Rôle du pharmacien d'officine dans la prise en charge des lombalgies et lomboradiculalgies d'origine commune

Les lombalgies et lomboradiculalgies d'origine commune présentent une forte prévalence dans la population française, puisqu'on estime que 60 à 90% des personnes souffriront de lombalgie au cours de leur vie. La prise en charge est difficile: le soulagement de la douleur et la récupération de la mobilité représentent l'essentiel du traitement, mais le risque de rechute et de passage à la chronicité est important. Le pharmacien d'officine peut participer à cette prise en charge à de nombreux niveaux: de la délivrance de médicaments et de matériel médical ou orthopédique, à l'activité de conseiller association thérapeutiques dites naturelles et informations concernant la prévention des rechutes. Le but de cette thèse est de faire le point sur les données actuelles concernant les lombalgies et lomboradiculalgies non compliquées et leurs traitements, médicamenteux ou non.Low back pain and radiculalgia of the common sort have a high prevalence in the French population, as it is estimated that 60 to 90% of the population will suffer from low back pain at some point during their lives. Medical care is particularity difficult: easing the pain and helping with the recovery of physical mobility represent the main part of the treatment, though there is a high risk of relapse and persistency of the pathology. Pharmacists can participate in the delivery of care at many levels, from delivering drugs and orthopaedic equipment to acting as counselors. The aim of the thesis is to review current information and data concerning low back pain and radiculalgia, as well as their treatments, whether medicinal or not.RENNES1-BU Santé (352382103) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Activation of ERK, Controlled by Rac1 and Cdc42 via Akt, Is Required for Anoikis

International audienceWe have recently reported that two Rho family GTPases, Rac1 and Cdc42, are intimately involved in the control of cell survival of murine fibroblasts linked to adherence to the extracellular matrix. Inhibition of either Rac1 or Cdc42 signaling in adherent cells mimics the loss of anchorage and efficiently induces apoptosis in both immortalized and primary cells. In both cases cell death is dependent on the wild-type p53 tumor suppressor and is accompanied by activation of endogenous p53. Here, we describe that the inhibition of Rac1 or Cdc42 signaling leads to MAPK ERK activation via a pathway involving PI(3)K, Akt, Raf, and MEK, but not Ras. The moderate level of ERK activation that accompanies anoikis is an essential component of proapoptotic signaling; whereas sustained, high-intensity ERK signaling promotes survival in the same experimental system

The role of copy-number variation in the reinforcement of sexual isolation between the two European subspecies of the house mouse

International audienceReinforcement has the potential to generate strong reproductive isolation through the evolution of barrier traits as a response to selection against maladaptive hybridisation, but the genetic changes associated with this process remain largely unexplored. Building upon the increasing evidence for a role of structural variants in adaptation and speciation, we addressed the role of copy number variation in the reinforcement of sexual isolation evidenced between the two European subspecies of the house mouse. We characterized copy-number divergence between populations of Mus musculus musculus that display assortative mate choice, and those that do not, using whole-genome resequencing data. Updating methods to detect deletions and tandem duplications (collectively: copy-number variants, CNVs) in Pool-Seq data, we developed an analytical pipeline dedicated to identifying genomic regions showing the expected pattern of copy-number displacement under a reinforcement scenario. This strategy allowed us to detect 1824 deletions and 7 tandem duplications that showed extreme differences in frequency between behavioural classes across replicate comparisons. A subset of 480 deletions and 4 tandem duplications were specifically associated with the derived trait of assortative mate choice. These “Choosiness-associated” CNVs occur in hundreds of genes. Consistent with our hypothesis, such genes included olfactory receptors potentially involved in the olfactory-based assortative mate choice in this system as well as one gene, Sp110, that is known to show patterns of differential expression between behavioural classes in an organ used in mate choice ¬– the vomeronasal organ. These results demonstrate that fine-scale structural changes are common and highly variable within species, despite being under-studied, and may be important targets of reinforcing selection in this system and others

Distinct requirements for the Sprouty domain for functional activity of Spred proteins

Sprouty and Spred {Sprouty-related EVH1 [Ena/VASP (vasodilator-stimulated phosphoprotein) homology 1] domain} proteins have been identified as antagonists of growth factor signalling pathways. We show here that Spred-1 and Spred-2 appear to have distinct mechanisms whereby they induce their effects, as the Sprouty domain of Spred-1 is not required to block MAPK (mitogen-activated protein kinase) activation, while that of Spred-2 is required. Similarly, deletion of the C-terminal Sprouty domain of Spred-1 does not affect cell-cycle progression of G(0)-synchronized cells through to S-phase following growth factor stimulation, while the Sprouty domain is required for Spred-2 function. We also demonstrate that the inhibitory function of Spred proteins is restricted to the Ras/MAPK pathway, that tyrosine phosphorylation is not required for this function, and that the Sprouty domain mediates heterodimer formation of Spred proteins. Growth-factor-mediated activation of the small GTPases, Ras and Rap1, was able to be regulated by Spred-1 and Spred-2, without affecting receptor activation. Taken together, these results highlight the potential for different functional roles of the Sprouty domain within the Spred family of proteins, suggesting that Spred proteins may use different mechanisms to induce inhibition of the MAPK pathway

Les implications chronoclimatiques, paléoenvironnementales et culturelles du Solutréen de la grotte Rochefort

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