Involvement of Matrix Metalloproteinases in COVID-19: Molecular Targets, Mechanisms, and Insights for Therapeutic Interventions.

MMPs are enzymes involved in SARS-CoV-2 pathogenesis. Notably, the proteolytic activation of MMPs can occur through angiotensin II, immune cells, cytokines, and pro-oxidant agents. However, comprehensive information regarding the impact of MMPs in the different physiological systems with disease progression is not fully understood. In the current study, we review the recent biological advances in understanding the function of MMPs and examine time-course changes in MMPs during COVID-19. In addition, we explore the interplay between pre-existing comorbidities, disease severity, and MMPs. The reviewed studies showed increases in different MMP classes in the cerebrospinal fluid, lung, myocardium, peripheral blood cells, serum, and plasma in patients with COVID-19 compared to non-infected individuals. Individuals with arthritis, obesity, diabetes, hypertension, autoimmune diseases, and cancer had higher MMP levels when infected. Furthermore, this up-regulation may be associated with disease severity and the hospitalization period. Clarifying the molecular pathways and specific mechanisms that mediate MMP activity is important in developing optimized interventions to improve health and clinical outcomes during COVID-19. Furthermore, better knowledge of MMPs will likely provide possible pharmacological and non-pharmacological interventions. This relevant topic might add new concepts and implications for public health in the near future.

The Influence of Hip and Knee Joint Angles on Quadriceps Muscle-Tendon Unit Properties during Maximal Voluntary Isometric Contraction.

Determining how the quadriceps femoris musculotendinous unit functions, according to hip and knee joint angles, may help with clinical decisions when prescribing knee extension exercises. We aimed to determine the effect of hip and knee joint angles on structure and neuromuscular functioning of all constituents of the quadriceps femoris and patellar tendon properties. Twenty young males were evaluated in four positions: seated and supine in both 20° and 60° of knee flexion (SIT20, SIT60, SUP20, and SUP60). Peak knee extension torque was determined during maximal voluntary isometric contraction (MVIC). Ultrasound imaging was used at rest and during MVIC to characterize quadriceps femoris muscle and tendon aponeurosis complex stiffness. We found that peak torque and neuromuscular efficiency were higher for SUP60 and SIT60 compared to SUP20 and SIT20 position. We found higher fascicle length and lower pennation angle in positions with the knee flexed at 60°. The tendon aponeurosis complex stiffness, tendon force, stiffness, stress, and Young's modulus seemed greater in more elongated positions (60°) than in shortened positions (20°). In conclusion, clinicians should consider positioning at 60° of knee flexion rather than 20°, regardless if seated or supine, during rehabilitation to load the musculotendinous unit enough to stimulate a cellular response.

Moderate Treadmill Training Induces Limited Effects on Quadriceps Muscle Hypertrophy in Mice Exposed to Cigarette Smoke Involving Metalloproteinase 2.

BACKGROUND: 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 µm2) 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.

Structural equation modelling provides insights to understand the construct of chronic pain in women with rheumatoid arthritis.

OBJECTIVES: We aimed to adopt a multidimensional approach and investigate the interconnections between biomarkers (cytokines, matrix metalloproteinases, and cortisol) and psychosocial aspects considering pain acceptance, the individual construct of pain perception in terms of blood inflammation biomarkers, anxiety, self-efficacy, and functional performance and to define the quality of life (QoL) in women with rheumatoid arthritis (RA). METHODS: An observational cross-sectional study with a total of 42-RA participants, with chronic pain and 42-women without rheumatic diseases or chronic pain were included. A structural equation model was used to investigate the association between independent variables. RESULTS: Women with RA presented high blood biomarker levels, representing an intense inflammatory process. The participants with RA reported moderate pain most of the time, a worsening QoL, functionality, engagement in activities, and a willingness to live with pain and self-efficacy. It was found that the higher the chronic pain, the greater the intensity of pain perceived by these women with RA, as well as, the worse the functionality, the higher the perceived pain. CONCLUSIONS: The exacerbation of pain perception leads to worsening of the experience of chronic pain. The new construct of pain experience should include functionality as a crucial factor in understanding the mechanisms underlying pain.

