Drug-delivery Ca-Mg silicate scaffolds encapsulated in PLGA.

The aim of this work is to develop dual-functional scaffolds for bone tissue regeneration and local antibiotic delivery applications. In this respect, bioresorbable bredigite (Ca7MgSi4O16) porous scaffolds were fabricated by a foam replica method, loaded with vancomycin hydrochloride and encapsulated in poly lactic-co-glycolic acid (PLGA) coatings. Field emission scanning electron microscopy, Archimedes porosimetry and Fourier-transform infrared spectroscopy were used to characterize the structure of the scaffolds. The drug delivery kinetics and cytocompatibility of the prepared scaffolds were also studied in vitro. The bare sample exhibited a burst release of vancomycin and low biocompatibility with respect to dental pulp stem cells based on the MTT assay due to the fast bioresorption of bredigite. While keeping the desirable characteristics of pores for tissue engineering, the biodegradable PLGA coatings modified the drug release kinetics, buffered physiological pH and hence improved the cell viability of the vancomycin-loaded scaffolds considerably.

[Periprocedural management of anticoagulation in patients undergoing atrial fibrillation ablation]. / Anticoagulation péri-interventionnelle lors d'ablation de fibrillation auriculaire.

Catheter ablation of atrial fibrillation (AF) has been increasingly performed and has become a standard of care treatment option for drug-refractory symptomatic patients. However, this procedure has been associated with major complications, like thromboembolic or bleeding events. Optimal periprocedural anticoagulation strategy is essential for minimizing these complications. In this article, we review current anticoagulation strategies, including use of oral anticoagulation with Vit-K-Antagonists, as well as use of direct oral anticoagulants in the periprocedural settings of AF ablation.

[Catheter ablation of ventricular tachycardia]. / Katheterablation von ventrikulären Tachykardien.

Since the last decade important advances in diagnostics, understanding and the ablation techniques of ventricular tachycardia (VT) have been made. Both, patients with idiopathic VT and patients with structural heart disease and scar-related VT undergo VT ablation, that targets the underlying substrate responsible for VT development. Use of 3-dimensional electro-anatomic mapping systems enables identification of scar-related slow conduction sites, that are the critical players in scar-related VT. Successful mapping and ablation of mono- and polymorphic VT and ventricular fibrillation is achieved at specialized centers and is associated with reduced hospitalizations and mortality in patients with recurrent ICD shocks. This article describes the mechanisms of VTs, current mapping and ablation techniques and the results and complications of VT ablation at experienced VT ablation centers.

Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells.

The protein kinase Akt is activated by growth factors and promotes cell survival and cell cycle progression. Here, we demonstrate that Akt phosphorylates the cell cycle inhibitory protein p21(Cip1) at Thr 145 in vitro and in intact cells as shown by in vitro kinase assays, site-directed mutagenesis, and phospho-peptide analysis. Akt-dependent phosphorylation of p21(Cip1) at Thr 145 prevents the complex formation of p21(Cip1) with PCNA, which inhibits DNA replication. In addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2 inhibitory activity of p21(Cip1). Immunohistochemistry and biochemical fractionation reveal that the decrease of PCNA binding and regulation of Cdk activity by p21(Cip1) phosphorylation is not caused by altered intracellular localization of p21(Cip1). As a functional consequence, phospho-mimetic mutagenesis of Thr 145 reverses the cell cycle-inhibitory properties of p21(Cip1), whereas the nonphosphorylatable p21(Cip1) T145A construct arrests cells in G(0) phase. These data suggest that the modulation of p21(Cip1) cell cycle functions by Akt-mediated phosphorylation regulates endothelial cell proliferation in response to stimuli that activate Akt.