteocondrodisplasias , Coelhos
9.
J Vis Exp ; (161)2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32804160

RESUMO

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. Mechanistic studies to improve our understanding of the underlying pathophysiology responsible for the development of premature TV failure are lacking. Due to the inability to conduct these studies in humans, an animal model is required. In this manuscript, we describe the protocols for a novel chronic recovery infant piglet heart model for the study of changes in the TV when placed under combined volume and pressure stress. In this model, volume loading of the right ventricle and the TV is achieved through the disruption of the pulmonary valve. Then pressure loading is accomplished through the placement of a pulmonary artery band. The success of this model is assessed at four weeks post intervention surgery through echocardiography, intracardiac pressure measurement, and pathologic examination of the heart specimens.


Assuntos
Ventrículos do Coração/fisiopatologia , Valva Tricúspide/fisiopatologia , Anestesia , Animais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Hemodinâmica , Imageamento Tridimensional , Masculino , Modelos Animais , Tamanho do Órgão , Pressão , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Valva Pulmonar/fisiopatologia , Valva Pulmonar/cirurgia , Suínos , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia
10.
J Orthop Res ; 38(9): 1974-1986, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32129515

RESUMO

In this study, the rabbit model with anterior cruciate ligament transection (ACLT) was used to investigate early degenerative changes in cartilage using multiparametric quantitative magnetic resonance imaging (qMRI). ACLT was surgically induced in the knees of skeletally mature New Zealand White rabbits (n = 14). ACL transected and contralateral knee compartments-medial femur, lateral femur, medial tibia, and lateral tibia-were harvested 2 (n = 8) and 8 weeks (n = 6) postsurgery. Twelve age-matched nonoperated rabbits served as control. qMRI was conducted at 9.4 T and included relaxation times T1 , T2 , continuous-wave T1ρ (CWT1ρ ), adiabatic T1ρ (AdT1ρ ), adiabatic T2ρ (AdT2ρ ), and relaxation along a fictitious field (TRAFF ). For reference, quantitative histology and biomechanical measurements were carried out. Posttraumatic changes were primarily noted in the superficial half of the cartilage. Prolonged T1 , T2 , CWT1ρ , and AdT1ρ were observed in the lateral femur 2 and 8 weeks post-ACLT, compared with the corresponding control and contralateral groups (P < .05). Collagen orientation was significantly altered in the lateral femur at 2 weeks post-ACLT compared with the corresponding control group. In the medial femur, all the studied relaxation time parameters, except TRAFF , were increased 8 weeks post-ACLT, as compared with the corresponding contralateral and control groups (P < .05). Similarly, significant proteoglycan loss was observed in the medial femur at 8 weeks following surgery (P < .05). Multiparametric MRI demonstrated early degenerative changes primarily in the superficial cartilage with T1 , T2 , CWT1ρ , and AdT1ρ sensitive to cartilage changes at 2 weeks after surgery.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Osteoartrite/diagnóstico por imagem , Animais , Lesões do Ligamento Cruzado Anterior/complicações , Modelos Animais de Doenças , Feminino , Osteoartrite/etiologia , Coelhos
11.
J Sport Health Sci ; 9(2): 132-139, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32099721

RESUMO

Background: Osteoarthritis is one of the leading causes of pain and disability worldwide, and a large percentage of patients with osteoarthritis are individuals who are also obese. In recent years, a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage (both with and without the superimposition of trauma), which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators. Of note, there is a disparity between whether the dietary challenges commence at weaning, representing a weanling onset, or at skeletal maturity, representing an adult onset of obesity. We wished to evaluate the effect of the dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose (HFS) diet to determine whether these factors may result in disparate outcomes, as there is evidence suggesting that these factors result in differential metabolic disturbances. Based on dietary exposure time, we hypothesized that rats fed an HFS diet for 14 weeks from weaning (HFS Weanling) would demonstrate an increase in knee joint damage scores, whereas rats exposed to the HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult) and rats exposed to a standard chow diet (Chow) would not display an increase in knee joint damage scores. Methods: Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning (HFS Weanling) or an HFS diet for 4 weeks, starting at 12 weeks of age (HFS Adult). At sacrifice, joints were scored using the modified Mankin Criteria, and serum was analyzed for a defined subset of inflammatory markers (Interleukin-6, leptin, monocyte chemoattractant protein-1, and tumor necrosis factor α). Results: When the HFS Weanling and HFS Adult groups were compared, both groups had a similar percent of body fat, although the HFS Weanling group had a significantly greater body mass than the HFS Adult group. The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group. Although knee joint damage scores were low in all 3 groups, we found, contrary to our hypothesis, that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups. Furthermore, we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group. Conclusion: These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group. Interestingly, when assessing various serum proinflammatory markers, no significant differences were detected between the HFS Adult and HFS Weanling groups. Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated, these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced. Moreover, increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Obesidade/complicações , Osteoartrite do Joelho/etiologia , Fatores Etários , Animais , Biomarcadores/sangue , Distribuição da Gordura Corporal , Índice de Massa Corporal , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/sangue , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Osteoartrite do Joelho/patologia , Ratos Sprague-Dawley
12.
J Biomech ; 98: 109450, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31740016

