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Dahan da Cunha Nascimento,1,* Nicholas Rolnick,2,* Isabella da Silva Almeida,3,* Gerson Cipriano Junior,4,* João Luiz Durigan3,* 1Physical Education Department, Universidade Católica de Brasília, Brasília, DF, Brazil; 2The Human Performance Mechanic Department, Lehman College, Bronx, NY, USA; 3Laboratory of Muscle and Tendon Plasticity, Faculdade de Ceilândia, Universidade de Brasília, Brasília, DF, Brazil; 4Graduate Program in Rehabilitation Science, Faculdade de Ceilândia, Universidade de Brasília, Brasília, DF, Brazil*These authors contributed equally to this workCorrespondence: João Luiz Durigan, Laboratory of Muscle and Tendon Plasticity, Faculdade de Ceilândia, Universidade de Brasília, Centro Metropolitano, conjunto A, lote 01, Brasília, DF, 72220-275, Brazil, Tel/Fax +55 (61) 3376-0252, Email joaodurigan@gmail.comAbstract: Null hypothesis significant testing (NHST) is the dominant statistical approach in the geriatric and rehabilitation fields. However, NHST is routinely misunderstood or misused. In this case, the findings from clinical trials would be taken as evidence of no effect, when in fact, a clinically relevant question may have a “non-significant” p-value. Conversely, findings are considered clinically relevant when significant differences are observed between groups. To assume that p-value is not an exclusive indicator of an association or the existence of an effect, researchers should be encouraged to report other statistical analysis approaches as Bayesian analysis and complementary statistical tools alongside the p-value (eg, effect size, confidence intervals, minimal clinically important difference, and magnitude-based inference) to improve interpretation of the findings of clinical trials by presenting a more efficient and comprehensive analysis. However, the focus on Bayesian analysis and secondary statistical analyses does not mean that NHST is less important. Only that, to observe a real intervention effect, researchers should use a combination of secondary statistical analyses in conjunction with NHST or Bayesian statistical analysis to reveal what p-values cannot show in the geriatric and rehabilitation studies (eg, the clinical importance of 1kg increase in handgrip strength in the intervention group of long-lived older adults compared to a control group). This paper provides potential insights for improving the interpretation of scientific data in rehabilitation and geriatric fields by utilizing Bayesian and secondary statistical analyses to better scrutinize the results of clinical trials where a p-value alone may not be appropriate to determine the efficacy of an intervention.Keywords: statistics, statistical significance, effect size, p-value

Clara Maria Pinheiro-Dardis,1 Vânia Ortega Gutierres,1 Renata Pires Assis,1 Sabrina Messa Peviani,2 Gabriel Borges Delfino,2 João Luiz Quagliotti Durigan,3 Tania de Fátima Salvini,2 Amanda Martins Baviera,1 Iguatemy Lourenço Brunetti1 1São Paulo State University (UNESP), School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, São Paulo, Brazil; 2Federal University of São Carlos (UFSCar), Department of Physical Therapy, São Carlos, São Paulo, Brazil; 3Physical Therapy Division, University of Brasilia, Brasilia, Federal District, Brazil Background: The aim of this study was to evaluate the changes in biomarkers of skeletal muscle proteolysis (atrogin-1, muscle RING finger-1 protein [MuRF-1]) and inflammation (nuclear factor kappa-B) in skeletal muscles of rats under two catabolic conditions, diabetes mellitus (DM) and acute joint inflammation, and the effects of insulin therapy. Materials and methods: Male Wistar rats were divided into groups without diabetes – normal (N), saline (NS), or Ɩ-carrageenan (NCa) injection into the tibiotarsal joint – and groups with diabetes – diabetes (D), plus insulin (DI), saline (DS), or Ɩ-carrageenan (DCa) injection into the tibiotarsal joint, or Ɩ-carrageenan injection and treatment with insulin (DCaI). Three days after Ɩ-carrageenan injection (17 days after diabetes induction), tibialis anterior (TA) and soleus (SO) skeletal muscles were used for analysis. Results: DM alone caused a significant decrease in the mass of TA and SO muscles, even with low levels of atrogenes (atrogin-1, MuRF-1), which could be interpreted as an adaptive mechanism to spare muscle proteins under this catabolic condition. The loss of muscle mass was exacerbated when Ɩ-carrageenan was administered in the joints of diabetic rats, in association with increased expression of atrogin-1, MuRF-1, and nuclear factor kappa-B. Treatment with insulin prevented the increase in atrogin-1 (TA, SO) and the loss of muscle mass (SO) in diabetic-carrageenan rats; in comparison with TA, SO muscle was more responsive to the anabolic actions of insulin. Conclusion: Acute joint inflammation overcame the adaptive mechanism in diabetic rats to prevent excessive loss of muscle mass, worsening the catabolic state. The treatment of diabetic-carrageenan rats with insulin prevented the loss of skeletal muscle mass mainly via atrogin-1 inhibition. Under the condition of DM and inflammation, muscles with the prevalence of slow-twitch, type 1 fibers were more responsive to insulin treatment, recovering the ability to grow. Keywords: diabetes mellitus, inflammation, muscle proteolysis, atrogenes, creatine kinase, NF-κB, insulin

Gracielle Vieira Ramos, 1, 2 Ivo Vieira de Sousa Neto, 3 Alessandra Choqueta Toledo-Arruda, 4, 5 Rita de Cassia Marqueti, 3 Rodolfo P Vieira, 6– 8 Milton A Martins, 5 Tânia F Salvini, 9 João Luiz Quaglioti Durigan 10 1Physical Therapy Division, University of Brasilia, Brasília, DF, Brazil; 2Department of Physical Therapy, University Paulista, Brasília, DF, Brazil; 3Laboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Brasília, DF, Brazil; 4Faculty of Physiotherapy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 5Department of Medicine Clinical (LIM 20), School of Medicine, University of São Paulo, São Paulo, Brazil; 6Universidade Brasil, Post-Graduation Program in Bioengineering, São Paulo, Brazil; 7Laboratory of Pulmonary and Exercise Immunology (LABPEI), Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE) and Nove de Julho University (UNINOVE), São Paulo, SP, Brazil; 8Federal University of Sao Paulo, Post-Graduation Program in Sciences of Human Movement and Rehabilitation, São Paulo, Brazil; 9Department of Physical Therapy, Federal University of São Carlos, São Carlos, Brazil; 10Rehabilitation Sciences Graduation Program, University of Brasilia, Brasília, DF, BrazilCorrespondence: Gracielle Vieira RamosDepartment of Physical Therapy, University Paulista, Sgas Quadra 913, s/nº - Conjunto B - Asa Sul, Brasília, DF, Brazil, 70390-130 Email graciellevieiraramos@gmail.comBackground: Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, cross-sectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS.Methods: Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks.Results: The CS exposure did not change CSA compared to the control group (p> 0.05), but minor fibers in the frequency distribution (< 1000 μm 2) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke+exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001).Conclusion: Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions.Keywords: physical exercise, chronic obstructive pulmonary disease, MMP-2, inflammation