Effects of different electrical stimulation currents and phase durations on submaximal and maximum torque, efficiency, and discomfort: a randomized crossover trial.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is an important therapeutic tool for rehabilitation. However, best stimulation parameters remain to be determined. OBJECTIVE: To determine the influence of different electrical stimulation currents and phase durations on torque, efficiency, and discomfort. METHODS: Using a cross-over design, kHz frequency alternating currents (KFAC) and pulsed currents (PC) with narrow (200 µs) or wide (500 µs) phase durations were randomly applied on knee extensor muscles of healthy participants with a minimum of seven days between sessions. The NMES-evoked torque, NMES-efficiency, and discomfort (visual 0-10 cm analogue scale) were measured for each stimulation intensity increments (10 mA). Statistics were conducted using a three-way analysis of variances (phase duration x current x intensity), followed by Tukey post-hoc. RESULTS: Twenty-four males (age 22.3 ±â€¯3.5years) were included. No effect of NMES current was observed for torque, efficiency, and discomfort. For wide phase durations (500 µs), torque significantly increased for all stimulation intensities. For narrow phase durations (200 µs) evoked torque significantly increased only after 40% of maximal stimulation intensity. Phase durations of 500 µs produced greater torque than 200 µs. Discomfort was greater with 500 µs when compared to 200 µs. Submaximal relative torque, for example 40% of maximum voluntary contraction (MVC), was obtained with ∼ 60% and ∼ 80% of the maximal current intensity for 500 µs and 200 µs, respectively. CONCLUSION: KFAC and PC current applied with the same phase duration induced similar relative submaximal and maximum evoked-torque, efficiency, and perceived discomfort. However, currents with 500 µs induced higher evoked-torque, current efficiency, and perceived discomfort.

Resistance Training Modulates the Matrix Metalloproteinase-2 Activity in Different Trabecular Bones in Aged Rats.

BACKGROUND: 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.

Resistance training decreases matrix metalloproteinase-2 activity in quadriceps tendon in a rat model of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease that induces peri-articular tissue degradation. OA induces an imbalance between synthesis and degradation of the extracellular matrix components in favor of catabolic events, promoting pathological remodeling and involving degradative enzymes, such as matrix metalloproteinases (MMPs). OBJECTIVE: This study aimed to investigate the effects of 8-weeks resistance training (RT) on MMP-2 activity in the quadriceps tendon and patellar tendon in an OA model. METHODS: Twenty-four Wistar rats were randomly divided into six groups: Control, Exercise, Sham, Sham with Exercise, OA, and OA with Exercise (OAE). The OA model was performed by anterior cruciate ligament transection surgery on the left knee. The 8-week RT consisted of climbing a 1.1-m vertical ladder three times per week with progressive weights secured to the animals' tails. MMP-2 activity was analyzed by zymography. RESULTS: The OAE group displayed lower pro, intermediate, and active MMP-2 activity in the quadriceps tendon compared with the OA group (p<0.05). For the patellar tendon, there was no significant difference between the OAE group compared with the other groups (p>0.05) for pro, intermediate, and active MMP-2 activity. Moreover, MMP-2 activity differed between tissues, the OA and OAE groups presented lower pro, intermediate, and active MMP-2 activity in the quadriceps tendon compared to the patellar tendon. CONCLUSION: RT induced down-regulated MMP-2 activity in the quadriceps tendon. RT is a potential therapeutic approach to minimize the deleterious effects of extracellular matrix degeneration.

Aerobic exercise training attenuates detrimental effects of cigarette smoke exposure on peripheral muscle through stimulation of the Nrf2 pathway and cytokines: a time-course study in mice.

Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 (P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2, Gsr, and Txn1 (P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks (P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks. Novelty Exercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways. Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS. These beneficial effects were evident after 12 weeks.

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet.