RESUMO

Anterior cruciate ligament (ACL) injury often leads to post-traumatic osteoarthritis (OA) and articular cartilage degradation, changing biomechanics of the tissue and chondrocytes, and altering the fixed charged density (FCD) and collagen network. However, changes in these properties are not known at a very early time point after ACL rupture, but recognizing early changes might be crucial for successful intervention. We investigated the effects of ACL transection (ACLT) in rabbits on the site-specific biomechanical properties of articular cartilage and chondrocytes, FCD content and collagen network organization, two weeks post-surgery. Unilateral ACLT was performed in eight rabbits, and femoral condyles, tibial plateaus, femoral grooves and patellae were harvested from experimental and contralateral knee joints. An intact control group was used as a reference. We analyzed chondrocyte morphology under pre- and static loading, cartilage biomechanical properties, FCD content and collagen fibril orientation. ACLT caused FCD loss in the lateral and medial femoral condyle, lateral tibial plateau, femoral groove and patellar cartilage (p < 0.05). Minor changes in the collagen orientation occurred in the femoral groove and lateral and medial femoral condyle cartilage (p < 0.05). Cartilage stiffness was reduced in the lateral and medial femoral condyles, and chondrocyte biomechanics was altered in the lateral femoral condyle and patellar cartilage (p < 0.05). We observed loss of FCD from articular cartilage two weeks after ACLT at several joint locations. These changes may have led to decreased cartilage stiffness and altered cell deformation behavior, especially in the femoral condyles.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Cartilagem Articular/citologia , Cartilagem Articular/metabolismo , Condrócitos/citologia , Fenômenos Mecânicos , Animais , Fenômenos Biomecânicos , Cartilagem Articular/fisiologia , Condrócitos/metabolismo , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Coelhos
13.
Int J Mol Sci ; 20(21)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689920

RESUMO

Muscle contraction is initiated by the interaction between actin and myosin filaments. The sliding of actin filaments relative to myosin filaments is produced by cross-bridge cycling, which is governed by the theoretical framework of the cross-bridge theory. The cross-bridge theory explains well a number of mechanical responses, such as isometric and concentric contractions. However, some experimental observations cannot be explained with the cross-bridge theory; for example, the increased isometric force after eccentric contractions. The steady-state, isometric force after an eccentric contraction is greater than that attained in a purely isometric contraction at the same muscle length and same activation level. This well-acknowledged and universally observed property is referred to as residual force enhancement (rFE). Since rFE cannot be explained by the cross-bridge theory, alternative mechanisms for explaining this force response have been proposed. In this review, we introduce the basic concepts of sarcomere length non-uniformity and titin elasticity, which are the primary candidates that have been used for explaining rFE, and discuss unresolved problems regarding these mechanisms, and how to proceed with future experiments in this exciting area of research.


Assuntos
Contração Muscular , Sarcômeros/metabolismo , Actinas/metabolismo , Animais , Conectina/química , Conectina/metabolismo , Humanos , Miosinas/metabolismo , Sarcômeros/fisiologia
14.
J Orthop Surg Res ; 14(1): 187, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227002

