Bìofìzičnij Vìsnik

5-8

Authors: V.G. Knigavko, E.B.Radzishevskaya, M.A. Bondarenko, O.V. Zaytseva, O.P. Meshcheryakova

The relevance of the work is caused by the fact the cancer is a significant factor in human mortality, and cancer incidence is increasing worldwide. As a consequence, the study of the process of carcinogenesis in general and Second tumors, in particular, is an important issue for medical physics. The aim of this study was to uncover the regularities of the secondary tumors formation in cancer patients. Such a study should enable the solution of a number of related problems, viz. estimation of the distribution of the a-genes among humans, which damage seems to be one of the most essential factors of carcinogenesis. To achieve the aim of the study the probabilistic mathematical modeling was employed, resulting in the generation of the mathematical models, capable of estimating such probabilities: 1) probability of the second tumor formation in a patient at some age, provided that the first tumor is formed in this patient at certain age; 2) probability of two tumors formation in a patient at certain age. Furthermore, the proposed models enable employment of the statistics of the second tumors to refine the parameters of the carcinogenesis model. In conclusion, the probabilistic mathematical modeling allows evaluation of a number of important quantitative characteristics of the carcinogenesis.

16-29

Authors: D. M. Glibitskiy, O. A. Gorobchenko, O. T. Nikolov, A. V. Shestopalova, M. A. Semenov

Analysis of the patterns formed during the drying of biological fluids is employed for research and diagnosis in medicine and agriculture. Saline solutions of native proteins and DNA are characterized by zigzag patterns, which could be quantitatively described using the specific length of zigzags Lspecific. The aim of this study was to analyze a wide number of characteristics in order to identify those most sensitive to the effects of various physical and chemical factors on the protein structure. We examined the films prepared from salt solutions of bovine serum albumin (BSA) under varying conditions, viz.: a proportional change in the concentration of the components, substitution of NaCl with NaF and NaBr, temperature treatment, gamma irradiation, and addition of trivalent iron and biologically active flavin mononucleotide. The results revealed that the distribution of zigzag segment lengths was approximately lognormal, and the distribution of angles between the segments was approximately logistic. Two parameters appeared to be the most informative, viz. the average length of the segments, mainly depending on Cl– concentration, and the number of segments, depending on: Cl– concentration, concentration of the non-aggregated (but not necessarily unfragmented) protein, and the excess concentration of ions and low molecular weight compounds.

42-50

Authors: O.K. Pakulova, V.K. Klochkov, N.S. Kavok, I.A. Kostina, A.S. Sopotova, V.A. Bondarenko

Rare-earth-based nanoparticles (REB NPs) have been employed in molecular and cell biology due to their unique features. However, their interaction with biosystems and the influence on cell functioning are poorly understood. In this study effect of REB NPs (composed of dielectric nanocrystalls of cerium dioxide and orthovanadates of gadolinium and yttrium) with different form-factor as well as REB NPs-cholesterol complexes on the adaptation of human erythrocytes to hypertonic lysis (4 M NaCl) has been evaluated spectrophotometrically. It appeared that the degree of cell damage in the presence of REP NPs under hyperosmotic conditions varied with geometric parameters of REB NPs. Specifically: i) ultra-small (2 nm) spherical CeO2 or GdYVO4:Eu3+ NPs, penetrating through the plasma membrane, ii) grain-like (8´30 nm) GdVO4:Eu3+ NPs, adsorbed on the membrane surface, iii) and spherical GdYVO4:Eu3+ NPs-cholesterol complexes promoted cell adaptation to hypertonic lysis. Furthermore, the composition of nanoparticles affected their stabilizing effect on the cells. E.g., orthovanadate NPs at 0.1 g/l had the highest antihemolytic activity after short preincubation, while cerium dioxide NPs showed the same effect after prolonged preincubation. In conclusion, REB NPs promoted hyperosmotic cell adaptation by the two different mechanisms, viz. membrane stabilization by the adsorption on the cell surface and/or penetration into the cell.

