Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.

BACKGROUND: Musculoskeletal pain is a condition that affects bones, muscles, and tendons and is present in various diseases and/or clinical conditions. This type of pain represents a growing problem with enormous socioeconomic impacts, highlighting the importance of developing treatments tailored to the patient's needs. TRP is a large family of non-selective cation channels involved in pain perception. Vanilloid (TRPV1 and TRPV4), ankyrin (TRPA1), and melastatin (TRPM8) are involved in physiological functions, including nociception, mediation of neuropeptide release, heat/cold sensing, and mechanical sensation. OBJECTIVE: In this context, we provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models. METHODS: This review describes preclinical models of muscle hyperalgesia induced by intramuscular administration of algogenic substances and/or induction of muscle damage by physical exercise in the masseter, gastrocnemius, and tibial muscles. RESULTS: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. CONCLUSION: Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.

Modified gastrocnemius splitting anatomic approach to the tibial plateau. Medium-term evaluation.

BACKGROUND: Posterior tibial plateau fractures, including avulsion fractures of the posterior cruciate ligament (PCL) insertion, represent a challenge for the orthopedic trauma surgeon. These injuries have gained a new perspective both diagnostically and therapeutically after the regular use of multiplanar computed tomography. In the herein study, we describe the outcome of patients sustaining a tibial plateau fracture with posterior articular involvement treated by open reduction and internal fixation (ORIF) using our modified gastrocnemius splitting anatomic approach. METHODS: This observational retrospective descriptive study was conducted at Complejo Medico de la Policia Federal Argentina Churruca-Visca. All patients were treated by ORIF by our team through our modified gastrocnemius splitting anatomic approach, and followed-up for a minimum of 12 months. RESULTS: A total of 18 patients sustaining plateau fracture were treated by this approach. Satisfactory tomographic reduction with articular gap and/or step-off <2 mm was achieved in 16. The mean time to the return to activities of daily living was 192.2 days. CONCLUSION: The modified gastrocnemius splitting anatomic approach represents a good alternative for the management of tibial plateau fractures involving the posterior quadrants.

Effect of M-wave Amplitude on Inter-evaluator Concordance and Number of Detected Innervation Zones in the Medial Gastrocnemius Using Multichannel Electromyography / Efecto de la Amplitud de la Onda M sobre la Concordancia entre Evaluadores y el Número de Zonas de Inervación Detectadas en el Gastrocnemio Medial Mediante Electromiografía Multicanal

SUMMARY: The Innervation Zones (IZ) correspond to clusters of neuromuscular junctions. The traditional method of locating IZs through voluntary muscle contractions may not be feasible in individuals with motor disorders. Imposed contractions by electrostimulation are an alternative. However, there is limited evidence regarding the factors that affect inter-evaluator concordance and the number of localized IZs when using imposed contraction. The main objective of this research was to determine the effect of the amplitude of compound motor action potentials (CMAPs) containing the M-wave on inter-evaluator agreement. As a secondary objective, was investigate the effect on the number of detected IZs. Twenty-four healthy volunteers (age: 21.2 ± 1.5years, weight: 67.4 ± 13.2kg, height: 1.68 ± 0.80m) participated in the study. Electrostimulation was applied to the tibial nerve to induce contraction of the medial gastrocnemius. The IZ were identified based on the M-wave recorded through multichannel electromyography. A receiver operating characteristic (ROC) analysis was conducted to assess sensitivity and specificity in detecting the IZs. Inter-rater agreement was evaluated using a two-way mixed effects test to determine the intraclass correlation coefficients (ICC). A p-value less than 0.05 was considered statistically significant. The ROC analysis revealed that for both evaluators, a specificity of 95% was achieved with an amplitude ≥30 %. The area under the ROC curve was 0.980 [0.964, 0.996], indicating a strong influence of CMAP amplitude on detection of IZs. The highest level of agreement (ICC = 0.788 [0.713, 0.844]) among the evaluators was observed with CMAP amplitudes equal to or greater than 80 % of the maximum M-wave. The findings of this study demonstrate that both the number and the inter-evaluator concordance for detecting IZs using imposed contractions are strongly influenced by the amplitude of the M-wave. Higher M-wave amplitudes were associated with improved concordance and increased IZ detection, making it crucial to standardize amplitude settings for reliable outcomes.

Las Zonas de Inervación (IZ) corresponden a grupos de uniones neuromusculares. El método tradicional para localizar IZs mediante contracciones musculares voluntarias puede no ser factible en personas con trastornos motores. Las contracciones impuestas mediante electro estimulación son una alternativa. Sin embargo, existe poca evidencia sobre los factores que afectan la concordancia entre evaluadores y el número de IZs localizadas al usar este tipo de contracciones. El objetivo de esta investigación fue determinar el efecto de la amplitud de los potenciales de acción motores compuestos (PAMCs) que contienen la onda M sobre la concordancia entre evaluadores. Como objetivo secundario, se investigó el efecto sobre el número de IZs detectadas. Veinticuatro voluntarios sanos (edad: 21.2 ± 1.5 años, peso: 67.4 ± 13.2 kg, altura: 1.68 ± 0.80 m) participaron en el estudio. Se aplicó electroestimulación al nervio tibial para inducir la contracción del gastrocnemio medial. Las IZs se identificaron según la onda M registrada mediante electromiografía multicanal. Se realizó un análisis de curva de las característica del receptor (ROC) para evaluar la sensibilidad y especificidad en la detección de las IZs. La concordancia entre evaluadores se evaluó utilizando una prueba de efectos mixtos de dos vías para determinar los coeficientes de correlación intraclase (ICC). Se consideró un valor de p menor que 0.05 como estadísticamente significativo. El análisis ROC reveló que para ambos evaluadores se logró una especificidad del 95% con una amplitud ≥30 %. El área bajo la curva ROC fue de 0.980 [0.964, 0.996], lo que indica una fuerte influencia de la amplitud del CMAP en la detección de las IZs. El nivel más alto de concordancia (ICC = 0.788 [0.713, 0.844]) entre los evaluadores se observó con amplitudes de CMAP iguales o mayores al 80 % de la onda M máxima. Los hallazgos de este estudio demuestran que tanto el número como la concordancia entre evaluadores para detectar IZs mediante contracciones impuestas están fuertemente influenciados por la amplitud de la onda M. Las amplitudes más altas de la onda M se asociaron con una concordancia mejorada y un aumento en la detección de IZs, lo que hace crucial estandarizar los ajustes de amplitud para obtener resultados confiables.

