Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

Objectives: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines.

Background: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes.

Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications.

The present study was performed to compare the influence of cytochrome P459 2C19 (CYP2C19) *2 and *17 genetic variants on the platelet response to clopidogrel and prasugrel maintenance therapy and to assess the relation between platelet reactivity and bleeding complications. A total of 730 patients were included (517 patients treated with clopidogrel 150 mg/day and 213 discharged with prasugrel 10 mg). Platelet reactivity was assessed at 1 month with the platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP).

CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome.

Objectives: The present study was designed to assess the effect of genetic variants on chronic biological response to prasugrel and bleeding complications.

Background: CYP2C19*2 loss-of-function allele and CYP2C19*17 gain-of-function allele have been linked with response to clopidogrel, but preliminary data did not show any significant influence of these alleles on prasugrel effect.

Methods: A total of 213 patients undergoing successful coronary stenting for acute coronary syndrome and discharged with prasugrel 10 mg daily were included.

Platelet reactivity in diabetic patients undergoing coronary stenting for acute coronary syndrome treated with clopidogrel loading dose followed by prasugrel maintenance therapy.

Background: Diabetes has been identified as a risk factor for impaired clopidogrel response, and these patients might have greater benefit with new P2Y12 blockers such as prasugrel. The present study was designed to assess response to thienopyridine in diabetic patients undergoing PCI for ACS.

Methods And Results: 107 diabetic patients undergoing PCI for ACS were included and treated by clopidogrel 600 mg loading dose and switched to prasugrel 10mg daily after PCI.

An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development.

Epileptic encephalopathies comprise a heterogeneous group of severe infantile disorders for which the pathophysiological basis of epilepsy is inaccurately clarified by genotype-phenotype analysis. Because a deficit of GABA neurons has been found in some of these syndromes, notably in patients with X-linked lissencephaly with abnormal genitalia, epilepsy was suggested to result from an imbalance in GABAergic inhibition, and the notion of "interneuronopathy" was proposed. Here, we studied the impact of a polyalanine expansion of aristaless-related homeobox (ARX) gene, a mutation notably found in West and Ohtahara syndromes.

Cell-autonomous and cell-to-cell signalling events in normal and altered neuronal migration.

The cerebral cortex is a complex six-layered structure that contains an important diversity of neurons, and has rich local and extrinsic connectivity. Among the mechanisms governing the cerebral cortex construction, neuronal migration is perhaps the most crucial as it ensures the timely formation of specific and selective neuronal circuits. Here, we review the main extrinsic and extrinsic factors involved in regulating neuronal migration in the cortex and describe some environmental factors interfering with their actions.

A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A.

Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown.