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

Thermophysical law of cooling of forgings in a thermos

Рассмотрены условия теплообмена и закон охлаждения поковок в термосах - теплоизолированных коробах, которые начинают использовать на металлургических комбинатах для замедленного охлаждения поковок после их противофлокенного отжига в печах с целью уменьшения длительности последнего. Сделан расчет коэффициента теплоотдачи в двух вариантах: без учета и с учетом теплопроводности через металлические поперечины, скрепляющие стенки, между которыми заложена теплоизоляция. Оказалось, что отмеченная теплопроводность в три раза увеличивает коэффициент теплоотдачи αэфф от поверхности поковок. На основании кривых охлаждения поковок и установленного закона охлаждения найдено экспериментальное значение αэфф, оказавшееся весьма близким к расчетному. Полученные результаты будут использованы для разработки технологии противофлокенной обработки поковок в термосах на ОАО «Уральская кузница». Conditions of heat transfer and the law of cooling of forgings in thermoses are considered. (Thermoses are heat-insulated boxes that are beginning to be used at metallurgical plants for slower cooling of forgings after furnace anti-flake annealing to reduce the duration of the latter.) Heat transfer coefficient is calculated in two versions: without and with allowance for heat conduction through the metal of the cross-tie wail, between which lies insulation. It was found that this heat conduction increases the heat transfer coefficient from the surface of forgings αeff by a factor of three. Based on cooling curves of forgings and established law of cooling the experimental value of αe f f was found, which proved to be very close to the calculated one. These results will be used to develop the technology of anti-flake treatment of forgings in thermoses at JSC «Urals Stampings»

Change of electronic structure in iron containing interstitial atoms of hydrogen

Моделирование растворения малых примесей водорода в ОЦК-железе с помощью программного пакета WIEN2k показало, что разбиение обратного пространства на 27 k-точек и использование Kmax=5,0 a.e.-1 дают достаточно точные значения энергии растворения. Тетраэдрическая позиция оказалась на 0,46 эВ стабильнее октаэдрической. Энергия растворения водорода в ней составила 0,307 эВ без учета релаксации и 0,190 эВ с учетом релаксации решетки. Modeling of dissolution of small impurities of hydrogen in bcc iron by means of the WIEN2k software package has shown that splitting of reciprocal space into 27 k-points and use Kmax=5,0 a.u.-1 give exact enough values of dissolution energy. The tetrahedral position has appeared 0,46 eV more stable than the octahedral position. Dissolution energy of hydrogen in it is 0,307 eV and 0,190 eV for the unrelaxed and relaxed structures respectively

Low radioactive NH4_4Cl flux

International audienceIn this work, we report the production process of a low-radioactive NH4Cl inorganic flux. A γ-ray screening with ultra-low background HPGe spectrometer at LSM underground laboratory and ICP-MS elemental analysis have been performed to estimate the radioactivity level and composition of the final product

Role of short-range order in thermodynamics of binary substitutional solid solutions

Показано, что в области относительно высоких температур квазихимическая модель переходит в модель регулярных растворов, но у энергии взаимообмена возникает температурная зависимость. Получены приближенные формулы, отражающие эту зависимость. Обсуждена обратная задача. It is shown that at relatively high temperatures the quasi-chemical model changes into the regular solution model, but with temperature-dependent interchange energy. Approximate formulae reflecting this dependence are obtained and the inverse problem is also discussed