5-10

Authors: V.M. Trusova

Using 8 web-algorithms, including Pasta2, AmylPred2, Tango, MetAmyl, Waltz, Aggrescan, BetaScan та FoldAmyloid, theoretical analysis of amino acid sequences of lysozyme, cytochrome c and N-terminal fragment of apolipoprotein A-I has been carried out, and amyloidogenic fragments of the proteins have been identified. The fragment was identified as amyloidogenic if it was determined by at least four algorithms. Comparative analysis of aggregation-prone regions of native and mutant proteins showed that that all mutants are characterized by same amyloidogenic segments as native proteins with the amyloidogenic potential being more pronounced for mutated proteins. It was shown that aggregation-prone regions of all proteins analyzed here, were rich in hydrophobic aliphatic (Ile, Val, Leu, Ala) and aromatic (Trp, Phe, Tyr) amino acid residues. Hydrophobic interactions were supposed to play key role in protein aggregation process.

19-26

Authors: K. А. Kuznetsov, О. Т. Nikolov, Y. G. Shckorbatov

Modulation of the biological effects produced by ionizing radiation (IR) using microwave and magnetic fields has important theoretical and practical applications. Response of human buccal epithelium cells to different physical agents (single and combined exposure to 0.5–5 Gy γ-radiation (60Co); microwaves with the frequency of 36.64 GHz and power densities of 0.1 and 1 W/m2, and static magnetic field with the intensity of 25 mT) has been investigated. The stress response of the cells was evaluated by counting heterochromatin granules quantity (HGQ) in the cell nuclei stained with orcein. Membrane permeability was assessed by the percentage of cells stained with indigocarmine (cells with damaged membrane). The increase of heterochromatin granules quantity (HGQ), i.e. chromatin condensation was detected at the doses of 2 Gy and higher. Changes in the cell membrane permeability to indigocarmine expressed the threshold effect. Membrane permeability reached the threshold at the doses of 2–3 Gy for the cells of different donors and did not change with the increase of the dose of γ-radiation. Cells obtained from different donors revealed some individual peculiarities in their reaction to γ-radiation. The static magnetic field and microwaves applied before or after γ-radiation decreased its impact, as revealed by means of HGQ assessment.

37-42

Authors: K. O. Vus, V. M. Trusova, G. P. Gorbenko, P. Kinnunen

Amyloid fibrils are the protein aggregates, whose formation is involved in the pathogenesis of Alzheimer’s disease, systemic amyloidosis, etc. Since there is no effective ways to treat these diseases, developing the new anti-amyloid drugs is of great importance. In this study a series of phospholipids have been tested for their ability to inhibit lysozyme and insulin amyloid fibril formation at acidic or neutral pH and elevated temperature. The lag time, elongation rate and fibrillization extent were estimated using Thioflavin T fluorescence assay. It is found that the oxidized and charged phospholipids, included into the liposomes, were the most effective inhibitors of the protein fibrillization. By comparing the magnitude and direction of the lipid effect in different lipid-protein systems it was concluded that the reduction of the amyloid fibril formation is governed by hydrophobic and specific liposome-protein interactions. It is hypothesized that the presence of the surface formed by the lipid polar heads is critical for reducing the protein fibrillization extent.

51-62

Authors: L.I. Kobylinska, T.S. Malyy, S.V. Apunevych, I.G. Mankovska, A.S. Voloshynovsky, O.M. Klyuchivska, R.S. Stoika, R.B. Lesyk, B.S. Zimenkovsky

This study was aimed at measurement of the transmission, luminescence spectra, and luminescence excitation spectra of three novel anticancer 4-thiazolidinone derivatives (ID 3288, ID 3882, ID 3833) in order to characterize the photoinduced cytotoxicity of these compounds against murineleukemia L1210 cell line. The luminescence and luminescence excitation spectra of the ID 3288, ID 3882 and ID 3833 powders differed significantly from those measured in aqueous solution. Furthermore, the luminescence of the ID 3288 powder had lower intensity as compared to that of the ID 3882 and ID 3833 powders. The luminescence of the ID 3882 aqueous solution showed the lowest intensity, while the ID 3833 demonstrated the highest intensity. The potential of application of the obtained results in the photodynamic anticancer chemotherapy has been discussed.

