Multicenter evaluation of the hemostatic activity of emicizumab in patients with severe hemophilia A.

Background: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis, and no laboratory assay has been validated to evaluate the hemostatic activity of emicizumab.

Objectives: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab.

Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass.

Background: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization.

TNF-α and IL-1β Exposure Modulates the Expression and Functionality of -Glycoprotein in Intestinal and Renal Barriers.

Inflammation is characterized by an increased secretion of proinflammatory cytokines known to alter the expression and functionality of drug transporters. Since -glycoprotein (-gp) plays a key role in the pharmacokinetics of several drugs, these modulations could further affect drug exposure. In this context, this study aims to investigate the impact of in vitro cytokine exposure on the expression and activity of -gp using the intestinal model Caco-2 and the human renal cells RPTEC/TERT1.

Tyrosine kinase inhibitors and direct oral anticoagulants: In vitro evaluation of drug-drug interaction mediated by P-glycoprotein.

Direct oral anticoagulants (DOACs) are now an option in the prevention and treatment of venous thromboembolic events (VTE) in patients with active cancer. Pharmacokinetics of DOACs are largely influenced by efflux transporters derived from ABC transporters, notably by P-glycoprotein (P-gp). The aim of this study was to assess the potential P-gp-mediated drug-drug interactions between 11 tyrosine kinase inhibitors (TKIs) with apixaban and rivaroxaban.

In Vitro Evaluation of P-gp-Mediated Drug-Drug Interactions Using the RPTEC/TERT1 Human Renal Cell Model.

Background And Objectives: In vitro evaluation of the P-glycoprotein (P-gp) inhibitory potential is an important issue when predicting clinically relevant drug-drug interactions (DDIs). Located within all physiological barriers, including intestine, liver, and kidneys, P-gp plays a major role in the pharmacokinetics of various therapeutic classes. However, few data are available about DDIs involving renal transporters during the active tubular secretion of drugs.

Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells.

Liquid deposit mimicking surface aerosolization in the airway is a promising strategy for targeting bronchopulmonary tumors with reduced doses of nanoparticle (NPs). In mimicking and studying such delivery approaches, the use of human in vitro 3D culture models can bridge the gap between 2D cell culture and small animal investigations. Here, we exposed airway epithelia to liquid-apical gadolinium-based AGuIX NPs in order to determine their safety profile.

Quantitative Flow Cytometric Evaluation of Oxidative Stress and Mitochondrial Impairment in RAW 264.7 Macrophages after Exposure to Pristine, Acid Functionalized, or Annealed Carbon Nanotubes.

Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on RAW264.

Effects of heparin and derivatives on podocytes: An in vitro functional and morphological evaluation.

Unfractionated heparin (UFH) and low molecular heparin derivatives (LMWH) display numerous biological properties in addition to their anticoagulant effects. However, due to the physicochemical heterogeneity of these drugs, a better understanding concerning their effects on human cells is clearly needed. Considering that heparins are mainly excreted by the kidney, we focused our attention on the effect of UFH and LMWH on human podocytes by functional and morphological/phenotypic in vitro analyses.

Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages.

To improve the biological properties of calcium phosphate (CaP) bone substitute, new chemical compositions are under development. In vivo such materials are subject to degradation that could lead to particles release and inflammatory reactions detrimental to the bone healing process. This study aimed at investigating the interactions between a murine macrophage cell line (RAW 264.

Quantification of nanoparticle endocytosis based on double fluorescent pH-sensitive nanoparticles.

Amorphous silica is a particularly interesting material because of its inertness and chemical stability. Silica nanoparticles have been recently developed for biomedical purposes but their innocuousness must be carefully investigated before clinical use. The relationship between nanoparticles physicochemical features, their uptake by cells and their biological activity represents a crucial issue, especially for the development of nanomedicine.

Evaluation of imatinib mesylate effects on glioblastoma aggressiveness with SPECT radiotracer 99mTc-(v)-DMSA.

In vitro and in vivo studies have demonstrated inhibition of glioblastoma growth by imatinib mesylate (Gleevec). Imatinib is an inhibitor of the tyrosine kinase activities of platelet-derived growth factor receptor (PDGF-r), which is involved in glioblastoma aggressiveness. In this study, we have investigated the link between 99mTc-(V)-DMSA, an imaging agent used in Single Photon Emission Computed Tomography, cellular accumulation and the biological effects of imatinib mediated by PDGF-r in a human glioblastoma cell line U87-MG.