Low-Level Photobiomodulation Therapy Modulates H2O2 Production, TRPC-6, and PGC-1α Levels in the Dystrophic Muscle.

Objective: This study evaluated photobiomodulation therapy (PBMT) effects on the factors involved in mitochondrial biogenesis, on the mitochondrial respiratory complexes, and on the transient receptor potential canonical channels (such as TRPC-1 and TRPC-6) in in vitro (mdx muscle cells) and in vivo studies (gastrocnemius muscle) from mdx mice, the dystrophin-deficient model of Duchenne muscular dystrophy (DMD). Background: There is no successful treatment for DMD, therefore demanding search for new therapies that can improve the muscle role, the quality of life, and the survival of dystrophic patients. Methods: The dystrophic primary muscle cells received PBMT at 0.6 J and 5 J, and the dystrophic gastrocnemius muscle received PBMT at 0.6 J. Results: The dystrophic muscle cells treated with PBMT (0.6 J and 5 J) showed no cytotoxicity and significantly lower levels in hydrogen peroxide (H2O2) production. We also demonstrated, for the first time, the capacity of PBMT, at a low dose (0.6 J), in reducing the TRPC-6 content and in raising the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) content in the dystrophic gastrocnemius muscle. Conclusions: PBMT modulates H2O2 production, TRPC-6, and PGC-1α content in the dystrophic muscle. These results suggest that laser therapy could act as an auxiliary therapy in the treatment of dystrophic patients.

In vivo absolute quantification of carnosine in the vastus lateralis muscle with 1H MRS using a surface coil and water as internal reference.

OBJECTIVE: To standardize a method for 1H MRS intramuscular absolute quantification of carnosine in the thigh, using a surface coil and water as internal reference. MATERIALS AND METHODS: Carnosine spectra were acquired in phantoms (5, 10, and 15 mM) as well as in the right gastrocnemius medialis (GM) and right vastus lateralis (VLM) muscles of young team sports athletes, using volume (VC) and surface (SC) coils on a 3 T scanner, with the same receiver gain. Water spectra were used as internal reference for the absolute quantification of carnosine. RESULTS: Phantom's experiments showed a maximum error of 7%, highlighting the validity of the measurements in the study setup. The carnosine concentrations (mmol/kg ww, mean ± SD) measured in the GM were 6.8 ± 2.2 with the VC (CcarVC) and 10.2 ± 3.0 with the SC (CcarSC) (P = 0.013; n = 9). Therefore, a correction was applied to these measurements (CcarVC = 0.6582*CcarSC), to make coils performance comparable (6.8 ± 2.2 for VC and 6.7 ± 2.0 for SC, P = 0.97). After that, only the SC was used to quantify carnosine in the VLM, where a concentration of 5.4 ± 1.5 (n = 30) was found, with significant differences between men (6.2 ± 1.3; n = 15) and women (4.6 ± 1.2; n = 15). The error in quantitation was 5.3-5.5% with both coils. CONCLUSION: The method using the SC and water as internal reference can be used to quantify carnosine in voluminous muscles and regions of the body in humans, where the VC is not suitable, such as the VLM.

Location In Vivo of the Innervation Zone in the Human Medial Gastrocnemius Using Imposed Contractions: A Comparison of the Usefulness of the M-Wave and H-Reflex.

The anatomical territory where the neuromuscular junctions are grouped corresponds to the innervation zone (IZ). This can be located in-vivo using high-density electromyography and voluntary muscle contractions. However, in patients with motor impairment, the use of contractions imposed by electrical stimulation (ES) could be an alternative. The present study has two aims: Firstly, to describe the location of the IZ in-vivo of the medial gastrocnemius (MG) using imposed contractions by ES. Secondly, to compare the usefulness of M-waves and H-reflexes to localize the IZs. Twenty-four volunteers participated (age: 21.2 ± 1.5 years). ES was elicited in the tibial nerve to obtain M-waves and H-reflexes in the MG. The evaluators used these responses to localize the IZs relative to anatomical landmarks. M-wave and H-reflex IZ frequency identification were compared. The IZs of the MG were mostly located in the cephalocaudal direction, at 39.7% of the leg length and 34% of the knee's condylar width. The IZs were most frequently identified in the M-wave (83.33%, 22/24) compared to the H-reflex (8.33%, 2/24) (p > 0.001). Imposed contractions revealed that the IZ of the MG is located at 39.7% of the leg length. To locate the IZs of the MG muscle, the M-wave is more useful than the H-reflex.

Colgajo pediculado de músculo gastrocnemio para la reconstrucción de tejidos blandos de tibia superior

La cirugía de colgajos ha cambiado el pronóstico de los traumas en la Ortopedia. En este estudio se muestra el uso del músculo gastrocnemio como colgajo pediculado para la reconstrucción de defectos de tejidos blandos en el tercio superior de tibia. Siete pacientes se sometieron a la reconstrucción y se les realizó un injerto de piel de espesor parcial para cubrir el músculo. Los colgajos transferidos sobrevivieron sin compromiso vascular, la cobertura del defecto fue satisfactoria y la herida tuvo buena cicatrización primaria. No se constató recurrencia de osteomielitis. Los sitios donantes sanaron sin discapacidad funcional. El seguimiento reveló óptimos resultados estéticos. La transferencia del músculo gastrocnemio es una técnica útil para cubrir defectos de tejidos blandos en la tibia superior; confiable para cobertura de hueso expuesto, relleno de cavidades y tratamiento de infecciones óseas.

