Freezing of Enkephalinergic Functions by Multiple Noxious Foci: A Source of Pain Sensitization?

BACKGROUND:The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments. METHODOLOGY/PRINCIPAL FINDINGS:Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously. CONCLUSION/SIGNIFICANCE:We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis

Capillary liquid chromatography with MS 3 for the determination of enkephalins in microdialysis samples from the striatum of anesthetized and freely–moving rats

In vivo microdialysis sampling was coupled to capillary liquid chromatography (LC)/electrospray ionization quadrupole ion trap mass spectrometry (MS) to monitor [Met]enkephalin and [Leu]enkephalin in the striatum of anesthetized and freely–moving rats. The LC system utilized a high-pressure pump to load 2.5 µl samples and desalt the 25 µm i.d. by 2 cm long column in 12 min. Samples were eluted with a separate pump at ∼100 nl min −1 . A rapid gradient effectively separated the endogenous neuropeptides in 4 min. A comparison was made for operating the mass spectrometer in the MS 2 and MS 3 modes for detection of the peptides. In standard solutions, the detection limits were similar at 1–2 pM (2–4 amol injected); however, the reproducibility was improved with MS 3 as the relative standard deviation was <5% compared with 20% for MS 2 for 60 pM samples. For dialysate solutions, reconstructed ion chromatograms and tandem mass spectra had much higher signal-to-noise ratios in the MS 3 mode, resulting in more confident detection at in vivo concentrations. The method was successfully used to monitor the peptides under basal conditions and with stimulation of peptide secretion by infusion of elevated K + concentration. Copyright © 2005 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35204/1/733_ftp.pd

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence

Étude sur la scolarité des enfants accompagnés en ITEP, Académie de Rouen, rentrée de septembre 2011

Dans l’Académie de Rouen, à la rentrée 2011, seuls 10 % des élèves manifestant un handicap dont le soin est assuré dans un Institut Thérapeutique Éducatif Pédagogique, bénéficient d’une inclusion scolaire en milieu ordinaire. La législation, depuis 2055, spécifie l’accueil en milieu scolaire ordinaire. Des directeurs d’ITEP décrivent la situation régionale, la comparent aux chiffres nationaux, montrent les difficultés et prennent position à partir des deux grandes possibilités de soins : les ITEP et les SESSAD

LES INTERACTIONS ENTRE LES OPIOIDES ET LE CGRP DANS LE CONTROLE SPINAL DE LA NOCICEPTION, ET LEURS MODIFICATIONS CHEZ LE RAT POLYARTHRITIQUE

LE CGRP ET LES OPIOIDES JOUENT DES ROLES CLES DANS LE CONTROLE DE L'INFORMATION DOULOUREUSE. LEURS INTERVENTIONS DEPENDRAIENT DU TYPE DE DOULEUR. AINSI, CHEZ LE RAT POLYARTRITIQUE, MODELE DE DOULEUR INFLAMMATOIRE CHRONIQUE, NOUS AVONS MIS EN EVIDENCE DES PHENOMENES PLASTIQUES QUI AFFECTENT LES SYSTEMES CGRP-, MET-ENKEPHALINE(ME)- ET DYNORPHINE(DYN)-ERGIQUES SPINAUX. LES DIFFERENCES OBSERVEES CHEZ LES ANIMAUX POLYARTHITIQUES PAR RAPPORT AUX RATS CONTROLES SONT LES SUIVANTES : 1) UNE AUGMENTATION DE LA LIBERATION SPINALE DE LA DYN ET DU CGRP. 2) UNE DIMINUTION DE LA LIBERATION SPINALE DE ME. 3) DES MODIFICATIONS DU CONTROLE OPIOIDERGIQUE DE LA LIBERATION DE CES 3 PEPTIDES : DES OPIOIDES ENDOGENES AGISSANT SUR DES RECEPTEURS EXERCENT UN CONTROLE INHIBITEUR TONIQUE PLUS MARQUE SUR LA LIBERATION DE CGRP ; LA STIMULATION DES RECEPTEURS PAR DES AGONISTES EXOGENES REDUIT LES LIBERATIONS DE CGRP ET DE DYN ; VIA DES RECEPTEURS , DES OPIOIDES ENDOGENES INHIBENT DE MANIERE TONIQUE LA LIBERATION DE CGRP ; LES LIBERATIONS DE DYN ET DE ME SONT RESPECTIVEMENT REDUITE ET AUGMENTEE PAR LA STIMULATION DES RECEPTEURS ; UN CONTROLE EXCITATEUR TONIQUE DE LA LIBERATION DE DYN EXERCE PAR DES OPIOIDES ENDOGENES AGISSANT SUR DES RECEPTEURS SE MET EN PLACE. ENFIN, LA MORPHINE AUGMENTE LA LIBERATION DE ME ET REDUIT CELLES DE CGRP ET DYN. GLOBALEMENT, UNE HYPERSENSIBILITE DES RECEPTEURS DES OPIOIDES, NOTAMMENT DES RECEPTEURS , APPARAIT CHEZ LE RAT POLYARTHRITIQUE. ELLE POURRAIT S'EXPLIQUER PAR LE NOMBRE ACCRU DE CELLULES EXPRIMANT CES RECEPTEURS DANS LES GANGLIONS RACHIDIENS DORSAUX. L'HYPOACTIVITE ME-ERGIQUE CONJUGUEE A L'HYPERACTIVITE CGRP- ET DYN-ERGIQUES SPINALES POURRAIENT CONTRIBUER A L'HYPERALGESIE LIEE A LA POLYARTHRITE.PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF