Generation of a heterozygous SCN5A knockout human induced pluripotent stem cell line by CRISPR/Cas9 edition.

Mutations leading to haploinsufficiency in SCN5A, the gene encoding the cardiac sodium channel Na1.5 α-subunit, are involved in life-threatening cardiac disorders. Using CRISPR/Cas9-mediated genome edition, we generated here a human induced-pluripotent stem cell (hiPSC) line carrying a heterozygous mutation in exon 2 of SCN5A, which leads to apparition of a premature stop codon.

Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex.

Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.

Aims: Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to β-adrenergic receptor (β-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functional role in large mammals.

Standard and Strain Measurements by Echocardiography Detect Early Overloaded Right Ventricular Dysfunction: Validation against Hemodynamic and Myocyte Contractility Changes in a Large Animal Model.

Background: Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment.

Methods: Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter).

[Cyclic nucleotide phosphodiesterases: role in the heart and therapeutic perspectives].

Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families that are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP, controlling specific cell functions in response to various neurohormonal stimuli. In the myocardium, the PDE3 and PDE4 families predominate, degrading cAMP and thereby regulating cardiac excitation-contraction coupling.

Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective.

Cyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby regulating multiple aspects of cardiac and vascular muscle functions. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families that are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP, controlling specific cell functions in response to various neurohormonal stimuli. In the myocardium and vascular smooth muscle, the PDE3 and PDE4 families predominate, degrading cAMP and thereby regulating cardiac excitation-contraction coupling and smooth muscle contractile tone.

Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors.

Aims: A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under β-adrenergic receptor (β-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors.

Differential regulation of cardiac excitation-contraction coupling by cAMP phosphodiesterase subtypes.

Aims: Multiple phosphodiesterases (PDEs) hydrolyze cAMP in cardiomyocytes, but the functional significance of this diversity is not well understood. Our goal here was to characterize the involvement of three different PDEs (PDE2-4) in cardiac excitation-contraction coupling (ECC).

Methods And Results: Sarcomere shortening and Ca(2+) transients were recorded simultaneously in adult rat ventricular myocytes and ECC protein phosphorylation by PKA was determined by western blot analysis.

[Leprosy and immune reconstitution syndrome in AIDS].

The immune reconstitution syndrome (IRS) has been typical of changes in the clinical presentations of opportunistic infections in AIDS patients since the introduction of HAART. Leprosy has joined the growing list of opportunistic infections associated with IRS.

[Delayed home screening of leprosy; experience of the screening team in Mayotte].

Mayotte, a French territory island located in the Indian Ocean near Madagascar, remains a leprosy endemic area. In 2006, leprosy was still a problem of public health with a prevalence of 3.94 per 10,000 inhabitants.

[Review: update on erythema nodosum leprosum].

Erythema nodosum leprosum (ENL) is an immunological reaction corresponding to vascularitis due to circulating immune complexes usually occurring during treatment of lepromatous leprosy. The precise mechanism underlying ENL are unclear but involvement of tumor necrosis factor alpha (TNFalpha) is suspected. Based on this suspicion pentoxifylline has been used instead of conventional treatments such as corticosteroids and thalidomide.

[Leprosy disclosed by polyarthritis].

Background: We report a case of leprosy observed in a French woman who had lived in Africa 30 years earlier. The clinical presentation was misleading, suggesting connective tissue disease.

Case Report: A 69-year-old woman was hospitalized in April 1996 for inflammatory joint disease.

The proportion of medical consultations motivated by skin diseases in the health centers of Bamako (Republic of Mali).

Background: Skin diseases have recently been identified as a public health problem in developing countries. However, most studies on skin diseases in developing countries, have been conducted in specialized dermatologic centers. Data on the proportion of consultations motivated by skin diseases in nonspecialized health centers in developing countries are scarce.

[Skin diseases disclosing human immunodeficiency virus infection in Mali].

Introduction: Several skin diseases are associated with human immunodeficiency virus (HIV) infection. In Africa, due to the difficult access to medical care and complementary examinations, certain diseases are of particular importance. In the present work, we report the skin manifestations observed in a dermatology unit of a large city in Africa over a 3 year period and which were the revealing signs of HIV infection.

Effect of HIV infection on leprosy: a three-year survey in Bamako, Mali.

From February 1992 until June 1994, all patients with histologically proven leprosy examined at the Leprology Unit of the Institut Marchoux in Bamako, Mali, were screened for HIV serology. In total, 740 leprosy patients have been tested; 553 known, previously treated leprosy cases and 187 new cases, mainly self-reporting and referred cases. The global seroprevalence in the sample was 1.

Determination of the minimal effective dosages of ofloxacin and sparfloxacin against M. leprae in the mouse foot pad system.

The minimal effective dosages (MEDs) of ofloxacin (OFLO) and sparfloxacin (SPFX) against 10 isolates of Mycobacterium leprae were measured in the mouse foot pad system. The drugs were administered either by gavage or by incorporation into the mouse diet in a range of concentrations. The results demonstrated that the MEDs of OFLO were 4 to 5 times higher than those of SPFX, thus confirming that, on a weight-to-weight basis, the anti-M.

[Bullous IgA linear dermatosis of children in Mali].

Introduction: Bullous IgA linear dermatosis is relatively frequent in children in Africa. The aim of this study was to evaluate the frequency of this disease among autoimmune bullous diseases in children in Mali.

Patients And Methods: Children with chronic bullous disease seen at the Marchoux Institute in Bamako and for whom direct immunofluorescence of the perilesional skin demonstrated immunoglobulin and/or complement deposits were included in the study population.