The role of interleukin-10 in mitigating endoplasmic reticulum stress in aged mice through exercise.

Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle.NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.

Cilostazol attenuates oxidative stress and apoptosis in the quadriceps muscle of the dystrophic mouse experimental model.

Duchenne muscular dystrophy (DMD) is the most severe and frequent form of muscular dystrophy. The mdx mouse is one of the most widely used experimental models to understand aspects of the biology of dystrophic skeletal muscles and the mechanisms of DMD. Oxidative stress and apoptosis are present in early stages of the disease in mdx mice. The high production of reactive oxygen species (ROS) causes activation of apoptotic death regulatory proteins due to DNA damage and breakdown of nuclear and mitochondrial membranes. The quadriceps (QUA) muscle of the mdx mouse is a good tool to study oxidative events. Previous studies have demonstrated that cilostazol exerts an anti-oxidant effect by decreasing the production of reactive oxygen species (ROS). The present study aimed to evaluate the ability of cilostazol to modulate oxidative stress and apoptosis in the QUA muscle of mdx mice. Fourteen-day-old mdx mice received cilostazol or saline for 14 days. C57BL/10 mice were used as a control. In the QUA muscle of mdx mice, cilostazol treatment decreased ROS production (-74%), the number of lipofuscin granules (-47%), lipid peroxidation (-11%), and the number of apoptotic cells (-66%). Thus cilostazol showed anti-oxidant and anti-apoptotic action in the QUA muscle of mdx mice.

Muscle oxygenation of the quadriceps and gastrocnemius during maximal aerobic effort / Oxigenación muscular de cuádriceps y gastrocnemio durante el esfuerzo aeróbico máximo / Oxigenação muscular de quadríceps e gastrocnêmio durante o esforço aeróbico máximo

ABSTRACT Introduction: Near infrared spectroscopy (NIRS) is a non-invasive technique that is used in the assessment of tissue oxygenation and the monitoring of physical activity. Objective: To determine the influence of sexual, anthropometric and ergospirometric factors on muscle oxygenation of the quadriceps and gastrocnemius, obtained by NIRS during a stress test. Methods: Twenty healthy subjects participated in this study (10 women). Two Humon Hex® devices were placed on the dominant side of the quadriceps and gastrocnemius muscles to measure muscle oxygen saturation (SmO2). The stress test was performed on a treadmill with electrocardiographic control and measurement of oxygen consumption. SmO2 was obtained at rest and after maximum effort during the stress test. In addition, the height, weight, skinfold and waist contour were measured. Bioimpedance was used to obtain the percentages of fat mass and muscle mass, which were used to calculate the relative fat mass (RFM). Results: The SmO2 of both muscles at rest is higher in males than in females. At maximum effort, the SmO2 of the quadriceps is similar in both groups. The SmO2 of both muscles is positively related to height, body mass, percentage of mass muscle and waist contour, and negatively with percentage of mass fat, RFM and skinfold thickness. The negative correlation between fat percentage and oxygen saturation is more evident in females. It was observed that the variables that quantify maximum effort are not related to the SmO2 values, except for the correlation between HR max and SmO2 of the gastrocnemius muscle in males. Conclusion: The SmO2 of recreational athletes is influenced by the location of the device and the fat mass of the subjects. The biggest differences between the sexes are in the gastrocnemius muscle. Level of Evidence II; Diagnostic Studies - Investigating a Diagnostic Test .

