Cognitive deficits and impaired hippocampal long-term potentiation in K ATP-induced DEND syndrome

ATP-sensitive potassium (

Reversible changes in pancreatic islet structure and function produced by elevated blood glucose

Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than KATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized

Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of Adult Mice

Tamoxifen (Tm)-inducible Cre recombinases are widely used to perform gene inactivation and lineage tracing studies in mice. Although the efficiency of inducible Cre-loxP recombination can be easily evaluated with reporter strains, the precise length of time that Tm induces nuclear translocation of CreERTm and subsequent recombination of a target allele is not well defined, and difficult to assess. To better understand the timeline of Tm activity in vivo, we developed a bioassay in which pancreatic islets with a Tm-inducible reporter (from Pdx1PB-CreERTm;R26RlacZ mice) were transplanted beneath the renal capsule of adult mice previously treated with three doses of 1 mg Tm, 8 mg Tm, or corn oil vehicle. Surprisingly, recombination in islet grafts, as assessed by expression of the β-galactosidase (β-gal) reporter, was observed days or weeks after Tm treatment, in a dose-dependent manner. Substantial recombination occurred in islet grafts long after administration of 3×8 mg Tm: in grafts transplanted 48 hours after the last Tm injection, 77.9±0.4% of β-cells were β-gal+; in β-cells placed after 1 week, 46.2±5.0% were β-gal+; after 2 weeks, 26.3±7.0% were β-gal+; and after 4 weeks, 1.9±0.9% were β-gal+. Islet grafts from mice given 3×1 mg Tm showed lower, but notable, recombination 48 hours (4.9±1.7%) and 1 week (4.5±1.9%) after Tm administration. These results show that Tm doses commonly used to induce Cre-loxP recombination may continue to label significant numbers of cells for weeks after Tm treatment, possibly confounding the interpretation of time-sensitive studies using Tm-dependent models. Therefore, investigators developing experimental approaches using Tm-inducible systems should consider both maximal recombination efficiency and the length of time that Tm-induced Cre-loxP recombination occurs

Case Report - Cardiomyopathie hypertrophique néonatale de diagnostic étiologique difficile

La cardiomyopathie hypertrophique néonatale est une entité rare, hétérogène regroupant plusieurs formes cliniques et donc de diagnostic étiologique difficile. Nous rapportons l’observation d’un nouveau né issu d’une grossesse gémellaire, ayant présenté à la naissance un tableau d’insuffisance cardiaque, l’échocardiographie avait conclut à une cardiomyopathie hypertrophique obstructive. Le bilan étiologique était négatif notamment une mère non diabétique. L’évolution était favorable avec régression de l’hypertrophie 2 semaines après la naissance. L’étiologie finalement suggérée était une cardiomyopathie secondaire à l’injection anténatale de corticoïdes dans le but d’accélérer la maturation pulmonaire. L’établissement par les sociétés savantes d’un consensus de bilan étiologique minimal standard selon une chronologie bien déterminée serait d’un grand apport dans la prise en charge de cette anomalie

Prevalence of Brugada-type ECG pattern and early ventricular repolarization pattern in Tunisian athletes

Sana Ouali1, Helmi Ben Salem1, Sami Hammas1, Elyes Neffeti1, Fahmi Remedi1, Abdallah Mahdhaoui2, Essia Boughzela1, Rafik Mankai31Department of Cardiology, Sahloul Hospital, Sousse, Tunisia; 2Department of Cardiology, Farhat Hached, Sousse, Tunisia; 3Central Sports Medicine Centre of El Menzah, TunisiaIntroduction: No data regarding the prevalence of the Brugada-type electrocardiogram (ECG) pattern and the early ventricular repolarization pattern (ERP) in the North African population were available. The aims of this study were to determine the frequency of Brugada-type ECG pattern and ERP in Tunisia and to evaluate ECG descriptors of ventricular repolarization in a population of athletes.Methods: Over a 2-year period, resting 12-lead ECG recordings were analyzed from athletes (n = 540; 348 males; age 18.3 ± 2.4 years). Brugada-type ECG pattern was defined as Type 1, 2, or 3, and ERP was characterized by an elevation of the J point in the inferior and/or lateral leads. The population was divided into three groups of athletes: ERP group; Brugada-type ECG pattern group; and control group, with neither ERP nor Brugada ECG pattern. Clinical and electrocardiographic parameters were compared among the study groups.Results: Nine subjects (1.66%) had a Brugada-type ECG pattern. None of them had the coved-type, 3 (0.6%) had the Type 2, and 6 (1.1%) had the Type 3. All subjects were asymptomatic. A Brugada-type ECG pattern was observed in seven males. No female had the Type 2 Brugada ECG pattern. ECG parameters were similar among Brugada-type ECG pattern and control athletes. ERP (119 subjects, 22%) was obtained in 98 males. Heart rate was lower, the QRS duration shorter and QT and Tpeak–Tend intervals were longer in ERP than control groups.Conclusion: The results indicate that the frequency of the Brugada-type ECG pattern and ERP were respectively 1.66% and 22.00% in athletes, being more prevalent in males. The ERP group experienced shorter QRS duration and longer Tpeak–Tend interval than in the control population.Keywords: J wave, ERP athletes, T wav