Muscle regeneration after high-dose radiation exposure: therapeutic potential of Hedgehog pathway modulation?

Purpose: Intentional or accidental exposure of relatively large as well as localized areas of the skin to ionizing radiation can lead to severe damage of many of its cellular components and cutaneous radiation syndrome. Patients can be treated with an invasive surgical procedure coupled with autologous cell therapy. However, this approach remains perfectible, especially for muscle repair. Indeed, a severe underlying muscle defect persists, in particular because of the damage to the satellite cells which ensure muscle regeneration. To overcome these shortcomings, a solution could be to develop new therapeutic strategies based on pharmacological treatments to improve post-irradiation muscle regeneration. In this study, we focus on the Hedgehog signaling pathway as a target, due to its involvement in myogenesis.Materials and methods: To evaluate the benefit of the pro-myogenic Hedgehog signaling pathway modulation, recombinant Sonic Hedgehog (rShh; agonist) or Cyclopamine (antagonist) were used in a stable cell line of mouse C2C12 myoblasts exposed to radiation (X-rays; 5 Gy). Our in vitro studies were carried out under either proliferation or differentiation conditions. Proliferation, migration, survival (apoptosis) and expression of myogenic genes/proteins were evaluated.Results: A high dose of radiation was shown to exert a serious negative impact in our in vitro model of mouse muscle progenitors after irradiation in proliferation or differentiation conditions. Interestingly, Hh pathway stimulation by rShh promotes the proliferation of myoblasts and their survival while its blockade by Cyclopamine significantly increases cell differentiation toward mature myotubes.Conclusion: These data suggest that, after irradiation, the sequence of activation and inhibition of the Hh pathway could allow rescue and proliferation of satellite cells, followed by their differentiation to regenerate new fibers. On the basis of these encouraging in vitro results, the second phase of our study will involve the in vivo validation of this treatment in a new murine model of ultra-localized muscle irradiation.

Attentional state and brain processes: state-dependent lateralization of EEG profiles in horses.

Lateralization of brain functions has been suggested to provide individuals with advantages, such as an increase of neural efficiency. The right hemisphere is likely to be specialized for processing attention for details and the left hemisphere for categorization of stimuli. Thus attentional processes actually may underlie lateralization. In the present study, we hypothesized that the attentional state of horses could be reflected in the lateralization of brain responses. We used i) a recently developed attention test to measure horses' visual attentional responses towards a standardized stimulus and ii) a recently developed portable EEG telemetric tool to measure brain responses. A particular emphasis was given to the types of waves (EEG power profile) and their side of production when horses were either attentive towards a visual stimulus or quiet standing. The results confirmed that a higher attentional state is associated with a higher proportion of gamma waves. There was moreover an interaction between the attentional state, the hemisphere and the EEG profile: attention towards the visual stimulus was associated with a significant increase of gamma wave proportion in the right hemisphere while "inattention" was associated with more alpha and beta waves in the left hemisphere. These first results are highly promising and contribute to the large debate on functional lateralization.

[Legionella pneumonia in an immunocompetent child]. / La légionellose chez l'enfant immunocompétent: a propos d'un cas.

We report a case of Legionella pneumonia in an immunocompetent child. Legionella pneumonia is a rare pathology among children, and even rarer when they are immuno-competent; a few cases have been reported in the literature. This is explained by the fact that infection occurs primarily to immuno-suppressed patients. Legionella bacteria are not systematically sought for in front of child's atypical pneumonia, contrary to Mycoplasma or Chlamydiae. In addition, a number of cases are probably not even noticed because either not serious (Pontiac fever), spontaneously cured, or cured with macrolides prescribed in the case of suspected pneumonia with Mycoplasma.

Supermirror phase anisotropy measurement.

The high sensitivity of the eigenstates of a large-finesse passive Fabry-Perot cavity is used to measure the residual anisotropy of supermirrors at strictly normal incidence. An experimental demonstration leads to the measurement of phase retardances of the order of 10(-6) rad.

Frequency fluctuations of stabilized lasers with anisotropic feedbacks.

A random phase method is proposed to determine the perturbation of the Allan variance of frequency stabilized lasers submitted to optical feedbacks. The role of different feedbacks is quantitatively described for both one-oscillating-eigenstate stabilized lasers and two-oscillating-eigenstate stabilized lasers. The importance of the feedback polarization is isolated in each system. In both cases, the experimental measurements of the Allan variance and of the peak-to-peak frequency variations due to a periodic modulation of the feedback phase are found to be in agreement with the theoretical predictions.

[Treatment of 2 newborn infants with autoimmune thrombocytopenia by high-dose intravenous gamma globulins]. / Traitement de deux nouveau-nés atteints de thrombocytopénies auto-immunes par les gammaglobulines intraveineuses à fortes doses.

We report 2 cases of neonatal auto-immune thrombocytopenia treated with high-dose intravenous gamma-globulins. Efficacy of treatment was immediate, inducing an increase in platelet levels which was transitory during the first 2 weeks but stabilized in the third week. Tolerance was excellent. Injections of 400 mg/kg/day repeated for 4 to 5 days should be preferred to a single dose of 1 to 2 g/kg.