RESUMEN Introducción: La espectroscopia de infrarrojo cercano (NIRS) es una técnica no invasiva usada en la evaluación de la oxigenación tisular y en la monitorización de la actividad física. Objetivos: Determinar la influencia de factores sexuales, antropométricos y ergoespirométricos sobre la oxigenación muscular de cuádriceps y del gastrocnemio, obtenidos por NIRS durante un test de esfuerzo. Métodos: Participaron en este estudio 20 individuos saludables (10 mujeres). Se colocaron dos dispositivos Humon Hex® en el lado dominante de los músculos cuádriceps y gastrocnemio para medir la saturación de oxígeno muscular (SmO2). El test de esfuerzo fue realizado en una cinta ergométrica con control electrocardiográfico y medición del consumo de oxígeno. La SmO2 fue obtenida en reposo y después de esfuerzo máximo durante el test. Además, fueron medidos altura, peso, pliegues cutáneos y contorno de la cintura. Fue usada bioimpedancia para obtener los porcentuales de masa grasa y masa muscular, que fueron usados para calcular la masa grasa relativa (MGR). Resultados: La SmO2 de ambos músculos en reposo es mayor en hombres que en mujeres. En el esfuerzo máximo la SmO2 del cuádriceps es semejante en los dos grupos. La SmO2 de ambos músculos es positivamente relacionada con altura, masa corporal, porcentual de masa muscular y contorno de la cintura y negativamente relacionada con el porcentaje de masa grasa, MGR y espesor de los pliegues cutáneos. La correlación negativa entre el porcentual de grasa y la saturación de oxígeno es más evidente en las mujeres. Se observó que variables que cuantifican el esfuerzo máximo no está relacionadas con los valores SmO2, excepto por la correlación entre FCmáx y SmO2 del músculo gastrocnemio en sexo masculino. Conclusión: La SmO2 de los atletas recreativos es influenciada por la localización del dispositivo y por la masa grasa de los individuos. Las mayores diferencias entre los sexos están en el músculo gastrocnemio. Nivel de Evidencia II; Estudios diagnósticos - Investigación de un examen para diagnóstico .

RESUMO Introdução: A espectroscopia de infravermelho próximo (NIRS) é uma técnica não invasiva usada na avaliação da oxigenação tecidual e no monitoramento da atividade física. Objetivos: Determinar a influência de fatores sexuais, antropométricos e ergoespirométricos sobre a oxigenação muscular do quadríceps e do gastrocnêmio obtidos por NIRS durante um teste de esforço. Métodos: Participaram deste estudo 20 indivíduos saudáveis (10 mulheres). Dois dispositivos Humon Hex® foram colocados no lado dominante dos músculos quadríceps e gastrocnêmio para medir a saturação de oxigênio muscular (SmO2). O teste de esforço foi realizado em uma esteira com controle eletrocardiográfico e mensuração do consumo de oxigênio. A SmO2foi obtida em repouso e depois de esforço máximo durante o teste. Além disso, foram medidos estatura, peso, dobras cutâneas e contorno da cintura. A bioimpedância foi usada para obter os percentuais de massa gorda e massa muscular, que foram usados para calcular a massa gorda relativa (MGR). Resultados: A SmO2de ambos os músculos em repouso é maior em homens do que em mulheres. No esforço máximo, a SmO2do quadríceps é semelhante nos dois os grupos. A SmO2de ambos os músculos é positivamente relacionada com estatura, massa corporal, percentual de massa muscular e contorno da cintura e negativamente relacionada com a porcentagem de massa gorda, MGR e espessura das dobras cutâneas. A correlação negativa entre o percentual de gordura e a saturação de oxigênio é mais evidente nas mulheres. Observou-se que variáveis que quantificam o esforço máximo não estão relacionadas com os valores SmO2, exceto pela correlação entre FCmáx e SmO2do músculo gastrocnêmio no sexo masculino. Conclusão: A SmO2dos atletas recreativos é influenciada pela localização do dispositivo e pela massa gorda dos indivíduos. As maiores diferenças entre os sexos estão no músculo gastrocnêmio. Nível de Evidência II; Estudos diagnósticos - Investigação de um exame para diagnóstico .

Effects of acute inspiratory loading during treadmill running on cerebral, locomotor and respiratory muscle oxygenation in women soccer players.