Flap surgery has changed trauma prognosis in Orthopedics. This study shows the use of the gastrocnemius muscle as a pedicled flap for the reconstruction of soft tissue defects in the upper third of the tibia. Seven patients underwent reconstruction and received a split-thickness skin graft to cover the muscle. The transferred flaps survived without vascular compromise, defect coverage was satisfactory, and the wound had good primary healing. No recurrence of osteomyelitis was found. The donor sites healed without functional disability. Follow-up revealed optimal aesthetic results. Gastrocnemius muscle transfer is a useful technique for covering soft tissue defects in the upper tibia, reliable for coverage of exposed bone, cavity filling, and treatment of bone infections.

Effect of varying dietary crude protein and metabolizable energy levels on leg abnormalities and performance in broiler chickens

Background: Nutrient restriction is a common strategy to prevent metabolic disorders in fast growing broiler chickens, but limited information is available regarding the impact of diets with low protein and energy on leg abnormalities Objective: Two experiments were conducted to evaluate the effect of varying crude protein (CP) and metabolizable energy (ME) levels on gastrocnemius tendon (GTeBS) and tibia breaking strength (TiBS), gait score (GS) and valgus/varus angulation (VAng). Methods: In Experiment 1, eight-d-old Ross 308 broilers (n=90) were randomly assigned into three treatments: 13/2,900 (13% CP and 2,900 kcal ME kg-1 of diet), 17/3,000 (17% CP and 3,000 kcal ME kg-1 of diet), and 21/3,025 or control (21% CP and 3,025 kcal ME kg-1 of diet). In Experiment 2, six-d-old Ross 308 chickens (n=192) were randomly distributed into two treatments: 16/3,000; 16% CP and 3,000 kcal ME kg-1 of diet and 21/3,000 or control; 21% CP and 3,000 kcal ME kg-1 of diet. In both experiments data were analyzed as one-way ANOVA. Results: In Experiment 1, broilers in the 17/3,000 and control treatments had similar (p>0.05) GTeBS (202 and 224 N, respectively), and TiBS (338 and 332 N, respectively). Birds in the 13/2,900 treatment showed higher GS (lower walking ability; 80% of birds with score >3), and greater VAng (53% of birds with score >2) than broilers in the control treatment (0% of birds with GS score >3 and 0% of birds with VAng score >2). Experiment 2, broilers in the 16/3,000 showed similar VAng, GS and TiBS than birds in the control treatment. However, birds in the 16/3,000 treatment showed lower (-26%) GTeBS than birds in the control treatment (p<0.05). Conclusions: Feeding broilers with 16% CP and 3,000 kcal ME kg-1 of diet did not affect tibia breaking strength, gait score and valgus/varus angulation. A diet containing 16% CP or less and 2,900-3,000 kcal ME kg-1 reduces tendon and tibia breaking strength.

Antecedentes: La restricción de nutrientes es una estrategia común para prevenir trastornos metabólicos en pollos de engorde, sin embargo, se dispone de información limitada sobre el impacto de las dietas bajas en proteína y energía en las anomalías de piernas. Objetivo: Se llevaron a cabo dos experimentos para evaluar el efecto de niveles variables de proteína cruda (PC) y energía metabolizable (EM) en la fuerza de rotura del tendón del gastrocnemio (GTeBS) y tibia (TiBS), la evaluación de marcha (GS) y la angulación en valgus/varus (VAng). Métodos: En el Experimento 1, pollos de engorde Ross 308 de ocho días de edad (n = 90) se asignaron al azar en tres tratamientos: 13/2.900; 13% PC y 2.900 kcal ME kg-1 de dieta, 17/3.000; 17% PC y 3.000 kcal ME kg-1 de dieta y 21/3.025 o control; 21% PC y 3.025 kcal ME kg-1 de dieta. En el Experimento 2, pollos Ross 308 de seis días de edad (n = 192) se distribuyeron aleatoriamente en dos tratamientos: 16/3.000; 16% PC y 3.000 kcal ME kg-1 de dieta y 21/3.000 o control; 21% PC y 3.000 kcal ME kg-1 de dieta. En ambos experimentos los datos se analizaron como ANOVA de una vía. Resultados: En el Experimento 1, los pollos de los tratamientos 17/3.000 y control tuvieron GTeBS (202 y 224 N, respectivamente) y TiBS (338 y 332 N, respectivamente) similares (p>0,05). Las aves del tratamiento 13/2.900 mostraron mayor GS (menor capacidad para caminar; 80% de las aves con puntaje >3) y mayor VAng (53% de las aves con puntaje >2) que los pollos del tratamiento control (0% de aves con un puntaje GS >3 y 0% de aves con un puntaje VAng >2). En el Experimento 2, los pollos del 16/3.000 mostraron VAng, GS y TiBS similares a los de las aves del tratamiento control. Sin embargo, las aves del tratamiento 16/3.000 mostraron menor (-26%) GTeBS que las aves control (p<0,05). Conclusiones: La alimentación de pollos de engorde con 16% PC y 3.000 kcal EM kg-1 de dieta no afecta la resistencia a la ruptura de la tibia, la marcha y la angulación valgus/varus. La dieta formulada con 16% de PC o menos y 2.900-3.000 kcal de EM kg-1 reduce la resistencia a la ruptura del tendón y de la tibia.

