Response of the metabosensitive fibers to electrically induced fatigue (EIF).

<p>Animals from all groups exhibited a significant (***, p<0.001) increase in afferent discharge frequency after a 3-min stimulation of the <i>gastrocnemius</i> muscle. <b>A.</b> Examples of recordings before (baseline activity) and after EIF. <b>B.</b> Comparison between the post-EIF changes indicate that the mean discharge rate was significantly (###, p<0.001) lower in the B0 group compared to the 3 other groups.</p

Response of the metabosensitive fibers to chemicals.

<p>Responses (F_impulses.s^-1) of tonically active muscle afferents during stepwise increase in potassium chloride (<b>A</b>) and lactic acid (<b>B</b>) concentration in injected solutions were recorded. Significant (**, p<0.01 and ***, p<0.001) increases in afferent discharge frequency, as compared to baseline recording, were observed in the Control and BoNT/A injected animals from B0 and B50 groups at all concentrations of KCl or LA solution tested. <b>A.</b> Intergroup comparison indicated that there is a significant difference (δ, p<0.05) in the KCl curve dose response for B100 group compared to other groups. Responses to KCl were significantly decreased in the B100 group for all concentrations. Compared to the respective concentrations of the other groups, the responses were significantly lower for 1 mM (£, p<0.05), 5 mM (§, p<0.05), 10 mM (#, p<0.05) and 20 mM ($, p<0.05). <b>B.</b> Intergroup comparison indicated that there is a significant difference (δ, p<0.05) in the LA curve dose response for B100 group compared to other groups. Responses to LA were significantly decreased for the 1 mM concentration in all BoNT/A groups (B0: §, p<0.05; B50: §, p<0.05 and B100: §§§, p<0.001) compared to the respective concentration of the Control group. Moreover, at the concentration of 1 mM, the B100 group also exhibited significant differences with B0 (ΩΩ, p<0.01) and B50 (χ, p<0.05) groups.</p

Response of the mechanosensitive fibers to calcaneal tendon vibrations.

<p>In all groups, a response (F_impulses.s^-1) persisting throughout the tendon vibration period was recorded for each vibration frequency. In Control and B100 groups, the changes in afferent discharge evoked by vibration are bimodal with peaks measured at 40 and 80 Hz (<i>black arrows</i>). In the B0 and B50 groups, only one peak is measured at 70 Hz (<i>white arrow</i>).</p

Implant-to-bone adhesion.

<p>Measurement of the maximum load value indicates that adhesion of the implants to the tibial crest bone is significantly (**: p<0.01) higher when implanted animals are submitted to high-salt diet (Ti-NaCl) compared to only implanted animals (Ti) or animals simultaneously submitted to high-salt diet and NEMS program (Ti-NaCl-Es).</p

Surface degradation of the implant.

<p>The surface of the implant is scanned before and 3 weeks after implantation and the range between higher and lower surface point is measured. Results indicate that the Ti-NaCl (implanted and submitted to high-salt diet) and Ti-NaCl-Es (implanted and simultaneously submitted to high-salt diet and NEMS program) groups present a significant higher (*: p<0.05) degradation of implant compared to Ti (non submitted to high-salt diet and NEMS program) group.</p

Design of the implant and NEMS device.

<p>Rat is positioned in supination. Straps located on thorax and abdomen avoid any movement interference. Foot is firmly held and stimulation electrodes are positioned on the skin right above the first 1/3 of FD muscle. Implant location is represented from digitalized implant and tibial bone made using a Computer Assisted Design system.</p

Muscle damages.

<p>Antibodies directed against activated caspase 3 are used on <i>flexor digitorum</i> and <i>tibialis anterior</i> muscles to evaluate cell death rate (number of dead cells per surface unit). No significant muscle damage is observed between muscles in each group. Furthermore, significant differences between Control and other groups are indicated by * for <i>flexor digitorum</i> and + for <i>tibialis anterior</i> (*** and +++, p<0.001). δ indicates significant intergroup differences for both muscles (δδδ, p<0.001).</p

Tensile test.

<p>A homemade device is used to measure the adhesion load between the implant and the bone. Briefly, tibial bone is placed, implant downwards, on a flat metal bracket containing a hole allowing the implant to be loaded by a tension device. Highly resistant wire is passed through the implant hole then connected to the load system. The mobile part of the testing device is slowly displaced to stretch the wire until the implant loosened. Graphic in lower part indicates the time-curve of force recorded and the maximum load value obtained just before the breakout of the implant marked by a thin arrow.</p

Vitamin D improves responses to muscle electrically-induced fatigue or to a chemical agent.

<p>Ventilatory response of the animals after muscle stimulation (<b>A</b>) and response of metabosensitive afferent fibre activity after active muscle electrical stimulation (<b>B</b>) or intramuscular capsaicin injection (<b>C</b>). The experiment was first assessed in the 6 initial groups (n = 6 per group) (right histograms) and then in the 3 final groups (n = 12 per group) (left histograms). Crosses (+) indicate that the response was significantly increased, when compared to the Vehicle group (+ p<0.05;++p<0.01;+++p<0.001).</p

Selected calcitriol-regulated genes involved in axogenesis and myelination.

<p>Selected list of transcripts, involved in axogenesis and myelination, whose expression is modified after the addition of calcitriol (100 nM), during 24 hours, to cultures of Schwann cells (SC) or co-cultures of DRG and SC. The symbol, the full name and the fold change of each gene are indicated. Under-expressed genes are in italic. Calcitriol-regulated genes in both Schwann cell and DRG/Schwann cell cultures are in bold.</p