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The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point. Quantitative analysis was carried out by HPLC-tandem mass spectrometry. DHQ was very quickly absorbed by the gastrointestinal tract and quickly eliminated from the body. Repeated administration of DHQ did not lead to its accumulation in the body but had an effect on the enzymatic system with a subsequent increase in DHQ exposure (accumulation factor >1 by AUC after repeated administration). [ABSTRACT FROM AUTHOR]

The specific JNK inhibitor and NO donor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) demonstrated pronounced neuroprotective properties in an in vivo model of ischemic stroke in rats. The pharmacokinetic behavior of IQ-1 was studied in two animal species (rats, rabbits) after intravenous administration in a dose of 1 mg/kg. IQ-1 concentrations in venous blood plasma were measured by the liquid chromatography—tandem mass spectrometry method. The pharmacokinetics of IQ-1 was adequately described by the two-compartmental model. The calculated C0 for IQ-1 in rabbit and rat plasma were 2239.83±1229.55 and 1552.50±182.23 ng/ml, respectively. Two animal species are characterized by extensive tissue distribution of IQ-1 (Vss exceeded the total body water in rabbits and rats by 3.6 and 5.6 times, respectively) and high clearance values (88-94% of hepatic blood flow). [ABSTRACT FROM AUTHOR]

It is established that the fractions of the characteristic intensities of OH group vibrations attributed to intramolecular H-bonds of O3–H···O5 and O2–H···O6 types and intermolecular H-bonds of O6–H···O3 type of air-dried samples are 0.12, 0.1, and 0.2 for UAM-100 membrane and 0.12, 0.1, and 0.19 for UAM-50 membrane. It is shown that the characteristic intensity of the ν(OH) absorption band grows from 9.55 to 10.3 in a working sample of the UAM-100 membrane and a drop in the symmetry index to 0.75 was explained by the oxidation of aldehyde groups at C1 pyranose ring to the carboxyl (–COOH). It is proved that the fractions of intermolecular bonds of О6–Н···О3 and intramolecular H-bonds of O3–H···O5 and O2–H···O6 are 0.15, 0.09, and 0.13 that indicates not only the structural rearrangement of the hydrogen bond system but also possibly the formation of weak hydrogen bonds between hydroxyl groups of pyranose rings and molecules of the sedimentary layer. [ABSTRACT FROM AUTHOR]

In this work, the effects of adsorbed water on the structural evolution in the PVDF layer of composite hydrophobic MFFC-3 and hydrophilic MFFC-3G membranes were studied using ATR IR spectroscopy. It has been found that adsorbed water molecules initiate the conformational rearrangement of PVDF polymer molecules in the hydrophilic membrane layer, while the conformation of PVDF polymer molecules in the hydrophobic membrane layer does not change. The deconvolution of the absorption bands of the stretching vibrations of OH groups was carried out using four Gaussians. Based on the frequencies of the Gaussian peaks, the energy was calculated and the hydrogen bonds of adsorbed water were classified. It is shown that the structure of adsorbed water with hydrogen bond energies EOH = 42.8, 35.7, 17.9, and 14 kJ/mol are "clusters" with three or four hydrogen bonds. Energy values EOH = 17.9, 10.6, 16.8, and 14 kJ/mol correspond to OH bonds of dimeric and monomeric water molecules. It is concluded that the structure of adsorbed water in the PVDF layer can be characterized by a mixed model of hydrogen bonds, consisting of monomeric, dimeric molecules, and associated clusters with hydrogen bond energies from 10.6 to 42.8 kJ/mol. A comparative analysis of the ATR IR spectra of water-saturated samples indicates that the adsorbed water molecules in the PVDF "polymer–water" interfacial space of the hydrophobic membrane do not form a layer of bound water, while, in the hydrophilic membrane, water enters the structure of molecules, forming a layer of bound water. [ABSTRACT FROM AUTHOR]

