Evaluación de sarcopenia y los parámetros de bioimpedancia relacionados con la fuerza muscular en la consulta preoperatoria de cirugía espinal / Evaluation of sarcopenia and bioimpedance parameters related to muscle strength in the pre-operative consultation for spinal surgery

Introducción: la sarcopenia se caracteriza por la pérdida de masa y función muscular. Los trastornos de la columna vertebral son un factor deriesgo del deterioro muscular. A su vez, la sarcopenia se asocia a resultados adversos en el postoperatorio de cirugía espinal.Objetivos: evaluar sarcopenia y la relación de la fuerza muscular con parámetros de la bioimpedancia en la consulta preoperatoria.Material y métodos: estudio observacional transversal. Se midieron fuerza muscular (dinamometría) y composición corporal (bioimpedanciapor espectroscopia) en el marco de la evaluación funcional del estado nutricional. Sarcopenia se definió según el Grupo de Trabajo Europeosobre Sarcopenia en Personas Mayores (EGWSOP2) y dinapenia/miopenia, en caso de baja fuerza o muscularidad aislada. La relación entre losvalores de la dinamometría y las variables de la bioimpedancia se resumió con el coeficiente de Spearman.Resultados: se incluyeron 22 pacientes. La mediana (RIQ) de edad fue de 60 (43-65) años y el 72 %, de sexo femenino. El diagnóstico y elprocedimiento quirúrgico más frecuentes fueron espondilolistesis (45 %) y fijación posterior (50 %). El índice de masa corporal (IMC) promedio fuede 28,3 (± 4,59) kg/m2. La presencia de sarcopenia, dinapenia y miopenia fue del 18,2 %, 13,6 % y 22,7 %, respectivamente. La dinamometríase correlacionó con el índice de tejido magro: 0,61 (p 0,002); masa celular corporal: 0,68 (p 0,000); músculo esquelético apendicular: 0,49 (p0,021); ángulo de fase: 0,46 (p 0,031); e índice de resistencia 200/5 kHz: -0,47 (p 0,028).Conclusión: la fuerza muscular se correlaciona con los parámetros de la bioimpedancia. La sarcopenia, dinapenia y miopenia es frecuente yobjetivable en la consulta preoperatoria de cirugía espinal.(AU)

Introduction: sarcopenia is characterized by loss of muscle mass and function. Spinal disorders are a risk factor for muscle deterioration. Inturn, sarcopenia is associated with adverse outcomes in the postoperative period of spinal surgery.Objectives: to evaluate sarcopenia and the relationship of muscle strength with bioimpedance parameters in the preoperative consultation.Material and methods: cross-sectional observational study. Muscle strength (dynamometry) and body composition (bioimpedance spectroscopy)were measured as part of the functional assessment of nutritional status. Sarcopenia was defined according to the European Working Groupon Sarcopenia in Older People 2019 (EGWSOP2) and dynapenia/myopenia in the case of low strength or isolated muscularity. The relationshipbetween the dynamometry values and the bioimpedance variables was summarized with the Spearman’s coefficient.Results: twenty-two patients were included. The median (IQR) age was 60 years (43-65) and 72 % were women. The most frequent diagnosisand surgical procedure was spondylolisthesis (45 %) and posterior fixation (50 %). The mean body mass index (BMI) was 28.3 (± 4.59) kg/m2.The presence of sarcopenia, dynapenia and myopenia was 18.2 %, 13.6 % and 22.7 %, respectively. Dynamometry was correlated with leantissue index: 0.61 (p 0.002); body cell mass: 0.68 (p 0.000); appendicular skeletal muscle: 0.49 (p 0.021); phase angle: 0.46 (p 0.031); andresistance index 200/5 kHz: -0.47 (p 0.028).Conclusion: muscle strength is correlated with bioimpedance parameters. Sarcopenia, dynapenia and myopenia are frequent and objectifiablein the preoperative spinal surgery consultation.(AU)

Ecdiesteroides y su actividad farmacológica sobre el músculo esquelético / Ecdysteroids and their pharmacological activity on skeletal muscle