Respiratory limitation can be a primary mechanism for exercise cessation in female athletes. This study aimed to assess the effects of inspiratory loading (IL) on intercostal muscles (IM), vastus lateralis (VL) and cerebral (Cox) muscles oxygenation in women soccer players during high-intensity dynamic exercise. Ten female soccer players were randomized to perform in order two constant-load tests on a treadmill until the exhaustion time (Tlim) (100 % of maximal oxygen uptake- V˙O2). They breathed freely or against a fixed inspiratory loading (IL) of 41 cm H2O (∼30 % of maximal inspiratory pressure). Oxygenated (Δ[OxyHb]), deoxygenated (Δ[DeoxyHb]), total hemoglobin (Δ[tHb]) and tissue saturation index (ΔTSI) were obtained by NIRs. Also, blood lactate [La-] was obtained. IL significantly reduced Tlim (224 ± 54 vs 78 ± 20; P < 0.05) and increased [La-], V˙O2, respiratory cycles and dyspnea when corrected to Tlim (P < 0.05). IL also resulted in decrease of Δ[OxyHb] of Cox and IM during exercise compared with rest condition. In addition, decrease of Δ[OxyHb] was observed on IM during exercise when contrasted with Sham (P < 0.05). Furthermore, significant higher Δ[DeoxyHb] of IM and significant lower Δ[DeoxyHb] of Cox were observed when IL was applied during exercise in contrast with Sham (P < 0.05). These results were accompanied with significant reduction of Δ[tHb] and ΔTSI of IM and VL when IL was applied (P < 0.05). High-intensity exercise with IL decreased respiratory and peripheral muscle oxygenation with negative impact on exercise performance. However, the increase in ventilatory work did not impact cerebral oxygenation in soccer players.

Kinesiotaping Diminishes Delayed Muscle Soreness but does not Improve Muscular Performance.

This study aimed at determining the effect of kinesio-taping (KT) on muscle performance and delayed onset muscle soreness (DOMS) after exercise induced muscle damaged. Sixty-six healthy men volunteered to participate (age:18-25 y/o), who performed 200 isokinetic lengthening contractions of the dominant quadriceps. Then subjects were randomized to either control (no treatment), sham (no tape tension), or KT (10% tape tension) groups. Muscle performance was assessed by peak torque and muscular work during maximal isometric and concentric isokinetic contractions. DOMS intensity was assessed using a visual analog scale. Measurements were taken pre-exercise (Pre), 48 h and 96 h post-exercise. Repeated measures ANOVA was used for comparisons within group, and ANCOVA for comparisons among groups. Muscle damage was confirmed in all participants by an increase in CK activity level (p<0.01). Decrease in isometric and isokinetic peak torque was detected at 48 h in the control and sham groups (p<0.01). Muscular work decreased in all groups at 48 h (p<0.01). No differences between groups were detected in muscular performance variables. Increase in DOMS intensity was determined in all groups at 48 h. Comparisons between groups showed lower DOMS intensity in the KT group at 48 h. KT decreased DOMS intensity perception after exercise-induced muscle damage; however, it did not impact muscular performance.

Relative lipid oxidation associates directly with mitochondrial fusion phenotype and mitochondria-sarcoplasmic reticulum interactions in human skeletal muscle.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Twelve healthy men were included [mean (standard deviation), 24.7 (1.5) yr old, 24.4 (2.6) kg/m2]. The respiratory quotient (RQ) was used to estimate relative lipid oxidation at rest and during exercise (50% maximal oxygen consumption, 600 kcal expended). A skeletal muscle biopsy was obtained from the vastus lateralis at rest. Transmission electron microscopy was used to determine mitochondrial size and mitochondria-sarcoplasmic reticulum interactions (≤50 nm of distance between organelles). Protein levels of fusion/fission regulators were measured in skeletal muscle by Western blot. Resting RQ and exercise RQ associated inversely with intermyofibrillar mitochondrial size (r = -0.66 and r = -0.60, respectively, P < 0.05). Resting RQ also associated inversely with the percentage of intermyofibrillar mitochondria-sarcoplasmic reticulum interactions (r = -0.62, P = 0.03). Finally, intermyofibrillar mitochondrial size associated inversely with lipid droplet density (r = -0.66, P = 0.01) but directly with mitochondria fusion-to-fission ratio (r = 0.61, P = 0.03). Our results show that whole body lipid oxidation is associated with skeletal muscle intermyofibrillar mitochondrial size, fusion phenotype, and mitochondria-sarcoplasmic-reticulum interactions in nondiabetic humans.

Effects of oral contraceptive use on female sexual salivary hormones and indirect markers of muscle damage following eccentric cycling in women.

PURPOSE: To determine the effects of oral contraceptive (OC) use on salivary concentrations of testosterone, estrogen, progesterone, and its effects on the changes in indirect markers of muscle damage following eccentric cycling in women. METHODS: 10 oral contraceptive users at follicular phase (OC-FOL), 10 non-oral contraceptives users at follicular phase (NOC-FOL), and 10 non-oral contraceptives users at ovulation phase (NOC-OV) participated. Subjects performed 30 min of eccentric cycling at 90% of their maximal concentric power output (PO). Maximal voluntary isometric contraction (MVC), creatine kinase activity (CK), muscle soreness (SOR), and pain pressure threshold of vastus lateralis (PPT-VL) was assessed before, immediately after, and 24-96 h after cycling. Salivary estrogen, progesterone and testosterone concentrations were measured before, 72 and 96 h after exercise. RESULTS: No difference in estrogen levels between users and non-users was observed. Testosterone was 45% lower in OC-FOL than NOC-FOL at 96 h post-exercise (P = 0.01). Progesterone was 30.8-fold higher in NOC-OV than OC-FOL and 9.7-fold higher than NOC-FOL at 96 h post-exercise. The NOC-FOL recovered all indirect markers of muscle damage by 72 h post-exercise (P > 0.05). NOC-OV recovered MVC strength and muscle soreness (SOR and PPT-VL) by 96 h post-exercise (P > 0.05). OC-FOL did not recover baseline values of MVC, SOR, CK, and PPT-VL by 96 h. CONCLUSION: These results suggest that recovery after exercise-induced muscle damage took longer in OC-FOL, followed by NOC-OV and by NOC-FOL, respectively. Furthermore, testosterone and progesterone levels may affect recovery of indirect markers of muscle damage in women.

Activation of protein synthesis, regeneration, and MAPK signaling pathways following repeated bouts of eccentric cycling.

The aim of this study was to examine the activation of skeletal muscle signaling pathways related to protein synthesis and the gene expression of regeneration/degradation markers following repeated bouts of eccentric cycling. Nine untrained men (25.4 ± 1.9 yr) performed two 30-min eccentric cycling bouts (ECC1, ECC2) at 85% of maximal concentric workload, separated by 2 wk. Muscle biopsies were taken from the vastus lateralis before and 2 h after each bout. Indirect markers of muscle damage were assessed before and 24-48 h after exercise. Changes in the Akt/mammalian target of rapamycin (mTOR)/rbosomal protein S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) and MAPK signaling pathways were measured by Western blot and changes in mRNA expression of IL-6 and IL-1ß, and myogenic regulatory factors (MRFs) were measured by real-time PCR. ECC1 induced greater increases in indirect markers of muscle damage compared with ECC2. Phosphorylation of S6K1 and rpS6 increased after both exercise bouts (P < 0.05), whereas phosphorylation of mTOR increased after ECC2 only (P = 0.03). Atrogin-1 mRNA expression decreased after ECC1 and ECC2 (P < 0.05) without changes in muscle RING-finger protein-1 mRNA. Basal mRNA levels of myoblast determination protein-1 (MyoD), MRF4, and myogenin were higher 2 wk after ECC1 (P < 0.05). MRF4 mRNA increased after ECC1 and ECC2 (P < 0.05), whereas MyoD mRNA expression increased only after ECC1 (P = 0.03). Phosphorylation of JNK and p38 MAPK increased after both exercise bouts (P < 0.05), similar to IL-6 and IL-1ß mRNA expression. All together, these results suggest that differential regulation of the mTOR pathway and MRF expression could mediate the repeated bout effect observed between an initial and secondary bout of eccentric exercise.

Effects of lung deflation induced by tiotropium/olodaterol on the cardiocirculatory responses to exertion in COPD.