A procedure is proposed for the extraction of 2,6-diisobornyl-4-methylphenol (IBP), the molecule with potential multi-target activity, and its active metabolite 2,6-diisobornyl-4-hydroxymethylphenol (IBP–OH) from human and rat plasma samples for further determination by liquid chromatography–tandem mass spectrometry. The solubility of IBP (in mg/mL) in various organic solvents is determined. In particular, the compound is readily soluble in chloroform (346 ± 14), methyl tert-butyl ether (98.6 ± 3.8), and ethyl acetate (96.8 ± 2.0). It is shown that the use of a mixture of chloroform and isopropanol (5 : 1, v/v) as an extraction system with simultaneous protein precipitation makes it possible to extract only 66 ± 10% of IBP, while the recovery of IBP–OH is 96 ± 7%. Pre-dilution of 200 µL of plasma with 300 µL saline increases IBP recovery to 100 ± 4%. Drying the extracts in a vacuum concentrator (air, 45°C) with the further reconstitution of the residues in 300 μL of acetonitrile facilitates the purification of biosamples and the preconcentration of analytes. The total sample preparation time does not exceed 70 min, and the duration of an analysis is 7 min, the injection volume is 2 µL. The procedure has been successfully tested on actual rat plasma samples after a single oral administration of IBP (10 mg/kg in oil) in the framework of pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Results of the structure evolution in MFFK-3 and PP-190 polymer films during the purification of water–organic solutions are described. X-ray diffraction analysis data show that significant changes in the microstructure of the working film samples occur in the intergranular amorphous phase due to the conformation of lamellar crystallites; in this case, the percentage of crystallinity of the MFFK-3 and PP-190 films decreases by 22 and 9%, respectively. Electron microscopy studies of the original and working samples of the MFFK-3 microfiltration membrane and the PP-190 prefilter on a JEOL JSM 6510 electron microscope at a magnification of 140–7000× are described. For the original and working samples of the MFFK-3 microfiltration membrane and the PP-190 prefilter, it is found that organic substances present in the feed solution are adsorbed on the surface of the active layer of the films. [ABSTRACT FROM AUTHOR]

The high level of mechanical characteristics of the mechanical parts produced related to an increase in their operation lifetime is embedded at the stage of metal forming. In this paper the boundary value problems of the modern theory of plasticity are considered with application to a thin layer, the formulation of which is based on the composition of a statically determined system including the partial differential equations of quasi-static equilibrium, the full plasticity condition, and the Cauchy equation for strains. The assumptions and constraints are based on the consequences of the well-known Prandtl solution formulated by Il'yushin. The problem is supplemented by nonsymmetric boundary conditions at the face ends. By means of variation of the current formulation of plastic flow problem for a thin layer, solutions are found, including the contact pressure and force parameters, for various generalizations of the Prandtl problem about the free spreading of a band occupying the linear domain and upset by flat dies performing the opposite motion. [ABSTRACT FROM AUTHOR]

Two-person games and cost/surplus sharing problems are worth of studying because they provide the basis for extension to the classes of such problems with variable population with the help of very powerful consistency properties. In this paper, a family of cost sharing methods for cost sharing problems with two agents [4] is extended to a class of solutions of two-person cooperative games that are larger than both costand surplus-sharing problems, since cooperative games have no constraints on the positivity of costs and surpluses. The tool for such an extension is a new invariance axiom—self-covariance [1]—that can be applied both to cost sharing methods and to cooperative game solutions. In particular, this axiom replaces the lower composition axiom, which is not applicable to methods used in profit-sharing problems. [ABSTRACT FROM AUTHOR]

We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism. [ABSTRACT FROM AUTHOR]

The reliability of liquid hobbing and the quality of castings is largely defined by the crystallization conditions. These conditions depend on changes in the liquid metal–dual phase zone–solid phase–tool system over time. A mathematical model of the liquid alloy solidification in the dual-phase zone during casting formation by liquid hobbing from the alloy АK7 is discussed. The solidification kinetics defining the structuring process is calculated by solving together the Fourier heat condition equations for the liquid melt, the dual-phase zone, and the hard crust. This study also evaluates the influence of the external pressure on the temperature fields and the time components of the solidification of thin-walled hollow castings. [ABSTRACT FROM AUTHOR]