Introducción: Los ecdiesteroides presentan cualidades únicas dentro del reino vegetal y animal. Su similitud a esteroides endógenos de mamíferos les otorga actividad biológica sobre el tejido muscular esquelético. Sin embargo, su mecanismo de acción está por definirse en su totalidad. Método: Se realizó una revisión narrativa utilizando la evidencia científica más relevante. Se consultaron de las bases de datos Medline, Google Scholar, Scielo y Wiley, incluyéndose y excluyéndose trabajos acordes a los criterios del autor. Resultados: La actividad de los ecdiesteroides, principalmente de la Ecdisterona (Ec), podría deberse a la interacción con Mas, receptor acoplado a proteína-G transmembrana (GPCR), y la posterior activación del receptor de estrógenos β (ER β) no nuclear. Dicho mecanismo de acción induce la activación de la ruta alternativa del Sistema Renina-Angiotensina-Aldosterona (RAA) aboliendo los mecanismos de degradación muscular y, mediante la activación indirecta de Erβ, se suprime la expresión del gen de la miostatina. Esta actividad biológica pudiera conferir a los ecdiesteroides propiedades farmacológicas óptimas para impedir la degradación proteico-muscular, tales como la regeneración y reparación del tejido. Conclusiones: Ec ha demostrado poseer propiedades farmacológicas interesantes para el abordaje alternativo de patologías musculodegenerativas por sus efectos anticatabólicos. Aunque prosigue la investigación para su implementación en la clínica, esta siendo utilizada en la industria deportiva y en ensayos para el tratamiento de diferentes patologías. (AU)

Introduction: Ecdysteroids present unique qualities within the plant and animal kingdoms. Their similarity to en-dogenous mammalian steroids allows them to present biological activity on skeletal muscle tissue. However, this molecule’s action mechanism remains to be fully understood. Method: A narrative review was carried out using the most relevant scientific evidence. Different databases such as Medline, Google Scholar, Scielo and Wiley were consulted. Works were included or excluded according to the author ́s criterium. Results: Ecdysteroids’ activity, mostly that of ecdysterone, might be due to the interaction with Mas receptor, a transmembrane G-Protein Coupled Receptor (GPCR), and the subsequent indirect activation of β-Estrogen Recep-tor ́s (β-ER) non-nuclear form. Said action mechanism induces the alternative pathway activation of the Renin-An-giotensin-Aldosterone System (RAAS), abolishing muscular degradation mechanism. Finally, through β-ER activa-tion, the myostatin gene is supressed. This biological activity could provide ecdysteroids optimal pharmacological properties to prevent muscular protein degradation. These include tissue regeneration and repair. Conclusions: Due to its anticatabolic effects, Ec has shown great pharmacological properties that could make it work as an alternative treatment for degenerative muscle pathologies. Although investigations regarding Ec are still in progress, it has already been used by the sports’ industry and in several clinical trials that focus on the treatment of other diseases. (AU)

Binge drinking leads to an oxidative and metabolic imbalance in skeletal muscle during adolescence in rats: endocrine repercussion

Binge drinking (BD) is an especially pro-oxidant model of alcohol consumption, mainly used by adolescents. It has recently been related to the hepatic IR-process. Skeletal muscle is known to be involved in insulin action and modulation through myokine secretion. However, there is no information on muscle metabolism and myokine secretion after BD exposure in adolescents. Two experimental groups of adolescent rats have been used: control and BD-exposed one. Oxidative balance, energy status and lipid, and protein metabolism have been analyzed in muscle, together with myokine serum levels (IL-6, myostatin, LIF, IL-5, fractalkine, FGF21, irisin, BDNF, FSTL1, apelin, FABP3, osteocrin, osteonectin (SPARC), and oncostatin). In muscle, BD affects the antioxidant enzyme balance leading to lipid and protein oxidation. Besides, it also increases the activation of AMPK and thus contributes to decrease SREBP1 and pmTOR and to increase FOXO3a expressions, promoting lipid and protein degradation. These alterations deeply affect the myokine secretion pattern. This is the first study to examine a general myokine response after exposure to BD. BD not only caused a detrimental imbalance in myokines related to muscle turnover, decreased those contributing to increase IR-process, decreased FST-1 and apelin and their cardioprotective function but also reduced the neuroprotective BDNF. Consequently, BD leads to an important metabolic and energetic disequilibrium in skeletal muscle, which contributes to exacerbate a general IR-process. (AU)

Hematoma gigante coagulado del gastrocnemio medial de localización atípica. Tratamiento con fibrinolíticos en el drenaje ecoguiado: a propósito de un caso / Giant coagulated hematoma of the medial gastrocnemius of atypical location. Treatment with fibrinolytics in ultrasound-guided drainage: a case report