5-9

Authors: M.A. Bondarenko, V.G. Knigavko, N.O. Gordiyenko, O.V. Zaytseva, T.R. Kocharova

Carcinogenesis is subject of the research. The research aims at creating the mathematical model of carcinogenesis allowing assessing the distribution in human population of the genes which when damaged lead to oncology diseases. The main task is to build a probability mathematical model describing the quasistationary equilibrium of two contrary processes, and namely: 1) the process of reduction in population of the number of the aforesaid genes due to their mutative damage; 2) increase in population of the number of these genes due to the fact that persons with a few genes of the kind in their genotype acquire oncological diseases with higher probability at early stages of their lives and do not manage to reproduce themselves before they die, and so the growth of the total population size is more due to the reproduction of individuals with a high number of the a-genes. Assessment of the distribution of these genes in the population was carried out by determining the probability that a randomly selected individual from the population has one of the possible values (according to the literature, from 0 to 8) of the aforementioned genes.

21-27

Authors: D. M. Glibitskiy, G. M. Glibitskiy, M. A. Semenov, A. V. Shestopalova

Analysis of the patterns on the dried films of biological fluids is a promising avenue of medical diagnostics and biosensors development. The aim of this work was to study the effect of iron and copper ions on the quantitative characteristics of textures and zigzag patterns (Z-structures) observed on the films of saline solutions of bovine serum albumin (BSA). In the experiment, 0.5 mg/ml BSA, 20 mM/l NaCl, 0.05 mM/l CuCl2 and 0.2÷0.05 mM/l FeCl3 were used. For textures, the area and fractal dimension were estimated, and for zigzag patterns, area and the specific length of the Z-structures were estimated. The effect of iron and copper ions on the geometrical parameters of Z-structures was analyzed. Spatial distributions of the fractal dimension of texture and the specific length of Z-structures were analyzed. It was shown that using the product of all four parameters increases the sensitivity of the method compared to using only one of the parameters. The method can be used in pharmacology and medical biochemistry for screening drugs and chemical compounds by their degree of influence on biopolymers.

34-45

Authors: M. A. Popirny, O. T. Nikolov, E. V. Skrylnik

The purpose of this work lies in studying the composition, physical and chemical properties of the second fraction of the humic acid (HA2) extracted from the typical black soil, depending on the intensity of the soil tillage. Physical and chemical properties of HA2 have been studied by using ultraviolet (UV) spectroscopy, infrared (IR) spectroscopy and electron spin resonance spectroscopy (ESR). It has been demonstrated that increase of the tillage intensity of the typical black soil leads to decrease in the total carbon content and the HA2 content due to displacement of balance between the conjugated processes of humus synthesis and decay towards destruction. UV spectroscopy indicates intense absorption of humic acids in the near UV region, that corresponds to the donor-acceptor mechanisms π-π* electrons of double bonds. Maximum absorption has been observed for the HA2 isolated from the black soil tilled by plowing. Moreover, the highest content of oxygen-containing functional groups and low quantity of aliphatic structures has been observed in the same sample. It has been shown that the nature of paramagnetic centers of the HA2 represented by chelate paramagnetic Fe3+-complex formed by rearrangement π-electron system of double bonds, depending on the tillage intensity of the typical black soil. It has been found that plowing of the typical black soil enhances the number of paramagnetic centers in HA2.

