12 research outputs found
325 Clinical presentation and long-term clinical outcomes of non immune, isolated atrioventricular block diagnosed in utero or early childhood
Étude des voies métaboliques de production d'hydrogène chez la microalgue Chlamydomonas reinhardtii et transposition en photobioréacteur
A partir du constat que la consommation énergétique et les risques environnementaux associés se sont considérablement accrus ces dernières années, des pistes nouvelles sont aujourd'hui étudiées pour développer l'utilisation d'énergies alternatives propres et renouvelables, et l'hydrogène semble dans ce contexte être une solution sérieuse. Sa production par voie photobiologique a fait l'objet de ce travail, dont l'objectif est d'exploiter les capacités photosynthétiques des microalgues afin d'élaborer à terme un procédé de production d'hydrogène à partir d'énergie solaire et d'eau sans dégagement parallèle de gaz à effet de serre. Des expérimentations pour la compréhension des phénomènes métaboliques intervenant dans la production d'hydrogène chez l'espèce Chlamydomonas reinhardtii - ont donc été menées et les résultats obtenus ont été transposés au niveau d'un photobioréacteur torique développé spécifiquement pour cette applicationConsidering the recent increase in energy consumption and associated environmental risks, new trails are followed today to develop the use of clean and renewable alternative energies, and in this context hydrogen seems to be a serious solution. The aim of this work is then to exploit microalgae photosynthetic capacities in order to devise a process for hydrogen production from only water and solar energy without greenhouse gas release. Experiments for the comprehension of the metabolic pathways implied in hydrogen production in Chlamydomonas reinhardtii species were thus carried out and the results obtained were scaled up to the level of a torus photobioreactor specifically developed for this application.NANTES-BU Sciences (441092104) / SudocNANTES-Ecole Centrale (441092306) / SudocSudocFranceF
Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii : Part I. Model development and parameter identification
International audienceChlamydomonas reinhardtii is a green micro-alga capable of turning its metabolism towards H 2 production under specific conditions. However this H 2 production, narrowly linked to the photosynthetic process, results from complex metabolic reactions highly dependent on the environmental conditions of the cells. A kinetic model has been developed to relate culture evolution from standard photo-synthetic growth to H 2 producing cells. It represents transition in sulfur-deprived conditions, known to lead to H 2 production in Chlamydomonas reinhardtii, and the two main processes then induced which are an over-accumulation of intracellular starch and a progressive reduction of PSII activity for anoxia achievement. Because these phenomena are directly linked to the photosynthetic growth, two kinetic models were associated, the first (one) introducing light dependency (Haldane type model associated to a radiative light transfer model), the second (one) making growth a function of available sulfur amount under extra-cellular and intracellular forms (Droop formulation). The model parameters identification was realized from experimental data obtained with especially designed experiments and a sensitivity analysis of the model to its parameters was also conducted. Model behavior was finally studied showing interdependency between light transfer conditions, photo-synthetic growth, sulfate uptake, photosynthetic activity and O 2 release, during transition from oxygenic growth to anoxic H 2 production conditions
Autotrophic and Mixotrophic Hydrogen Photoproduction in Sulfur-Deprived Chlamydomonas Cells
In Chlamydomonas reinhardtii cells, H(2) photoproduction can be induced in conditions of sulfur deprivation in the presence of acetate. The decrease in photosystem II (PSII) activity induced by sulfur deprivation leads to anoxia, respiration becoming higher than photosynthesis, thereby allowing H(2) production. Two different electron transfer pathways, one PSII dependent and the other PSII independent, have been proposed to account for H(2) photoproduction. In this study, we investigated the contribution of both pathways as well as the acetate requirement for H(2) production in conditions of sulfur deficiency. By using 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a PSII inhibitor, which was added at different times after the beginning of sulfur deprivation, we show that PSII-independent H(2) photoproduction depends on previously accumulated starch resulting from previous photosynthetic activity. Starch accumulation was observed in response to sulfur deprivation in mixotrophic conditions (presence of acetate) but also in photoautotrophic conditions. However, no H(2) production was measured in photoautotrophy if PSII was not inhibited by DCMU, due to the fact that anoxia was not reached. When DCMU was added at optimal starch accumulation, significant H(2) production was measured. H(2) production was enhanced in autotrophic conditions by removing O(2) using N(2) bubbling, thereby showing that substantial H(2) production can be achieved in the absence of acetate by using the PSII-independent pathway. Based on these data, we discuss the possibilities of designing autotrophic protocols for algal H(2) photoproduction