The increase in high-energy dietary intakes is a well-known risk factor for many diseases, and can also negatively impact the tendon. Ancestral lifestyle can mitigate the metabolic harmful effects of offspring exposed to high-fat diet (HF). However, the influence of paternal exercise on molecular pathways associated to offspring tendon remodeling remains to be determined. We investigated the effects of 8 weeks of paternal resistance training (RT) on offspring tendon proteome exposed to standard diet or HF diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, three times per week, with 8-12 dynamic movements per climb in a stair climbing apparatus). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups (five animals per group): offspring from sedentary fathers were exposed either to control diet (SFO-C), or to high-fat diet (SFO-HF); offspring from trained fathers were exposed to control diet (TFO-C) or to a high-fat diet (TFO-HF). The Nano-LC-MS/MS analysis revealed 383 regulated proteins among offspring groups. HF diet induced a decrease of abundance in tendon proteins related to extracellular matrix organization, transport, immune response and translation. On the other hand, the changes in the offspring tendon proteome in response to paternal RT were more pronounced when the offspring were exposed to HF diet, resulting in positive regulation of proteins essential for the maintenance of tendon integrity. Most of the modulated proteins are associated to biological pathways related to tendon protection and damage recovery, such as extracellular matrix organization and transport. The present study demonstrated that the father's lifestyle could be crucial for tendon homeostasis in the first generation. Our results provide important insights into the molecular mechanisms involved in paternal intergenerational effects and potential protective outcomes of paternal RT.

Paternal Resistance Training Induced Modifications in the Left Ventricle Proteome Independent of Offspring Diet.

Ancestral obesogenic exposure is able to trigger harmful effects in the offspring left ventricle (LV) which could lead to cardiovascular diseases. However, the impact of the father's lifestyle on the offspring LV is largely unexplored. The aim of this study was to investigate the effects of 8 weeks of paternal resistance training (RT) on the offspring left ventricle (LV) proteome exposed to control or high-fat (HF) diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, 3 times per week with weights secured to the animals' tails). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into 4 groups (5 animals per group): offspring from sedentary fathers, exposed to control diet (SFO-C); offspring from trained fathers, exposed to control diet (TFO-C); offspring from sedentary fathers, exposed to high-fat diet (SFO-HF); and offspring from trained fathers, exposed to high-fat diet (TFO-HF). The LC-MS/MS analysis revealed 537 regulated proteins among groups. Offspring exposure to HF diet caused reduction in the abundance levels of proteins related to cell component organization, metabolic processes, and transport. Proteins related to antioxidant activity, transport, and transcription regulation were increased in TFO-C and TFO-HF as compared with the SFO-C and SFO-HF groups. Paternal RT demonstrated to be an important intervention capable of inducing significant effects on the LV proteome regardless of offspring diet due to the increase of proteins involved into LV homeostasis maintenance. This study contributes to a better understanding of the molecular aspects involved in transgenerational inheritance.

Proteomic changes in skeletal muscle of aged rats in response to resistance training.

Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross-sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty-four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12-week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC-ESI-MS/MS. One-hundred and thirty-one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti-oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age-related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing. SIGNIFICANCE OF THE STUDY: Protein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti-oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays.

Confiabilidade da ultrassonografia de músculos esqueléticos em pacientes críticos de trauma / Reliability of skeletal muscle ultrasound in critically ill trauma patients

RESUMO Objetivo: Avaliar a segurança e a viabilidade da avaliação por ultrassonografia do quadríceps no pronto-socorro, e avaliar a confiabilidade intra e entre avaliadores para aquisição e análise de imagens de ultrassonografia da espessura e da ecogenicidade muscular em pacientes críticos de trauma. Métodos: Estudo de precisão diagnóstica realizado por meio de exames e avaliações feitos por profissionais de saúde com diferentes níveis de especialização. Dois examinadores (um especialista e um novato) procederam à aquisição de imagens de ultrassom de dez pacientes. Um avaliador experiente, cego quanto aos examinadores, quantificou as imagens obtidas. Em um grupo à parte de dez pacientes, dois avaliadores (um especialista e um novato) quantificaram a espessura do músculo quadríceps femoral, assim como sua ecogenicidade (métodos quadrado ou tracejado) em imagens adquiridas por um examinador. Resultados: Identificou-se excelente confiabilidade quanto à aquisição da imagem e à sua análise (coeficientes de correlação intraclasses > 0,987; p < 0,001). O erro padrão dos valores de mensurações variou de 0,01 a 0,06 cm, para a espessura muscular, e de 0,75 a 2,04 unidades arbitrárias, para ecogenicidade muscular. Os valores de ecogenicidade foram mais elevados quando se utilizou o método quadrado do que quando se utilizou o método tracejado (p = 0,003). Conclusão: A ultrassonografia é um método seguro, viável e confiável para avaliação muscular em pacientes críticos de trauma, independentemente do nível de especialização do avaliador.