Antecedentes: A restrição de nutrientes é uma estratégia comum para prevenir distúrbios metabólicos em frangos de corte, no entanto, há informações limitadas disponíveis sobre o impacto de dietas de baixa proteína e baixa energia nas anormalidades de pernas destas aves. Objetivo: Dois experimentos foram realizados para avaliar o efeito de diferentes níveis de proteína bruta (PB) e energia metabolizável (EM) em força de ruptura do tendão do músculo gastrocnêmio (GTeBS), forca de ruptura da tíbia (TiBS), gait score (GS) e angulação em valgus/varus (VAng). Métodos: Experimento 1, foram utilizados 308 frangos de corte machos da linhagem Ross com oito dias de idade (n = 90) distribuidos aleatoriamente em três tratamentos: dieta controle com 21% PB e 3.025 kcal EM kg-1 13/2.900; dieta con 13% PB e 2.900 kcal EM kg-1, y 17% PB e 3.000 kcal EM kg-1 . Experimento 2, foram utilizados 308 frangos de corte da linhagem Ross com seis dias de idade (n = 192) distribuídos aleatoriamente em dois tratamentos: dieta controle con 21% PB e 3.000 kcal EM kg-1 e dieta com 16% PB e 3.000 kcal EM kg-1 . Em ambos os experimentos, os dados foram submetidos a ANOVA. Resultados: Experimento 1, os frangos de corte submetidos ao dos tratamentos 17/3.000 e controle nao apresentaram diferencas significativas (p>0,05) para as variáveis GteBS (202 y 224 N, respectivamente) e TiBS (338 y 332 N, respectivamente). Os frangos submetidos ao 13/2.900 apresentaram maior frequência de GS (menor capacidade de locomocao; 80% das aves com pontuação>3) e maior VAng (53% das aves com pontuação>2) do que os frangos do tratamento controle (0% das aves com pontuação GS>3 e 0% das aves com pontuação VAng>2). Experimento 2, os frangos do 16/3.000 apresentaram VAng, GS e TiBS semelhantes aos das aves do tratamento controle. Entretanto, as aves do tratamento 16/3.000 apresentaram GTeBS mais baixo (-26%) em comparacao as aves do tratamento de controle (p<0,05). Conclusões: A dieta com 16% PB e 3.000 kcal EM kg-1 não afetou a forca de ruptura da tíbia, gaite score marcha e angulação em valgus/varus de frangos de corte. Uma dieta com níveis de 16% de PB ou menos e 2.900-3.000 kcal EM kg-1 reduziu a resistência à ruptura do tendão e a resistência de tibia de frangos de corte.

Study on the mechanisms of Suaeda rigida polysaccharides on the heart inhibition and skeletal muscle promotion in the frog / [Estudo sobre os mecanismos dos polissacarídeos de Suaeda rigida na inibição do coração e promoção da musculatura esquelética no sapo]

The objectives of this study were to investigate the effects of different concentrations of Suaeda rigida polysaccharides (SRPs) on the physiological characteristics of the frog heart and gastrocnemius muscle, compare their similarities and differences, and analyze the mechanisms. CaCl2 and acetylcholine (Ach) were selected respectively to be co-incubated with the high concentration SRPs to observe the effects on the heart contraction of frog. The effects of different concentrations of the SRPs on the activities of acetylcholinesterase (A-CHE), Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the isolated frog heart were detected by UV-Vis spectrophotometry. The gastrocnemius muscle was immersed in the high concentration of SRPs for 10 min, and the systolic indexes were recorded. The effects of SRPs on the Ach content and A-CHE activity at the sciatic nerve-gastrocnemius junction were determined by UV-Vis spectrophotometry and enzyme-linked immunosorbent assay (ELISA). The results showed that the SRPs had significant inhibitory effects on the contractile amplitude of isolated heart and the contractile amplitude induced by CaCl2 and Ach, respectively (P<0.01). The activity of Ca2+-Mg2+-ATPase was significantly promoted, and the activity of A-CHE was significantly inhibited (P<0.01). The contraction amplitude, contraction rate, relaxation rate of gastrocnemius muscle and the Ach content at the junction of sciatic nerve-gastrocnemius muscle were significantly increased (P<0.01), and the activity of A-CHE at the junction was significantly inhibited (P<0.01) by the SRPs. All the results suggested that the SRPs could inhibit the contraction of heart and promote the contraction and relaxation of skeletal muscle. The mechanism was related to blocking the fast INa channel, inhibiting the ICa-L and activating the M receptors of myocardial membrane and then inhibiting external Ca2+ influx, increasing Ca2+-Mg2+-ATPase activity, decreasing a-che activity.

Os objetivos deste estudo foram investigar os efeitos de diferentes concentrações de Suaeda rigida polissacarídeos (SRPs) sobre as características fisiológicas do coração de rã e do músculo gastrocnêmio, comparar suas semelhanças e diferenças, e analisar os mecanismos. CaCl2 e acetilcolina (Ach) foram selecionados respectivamente para serem co-incubados com os SRPs de alta concentração para observar os efeitos sobre a contração do coração de rã. Os efeitos das diferentes concentrações dos SRPs sobre as atividades da acetilcolinesterase (A-CHE), Na+-K+-ATPase e Ca2+-Mg2+-ATPase no coração isolado de rã foram detectados pela espectrofotometria UV-Vis. O músculo gastrocnêmio foi imerso na alta concentração de SRP por 10 min, e os índices sistólicos foram registrados. Os efeitos das SRPs no conteúdo de Ach e na atividade de A-CHE na junção nervo-gastrocnêmio ciático foram determinados pela espectrofotometria UV-Vis e pelo ensaio de imunoabsorção enzimática (ELISA). Os resultados mostraram que os SRPs tiveram efeitos inibidores significativos sobre a amplitude contrátil do coração isolado e a amplitude contrátil induzida por CaCl2 e Ach, respectivamente (P<0,01). A atividade do Ca2+-Mg2+-ATPase foi significativamente promovida e a atividade do A-CHE foi significativamente inibida (P<0,01). A amplitude de contração, a taxa de contração, a taxa de relaxamento do músculo gastrocnêmio e o conteúdo de Ach na junção do músculo nervo ciático-gastrocnêmio foram significativamente aumentados (P<0,01), e a atividade do A-CHE na junção foi significativamente inibida (P<0,01) pelas SRPs. Todos os resultados sugeriram que os SRPs poderiam inibir a contração do coração e promover a contração e o relaxamento do músculo esquelético. O mecanismo estava relacionado ao bloqueio do canal INa rápido, inibindo a ICa-L e ativando os receptores M da membrana miocárdica e depois inibindo o influxo externo de Ca2+, aumentando a atividade de Ca2+-Mg2+-ATPase, diminuindo a atividade a-che.