A procedure for the determination of dexketoprofen trometamol in human plasma by liquid chromatography–mass spectrometry (HPLC–MS/MS) using ibuprofen as an internal standard was proposed and validated. The matrix effect on the analyte response value was estimated; its short-term and long-term stability in a biological matrix and an aqueous acetonitrile solution was investigated. In addition, the stability of the analyte after freezing and thawing of samples was studied. It was shown that the dilution of samples by one half does not affect the accuracy and precision of the analysis. The limit of detection and the lower limit of quantification were 0.01 µg/mL; the linearity range was 0.01–8.50 µg/mL (R2 = 0.9974); the total analysis time was 3.5 min. Intra- and interday accuracy values were in the ranges 96.66–100.00% and 94.97–97.92%, respectively. Sample preparation, including liquid–liquid extraction with ethyl acetate in an acidic medium, is simple and fast. The developed procedure was successfully tested on real plasma samples from healthy volunteers in the framework of a comparative study of the pharmacokinetics and bioequivalence of a generic drug. [ABSTRACT FROM AUTHOR]

We studied pharmacokinetics of a new analgesic based on a hexaazaisowurtzitane derivative (thiowurtzine, TWZ). A method for measuring TWZ in organs and tissues by HPLC/MS/MS was developed and validated. The sensitivity of the method under conditions of intragastric administration of TWZ to rats in a dose of 100 mg/kg is 0.5 ng/ml (calibration curve 0.5-400 ng/ml). The concentrations of the substance (Cmax) in the plasma, organs, and tissues of animals were 20-100 ng/ml, the time to reach the maximum concentration after a single dose (Tmax) was 2 h. The mean retention time of the substance in the body ranged from 5.67 to 17.15 h after administration. The highest concentrations were found in excretory organs (liver and kidneys), the substance also actively penetrated into muscle tissue. The medium concentrations were found in the brain and adipose tissue. The tropism to the heart tissues was minimal. [ABSTRACT FROM AUTHOR]

Acomparative study of the pharmacokinetics, bioequivalence, and safety of two marketed meldonium dosage forms Meldonium Organika (meldonium, 500 mg capsules, Organika Co., Russia) and Mildronate® (meldonium, 500 mg capsules, Grindex Co., Latvia) was carried out for a group of healthy volunteers in an open randomized 2-period cross-validation test. It was established that 90% confidence intervals for the ratio of geometric means of pharmacokinetic parameters AUC0-t (86.32 – 102.48%), AUC0-∞ (85.30 – 101.68%), and Cmax (84.92 – 101.76%) did not go beyond permissible limits of 80.00 – 125.00%. A conclusion was made about the bioequivalence of the aforementioned meldonium preparations based on the drug pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Cyclically changing thermomechanical loads causing the stress–strain state of dies are part of the crushing mechanism of surface and crack propagation in stress concentration zones. In order to evaluate the maximum stresses causing the critical strains of a die, a mathematical model is developed making it possible to predict the durability of a die's working parts. The durability of punches and matrixes is estimated by the average number of loading cycles up to the breakdown of the tool according to the criteria of low-cycle strength and plastic crushing. [ABSTRACT FROM AUTHOR]

This paper defines the self-covariance property for the solutions of transferable utility cooperative games (TU-games) as a weakening of their covariance. Self-covariant solutions are positively homogenous and satisfy a "restricted" translation covariance so that feasible shifts are only the solution vectors themselves and their multipliers. A description of all non-empty, single-valued, efficient, anonymous, weakly and self-covariant solutions in the class of twoplayer TU-games is given. As demonstrated below, among them there exist just three solutions admitting consistent extensions in the Davis-Maschler sense. They are the equal share solution, the standard solution, and the constrained egalitarian solution for superadditive two-player TUgames. For the third solution mentioned, characterizations of some consistent extensions to the class of all TU-games are given. [ABSTRACT FROM AUTHOR]

The rational use of metal is determined by the use of alternative methods to produce blanks, including forging a crystallizing metal. Application of external pressure to the melt during crystallization completely eliminates gas porosity, which improves the mechanical characteristics of the products, and substantially increases the crystallization rate, which improves the life of dies. The results of mathematical modeling underlie the selection of thermomechanical conditions for forging of metals (iron, steel, and aluminum alloys) that crystallize under pressure. A number of liquid metal forging processes are mastered. [ABSTRACT FROM AUTHOR]