A propósito de un paciente de 57 años con rotura de gastrocnemio medial y hematoma gigante coagulado de localización atípica, se revisan las consideraciones epidemiológicas, las pruebas de diagnóstico a realizar y el tratamiento utilizado (drenaje del hematoma mediante punciones seriadas ecoguiadas con la utilización de urocinasa intracavitaria), además de describir su evolución clínica.(AU)

Regarding a 57-year-old patient with medial gastrocnemius tear and a giant coagulated hematoma of atypical location, the epidemiology, diagnostic test and treatment used are reviewed (hematoma drainage by means of serial punctures, echo-guided, with the use of intracavitary urokinase), as well as its clinical evolution is described.(AU)

Cardiac autonomic regulation in response to functional power threshold testing in elite cyclists / Regulación autonómica cardiaca en respuesta a la prueba de umbral de potencia funcional en ciclistas deélite

Objective: To evaluate the impact of a functional power threshold test (FTP) on cardiac autonomic regulation indicators in high performance cyclists.Methods: A total of 12 male elite cyclists (mean age 36.1 ± 11.2 years) were recruited. Body composition parameters were measured usingbioimpedancemetry and heart rate variability (HRV) before and after the application of the FTP assessment. Results: We observed that a greater sympathetic nervous system (SNS) index and Stress index on baseline were correlated with a smaller decrease in theparasympathetic nervous system (PNS) activity in response to the FTP test (ρ= 0.69, p = 0.013). Concerning morphological parameters, the skeletalmuscle index (SMI) was the only one that was inversely correlated with ∆PNS (ρ= -0.69, p = 0.02) whereas the muscle-bone index (MBI) displayed apositive correlation with ∆SNS (ρ = 0.82, p = 0.001). In fully adjusted models we found that waist-to-hip ratio (β= 7.90, CI95%[4.16, 11.63], t(8) = 4.88, p =0.001) and SMI significantly influenced ∆PNS (β = -1.38, CI95%[-1.84, -0.92], t(8) = -6.94, p < 0.001), whereas MBI (β= 10.26, CI95%[8.10, 12.42], t(8) =10.96, p < 0.001) and the interaction between the latter and Power achieved during FTP influenced ∆SNS (β = -0.05, CI95%[-0.09, -4.99e-03], t(8) = -2.56, p= 0.033). Conclusion: Our findings indicate that the SMI had a negative effect on the ∆PNS, while the MBI was positively correlated with the ∆SNS in cyclists. Thesefindings suggest that a higher SMI and MBI could have a detrimental impact on the cardiac autonomic response to maximal aerobic exercise in high-performance cyclists, such as FTP.(AU)

Objetivo: Evaluar el impacto de una prueba de umbral de potencia funcional (FTP) sobre los indicadores de regulación autonómica cardiaca en ciclistasde alto rendimiento. Métodos: Se reclutó a un total de 12 ciclistas de élite masculinos (edad media 36.1 ± 11.2 años). Se midieron los parámetros de composición corporalmediante bioimpedanciometría y la variabilidad de la frecuencia cardiaca (HRV) antes y después de la aplicación de la evaluación del FTP. Resultados: Observamos que un mayor índice del sistema nervioso simpático (SNS) e índice de estrés basalmente se correlacionaron con una menordisminución de la actividad del sistema nervioso parasimpático (PNS) en respuesta a la prueba FTP (ρ= 0.69, p = 0.013). En cuanto a los parámetrosmorfológicos, el índice músculo esquelético (SMI) fue el único que se correlacionó inversamente con el ∆PNS (ρ= -0.69, p = 0.02) mientras que el índicemúsculo-hueso (MBI) mostró una correlación positiva con ∆SNS (ρ = 0.82, p = 0.001). En los modelos totalmente ajustados encontramos que la relacióncintura-cadera (β= 7.90, CI95%[4.16, 11.63], t(8) = 4.88, p = 0.001) y el SMI influían significativamente en el ∆PNS (β= -1.38, CI95%[-1.84, -0.92], t(8) = -6.94,p < 0.001), mientras que el MBI (β = 10.26, CI95%[8.10, 12.42], t(8) = 10.96, p < 0.001) y la interacción entre este último y la Potencia alcanzada durante elFTP influían en el ∆SNS (β= -0.05, CI95%[-0.09, -4.99e-03], t(8) = -2.56, p = 0.033). Conclusión: Nuestros hallazgos indican que el SMI tuvo un efecto negativo sobre el ∆PNS, mientras que el MBI se correlacionó positivamente con el ∆SNSen ciclistas. Estos hallazgos sugieren que un mayor SMI y MBI podrían tener un impacto perjudicial en la respuesta autonómica cardíaca al ejercicioaeróbico máximo en ciclistas de alto rendimiento, como el FTP.(AU)