Exercise training decreases oxidative stress in skeletal muscle of rats with pulmonary arterial hypertension.

The effects of exercise training on oxidative stress in gastrocnemius of rats with pulmonary hypertension were studied. Four groups were established: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), trained monocrotaline (TM). Exercise was applied for 4 weeks, 5 days/week, 50-60 min/session, at 60% of VO2 max. Right ventricular (RV) pressures were measured, heart and gastrocnemius were removed for morphometric/biochemical analysis. Lipid peroxidation (LPO), H2O2, GSH/GSSG, and activity/expression of antioxidant enzymes were evaluated. Increased RV hypertrophy, systolic and end-diastolic pressures (RVEDP) were observed in SM animals, and the RVEDP was decreased in TM vs. SM. H2O2, SOD-1, and LPO were higher in the SM group than in SC. In TM, H2O2 was further increased when compared to SM, with a rise in antioxidant defences and a decrease in LPO. GSH/GSSG was higher only in the TC group. Exercise induced an efficient antioxidant adaptation, preventing oxidative damage to lipids.

Role of phenolic compounds from brazilian native fruits on obesity-induced insulin resistance in skeletal muscle / Papel dos compostos fenólicos de frutos nativos brasileiros sobre a resistência à insulina do músculo esquelético induzida por obesidade

Skeletal muscle is an important metabolic tissue in glucose uptake and thus in glycemic homeostasis. Evidence suggests that phenolic compounds may exert beneficial health effects against metabolic disorders associated to obesity including its state of peripheral insulin resistance. The objective of this work was to investigate the role of phenolic compounds present in two Brazilian native fruits, cambuci (Campomanesia phaea Berg.) and jaboticaba (Plinia jaboticaba (Vell.) Berg), on the insulin resistance in the skeletal muscle of obese mice fed a high-fat-sucrose diet (HFS). For this, two independent experimental protocols were used for each fruit, where male C57BL/6J mice fed the HFS diet for the induction to obesity were used. Once the condition of obesity was established, animals started to receive daily oral administration (by gavage) of extracts enriched in phenolic compounds obtained from each fruit, in doses reachable through the diet. At the end of the experiments, the animals were euthanized and their tissue and organs collected. The animals receiving extracts of jaboticaba and cambuci, regardless of the dose, presented lower body weight gain in relation to the HFS group. The results for weekly fasting glycemia and glucose tolerance of the animals that received the phenolic extracts of both fruits showed an improvement in glycemic homeostasis even when fed with the deleterious diet. In the gastrocnemius muscle of the animals was demonstrated that cambuci and jaboticaba extracts significantly increased the content of glucose transporter protein 4 (GLUT-4) and AMPactivated protein kinase (AMPK-Thr172), which has a broad role in metabolic regulation. Regarding inflammation, the administration of extracts from both fruits favored the reduction of phosphorylation and activation of the nuclear factor-κe (NF-κB) and the expression of some genes such as IL-6, TNF-α, IL-1ß, and JNK, whose increase has been associated with insulin resistance. In conclusion, this study suggests that the phenolics present in both native fruits may be important therapeutic agents in the reduction of muscle insulin resistance and inflammation associated with obesity

O músculo esquelético é um tecido metabólico importante na captação de glicose e, portanto, na homeostasia glicêmica. Evidências sugerem que compostos fenólicos podem exercer efeitos benéficos à saúde contra distúrbios metabólicos associados à obesidade incluindo o seu quadro de resistência à insulina. O objetivo deste trabalho foi investigar o papel dos compostos fenólicos presentes em dois frutos nativos brasileiros, cambuci (Campomanesia phaea Berg.) e jaboticaba (Plinia jaboticaba (Vell.) Berg), na resistência à insulina no músculo esquelético de camundongos obesos alimentados com dieta rica em gorduras e sacarose (HFS, high-fat highsucrose diet). Para tal, foram utilizados dois protocolos experimentais independentes para cada fruto, onde foram usados camundongos machos C57BL/6J alimentados com dieta HFS para indução à obesidade. Uma vez instaurado o quadro de obesidade, os animais passaram a receber a administração diária, por gavagem, de extratos enriquecidos em compostos fenólicos obtidos a partir dos frutos, em doses atingíveis através da dieta. Ao final do período experimental os animais foram eutanasiados e seus tecidos e órgãos coletados. Os animais tratados com os extratos de jaboticaba e cambuci, independente da dose, apresentaram menor ganho de massa corporal em relação ao grupo HFS. Os resultados para glicemia de jejum semanal e a tolerância à glicose dos animais que receberam os extratos fenólicos de ambos os frutos demonstraram melhora na homeostase glicêmica, mesmo alimentados com a dieta deletéria HFS. No músculo gastrocnemius dos animais foi demonstrado que os extratos de cambuci e jaboticaba aumentaram significativamente o conteúdo da proteína transportadora de glicose 4 (GLUT-4) e da proteína quinase ativada por AMP (AMPK-Thr172), que possui um papel amplo na regulação metabólica. No que tange à inflamação, a administração dos extratos de ambos os frutos favoreceu a diminuição da fosforilação e ativação do fator nuclear-κB (NF-κB) e a expressão de alguns genes como IL-6, TNF-α, IL-1ß, e JNK cujo aumento tem sido associado com a resistência à insulina. Deste modo, este estudo sugere que os fenólicos presentes em ambos os frutos nativos podem ser agentes terapêuticos importantes na atenuação da resistência à insulina muscular e da inflamação associada à obesidade

Paternal Resistance Exercise Modulates Skeletal Muscle Remodeling Pathways in Fathers and Male Offspring Submitted to a High-Fat Diet.