ABSTRACT Objective: To evaluate the safety and feasibility of the ultrasound assessment of quadriceps in the emergency setting. To assess the intra- and interrater reliability for the acquisition and analysis of ultrasound images of muscle thickness and echogenicity in critically ill trauma patients between health professionals with different levels of expertise. Methods: Diagnostic accuracy study. Two examiners (expert and novice) acquired ultrasound images from ten patients; an experienced, blinded analyst quantified the images. In a separate group of ten patients, two analysts (expert and novice) quantified quadriceps muscle thickness and echogenicity (square or trace method) from images acquired by one examiner. Results: Excellent reliability was found for image acquisition and analysis (intraclass correlation coefficients > 0.987; p < 0.001). The standard error of the measurement values ranged from 0.01 - 0.06cm for muscle thickness and from 0.75 - 2.04 arbitrary units for muscle echogenicity. The coefficients of variation were < 6% for thickness and echogenicity. The echogenicity values were higher when using the square technique than when using the tracing technique (p = 0.003). Conclusion: Ultrasound is safe, feasible, and reliable for muscle assessment in critically ill trauma patients, regardless of the assessor's level of expertise.

Calcaneal Tendon Plasticity Following Gastrocnemius Muscle Injury in Rat.

Cross-talk between skeletal muscle and tendon is important for tissue homeostasis. Whereas the skeletal muscle response to tendon injury has been well-studied, to the best of our knowledge the tendon response to skeletal muscle injury has been neglected. Thus, we investigated calcaneal tendon extracellular matrix (ECM) remodeling after gastrocnemius muscle injury using a rat model. Wistar rats were randomly divided into four groups: control group (C; animals that were not exposed to muscle injury) and harvested at different time points post gastrocnemius muscle injury (3, 14, and 28 days) for gene expression, morphological, and biomechanical analyses. At 3 days post injury, we observed mRNA-level dysregulation of signaling pathways associated with collagen I accompanied with disrupted biomechanical properties. At 14 days post injury, we found reduced collagen content histologically accompanied by invasion of blood vessels into the tendon proper and an abundance of peritendinous sheath cells. Finally, at 28 days post injury, there were signs of recovery at the gene expression level including upregulation of transcription factors related to ECM synthesis, remodeling, and repair. At this time point, tendons also presented with increased peritendinous sheath cells, decreased adipose cells, higher Young's modulus, and lower strain to failure compared to the uninjured controls and all post injury time points. In summary, we demonstrate that the calcaneal tendon undergoes extensive ECM remodeling in response to gastrocnemius muscle injury leading to altered functional properties in a rat model. Tendon plasticity in response to skeletal muscle injury merits further investigation to understand its physiological relevance and potential clinical implications.

Reliability of skeletal muscle ultrasound in critically ill trauma patients. / Confiabilidade da ultrassonografia de músculos esqueléticos em pacientes críticos de trauma.

OBJECTIVE: To evaluate the safety and feasibility of the ultrasound assessment of quadriceps in the emergency setting. To assess the intra- and interrater reliability for the acquisition and analysis of ultrasound images of muscle thickness and echogenicity in critically ill trauma patients between health professionals with different levels of expertise. METHODS: Diagnostic accuracy study. Two examiners (expert and novice) acquired ultrasound images from ten patients; an experienced, blinded analyst quantified the images. In a separate group of ten patients, two analysts (expert and novice) quantified quadriceps muscle thickness and echogenicity (square or trace method) from images acquired by one examiner. RESULTS: Excellent reliability was found for image acquisition and analysis (intraclass correlation coefficients > 0.987; p < 0.001). The standard error of the measurement values ranged from 0.01 - 0.06cm for muscle thickness and from 0.75 - 2.04 arbitrary units for muscle echogenicity. The coefficients of variation were < 6% for thickness and echogenicity. The echogenicity values were higher when using the square technique than when using the tracing technique (p = 0.003). CONCLUSION: Ultrasound is safe, feasible, and reliable for muscle assessment in critically ill trauma patients, regardless of the assessor's level of expertise.