Identification of a strong genetic background for progressive cardiac conduction defect by epidemiological approach
International audienceINTRODUCTION:Progressive cardiac conduction defect (PCCD) is a frequent disease attributed to degeneration and fibrosis of the His bundle. Over the past years, gene defects have been identified demonstrating that PCCD could be a genetic disease. The aim of this study was to show a familial aggregation for PCCD using a genetic epidemiological approach to improve in fine genetic knowledge of the transmission of the disease.METHODS AND RESULTS:Using the French social security number, the authors have been able to determine the city of birth of the 6667 patients implanted with a pacemaker (PM) for PCCD between 1995 and 2005 in the western part of France. The authors then mapped the frequency of PM implantations for PCCD. A large heterogeneity of the frequency of the disease has been observed, with a frequency of 0.21% in the major city (Nantes) ranging up to 2.28% in specific parishes. Familial studies performed in the parishes with the highest frequency of the disease allowed the authors to identify five large families with PCCD. Clinical investigations demonstrated phenotype heterogeneity between families. Three patterns have been differentiated.CONCLUSIONS:This study demonstrates a disparate geographical repartition of the frequency of PM implantation in the area of the authors at least in part related to a hereditary factor. The identification of five large families affected by PCCD using epidemiological approach underlines the existence of a major genetic background in PCCD
0332 : QUIDAM Study: assessment of hydroquinidine therapy in the management of Brugada syndrome patients at high arrhythmic risk and implanted with an ICD
International audienceBackground During last decades, the knowledge in pathophysiological mechanisms of Brugada Syndrome improved. ICD implantation is the only effective treatment to decrease arrhythmic mortality in high-risk patients. Based on experimental and clinical data hydroquinidine seems to be a promising alternative for the management of ventricular arrhythmia and SCD but need to be evaluated. Methods Fifty patients were included in this French multicentric, randomised, double-blind study. Hydroquinidine or placebo treatment was given during two 18 months cross-over phases. Arrhythmic events, ECG parameters and clinical events were evaluated. Results Twenty-six (52%) patients completed the study. Thirty-four (68%) presented side effects, mainly gastrointestinal, related to hydroquinidine therapy in whom 13 had to stopped. One appropriate ICD shock, one ventricular fibrillation with self-resolution and one inappropriate ICD shock occurred in absence of hydroquinidine therapy. Not one of these event occurred under hydroquinidine. No statistical analysis has been done, regarding this low number of arrhythmic events. Hydroquinidine, at short (3 hours after first taking) or long-term, significantly lengthen QT interval, QTc (respectively 404 vs 417sm and 409 vs 433ms), Tpe and Tpe max (respectively 94,8 vs 106,6 ms and 89,4 vs 107,7ms) without any change on J-point elevation nor Tpe/QTc ratio. QTc interval was significantly longer (433 vs 417ms) during long than short-term treatment without any other effect on ECG parameters. Conclusion High rates of hydroquinidine side effects and low number of arrhythmic events give difficulties to conduct large studies to prove its efficiency in Brugada Syndrome. Hydroquinidine lengthens and increases the repolarisation dispersal, with electrocardiographic effects generally similar during short and long-term treatment. These considerations should not stop its use in daily clinical practice, especially for management of electrical storms. The author hereby declares no conflict of interestFigure Flow chart of QUIDAM stud
Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I
BACKGROUND
Progressive cardiac conduction disease (PCCD) is one of the most common cardiac conduction disturbances. It has been causally related to rare mutations in several genes including SCN5A, SCN1B, TRPM4, LMNA and GJA5.
