Extended exposure to microgravity leads to significant musculoskeletal adaptations. Contractile parameters of four skeletal muscles (biceps brachii-BB, vastus medialis-VM, biceps femoris-BF and gastrocnemius medialis-GM) were measured in ten healthy males (aged 22.3 +/- 2.2 years) during 35 days of horizontal bed rest by a mechanomyography-based method termed 'tensiomyography' (TMG). Two contractile parameters: contraction time (Tc) and maximal displacement (Dm) were individually measured from electrically evoked maximal single twitch TMG response of all four muscles before and after bed rest. Significant changes in Tc were found after bed rest, as shown by an increase in GM muscle Tc by 18% (p < 0.01). Dm values significantly increased (p < 0.01) after bed rest, by 24, 26 and 30% in the VM, BF and GM muscles, respectively. In the GM, the change in Dm significantly correlated with the decrease in muscle thickness (r = -0.70, p < 0.01). In conclusion, bed rest induced changes in both Dm and Tc of the TMG signal; changes in Dm being inversely related to those of muscle thickness. Amongst the investigated muscles, most affected, in terms of atrophy and mechanical alterations, were those of the lower limbs. The observed increase in Dm may be attributed to a decrease in muscle, as well as tendon stiffness, causing larger muscle fibre and non-contractile tissue oscillations following contraction.

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The aim of this study was to elucidate the mechanisms responsible for the effects of innervation on the maturation of excitation-contraction coupling apparatus in human skeletal muscle. For this purpose, we compared the establishment of the excitation-contraction coupling mechanism in myotubes differentiated in four different experimental paradigms: 1) aneurally cultured, 2) cocultured with fetal rat spinal cord explants, 3) aneurally cultured in medium conditioned by cocultures, and 4) aneurally cultured in medium supplemented with purified recombinant chick neural agrin. Ca(2+) imaging indicated that coculturing human muscle cells with rat spinal cord explants increased the fraction of cells showing a functional excitation-contraction coupling mechanism. The effect of spinal cord explants was mimicked by treatment with medium conditioned by cocultures or by addition of 1 nM of recombinant neural agrin to the medium. The treatment with neural agrin increased the number of human muscle cells in which functional ryanodine receptors (RyRs) and dihydropyridine-sensitive L-type Ca(2+) channels were detectable. Our data are consistent with the hypothesis that agrin, released from neurons, controls the maturation of the excitation-contraction coupling mechanism and that this effect is due to modulation of both RyRs and L-type Ca(2+) channels. Thus, a novel role for neural agrin in skeletal muscle maturation is proposed.

As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS) components in subjects prior to the onset of insulin resistance (IR). Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

Oxidative stress is often associated to inactivity-mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers. To assess muscle glutathione synthesis, we applied a novel single-biopsy and double-tracer ( Muscle glutathione absolute synthesis rate increased following bed rest from 5.5 ± 1.1 to 11.0 ± 1.5 mmol (kg wet tissue) −1 day −1 (mean ± s.e.m.; n = 9; P = 0.02) while glutathione concentration failed to change significantly. Bed rest induced vastus lateralis muscle atrophy, as assessed by pennation angle changes measured by ultrasonography (from 18.6 ± 1.0 to 15.3 ± 0.9 deg; P = 0.01) and thickness changes (from 2.3 ± 0.2 to 1.9 ± 0.1 cm; P < 0.001). Moreover, bed rest increased protein oxidative stress, as measured by muscle protein carbonylation changes (from 0.6 ± 0.1 to 1.00 ± 0.1 Oxydized-to-total protein ratio; P < 0.04).In conclusion, we developed in erythrocytes a new minimally invasive method to determine peptide synthesis rate in human tissues. Application of the new method to skeletal muscle suggests that disuse atrophy is associated to oxidative stress induction as well as to compensatory activation of the glutathione system.

Background. Adult skeletal muscle is considered resistant to ionizing radiation unless higher doses of radia

Weight loss in combination with increased physical activity, a negative energy balance, and diet adjustment was associated with lower inflammation and consequently with lower cardiovascular risk factors.