Biomedical subjects
Publications and source records attributed to V I Sergienko.
Intensification of lipid peroxidation against the background of exhaustion of the antioxidant protective system was demonstrated in 70 rats with experimental bile peritonitis. Free radical oxidation primarily concerned free lipids and fatty acids in the plasma and to a lesser extent erythrocyte membrane lipids.
The development of experimental bile peritonitis was accompanied by a variety of homeostatic changes. The disease is characterized by a specific clinical and laboratory syndrome.
Combined postoperation treatment with sodium hypochlorite and alpha-tocopherol broke the chain of free radical reactions in lipids and promoted normalization of LPO processes in the plasma and erythrocytes of 250 rats with experimental bile peritonitis.
We compared the normalizing effects of various methods of hemocorrection on homeostasis in animals with bile peritonitis. Combined treatment with hypochlorite and UV irradiation produced a potent membrane-stabilizing effect and increased adaptability of erythropoiesis.
The effect of panavir on Parkinson's syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was studied in C57Bl/6 mice and outbred albino rats. Two injections of panavir significantly reduced the severity of oligokinesia and autonomic manifestations of experimentally induced Parkinson's syndrome.
Combined use of sodium hypochlorite and intravenous laser irradiation of the blood in the postoperation therapy of 24-h bile peritonitis improved recovery of engulfing and digestive activity of neutrophilic granulocytes in the early postoperation period. Enzyme activity of neutrophilic granulocytes in earlier postoperation periods returned to normal after treatment with sodium hypochlorite alone.
We studied the relationship between blood cortisol level and hemogram parameters in animals with bile peritonitis. A strong correlation was revealed between variations in cortisol concentration and leukocyte count. We found differences in the hormonal regulation of individual cell populations in the peripheral blood.
It was shown with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone that myeloperoxidase (MPO) in the presence of its substrates H2O2 and Cl- as well as activated neutrophils destroy tert-butyl hydroperoxide producing two adducts of O-centered radicals which were identified as peroxyl and alcoxyl radicals. Inhibitory analysis performed with traps of hypochlorite (taurine and methionine), free radical scavengers (2,6-di-tret-butyl-4-methylphenol and mannitol), and MPO inhibitors (salicylhydroxamic acid and 4-aminobenzoic acid hydrazide) revealed that the destruction of the hydroperoxide group in the presence of isolated MPO or activated neutrophils was directly caused by the activity of MPO: some radical intermediates appeared as a result of the chlorination cycle of MPO at the stage of hypochlorite generation, whereas the other radicals were produced independently of hypochlorite, presumably with involvement of the peroxidase cycle of MPO. The data suggest that the activated neutrophils located in the inflammatory foci and secreting MPO into the extracellular space can convert hydroperoxides into free radicals initiating lipid peroxidation and other free radical reactions and, thus, promoting destruction of protein-lipid complexes (biological membranes, blood lipoproteins, etc.).
Comparison of antiaggregation capacity of N-chloramine acids with different position of the chloramine group in the molecule showed that in the most efficient compounds the distance between the chloramine and carboxyl groups was 3-5 carbon atoms. This feature of antiaggregation activity was not related to the difference in oxidation capacity of N-chloramine acids. It was hypothesized that the revealed structural dependence of antiaggregation activity of N-chloramine acids is determined by the structure of platelet membrane, in particular, the presence of a negatively charged group near the site of interaction between N-chloramine acids and platelet membrane.
Strangulation colorectal obstruction was modeled in 60 Wistar rats. Necrotic segment of the intestine was resected under conditions of peritonitis and end-to-end intestinal anastomosis was performed on a PCV catheter conducted through the anus. Sodium hypochlorite and ozone solution were used for sanitation of the abdominal cavity and intestinal lavage, and the intestinal anastomosis was coated with Ozonide (ozonized oil). The use of physicochemical methods notably reduced the incidence of postoperative pyoinflammatory complications, incompetence of intestinal anastomosis sutures, and animal mortality.
Complete nucleotide cDNA sequence (29715 nucleotides) of SARS-associated coronavirus (strain SoD) isolated for the first time in the territory of the Russian Federation was determined. Phylogenetic analysis revealed maximum similarity between strain SoD genome and Frankfurt 1 strain genome. Three nucleotide substitutions determining two amino acid substitutions were detected.
Genetic polymorphism of Russian population of N. gonorrhoeae was detected and a system for genotyping of its clinical strains was introduced into practice. Comparative analysis of the prevalence of N. gonorrhoeae genotypes in Russia and abroad was carried out. For adaptation of the methods of molecular typing of N. gonorrhoeae strains and its approbation on clinical strains isolated in Russia 41 clinical strains of N. gonorrhoeae were typed. The predominance of PIB serovar (83%) was demonstrated.
