Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates

Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.     

Modified binary hammerhead ribozymes with high catalytic activity

A series of binary hammerhead ribozymes was designed and assessed in terms of cleavage activity and nuclease resistance. Enhanced nuclease resistance of binary ribozymes was achieved by incorporation of Z-modified nucleotides at the selective positions along with addition of 3'-3-linked thymidine cap. These modified binary ribozymes efficiently cleave 190-nucleotides long MDR1 mRNA fragment and display catalytic activity much higher then respective full-length analogs.     

Acceleration of impurity ions in the coulomb explosion of a relativistic spherical cluster with a complex ion composition

A semi-analytical model of the acceleration of light impurity ions to relativistic energies in the Coulomb explosion of a spherically symmetric homogeneous microtarget (cluster) consisting of ions of two types has been proposed. The spatiotemporal and spectral characteristics of accelerated impurity ions, which have a quasi-monochromatic spectrum, have been determined. The properties of high-energy impurity ions have been studied as functions of the total charge of the cluster and its ion composition.     

Realization of antimalarial measures in the period of eradication of the consequences of a flood in the Stavropol Territory in 2002

As the result of the high flood, an increase in the area of anopheligenic water reservoirs occurred on the inundated territories, which created favorable conditions for the proliferation of Anopheles mosquitoes, the vectors of malarial plasmodia, thus creating the threat of the formation of the local sources of malaria in case of its penetration from other regions unfavorable with respect to this disease. In the affected towns and regions hydrotechnical measures aimed at decreasing the surface of anopheligenic water reservoirs, as well as measures aimed at the decrease in the number of the larval and imaginal stages in the development of mosquitoes, were taken, which made it possible to prevent the probable epidemiological aggravations in malaria.     

Crimean-Congo hemorrhagic fever in Rostov Province: the epidemiological characteristics of an outbreak

The results of the epidemiological analysis of the outbreak of hemorrhagic fever which was caused by Crimean-Congo hemorrhagic fever virus and occurred during the period of July 3-19, 1999, in the Oblivskaya district of Rostov Province are presented. The specific epidemiological features of the outbreak have been determined. The possible versions of the appearance of the focus of infection and the role of Ixodes ticks in the circulation of the infective agent are discussed.     

The role of sodium-proton exchange in the regulation of the electric and contractile activity of smooth muscles

The Na+/H+-exchange inhibitor aethylisopropylamyloride was found to enhance the membrane resistance, the AP duration, and the duration of the guinea pig ureter's smooth muscle contraction. Tetraethylammonium and incubation in the Ca-free EG-TA-containing solution eliminated the activating effect of this inhibitor. Gramycidin A shortens the AP plateau. The Na+/H+-exchange mechanism seems to act under normal conditions. Alterations occurring in electrical and contractile activities of smooth muscle under the effect of the Na+/H+-exchange seem to result from the changes in the membrane Ca-dependent potassium conductivity.     

Substrate specificity of brain cholinesterase activity of evolutionary old species of fishes

An analysis of brain cholinesterase properties in 3 species of cartilaginous fishes and 1 species of chondrostei, was conducted for the first time. The skates brain enzymes, as to substrate specificity, are shown to be referred to acetylcholinesterases, and the shark brain cholinesterase - to atypical acetylcholinesterase. Kaluga brain cholinesterase, as to its substrate specificity, differes from brain enzymes of cartilaginous fishes. The differences in properties of the nervous tissue cholinestarase of the investigated fish species are the parameters of evolutionary divergence of species.