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11 juillet 2013 4 11 /07 /juillet /2013 22:01
La presse spécialisée continue à s’interroger sur la question du traitement des dépressions pendant la grossesse ou/et la lactation : le médecin doit « peser les risques et les bénéfices » du traitement antidépresseur, rappelle ainsi l’éditorialiste de The American Journal of Psychiatry. Certaines études ont montré que « des femmes souffrant de dépression majeure durant la grossesse ont un risque accru d’avoir un enfant prématuré, ou avec un petit poids de naissance et un retard de croissance intra-utérin. » Le problème se complique en constatant que le recours aux antidépresseurs durant la grossesse se trouve, lui aussi, « associé à des résultats négatifs. » Par exemple, précise l’auteur, les femmes traitées par un inhibiteur sélectif de la recapture de la sérotonine (ISRS) ont un risque « deux à trois fois plus élevé d’avoir un enfant prématuré ou un bébé de faible poids à la naissance » que celles non exposées à ces médicaments au cours de leur grossesse.
Heureusement, certains indices demeurent relativement positifs : la comparaison avec les mères sans état dépressif majeur ni exposition aux antidépresseurs durant la grossesse ou le post-partum a montré que chez les femmes avec dépression périnatale, « ni l’existence d’une dépression majeure non traitée, ni l’administration d’un médicament de type ISRS n’ont une incidence significative sur le poids de l’enfant, sa taille, ni son périmètre crânien jusqu’à l’âge d’un an. »
Ces données sont plutôt rassurantes car on sait en effet que, « dans les premiers stades du développement infantile du moins », un retard de croissance de l’enfant peut entraîner, à terme, des conséquences « médicales et médico-sociales » : risque de déficience ou de handicap intellectuel, répercussion sur le niveau d’éducation et le statut professionnel ultérieur, intégration socio-familiale…
Le praticien et sa patiente se trouvent donc confrontés à une problématique de type « Charybde ou Scylla » où la décision de traiter une dépression puerpérale doit être soigneusement pesée, au cas par cas, en fonction du contexte particulier et du rapport escompté bénéfices/risques.


Dr Alain Cohen Publié le 11/07/2013

Parry BL : To treat or not to treat perinatal depression with antidepressant medication:
effects on infant growth. Am J Psychiatry 2013; 170:5, 453–454.
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10 juillet 2013 3 10 /07 /juillet /2013 21:10
Environ un enfant sur 150 souffre de troubles du spectre autistique (TSA) dans le monde. Plusieurs études suggèrent un rôle étiologique de la réponse immunitaire dans certaines formes de TSA. Une équipe de l’Université de Californie de Davies a démontré, lors de travaux précédents, que des auto-anticorps de la mère sont associés à une exacerbation de certains troubles chez les enfants autistes et reconnaissent des antigènes détectés dans la circulation fœtale. Ces auto-anticorps pourraient avoir un rôle étiologique dans les TSA d’après des études chez les rongeurs et le primate. Les chercheurs de Davies franchissent aujourd’hui une étape importante en identifiant des antigènes cibles des auto-anticorps maternels liés à l’autisme (AMA) et en caractérisant, pour les plus fréquents d’entre eux, les troubles comportementaux observés en corrélation chez les enfants. Des auto-anticorps ciblant des protéines cérébrales chez 23 % des mères d’enfants autistes L’étude, à caractère rétrospectif, inclut 246 mères d’enfants atteints de TSA et 149 mères d’enfants contrôles issues de la cohorte CHARGE (CHildhood Autism Risks from Genetics and Environment), et leurs enfants soit 246 souffrant de TSA ou d’autisme et 149 enfants de la population générale ayant un développement typique. Les chercheurs utilisent une approche protéomique avec détermination de la séquence des protéines en spectrométrie de masse en tandem, et confirmation par transfert de protéines (western