OBJETIVO: Avaliar a segurança e a viabilidade da avaliação por ultrassonografia do quadríceps no pronto-socorro, e avaliar a confiabilidade intra e entre avaliadores para aquisição e análise de imagens de ultrassonografia da espessura e da ecogenicidade muscular em pacientes críticos de trauma. MÉTODOS: Estudo de precisão diagnóstica realizado por meio de exames e avaliações feitos por profissionais de saúde com diferentes níveis de especialização. Dois examinadores (um especialista e um novato) procederam à aquisição de imagens de ultrassom de dez pacientes. Um avaliador experiente, cego quanto aos examinadores, quantificou as imagens obtidas. Em um grupo à parte de dez pacientes, dois avaliadores (um especialista e um novato) quantificaram a espessura do músculo quadríceps femoral, assim como sua ecogenicidade (métodos quadrado ou tracejado) em imagens adquiridas por um examinador. RESULTADOS: Identificou-se excelente confiabilidade quanto à aquisição da imagem e à sua análise (coeficientes de correlação intraclasses > 0,987; p < 0,001). O erro padrão dos valores de mensurações variou de 0,01 a 0,06 cm, para a espessura muscular, e de 0,75 a 2,04 unidades arbitrárias, para ecogenicidade muscular. Os valores de ecogenicidade foram mais elevados quando se utilizou o método quadrado do que quando se utilizou o método tracejado (p = 0,003). CONCLUSÃO: A ultrassonografia é um método seguro, viável e confiável para avaliação muscular em pacientes críticos de trauma, independentemente do nível de especialização do avaliador.

Current evidence demonstrates similar effects of kilohertz-frequency and low-frequency current on quadriceps evoked torque and discomfort in healthy individuals: a systematic review with meta-analysis.

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.

Nandrolone increases angiotensin-I converting enzyme activity in rats tendons / Nandrolona aumenta a atividade da enzima conversora de angiotensina em tendões de ratos / La nandrolona aumenta la actividad de la enzima de conversión angiotensina en tendones de ratones

INTRODUCTION: The renin-angiotensin system (RAS) has been associated with several biological processes of the human body, regulating, among others blood pressure and water and electrolytes balance. Moreover, RAS also regulates connective tissue growth. Recently, studies have shown that the use of nandrolone modifies the angiotensin-I converting enzyme (ACE) activity and increases collagen deposition in the heart. OBJECTIVE: The aim of study was to evaluate the Angiotensin-I converting enzyme (ACE) activity in the superficial flexor tendon (SFT) and in serum after load exercise in combination with anabolic androgenic steroid (AAS) administration after training session and six weeks of detraining. METHODS: Forty-eight Wistar rats were used into two groups (G1 and G2) subdivided into four subgroups: Sedentary (S); trained (T); AAS-treated (Deca-Durabolin(r), 5mg/kg, twice a week) sedentary rats (AAS) and AAS-treated and trained animals (AAST). Trained groups performed jumps in water: four series of 10 jumps each, followed by a 30 sec interval between the series, for seven weeks. RESULTS: Training increased ACE activity in the SFT compared to the control group (p <0.05). Both AAS and AAST groups presented higher ACE activity levels (p < 0.05). The AAST increased the ACE activity only compared to the trained animals. Only the AAST group presented significant higher levels of ACE in the serum. In the G2 group, all experimental groups presented decreased ACE activity in the serum and in the tendon, as compared to the control group. CONCLUSION: This study indicates that AAS administration and its combination with exercise increased ACE activity of tendons. AAS abuse could compromise tendon adaptation causing maladaptive remodeling. .