Exercise-derived skeletal myogenic exosomes as mediators of intercellular crosstalk: a major player in health, disease, and exercise

Exosomes are extracellular membrane vesicles that contain biological macromolecules such as RNAs and proteins. It plays an essential role in physiological and pathological processes as carrier of biologically active substances and new mediator of intercellular communication. It has been reported that myokines secreted by the skeletal muscle are wrapped in small vesicles (e.g., exosomes), secreted into the circulation, and then regulate the receptor cells. This review discussed the regulation of microRNAs (miRNAs), proteins, lipids, and other cargoes carried by skeletal muscle-derived exosomes (SkMCs-Exs) on the body and their effects on pathological states, including injury atrophy, aging, and vascular porosis. We also discussed the role of exercise in regulating skeletal muscle-derived exosomes and its physiological significance. (AU)

Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation

Hypobaric hypoxia (HH) leads to various adverse effects on skeletal muscles, including atrophy and reduced oxidative work capacity. However, the effects of HH on muscle fatigue resistance and myofiber remodeling are largely unexplored. Therefore, the present study aimed to explore the impact of HH on slow-oxidative fibers and to evaluate the ameliorative potential of exercise preconditioning and nanocurcumin formulation on muscle anti-fatigue ability. C2C12 cells (murine myoblasts) were used to assess the effect of hypoxia (0.5%, 24 h) with and without the nanocurcumin formulation (NCF) on myofiber phenotypic conversion. To further validate this hypothesis, male Sprague Dawley rats were exposed to a simulated HH (7620 m) for 7 days, along with NCF administration and/or exercise training. Both in vitro and in vivo studies revealed a significant reduction in slow-oxidative fibers (p < 0.01, 61% vs. normoxia control) under hypoxia. There was also a marked decrease in exhaustion time (p < 0.01, 65% vs. normoxia) in hypoxia control rats, indicating a reduced work capacity. Exercise preconditioning along with NCF supplementation significantly increased the slow-oxidative fiber proportion and exhaustion time while maintaining mitochondrial homeostasis. These findings suggest that HH leads to an increased transition of slow-oxidative fibers to fast glycolytic fibers and increased muscular fatigue. Administration of NCF in combination with exercise preconditioning restored this myofiber remodeling and improved muscle anti-fatigue ability. (AU)

Eccentric and concentric exercises induce different adaptions in adipose tissue biology

Alterations in adipose tissue (AT) metabolism related to inflammation and adipokine’s production lead to perturbations in its capacity to store lipids and release fatty acids (FA) during feeding/fasting transition or during exercise. Exercise has a beneficial effect on AT metabolism, but conventional trainings are not always suitable for patients with functional limitations. Dynamic eccentric (ECC) exercise prevents the accumulation of AT and may then overcome those limitations. Consequently, this study aimed at investigating AT’s adaptations after ECC training. Nine-week-old male rats were randomly assigned to a control sedentary or three-trained groups for which treadmill slopes modulated exercise oxygen consumption (VO2) and mechanical work (n = 15 per group): (1) + 15% uphill-concentric group (CONC), (2) − 15% downhill group (ECC15, same mechanical work as CONC) and (3) − 30% downhill group (ECC30, same VO2, or oxygen cost as CONC). Body composition and energy expenditure (EE) were measured before and after 8 weeks of training. Subcutaneous AT was collected to study total FA profile and gene expression. Higher total EE was driven by lean mass gain in trained animals. In AT, there was a decrease in arachidonic acid with CONC or ECC15 training. Increased adiponectin, leptin, lipases, Glut4 and Igf1 mRNA levels in ECC15 group suggested major metabolic adaption in AT. In conclusion, ECC could induce beneficial modifications in AT fatty acid profile and the expression of key genes related to metabolism and insulin sensitivity. (AU)

Lipoxin A4 attenuated dexamethasone-induced muscle atrophy via activation of PGC-1a/Nrf2/TFAM pathway