blot). Ils identifient 7 principaux antigènes cibles des AMA qui sont des protéines cérébrales fœtales, les lactate déhydrogénases A et B, la cypine, la phosphoprotéine 1 induite par le stress (STIP1), les CRMP1 et CRMP2 (collapsin response mediator proteins) et la protéine YBX1 de fixation à YB (Y box). La réactivité maternelle à ces antigènes, individuellement ou en combinaison, est associée significativement à la survenue de TSA chez l'enfant (Odds ratio [OR] individuels [sauf pour l’association avec la cypine qui n’est pas significative] de 1,57 à 2,7 ; significativités p de 0,065 à <0,0001). Au total près de 23 % des mères d’enfant atteint de TSA ont une combinaison d’auto-anticorps ciblant 2 des 7 protéines ou plus (OR 21,7 intervalle de confiance à 95 % [IC 95%] 5,2-90, p <0,0001), contre 1 % des contrôles. Les enfants ont des troubles comportementaux plus marqués en cas d’auto-anticorps chez la mère Quelques corrélations sont notées entre le statut maternel en auto-anticorps réactifs à ces protéines et le comportement des enfants autistes ou TSA. Par rapport aux enfants atteints dont les mères n’ont pas cette réactivité, on observe chez ceux dont les mères sont positives des détériorations plus importantes à la sous-échelle des comportements stéréotypés du score ABC (Autism Behavior Checklist) : LDH (P = 0,024), CRMP1 (tendance à la significativité P = 0, 055), combinaison LDH et STIP1 (P=0,015), ou LDH/STIP1/CRMP1 (P = 0,007). En outre, le score ABC total reflète une dégradation globalement accrue chez les enfants des mères réactives pour la LDH et la CRMP1 (p=0,046) ainsi que pour la combinaison LDH/STIP1/CRMP1 (tendance à la significativité P=0,06). Chacun des antigènes mis en évidence ici est connu pour avoir un rôle critique dans le cerveau en développement. Des auto-anticorps maternels contre des protéines cérébrales fœtales pourraient donc conduire à des altérations neurodéveloppementales caractéristiques des TSA dans un sous-groupe de cas. De plus, avec leur spécificité exceptionnellement élevée >99 %, plusieurs profils en auto-anticorps pourraient constituer les premiers véritables biomarqueurs du risque de TSA, avec des applications cliniques dans le diagnostic précoce. Une étude prospective est en cours pour déterminer la valeur prédictive des AMA. Dominique Monnier 10/07/2013 Braunschweig D et coll. : Autism-specific maternal autoantibodies recognize critical proteins in developing brain Transl Psychiatry 2013, e277. Publication avancée en ligne le 9 juillet. doi:10.1038/tp.2013.50
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10 juillet 2013 3 10 /07 /juillet /2013 20:36
AuthorsTang H, et al. Show all Journal Gene Ther. 2013 Jul;20(7):770-8. doi: 10.1038/gt.2012.96. Epub 2013 Jan 3. Affiliation 1] University of Pittsburgh Cancer Institute, Departments of Surgery and Immunology, University of Pittsburgh, Pittsburgh, PA, USA [2] Institute of Clinical and Basic Medical Sciences, The First People's Hospital of Yunnan Province (The Kunhua Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China. Abstract Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycycline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing. PMID 23282955 [PubMed - in process] PMCID PMC3620681 [Available on 2014/1/1] Full text: Nature Publishing Group Related CitationsShow all Induction of the DNA damage response by IAP inhibition triggers natural immunity via upregulation of NKG2D ligands in Hodgkin lymphoma in vitro. Inhibition of Glycogen Synthase Kinase-3 Increases NKG2D Ligand MICA Expression and Sensitivity to NK Cell-Mediated Cytotoxicity in Multiple Myeloma Cells: Role of STAT3. Generation of soluble NKG2D ligands: proteolytic cleavage, exosome secretion, and functional implications. Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68. Shedding of endogenous MHC class I-related chain molecules A and B from different human tumor entities: Heterogeneous involvement of the "a disintegrin and metalloproteases" 10 and 17.