RESUMO

BACKGROUND: Cerebral palsy (CP) is the most common cause of childhood disability, typified by a static encephalopathy with peripheral musculoskeletal manifestations-most commonly related to spasticity-that are progressive with age. Hip displacement is one of the most common manifestations, observed to lead to painful degenerative arthritis over time. Despite the key role that spasticity-related adductor muscle contractures are thought to play in the development of hip displacement in CP, basic science research in this area to date has been limited. This study was initiated to correlate hip adductor muscle changes intrinsic to the sarcomere-specifically, titin isoforms and sarcomere length-to the severity of hip displacement in children with spastic cerebral palsy. METHODS: Single gracilis muscle biopsies were obtained from children with CP (Gross Motor Function Classification System (GMFCS) III-V; n = 10) who underwent adductor muscle release surgery for the treatment of hip displacement. Gel electrophoresis was used to estimate titin molecular weight. Sarcomere lengths were measured from muscle fascicles using laser diffraction. The severity of hip displacement was determined by measuring by Reimers migration percentage (MP) from anteroposterior pelvic x-rays. Correlation analyses between titin, sarcomere lengths, and MP were performed. RESULTS: The mean molecular weight of titin was 3588 kDa. The mean sarcomere length was 3.51 µm. Increased MP was found to be associated with heavier isoforms of titin (R2 = 0.65, p < 0.05) and with increased sarcomere lengths (R2 = 0.65, p < 0.05). Heavier isoforms of titin were also associated with increased sarcomere lengths (R2 = 0.80, p < 0.05). CONCLUSIONS: Our results suggest that both larger titin isoforms and sarcomere lengths are positively correlated with increased severity of hip displacement and may represent adaptations in response to concomitant increases in spasticity and muscle shortening. TRIAL REGISTRATION: As this study does not report the results of a health care intervention on human participants, it has not been registered.


Assuntos
Paralisia Cerebral/patologia , Luxação do Quadril/etiologia , Músculo Esquelético/patologia , Sarcômeros/patologia , Biópsia , Paralisia Cerebral/complicações , Criança , Pré-Escolar , Feminino , Músculo Grácil/patologia , Luxação do Quadril/patologia , Humanos , Projetos Piloto
15.
J Biomech ; 87: 100-106, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30853092

RESUMO

Cerebral palsy (CP) is the result of a static brain lesion which causes spasticity and muscle contracture. The source of the increased passive stiffness in patients is not understood and while whole muscle down to single muscle fibres have been investigated, the smallest functional unit of muscle (the sarcomere) has not been. Muscle biopsies (adductor longus and gracilis) from pediatric patients were obtained (CP n = 9 and control n = 2) and analyzed for mechanical stiffness, in-vivo sarcomere length and titin isoforms. Adductor longus muscle was the focus of this study and the results for sarcomere length showed a significant increase in length for CP (3.6 µm) compared to controls (2.6 µm). Passive stress at the same sarcomere length for CP compared to control was significantly lower in CP and the elastic modulus for the physiological range of muscle was lower in CP compared to control (98.2 kPa and 166.1 kPa, respectively). Our results show that CP muscle at its most reduced level (the myofibril) is more compliant compared to normal, which is completely opposite to what is observed at higher structural levels (single fibres, muscle fibre bundles and whole muscle). It is noteworthy that at the in vivo sarcomere length in CP, the passive forces are greater than normal, purely as a functional of these more compliant sarcomeres operating at long lengths. Titin isoforms were not different between CP and non-CP adductor longus but titin:nebulin was reduced in CP muscle, which may be due to titin loss or an over-expression of nebulin in CP muscles.


Assuntos
Paralisia Cerebral/fisiopatologia , Músculo Esquelético/patologia , Miofibrilas/patologia , Fenômenos Biofísicos , Biópsia , Criança , Pré-Escolar , Conectina/química , Conectina/metabolismo , Humanos , Espasticidade Muscular/patologia , Sarcômeros/fisiologia
16.
Sci Rep ; 8(1): 12051, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-30104576

RESUMO

Micro-computed tomography (µCT) is a standard method for bone morphometric evaluation. However, the scan time can be long and the radiation dose during the scan may have adverse effects on test subjects, therefore both of them should be minimized. This could be achieved by applying iterative reconstruction (IR) on sparse projection data, as IR is capable of producing reconstructions of sufficient image quality with less projection data than the traditional algorithm requires. In this work, the performance of three IR algorithms was assessed for quantitative bone imaging from low-resolution data in the evaluation of the rabbit model of osteoarthritis. Subchondral bone images were reconstructed with a conjugate gradient least squares algorithm, a total variation regularization scheme, and a discrete algebraic reconstruction technique to obtain quantitative bone morphometry, and the results obtained in this manner were compared with those obtained from the reference reconstruction. Our approaches were sufficient to identify changes in bone structure in early osteoarthritis, and these changes were preserved even when minimal data were provided for the reconstruction. Thus, our results suggest that IR algorithms give reliable performance with sparse projection data, thereby recommending them for use in µCT studies where time and radiation exposure are preferably minimized.