INTRODUÇÃO: O sistema renina-angiotensina (SRA) tem sido associado a importantes processos biológicos do corpo humano, regulando, entre outros processos, a pressão arterial e balanço hidroeletrolítico. Além disso, o SRA também regula o crescimento do tecido conjuntivo. Recentemente, foi demonstrado que a utilização de nandrolona modifica a atividade da enzima conversora de angiotensina (ECA) e aumenta a deposição de colágeno no coração. OBJETIVO: O objetivo do estudo foi avaliar a atividade de ECA no tendão flexor superficial (TFS) e no soro após exercício de força com administração de esteroides anabólicos androgênicos (EAA) durante sete semanas e após seis semanas de destreinamento. MÉTODOS: Quarenta e oito ratos da linhagem Wistar foram divididos em dois grupos (G1 e G2) e subdivididos em quatro subgrupos: Sedentários (S); treinados (T); sedentários com EAA (EAAS) (Deca-Durabolin(r) - 5mg/kg, duas vezes por semana) e treinados com administração de EAA (EAAT). Os grupos treinados realizaram saltos na água: quatro séries de 10 saltos cada, com intervalo de 30 seg entre as séries. RESULTADOS: O treinamento aumentou a atividade de ECA no TFS em comparação ao controle (p<0,05). Os grupos tratados com EAA apresentaram maiores níveis de ECA (p<0,05). O grupo EAA-T mostrou atividade de ECA mais elevada quando comparada ao grupo T. Além disso, o grupo EAA-T apresentou maiores níveis de ECA no soro. No grupo G2, todos os subgrupos diminuíram a atividade de ECA tanto no soro quanto no tendão. CONCLUSÃO: Este estudo indica que a administração de EAA e sua combinação com o exercício aumenta a atividade de ECA nos tendões. O uso abusivo de EAA pode comprometer a adaptação tendínea no qual pode provocar remodelamento mal adaptativas. .

INTRODUCCIÓN: El sistema renina-angiotensina (RAS) ha sido asociado con varios procesos biológicos del cuerpo humano, entre ellos, regular la presión arterial y el contenido de electrolitos. Además, el RAS también regula el tejido conectivo. Recientemente, estudios han demostrado que el uso de nandrolona modifica la actividad de ACE e incrementa la deposición de colágeno en el corazón. OBJETIVO: En este modo, el objetivo del estudio fue evaluar la actividad de la enzima de conversión angiotensina (ACE) en el tendón flexor superficial (TFS) y en el suero después del ejercicio de resistencia en combinación con la administración de esteroides anabólico-androgénicos (AAS) después de la sesión de entrenamiento, y seis semanas de desentrenamiento. MÉTODOS: Cuarenta y ocho ratones Wistar fueron divididos en dos grupos (G1 y G2) y subdivididos en cuatro grupos: sedentarios (S); entrenados (T); ratas sedentarias tratadas con AAS (Deca-Durabolin(r) - 5 mg / kg dos veces a la semana) (AAS) y animales entrenados y tratados con AAS (AAST). Los grupos entrenados realizaron saltos en el agua: cuatro series de 10 saltos cada uno, con 30 segundos de intervalo entre las series, durante siete semanas. RESULTADOS: El entrenamiento aumentó la actividad de ECA en TFS en comparación con el control (p <0,05). Los grupos AAS y AAST mostraron mayores niveles de ACE (p <0,05). El grupo AAST mostró alta actividad de ECA en comparación con el grupo T. Además, el AAST mostró niveles más altos de ACE en el suero. En G2, todos los grupos disminuyeron la la actividad ACE tanto en el suero como en el tendón si comparados con el grupo control. CONCLUSIÓN: Este estudio indica que la administración de AAS y su combinación con el ejercicio aumenta la actividad de ECA en los tendones. El uso abusivo de AAS puede comprometer la adaptación del tendón, lo que puede causar remodelaciones mal adaptativas. .

Gene expression in distinct regions of rat tendons in response to jump training combined with anabolic androgenic steroid administration.

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-ß-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.