34 research outputs found
N011 Culture et délivrance au niveau du tissu cardiaque de cardiomyocytes issus de cellules souches embryonnaires humaines au moyen de matrices tridimensionelles poreuses à base de polysaccharides
Un intĂ©rĂȘt particulier a Ă©tĂ© portĂ© ces derniĂšres annĂ©es Ă la thĂ©rapie cellulaire rĂ©paratrice cardiaque. Les cellules souches embryonnaires humaines (hES) sont une source prouvĂ©e de cardiomyocytes et les premiĂšres donnĂ©es in vivo suggĂšrent leurs capacitĂ©s fonctionnelles Ă type dâeffet pacemaker ou rĂ©paratrices dâinfarctus du myocarde. Nous avons Ă©tudiĂ© un mode de dĂ©livrance des cellules hES dans le tissu cardiaque basĂ© sur une matrice 3D servant de support Ă la fois pour la culture des cellules et pour leur implantation au contact du myocarde.Des matrices poreuses de polysaccharides (pullulane et dextrane) ont Ă©tĂ© prĂ©parĂ©es par rĂ©ticulation chimique permettant de rĂ©aliser des films avec des pores de 100 Ă 200 microns. Les matrices ont Ă©tĂ© recouvertes de diffĂ©rentes protĂ©ines; les cellules hES indiffĂ©renciĂ©es ont Ă©tĂ© cultivĂ©es sur fibroblastes murins, en milieu supplĂ©mentĂ© avec du sĂ©rum knock-out et du FGF2. Dans une premiĂšre partie in vitro, nous avons mis en Ă©vidence par q-RT-PCR, observation microscopique et imagerie confocale, la diffĂ©renciation en cardiomyocytes de cellules hES directement cultivĂ©es dans les matrices en prĂ©sence dâun milieu inducteur de diffĂ©rentiation; les matrices permettaient aussi la culture, lâexpansion et la survie Ă long terme de parties battantes obtenues Ă partir de corps embryoĂŻdes issus dâhES et isolĂ©es manuellement. Nous avons ensuite Ă©tudiĂ© le devenir des cellules hES dans un modĂšle de lĂ©sions cardiaques par dĂ©pĂŽt de films poreux cellularisĂ©s sur les cĆurs infarcis de souris NOD SCID. Lâidentification est confirmĂ©e pour les cardiomyocytes issus dâES dâune lignĂ©e de cellules hES H9 GFP+ ainsi que dâune lignĂ©e de cellules hES dans laquelle lâexpression de la GFP est sous contrĂŽle dâun promoteur spĂ©cifique du tissu cardiaque, Nkx2.5. Nous avons ainsi mis en Ă©vidence la migration des cellules ES Ă diffĂ©rents stades de diffĂ©renciation Ă partir des matrices 3D vers les souris NOD SCID ainsi que leur diffĂ©renciation en cardiomyocytes. Les donnĂ©es de PCR quantitative sur la base du transgĂšne GFP mettent en Ă©vidence une meilleure survie des ES dĂ©livrĂ©es par lâintermĂ©diaire des matrices 3D en comparaison avec une administration directe. Une Ă©tude fonctionnelle comparative est en cours
Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype
Objective: Neurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants in NEFH have recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC).
Methods: In this large observational study, we present phenotypeâgenotype correlations on 30 affected and 3 asymptomatic mutation carriers from eight families.
Results: The majority of patients presented in adulthood with motor-predominant and lower limb-predominant symptoms and the average age of onset was 31.0±15.1 years. A prominent feature was the development of proximal weakness early in the course of the disease. The disease progressed rapidly, unlike other Charcot-Marie-Tooth disease (CMT) subtypes, and half of the patients (53%) needed to use a wheelchair on average 24.1 years after symptom onset. Furthermore, 40% of patients had evidence of early ankle plantarflexion weakness, a feature which is observed in only a handful of CMT subtypes. Neurophysiological studies and MRI of the lower limbs confirmed the presence of a non-length-dependent neuropathy in the majority of patients.
All families harboured heterozygous frameshift variants in the last exon of NEFH, resulting in a reading frameshift to an alternate open reading frame and the translation of approximately 42 additional amino acids from the 3' untranslated region (3âČ-UTR).
Conclusions: This phenotypeâgenotype study highlights the unusual phenotype of CMT2CC, which is more akin to spinal muscular atrophy rather than classic CMT. Furthermore, the study will enable more informative discussions on the natural history of the disease and will aid in NEFH variant interpretation in the context of the diseaseâs unique molecular genetics
Coronary artery surgery: cardiotomy suction or cell salvage?