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10 juillet 2013 3 10 /07 /juillet /2013 08:37
Une patiente est décédée à Versailles (Yvelines) à la suite d’un bug informatique. Selon un rapport, ces dysfonctionnements sont fréquents. Le monde des blouses blanches est confronté à une épidémie de bugs informatiques qui provoquent des sueurs froides dans les salles de réanimation. Voire des vrais drames, comme à l’hôpital de Versailles (Yvelines). En novembre 2011, une patiente décède à la suite d’une allergie médicamenteuse. Or on sait désormais, grâce au rapport de la commission régionale de conciliation et d’indemnisation en date du 4 mars 2013, que ce décès est dû à une défaillance informatique. Lydia Cohen, victime d’un bug à Versailles « Des milliers de patients potentiellement en danger » Des défaillances partout en France Les sociétés informatiques se défendent Le document, que nous avons pu consulter, est encore plus inquiétant : il estime que la menace de défaillance est réelle dans de nombreux hôpitaux avec des conséquences potentiellement gravissimes pour les patients. Les experts écrivent noir sur blanc que « ces systèmes, en place dans de nombreux établissements, n’assurent pas une sécurité fine, en particulier dans le domaine des éventuelles allergies ». Leur certification sera effective… en 2015 Ce constat alarmant a poussé Alain-Michel Ceretti, fondateur de l’association de patients le Lien, à réclamer d’urgence à la ministre de la Santé, Marisol Touraine, de « retirer le plus vite possible les logiciels qui dysfonctionnent ». Contacté hier, le ministère a renvoyé la balle vers les agences de l’Etat. « Nous avons reçu plusieurs dizaines de signalements de dysfonctionnements sur ces logiciels depuis 2012 », reconnaît l’Agence nationale de sécurité du médicament. Certains font froid dans le dos. Ainsi, le fabricant du logiciel Chimio — destiné à prendre en charge les cancers — envoie un message pour signaler « qu’il a détecté un problème sur une version de Chimio 3.1 dans le report des réductions des doses d’une cure sur la cure suivante », et qu’il demande à ses clients « de le remplacer par la version suivante ». Au départ pourtant, l’idée de substituer les vieux dossiers papier était excellente. Un arrêté du ministère de la Santé d’avril 2011 préconisait sa généralisation. Cela faisait suite au drame du petit Ilyès, un enfant décédé à l’hôpital Saint-Vincent-de-Paul (Paris, XIVe), en raison d’une erreur de prescription médicamenteuse de l’infirmière. La désorganisation du service avait été pointée du doigt. « Faire confiance aux logiciels ne remplacera jamais les médecins », conclut avec bon sens le docteur Yves Rebuffat, anesthésiste, et vice-président du syndicat SNPHAR-E. La solution passe par une certification de ces centaines de logiciels. Elle sera effective… en 2015. MARC PAYET ET SÉBASTIEN RAMNOUX | Publié le 10.07.2013
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10 juillet 2013 3 10 /07 /juillet /2013 08:29
Des résidus de pesticides interdits ont été retrouvés dans des fraises cultivées en France et en Espagne, selon une étude de l'ONG française Générations futures, qui appelle à «une action forte pour faire rapidement cesser cette situation». Dans un communiqué publié mardi, l'ONG annonce avoir fait analyser 49 échantillons de fraises venues de France et d'Espagne et vendues dans des magasins de Picardie et de Haute-Normandie et a découvert que quatre de ces échantillons contenaient des pesticides interdits en Europe depuis plusieurs années et cinq autres échantillons comprenaient des pesticides interdits sur les fraises. La pression grandit sur les pesticides, impliqués dans des maladies graves Deux échantillons français contenaient de l'endosulfan, un insecticide interdit en Europe depuis 2005 et deux échantillons espagnols avaient du carbosulfan, insecticide interdit depuis 2007. Par ailleurs, trois échantillons français contenaient des substances autorisées en France mais pas sur la fraise: il s'agit de la flonicamide et de l'acétamipride. Deux autres échantillons espagnols contenaient aussi des substances autorisées en Espagne mais pas sur la fraise : le spirotetramat et le dimetomorphe. «C'est maintenant à la Répression des fraudes d'enquêter sur la présence de ces pesticides interdits», a commenté François Veillerette, porte-parole de Générations futures. «Nous voulons une explication», a-t-il ajouté. 91% des échantillons analysés contiennent des pesticides Générations futures s'élève par ailleurs contre la présence de pesticides, mais dans des limites autorisées, dans 91% des 49 échantillons analysés. «Nous n'avons relevé qu'un seul dépassement de Limite maximale en résidu (LMR) pour l'acrinathrine», indique l'ONG. Soulignant que parmi ces 37 molécules différentes retrouvées, huit sont des perturbateurs endocriniens, soupçonnés d'altérer la croissance, le développement, le comportement et d'être à l'origine de certains cancers, Générations futures appelle «nos dirigeants à prendre des mesures immédiates et fortes et à adopter une stratégie nationale ambitieuse sur les perturbateurs endocriniens.» Le gouvernement, qui a engagé une concertation nationale à ce sujet, doit prochainement présenter sa stratégie nationale sur les perturbateurs endocriniens Publié le 09.07.2013
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10 juillet 2013 3 10 /07 /juillet /2013 07:13
« L'exercice physique peut modifier l'activité des gènes » « les cellules adipeuses contiennent des gènes qui, lorsqu'ils s'expriment, favorisent de nombreuses maladies telles que le diabète et l'obésité », et fait savoir que « des chercheurs suédois ont cherché à savoir s'il était possible de modifier favorablement, grâce à la pratique régulière d'un sport, l'expression des gènes des cellules adipeuses ». « ont enrôlé 30 hommes, initialement peu actifs, proches de la quarantaine. La moitié d'entre eux avaient des antécédents familiaux de diabète. […] Une biopsie de graisse abdominale a été réalisée au début de l'étude puis 6 mois plus tard, et le niveau d'expression des gènes mesuré par la méthylation de l'ADN, synonyme de blocage de l'activité ». « Les résultats, publiés dans la revue PLOS Genetics, confirment l'amélioration attendue », observe le Pr Charlotte Ling, de l'Université de Lund (Malmö) : « C'est la première fois que l'on démontre que l'exercice physique, à raison de 2 séances par semaine pendant 6 mois, peut modifier la méthylation de plus de 7.000 gènes contenus dans les cellules adipeuses d'hommes d'âge moyen ». « Une amélioration qui se voit aussi dans des paramètres plus classiques, ajoute la chercheuse : «Réduction du rapport taille-hanches, augmentation de la condition physique, diminution de la pression artérielle et de la fréquence cardiaque» ». « pour le Pr Philippe Amouyel, directeur de l'unité Inserm Santé publique et épidémiologie moléculaire des maladies liées au vieillissement (CHU de Lille), «le profil de risque cardiovasculaire s'améliore indéniablement», mais il est trop tôt pour tirer des conclusions en ce qui concerne les modifications observées sur les gènes impliqués dans l'obésité et le diabète ».