A game with restricted (incomplete) cooperation is a triple ( N, v, Ω), where N represents a finite set of players, Ω ⊂ 2 is a set of feasible coalitions such that N ∈ Ω, and v: Ω → R denotes a characteristic function. Unlike the classical TU games, the core of a game with restricted cooperation can be unbounded. Recently Grabisch and Sudhölter [9] proposed a new solution concept-the bounded core-that associates a game ( N, v,Ω) with the union of all bounded faces of the core. The bounded core can be empty even if the core is nonempty. This paper gives two axiomatizations of the bounded core. The first axiomatization characterizes the bounded core for the class G of all games with restricted cooperation, whereas the second one for the subclass G ⊂ G of the games with nonempty bounded cores. [ABSTRACT FROM AUTHOR]

The flow of a thin plastic layer between two rigid plates approaching each other in the normal direction is considered. The kinematics of plastic layer flow is studied. An evolution equation describing the free boundary of the flow region is derived. The similarity solutions to this equation are analyzed. It is shown that the evolution equation can be reduced to a particular case of the nonlinear heat conduction equation. New exact particular solutions to the evolution equation are obtained using the variable separation method and the method of self-similar transformations. [ABSTRACT FROM AUTHOR]

The development of new shaping technologies for pipe blanks requires simulation of the stress and strain fields, which permits assessment of the limiting stress and strain values. The stress-strain state of a pipe blank in expansion (including nonuniform expansion) is analyzed in the present work. Joint solution of the equilibrium equations and plasticity condition is employed here; that is the traditional approach. Analytical dependences of the stress in the wall of the pipe blank on the technological parameters are obtained; the basic formulas for estimating the strain are also presented. Experiments confirm the results. [ABSTRACT FROM AUTHOR]

Dimensionless invariants for assessing the stress-strain state in specific stamping operations are analyzed. Their influence on the stability of plastic deformation is discussed. [ABSTRACT FROM AUTHOR]

The stress state of metal in the plastic region is considered. The type of stress state is characterized. The remaining plasticity of a deformable metal in axisymmetric extension is estimated on the basis of a phenomenological measure of the deformability. [ABSTRACT FROM AUTHOR]

Excretion of highly lipophilic (log P = 8.14) 4-methyl-2,6-diisobornylphenol (IBP) from rats was evaluated from renal excretion and elimination through the gastrointestinal tract (GIT) with feces and bile. A total of 81% of the administered dose was detected in feces after a single intragastric administration of IBP at a dose of 20 mg/kg in starch paste. The excretion kinetics through the GIT were represented by two elimination phases, i.e., rapid (within 24 h after IBP administration) accounting for elimination of 70% of the administered dose and slow (24 - 96 g) presumably related to elimination of IBP stored in tissues and organs. The bile IBP concentrations were an order of magnitude less than those in blood plasma. However, the times to reach the maximum concentration differed little. Renal excretion turned out to be minor despite the high kidney concentrations. Total elimination of IBP with urine for 4 d was ~0.01% of the administered dose. [ABSTRACT FROM AUTHOR]

The complex-forming properties of a silica gel-polyaniline composite with 8-hydroxyquinoline covalently immobilized by the Mannich reaction with respect to Pb(II), Cd(II), Cu(II), Ni(II), Co(II), Al(III), Fe(III), and Mo(VI) ions were studied. The resulting adsorbent had a high sorption capacity and satisfactory kinetic characteristics, which allowed us to use it for the separation or preconcentration of transition metal ions. Data on the composition and structure of the test metal complexes with 8-hydroxyquinoline immobilized on the composite surface were obtained from an analysis of electronic diffuse reflectance spectra and corresponding adsorption isotherms. [ABSTRACT FROM AUTHOR]

