Структура распределения генетических детерминант эффективности и безопасности нестероидных противовоспалительных препаратов в российской популяции: фокус на CYP2C8, PTGS1 и PTGS2

The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) may be determined by the polymorphic nature of the CYP2C8, PTGS1 and PTGS2 genes.Objective: to analyze the nature of the distribution of CYP2C8*3 (rs10509681), CYP2C8*3 (rs11572080), PTGS1 (rs10306135), PTGS1 (rs12353214) and PTGS2 (rs20417) among residents of the North Caucasus.Patients and methods. The study involved 676 volunteers from Russian, Balkar, Kabardian and Ossetian ethnic groups. Carriage of polymorphic markers CYP2C8, PTGS1 and PTGS2 was determined using real-time polymerase chain reaction.Results and discussion. There were no significant differences between the groups in the rs10509681 and rs11572080 variants of the CYP2C8 gene. In all groups, the carriage of a combination of CYP2C8 and CYP2C9 alleles, encoding the phenotype of normal metabolizers, prevailed with a frequency of about 75% or more. The rs10306135 variant of the PTGS1 gene was found in 5.9% of Russians, 1.1% of Balkars, 5.3% of Kabardians, and 10.6% of Ossetians; variant rs12353214 – in 19.1; 9.4; 10.8 and 9.2%, rs20417 polymorphism of the PTGS2 gene in 0.4; 5; 2.8 and 3.1% respectively.Conclusion. The data obtained can be used to develop a more rational approach to the prescription of NSAIDs, taking into account the genetic characteristics of the local population in ethnic regions.Эффективность и безопасность применения нестероидных противовоспалительных препаратов (НПВП) может определяться полиморфной природой генов CYP2C8, PTGS1 и PTGS2.Цель исследования – анализ характера распределения CYP2C8*3 (rs10509681), CYP2C8*3 (rs11572080), PTGS1 (rs10306135), PTGS1 (rs12353214) и PTGS2 (rs20417) среди жителей Северного Кавказа.Пациенты и методы. В исследовании участвовали 676 добровольцев из русской, балкарской, кабардинской и осетинской этнических групп. Носительство полиморфных маркеров CYP2C8, PTGS1 и PTGS2 определялось с помощью полимеразной цепной реакции в режиме реального времени.Результаты и обсуждение. Значимых различий между группами по вариантам rs10509681 и rs11572080 гена CYP2C8 не получено. Во всех группах преобладало носительство комбинации аллелей CYP2C8 и CYP2C9, кодирующих фенотип нормальных метаболизаторов с частотой около 75% и более. Вариант rs10306135 гена PTGS1 выявлен у 5,9% русских, 1,1% балкарцев, 5,3% кабардинцев и 10,6% осетин; вариант rs12353214 – у 19,1; 9,4; 10,8 и 9,2%, полиморфизм rs20417 гена PTGS2 – у 0,4; 5; 2,8 и 3,1% соответственно.Заключение. Полученные данные могут быть использованы при разработке более рационального подхода к назначению НПВП, учитывающего генетические особенности местного населения в этнических регионах

Study of the stochastic clustering on the refractory material surface under the effect of plasma load in the PLM device

Tungsten plates were tested in stationary helium discharges in the PLM device. The duration of discharges in the PLM reached 200 minutes. A distinctive feature of this device is the stationary plasma confinement, which is advantageous for testing fusion materials, including materials of the divertor and first wall of a fusion reactor. During plasma irradiation in the PLM, the thermal load on the surface of the tested plates was more than 1 MW/m(2). The temperature of the tested plates amounted to 1000 degrees C and more. Stochastic nanostructures with dimensions of the structural elements of less than 50 nm, including fuzz-type structures, were observed on the processed surfaces of the samples

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Characterological features of otosclerosis in the Sverdlovsk region

In the Sverdlovsk region surdological consultations show 50 to 60 cases ot otosclerosis per year, which make up 0.37% of all cases of hearing ailments. Approximately 40 patients undergo surgery every year - sparing piston stapedoplastics without dismemberment of the anvil-stapes joint and the stapes muscle tendon. This method of treatment lessens labyrinth oppression in the post-operative period and prevents the possibility of necrosis of the long bone outgrowth of the anvil.На сурдологическом приеме в Свердловской области выявляется 50 - 60 случаев отосклероза в год, что составляет 0,37 % случаев тугоухости. Целью работы явилось изучение динамики развития отосклероза в Свердловской области, анализ результатов хирургического лечения больных и разработка рекомендаций по послеоперационной реабилитации. Около 40 больным ежегодно осуществляется хирургическое лечение - поршневая стапедопластика щадящим способом с сохранением наковальне-стремечкового сочленения и сухожилия стременной мышцы. Данный способ лечения уменьшает риск угнетения лабиринта в послеоперационном периоде и предотвращает возможность некроза длинного отростка наковальни

Pharmacogenetic Aspects of Postoperative Anesthesia with Ketoprofen in Cardiac Surgery Patients