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10 juillet 2013 3 10 /07 /juillet /2013 07:12
Innate immune recognition of the microbiota promotes host-microbial symbiosis Hiutung Chu & Sarkis K Mazmanian AffiliationsCorresponding author Nature Immunology 14, 668–675 (2013) doi:10.1038/ni.2635 Received 08 April 2013 Accepted 02 May 2013 Published online 18 June 2013 Pattern-recognition receptors (PRRs) are traditionally known to sense microbial molecules during infection to initiate inflammatory responses. However, ligands for PRRs are not exclusive to pathogens and are abundantly produced by the resident microbiota during normal colonization. Mechanism(s) that underlie this paradox have remained unclear. Recent studies reveal that gut bacterial ligands from the microbiota signal through PRRs to promote development of host tissue and the immune system, and protection from disease. Evidence from both invertebrate and vertebrate models reveals that innate immune receptors are required to promote long-term colonization by the microbiota. 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Commensal bacteria at the interface of host metabolism and the immune system Jonathan R Brestoff & David Artis AffiliationsCorresponding author Nature Immunology 14, 676–684 (2013) doi:10.1038/ni.2640 Received 19 March 2013 Accepted 10 May 2013 Published online 18 June 2013 The mammalian gastrointestinal tract, the site of digestion and nutrient absorption, harbors trillions of beneficial commensal microbes from all three domains of life. Commensal bacteria, in particular, are key participants in the digestion of food, and are responsible for the extraction and synthesis of nutrients and other metabolites that are essential for the maintenance of mammalian health. Many of these nutrients and metabolites derived from commensal bacteria have been implicated in the development, homeostasis and function of the immune system, suggesting that commensal bacteria may influence host immunity via nutrient- and metabolite-dependent mechanisms. 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The role of the immune system in governing host-microbe interactions in the intestine Eric M Brown, Manish Sadarangani & B Brett Finlay AffiliationsCorresponding author Nature Immunology 14, 660–667 (2013) doi:10.1038/ni.2611 Received 15 February 2013 Accepted 11 April 2013 Published online 18 June 2013 The mammalian intestinal tract harbors a diverse community of trillions of microorganisms, which have co-evolved with the host immune system for millions of years. Many of these microorganisms perform functions critical for host physiology, but the host must remain vigilant to control the microbial community so that the symbiotic nature of the relationship is maintained. To facilitate homeostasis, the immune system ensures that the diverse microbial load is tolerated and anatomically contained, while remaining responsive to microbial breaches and invasion. 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Control of pathogens and pathobionts by the gut microbiota Nobuhiko Kamada, Grace Y Chen, Naohiro Inohara & Gabriel Núñez AffiliationsCorresponding author Nature Immunology 14, 685–690 (2013) doi:10.1038/ni.2608 Received 27 February 2013 Accepted 09 April 2013 Published online 18 June 2013 A dense resident microbial community in the gut, referred as the commensal microbiota, coevolved with the host and is essential for many host physiological processes that include enhancement of the intestinal epithelial barrier, development of the immune system and acquisition of nutrients. A major function of the microbiota is protection against colonization by pathogens and overgrowth of indigenous pathobionts that can result from the disruption of the healthy microbial community. The mechanisms that regulate the ability of the microbiota to restrain pathogen growth are complex and include competitive metabolic interactions, localization to intestinal niches and induction of host immune responses. 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