Covalent bonding of polyhexamethyleneguanidine amides of maleic and o-phthalic acids to the aminated silica surface was performed. The complexing properties of the obtained composite adsorbents with respect to Zn(II), Cu(II), Fe(III), Co(II), Pb(II), Ni(II), Mn(II), Mo(VI), and Cr(VI) ions were studied. The Mo(VI) and Cr(VI) reduction was detected on the modified silica surface bearing polyhexamethyleneguanidine amide with o-phthalic acid. The formation of different-ligand complexes with transition metal cations adsorbed on the synthesized composite surface was studied. [ABSTRACT FROM AUTHOR]

The possibility was determined for covalent binding of amide of maleic acid and polyhexamethyleneguanidine to a silica gel surface previously activated with cyanur chloride. Adsorption of Zn(II), Cd(II), Pb(II), Cu(II), Mn(II), Ni(II), Fe(III), and Co(II) cations from aqueous solution with a modified silica obtained was studied. The possibility of subsequent formation on the surface of mixed ligand complexes [ABSTRACT FROM AUTHOR]

Experiments of outbred rats with modeled xenobiotic load with acetylsalicylic acid (250 mg/kg for 7 days) revealed inhibition of mitochondrial respiration rate in states of rest and active phosphorylation, inhibition of succinate-dependent oxidation pathway, and a decrease in energization of organelles in the heart. For correction of the observed changes in energy production, succinic acid was preventively administered in a dose of 50 mg/kg for 7 days, which abolished the negative metabolic shifts in myocardial mitochondria. Comparison of pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinate treatment performed on rabbits revealed complete coincidence of the studied parameters, which attests to the possibility of prevention of mitochondrial dysregulations with this Krebs cycle intermediate. [ABSTRACT FROM AUTHOR]

We studied the effects of ethanol on the energy production system in the brain and liver in acute and chronic intoxications. Ethanol was found to inhibit mitochondrial respiratory chain in the liver. Acute ethanol intoxication results in uncoupling of oxidative phosphorylation. NAD-dependent respiration prevails in chronic intoxication. In the brain, ethanol exposure induces a compensated low-energy shift with activation of fast mitochondrial metabolic cluster and uncoupling of oxidative phosphorylation. [ABSTRACT FROM AUTHOR]

We compared bioavailability of 4-methyl-2,6-diisobornylphenol after single intragastric administration to rats in a dose of 200 mg/kg in starch suspension and in almond oil. Absorption of 4-methyl-2,6-diisobornylphenol in the gastrointestinal tract after administration in almond oil was much more efficient than after administration in aqueous starch mucus. [ABSTRACT FROM AUTHOR]

The sorption properties of silica gel with γ-mercaptopropyl groups chemically immobilized on its surface toward Pb(II), Cd(II), and Zn(II) at MPC levels in natural water in Ukraine were studied. The mutual effect of Pb(II), Cd(II), and Zn(II) in the sorption-X-ray fluorescence determination of their trace amounts with preextraction on silica gel with γ-mercaptopropyl groups was examined [ABSTRACT FROM AUTHOR]

Laws were determined for the formation of colored mixed-ligand complexes in the interactions of lead(II), cadmium(II), and zinc(II) coordinated to the surface of sulfur-containing chemically modified silicas with the following analytical reagents: 4-(2-pyridylazo)resorcinol, Eriochrome black, Sulfarsazen, and murexide. The structure of the mixed-ligand complexes was studied by diffuse-reflectance spectroscopy, and the applicability of these complexes to the sorption/photometric determination of the above metals was demonstrated. [ABSTRACT FROM AUTHOR]

We present the results of comprehensive investigations that include remote spectral measurements under field conditions, laboratory experiments, and mathematical simulation of the radiative regime of winter rye sowings. [ABSTRACT FROM AUTHOR]

Noncooperative games in normal form and in characteristic function form are considered. The supergame of the noncooperative game is defined as an infinite sequence of plays of the original game. The notions of strong Pareto equilibrium point (s.p.e.p.) and essential core are introduced. A relationship between the essential core of a noncooperative game and the set of s.p.e.p. of its supergame is asserted. This result is similar to that of Aumann for cooperative games without side payments. [ABSTRACT FROM AUTHOR]