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Treadmill walking exercise is not always effective for prevention of detrimental effects on soleus muscle caused by gravitational unloading. Thus, the effects of walking speed and/or uphill inclination on the mobilization of leg muscles were studied to reconsider the optimum prescription for the countermeasure. The subjects performed barefoot walking exercise on a treadmill at 4 and 6 km/h and at a 0, 6, 10, and 15% uphill incline. The activity of electromyogram (EMG) was recorded in soleus, lateral portion of gastrocnemius, and tibialis anterior muscles. In addition, the total time spent for each step (step duration from landing to the next landing of the left foot) and the time soleus was active per step (EMG burst duration) during each step were determined. Furthermore, video was recorded to measure the ankle and knee joint angles in the front and back foot, when the front foot landed on the treadmill. Most of the subjects stepped down using the heel (rear-foot strike), but one subject stepped down using the fore-foot (fore-foot strike). The EMG activity of soleus in the rear-foot strikers was elevated with an increase in treadmill inclination and/or speed. In contrast, soleus EMG activity was decreased in the fore-foot striker under the same conditions, whereas the EMG activity of gastrocnemius was increased. These results indicate that individual differences in foot-strike patterns should be considered for the optimum prescription of walking as an exercise countermeasure and suggest that similar considerations may be warranted for other exercise countermeasures.

Background Although rat anti-mouse IL-6 receptor (IL-6R) antibody (MR16-1) has been reported to effectively ameliorate various tissue damages, its effect on skeletal muscle regeneration has not been determined. Moreover, the localization, persistence and duration of action of this reagent in damaged tissues after systemic administration have not been assessed. Methods The MR16-1 was administered i.p. immediately after cardiotoxin (CTX)-induced muscle damage on mice. Results MR16-1 administered i.p. was observed only to the damaged muscle. This delivered MR16-1 was dramatically decreased from 3 to 7 days post-injury concomitantly with a reduction of IL-6R expression. This reduction of the MR16-1 level in the damaged muscle was not rescued by additional administration of MR16-1, suggesting the short half-life of MR16-1 was not the factor for the remaining levels. In addition, a significant inhibitory effect of MR16-1 on phosphorylation of the signal transducer and activator of transcription 3 was observed in the macrophage-enriched area of damaged muscle 3 days after injury. Finally, the acceleration of muscle regeneration observed at day 7 post-injury following MR16-1 treatment was associated with reduced expression of fibrosis-related genes, such as interleukin-10 and arginase, in the infiltrated macrophages. Conclusions These results suggest that MR16-1 which was found primarily localized in infiltrated macrophages in the damaged muscle might facilitate muscle regeneration via immune modulation. General significance: These findings are deemed to provide further insight into the understanding not only of MR16-1 treatment on muscle regeneration, but also of the other anti-cytokine treatment on the cytokine-related disease.

Effect of peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, WY-14,643 (WY) and/or clofibrate, on the leucine-induced phosphorylation of translational targets in C2C12 myoblasts was studied. C2C12 cells were treated with WY or clofibrate for 24 h prior to stimulation with leucine. Western blot analyses revealed that the leucine-induced phosphorylation of p70 S6 kinase (p70S6K), a key regulator of translation initiation, was significantly higher in WY-treated cells than in control and clofibrate-treated cells. Phosphorylation of extracellular-regulated kinase (ERK1/2) was higher in WY-treated cells. WY treatment also increased the leucine-induced phosphorylation of ribosomal protein S6 and eukaryotic initiation factor 4B. In contrast, eukaryotic elongation factor 2, a marker for peptide chain elongation process, was significantly activated (dephosphorylated) only in leucine-stimulated control cells. Pre-treatment of the cells with PD98059 (ERK1/2 kinase inhibitor) prevented the phosphorylation of ERK1/2 and decreased the leucine-induced phosphorylation of p70S6K. It is concluded that WY increased the leucine-induced phosphorylation of target proteins involving in translation initiation via ERK/p70S6K pathway, but impaired the signaling for elongation process, suggesting that p70S6K phosphorylation may be essential, but not sufficient for the activation of entire targets for protein translation in WY-treated cells.