Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis

(1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransformation. (2) Materials and Methods: a two-center prospective non-randomized study of CPF pharmacokinetics with sequential enrollment of patients (n-33, mean age 9.03 years, male-33.36%), over a period from 2016 to 2021. All patients received tablets of the original CPF drug Cyprobay® at a dose of 16.5 mg/kg to 28.80 mg/kg. Blood sampling schedule: 0 (before taking the drug), 1.5 h; 3.0 h; 4.5 h; 6.0 h; 7.5 h after the first dosing. CPF serum concentrations were analyzed by high performance liquid chromatography mass spectrometry. The genotype of biotransformation enzymes was studied using total DNA isolated from whole blood leukocytes by the standard method. (4) Results: a possible relationship between the CA genotype of the CYP2C9 gene (c.1075A > C), the GG genotype of the CYP2D6*4 gene (1846G > A), the AG genotype of the GSTP1 gene (c.313A > G), the GCLC* genotype 7/7 and the CPF concentration in plasma (increased value of the area under the concentration–time curve) was established. Conclusions: Gene polymorphism of biotransformation enzymes may affect ciprofloxacin pharmacokinetics in children

Thermodynamic Studies and Optimization of the Method for Obtaining Neodymium Fluoride for the Production of Magnetic Sensors’ Sensitive Elements

Rare earth metals (REM) with magnetic properties find application in the recently developed high-tech industries. Sensor magnetic systems based on neodymium are increasingly in demand in modern engineering and geological surveys due to their favorable combination of properties of magnetic materials based on rare earth metals. One of the problems is to obtain high-quality materials for the production of such magnetic sensors. It should be noted that the high activity of REM does not allow obtaining master alloys and REM-based alloys from metallic materials; it is advisable to use halide compounds. This work discusses a method for producing neodymium fluoride from its oxide. REM fluorides can be obtained by fluorinating the oxides of these metals. Various fluorine-containing compounds or elemental fluorine are usually used as fluorinating reagents, which have their own advantages and disadvantages. The thermodynamic and technological analysis of neodymium fluoride production processes has shown the most acceptable fluorinating agent is ammonium hydrofluoride, which was used in this work. In order to increase the productivity and degree of chemical transformation, it was proposed to perform heating stepwise; i.e., at the initial stage, heat at a speed of 3 degrees per minute, after which the heating speed was reduced to 2 degrees per minute, and finally the speed was reduced to 1 degree per minute. Due to proposed heating mode, the same productivity and yield of chemical transformation were achieved, with an increased efficiency up to 30%, which can significantly reduce the cost of production. The obtained product is used in the production of neodymium-based alloys by metallothermic reduction of a mixture of fluorides. The sensor material obtained in this way is characterized by a low (less than 0.05%) oxygen content

Reactogenicity, safety and immunological efficacy of the live, pentavalent rotavirus vaccine in childhood immunization (results of the multicenter clinical trial)

Introduction. Rotavirus infection (RVI) is the most common cause of severe gastroenteritis in infants and young children worldwide: 600,000 children die annually; it accounts for approximately 3 million hospitalizations and 25 million physician visits each year among children. Preventive vaccination is universally recognized as the most effective measure against this infection.The purpose of the study is assessment of reactogenicity, safety and immunogenicity of the pentavalent live vaccine for RVI prevention in childhood immunization.Materials and methods. The first multicenter prospective, randomized, double-blind, placebo-controlled clinical trial of the pentavalent live vaccine for RVI prevention was conducted in Russia among healthy infants aged 2 months at the time of the first vaccination.Results. The vaccine had a satisfactory safety profile and high immunologic activity when administered in a threedose series for childhood immunization. No negative changes in the children’s health condition were detected during the surveillance monitoring.Discussion. The seroconversion rates, the seroconversion factor and the geometric mean antibody titer were consistent with the results obtained during trials of the above vaccine and its equivalents in other countries

Combination of 3‑<i>O</i>‑Levulinoyl and 6‑<i>O</i>‑Trifluorobenzoyl Groups Ensures α‑Selectivity in Glucosylations: Synthesis of the Oligosaccharides Related to <i>Aspergillus fumigatus</i> α‑(1 → 3)‑d‑Glucan

Stereospecific α-glucosylation of primary and secondary OH-group at carbohydrate acceptors is achieved using glucosyl N-phenyl-trifluoroacetimidate (PTFAI) donor protected with an electron-withdrawing 2,4,5-trifluorobenzoyl (TFB) group at O-6 and the participating levulinoyl (Lev) group at O-3. New factors have been revealed that might explain α-stereoselectivity in the case of TFB and pentafluorobenzoyl (PFB) groups at O-6. They are of conformational nature and confirmed by DFT calculations. The potential of this donor, as well as the orthogonality of TFB and Lev protecting groups, is showcased by the synthesis of α-(1 → 3)-linked pentaglucoside corresponding to Aspergillus fumigatus α-(1 → 3)-d-glucan and of its hexasaccharide derivative, bearing β-glucosamine residue at the non-reducing end

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| &lt; 0.8) in the transverse momentum range 1 &lt; pt &lt; 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Linear and non-linear flow mode in Pb–Pb collisions at √sNN = 2.76 TeV

The second and the third order anisotropic flow, V2 and V3, are mostly determined by the corresponding initial spatial anisotropy coefficients, ε2 and ε3, in the initial density distribution. In addition to their dependence on the same order initial anisotropy coefficient, higher order anisotropic flow, Vn (n > 3), can also have a significant contribution from lower order initial anisotropy coefficients, which leads to mode-coupling effects. In this Letter we investigate the linear and non-linear modes in higher order anisotropic flow Vn for n = 4, 5, 6 with the ALICE detector at the Large Hadron Collider. The measurements are done for particles in the pseudorapidity range |η| < 0.8 and the transverse momentum range 0.2 < pT < 5.0 GeV/c as a function of collision centrality. The results are compared with theoretical calculations and provide important constraints on the initial conditions, including initial spatial geometry and its fluctuations, as well as the ratio of the shear viscosity to entropy density of the produced system