BACKGROUND: Hyperinflation has been associated with negative cardiocirculatory consequences in patients with chronic obstructive pulmonary disease (COPD). These abnormalities are likely to worsen when the demands for O2 increase, e.g., under the stress of exercise. Thus, pharmacologically-induced lung deflation may improve cardiopulmonary interactions and exertional cardiac output leading to higher limb muscle blood flow and oxygenation in hyperinflated patients with COPD. METHODS: 20 patients (residual volume = 201.6 ±â€¯63.6% predicted) performed endurance cardiopulmonary exercise tests (75% peak) 1 h after placebo or tiotropium/olodaterol 5/5 µg via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Cardiac output was assessed by signal-morphology impedance cardiography. Near-infrared spectroscopy determined quadriceps blood flow (indocyanine green dye) and intra-muscular oxygenation. RESULTS: Tiotropium/olodaterol was associated with marked lung deflation (p < 0.01): residual volume decreased by at least 0.4 L in 14/20 patients (70%). The downward shift in the resting static lung volumes was associated with less exertional inspiratory constraints and dyspnoea thereby increasing exercise endurance by ~50%. Contrary to our premises, however, neither central and peripheral hemodynamics nor muscle oxygenation improved after active intervention compared to placebo. These results were consistent with those found in a subgroup of patients showing the largest decrements in residual volume (p < 0.05). CONCLUSIONS: The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes are not translated into enhanced cardiocirculatory responses to exertion in hyperinflated patients with COPD. Improvement in exercise tolerance after dual bronchodilation is unlikely to be mechanistically linked to higher muscle blood flow and/or O2 delivery.

Myofibrillar protein synthesis and muscle hypertrophy individualized responses to systematically changing resistance training variables in trained young men.

The manipulation of resistance training (RT) variables is used among athletes, recreational exercisers, and compromised populations (e.g., elderly) attempting to potentiate muscle hypertrophy. However, it is unknown whether an individual's inherent predisposition dictates the RT-induced muscle hypertrophic response. Resistance-trained young [26 (3) y] men (n = 20) performed 8 wk unilateral RT (2 times/wk), with 1 leg randomly assigned to a standard progressive RT [control (CON)] and the contralateral leg to a variable RT (VAR; modulating exercise load, volume, contraction type, and interset rest interval). The VAR leg completed all 4 RT variations every 2 wk. Bilateral vastus lateralis cross-sectional area (CSA) was measured, pre- and post-RT and acute integrated myofibrillar protein synthesis (MyoPS) rates were assessed at rest and over 48 h following the final RT session. Muscle CSA increase was similar between CON and VAR (P > 0.05), despite higher total training volume (TTV) in VAR (P < 0.05). The 0-48-h integrated MyoPS increase postexercise was slightly greater for VAR than CON (P < 0.05). All participants were considered "responders" to RT, although none benefited to a greater extent from a specific protocol. Between-subjects variability (MyoPS, 3.30%; CSA, 37.8%) was 40-fold greater than the intrasubject (between legs) variability (MyoPS, 0.08%; CSA, 0.9%). The higher TTV and greater MyoPS response in VAR did not translate to a greater muscle hypertrophic response. Manipulating common RT variables elicited similar muscle hypertrophy than a standard progressive RT program in trained young men. Intrinsic individual factors are key determinants of the MyoPS and change in muscle CSA compared with extrinsic manipulation of common RT variables.NEW & NOTEWORTHY Systematically manipulating resistance training (RT) variables during RT augments the stimulation of myofibrillar protein synthesis (MyoPS) and training volume but fails to potentiate muscle hypertrophy compared with a standard progressive RT. Any modest further MyoPS increase and higher training volumes do not reflect in a greater hypertrophic response. Between-subject variability was 40-fold greater than the variability promoted by extrinsic manipulation of RT variables, indicating that individual intrinsic factors are stronger determinants of the hypertrophic response.

Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats.