Ivo Vieira de Sousa Neto,1 João Luiz Quaglioti Durigan,1,2 Gonçalo Carreiro de Farias Junior,2 Fabio Henrique Bogni,3 Amanda Lima Ruivo,1 Juliana Oliveira de Araújo,1 Keico Okino Nonaka,3 Heloísa Selistre-de-Araújo,3 Rita de Cássia Marqueti1,2 1Laboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Distrito Federal, Brazil; 2Graduate Program in Rehabilitation Sciences, Universidade de Brasília, Distrito Federal, Brazil; 3Department of Physiological Sciences, Universidade Federal de São Carlos, São Paulo, BrazilCorrespondence: Ivo Vieira de Sousa Neto; Rita de Cássia MarquetiLaboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Distrito Federal, BrazilEmail ivoneto04@hotmail.com; marqueti@gmail.comBackground: Aging decreases osteogenic ability, inducing harmful effects on the bone extracellular matrix (ECM), while exercise training has been indicated as a tool to counteract bone disorders related to advancing age. The modulation of bone ECM is regulated by several types of matrix metalloproteinase (MMP); however, MMP-2 activity in different trabecular bones in response to resistance training (RT) has been neglected. Remodeling differs in different bones under the application of the same mechanical loading. Thus, we investigated the effects of 12 weeks of RT on MMP-2 activity in the lumbar vertebra (L6), tibia, and femur of young (3 months) and older rats (21 months).Methods: Twenty Wistar rats were divided into four groups (five animals per group): young sedentary or trained and older sedentary or trained. The 12-week RT consisted of climbing a 1.1-m vertical ladder three times per week with progressive weights secured to the animals’ tails. The animals were killed 48 h after the end of the experimental period. The MMP-2 activity was assessed by the zymography method.Results: The aging process induced lower MMP-2 activity in the lumbar vertebrae and tibia (p=0.01). RT upregulated pro, intermediate, and active MMP-2 activity in the tibia of young rats (p=0.001). RT also upregulated pro and active MMP-2 activity in the lumbar vertebrae and tibia with advancing age (p=0.01). There was no significant difference (p> 0.05) between groups for MMP-2 of the femur, regardless of age and RT.Conclusion: The aging process impairs MMP-2 activity, but RT is a potential therapeutic approach to minimize the deleterious effects of ECM degeneration in different aged bones. Distinct MMP-2 responses to exercise training may result in specific remodeling processes.Keywords: senescent, skeletal system, remodeling, matrix metalloproteinase, exercise

Objective: The present study aimed to determine the association between neuromuscular function, motor function impairment, and muscle and tendon structures in individuals with spinal cord injury (SCI) compared to a control (non-disabled) population., Design: A cross-sectional study with a control group., Setting: Center of Adapted Sports Training and Special Physical Education., Participants: Fifteen individuals with SCI and motor function impairments participated in the study. A paired non-disabled group was recruited for comparison., Interventions: Not applicable., Outcome Measures: Muscle (biceps brachii, rectus femoris, vastus lateralis, vastus medialis, and tibialis anterior) and tendon (quadriceps and patellar tendons) structures were assessed by ultrasound imaging (thickness, pennation angle, fascicle length, and echogenicity). Neuromuscular electrophysiological disorders were also assessed using electrodiagnosis techniques (stimulus non-responsivity and chronaxie) in the same muscles., Results: Except for the biceps brachii muscle, muscle thickness, pennation angle, and fascicle length were lower ( p  < 0.01) while echogenicity and chronaxie were greater ( p  < 0.01) in SCI participants. The SCI participants had a higher prevalence of neuromuscular electrophysiological disorders for all muscles, except the biceps brachii., Conclusion: Neuromuscular disorders occur in association with muscle and tendon maladaptation in individuals with chronic SCI. A higher prevalence of electrophysiological disorders suggests an acquired polyneuromyopathy for muscles with motor function impairment even though the muscle was innerved, in addition to widespread muscle atrophy.

Background and Objectives: To analyze the effects of aerobic, resistance, and combined training on peripheral and central components related to cardiorespiratory capacity after HTx. Materials and Methods : No time restriction was applied for study inclusion. MEDLINE/PubMed; EMBASE, CENTRAL, and PEDro databases were investigated. Studies reporting heart transplanted patients older than 19 years following aerobic, resistance, and combined training according. The outcomes included: V'O 2 peak, VE/V'CO 2 slope, heart rate (HR peak), systolic and diastolic blood pressure (SBP and DBP peak), maximum repetition test(1RM), sit-to-stand test, and flow-mediated dilation (FMD). The studies were selected by consensus. Four hundred ninety-two studies initially met the selection criteria. Cochrane handbook was used for abstracting data and assessing data quality and validity. Independent extraction by two observers was applied. Results : Isolated aerobic training leads to a greater increase in V'O 2 peak than combined training compared to the control group ( p < 0.001, I2 = 0%). However, no significant differences were found in the subgroup comparison ( p = 0.19, I2 = 42.1%). HR peak increased similarly after aerobic and combined training. High-intensity interval training (HIIT) was better than moderate continuous intensity to increase the V'O 2 after long term in HTx. Still, there is scarce evidence of HIIT on muscle strength and FMD. No change on VE/V'CO 2 slope, FMD, and SBP, DBP peak. 1RM and the sit-to-stand test increased after resistance training ( p < 0.001, I2 = 70%) and CT ( p < 0.001, I2 = 0%) when compared to control. Conclusions : Aerobic and combined training effectively improve VO 2 peak and muscle strength, respectively. HIIT seems the better choice for cardiorespiratory capacity improvements. More studies are needed to examine the impact of training modalities on VE/V'CO 2 slope and FMD.

Introduction: Exercise training is strongly recommended as a therapeutic approach to treat individuals with heart failure. High-intensity exercise training modalities still controversial in this population. The study aims to preliminary assess the consequences of high-intensity exercise training modalities, aerobic interval training (HIIT) and progressive high circuit-resistance training (CRT), on primarily endothelial function and cardiorespiratory fitness, and secondly on muscle strength and physical performance in heart failure patients., Methods: This preliminary multicentric randomized controlled trial comprised 23 heart failure patients, aged 56 ± 10 years old, mainly New York Heart Association classification I and II (%), hemodynamically stable, who compromise at least 36 exercise sessions of a randomly assigned intervention (HIIT, CRT or control group). Endothelial function, cardiopulmonary exercise testing, muscle strength and physical performance were completed at baseline and post-intervention., Results: Although no effects on endothelial function; both HIIT and CRT modalities were able to produce a positive effect on [Formula: see text] peak (HIIT = +2.1±6.5, CRT = +3.0±4.2 and control group = -0.1± 5.3 mL/kg/min, time*group p-value<0,05) and METs (HIIT = +0.6±1.8, CRT = +0.9±1.2 and control group = 0±1.6, time*group p-value<0,05). Only HIIT increased isokinetic torque peak (HIIT = +8.8±55.8, CRT = 0.0±60.7 and control group = 1.6±57.6 Nm) matched p-value<0,05. Regarding the physical performance, the CRT modality reduced chair stand test completion time (HIIT = -0.7±3.1, CRT = -3.3±3.2 and control group = -0.3±2.5 s, matched p-value<0,05 and HIIT improved global physical performance(time*group p<0,05)., Conclusion: This preliminary study trends to indicate for the first time that high-intensity interval training promotes a jointly superior effect compared to progressive high intensity circuit-resistance training by improving cardiorespiratory fitness, muscular strength, and physical performance. Further research with larger cohort is necessary., Clinical Trial Registration Number: ReBEC RBR-668c8v., Competing Interests: The authors have declared that no competing interests exist.

Exercise interventions have been recommended for people with non-specific low back pain. The literature is scarce regarding the effects of exercise on muscle strength, endurance, and electrical activity of lumbar extensor muscles. Electronic searches were carried out from May 2020 until August 2020 in the following databases: PUBMED, CENTRAL, EMBASE, PEDro, SPORTDiscus, Scielo, and LILACS. Only randomized controlled trials with passive and active control groups were included. The methodological quality of the included studies was performed using the Physiotherapy Evidence Database Scale. Eight studies, involving 508 participants, were included in metanalytical procedures. Exercise interventions demonstrated superior effects on muscle activity (Electromyography) when compared with active controls (p < 0.0001). Exercise interventions demonstrated superior effects on muscle endurance (Sorensen Test) when compared with passive (p = 0.0340) and active controls (p = 0.0276). Exercise interventions demonstrated superior effects on muscle strength (Machine) when compared with passive controls (p = 0.0092). Exercise interventions can improve muscle strength, endurance, and electrical activity in people with non-specific low back pain., (© 2021. The Author(s).)

Background: Pilates is a form of exercise commonly used in rehabilitation settings that improves muscular fitness and flexibility. However, it is unknown whether the energy expenditure (EE) from Pilates sessions could also lead to the intensity suggested by health organizations to improve physical fitness. This study aimed to quantify and compare the intensity and the EE of two different Pilates sessions (mat and apparatus)., Methods: 18 healthy females (age: 22 ± 3 years; height: 1.6 ± 0.1m; body mass: 61.0 ± 10.0 kg; body mass index: 21 ± 3 kg/m 2 ) performed two different sessions. Each session involved the performance of 15 exercises. Oxygen consumption (V˙O 2 ) was measured continuously and then converted to EE in Kcal/min. Blood lactate, heart rate (HR), and blood pressure (BP) were also measured. A repeated measures two-way ANOVA (time X group) determined differences between sessions. Bonferroni's post hoc analysis was used to identify significant differences between measures., Results: The Reformer apparatus and Mat sessions presented an EE of 2.59 ± 0.53 and 1.93 ± 0.26 kcal/min, respectively. V˙O 2 was higher for the Reformer session (8.67 ± 1.15 ml/kg/min) when compared to Mat (6.44 ± 0.73 ml/kg/min). There was no significant increase in blood lactate, HR, and BP for either session above resting values., Conclusion: The Pilates sessions analyzed in this study elicit low cardiovascular stress, leading to low EE levels. However, a typical session performed on the Reformer apparatus presented a higher EE, V˙O 2, and HR compared to the Mat Pilates session., Competing Interests: Declaration of competing interest The authors reported no potential conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: This study was performed to assess the effect of the phonophoretic application of a nanoemulsion incorporating glucosamine and chondroitin sulfate (NANO-CG) associated with kinesiotherapy on the reduction of pain and stiffness in knee chondropathy. Materials & methods: NANO-CG was tested in vitro and in vivo prior to being applied in a randomized and controlled clinical trial. Results: Cell viability and hen's egg test-chorionallantonic membrane tests indicated the NANO-CG is safe for topical application. Permeation tests showed NANO-CG enhances drug permeation through the skin. There was no statistical significance between treated groups in this preliminary study, however, pain reduction and complete recovery of articular cartilage were observed in some patients treated with NANO-CG. Conclusion: We demonstrate that NANO-CG may be a promising candidate for the therapy of knee chondropathy.

The aim of this study was to investigate the effects of different resistance training (RT) volumes on MMP activity in skeletal muscle, visceral adipose tissue and circulation. 21 Wistar rats were randomly divided into 3 groups (n=7 per group): sedentary control (SC); RT with 4 ladder climbs (RT-4; 50, 75, 90 and 100% of their maximal carrying capacity) and RT with 8 ladder climbs (RT-8 with 2 sets for each load). The 8-week RT consisted of climbing a 1.1-m vertical ladder with weights secured to the animals' tails. MMP-2 and -9 activity were analyzed by zymography. RT-8 displayed higher active MMP-2 activity as compared with SC and RT-4 in skeletal muscle (p<0.05). There was no significant difference between groups for pro and intermediate-MMP-2 activity in visceral adipose tissue, while RT-8 presented lower active MMP-2 activity as compared with SC (p<0.05). Plasma pro and active MMP-2 and MMP-9 activity was lower in RT-8 as compared with RT-4 (p<0.05). These results suggest that higher volume RT up-regulates MMP-2 activity in skeletal muscle, while down-regulating MMP-2 in visceral adipose tissue. Moreover, it induces a decrease of MMP-2, 9 activity in circulation. Different tissue and circulatory MMP responses to RT may result in specific remodeling., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study investigated the effects of 5 and 15°C cold-water immersion on recovery from exercise resulting in exercise-induced muscle damage. 42 college-aged men performed 5×20 drop-jumps and were randomly allocated into one of 3 groups: (1) 5°C; (2) 15°C; or (3) control. After exercise, individuals from the cold-water immersion groups had their lower limbs immerged in iced water for 20 min. Isometric knee extensor torque, countermovement jump, muscle soreness, and creatine kinase were measured before, immediately after, 24, 48, 72, 96 and 168 h post-exercise. There was no between-group difference in isometric strength recovery (p=0.73). However, countermovement jump recovered quicker in cold-water immersion groups compared to control group (p<0.05). Countermovement jump returned to baseline after 72 h in 15°C, 5°C group recovered after 96 h and control did not recovered at any time point measured. Also, creatine kinase returned to baseline at 72 h and remained stable for all remaining measurements for 15°C group, whereas remained elevated past 168 h in both 5°C and control groups. There was a trend toward lower muscle soreness (p=0.06) in 15°C group compared to control at 24 h post-exercise. The result suggests that cold-water immersion promote recovery of stretch-shortening cycle performance, but not influence the recovery of maximal contractile force. Immersion at warmer temperature may be more effective than colder temperatures promoting recovery from strenuous exercise., (© Georg Thieme Verlag KG Stuttgart · New York.)