Prolonged dexamethasone (DEX) administration causes skeletal muscle atrophy through induction of both oxidative stress and mitochondrial dysfunction. Lipoxin A4 (LXA4) is a recognized antioxidant but its effect against DEX-induced muscle atrophy has not been studied yet. This study aimed to assess the potential ameliorating effect of LXA4 on DEX-induced muscle atrophy and investigate the possible involvement of the mitochondrial dynamics pathway and the redox state in this effect. Forty male rats were divided into four groups; normal control, LXA4-treated, DEX-treated, and LXA4 plus DEX-treated. At the end of the experiment, LXA4 counteracted the effect of DEX on different parameters including muscle weight, muscle strength, serum creatine kinase activity, malondialdehyde and protein carbonyl contents, Na/K-ATPase and citrate synthase activities, mitochondrial transmembrane potential, mitochondrial transcription factor (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). These findings signify the promising therapeutic effect of LXA4 against DEX-induced skeletal muscle atrophy and indicate the possible involvement of LXA4-induced mitochondrial activation in addition to its well-known antioxidant effects. (AU)

Effects of exercise on irisin in subjects with overweight or obesity. A systematic review of clinical studies / Efectos del ejercicio sobre la irisina en personas con sobrepeso u obesidad. Una revisión sistemática de estudios clínicos

Irisin is an adipomyokine involved in white adipose tissue browning, therefore, could be a key protein in metabolic health. However, exercise effects on irisin in subjects with overweight and/or obesity are conflicting. Therefore, this systematic review aims to search and analyse the literature available on this topic. From three databases: PubMed, ScienceDirect, and Medline, clinical studies published between 2010 and 2021 were considered. From 134 found, 14 studies were included. Only six reported plasma increases after exercise (~1.2 to 3-fold from pre-exercise levels). In addition, only 1 reported significant increases in skeletal muscle irisin mRNA levels (~2-fold). Also, irisin was measured from subcutaneous adipose tissue and saliva, where a ~2-fold increase in its protein levels was found in the latter. Exercise seems to increase the circulatory concentrations of irisin in subjects with overweight or obesity. However, this response is highly variable, therefore, a more integrative approach is urgently needed. (AU)

La irisina es una adipomioquina relacionada a la transformación del tejido adiposo blanco a marrón, por tanto, podría ser una proteína clave para la salud metabólica. Sin embargo, los efectos del ejercicio sobre la irisina en personas con sobrepeso u obesidad son poco claros. Por lo anterior, esta revisión sistemática apunta a buscar y analizar la literatura disponible en este tema. Desde tres bases de datos: PubMed, ScienceDirect y Medline se buscaron estudios clínicos publicados entre el 2010 y 2021. De 134 estudios encontrados, 14 fueron incluidos. Solo 6 reportaron incrementos plasmáticos de irisina después del ejercicio (~1.2 a 3-veces respecto a niveles preejercicio). Además, solo 1 estudio describió incrementos significativos en el ARNm de irisina en el músculo esquelético (~2 veces sobre niveles preejercicio). La irisina también se medió desde tejido adiposo subcutáneo y saliva, encontrándose una elevación de (~2 veces sobre niveles preejercicio) en esta última. El ejercicio físico incrementaría las concentraciones circulatorias de irisina en personas con sobrepeso u obesidad. Sin embargo, esta respuesta es muy variable, por lo que se requiere una mirada más integrativa a la hora de estudiar este fenómeno. (AU)

Relationship between anaerobic work capacity and critical oxygenation in athletes / Relación entre la capacidad de trabajo anaeróbico y la oxigenación crítica en deportistas / Relação entre capacidade de trabalho anaeróbico e oxigenação crítica em atletas

Objective: Anaerobic work capacity (AWC) is understood as the maximum power that the athlete can withstand over time, conditioned by high intensityeffort and it is important to interpret it for the performance improvement. In addition, the muscle oxygen saturation (SmO2) provides information onmuscle metabolism and hemodynamics. Likewise, critical oxygenation (CO) is the highest metabolic rate that results in a fully oxidative energy supplythat reaches a stable state at the substrate level. The main problem is that SmO2 generally offers a traditional laboratory interpretation withoutapplication in field tests, Therefore, the purpose of this study is to provide the use of CO as an indicator of AWC performance in high intensity exercise. Methods: Twenty-two male rugby players participated. Peak torques during an isokinetic fatigue test and muscle oxygen consumption (mVO2) and SmO2in the vastus lateralis were measured. A correlation and multiple regression analysis were applied to find an explanatory prediction model of the AWC. Results: A greater SmO2 amplitude and CO would mean less anaerobic work (r = -0.58 and r=-0.63) and less force production. In addition, CO along withweight (kg) can explain the AWC by 64% during high intensity exercise. Conclusion: The measurement of critical oxygenation is associated with the AWC, so should be considered a performance factor. These parameters couldbe included in NIRS sensors to evaluate muscle metabolism.(AU)

