Gene clustering of the small leucine -rich repeat gene family

The small leucine-rich repeat proteoglycans (or SLRPs) are a group of extracellular proteins (ECM) that belong to the leucine-rich repeat (LRR) superfamily of proteins. The LRR is a protein folding motif composed of 20–30 amino acids with leucines in conserved positions. LRR-containing proteins are present in a broad spectrum of organisms and possess diverse cellular functions and localization. In mammals, the SLRPs are abundant in connective tissues, such as bones, cartilage, tendons, skin, and blood vessels. We have discovered a new member of the class I small leucine rich repeat proteoglycan (SLRP) family which is distinct from the other class I SLRPs since it possesses a unique stretch of aspartate residues at its N-terminus. For this reason, we called the molecule asporin. The deduced amino acid sequence is about 50% identical (and 70% similar) to decorin and biglycan. However, asporin does not contain a serine/glycine dipeptide sequence required for the assembly of O-linked glycosaminoglycans and is probably not a proteoglycan. The tissue expression of asporin partially overlaps with the expression of decorin and biglycan. During mouse embryonic development, asporin mRNA expression was detected primarily in the skeleton and other specialized connective tissues; very little asporin message was detected in the major parenchymal organs. The mouse asporin gene structure is similar to that of biglycan and decorin with 8 exons. The asporin gene is localized to human chromosome 9q22-9g21.3 where asporin is part of a SLRP gene cluster that includes ECM2, osteoadherin, and osteoglycin. This gene cluster of four LRR-encoding genes is embedded in a 238 kilobase intron of another novel gene named Tes9orf that is expressed primarily in the testes of the adult mouse. The SLRP genes are not present in Drosophila or C. elegans , but reside in three separate gene clusters in the puffer fish, mice and humans. Targeted disruption of individual mouse SLRP genes display minor connective tissue defects such as skin fragility, tendon laxity, minor growth plate defects, and mild osteoporosis. However, double and triple knockouts of SLRP genes exacerbate these phenotypes. Both the double epiphycan/biglycan and the triple PRELP/fibromodulin/biglycan knockout mice exhibit premature osteoarthritis. ^

Strength and stiffness of repaired tendons

Rotator cuff tears of the shoulder are a common cause of pain and disability. Although surgery is frequently beneficial, re-tearing of the tendons is likely to re-occur. In many cases even if the reparation is successful it will still generate discomfort, problems with mobility, as well as a sharp pain. This project is funded in the cooperation with the Hospital Clinico San Carlos de Madrid. The purpose of this work is to analyze the effect of the surgical repair and the application of different therapies, including mesenchymal stem cell therapy on the biomechanical properties (strength and stiffness) of the repaired tendon. An animal model of rotator cuff tendon reparations has been developed on laboratory rats.To obtain the mechanical response of the healthy and repaired tendons, it was necessary to develop an experimental set up to reproduce the in-vivo working conditions of the tendons (37 ºC, immersed in physiological serum), and especially the load transfer. The biomechanical properties (maximum load and stiffness) have been measured in healthy and repaired tendons. A total of 70 rats are used in this particular study. It has been found that the repaired tendon is stronger than the original on. However, the repaired tendons demonstrate less flexibility than the healthy (original) ones prior to the damage

Epidemiology of injuries in First Division Spanish football

Abstract The aim was to examine the injuries sustained by Spanish football players in the First Division and to compare injury-related variables in the context of both competition and training. The injury data were prospectively collected from 16 teams (427 players) using a specific web-based survey during the 2008/2009 season. A total of 1293 injuries were identified (145 were recurring injuries). The overall injury incidence was 5.65 injuries per 1000 h of exposure. Injuries were much more common during competition than during training (43.53 vs. 3.55 injuries per 1000 h of exposure, P menor que 0.05). Most of the injuries (89.6%) involved the lower extremities, and overuse (65.7%) was the main cause. Muscle and tendon injuries were the most common types of injury (53.8%) among the players. The incidence of training injuries was greater during the pre-season and tended to decrease throughout the season, while the incidence of competition injuries increased throughout the season (all P menor que 0.05). In conclusion, the results of this study suggest the need for injury prevention protocols in the First Division of the Spanish Football League to reduce the number of overuse injuries in the muscles and tendons in the lower extremities. In addition, special attention should be paid during the pre-season and the competitive phase II (the last four months of the season) in order to prevent training and competition injuries, respectively.