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1ß, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets.

An accessory muscle of the posterior compartment of leg of clinical significance: a cadaveric case report / Un músculo accesorio del compartimento posterior de la pierna de importancia clínica: reporte de un caso cadavérico

SUMMARY: Accessory and anomalous muscles are common in humans, although their unique morphologic characteristics can make accurate identification difficult. In this case report, we attempt to identify an anomalous accessory muscle of the posterior compartment of the leg [Compartimentum posterius cruris] detected during cadaveric dissection and discuss its clinical significance. The muscle was found on the right lower limb of an 81-year-old female cadaver and extended from the distal femur to attach to the gastrocnemius muscle at the point where the medial and lateral heads fuse. At its origin, the muscle was found lateral to the popliteal vessels and crossed posterior to these vessels and tibial nerve. It displayed characteristics similar to both an accessory plantaris muscle and gastrocnemius tertius, thus making its ultimate identification difficult. Though the muscle displayed a morphologically similar appearance to the plantaris, we suggest that its common insertion with the gastrocnemius best identifies it as a gastrocnemius tertius. In addition, due to its relationship with the popliteal neurovasculature, it is possible that this muscle could have resulted in neurovascular entrapment although it is unknown whether or not this cadaver exhibited symptoms.

RESUMEN: Los músculos accesorios y anómalos son comunes en los seres humanos, aunque sus características morfológicas pueden dificultar la identificación precisa. En este reporte de caso, intentamos identificar un músculo accesorio anómalo del compartimento posterior de la pierna [Compartimentum posterius cruris] detectado durante la disección cadavérica y discutir su importancia clínica. El músculo fue encontrado en el miembro inferior derecho de una mujer de 81 años de edad y se extendía desde la parte distal del fémur para unirse al músculo gastrocnemio en la fusión de sus cabezas medial y lateral. En su origen, el músculo se encontraba lateral a los vasos poplíteos y cruzaba posteriormente a estos vasos y al nervio tibial, presentando características similares tanto al músculo plantar accesorio como al gastrocnemio tercero, lo que dificultaba su identificación final. Similar al músculo plantar, sugerimos que debido a su inserción común con el gastrocnemio lo identifica mejor como un músculo gastrocnemio tercero. Además, debido a su relación con la neurovasculatura poplítea, es posible que este músculo haya dado lugar a un síndrome de compresión neurovascular aunque se desconoce si este individuó presentó síntomas o no en vivo.

Morphological Changes in the Motor Endplate and in the Belly Muscle Induced by Previous Static Stretching to the Climbing Protocol.

Static stretching provides benefits to the range of motion, modulates intramuscular connective tissue, and is incorporated into warm-up exercises. In this study, we present the effects in the motor endplate and belly muscle resulting from previous static stretching to climbing training. Twenty-four adult male Wistar rats were divided into four groups (n = 6 each): Sedentary (Sed), Climbing (Clb), Static stretching (Ss), and Static stretching prior to climbing (Ssc). The animals (Clb, Ss, and Ssc groups) were subjected to a training protocol 3×/week for 8 weeks, and the Ssc group was subjected to the Ss and Clb protocols in the same session. Samples from the animals were processed for immunostaining, histochemistry, and light microscopy. The Clb group presented a higher motor endplate; the Ss group presented no changes in the motor endplate; and the Ssc group demonstrated a higher compactness. We concluded that static stretching prior to the climbing protocol maintained the density of the motor endplate and increased the compactness of the neuromuscular junction structure. Also, there was a reduction in the myofibers' diameter (Type I and IIa), an increase in myofibrillar densities (Type I and IIx, and total), and the reorganization of the myonuclei and the interstitium.

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice.

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.

Reliability of a simple novel field test for the measurement of plantar flexor muscle strength / Confiabilidade de um novo teste de campo simples para medir a força dos músculos flexores plantares / Confiabilidad de un nuevo test de campo simple para medir la fuerza de los músculos flexores plantares

ABSTRACT Introduction When a person is in a standing position, the plantar flexor muscles are involved in most static and dynamic body movements. Objectives The aim of this study was to investigate the trial to trial and factorial reliability of measuring the contractile characteristics of PF muscles using a simple novel field test. Methods The sample consisted of 452 healthy subjects, 120 male and 332 female. The research was conducted by means of the trial to trial testing method, using isometric dynamometry performed in field conditions. ANOVA was used to estimate the differences among the trials, Cronbach's alpha and interclass correlation to estimate the correlations among the trials, and principal component analysis to evaluate the contribution of each trial to overall variability. Results The main findings of this study are that trials differed significantly (p<0.000) for maximal force (Fmax) and maximal rate of force development (RFDmax), indicating that the three procedural trials were necessary. The trials were highly correlated (Fmax, RFDmax, r>0.9), proving that measuring was reliable, and the factorial analysis separated the second and third trials, the second trial accounting for most of the total variability. Conclusions The simple novel field test for the measurement of plantar flexor contractile characteristics recommended by this study proved to be as highly reliable as laboratory testing, but was easy to perform in conditions outside of scientific or diagnostic institutions, which greatly facilitates the work of scientists, coaches and professionals. Level of Evidence II; Diagnostic Studies - Investigating a diagnostics test.