Objetivo: La capacidad de trabajo anaeróbico (AWC) se entiende como la potencia máxima que el deportista puede soportar a lo largo del tiempo,condicionada por un esfuerzo de alta intensidad y es importante interpretarla para la mejora del rendimiento. Además, la saturación de oxígenomuscular (SmO2) proporciona información sobre el metabolismo muscular y la hemodinámica. Asimismo, la oxigenación crítica (OC) es la tasametabólica más alta que da como resultado un suministro de energía completamente oxidativo que alcanza un estado estable a nivel de sustrato. Elprincipal problema es que SmO2 generalmente ofrece una interpretación de laboratorio tradicional sin aplicación en pruebas de campo, por lo tanto, elpropósito de este estudio es proporcionar el uso de OC como indicador del rendimiento de AWC en ejercicio de alta intensidad. Métodos: Participaron 22 jugadores masculinos de rugby. Se midieron los picos máximos después de una prueba de fatiga isocinética y el consumo deoxígeno muscular (mVO2) y SmO2 en el musculo vasto lateral. Se aplicó un análisis de correlación y regresión múltiple para encontrar un modelo depredicción explicativo del AWC. Resultados: Una mayor amplitud de SmO2 y OC supondría un menor trabajo anaeróbico (r = -0,58 y r=-0,63) y una menor producción de fuerza. Además,el CO junto con el peso (kg) pueden explicar el AWC en un 64 % durante el ejercicio de alta intensidad. Conclusión: La medición de la oxigenación crítica está asociada a la AWC, por lo que debe considerarse un factor de rendimiento. Estos parámetrospodrían incluirse en sensores NIRS para valorar el metabolismo muscular.(AU)

Objetivo: A capacidade anaeróbica de trabalho (AWC) é entendida como a potência máxima que o atleta pode suportar ao longo do tempo, condicionadapor um esforço de alta intensidade, sendo importante interpretá-la para melhorar o desempenho. Além disso, a saturação muscular de oxigênio (SmO2)fornece informações sobre o metabolismo muscular e a hemodinâmica. Da mesma forma, a oxigenação crítica (OC) é a taxa metabólica mais alta queresulta em um suprimento de energia totalmente oxidativo atingindo um estado estável no nível do substrato. O principal problema é que o SmO2geralmente oferece uma interpretação laboratorial tradicional sem aplicação em testes de campo, portanto, o objetivo deste estudo é fornecer o uso doCO como indicador de desempenho de AWC em exercícios de alta intensidade. Métodos:Participaram 22 jogadores de rugby do sexo masculino. Foram medidos os picos máximos após um teste de fadiga isocinética e o consumo deoxigênio muscular (mVO2) e SmO2 no músculo vasto lateral. Uma análise de correlação e regressão múltipla foi aplicada para encontrar um modeloexplicativo de predição do AWC. Resultados: Uma maior amplitude de SmO2 e CO implicaria em menor trabalho anaeróbio (r = -0,58 er = -0,63) e menor produção de força. Além disso, oCO junto com o peso (kg) pode explicar a AWC em 64% durante o exercício de alta intensidade. Conclusão: A medida oxigenação crítica prevê AWC, portanto, deve ser considerada um fator de desempenho. Esses parâmetros podem ser incluídos emsensores NIRS para a medição do metabolismo muscular.(AU)

TLR4 activation inhibits the proliferation and osteogenic differentiation of skeletal muscle stem cells by downregulating LGI1

Skeletal muscle stem cells (SMSCs) are vital to the growth, maintenance, and repair of the muscles; emerging evidence has indicated that Toll-like receptor 4 (TLR4) can potentially regulate muscle regeneration. In present study, in vitro and in vivo experiments were performed to explore the correlation of TLR4 with leucine-rich glioma-inactivated 1 (LGI1) as well as their effects on the proliferation and osteogenesis potential of SMSCs. In order to examine the regulatory mechanisms of TLR4 and LGI1 in SMSCs, the obtained cells were treated with lipopolysaccharide (LPS, used as an activator of TLR4) of different concentration at different time points as well as the siRNA against LGI1. Subsequently, a series of detection was undertaken in order to measure the proliferation and differentiation potential of SMSCs, which involved detection of the related factors, cell activity, and the sphere-forming capability. Following LPS treatment, the increased TLR4 expression and reduced LGI1 expression were observed. Consequently, we also discovered that Erk signaling pathway was inactivated and cell proliferation and osteogenesis capabilities declined, presented by the downregulation of related factors such as cyclin B1 and runt-related transcription factor 2. Moreover, the cell activity and sphere-formation performance of SMSCs were also declined. These results were also validated in rats with cecal ligation and perforation-induced rat models with sepsis. In conclusion, the present study reveals a regulatory mechanism in SMSCs whereby LGI1 expression is reduced by TLR4, thus impeding cell proliferation and osteogenesis, highlighting TLR4 as a potential therapeutic target against many diseases related to SMSCs. (AU)