Mapping strain exerted on blood vessel walls using deuterium double-quantum-filtered MRI

A technique is described for displaying distinct tissue layers of large blood vessel walls as well as measuring their mechanical strain. The technique is based on deuterium double-quantum-filtered (DQF) spectroscopic imaging. The effectiveness of the double-quantum filtration in suppressing the signal of bulk water is demonstrated on a phantom consisting of rat tail tendon fibers. Only intrafibrillar water is displayed, excluding all other signals of water molecules that reorient isotropically. One- and two-dimensional spectroscopic imaging of bovine aorta and coronary arteries show the characteristic DQF spectrum of each of the tissue layers. This property is used to obtain separate images of the outer layer, the tunica adventitia, or the intermediate layer, the tunica media, or both. To visualize the effect of elongation, the average residual quadrupole splitting <Δνq> is calculated for each pixel. Two-dimensional deuterium quadrupolar splitting images are obtained for a fully relaxed and a 55% elongated sample of bovine coronary artery. These images indicate that the strong effect of strain is associated with water molecules in the tunica adventitia whereas the DQF NMR signal of water in the tunica media is apparently strain-insensitive. After appropriate calibration, these average quadrupolar splitting images can be interpreted as strain maps.

Epidermal muscle attachment site-specific target gene expression and interference with myotube guidance in response to ectopic stripe expression in the developing Drosophila epidermis

The egr-type zinc-finger transcription factor encoded by the Drosophila gene stripe (sr) is expressed in a subset of epidermal cells to which muscles attach during late stages of embryogenesis. We report loss-of-function and gain-of-function experiments indicating that sr activity provides ectodermal cells with properties required for the establishment of a normal muscle pattern during embryogenesis and for the differentiation of tendon-like epidermal muscle attachment sites (EMA). Our results show that sr encodes a transcriptional activator which acts as an autoregulated developmental switch gene. sr activity controls the expression of EMA-specific target genes in cells of ectodermal but not of mesodermal origin. sr-expressing ectodermal cells generate long-range signals that interfere with the spatial orientation of the elongating myotubes.

Biomechanics of the movable pretarsal adhesive organ in ants and bees

Hymenoptera attach to smooth surfaces with a flexible pad, the arolium, between the claws. Here we investigate its movement in Asian weaver ants (Oecophylla smaragdina) and honeybees (Apis mellifera).  When ants run upside down on a smooth surface, the arolium is unfolded and folded back with each step. Its extension is strictly coupled with the retraction of the claws. Experimental pull on the claw-flexor tendon revealed that the claw-flexor muscle not only retracts the claws, but also moves the arolium. The elicited arolium movement comprises (i) about a 90° rotation (extension) mediated by the interaction of the two rigid pretarsal sclerites arcus and manubrium and (ii) a lateral expansion and increase in volume. In severed legs of O. smaragdina ants, an increase in hemolymph pressure of 15 kPa was sufficient to inflate the arolium to its full size. Apart from being actively extended, an arolium in contact also can unfold passively when the leg is subject to a pull toward the body.  We propose a combined mechanical–hydraulic model for arolium movement: (i) the arolium is engaged by the action of the unguitractor, which mechanically extends the arolium; (ii) compression of the arolium gland reservoir pumps liquid into the arolium; (iii) arolia partly in contact with the surface are unfolded passively when the legs are pulled toward the body; and (iv) the arolium deflates and moves back to its default position by elastic recoil of the cuticle.