Coronary artery bypass grafting (CABG) today results in what may be regarded as acceptable levels of blood loss with many institutions avoiding allogeneic red cell transfusion in over 60% of their patients. The majority of cardiac surgeons employ cardiotomy suction to preserve autologous blood during on-pump coronary artery bypass surgery; however the use of cardiotomy suction is associated with a more pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. This leads to a tendency to increased blood loss, transfusion requirement and organ dysfunction. Conversely, the avoidance of cardiotomy suction in coronary artery bypass surgery is not associated with an increased transfusion requirement. There is therefore no indication for the routine use of cardiotomy suction in on-pump coronary artery surgery
Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors
Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)
Efficacité différentielle de l'aprotinine et de l'acide tranexamique selon le type de chirurgie cardiaque
Objective: To analyse the effectiveness and toxicity of aprotinin compared with tranexamic acid according to the type of cardiac surgery: coronary artery bypass or valve surgery. Setting: A French general hospital of 700 acute beds. Method: A retrospective study of benefit/risk ratio of aprotinin in adult cardiac surgery, which compare two periods (2000 vs. 2005) where mainly only anti-fibrinolytic treatment changed. Aprotinin was compared with tranexamic acid according to the type of surgery: coronary artery bypass or valve surgery. This study was conducted before the marketing application authorization of aprotinin was suspended. Main outcome measure: Blood loss during the first 24 h after intervention. The second outcome measures were mortality and spontaneous declaration of adverse drug effects. Results: Six hundred and seventy-six patients were included in our study. For coronary artery bypass, aprotinin appeared to be more effective than tranexamic acid to reduce blood loss after intervention (719 ± 41 mL vs. 947 ± 34 mL; p < 0.0001 during the first 24 h). For valvular surgery, there was no difference between the two anti-fibrinolytic drugs to decrease postoperative bleeding. No acute toxic effects were reported through the data bank of the department of cardiovascular surgery. Conclusions: Our preliminary results indicated that tolerance to aprotinin was as good as for tranexamic acid. Concerning its effectiveness, results differed according to the type of surgery. The benefit/risk ratio of aprotinin in our study was positive for coronary artery bypass surgery, but the use of tranexamic acid in valve surgery was as efficient and much less expensive than aprotinin. Our data suggest that even if the marketing application authorization of aprotinin was suspended, this drug should have clinical benefit for coronary artery bypass surgery. Therefore, our study shows that it is difficult to reach an unequivocal result about the use of aprotinin. Further investigations of aprotinin must be conducted in different types of cardiac surgery and among different patients populations like in pediatrics in which its efficiency and safety profiles are not clear. © 2010 Elsevier Masson SAS. All rights reserved.Objectifs Ătude de lâefficacitĂ© et de la toxicitĂ© de lâaprotinine comparativement Ă lâacide tranexamique selon deux types de chirurgie : pontage coronarien ou chirurgie valvulaire. Contexte Centre hospitalier français de 700 lits. Patients et mĂ©thode Ătude rĂ©trospective mesurant le rapport bĂ©nĂ©fice/risque de lâaprotinine utilisĂ©e chez lâadulte en chirurgie cardiaque comparant deux pĂ©riodes (2000 versus 2005) dont les changements en pratique concernaient essentiellement les traitements hĂ©mostatiques. Lâaprotinine a Ă©tĂ© comparĂ©e Ă lâacide tranexamique selon deux types de chirurgie : le pontage coronarien et la chirurgie valvulaire. Cette Ă©tude a Ă©tĂ© effectuĂ©e avant le retrait de commercialisation de lâaprotinine. Principal critĂšre dâĂ©valuation Volume de perte sanguine durant les premiĂšres 24 heures aprĂšs lâintervention. Les critĂšres secondaires dâĂ©valuation Ă©taient le taux de mortalitĂ© et dâeffets indĂ©sirables. RĂ©sultats Six cent soixante-seize patients ont Ă©tĂ© inclus dans lâĂ©tude. Dans le cas du pontage coronarien, lâaprotinine semblait diminuer les pertes sanguines plus efficacement que lâacide tranexamique (719 ± 41 mL versus 947 ± 34 mL ; p < 0,0001 durant les premiĂšres 24 heures). En chirurgie valvulaire, aucune diffĂ©rence significative nâa Ă©tĂ© observĂ©e entre les deux hĂ©mostatiques quant Ă la diminution des saignements postopĂ©ratoires. Aucun effet indĂ©sirable aigu nâa Ă©tĂ© relevĂ© dans la base de donnĂ©es du dĂ©partement de chirurgie cardiaque. Conclusions Cette Ă©tude a montrĂ© que lâaprotinine et lâacide tranexamique ont un profil de tolĂ©rance similaire. Concernant lâefficacitĂ©, nos rĂ©sultats diffĂšrent selon le type de chirurgie. Le ratio bĂ©nĂ©fice/risque est en faveur de lâaprotinine pour le pontage coronarien, mais lâutilisation de lâacide tranexamique en chirurgie valvulaire est aussi efficace mais beaucoup moins chĂšre que lâaprotinine. Nos rĂ©sultats suggĂšrent que mĂȘme si lâaprotinine a Ă©tĂ© retirĂ©e du marchĂ©, elle pouvait prĂ©senter un intĂ©rĂȘt clinique dans le pontage coronarien. Par consĂ©quent, notre Ă©tude a montrĂ© quâil est difficile dâaboutir Ă un rĂ©sultat univoque concernant lâutilisation de lâaprotinine. Dâautres investigations seraient nĂ©cessaires afin dâĂ©tudier lâaprotinine dans dâautres types de chirurgie cardiaque et chez diffĂ©rentes populations de patients, notamment chez les enfants dont les profils dâefficacitĂ© et de tolĂ©rance de lâaprotinine ne sont pas encore Ă©tablis
Effective limb transduction with phenotypic correction after injection of rAAV8-U7snRNA in GRMD dogs
International audienc
Biodistribution and shedding of rAAV8-U7 snRNA vectors after locoregional injection in the forelimb of GRMD dogs
National audienc