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    Heterogeneity of the early outward current in ventricular cells isolated from normal and hypertrophied rat hearts

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    International audience1. The nature, magnitude and kinetics of the 4-aminopyridine-sensitive early outward current (Ito) were analysed in isolated ventricular myocytes from the septum, the apex and the left ventricular free wall of rat ventricles using the whole-cell voltage clamp method. The modulatory effect of pressure overload-induced cardiac hypertrophy on the regional variations of Ito was assessed in each topographical class of cells. 2. Voltage clamp experiments were performed at room temperature (20-25°C) in the absence of Na+ on both sides of the membrane and in the presence of 3 mM CoCl2. Ito was studied from a holding potential of-80 mV and determined by subtraction of total outward currents elicited by the same protocols in the presence of 3 mm 4-aminopyridine (4-AP) from those obtained in its absence. 3. In normal hearts, membrane passive properties were very similar in each topographical class of cells. Our results confirmed that the predominant early outward current in rat ventricular cells was 4-AP-sensitive, time and voltage dependent, and demonstrated that the magnitude of the current varied on a regional basis: current density of Ito in left ventricular free wall cells (30-1 +9-2 pA/pF at + 60 mV) was larger than in apex cells (20-2 + 1-7 pA/pF) or in septum cells (1 1-9 + 3-3 pA/pF). We noticed a larger variability in data from left ventricular free wall compared with other regions. 4. No shift in steady-state voltage dependence of Ito activation and inactivation was found. However, the maximal computed chord conductances were (in ,uS/pF): 0 18 + 0-07 for left ventricular free wall cells, 0-13 + 0-02 for apex cells, and 0-08 + 0-02 for septum cells. These findings might reflect a differential distribution in functional channel densities. 5. No difference in voltage-dependent Ito activation kinetics was present with respect to topography. However, inactivation time constants in septum were longer than those of both other groups. 6. Left ventricular hypertrophy was induced by abdominal aortic constriction and MS 156

    Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method.

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    To investigate the molecular basis of familial hypercholesterolemia (FH) in France, we applied the single strand conformation polymorphism (SSCP) method to the promoter region and the 18 exons of the low density lipoprotein receptor (LDLR) gene. Seven probands, 4 heterozygotes, 2 compound heterozygotes, and 1 homozygote, belonging to FH families were tested. In all cases, previous genetic analysis and/or LDL receptor fibroblast assay had shown that the disease was due to defects in the LDLR gene. Out of the nine mutations expected, one nonsense mutation in exon 2 and six missense mutations were identified in exons 3, 6, 8, 11, and 15. Two of the latter were found in exon 6. In each family, cosegregation of the base substitution and the disease was observed. Ninety-five control subjects were screened for the presence of the six missense mutations. None was detected, implying that the mutations identified are deleterious. Our results indicate that the SSCP analysis of amplified genomic DNA fragments can be successfully used to rapidly screen mutation containing exons in large genes. Furthermore, all these mutations are newly described and demonstrate heterogeneity of LDLR gene mutations responsible for FH in the French population, as in other reported Caucasian populations

    Response to Re: COVID-19, sweat, tears… and myopia?

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    [Psychopharmacotherapeutic guidelines : a challenge during health crisis]

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    International audienceThe construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward

    ARDS in patients with chest trauma: Better safe than sorry.

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    [Jugular venous and arterial concentrations of serum S100B protein in patients with severe head injury].

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    International audienceIt is important for physicians in intensive care units to be able to predict the presence and severity of central nervous system injury in patients with severe head injury (SHI). The extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury. However, only two studies were realized with jugular venous blood samples. The purpose of our study is to compare the interest between jugular venous and arterial concentrations evaluation of serum S100B protein in patients with SHI. We recruited 17 patients with a SHI, admitted to the intensive care unit. Paired arterial and jugular venous samples were taken at kinetically after injury. S100B median was 0.16 μg/L in arterial and 0.25 μg/L in jugular. This arterio-jugular difference is significant. However, there was any significant arterio-jugular difference in the patients group showing an unfavourable outcome or for the earlier samples (earlier than 24h). We observed there was no significant decrease of S100B in jugular, unlike in arterial, 24h after the head injury in the patients group showing an unfavourable outcome. Determination of S100B concentration in jugular samples appears to be better than in arterial to predict clinical outcome after brain injury

    [Endovascular treatment of SVC syndrome from neoplastic origin: a review of 34 cases].

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    International audienceTo report our experience with the treatment of 34 patients with SVC syndrome from neoplastic origin using the Wallstent

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