Efeito da aplicação do ultrassom terapêutico durante 4 e 5 minutos por área do transdutor no processo de reparação de tendão de ratos

O objetivo deste estudo foi avaliar o efeito dos tempos de aplicação 3, 4 e 5 minutos por ERA do ultrassom terapêutico (UST) na organização das fibras de colágeno em lesão do tendão do calcâneo de ratos. Foram utilizados quarenta ratos machos Wistar, dos quais 32 sofreram tenotomia total do tendão do calcâneo e foram divididos em 5 grupos: GC, sem tenotomia e tratamento; GT, com tenotomia e sem tratamento; UST3, UST4 e UST5 submetidos à tenotomia e tratados com UST nos tempos de 3, 4 e 5 minutos por área de radiação efetiva respectivamente. Os animais foram submetidos à primeira aplicação do UST foi 24 horas após a cirurgia de tenotomia. A irradiação ultrassônica foi aplicada com os seguintes parâmetros: 1 MHz, modo pulsado com 20% do ciclo de trabalho (2 ms de emissão / 8 ms de intervalo), frequência de 100 Hz, 0,5 W / cm² de intensidade e ERA de 0,5 cm². A aplicação foi realizada 1x/dia. Os animais foram sacrificados após a 10ª sessão de tratamento, no 12º dia pós-operatório. Os tendões foram retirados cirurgicamente para análise da organização das fibras colágenas através do método de birrefringência (retardo óptico - OR). As fibras colágenas mostraram melhor agregação e organização no grupo UST3, UST4 e UST5 quando comparado ao GT (p<0.05) e o UST5 apresentou melhor resposta na comparação intergrupos. Conclui-se que o UST, aplicado no tempo de 5 minutos por área de radiação efetiva, apresentou a melhor dose-resposta quanto à organização das fibras colágenas no reparo tecidual de tendões de ratos

Arthroscopic stabilisation of an acute acromioclavicular dislocation grade III in a patient with ectopic insertion of the pectoralis minor: technical considerations

The different approaches used in arthroscopic stabilisation of the acromioclavicular joint are well known. However, and despite a great incidence of ectopic pectoralis minor insertion, an alternative choice for the use of arthroscopic portal has not being sufficiently described. Here, we describe a case of acute acromioclavicular dislocation grade III. The arthroscopic stabilisation was achieved using the TightRope (Arthrex, Naples, USA) implant. Through this technique, the approach to the articular portion of the coracoid process can be made intra-articularly or from the subacromial space. We accessed intra-articularly, by opening the rotator interval to reach the coracoid process from the joint cavity. After opening the rotator interval, an ectopic insertion of the pectoralis minor was observed. The choice of approach of the coracoid process from the subacromial space would have complicated the intervention, making it necessary to sever the ectopic tendon to complete the technique, lengthening the surgical time and increasing the chance of complications. For this reason, the use of a standard posterior portal providing intra-articular arthroscopic access through the rotator interval is recommended since the aforementioned anatomical variation is not infrequent. Level of evidence Therapeutic studies—investigating the results of treatment, Level V.

Shoulder pain in overhead athletes : a systematic review of orthopaedic causes

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

MR morphometry of posterior tibialis muscle in adult acquired flat foot

We conducted magnetic resonance imaging of the posterior tibial (PT) and flexor digitorum longus (FDL) muscle bellies in 12 patients undergoing surgical treatment for unilateral posterior tibial tendon (PTT) dysfunction. All patients had atrophy of the PT muscle compared to the normal leg (mean 10.7%, p=0.008). In those patients with a complete rupture of PTT there was replacement of the PT muscle by fatty infiltration. Conversely, the FDL muscle showed a compensatory hypertrophy (mean 17.2%, p

Temporal expression of fibroblast growth factor receptors during primary ligament repair

Following injury, it is inherently difficult to completely restore the biomechanical properties of ligaments. Relatively little is known about the cellular mechanisms controlling ligament healing. Numerous studies have implicated fibroblast growth factors (FGFs) as key molecules during the initiation of the cellular proliferation, differentiation, migration and matrix deposition that characterise wound healing. While current surgical emphasis concentrates on growth factor intervention, the role of their cognate receptors (FGFRs) has largely been overlooked. Following transection of the medial collateral ligament (MCL) in rabbits, we examined FGFR expression over a 14-day healing period. Using semiquantitative RT-PCR, we observed a significant upregulation in FGFR2 expression after 3 days. By 7 days post injury, FGFR2 expression fell to basal levels in line with those of FGFR1 and 3, both of which remained unaffected by surgical transection. These results demonstrate a role for FGFR2 in fibroblast and endothelial cell proliferation in damaged ligament, and suggest a window for FGF therapy.

Motor unit synchronization between medial and lateral vasti muscles

Objective: Accurate neuromuscular control of the patellofemoral joint is important in knee joint mechanics. Strategies to coordinate the vasti muscles, such as motor unit synchronization, may simplify control of patellar tracking. This study investigated motor unit synchronization between vastus medialis (VM) and lateralis (VL). Methods: Electromyographic (EMG) recordings of single motor unit action potentials (MUAPs) were made from VM and single- and multi-unit recordings were made from VL. Synchronization was quantified from peaks in the cross-correlogram generated from single MUAP pairs in VL and VM. The proportion of motor units in VM with synchronized firing in VL was also quantified from peaks in averages of multiunit VL EMG triggered from the VM MUAP. Results: A high degree of synchronization of motor unit firing between VM and VL was identified. Results were similar for cross-correlation (similar to 45% of cases) and triggered averages (similar to 41% of cases). Conclusions: The data suggest that synchronization between VM and VL is higher than expected. Agreement between traditional cross-correlation and triggered averaging methods suggest that this new technique may provide a more clinically viable method to quantify synchronization. Significance: High synchronization between VM and VL may provide a solution to simplify control of the mechanically unstable patellofemoral joint. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of weightbearing exercise with low frequency, whole body vibration on lumbosacral proprioception: A pilot study on normal subjects

Patients with low back pain (LBP) often present with impaired proprioception of the lumbopelvic region. For this reason, proprioception training usually forms part of the rehabilitation protocols. New exercise equipment that produces whole body, low frequency vibration (WBV) has been developed to improve muscle function, and reportedly improves proprioception. The aim of this pilot study was to investigate whether weightbearing exercise given in conjunction with WBV would affect lumbosacral position sense in healthy individuals. For this purpose, twenty-five young individuals with no LBP were assigned randomly to an experimental or control group. The experimental group received WBV for five minutes while holding a static, semi-squat position. The control group adopted the same weightbearing position for equal time but received no vibration. A two-dimensional motion analysis system measured the repositioning accuracy of pelvic tilting in standing. The experimental (WBV) group demonstrated a significant improvement in repositioning accuracy over time (mean 0.78 degrees) representing 39% improvement. It was concluded that WBV may induce improvements in lumbosacral repositioning accuracy when combined with a weightbearing exercise. Future studies with WBV should focus on evaluating its effects with different types of exercise, the exercise time needed for optimal outcomes, and the effects on proprioception deficits in LBP patients.

Muscle fiber and motor unit behavior in the longest human skeletal muscle

The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers.

Disrupted cortical proprioceptive representation evokes symptoms of peculiarity, foreignness and swelling, but not pain

Objectives. It has been proposed that disruption of the internal proprioceptive representation, via incongruent sensory input, may underpin pathological pain states, but experimental evidence relies on conflicting visual input, which is not clinically relevant. We aimed to determine the symptomatic effect of incongruent proprioceptive input, imparted by vibration of the wrist tendons, which evokes the illusion of perpetual wrist flexion and disrupts cortical proprioceptive representation. Methods. Twenty-nine healthy and naive volunteers reported symptoms during five conditions: control, active and passive wrist flexion, extensor carpi radialis tendon vibration to evoke illusion of perpetual wrist flexion, and ulnar styloid (sham) vibration. No advice was given about possible illusions. Results. Twenty-one subjects reported the illusion of perpetual wrist flexion during tendon vibration. There was no effect of condition or of whether or not subjects reported an illusion on discomfort/pain (P > 0.28). Peculiarity, swelling and foreignness were greater during tendon vibration than during the other conditions, and greater during tendon vibration in those who reported an illusion of wrist flexion than in those who did not (P < 0.05 for all). Symptoms were reported by at least two subjects in each condition and four subjects reported systemic symptoms (e.g. nausea). Conclusions. In healthy volunteers, incongruent proprioceptive input does not cause discomfort or pain but does evoke feelings of peculiarity, swelling and foreignness in the limb.