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Biomedical subjects

L V Iurchenko

Publications and source records attributed to L V Iurchenko.

9 recordsLinked to original sources

[The use of controlled hypotonia in endonasal microsurgical interventions on the paranasal sinuses in patients with chronic rhinosinusitis].

The technique of controlled hypotonia was developed for adequate management of anesthesia in endonasal microsurgical interventions on the paranasal sinuses in patients with chronic rhinosinusitis. A total of 92 patients with chronic polypous rhinosinusitis aged 18 to 65 years were operated using the following variants of anesthesia: local, local in combination with neuroleptanalgesia and/or ataralgesia with controlled hypotonia, endotracheal oxide-fluoroxene and endotracheal oxide-oxygen anesthesias with neuroleptanalgesia and/or ataralgesia with controlled hypotonia. This was achieved with clofelin. Controlled hypotonia reduces blood loss in endonasal microsurgery on the paranasal sinuses in patients with chronic polypous rhinosinusitis compared to patients unexposed to controlled hypotonia.

Adolescent↗

[Suppression of transcription of influenza virus RNA by oligonucleotide derivatives].

The inhibitory effects of oligonucleotide derivatives on the transcription of virus RNA in an in vitro system and synthesis of virus proteins was studied. Oligonucleotide derivatives d(T)3, d(T)4, d(T)8, d(T)10, d(CCAAACA), d(TCACCCTC), d(TTCCCATT), d(AATACTCT) and d(TGACCCTCTTCCCATT), that bear residues of ethidium, deuteroporphyrin and its complexes with Fe3+, hemin, cholesterol, deuterocholesterol, estrone and naphthoquinone at the 5'-end phosphate and/or at the 3'-end phosphate were studied. Unmodified oligonucleotides and their derivatives had a negligible effect on the synthesis of cellular proteins, but did inhibit the synthesis of influenza virus proteins. The majority of structural modifications increased the inhibitory effect of oligonucleotides. It was shown that the oligonucleotide derivatives carrying residues of porphyrin, quinone, ethidium, cholesterol, deuterotestosterone and estrone at concentrations near 10 mM inhibit virus development to 50-80%. A clear inhibitory effect (20-25%) of deuteroporphyrin, cholesterol and ethidium derivatives was revealed even at concentration 0.1 mM. The obtained results testified that the inhibition of influenza virus development is dependent on the interaction of oligonucleotide derivatives with the transcription complex proteins.

Animals↗

[Suppression of translation in vitro of the mRNA of the M1 protein of influenza virus using antisense oligonucleotides].

Effect of antisense oligonucleotides on the in vitro translation of the influenza virus M1 protein mRNA was investigated. The most efficient arrest of mRNA translation was achieved by simultaneous action of two or three oligonucleotides (14-16-mers) complementary to the juxtaposed sequences in the 5'-terminus of the molecule around and upstream of the initiation codon.

Animals↗

[Mechanism for suppression mRNA translation with antisense oligonucleotides].

Experimental studies of the effects of antisense oligonucleotides on translation of mRNAs in cell-free systems are reviewed. Oligonucleotides complementary to the leader sequences or to the sequence overlapping the initiating codon region of mRNAs inhibit translation of the messengers. In the presence of ribonuclease H, oligodeoxyribonucleotides and their phosphorothioate analogs complementary either to the mentioned mRNA regions or to the mRNA coding sequence suppress the translation due to the RNAs cleavage. This inhibition-enhancing mechanism does not operate in the case of the oligonucleotide analogs--oligonucleoside methylphosphonates and oligonucleotides built of the alpha-nucleosides, since the complexes formed by RNA and these analogs are not substrates of the ribonuclease H. The translation inhibition efficiency is determined by the oligonucleotides lengths and by the availability of the complementary sequence in the mRNA structure. The oligonucleotides inhibitory power can be improved by the coupling to the oligonucleotides of the intercalating groups and the reactive groups.

Cell-Free System↗

[Synthesis, properties and interaction with eukaryotic cells of alkylating derivatives of oligodeoxyribonucleotides containing cholesterol or phenazinium residue covalently bound to the 3'-terminus].

Radioactive alkylating 5'-[32P]-[4-(N-2-chlorethyl)N-methylaminobenzyl]-5'-phospham ide decadeoxyribothymidilate derivatives containing either free hydroxyl group (reagent I), hydrophobic cholesterol residue (reagent II) or polyaromatic phenazinium residue (reagent III) at 3'-termini were synthesized. The products were purified by HPLC and used for oligonucleotide-directed alkylating of DNA in isolated rat liver nuclei, Krebs-2 ascite carcinoma cells and L-929 murine fibroblasts. The uptake of reagent II by the cells was two orders of magnitude higher than that of reagent I and III. Intracellular alkylation of DNA by reagent II both in isolated nuclei and in living cells was about one order of magnitude higher than in the case of reagent I. The presence of phenazinium at 3'-termini of the reagent III leads to a sufficient increase of the alkylation extent compared to reagent I despite a quite low extent of its uptake by the cells.

Alkylating Agents↗

[Interaction of alkylating oligonucleotide derivatives with mammalian cells. A study of the uptake mechanism of derivative cells].

Interaction of alkylating deoxyribooligonucleotide derivatives, bearing 4-[(N-2-chloroethyl-N-methyl)amino]benzylamine residues at their 5'-terminal phosphates, with mouse fibroblasts L929 and with ascite carcinoma cells Krebs 2 has been investigated. It was found, that the derivatives are taken up by the cells according to the endocytosis mechanism. At high concentration of the oligonucleotide derivatives in the cultivation medium (greater than 10 microM), the fluid phase endocytosis is the major pathway of uptake; binding of the derivatives by the cells is partially reversible and their intracellular mean concentration approaches 1/20 of their extracellular concentration. At low concentration of the oligonucleotide derivatives, the predominant mechanism is the more efficient adsorption endocytosis; at concentration of the derivatives less than 0.5 microM, their mean intracellular concentration exceeds that in the culture medium. Stability of the oligonucleotide derivatives in cells depends on their nucleotide composition. Their nucleolytic degradation rate is low enough to allow them to react with cellular biopolymers.

Alkylating Agents↗

[Infection by influenza virus induces production of nucleases by fibroblasts].

The stability of oligodeoxyribonucleotides and activity of DNAses and RNAses in chicken fibroblasts and in the cells infected by influenza virus have been investigated. It was found that viral infection results in an increase of nucleolytic activity in cells. The fact should be taken into account when planning experiments with antisense oligonucleotides and virus infected cells.

Animals↗

[Suppression of influenza virus NP-protein mRNA translation in vitro with derivatives of an antisense oligonucleotide].

Inhibition of the influenza virus protein NP mRNA with derivatives of an antisense oligonucleotide complementary to the 5' terminus of the mRNA was investigated. The derivatives were prepared by conjugation of aromatic 2-chloroethylamine, cholesterol, porphyrin, and phenazine groups to the 5'-terminal phosphate of the oligonucleotide. The most efficient inhibitors were found to be the conjugates bearing the alkylating, cholesterol and phenaznium groups.

Base Sequence↗