Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels.

Small stress proteins [small heat shock proteins (sHsps)] are molecular chaperones that modulate the ability of cells to respond to oxidative stress. The current knowledge concerning the protective mechanism generated by the expression of mammalian heat shock protein-27 (Hsp27) that allows cells to increase their resistance to oxidative stress is presented. We describe the effects mediated by Hsp27 expression toward crucial enzymes such as glucose-6-phosphate dehydrogenase and glutathione reductase that uphold glutathione in its reduced form.

QT interval monitoring during clinical studies with mizolastine, a new H1 antihistamine.

Background: Some H1 antihistamines are at risk for rare but severe dysrhythmias due to an effect on the ventricular repolarization.

Objective: To present an overview of the QT interval monitoring performed during the clinical development of mizolastine, a new selective second-generation H1 antihistamine.

Methods: The ECGs database analysis of clinical studies conducted in volunteers and patients is summarized and focused on the results of reported studies and studies specifically designed for the assessment of the effect of mizolastine on cardiac repolarization, through the QT interval measurements.

Study of cardiac repolarization in healthy volunteers performed with mizolastine, a new H1-receptor antagonist.

Aims: The occurrence of serious dysrhythmias, such as torsades de pointes, with terfenadine and astemizole had led to a reexamination of the potential effect of H1 antihistamines on cardiac repolarization. Mizolastine is a potent, selective, nonsedating peripherally acting H1-receptor antagonist which is registered for rhinitis and urticaria at a recommended dose of 10 mg once daily. The present study was carried out to investigate the effects of therapeutic and supratherapeutic doses of mizolastine, on ventricular repolarization in healthy volunteers.

Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery.

The protective activity of small stress proteins (sHsp) against H2O2-mediated cell death in the highly sensitive murine L929 fibroblast has been analyzed. We report here that the human Hsp27- and murine Hsp25-mediated rise in glutathione (GSH) levels as well as the maintenance of this redox modulator in its reduced form was directly responsible for the protection observed at the level of cell morphology and mitochondrial membrane potential. sHsp expression also buffered the increase in protein oxidation following H2O2 treatment and protected several key enzymes against inactivation.

Safety and pharmacokinetics of a single oral dose of amisulpride in healthy elderly volunteers.

Objective: Amisulpride is a substituted benzamide neuroleptic, which binds selectively to dopamine D2 and D3 receptors, mainly in the limbic structures. States of delusion and agitation occur frequently in the population aged more than 65 years, especially in demented patients and this sometimes requires the use of neuroleptics. The objectives of this study were to determine the safety and the pharmacokinetic profile of 50 mg of amisulpride administered orally as a single dose to elderly volunteers.