RESUMO Introdução Quando uma pessoa está em pé, os músculos flexores plantares são envolvidos na maioria dos movimentos corporais estáticos e dinâmicos. Objetivos O objetivo deste estudo foi investigar a confiabilidade teste-reteste e fatorial da mensuração das características contráteis dos músculos plantares, usando um novo teste de campo simples. Métodos A amostra consistiu em 452 indivíduos saudáveis, 120 homens e 332 mulheres. O estudo foi realizado pelo método de teste-reteste, com dinamometria isométrica conduzida em condições de campo. Empregou-se a ANOVA para estimar a diferença entre os testes o alfa de Cronbach e a correlação interclasse para estimar a correlação entre os testes e análise de componentes principais , para avaliar a contribuição de cada teste para a variabilidade global. Resultados Os principais achados deste estudo são que os testes diferiram significativamente (p < 0,000) para a força máxima (Fmáx) e a taxa máxima de desenvolvimento de força (TDFmáx), indicando que os três testes de procedimento foram necessários. Os testes foram altamente correlacionados (Fmáx, TDFmáx, r > 0,9), provando que a medição era confiável, e a análise fatorial separou o segundo e o terceiro testes, sendo que o segundo teste apresentou a maior parte da variabilidade total. Conclusões O novo teste de campo simples para medição das características contráteis dos flexores plantares recomendado por este estudo provou ser tão confiável quanto os testes de laboratório e, ao mesmo tempo, mais fácil de realizar fora das instituições científicas ou de diagnóstico, o que facilita muito o trabalho de cientistas, treinadores e profissionais. Nível de Evidência II; Estudos Diagnósticos - Investigação de um exame para diagnóstico.

RESUMEN Introducción Cuando una persona está de pie, los músculos flexores plantares son involucrados en la mayoría de los movimientos corporales estáticos y dinámicos. Objetivos El objetivo de este estudio fue investigar la confiabilidad test-retest y factorial de la medición de las características contráctiles de los músculos plantares, usando un nuevo test de campo simple. Métodos La muestra consistió en 452 individuos saludables, 120 hombres y 332 mujeres. El estudio fue realizado a través del método de test-retest, con dinamometría isométrica conducida en condiciones de campo. Se empleó ANOVA para estimar la diferencia entre los tests, alpha de Crombach y la correlación interclase para estimar la correlación entre los tests y el análisis de componentes principales, para evaluar la contribución de cada test para la variabilidad global. Resultados Los principales hallazgos de este estudio son que los tests difirieron significativamente (p<0,000) para la fuerza máxima (Fmáx) y la tasa máxima de desarrollo de fuerza (TDFmáx) indicando que los tres tests de procedimiento fueron necesarios. Los tests fueron altamente correlacionados (Fmáx, TDFmáx, r>0,9) probando que la medición era confiable, y el análisis factorial separó el segundo y tercer test, siendo que el segundo test presentó la mayor parte de variabilidad total. Conclusiones El nuevo test de campo simple para medición de las características contráctiles de los flexores plantares recomendado por este estudio probó ser tan confiable como los tests de laboratorio y, al mismo tiempo, más fácil de realizar fuera de las instituciones científicas o de diagnóstico, lo que facilita mucho el trabajo de científicos, entrenadores y profesionales. Nivel de evidencia II; Estudios diagnósticos - Investigación de un examen para diagnóstico.

Characterisation of nociception and inflammation observed in a traumatic muscle injury model in rats.

Muscle pain is the most prevalent type of pain in the world, but treatment remains ineffective. Thus, it is relevant to develop trustable animal models to understand the involved pain mechanisms. Therefore, this study characterised the nociception and inflammation in a traumatic muscle injury model in rats. A single blunt trauma impact on the right gastrocnemius muscle of male Wistar rats (250-350 g) was used as model for muscle pain. Animals were divided into four groups (sham/no treatment; sham/diclofenac 1%; injury/no treatment; injury/diclofenac 1%) and the topical treatment with a cream containing 1% monosodium diclofenac (applied at 2, 6, 12, 24, and 46 h after muscle injury; 200 mg/muscle) was used as an anti-inflammatory control. Nociception (mechanical and cold allodynia, or nociceptive score) and locomotor activity were evaluated at 26 and 48 h after injury. Also, inflammatory and oxidative parameters were evaluated in gastrocnemius muscle and the creatine kinase (CK) activity and lactate/glicose levels in rat's serum and plasma, respectively. Muscle injury caused mechanical and cold allodynia, and increased nociceptive scores, without inducing locomotor impairment. This model also increased the inflammatory cells infiltration (seen by myeloperoxidase and N-acetyl-ß-D-glucosaminidase activities and histological procedure), nitric oxide, interleukin (IL)-1ß, IL-6, and dichlorofluorescein fluorescence in muscle samples; and CK activity and lactate/glicose ratio. The treatment with 1% monosodium diclofenac reduced inflammatory cells infiltration, dichlorofluorescein fluorescence and lactate/glicose levels. Thus, we characterised the traumatic muscle injury as a reproducible model of muscle pain, which makes it possible to evaluate promising antinociceptive and anti-inflammatory therapies.

Protective effects of honey, Apis mellifera meda skorikov, on ischemia-reperfusion induced muscle injury / Efectos protectores de la miel, Apis mellifera meda skorikov, sobre la lesión muscular inducida por isquemia-reperfusión

Honey is a natural antioxidant that its protective effects have been proven against ischemia-reperfusion (IR) injury. The aim of this study was to evaluate the ameliorative effect of Persian Honey, Apis mellifera meda skorikov, on gastrocnemius muscle IR injury. Eighty adult male Sprague-Dawley rats weighing 250-300 g were used. They were divided into ten groups (N=8 per group). The ischemia was conducted with a silk suture 6-0 using the slipknot technique. All groups were rendered in ischemic for 3 h, and reperfused for various times of 3 days (3-day reperfusion), 7 days (7-day reperfusion), 14 days (14-day reperfusion), and 28 days (28-day reperfusion). Half of the groups had experimental honey (5 %) treatment immediately after ischemia. After reperfusion, the rats, based on the grouping, were killed with high doses of anesthetic, and the gastrocnemius muscles were removed and fixed. After the tissue processing, the evaluation of edema and mast cells infiltration was performed with hematoxylin-eosin and toluidine blue staining, respectively. TNF-α was detected with immunohistochemistry method. The amount of TNF-α as an index of acute inflammatory except the 3rd day significantly decreased on the other day of reperfusion (7th, 147th and 287th days). The mast cells infiltration was significantly decreased on 77th and 147th days. The tissue edema was decreased significantly in honey administrated group in the comparison with placebo groups. Honey administration can reduce damage caused by ischemia-reperfusion in the rat gastrocnemius muscle.