5-15

Authors: O. V. Vashchenko, N. A. Kasian, V. A. Pashynska, M. V. Kosevich, A. O. Sadchenko, D. N. Tishko, T. V. Tishko, V. P. Titar, L. N. Lisetski

Intermolecular interactions between decamethoxinum (DEC) and acetylsalicylic acid (ASА) have been studied in the phospholipid-containing systems of escalating complexity levels. The host media for these substances were solvents, L-α-dipalmitoylphosphatidylcholine (DPPC) membranes, and samples of human erythrocytes. Peculiar effects caused by DEC-ASА interaction have been observed in each system using appropriate techniques: (a) DEC-ASА non-covalent complexes formation in DPPC-containing systems were revealed by mass spectrometry with electrospray ionization; (b) joint DEC-ASА action on DPPC model membranes led to increasing of membrane melting temperature Tm, whereas individual drugs caused pronounced Tm decreasing, which was demonstrated by differential scanning calorimetry; (c) deceleration of DEC-induced haemolysis of erythrocytes under joint DEC-ASА application was observed by optical microscopy.

24-33

Authors: A.S. Khrebtova, N.A. Gladkovskaya, E.G. Bereznyak, E.V. Dukhopelnikov, A.V. Fomin, A.V. Zinchenko

An interaction of actinocin derivatives Act II and Act III with DNA is studied by differential scanning calorimetry and spectrophotometry. The equilibrium concentrations of intercalational and external types of complexes in Act – DNA systems at different relative DNA concentration are calculated from spectrophotometric titration data. The binding parameters for each type of actinocin derivatives – DNA complexes are obtained. The heat capacity curves of Act – DNA complexes were obtained at different relative ligand concentrations. Calorimetric study achieved that intercalation binding type leads to increase of enthalpy, entropy and melting temperature of DNA, while the external type induces the rise of the helix thermal stability only. The comparison of helix – coil transition parameters of DNA in the complexes with actinocin derivatives and proflavine is performed. The effect of ligands on DNA melting parameters correlates to binding constants obtained by spectrophotometry.

43-51

Authors: N.О. Bodnarchuk, N.P. Harasym L.I. Petrukh, D.I. Sanagurski

The aim of work was to study the influence of flurenizyd (antimicrobial, antituberculosis, antichlamydia, immunomodulatory, antioxidant, hepatoprotective, anti-inflammatory medicine) on the antioxidant homoeostasis of loach embryos (Misgurnus fossilis L.) during early embryogenesis. Glutathioneperoxidase and glutathione-S-transferase activity was studied under the action of flurenizyd in concentrations 0.01; 0.05; 0.15; 1; 5; 15 mM, at the embryos of loach on the stage of development of the first (2 blastodmeres), fourth (16 blastodmeres), sixth (64 blastodmeres), eighth (256 blastodmeres), tenth (1024 blastodmeres) division of zygote (before the stage of de-synchronization). The two-factor analysis of variance was conducted to figure out the degree of flurenizyd influence, time of development and miscellaneous factors on activity of the enzymes of cell’s glutathione antioxidant defence system. It was shown that flurenizyd violates work of glutathioneperoxidase on all stages of development of loach embryos in particular predetermines the increase of their activity on the stage of development of 2, 16 and 256 blastomeres. The investigated antibiotic violates work of glutathione-S-transferase in the process of early embryogenesis of loach embryos Misgurnus fossilis L. In a maximal concentration (15 мМ) flurenizyd decreases activity of enzyme, starting from the initial stages of development of loach embryos. Two-factor analysis of variance indicated, that on glutathioneperoxidase and glutathione-S-transferase activity of loach embryos considerable influence is made by the miscellaneous factors, like external factors affecting the development of embryos. Time of development, in a greater degree, influences the work of glutathioneperoxidase during early embryogenesis, compared to flurenizyd that indicates indirect influence of the investigated antibiotic on glutathioneperoxidase. Considerable influence of flurenizyd on glutathione-S-transferase activity testifies its direct effect on a structure of the enzyme.