With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication., (© FASEB.)

The association of ageing with obesity commits elderly women and has been correlated with multiple degenerative processes, which could be occasioned by an enhancing in levels of matrix metalloproteinase-2 and metalloproteinase-9 (MMPs) as well by an cytokine unbalance that included an enhancing on interleukin-6 (IL-6). Furthermore, other factors could be also related to degenerative process, as they could be reduced by eccentric resistance exercise (ERE), which seems particularly important to initiate resistance training in obese older adults. In this view, this study aims to determinate the effects of an acute ERE session on serum MMP-2, MMP-9 and IL-6 in elderly obese women. Ten elderly obese women participated in this study and completed a 10 repetitions maximum test (10 RM) utilizing leg extension exercise. Subjects then completed an acute ERE session consisting of seven sets of 10 repetitions at 110% of 10 RM with a rest of 3 min between sets. Blood samples were collected before, immediately after, 3, 24 and 48 h following the ERE session. Zymograms were utilized to measure the MMP-2 and MMP-9 enzymes from all individuals. Moreover, IL-6 concentration was also determinated. After ERE session, MMP-2 and MMP-9 decreased, remaining significantly below baseline values after 48 h (P<0·05). Although not statistically significant, there was a tendency for IL-6 to decrease 48 h after the ERE when compared with 3 h (P = 0·06). An acute ERE session decreases MMP-9, MMP-2 and IL-6 in elderly obese women, possibly indicating a transient protection against the low grade inflammation present in this specific population., (© 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

The aim of the present study was to compare the response of systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP) following combined training with 1 set or with 3 sets of resistance exercise (RE). Sixteen women with metabolic syndrome (MetS) were randomly assigned to perform two combined exercise protocols and a control session (CON): 1-set, 30 min of aerobic exercise (AE) at 65-70% of reserve heart rate and 1 set of 8-12 repetitions at 80% of 10-RM in six resistance exercises; 3-sets, same protocol but with 3 sets; and CON, 30 min of seated rest. The SBP, MBP and DBP were measured before and every 15 min during 90 min following the experimental sessions. The SBP displayed a decrease (P ≤ 0.05) during the 90 min following the RE session with 1-set and 3-set, while MBP was decreased (P ≤ 0.05) up to 75 min after 1-set and up to 30 min after the 3-set exercise session compared with pre-intervention values. There was a decrease in DBP only for the greatest individual decrease following 1-set (-6.1 mmHg) and 3-set (-4.9 mmHg) combined exercise sessions, without differences between them. The rate-pressure product and heart rate remained significantly higher (P ≤ 0.05) 75 min and 90 min after the combined exercise session with 1- and 3-sets compared with the CON, respectively. In conclusion, a low-volume RE combined with AE resulted in similar decrease of SBP when compared with RE with 3-sets in women with MetS, which could be beneficial in situations of limited time., (© 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: Subcutaneous adipose tissue may influence the transmission of electrical stimuli through to the skin, thus affecting both evoked torque and comfort perception associated with neuromuscular electrical stimulation (NMES). This could seriously affect the effectiveness of NMES for either rehabilitation or sports purposes., Objective: To investigate the effects of skinfold thickness (SFT) on maximal NMES current intensity, NMES-evoked torque, and NMES-induced discomfort., Method: First, we compared NMES current intensity, NMES-induced discomfort, and NMES-evoked torque between two subgroups of subjects with thicker (n=10; 20.7 mm) vs. thinner (n=10; 29.4 mm) SFT. Second, we correlated SFT to NMES current intensity, NMES-induced discomfort, and NMES-evoked knee extension torque in 20 healthy women. The NMES-evoked torque was normalized to the maximal voluntary contraction (MVC) torque. The discomfort induced by NMES was assessed with a visual analog scale (VAS)., Results: NMES-evoked torque was 27.5% lower in subjects with thicker SFT (p=0.01) while maximal current intensity was 24.2% lower in subjects with thinner SFT (p=0.01). A positive correlation was found between current intensity and SFT (r=0.540, p=0.017). A negative correlation was found between NMES-evoked torque and SFT (r=-0.563, p=0.012). No significant correlation was observed between discomfort scores and SFT (rs=0.15, p=0.53)., Conclusion: These results suggest that the amount of subcutaneous adipose tissue (as reflected by skinfold thickness) affected NMES current intensity and NMES-evoked torque, but had no effect on discomfort perception. Our findings may help physical therapists to better understand the impact of SFT on NMES and to design more rational stimulation strategies.

To evaluate the effects of a single session of partial-body cryotherapy (PBC) on muscle recovery, 26 young men performed a muscle-damaging protocol that consisted of five sets of 20 drop jumps with 2-min rest intervals between sets. After the exercise, the PBC group (n = 13) was exposed to 3 min of PBC at -110 °C, and the control group (n = 13) was exposed to 3 min at 21 °C. Anterior thigh muscle thickness, isometric peak torque, and muscle soreness of knee extensors were measured pre, post, 24, 48, 72, and 96 h following exercise. Peak torque did not return to baseline in control group (P < 0.05), whereas the PBC group recovered peak torques 96 h post exercise (P > 0.05). Peak torque was also higher after PBC at 72 and 96 h compared with control group (P < 0.05). Muscle thickness increased after 24 h in the control group (P < 0.05) and was significantly higher compared with the PBC group at 24 and 96 h (P < 0.05). Muscle soreness returned to baseline for the PBC group at 72 h compared with 96 h for controls. These results indicate that PBC after strenuous exercise may enhance recovery from muscle damage., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of the present study was to evaluate the effect of leucine treatment (0.30 mM) on muscle weight and signaling of myoproteins related to synthesis and degradation pathways of soleus muscle following seven days of complete sciatic nerve lesion. Wistar rats (n = 24) of 3-4 months of age (192 ± 23 g) were used. The animals were randomly distributed into four experimental groups (n = 6/group): control, treated with leucine (L), denervated (D) and denervated treated with leucine (DL). Dependent measures were proteins levels of AKT, AMPK, mTOR, and ACC performed by Western blot. Leucine induced a reduction in the phosphorylation of AMPK (p < 0.05) by 16% in the L and by 68% in the DL groups as compared with control group. Denervation increased AMPK by 24% in the D group as compared with the control group (p < 0.05). AKT was also modulated by denervation and leucine treatment, highlighted by the elevation of AKT phosphorylation in the D (65%), L (98%) and DL (146%) groups as compared with the control group (p < 0.05). AKT phosphorylation was 49% higher in the D group as compared with the DL group. Furthermore, denervation decreased mTOR phosphorylation by 29% in the D group as compared with the control group. However, leucine treatment induced an increase of 49% in the phosphorylation of mTOR in the L group as compared with the control group, and an increase of 154% in the DL as compared with the D group (p < 0.05). ACC phosphorylation was 20% greater in the D group than the control group. Furthermore, ACC in the soleus was 22% lower in the in the L group and 50% lower in the DL group than the respective control group (p < 0.05). In conclusion, leucine treatment minimized the deleterious effects of denervation on rat soleus muscle by increasing anabolic (AKT and mTOR) and decreasing catabolic (AMPK) pathways. These results may be interesting for muscle recovery following acute denervation, which may contribute to musculoskeletal rehabilitation after denervation.