METHODS AND RESULTS
In this study, by applying targeted next-generation sequencing (NGS) in 95 unrelated patients with PCCD, we have identified 13 rare variants in the TRPM4 gene, two of which are currently absent from public databases. This gene encodes a cardiac calcium-activated cationic channel which precise role and importance in cardiac conduction and disease is still debated. One novel variant, TRPM4-p.I376T, is carried by the proband of a large French 4-generation pedigree. Systematic familial screening showed that a total of 13 family members carry the mutation, including 10 out of the 11 tested affected individuals versus only 1 out of the 21 unaffected ones. Functional and biochemical analyses were performed using HEK293 cells, in whole-cell patch-clamp configuration and Western blotting. TRPM4-p.I376T results in an increased current density concomitant to an augmented TRPM4 channel expression at the cell surface.
CONCLUSIONS
This study is the first extensive NGS-based screening of TRPM4 coding variants in patients with PCCD. It reports the third largest pedigree diagnosed with isolated Progressive Familial Heart Block type I and confirms that this subtype of PCCD is caused by mutation-induced gain-of-expression and function of the TRPM4 ion channel
Characteristics and long-term outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study.
International audienceAIMS: The natural history of congenital or childhood non-immune, isolated atrioventricular (AV) block is poorly defined. METHODS AND RESULTS: We retrospectively studied 141 children with isolated, non-immune AV block diagnosed in utero, or up to 15 years of age, at 13 French medical centres, between 1980 and 2009. Patients with structural heart disease or maternal antibodies were excluded. Atrioventricular block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. There was progression to complete AV block in 29/41 (70.7%) patients with incomplete AV block over 2.8 ± 3.4 years (1-155 months), but all patients with incomplete AV block may not have been included in the study. Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean interval between diagnosis of AV block and pacemaker implants was 2.6 ± 3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a mean follow-up of 11.6 ± 6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy (DCM). The long-term follow-up was uncomplicated in 127 children (90.1%). CONCLUSION: In this large multicentre study, the long-term outcome of congenital or childhood non-immune, isolated AV block was favourable, regardless of the patient's age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few
Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block.
International audienceBACKGROUND: The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. METHODS AND RESULTS: A multicenter retrospective study (13 French referral centers, from 1980-2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0 ± 6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%-100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. CONCLUSIONS: ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block
Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation
International audienceBACKGROUND: Inherited cardiac conduction disease is a rare bradyarrhythmia associated with mutations in various genes that affect action potential propagation. It is often characterized by isolated conduction disturbance of the His-Purkinje system, but it is rarely described as a syndromic form. OBJECTIVES: The authors sought to identify the genetic defect in families with a novel bradyarrhythmia syndrome associated with bone malformation. METHODS: The authors genetically screened 15 European cases with genotype-negative de novo atrioventricular (AV) block and their parents by trio whole-exome sequencing, plus 31 Japanese cases with genotype-negative familial AV block or sick sinus syndrome by targeted exon sequencing of 457 susceptibility genes. Functional consequences of the mutation were evaluated using an in vitro cell expression system and in vivo knockout mice. RESULTS: The authors identified a connexin-45 (Cx45) mutation (p.R75H) in 2 unrelated families (a de novo French case and a 3-generation Japanese family) who presented with progressive AV block, which resulted in atrial standstill without ventricular conduction abnormalities. Affected individuals shared a common extracardiac phenotype: a brachyfacial pattern, finger deformity, and dental dysplasia. Mutant Cx45 expressed in Neuro-2a cells showed normal hemichannel assembly and plaque formation. However, Lucifer yellow dye transfer and gap junction conductance between cell pairs were severely impaired, which suggested that mutant Cx45 impedes gap junction communication in a dominant-negative manner. Tamoxifen-induced, cardiac-specific Cx45 knockout mice showed sinus node dysfunction and atrial arrhythmia, recapitulating the intra-atrial disturbance. CONCLUSIONS: Altogether, the authors showed that Cx45 mutant p.R75H is responsible for a novel disease entity of progressive atrial conduction system defects associated with craniofacial and dentodigital malformation