Genetic causes of resistance to vitamin K antagonists in Polish patients: a novel p.Ile123Met mutation in VKORC1 gene.

: Mutations in the genes encoding vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) largely contribute to the inter-individual variations in vitamin K antagonists (VKAs) dose requirements. Up to 50% of the dosage variability can be explained by genetic polymorphisms in these genes. We sought to identify the mutations responsible for VKA resistance in a series of Polish patients.

Bleeding predictors in patients following venous thromboembolism treated with vitamin K antagonists: Association with increased number of single nucleotide polymorphisms.

Introduction: Single nucleotide polymorphisms (SNP) in genes encoding proteins involved in metabolism and action of vitamin K antagonists (VKA) affect anticoagulation stability. We investigated how those polymorphisms influence bleeding rates in patients following venous thromboembolism (VTE).

Materials And Methods: In 324 patients following unprovoked VTE, 143 (44%) on warfarin and 181 (56%) on acenocoumarol, we recorded bleeds within the preceding 24 months.

Warfarin Metabolites in Patients Following Cardiac Valve Implantation: A Contribution of Clinical and Genetic Factors.

Introduction: Warfarin, a racemic mixture of S- and R-enantiomers, is the cornerstone of therapy in patients following cardiac valve replacement. S-warfarin is metabolized to 7-S-hydroxywarfarin by the cytochrome P450 isoform 2C9 encoded by CYP2C9 gene. R-warfarin is metabolized by multiple cytochromes P450.

An automated method for fibrin clot permeability assessment.

The fibrin clot permeability coefficient (Ks) is a useful measure of porosity of the fibrin network, which is determined by a number of genetic and environmental factors. Currently available methods to evaluate Ks are time-consuming, require constant supervision and provide only one parameter. We present an automated method in which drops are weighed individually, buffer is dosed by the pump and well defined clot washing is controlled by the software.

Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: a potential role of CYP4F2 and GGCX polymorphisms.

Introduction: VKORC1 and cytochrome CYP2C9 genetic variants contribute largely to inter-individual variations in vitamin K antagonists (VKAs) dose requirements. Cytochrome P450 4F2 isoform (CYP4F2), gamma-glutamyl carboxylase (GGCX) and apolipoprotein E (APOE) polymorphisms have been suggested to be of minor significance.

Materials And Methods: We sought to assess the impact of those polymorphisms on dose requirements in Central-Eastern European cohort of 479 patients receiving acenocoumarol (n=260) or warfarin (n=219).

Influence of fatty acids on mitochondrial metabolism of adipocyte progenitors and endothelial cells.

Context: In obesity, the cells are exposed to excessive amounts of nutrients, especially free fatty acids (FFAs) that induce a variety of metabolic changes.

Objective: We investigated the effect of FFAs on the mitochondrial function in different cell populations under stress conditions.

Methods: Human adipose tissue progenitor cells (SVF) or endothelial cells (HUVECs) were incubated with 30μM of selected saturated or unsaturated FFA for 24 h, at times supplemented with 5ng/mL tumour necrosis factor alpha (TNFα) for the last 4 h.