Background: Matrix metalloproteinases (MMPs) are a major group of enzymes that play essential roles in normal functioning of diverse tissues during growth, development, and aging. However, among the MMPs little is known regarding the role of exercise in MMP-9 and MMP-2 function in humans., Objective: The aim of this study was to provide a systematic comprehensive review of the literature examining the effect of different exercise interventions on MMP-9 and MMP-2 in human investigations., Data Sources: A comprehensive systematic database search was performed, including PubMed/MEDLINE, Scopus, ScienceDirect, and Web of Science., Study Selection: Both the acute and chronic effects of exercise were included for evaluation in this systematic review. Inclusion criteria included the use of any type of planned, structured, and repetitive movement and its effects on the MMP-2 and MMP-9 response (obtained from plasma samples), participants (humans only) of any age with or without diseases, sedentary participants and those involved in light, moderate, and vigorous activity, randomized controlled trials (RCTs) and clinical trials (CTs), full text article citations with no restrictions in terms of language, and scored at least 5/11 on the Physiotherapy Evidence Database (PEDro) quality scale., Study Appraisal and Synthesis Methods: The PEDro scale was used to appraise study quality of RCTs and CTs. Two reviewers independently reviewed the full texts of all potentially relevant articles for eligibility and disagreements were discussed and resolved., Results: Seven studies met the previously determined quality indicators and were reviewed; three were RCTs and four were CTs. In general, the quality of the studies ranged from 5 to 9 out of a maximum of 11 on the PEDro quality criteria scale. Results revealed that chronic aerobic training induces a decrease in MMP-9 and MMP-2 levels, possibly indicating a cardioprotective effect, while resistance exercise training displayed conflicting results., Conclusion: Alterations in MMP-9 and MMP-2 plasma concentrations may be valuable biomarkers to reflect the influence of exercise on the inflammatory state. Nevertheless, the limited evidence available regarding the effects of exercise on the MMP-9 and MMP-2 response in human participants suggests that further studies are needed to fully define the connection between the role of exercise on the MMP-9 and MMP-2 response.

Introduction: We studied the effects of different neuromuscular electrical stimulation (NMES) currents, 2 kHz-frequency alternating currents (KACs, Russian and Aussie) and 2 pulsed currents (PCs), on isometric knee extension torque and discomfort level, both in isolation and combined, with maximum voluntary contraction (MVC)., Methods: Twenty-one women (age 21.6 ± 2.5 years) were studied. We evaluated torque evoked by NMES or NMES combined with maximum voluntary contraction of the quadriceps muscle of healthy women. Discomfort level was measured using a visual analog pain scale., Results: Despite comparable levels of discomfort, evoked torque was lower for Russian current compared with the other modalities (Russian 50.8%, Aussie 71.7%, PC500 76.9%, and PC200 70.1%; P < 0.001). There was no advantage in combining NMES with MVC compared with isolated NMES., Conclusions: The Aussie and PC approaches proved superior to Russian current for inducing isometric knee extension torque. This information is important in guiding decision making with regard to NMES protocols for muscle strengthening., (© 2014 Wiley Periodicals, Inc.)

Background: Neuromuscular electrical stimulation (NMES) is widely utilized to enhance muscle performance. However, the optimal NMES waveform with respect to treatment effect has not been established., Objective: To investigate the effects of kilohertz-frequency alternating current (KFAC) and low-frequency pulsed current (PC) on quadriceps evoked torque and self-reported discomfort., Data Sources: PubMed, The Cochrane Library, EMBASE, MEDLINE, Physiotherapy Evidence Database (PEDro), SinoMed, ISI Web of Knowledge, and CINAHL were searched for randomized controlled trials (RCTs) and quasi-randomized controlled trials (QRCTs)., Study Selection: Two reviewers independently selected potential studies according to the inclusion criteria, extracted data, and assessed methodological quality., Data Extraction and Synthesis: Studies were eligible if they compared KFAC versus PC interventions. Studies that included outcome measures for percentage of maximal isometric voluntary contraction (%MIVC) torque and self-reported discomfort level were eligible for evaluation. Seven studies involving 127 individuals were included. The methodological quality of eligible trials was moderate, with a mean of 5 on the 10-point PEDro scale. Overall, PC was no better than KFAC in terms of evoked torque and there was no difference in self-reported discomfort level., Conclusion: KFAC and PC have similar effects on quadriceps evoked torque and self-reported discomfort level in healthy individuals. The small number and overall methodological quality of currently available studies included in this meta-analysis indicate that new RCTs are needed to better determine optimal NMES treatment parameters.

Objective: The aim of this study was to assess the effect of neuromuscular electrical stimulation (NMES) on the extracellular matrix remodeling of the quadriceps muscle after anterior cruciate ligament (ACL) transection in rats. The hypothesis of this study was that ACL transection would induce maladaptive modifications in the extracellular matrix through the increase in connective tissue (CT) accumulation and net degradation of type IV collagen of the quadriceps muscle. In addition, clinical-like NMES, applied to the quadriceps muscle immediately after the ACL transection, would reduce the accumulation of the CT content and net degradation of type IV collagen., Design: Wistar male rats were randomized into five different groups: ACL (surgery and ACL transection), Sham (surgery without ACL transection), ACLES (surgery, ACL transection, and NMES), ShamES (surgery without ACL transection, but NMES), and Control (intact animals). The vastus medialis, rectus femoris, and vastus lateralis muscles of the quadriceps were harvested 1, 2, 3, 7, and 15 days after surgery. Matrix metalloproteinase-2 (MMP-2) (messenger RNA [mRNA] levels and activity), collagen IV (mRNA and protein levels), and CT density were assessed., Results: The ACL transection increased the CT content and MMP-2 mRNA levels and decreased collagen IV mRNA and protein levels. NMES minimized the CT density in all muscles and reduced the MMP-2 mRNA levels mainly in the vastus lateralis muscle at 7 days. Moreover, type IV collagen mRNA levels were increased in all muscles at 7 days, as was the protein level only at 15 days, in the NMES groups., Conclusions: This study showed that ACL transection increases CT content and MMP-2 mRNA levels and induces rapid changes in basement membranes, causing net degradation of type IV collagen during the first 2 wks after ACL injury. Furthermore, clinical-like NMES minimized the accumulation of CT density, regulated the MMP-2 mRNA levels, and increased both type IV collagen mRNA and protein levels.

Fibromyalgia (FM) has been associated with cardiac autonomic abnormalities and pain. Heart rate variability (HRV) is reduced in FM with autonomic tone dominated by sympathetic activity. The purpose of this study was to evaluate the effects of one session of a posteroanterior glide technique on both autonomic modulation and pain in woman with FM. This was a controlled trial with immediate followup; twenty premenopausal women were allocated into 2 groups: (i) women diagnosed with FM (n = 10) and (ii) healthy women (n = 10). Both groups received one session of Maitland mobilization grade III posteroanterior central pressure glide, at 2 Hz for 60 s at each vertebral segment. Autonomic modulation was assessed by HRV and pain by a numeric pain scale before and after the intervention. For HRV analyses, heart rate and RR intervals were recorded for 10 minutes. FM subjects demonstrated reduced HRV compared to controls. Although the mobilization technique did not significantly reduce pain, it was able to improve HRV quantified by an increase in rMSSD and SD1 indices, reflecting an improved autonomic profile through increased vagal activity. In conclusion, women with FM presented with impaired cardiac autonomic modulation. One session of Maitland spine mobilization was able to acutely improve HRV.

Introduction: Neuromuscular electrical stimulation (NMES) is used to improve quadriceps mass after anterior cruciate ligament (ACL) injury. We studied the effect of NMES on mRNA levels of atrophy genes in the quadriceps muscle of rats after ACL transection., Methods: mRNA levels of atrogin-1, MuRF-1, and myostatin were assessed by quantitative PCR and the polyubiquitinated proteins by Western blot at 1, 2, 3, 7, and 15 days postinjury., Results: NMES minimized the accumulation of atrogenes and myostatin according to time period. NMES also prevented reduction in muscle mass in all muscles of the ACLES group at 3 days., Conclusions: Use of NMES decreased the accumulation of atrogenes and myostatin mRNA in the quadriceps muscles, inhibiting early atrophy at 3 days, although it did not prevent atrophy at 7 and 15 days after ACL transection. This study highlights the importance of therapeutic NMES interventions in the acute phase after ACL transection., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: The aim of this study was to assess the mRNA levels of atrogin-1, muscle ring finger 1, and myostatin in rat quadriceps after anterior cruciate ligament (ACL) transection., Design: Wistar rats were randomized into three different groups: ACL (surgery and ACL transection), sham (surgery without ACL transection), and control. Vastus medialis, rectus femoris, and vastus lateralis muscles were harvested at 1, 2, 3, 7, and 15 days after ACL transection. The mRNA levels of atrogin-1, muscle ring finger 1, and myostatin, as well as the ubiquitinated protein content, muscle mass, and cross-sectional area of the muscle fibers, were evaluated., Results: Elevated levels of atrogin-1, muscle ring finger 1, and myostatin mRNA were detected in all tested muscles at most time points. The ubiquitinated protein content was increased at 3 days in the ACL and sham groups. The muscle mass of the ACL group was reduced at 3, 7, and 15 days (vastus lateralis and vastus medialis) and at 7 and 15 days (rectus femoris), whereas it was reduced in the sham group at 3 and 7 days (vastus lateralis and vastus medialis) and at 7 days (rectus femoris). The cross-sectional area of vastus medialis was reduced at 3, 7, and 15 days in the ACL group and at 3 and 7 days in the sham group. The cross-sectional area of the vastus lateralis was reduced at 7 and 15 days in the ACL group and at 7 days in the sham group. Whereas muscle mass and cross-sectional area recovery was noted in the sham group, no recovery was observed in the ACL group., Conclusions: Quadriceps atrophy after ACL transection involves increased levels of myostatin, atrogin-1, and muscle ring finger 1 mRNA and the accumulation of ubiquitinated protein.

Background: Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown., Objective: This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats., Subjects and Methods: The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction., Results: The results showed significant elevation ( p <0.05) in MyoD and VEGF genes expression levels. Moreover, capillary blood count was more prominent in elderly rats in laser irradiated groups when compared to young animals., Conclusion: In conclusion, LILT increased the maturation of satellite cells into myoblasts and myotubes, enhancing the regenerative process of aged rats irradiated with laser.

Background: This review will describe the main cellular mechanisms involved in the reduction and increase of myoproteins synthesis commonly associated with muscle atrophy and hypertrophy, respectively., Objective: We analyzed the effects of electrical stimulation (ES) and stretching exercise on the molecular pathways involved in muscle atrophy and hypertrophy. We also described the main effects and limits of these resources in the skeletal muscle, particularly on the denervated muscle., Discussion: Recently, our studies showed that the ES applied in a similar manner as performed in clinical practice is able to attenuate the increase of genes expression involved in muscle atrophy. However, ES was not effective to prevent the loss of muscle mass caused by denervation. Regarding to stretching exercises, their mechanisms of action on the denervated muscle are not fully understood and studies on this area are scarce. Studies from our laboratory have found that stretching exercise increased the extracellular matrix remodeling and decreased genes expression related to atrophy in denervated muscle. Nevertheless, it was not enough to prevent muscle atrophy after denervation., Conclusions: In spite of the use of stretching exercise and ES in clinical practice in order to minimize the atrophy of denervated muscle, there is still lack of scientific evidence to justify the effectiveness of these resources to prevent muscle atrophy in denervated muscle.