Aim. Evaluation of the effect of polymorphisms of the CYP2D6, CYP2C8 genes on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.Material and methods. The study included 90 patients with an established diagnosis of coronary artery disease and postoperative period after cardiac surgery. Patients received ketoprofen 100 mg intramuscularly 2 times a day for 5 days. The intensity of pain was rated by Numeric Rating Scale. The severity of dyspepsia was assessed by the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. DNA was isolated from venous blood using an automated system. Single nucleotide polymorphisms CYP2C8 (C>T) rs11572080, CYP2D6*4 (1846G>A) rs3892097 were determined by the real-time polymerase chain reaction method.Results. In patients with genotypes GA and GG for the allelic variant CYP2D6*4, significant differences in the intensity of pain syndrome were found on days 4 and 5 of the postoperative period: 3,91±2,17 and 4,95±1,8 points (p=0,04), 3,52±1,95 and 4,5±1,7 points (p=0,04) in patients with GA and GG genotypes on days 4 and 5, respectively. In patients with the CT genotype for the CYP2C8 rs11572080, the severity of dyspepsia by GSRS was significantly higher than in patients with the CC genotype: 22,67±7,64 and 18,97±4,25 points, respectively.Conclusion. Patients with the GA genotype for the CYP2D6*4 allelic variant showed a lower intensity of pain syndrome than the GG genotype. In patients with the CT genotype for the CYP2C8 rs11572080, higher dyspepsia was revealed than in the CC genotype

Seed-mediated atomic-scale reconstruction of silver manganate nanoplates for oxygen reduction towards high-energy aluminum-air flow batteries

Aluminum-air batteries are promising candidates for next-generation high-energy-density storage, but the inherent limitations hinder their practical use. Here, we show that silver nanoparticle-mediated silver manganate nanoplates are a highly active and chemically stable catalyst for oxygen reduction in alkaline media. By means of atomic-resolved transmission electron microscopy, we find that the formation of stripe patterns on the surface of a silver manganate nanoplate originates from the zigzag atomic arrangement of silver and manganese, creating a high concentration of dislocations in the crystal lattice. This structure can provide high electrical conductivity with low electrode resistance and abundant active sites for ion adsorption. The catalyst exhibits outstanding performance in a flow-based aluminum-air battery, demonstrating high gravimetric and volumetric energy densities of similar to 2552 Wh kg(Al)(-1) and similar to 6890 Wh I-Al(-1) at 100 mA cm(-2), as well as high stability during a mechanical recharging process

Extreme photometric and polarimetric variability of blazar S4 0954+65 at its maximum optical and γ-ray brightness levels

In 2022 the BL Lac object S4 0954+65 underwent a major variability phase, reaching its historical maximum brightness in the optical and γ -ray bands. We present optical photometric and polarimetric data acquired by the Whole Earth Blazar Telescope (WEBT) Collaboration from 2022 April 6 to July 6. Many episodes of unprecedented fast variability were detected, implying an upper limit to the size of the emitting region as low as 10−4 parsec. The WEBT data show rapid variability in both the degree and angle of polarization. We analyse different models to explain the polarization behaviour in the framework of a twisting jet model, which assumes that the long-term trend of the flux is produced by variations in the emitting region viewing angle. All the models can reproduce the average trend of the polarization degree, and can account for its general anticorrelation with the flux, but the dispersion of the data requires the presence of intrinsic mechanisms, such as turbulence, shocks, or magnetic reconnection. The WEBT optical data are compared to γ -ray data from the Fermi satellite. These are analysed with both fixed and adaptive binning procedures. We show that the strong correlation between optical and γ -ray data without measurable delay assumes different slopes in faint and high brightness states, and this is compatible with a scenario where in faint states we mainly see the imprint of the geometrical effects, while in bright states the synchrotron self-Compton process dominates

Multiwavelength behaviour of the blazar 3C 279: decade-long study from γ-ray to radio

We report the results of decade-long (2008–2018) γ-ray to 1 GHz radio monitoring of the blazar 3C 279, including GASP/WEBT, Fermi and Swift data, as well as polarimetric and spectroscopic data. The X-ray and γ-ray light curves correlate well, with no delay ≳3 h, implying general cospatiality of the emission regions. The γ-ray–optical flux–flux relation changes with activity state, ranging from a linear to a more complex dependence. The behaviour of the Stokes parameters at optical and radio wavelengths, including 43 GHz Very Long Baseline Array images, supports either a predominantly helical magnetic field or motion of the radiating plasma along a spiral path. Apparent speeds of emission knots range from 10 to 37c, with the highest values requiring bulk Lorentz factors close to those needed to explain γ-ray variability on very short time-scales. The Mg II emission line flux in the ‘blue’ and ‘red’ wings correlates with the optical synchrotron continuum flux density, possibly providing a variable source of seed photons for inverse Compton scattering. In the radio bands, we find progressive delays of the most prominent light-curve maxima with decreasing frequency, as expected from the frequency dependence of the τ = 1 surface of synchrotron self-absorption. The global maximum in the 86 GHz light curve becomes less prominent at lower frequencies, while a local maximum, appearing in 2014, strengthens toward decreasing frequencies, becoming pronounced at ∼5 GHz. These tendencies suggest different Doppler boosting of stratified radio-emitting zones in the jet