As we reported previously, hypochlorite interacting with organic hydroperoxides causes their decomposition ((1995) Biochemistry (Moscow), 60, 1079-1086). This interaction was supposed to be a free-radical process and serve as a source of free radicals initiating lipid peroxidation (LP). The present study is the first attempt to detect and identify free radicals produced in the reaction of hypochlorite with tert-butyl hydroperoxide, (CH3)3COOH, which we have used as an example of organic hydroperoxides. We have used a direct method for free radical detection, EPR of spin trapping, and the following spin traps: N-tert-butyl-alpha-phenylnitrone (PBN) and alpha-(4-pyridyl-1-oxyl)-N-tert-butylnitrone (4-POBN). When hypochlorite was added to (CH3)3COOH in the presence of a spin trap, an EPR spectrum appeared representing a superposition of two signals. One of them belonged to a spin adduct formed as a result of direct interaction of hypochlorite with the spin trap (hyperfine splitting constants were: abetaH = 0.148 mT; aN = 1.537 mT; and deltaHPP = 0.042 mT for 4-POBN and abetaH = 0.190 mT; aN = 1.558 mT; and deltaHPP = 0.074 mT for PBN). The other signal was produced by hypochlorite interactions with (CH3)3COOH itself (hyperfine splitting constants were: abetaH = 0.233 mT; aN = 1.484 mT; deltaHPP = 0.063 mT and abetaH = 0.360 mT; aN = 1.547 mT; deltaHPP = 0.063 mT for 4-POBN and PBN, respectively). Comparison of spectral characteristics of this spin adduct with those of tert-butoxyl or tert-butyl peroxyl radicals produced in known reactions of (CH3)3COOH with Fe2+ and Ce4+, respectively, showed that the radical (CH3)3COO* is produced from the interaction of hypochlorite with (CH3)3COOH. Like Ce4+ but not Fe2+, hypochlorite addition to (CH3)3COOH was accompanied by a bright flash of chemiluminescence characteristic of the reactions in which peroxyl radicals are produced. Thus, all these results suggest peroxyl radical production in the reaction of hypochlorite with hydroperoxide. This reaction is one of the most possible ways for the initiation of free-radical LP that occurs in vivo, when hypochlorite interacts with unsaturated lipids comprising natural protein-lipid complexes, such as lipoproteins and biological membranes.
Intravenous injection of chloramine derivatives of amino acids and taurine reduced the mortality rate in mice with thrombosis induced by intravenous injection of ADP or collagen-epinephrine mixture. Intravenous injection of N,N-dichlorotaurine caused 50% inhibition of platelet aggregation induced by ADP and measured in the platelet-enriched plasma in vitro. The antithrombotic effect of chloramine derivatives of amino acids and taurine is related to their ability to suppress functional activity of platelets.
Two fragments (1.9 and 1.8 kb) including, respectively, "structural" genes (A, B, and lysis polypeptide) and "replicase" gene, were obtained by reverse transcription PCR on the template of bacteriophage MS2 genome RNA. The fragments contained a common sequence which allowed the assembly of the entire functional genome sDNA. 1.8 kb fragment was subjected to two independent modifications: 1) so that the replicase gene could be replaced by other sequences no more than 1.5 kb in size and 2) it was inserted (on an artifician Tn-like structure) into E. coli chromosome. A system for replication of MS2-like corpuscles was thus created, containing a "shortened" genome and having extra genes. For extra genes, aminoglycoside-3'-phosphotransferase (kanamycin resistance) or a sequence of antiviral genetic program directed against hepatitis C virus were used.
Enzyme immunoassay showed penetration of two glia-specific antigens, glial fibrillar acid protein GFAP and specific brain glycoprotein alpha(2)GP, through the blood-brain barrier in rats treated with toxic doses of sodium barbital. The permeability of the blood-brain barrier was completely normalized 3 days after treatment. This method can be used in clinical practice for evaluation of the severity of impairment and dynamics of normalization of blood-brain barrier properties during acute intoxication with barbiturates.
Hypochlorite produced in vivo by activated neutrophils, monocytes, and macrophages modifies blood lipoproteins and intensifies free radical lipid peroxidation, which probably plays a key role in the early stages of atherosclerotic vascular damages.
A new etiopathogenetic concept of psoriasis is proposed, which considers psoriasis as a typical inflammatory process characterized by increased antioxidant activity and overexpression of apoptotic receptors. Under these conditions, hyperstimulation of germinative layer cells proliferation dramatically accelerates keratinocyte passage towards apoptotic effect of atmospheric oxygen and its reactive species dooming to death cells with enhanced expression of apoptotic receptors. Oxidative stress of nondifferentiated keratinocytes triggers the formation of defective horny layer, the key mechanism of psoriasis.