[Kinetics of the lactone-carboxylate transition of hybrid camptothecin-netropsin molecules]. / Kinetika lakton/karboksilatnogo perekhoda gibridnoi molekuly kamptotetsin-netropsin.

The kinetics of the hydrolysis of the lactone ring of a hybrid molecule containing the molecules of the antitumor drug camptothecin and a derivative of the antibiotic netropsines, which is highly affine and specific to the DNA A-T sequences was investigated. It was shown that intramolecular interaction significantly slows down the rate of hydrolysis but does not change the equilibrium ratio of concentrations of the lactone and carboxylate forms of the camptothecin fragment of the hybrid molecule, which corresponds to the pH value. The use of intramolecular interaction for controlling the kinetics of the lactone/carboxylate transition makes it possible to create the drugs of the camptothecin family, which preserve the biologically active lactone form under the physiological conditions for a longer time and, therefore, are more effective as anticancer agents.

[Study of P-glycoprotein effect on the lipid monolayer properties by the Langmuir-Blodgett technique]. / Issledovanie metodom Lengmiura-Blodzhett vliianiia P-glikoproteina na svoistva lipidnykh monosloev.

Expression of the P-glycoprotein (Pgp) is proved to be one of the main reasons for the development of the multidrug resistance (MDR) phenotype by cancer cells. The effect of Pgp on the properties of lipid monolayers was studied using membrane fractions of sensitive and Pgp over-expressing multidrug resistance cancer cells containing 11, 24 or 32% of Pgp relative to the total content of membrane proteins. The effect of the Pgp membrane concentration on the properties of monolayers prepared from the membrane fractions was analyzed by the Langmuir-Blodgett method. The subphase composition was found to play a critical role in the stability of monolayers at any Pgp concentration. The optimal subphase comprised 10 mM tris-HCl buffer, pH 6.5, which made it possible to create very stable monolayer films with the pressure of collapse of about 30-40 mN/m. Monolayers prepared from membrane fractions of sensitive cells and cells containing the maximum (32%) amount of Pgp were found to be much more stable compared with fractions comprising 11 or 24% of Pgp. The analysis of monolayer compression dynamics revealed three distinct stages: (1) the self-organization of lipid molecules, which is characterized by an abrupt change of surface potential; (2) the compression of Pgp molecules at the constant potential of monolayers; and (3) the compression of lipid molecules, which is characterized by a quasilinear increase of both pressure and surface potential. It was shown that the specific surface areas of monolayers formed from sensitive and Pgp-enriched membranes containing 11 or 24% of Pgp are very similar, whereas the surface area of the monolayer formed from membranes containing 32% of Pgp is nearly 1.5-fold greater. This fact may reflect the effect of the threshold rearrangement of the structure of lipid molecules or cooperative modifications of lipid-Pgp interactions induced by the increase in the Pgp content from 24 to 32%. The effect of verapamil, a well-known Pgp modulator, on the properties of monolayers was studied. It was show that verapamil is able to induce changes of the surface of Pgp-containing monolayers, and these modifications are maximal at the Pgp:verapamil 1:1 molar ratio. The data present the first experimental evidence for the possible intervention of Pgp modulator into the processes of lipid-lipid or lipid-Pgp cooperative interactions within Pgp-enriched membranes.

[Standards for reviewing preparations in the study of ixodid tick nymphs by dark-field microscopy in borreliosis foci]. / Normy prosmotra preparatov pri issledovanii nimf iksodovykh kleshchei metodom temnopol'noi mikroskopii v ochagakh borreliozov.

The results of dark-field microscopy of 73 positive preparations from the unfed Ixodes persulcatus Sch. nymphs collected in the Perm Region of Russia have been analysed. The preparations were prepared by cutting the ticks placed into a physiological saline drop with needles. The numbers of Borrelia in the preparations varied from 0.4 to 173.6 per 100 microscopic fields (mean 22.9). It has been demonstrated that if all the standard conditions are fulfilled (magnification 600), drop volume 0.005 mil covering 18 x 18 mm glasses), it is practically impossible to overlook an infected nymph while examining 250 microscopic fields in such a preparation. The above-described conditions ensure valid reliable results of Borrelia calculation and their concentration measurements. The differences in the individual Borrelia infection rates in nymphs may be expressed by using the scale: low (up to 10), moderate (10.1-50), and high (above 50 Borrelia per 100 microscopic fields).