A chronic low-dose magnesium L-lactate administration has a beneficial effect on the myocardium and the skeletal muscles

The purpose of this study was to determine whether magnesium L-lactate is responsible for having a beneficial effect on the myocardium and the skeletal muscles and how this substrate acts at the molecular level. Twenty seven young male Wistar rats were supplied with a magnesium L-lactate (L) solution, a magnesium chloride (M) solution and/or water (W) as a vehicle for 10 weeks. The treated animals absorbed the L and M solutions as they wished since they also had free access to water. After 9 weeks of treatment, in vivo cardiac function was determined ultrasonically. The animals were sacrificed at the end of the tenth week of treatment and the heart was perfused according to the Langendorff method by using a technique allowing the determination of cardiomyocyte activity (same coronary flow in the two groups). Blood was collected and skeletal muscles of the hind legs were weighed. The myocardial expressions of the sodium/proton exchange 1 (NHE1) and sodium/calcium exchange 1 (NCX1), intracellular calcium accumulation, myocardial magnesium content, as well as systemic and tissue oxidative stress, were determined. Animals of the L group absorbed systematically a low dose of L-lactate (31.5 ± 4.3 µg/100 g of body weight/day) which was approximately four times higher than that ingested in the W group through the diet supplied. Ex vivo cardiomyocyte contractility and the mass of some skeletal muscles (tibialis anterior) were increased by the L treatment. Myocardial calcium was decreased, as was evidenced by an increase in total CaMKII expression, without any change in the ratio between phosphorylated CaMKII and total CaMKII. Cardiac magnesium tended to be elevated. Our results suggest that the increased intracellular magnesium concentration was related to L-lactate-induced cytosolic acidosis and to the activation of the NHE1/NCX1 axis. Interestingly, systemic oxidative stress was reduced by the L treatment whereas the lipid profile of the animals was unaltered. (AU)

Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition

Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency. (AU)

Skeletal muscle relaxant activity of different formulation of span 60 niosomes / Actividad relajante del músculo esquelético de diferentes formulaciones de niosomas span 60

Introduction: Spasticity is a disease of motor neurons that manifests as accelerated muscle tone and stiffness. The niosomes can be formulated with the aid of proper adjustment of process parameters to enhance baclofen entrapment and sustaining the drug release. Method: The main purpose of this study is to compare different formulations of span 60 niosomes containing baclofen for skeletal muscle relaxant activity on mice (Swiss albino mice) by rota rod method. Results: The particle size of formulated niosomes was in the range of 3.62±0.54-4.08±0.64 µm and these were smooth, circular fit and generally small multilamellar. Entrapment efficiency of optimized formulation was 88.44±0.28 %. The most extreme % cumulative drug release was 87.88±8.66% after 10 h. The formulation stored at 4±2 °C temperature shows better stability (96.65±0.45) contrasted with raised temperature. Swiss albino mice were utilized for in vivo study and displayed improved muscle relaxant action as far as no. of tumbles from rota rod apparatus (p value =0.001) are concerned. Conclusions: Nonetheless, diazepam treated mice were observed to have higher muscle relaxation than any dose of formulation tested. The formulation F9 shows better skeletal muscle relaxant activity as compared to F6, F7, F8 and F10 on mice (Swiss albino mice) by the rota rod technique. (AU)