Knee osteoarthritis (KOA) is associated with muscle weakness, but it is unclear which structures are involved in the muscle changes. This study assessed morphological alterations and the expression of genes and proteins linked to muscular atrophy and neuromuscular junctions (NMJs) in KOA, induced by anterior cruciate ligament transection (ACLT) in rats. Two groups of rats were assessed: control (without intervention) and KOA (ACLT surgery in the right knee). After 8 weeks, quadriceps, tibialis anterior (TA) and gastrocnemius muscles were analyzed (area of muscle fibers, NMJ, gene and protein expression). KOA group showed atrophy in quadriceps (15.7%) and TA (33%), with an increase in atrogin-1 and muscle RING-finger protein-1 (MuRF-1). KOA group showed quadriceps NMJ remodeling (reduction area and perimeter) and decrease in NMJ diameter in TA muscle. The expression of nicotinic acetylcholine receptor (nAChR) γ-nAChR increased and that of α-nAChR and muscle specific tyrosine kinase (MuSK) declined in the quadriceps, with a decrease in ε-nAChR in TA. MuRF-1 protein expression increased in quadriceps and TA, with no changes in neural cell adhesion molecule (NCAM). In conclusion, ACLT-induced KOA promotes NMJ remodeling and atrophy in quadriceps and TA muscles, associated with inflammatory signs and changes in muscle gene and protein expression.

Effects of light-emitting diode therapy (LEDT) on cardiopulmonary and hemodynamic adjustments during aerobic exercise and glucose levels in patients with diabetes mellitus: A randomized, crossover, double-blind and placebo-controlled clinical trial.

The aim of this study was to evaluate the acute effects of light-emitting diode therapy (LEDT) on cardiopulmonary adjustments and muscle oxygenation dynamics during transition to moderate exercise, as well as in glucose and lactate levels in patients with type 2 diabetes mellitus (T2DM). Sixteen individuals with T2DM (age 55.1±5.4 years) performed four separate tests receiving LEDT or placebo in random order, at intervals of at least 14 days. A light-emitting diode array (50GaAIAs LEDs, 850nm, 75mW per diode) was used to perform LEDT bilaterally on the quadriceps femoris and triceps surae muscles for 40s at each site. After, a moderate cycling exercise was performed and oxygen uptake, muscular deoxyhemoglobin, heart rate and cardiac output were measured. Lactate and glucose levels were measured before LEDT/placebo and after the exercise. The LEDT decreased the glucose levels after the exercise compared with values before LEDT (173.7±61.0 to 143.5±53.5 mg/dl, P=0.02) and it did not affect the cardiopulmonary and hemodynamic adjustments in exercise, as well as lactate levels in both groups. In conclusion, the LEDT in combination with moderate exercise acutely decreased the glucose levels in men with T2DM.

Influence of a periodized circuit training protocol on intermuscular adipose tissue of patients with knee osteoarthritis: protocol for a randomized controlled trial.

BACKGROUND: The objective of this study is to analyze the influence of a 14-week periodized circuit training protocol on patients with knee osteoarthritis (OA), in randomized intervention groups, on thigh intermuscular adipose tissue (interMAT), body composition, systemic inflammation, cartilage degradation, and its repercussion on pain, functional performance and quality of life. METHODS: This study presents a protocol for a randomized controlled trial. Sixty selected participants diagnosed with knee OA grades II and III, 40-65 years old and BMI < 30 kg/m2, will be randomly divided into three groups:periodized circuit training, strength training, and educational protocol. The circuit training and strength training protocols consist of 14-week training protocols conducted 3 times a week. The circuit training group will perform selected exercises previously stratified as light, moderate, and intense, arranged progressively in a circuit model, the strength group will perform regular strength exercises, and the educational protocol group will participate in a 14-week protocol with lectures twice a month about healthy lifestyles. Baseline and follow-up evaluations will be conducted for thigh interMAT (computed tomography), body composition (DXA), inflammation (IL-1ß, IL-6, IL-10, TNF-α, leptin, and adiponectin), and joint degradation biomarkers (uCTX-II and sCOMP), performance-based tests (30s Chair Stand Test, 40 m Fast-paced Walk Test and Stair Climb Test), quadriceps and hamstring maximal isometric voluntary contraction (MIVC), and questionnaires (WOMAC and pain catastrophizing scale). Repeated measures ANOVA will be used to compare differences between groups (circuit training X strength training X educational protocol) at the different times of assessment (baseline x follow-up or baseline x during protocol x follow-up) for each of the dependent variables. When significant main effects were found, the pots hoc Bonferroni test will be used to identify statistical differences. A significance level of 5% (p < 0.05) will be adopted. DISCUSSION: This will be the first randomized controlled trial to assess the effects of a circuit training protocol on patients with knee OA on thigh intermuscular adipose tissue (interMAT). Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of a low-cost, non-pharmacological, and non-invasive treatment for knee OA patients has the potential for immediate and high clinical impact. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02761590 , registered in May 4, 2016.

