Effect of ABCB1 Gene Carriage and Drug-Drug Interactions on Apixaban and Rivaroxaban Pharmacokinetics and Clinical Outcomes in Patients with Atrial Fibrillation and Deep Vein Thrombosis

Aim. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.Material and methods. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.Results. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.Conclusion. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers

Development of methods for the preparation of radiopure ⁸²Se sources for the SuperNEMO neutrinoless double-beta decay experiment

A radiochemical method for producing 82Se sources with an ultra-low level of contamination of natural radionuclides (40K, decay products of 232Th and 238U) has been developed based on cation-exchange chromatographic purification with reverse removal of impurities. It includes chromatographic separation (purification), reduction, conditioning (which includes decantation, centrifugation, washing, grinding, and drying), and 82Se foil production. The conditioning stage, during which highly dispersed elemental selenium is obtained by the reduction of purified selenious acid (H2SeO3) with sulfur dioxide (SO2) represents the crucial step in the preparation of radiopure 82Se samples. The natural selenium (600 g) was first produced in this procedure in order to refine the method. The technique developed was then used to produce 2.5 kg of radiopure enriched selenium (82Se). The produced 82Se samples were wrapped in polyethylene (12 μm thick) and radionuclides present in the sample were analyzed with the BiPo-3 detector. The radiopurity of the plastic materials (chromatographic column material and polypropylene chemical vessels), which were used at all stages, was determined by instrumental neutron activation analysis. The radiopurity of the 82Se foils was checked by measurements with the BiPo-3 spectrometer, which confirmed the high purity of the final product. The measured contamination level for 208Tl was 8-54 μBq/kg, and for 214Bi the detection limit of 600 μBq/kg has been reached.</p

The Rectifying Contact of Hydrated Different Size YSZ Nanoparticles for Advanced Electronics

The paper considers the new effects of the nanoscale state of matter, which open up prospects for the development of electronic devices using new physical principles. The contacts of chemically homogeneous nanoparticles of yttrium-stabilized zirconium oxide (ZrO2&mdash;x mol% Y2O3, x = 0, 3, 4, 8; YSZ) with different sizes of 7.5 nm and 9 nm; 7.5 nm and 11 nm; and 7.5 nm and 14 nm, respectively, was studied on direct current using nanostructured objects in the form of compacts obtained by high-hydrostatic pressure (HP-compacts of 300MPa). A unique size effect of the nonlinear (rectifying-type contact) dependence of the electrical properties (in the region U &lt; 2.5 V, I &le; 2.7 mA) of the contact of different-sized YSZ nanoparticles of the same chemical composition is revealed, which indicates the possibility of creating semiconductor structures of a new type (homogeneous electronics). The electronic structure of the near-surface regions of nanoparticles of studied oxide materials and the possibility of obtaining specifically rectifying properties of the contacts were studied theoretically. Models of surface states of the Tamm-type are constructed considering the Coulomb long-range action. The discovered energy variance and its dependence on the curvature of the surface of nanoparticles made it possible to study the conditions for the formation of a contact potential difference in cases of nanoparticles of the same radius (synergistic effect), different radii (doped and undoped variants), as well as to discover the possibility of describing a group of powder particles within the Anderson model. The determined effect makes it possible to solve the problem of diffusion instability of semiconductor heterojunctions and opens up prospects for creating electronic devices with a fundamentally new level of properties for use in various fields of the economy and breakthrough critical technologies