Introducción: La espasticidad es una enfermedad de las neuronas motoras que se manifiesta como aceleración del tono muscular y rigidez. Los niosomas se pueden formular con la ayuda de un ajuste adecuado de los parámetros del proceso para mejorar el atrapamiento del baclofeno y mantener la liberación del fármaco. Método: El objetivo principal de este estudio es comparar diferentes formulaciones de niosomas span 60 que contienen baclofeno para la actividad relajante del músculo esquelético en ratones (ratones albinos suizos) mediante el método de rota rod. Resultados: El tamaño de partícula de los niosomas formulados estaba en el rango de 3,62 ± 0,54-4,08 ± 0,64 µm y eran suaves, de ajuste circular y generalmente multilaminares pequeños. La eficiencia de atrapamiento de la formulación optimizada fue 88,44 ± 0,28%. El porcentaje de liberación acumulada de fármaco más extremo fue 87,88 ± 8,66% después de 10 h. La formulación almacenada a una temperatura de 4 ± 2 ° C muestra una mejor estabilidad (96,65 ± 0,45) en comparación con la temperatura elevada. Se utilizaron ratones albinos suizos para el estudio in vivo y mostraron una acción relajante muscular mejorada hasta donde no. de caídas desde el aparato de varilla de rotación (valor de p = 0,001). Conclusiones: No obstante, se observó que los ratones tratados con diazepam tenían una mayor relajación muscular que cualquier dosis de formulación probada. La formulación F9 muestra una mejor actividad relajante del músculo esquelético en comparación con F6, F7, F8 y F10 en ratones (ratones albinos suizos) mediante la técnica de rota rod. (AU)

Evidencia del manejo de miopatías asociadas a estatina con coenzima Q10 / Evidence for the management of myopathies associated with statin with coenzyme Q10

Introducción: La incidencia de eventos cardiovasculares fatales es muy elevada y el tratamiento con estatinas es vital para reducir este riesgo en muchos pacientes, sin embargo, sus efectos adversos sobre el músculo esquelético dificultan la adherencia o la continuación del mismo. Se ha propuesto la suplementación de coenzima Q10 para revertir mialgias asociadas a el empleo de estatinas. Los ensayos clínicos que se realizaron en los últimos 10 años obtuvieron resultados contrapuestos. El objetivo de este trabajo es revisar la evidencia sobre la eficacia del empleo de suplementos de coenzima Q10 en para mitigar las miopatías causadas por las estatinas. Metodología: Se realizó una búsqueda sistemática de la literatura publicada hasta Julio de 2020. Las bases de datos consultadas fueron MEDLINE y SCOPUS. También se consultaron instituciones como la Agencia Española del Medicamento y Productos Sanitarios (AEMPS), la European Medicines Agency (EMA) y la Food and Drug Administration (FDA). Resultados: La etiología de las mialgias asociadas a estatinas sigue siendo desconocida y la evidencia encontrada en los ensayos clínicos y metaanalisis obtuvieron conclusiones dispares. La European Medicine Agency (EMA) solo considera el empleo de suplementos en síndrome de deficiencia primaria de coenzima Q10, mientras en Reino Unido el National Institute for Health and Care Excellence (NICE) y el National Institute of Health (NIH) no recomiendan el empleo de estos suplementos para tratar mialgias asociadas al empleo de estatinas. Conclusiones: El conjunto de los estudios analizados no consiguió una evidencia unánime para poder recomendar este empleo de suplementos de coenzima Q10 de modo confiable. Se necesitan estudios mejor diseñados que aporten reproducibilidad y robustez a futuros ensayos clínicos. (AU)

Introduction: The incidence of fatal cardiovascular events is very high and statin treatment is vital to reduce this risk in many patients, however, its adverse effects on skeletal muscle make it difficult to adhere or continue it. Coenzyme Q10 supplementation has been proposed to reverse myalgia associated with the use of statins. The clinical trials carried out in the last 10 years obtained conflicting results. The aim of the present work is to review the evidence on the efficacy of the use of coenzyme Q10 supplements in mitigating myopathies caused by statins. Methodology: A systematic review of the published literature until July 2020 was undertaken. The searched databases were MEDLINE and SCOPUS. Institutions such as the Agencia Española del Medicamento y productos Sanitarios (AEMPS), European Medicines Agency (EMA) and Food and Drug Administration were also consulted. Results: The etiology of statin-associated myalgias remains unknown, and the evidence found in clinical trials and meta-analysis drew disparate conclusions. The European Medicine Agency (EMA) only considers the use of supplements in primary coenzyme Q10 deficiency syndrome, while in the United Kingdom the National Institute for Health and Care Excellence (NICE) and the National Institute of Health (NIH) do not recommend the use of these supplements to treat myalgias associated with the use of statins. Conclusions: The set of studies analyzed did not obtain unanimous evidence to be able to reliably recommend this use of coenzyme Q10 supplements. Better designed studies that provide reproducibility and robustness to future clinical trials are needed. (AU)