GABAergic contribution to the muscle mechanoreflex-mediated heart rate responses at the onset of exercise in humans.

Previous studies have indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. On the basis of previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset are primarily mediated by muscle mechanoreceptor afferents. Therefore, in this study, we sought to determine whether central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans. Twenty-eight healthy subjects (14 men and 14 women) aged between 18 and 35 yr randomly performed three bouts of 5-s passive and active cycling under placebo and after oral administration of diazepam (10 mg), a benzodiazepine that produces an enhancement in GABAA activity. Beat-to-beat HR (electrocardiography) and arterial blood pressure (finger photopletysmography) were continuously measured. Electromyography of the vastus lateralis was obtained to confirm no electrical activity during passive trials. HR increased from rest under placebo and further increased after administration of diazepam in both passive (change: 12 ± 1 vs. 17 ± 1 beats/min, P < 0.01) and active (change: 14 ± 1 vs. 18 ± 1 beats/min, P < 0.01) cycling. Arterial blood pressure increased from rest similarly during all conditions ( P > 0.05). Importantly, no sex-related differences were found in any variables during experiments. These findings demonstrate, for the first time, that the GABAergic mechanisms significantly contribute to the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans. NEW & NOTEWORTHY We found that passive and voluntary cycling evokes similar increases in heart rate and that these responses were enhanced after diazepam administration, a benzodiazepine that enhances GABAA activity. These findings suggest that the GABAergic system may contribute to the muscle mechanoreflex-mediated vagal withdrawal at the onset of exercise in humans.

Exercise training improves neurovascular control and calcium cycling gene expression in patients with heart failure with cardiac resynchronization therapy.

Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca2+-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o2 peak, MSNA (microneurography), forearm blood flow, and Ca2+-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o2 peak were significantly increased in the ET group (P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET (P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET (P = 0.0004), but not in the NoET, group. The expression of the Na+/Ca2+ exchanger (P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca2+-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.

Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency.

OBJECTIVE: To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in patients with heart failure (HF) with testosterone deficiency. PATIENTS AND METHODS: From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis. RESULTS: Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group. CONCLUSION: Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.

The effect of prenatal exposure to 1800 MHz electromagnetic field on calcineurin and bone development in rats.

PURPOSE: To investigated the effects of exposure to an 1800 MHz electromagnetic field (EMF) on bone development during the prenatal period in rats. METHODS: Pregnant rats in the experimental group were exposed to radiation for six, 12, and 24 hours daily for 20 days. No radiation was given to the pregnant rats in the control group. We distributed the newborn rats into four groups according to prenatal EMF exposure as follows: Group 1 was not exposed to EMF; groups 2, 3, and 4 were exposed to EMF for six, 12, and 24 hours a day, respectively. The rats were evaluated at the end of the 60th day following birth. RESULTS: Increasing the duration of EMF exposure during the prenatal period resulted in a significant reduction of resting cartilage levels and a significant increase in the number of apoptotic chondrocytes and myocytes. There was also a reduction in calcineurin activities in both bone and muscle tissues. We observed that the development of the femur, tibia, and ulna were negatively affected, especially with a daily EMF exposure of 24 hours. CONCLUSION: Bone and muscle tissue development was negatively affected due to prenatal exposure to 1800 MHz radiofrequency electromagnetic field.

Carbohydrate Mouth Rinse Maintains Muscle Electromyographic Activity and Increases Time to Exhaustion during Moderate but not High-Intensity Cycling Exercise.