Assuntos
Ligamento Cruzado Anterior/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Articulação do Joelho/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Microtomografia por Raio-X/métodos , Algoritmos , Animais , Ligamento Cruzado Anterior/cirurgia , Osso e Ossos/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Coelhos
17.
Orthop J Sports Med ; 5(7): 2325967117714756, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28812037

RESUMO

BACKGROUND: Anterior cruciate ligament (ACL) tear is the most frequent injury in alpine ski racing, and there is a high prevalence of ACL reinjury. Limited data exist on the concurrent pathology with primary ACL tears in elite alpine ski racers and the magnitude of injury progression after primary ACL reconstruction (ACLR). PURPOSE: To evaluate (1) the involvement of intra-articular and multiligament pathologies at the time of primary ACLR, (2) the subsequent progression in meniscal/chondral injuries, and (3) the occurrence of ACL reinjury in elite alpine ski racers. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Primary ACLR operative reports (n = 28) were obtained for 32 elite alpine ski racers along with the reports of 20 operative procedures that occurred subsequent to primary ACLR. Operative reports were evaluated to identify the presence/location of multiligament injury, meniscal tears, and chondral lesions. RESULTS: At the time of primary ACLR, a majority of knees (82%; 23/28) demonstrated concurrent injury compared with isolated ACL tears; 32% of knees sustained multiligament injuries (9/28), and 8 involved the ipsilateral medial collateral ligament (MCL). Of the ACL-injured knees, 54% had chondral lesions, of which 73% were sustained in the lateral knee compartment, and 82% of meniscal tears (14/17) were complex in nature. Bilateral ACL tears were seen in 22% of the participants, and 28% underwent ACL revision. In the case of ACL revision or future meniscal/chondral surgery, 60% of meniscal tears and 80% of chondral lesions had worsened since the time of primary ACLR. CONCLUSION: Concurrent injury was common in this group of elite ski racers. Primary ACL tears were typically accompanied by lateral compartment chondral lesions and complex meniscal tears that worsened over time. ACL/MCL tears were the most common multiligament injury pattern.

18.
J Exp Biol ; 220(Pt 8): 1509-1515, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28232399

RESUMO

The steady-state isometric force after active shortening of a skeletal muscle is lower than the purely isometric force at the corresponding length. This property of skeletal muscle is known as force depression. The purpose of this study was to investigate whether the energy cost of force production at the steady state after active shortening was reduced compared with the energy cost of force production for a purely isometric contraction performed at the corresponding length (same length, same activation). Experiments were performed in skinned fibres isolated from rabbit psoas muscle. Skinned fibres were actively shortened from an average sarcomere length of 3.0 µm to an average sarcomere length of 2.4 µm. Purely isometric reference contractions were performed at an average sarcomere length of 2.4 µm. Simultaneously with the force measurements, the ATP cost was measured during the last 30 s of isometric contractions using an enzyme-coupled assay. Stiffness was calculated during a quick stretch-release cycle of 0.2% fibre length performed once the steady state had been reached after active shortening and during the purely isometric reference contractions. Force and stiffness following active shortening were decreased by 10.0±1.8% and 11.0±2.2%, respectively, compared with the isometric reference contractions. Similarly, ATPase activity per second (not normalized to the force) showed a decrease of 15.6±3.0% in the force-depressed state compared with the purely isometric reference state. However, ATPase activity per second per unit of force was similar for the isometric contractions following active shortening (28.7±2.4 mmol l-1 mN-1 s mm3) and the corresponding purely isometric reference contraction (30.9±2.8 mmol l-1 mN-1 s mm3). Furthermore, the reduction in absolute ATPase activity per second was significantly correlated with force depression and stiffness depression. These results are in accordance with the idea that force depression following active shortening is primarily caused by a decrease in the proportion of attached cross-bridges. Furthermore, these findings, along with previously reported results showing a decrease in ATP consumption per unit of force after active muscle stretching, suggest that the mechanisms involved in the steady-state force after active muscle shortening and active muscle lengthening are of distinctly different origin.