The aim of this study was to evaluate the expression of key genes responsible for tendon remodeling of the proximal and distal regions of calcaneal tendon (CT), intermediate and distal region of superficial flexor tendon (SFT) and proximal, intermediate and distal region of deep flexor tendon (DFT) submitted to 7 weeks of jumping water load exercise in combination with AAS administration. Wistar male rats were grouped as follows: sedentary (S), trained (jumping water load exercise) (T), sedentary animals treated with AAS (5 mg/kg, twice a week) and animals treated with AAS and trained (AAST). mRNA levels of COL1A1, COL3A1, TIMP-1, TIMP-2, MMP-2, IGF-IEa, GAPDH, CTGF and TGF-β-1 were evaluated by quantitative PCR. Our main results indicated that mRNA levels alter in different regions in each tendon of sedentary animals. The training did not alter the expression of COL1A1, COL3A, IGF-IEa and MMP-2 genes, while AAS administration or its combination with training reduced their expression. This study indicated that exercise did not alter the expression of collagen and related growth factors in different regions of rat tendon. Moreover, the pattern of gene expression was distinct in the different tendon regions of sedentary animals. Although, the RNA yield levels of CT, SFT and DFT were not distinct in each region, these regions possess not only the structural and biochemical difference, but also divergence in the expression of key genes involved in tendon adaptation.

Objective: The aim of this study was to evaluate the effect of tibiotarsal joint inflammation in rat tibialis anterior muscle through muscle fiber cross-sectional area (CSA) and gene expression (atrogin-1, muscle ring finger-1 [MuRF1], myogenic differentiation-1 [MyoD], p38 mitogen-activated protein kinase [p38MAPK], nuclear factor kappa B-dependent [NFκB], tumor necrosis factor-alpha [TNF-α])., Design: Wistar rats were randomly divided into three periods (2, 7, and 15 days) and assigned into four groups within each experimental period: control, sham, inflammation, and immobilization. Real-time polymerase chain reaction, Western blot, immunofluorescence, and muscle fiber CSA analyses were performed., Results: At 2 days, the inflammation group increased atrogin-1, MuRF1, and myostatin and reduced MyoD expression. At 7 days, the inflammation group increased atrogin-1, MuRF1, NFκB, p38MAPK, MyoD, myostatin, and TNF-α expression and TNF-α protein and reduced muscle fiber CSA. At 15 days, gene and protein expression in the inflammation group returned to basal levels, and CSA values were similar to those in control and sham groups. The immobilization groups have a similar pattern in all experimental periods, with increased atrogin-1, MuRF1, NFκB, and TNF-α gene expression and reduced muscle fiber CSA. The sham group had increased myostatin and atrogin-1 expression at 2 days and increased MyoD and myostatin expression at 7 days., Conclusions: Joint inflammation stimulated the expression of muscle factors related to atrophy, growth, differentiation, and mass regulation followed by muscle atrophy.

Alternagin-C (ALT-C) is a disintegrin-like, Cys-rich protein isolated from Bothrops alternatus snake venom, which has been shown to induce in vivo angiogenesis. Therefore, this protein could be interesting as a new approach for tissue regeneration studies. Here the effects of ALT-C on fibroblasts and inflammatory cells, collagen type III and type I and TGF-α expression in a rat wounded skin model were studied. Thirty-five male Wistar rats (weight 270 ± 20 g) were divided into seven groups with five animals in each of the following groups: a control group which wounded animals received treatment with natrozol(®) gel only; ALT-C10, ALT-C60 and ALT-C100 groups of wounded animals that were treated with the same amount of gel containing 10, 60 and 100 ng of ALT-C, respectively. Animals were treated once a day with 20 µl of gel associated or not with ALT-C for 1, 3, 5 or 7 days. ALT-C treatment increased the fibroblast density, collagen deposition and accelerated the inflammatory process, mostly in the ALT-C60 group. These results indicate that ALT-C improves wound repair process in rat skin. Thus, ALT-C could be a candidate to the development of a novel therapeutic strategy for wounded skin repair., (© 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.)

Objective: To evaluate the effects of electrical stimulation (ES), stretching and their combined effects in matrix metalloproteinases (MMPs) gene expression and activity during early denervation of rat tibialis anterior (TA) muscle by axonotmesis., Methods: Thirty adult male Wistar rats were divided into five groups: normal (N), denervated TA (D), denervated TA submitted to daily ES (D + ES), denervated TA submitted to daily stretching (D + St) and denervated TA submitted daily to both ES and stretching concurrently (D + ES + St). Both zimographic analysis and real time polymerase chain reaction of MMPs were used to muscular evaluation. In addition, muscle fiber cross-section area (CSA) was also evaluated., Results: Stretching increased MMP-2 activity in denervated muscle when performed alone as well as in association with ES (p<0·01). Both stretching and ES, individually and in association, increased MMP-2 gene expression in denervated muscle compared to N and D (p<0·05). All denervated groups decreased muscle fiber CSA compared to N (p<0·05)., Discussion: While stretching is the main stimulus leading to the activation of MMP-2, both ES and stretching are able to increase MMP-2 gene expression in rat denervated muscle suggesting ECM remodeling.

Denervation causes muscle atrophy and incapacity in humans. Although electrical stimulation (ES) and stretching (St) are commonly used in rehabilitation, it is still unclear whether they stimulate or impair muscle recovery and reinnervation. The purpose of this study was to evaluate the effects of ES and St, alone and combined (ES + St), on the expression of genes that regulate muscle mass (MyoD, Runx1, atrogin-1, MuRF1 and myostatin), on muscle fibre cross-sectional area and excitability, and on the expression of the neural cell adhesion molecule (N-CAM) in denervated rat muscle. ES, St and ES + St reduced the accumulation of MyoD, atrogin-1 and MuRF1 and maintained Runx1 and myostatin expressions at normal levels in denervated muscles. None of the physical interventions prevented muscle fibre atrophy or N-CAM expression in denervated muscles. In conclusion, although ES, St and ES + St changed gene expression, they were insufficient to avoid muscle fibre atrophy due to denervation.

Matrix metalloproteinases (MMPs) are crucial to the development and maintenance of healthy tissue and are mainly involved in extracellular matrix (ECM) remodeling of skeletal muscle. This study evaluated the effects of chronic allergic airway inflammation (CAAI), induced by ovalbumin, and aerobic training in the MMPs activity in mouse diaphragm muscle. Thirty mice were divided into 6 groups: 1) control; 2) ovalbumin; 3) treadmill trained at 50% of maximum speed; 4) ovalbumin and trained at 50%; 5) trained at 75%; 6) ovalbumin and trained at 75%. CAAI did not alter MMPs activities in diaphragm muscle. Nevertheless, both treadmill aerobic trainings, associated with CAAI increased the MMP-2 and -1 activities. Furthermore, MMP-9 was not detected in any group. Together, these findings suggest an ECM remodeling in diaphragm muscle of asthmatic mice submitted to physical training. This result may be useful for a better understanding of functional significance of changes in the MMPs activity in response to physical training in asthma.