The aim was to investigate the influence of a carbohydrate (CHO) mouth rinse on the vastus lateralis (VL) and rectus femoris (RF) electromyographic activity (EMG) and time to exhaustion (TE) during moderate (MIE) and high-intensity cycling exercise (HIE). Thirteen participants cycled at 80% of their respiratory compensation point and at 110% of their peak power output to the point of exhaustion. Before the trials and every 15 min during MIE, participants rinsed with the CHO or Placebo (PLA) solutions. The root mean square was calculated. CHO had no effect on the TE during HIE (CHO: 177.3 ± 42.2 s; PLA: 163.0 ± 26.7 s, p = 0.10), but the TE was increased during MIE (CHO: 76.6 ± 19.7 min; PLA: 65.4 ± 15.2 min; p = 0.01). The EMG activity in the VL was higher than PLA at 30 min (CHO: 10.5% ± 2.6%; PLA: 7.7% ± 3.3%; p = 0.01) and before exhaustion (CHO: 10.3% ± 2.5%; PLA: 8.0% ± 2.9%; p = 0.01) with CHO rinsing. There was no CHO effect on the EMG activity of RF during MIE or for VL and RF during HIE. CHO mouth rinse maintains EMG activity and enhances performance for MIE but not for HIE.

The effect of prenatal exposure to 1800 MHz electromagnetic field on calcineurin and bone development in rats

PURPOSE: To investigated the effects of exposure to an 1800 MHz electromagnetic field (EMF) on bone development during the prenatal period in rats. METHODS: Pregnant rats in the experimental group were exposed to radiation for six, 12, and 24 hours daily for 20 days. No radiation was given to the pregnant rats in the control group. We distributed the newborn rats into four groups according to prenatal EMF exposure as follows: Group 1 was not exposed to EMF; groups 2, 3, and 4 were exposed to EMF for six, 12, and 24 hours a day, respectively. The rats were evaluated at the end of the 60th day following birth. RESULTS: Increasing the duration of EMF exposure during the prenatal period resulted in a significant reduction of resting cartilage levels and a significant increase in the number of apoptotic chondrocytes and myocytes. There was also a reduction in calcineurin activities in both bone and muscle tissues. We observed that the development of the femur, tibia, and ulna were negatively affected, especially with a daily EMF exposure of 24 hours. CONCLUSION: Bone and muscle tissue development was negatively affected due to prenatal exposure to 1800 MHz radiofrequency electromagnetic field.

Effect of time-dependent cryotherapy on redox balance of quadriceps injuries.

Muscle trauma represents a high number of injuries in professional sport and recreation and may occur through several mechanisms. This study aims at analyzing time-dependent effects of cryotherapy on the redox balance in lesioned quadriceps muscles in F1 mice. Twenty male F1 mice were divided into five groups: (a) animals were not subjected to muscle lesioning or treatment (CTR); (b) quadriceps muscle was lesioned without treatment (L); (c) quadriceps muscle was lesioned and treated with cryotherapy for 5 min (LC5); (d) quadriceps muscle was lesioned and treated with cryotherapy for 20 min (LC20); and quadriceps muscle was lesioned and treated with cryotherapy for 40 min (LC40). The mice were euthanized; the quadriceps muscles were collected and subjected to analyses for levels of protein, hydroperoxides, nitrite, catalase (CAT) activity, oxidized glutathione (GSSG) and reduced glutathione (GSH). Protein levels were reduced in L (-39%; p < 0.05), LC5 (-54%; p < 0.05), LC20 (-40%; p < 0.05) and LC40 (-50%; p < 0.05) compared to CTR. There was an increase in lipid peroxidation in L (158%; p < 0.05), LC5 (300%; p < 0.01), LC20 (292%; p < 0.01) and LC40 (362%; p < 0.01) compared to CTR. We observed a significant increase in CAT activity in L (164%; p < 0.05) and LC5 (193%; p < 0.01) compared to CTR; a significant reduction in GSH in L (-60%; p < 0.05) and LC20 (-61%; p < 0.05) compared to CTR; and a significant increase in GSSG in LC5 (171%; p < 0.05) compared to CTR. In addition, GSH/GSSG was reduced in L (-89%; p < 0.01), LC5 (-95%; p < 0.01), LC20 (-59%; p < 0.05), and LC40 (-82%; p < 0.01) compared to CTR. This study showed that the cryotherapy does not improve the oxidative stress in lesioned muscles.