Assuntos
Adenosina Trifosfatases/metabolismo , Contração Isométrica , Fibras Musculares Esqueléticas/fisiologia , Animais , Fenômenos Biomecânicos , Metabolismo Energético , Feminino , Coelhos , Sarcômeros/fisiologia
19.
Am J Physiol Cell Physiol ; 310(4): C318-27, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26632598

RESUMO

Normal adult aging is associated with impaired muscle contractile function; however, to what extent cross-bridge kinetics are altered in aging muscle is not clear. We used a slacken restretch maneuver on single muscle fiber segments biopsied from the vastus lateralis of young adults (∼23 yr), older nonathlete (NA) adults (∼80 yr), and age-matched world class masters athletes (MA; ∼80 yr) to assess the rate of force redevelopment (ktr) and cross-bridge kinetics. A post hoc analysis was performed, and only the mechanical properties of "slow type" fibers based on unloaded shortening velocity (Vo) measurements are reported. The MA and NA were ∼54 and 43% weaker, respectively, for specific force compared with young. Similarly, when force was normalized to cross-sectional area determined via the fiber shape angularity data, both old groups did not differ, and the MA and NA were ∼43 and 48% weaker, respectively, compared with young (P < 0.05). Vo for both MA and NA old groups was 62 and 46% slower, respectively, compared with young. Both MA and NA adults had approximately two times slower values for ktr compared with young. The slower Vo in both old groups relative to young, coupled with a similarly reduced ktr, suggests impaired cross-bridge kinetics are responsible for impaired single fiber contractile properties with aging. These results challenge the widely accepted resilience of slow type fibers to cellular aging.


Assuntos
Envelhecimento , Atletas , Contração Muscular , Fibras Musculares Esqueléticas , Força Muscular , Músculo Quadríceps/fisiopatologia , Sarcopenia/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Imunofluorescência , Humanos , Cinética , Masculino , Fibras Musculares Esqueléticas/química , Cadeias Pesadas de Miosina/análise , Músculo Quadríceps/química , Sarcopenia/diagnóstico , Sarcopenia/metabolismo , Adulto Jovem
20.
Med Sci Sports Exerc ; 47(1): 109-19, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24824771

RESUMO

PURPOSE: Because of the importance of hamstrings (HAM) and quadriceps (QUAD) strength for anterior cruciate ligament (ACL) injury prevention and the high incidence of ACL injury in ski racing, HAM and QUAD maximal and explosive strength were assessed in ski racers with and without ACL reconstruction (ACL-R). METHODS: Uninjured (n = 13 males, n = 8 females) and ACL-R (n = 3 males, n = 5 females, 25.0 ± 11.3 months after operation) elite ski racers performed maximal voluntary isometric HAM and QUAD contractions to obtain maximal torque (MVC) and rate of torque development (RTD) at 0-50, 0-100, 0-150, and 0-200 ms. MVC and RTD (per kilogram body mass) were calculated for the uninjured group to compare between sexes and to compare the control group with the ACL-R limb and unaffected limb of the ACL-R skiers. HAM/QUAD MVC and RTD strength ratios (H/Q ratios) were also compared. RESULTS: The ACL-R limb demonstrated significant HAM and QUAD deficits compared with the contralateral limb for MVC and late-phase RTD (P < 0.05). Uninjured male skiers also displayed a limb difference for HAM MVC and RTD at 150 ms (P < 0.05). QUAD MVC and RTD deficits were observed in the affected limb of ACL-R skiers, which led to an inflated H/Q ratio (50 ms) compared with that in uninjured controls (P < 0.05). Compared with male skiers, females displayed greater relative HAM RTD (50 ms) and an elevated H/Q RTD ratio (50 ms), suggesting enhanced ACL protection (P < 0.05). CONCLUSIONS: Because of the strength demands of ski racing, our results suggest the importance of including HAM and QUAD strength assessments in the physical evaluation of uninjured skiers. Furthermore, HAM and QUAD strength should be assessed over a long-term period after surgery to identify chronic strength deficits in ACL-R ski racers.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Força Muscular , Músculo Quadríceps/fisiopatologia , Esqui/lesões , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Feminino , Voluntários Saudáveis , Humanos , Contração Isométrica , Traumatismos do Joelho/prevenção & controle , Masculino , Debilidade Muscular/diagnóstico , Fatores Sexuais , Esqui/fisiologia , Coxa da Perna , Torque , Adulto Jovem
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