We evaluated the effects of chronic allergic airway inflammation and of treadmill training (12 weeks) of low and moderate intensity on muscle fiber cross-sectional area and mRNA levels of atrogin-1 and MuRF1 in the mouse tibialis anterior muscle. Six 4-month-old male BALB/c mice (28.5 +/- 0.8 g) per group were examined: 1) control, non-sensitized and non-trained (C); 2) ovalbumin sensitized (OA, 20 microg per mouse); 3) non-sensitized and trained at 50% maximum speed &#95; low intensity (PT50%); 4) non-sensitized and trained at 75% maximum speed &#95; moderate intensity (PT75%); 5) OA-sensitized and trained at 50% (OA+PT50%), 6) OA-sensitized and trained at 75% (OA+PT75%). There was no difference in muscle fiber cross-sectional area among groups and no difference in atrogin-1 and MuRF1 expression between C and OA groups. All exercised groups showed significantly decreased expression of atrogin-1 compared to C (1.01 +/- 0.2-fold): PT50% = 0.71 +/- 0.12-fold; OA+PT50% = 0.74 +/- 0.03-fold; PT75% = 0.71 +/- 0.09-fold; OA+PT75% = 0.74 +/- 0.09-fold. Similarly significant results were obtained regarding MuRF1 gene expression compared to C (1.01 +/- 0.23-fold): PT50% = 0.53 +/- 0.20-fold; OA+PT50% = 0.55 +/- 0.11-fold; PT75% = 0.35 +/- 0.15-fold; OA+PT75% = 0.37 +/- 0.08-fold. A short period of OA did not induce skeletal muscle atrophy in the mouse tibialis anterior muscle and aerobic training at low and moderate intensity negatively regulates the atrophy pathway in skeletal muscle of healthy mice or mice with allergic lung inflammation.

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 microg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 +/- 0.09 vs 0.69 +/- 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 +/- 5.3 vs 81.3 +/- 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 +/- 0.09 vs 0.26 +/- 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 +/- 560.2 vs 1438.1 +/- 352.2 microm(2); P < 0.05) and an increase in connective tissue (216.5%, 8.82 +/- 3.55 vs 27.92 +/- 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 +/- 4.6 vs 94.2 +/- 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 +/- 0.05 vs 0.50 +/- 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 +/- 352.2 vs 1724.8 +/- 365.5 microm(2); P < 0.05) and a reduction in connective tissue (52.2%, 27.92 +/- 5.36 vs 13.34 +/- 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

This study evaluated the effects of alternagin-C (ALT-C) on mRNA levels of VEGF, MyoD and matrix metalloproteinase 2 (MMP-2) and on activity of MMPs in injured tibialis anterior (TA) muscle induced by cryolesioning in rats. Thirty-six Wistar rats (3 months old, 258.9+/-27 g) were divided into five groups: (1) control group; (2) injured TA and analyzed 3 days later; (3) injured TA treated with ALT-C and analyzed 3 days later; (4) injured TA and analyzed 7 days later and (5) injured TA treated with ALT-C and analyzed 7 days later. The injured muscle received 25 microl of ALT-C (50 nM). The injured and uninjured muscle areas were quantified by light microscopy. The MMP activity was evaluated through zymography, and mRNA of MyoD, VEGF and MMP-2 was assessed by quantitative polymerase chain reaction. ALT-C neither reduced the muscle injury area nor altered the pattern of MyoD and VEGF expression in injured muscles. However, ALT-C reduces both MMP-2 mRNA and gelatinolytic activity in injured muscles. The study indicates that ALT-C, at the tested concentrations, did not improve muscle regeneration process in rats. The effect on MMP-2 mRNA and gelatinolytic activity suggests that ALT-C changes the overall balance of ECM protein turnover during muscle regeneration.

Muscle-fiber atrophy occurs concomitantly with intramuscular connective tissue proliferation following denervation. These events contribute to the impairment of mechanical and functional properties of denervated muscles and compromise their recovery. Electrical stimulation (ES) is used in human rehabilitation to treat denervated muscles. However, the effects of this therapy on the intramuscular extracellular matrix (ECM) remain uncertain. Metalloproteinases (MMPs) are responsible by remodeling ECM in many neuromuscular disorders. This study evaluates the effect of ES on the activity of two important MMPs, MMP-2 and MMP-9, both involved in ECM remodeling of rat denervated muscles. Thirty-four Wistar rats (3 months old, 356 +/- 38.7 g) were divided into five groups: denervated (D); D+ES; sham denervation; normal (N); and N+ES. Twenty maximal muscle contractions were stimulated every 48 h using surface electrodes, as generally used in the rehabilitation of human denervated muscle. Both zymographic analysis and real-time polymerase chain reaction (PCR) of MMPs were used to evaluate muscle after denervation for 28 days. Both the D and D+ES groups showed increased MMP-2 activity compared with the N group (P < 0.05). Furthermore, only the D+ES had increased MMP-2 gene expression compared with the N group (P < 0.05). MMP-9 activity was not detected in any of the groups. The results of this study indicate that denervation increases MMP-2 activity, and ES regulates MMP-2 gene expression in rat denervated skeletal muscle. These findings clarify the effects of ES on the ECM of denervated muscle and may be helpful in designing new therapeutic strategies for rehabilitation in patients with denervation of muscle.

The objective of the present study was to propose an orthosis of light material that would be functional for the animal and that would maintain only the ankle joint immobilized. Male Wistar rats (3 to 4 months old, 250-300 g) were divided into 2 groups (N = 6): control and immobilized for 7 days. Rats were anesthetized with sodium pentobarbital (40 mg/kg weight) and the left hindlimb was immobilized with the orthoses composed of acrylic resin model, abdominal belt and lateral supports. The following analyses were performed: glycogen content of the soleus, extensor digitorum longus, white gastrocnemius, red gastrocnemius, and tibialis anterior muscles by the phenol sulfuric method, and the weight, fiber area and intramuscular connective tissue of the soleus by the planimetric system. Data were analyzed statistically by the Kolmogorov-Smirnov, Student t and Wilcoxon tests. Immobilization decreased glycogen in all muscles (P < 0.05; soleus: 31.6%, white gastrocnemius: 56.6%, red gastrocnemius: 39%, extensor digitorum longus: 41.7%, tibialis anterior: 45.2%) in addition to reducing soleus weight by 34% (P < 0.05). Furthermore, immobilization promoted reduction of the fiber area (43%, P < 0.05) and increased the connective tissue (200%, P < 0.05). The orthosis model was efficient comparing with another alternative immobilization model, like plaster casts, in promoting skeletal muscle alterations, indicating that it could be used as a new model in other studies related to muscle disuse.