La miel es un antioxidante natural; sus efectos protectores han sido probados contra la lesión por isquemiareperfusión (IR). El objetivo de este estudio fue evaluar el efecto de mejora de la miel persa Apis mellifera meda skorikov, en la lesión por IR del músculo gastrocnemio. Se utilizaron 80 ratas Sprague-Dawley macho adultas con un peso entre 250 y 300 g divididas en diez grupos (N = 8 por grupo). La isquemia se realizó con una sutura de seda 6-0 utilizando la técnica slipknot permaneciendo isquémicos durante 3 h. La reperfusión se realizó durante varios tiempos de 3 días, 7 días (reperfusión de 7 días), 14 días (reperfusión de 14 días) y 28 días (28 días reperfusión). La mitad de los grupos recibió tratamiento experimental con miel (5 %) inmediatamente después de la isquemia. Después de la reperfusión, las ratas, fueron sacrificadas con altas dosis de anestésico, y los músculos gastrocnemios fueron removidos y fijados. Después de procesar el tejido, se realizó la evaluación del edema y la infiltración de mastocitos se realizó con tinción de hematoxilina-eosina y azul de toluidina, respectivamente. TNF-α se detectó con el método de inmunohistoquímica. La cantidad de TNF-α como índice de inflamación inflamatoria aguda, excepto en el tercer día, disminuyó significativamente al día siguiente de la reperfusión (7, 14 y 28 días). La infiltración de mastocitos disminuyó significativamente a los 7 y 14 días. El edema tisular disminuyó significativamente en el grupo administrado con miel en comparación con los grupos placebo. El tratamiento con miel puede reducir el daño causado por la isquemia-reperfusión en el músculo gastrocnemio de la rata.

Effects of aerobic and resistance exercise on cardiac remodelling and skeletal muscle oxidative stress of infarcted rats.

We compared the influence of aerobic and resistance exercise on cardiac remodelling, physical capacity and skeletal muscle oxidative stress in rats with MI-induced heart failure. Three months after MI induction, Wistar rats were divided into four groups: Sham; sedentary MI (S-MI); aerobic exercised MI (A-MI); and resistance exercised MI (R-MI). Exercised rats trained three times a week for 12 weeks on a treadmill or ladder. Statistical analysis was performed by ANOVA or Kruskal-Wallis test. Functional aerobic capacity was greater in A-MI and strength gain higher in R-MI. Echocardiographic parameters did not differ between infarct groups. Reactive oxygen species production, evaluated by fluorescence, was higher in S-MI than Sham, and lipid hydroperoxide concentration was lower in A-MI than the other groups. Glutathione peroxidase activity was higher in A-MI than S-MI and R-MI. Superoxide dismutase was lower in S-MI than Sham and R-MI. Gastrocnemius cross-sectional area, satellite cell activation and expression of the ubiquitin-proteasome system proteins did not differ between groups. In conclusion, aerobic exercise and resistance exercise improve functional capacity and maximum load carrying, respectively, without changing cardiac remodelling in infarcted rats. In the gastrocnemius, infarction increases oxidative stress and changes antioxidant enzyme activities. Aerobic exercise reduces oxidative stress and attenuates superoxide dismutase and glutathione peroxidase changes.

Aerobic training induces differential expression of genes involved in lipid metabolism in skeletal muscle and white adipose tissues.

Aerobic training induces adaptive responses in skeletal muscles and white adipose tissues, thus facilitating lipid utilization as energy substrates during a physical exercise session. However, the effects of training on cytokines levels and on transcription factors involved in lipid metabolism in muscle and different white adipose depots are still unclear; therefore, these were the aims of the present study. Nineteen adult male Wistar rats were randomly assigned to a trained group or a control, non-trained group. The 10-week training protocol consisted of running on a treadmill, during 1 hour per day, 5 days per week, at 75% of maximum aerobic speed. As expected, trained rats improved their aerobic performance and had augmented citrate synthase activity in the soleus, while the control rats did not. Although body weight was not different between groups, the adiposity index and white adipose depots (ie, epididymal and retroperitoneal) were reduced in trained rats. Training reduced serum concentration of insulin, but failed to change serum concentrations of glucose, triacylglycerol, total cholesterol, and nonesterified fatty acids. Training increased sterol regulatory element-binding protein-1c expression in the gastrocnemius and epididymal adipose tissue, and reduced peroxisome proliferator-activated receptor γ (PPARγ) expression in most of the tissues analyzed. The expression of PPARα and carnitine palmitoyltransferase 1 increased in the gastrocnemius and mesenteric adipose tissue but reduced in epididymal adipose tissue. Triacylglycerol content and tribbles 3 expression reduced in the gastrocnemius of trained rats. Tumor necrosis factor-α and interleukin-6 were increased in all adipose depots evaluated. Collectively, our data indicate that the 10-week aerobic training changed gene expression to improve muscle oxidative metabolism and facilitate lipid degradation in adipose tissues. Our data also highlight the existence of adaptive responses that are distinct between the skeletal muscle and white adipose tissue and between different adipose depots.