Lipidic nanocapsule drug delivery: neuronal protection for cochlear implant optimization

Objective: Sensorineural hearing loss leads to the progressive degeneration of spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which should be suppressed to assure a close nerve–electrode interaction, the density of healthy SGC is one factor that influences the efficiency of cochlear implants (CI), the choice of treatment for affected patients. Rolipram, a phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory effects and might also reduce SGC degeneration and fibrosis, but it has to pass the cellular membrane to be biologically active. Methods: Lipidic nanocapsules (LNC) can be used as biodegradable drug carriers to increase the efficacy of conventional application methods. We examined the biological effects of rolipram and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor necrosis factor-α (TNF-α) production in vitro and on SGC survival in systemically-deafened guinea pigs in vivo. Results: Our results prove that rolipram does not have a beneficial effect on cultured SGC. Incorporation of rolipram in LNC increased the survival of SGC significantly. In the DC study, rolipram significantly inhibited TNF-α in a dose-dependent manner. The rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo data do not confirm the in vitro results. Conclusion: By transporting rolipram into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in vitro, but not in vivo. This might be due to dilution of test substances by perilymph or an inadequate release of rolipram based on differing in vivo and in vitro conditions. Nevertheless, based on in vitro results, proving a significantly increased neuronal survival when using LNC-rolipram compared to pure rolipram and pure LNC application, we believe that the combination of rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after CI implantation. We conclude that rolipram is a promising drug that can be used in inner ear therapy and that LNC have potential as an inner ear drug-delivery system. Further experiments with modified conditions might reveal in vivo biological effects

Using a dynamical model to study the impact of a toxoid vaccine on the evolution of a bacterium: The example of diphtheria

International audienceVaccines are one of humankind's greatest weapons against infectious diseases. However, their usefulness is often questioned and the public tends to distrust vaccines. A mathematical model published in the early 2000s predicts the selection of more virulent strains of pathogens when populations are protected with imperfect vaccines, i.e., vaccines which reduce but do not entirely block pathogen transmission, such as toxoid vaccines. In this study, we built a disease-specific competition model to analyze the evolution of diphtheria's virulence under the pressure of a toxoid vaccine. Our results show that i) high vaccine coverage favors the emergence and increase prevalence of avirulent (or less virulent) strains of Corynebacterium diphtheriae (the etiologic agent of diphtheria) and ii) that competition between strains is crucial in the eradication of toxigenic strains when toxoid vaccines are used. We conclude that the use of toxoid vaccines could lead to disease eradication if the interaction between strains is taken into account. Our results could extend to biologically similar systems such as pertussis

Combined therapy for critical limb ischaemia: Biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells

International audienceWe propose a regenerative solution in the treatment of critical limb ischaemia (CLI). Poly‐lactic/glycolic acid microcarriers were prepared and coated with laminin to be sterilized through γ‐irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin‐induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischaemic limb was then reported, and tissue reperfusion was evaluated through fluorescence molecular tomography. Microcarriers were stable and functional after γ‐irradiation until at least 12 months of storage. Mice that received an injection of SVF cells in the ischaemic limb have 22% of supplementary blood supply within this limb 7 days after surgery compared with vehicle, whereas no difference was observed at Day 14. With the combined therapy, the improvement of blood flow is significantly higher compared with vehicle, of about 31% at Day 7 and of about 11% at Day 14. Injection of SVF cells induces a significant 27% decrease of necrosis compared with vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: −37% compared with control. Although SVF cells injection leads to a non‐significant 22% proprioception recovery, the combined therapy induces a significant recovery of about 27% compared with vehicle. We show that the combination of SVF cells from adipose tissue with laminin‐coated poly‐lactic/glycolic acid microcarriers is efficient for critical limb ischaemia therapy in a diabetic mouse model

Ecologie de la santé: Pour une nouvelle lecture de nos maux

Prod 2017-108 EA BIOmE CT ? INRANational audienceQuand l'écologie pose son diagnostic. L'actualité nous le rappelle sans cesse : les maladies comme le paludisme, le Sida, ébola ou zika sont difficiles à combattre, et les maladies chroniques de type cancer, diabète ou maladies cardio-vasculaires toujours plus meurtrières. Pour la première fois de son histoire, l'humanité voit même son espérance de vie diminuer. Pour comprendre les raisons de cette crise sanitaire, l'écologie scientifique pose un autre regard sur la santé qui prend en considération les transformations de l'environnement et l'évolution de nos modes de vie. Cette nouvelle approche évolutive et écologique des problèmes de santé tente d'élucider les mécanismes en jeu dans la transmission et l'émergence de nouveaux pathogènes, mais aussi dans la résistance toujours croissante aux antibiotiques. Elle permet de mesurer l'effet des facteurs environnementaux sur la santé : concentration urbaine et industrielle et nouveaux comportements induits en matière d'alimentation et d'activités physiques. Cet ouvrage rédigé par des spécialistes issus des laboratoires du CNRS ou associés fait le point sur les recherches en écologie de la santé. Il permet à chacun de comprendre pourquoi il est essentiel de remonter aux sources environnementales et comportementales de nos maux, et de ne pas se limiter aux symptômes