[Influenza viruses and atherosclerosis: the role of atherosclerotic plaques in prolonging the persistent form of influenza infection]. / Virusy grippa i ateroskleroz: rol' ateroskleroticheskikh bliashek v podderzhanii persistentnoi formy grippoznoi infektsii.

It was established that viral particles, like low-density lipoproteins (LDLP), when subjected to some modification changes, lost their ability to be internalized by tissue somatic cells and acquired tropism to macrophage cells. The data, obtained by us by using the polymerase chain reaction (PCR) method, made it possible to assert that atherosclerotic plaques, isolated from vessels of patients with ischemic heart disease (IHD) who underwent coronary bypass, contained RNA of the A(HINI) and AH3N3) influenza viruses. Whereas, the vessel portions, undamaged by atherosclerosis, did not contain any genetic substances of influenza viruses. It was for the first time that an experimentally supported understanding was expressed on that the atherosclerotic plaques serve as a "reservoir" for influenza viruses. It is also suggested that the mentioned plaques can be the carriers of influenza viruses for a long time, thus, prolonging the persistent form of influenza infection in the human body.

[Influenza virus infection in progressing atherosclerosis]. / Infektsiia virusami grippa pri progressiruiushchem ateroskleroze.

AIM: To study relationship between influenza virus infection and activity of clinical presentations of atherosclerosis. METHODS AND RESULTS: Average blood level of IgG to influenza A virus was significantly higher in patients with progressing forms of ischemic heart disease then in patients without objective signs of exacerbation of atherosclerotic process. Mean titles of antibodies to parainfluenza virus and adenoviruses were similar in both groups of patients. Direct detection of viral DNA by polymerase chain reaction was carried out in samples of aortic wall taken during coronary artery bypass surgery with the use of primers for hemagglutinin of H1N1, H3N2 viruses. RNA of influenza virus was found in these samples. CONCLUSION: The presence of viral RNA in vascular atherosclerotic lesions could be indicative of possible pathogenetic role of influenza infection in progression of clinical course of atherosclerosis.

[The use of cycloferon in the therapy of experimental herpetic keratitis]. / Ispol'zovanie tsikloferona v terapii éksperimental'nogo gerpeticheskogo keratita.

The cycloferon efficacy was investigated in the treatment of experimental herpesvirus kerato-conjunctivitis in rabbits. The model was demonstrated to reflect the main aspects of herpesvirus eye lesions in humans. Cycloferon application similarly to that of known interferon inducer poludan has been shown to enhance processes of inflammation and subsequent regeneration of eye tissues as well as to decrease mortality of animals due to the generalization of infection.

[Reticuloendothelial system and persistence of influenza virus in the body]. / Retikuloéndotelial'naia sistema i persistentsiia virusa grippa v organizme.

The method of in situ transcription was used to detect influenza virus genome in the organs of infected mice. Virus-specific RNA was found in the alveolar macrophages 5 months after infection, this confirming the capacity of the virus to persist in vivo in these cells for a long time. Evidence in favor of influenza virus modification in an infected host body is presented, which fact dramatically affects virus interactions with macrophages. Problems in the development of acute and persistent infections and influenza virus persistence in reticuloendothelial cells are discussed.

[Study of the nature and mechanism of action of virus neutralizing inhibitors of the blood]. / Izuchenie prirody i mekhanizma deistviia virusneitralizuiushchikh ingibitorov syvorotki krovi.

Low-density lipoproteins (LDL, d 1.0.40-1.053 g/ml) and high-density lipoproteins (subfraction 3 of HDL, d 1.210 g/ml) were isolated by preparative ultracentrifugation at the NaBr density gradient. The findings have led to the conclusion that LDL or beta-LP are not thermolabile, but they represent a thermoresistant serum virus-inhibiting factor. At the same time HDL3 has pronounced thermolabile properties. The mechanisms of action of the above factors are explained in the paper.

[The receptor-mediated endocytosis of influenza viruses and low-density lipoproteins by tissue cells]. / Retseptoroposredovannyi éndotsitoz virusov grippa i lipoproteidov nizkoi plotnosti kletkami tkanei.

The experimental data obtained by immunological, immunomorphological, biochemical, and virological methods are presented which substantiate a concept that various strains of influenza virus under study may penetrate tissue cells at sites of high affinity usually meant for low-density lipoproteins (LDLP) providing the cells with cholesterol for construction of outer and inner membranes. A computer analysis of a bank of data on the primary structure of proteins (the package of GENBER programme) revealed significant similarity of amino acid sequences between the area of viral hemagglutinin site attachment to cells and corresponding amino acids comprising apoB LDLP. The presented proofs are a convincing example of virus particles mimicry realized at the molecular level and give new concepts concerning the mechanisms of virus penetration into body cells which are important for the development of a principally new approach to creation of highly effective antiviral compounds. Moreover, the observed phenomenon may serve for explanation of the nature and mechanism of action of the so-called thermostable virus-neutralizing blood serum inhibitor.

[The effect of microwave irradiation on the peroxide modification of low density lipoproteins in human blood serum]. / Vliianie mikrovolnovogo oblucheniia na perekisnuiu modifikatsiiu lipoproteidov nizkoi plotnosti syvorotki krovi cheloveka.

In experiments in vitro the electromagnetic field of 2375 mHz, 500 microW/cm2 was shown to influence peroxide modification of low density lipoproteids. It was also shown that this modifying effect was prevented by high density lipoproteids that decreased the level of lipid peroxidation.

[Protective effect of high density lipoproteins, their subfractions and lecithin-cholesterol-acyltransferases on the peroxidation modification of low density lipoproteins]. / Zashchitnoe deistvie lipoproteidov vysokoi plotnosti, ikh podfraktsii i letsitin-kholesterin-atsiltransferazy v perekisnoi modifikatsii lipoproteidov nizkoi plotnosti.

The role of high density lipoproteins (HDL), their subfractions (HDL2 and HDL3) and lecithin: cholesterol acyltransferase (LCAT) on peroxidative modification of low density lipoproteins (LDL) in vitro was studied. Peroxidative modification was estimated by the formation of malonic dialdehyde (MDA) and LDL aggregates during LDL incubation at 37 degrees C for several days without Fe2+ or for 2 hours in the presence of Fe2+ in EDTA-free media. It was shown that the addition of HDL3 (but not HDL2) markedly decreases the formation of both MDA and LDL aggregates. Since LCAT is bound to HDL3, its effect was examined. An addition of LCAT isolated from human plasma (650-fold purification) at a concentration of 450 micrograms/ml resulted in a complete inhibition of LDL peroxidation and LDL aggregate formation. Heat-inactivated LCAT had no effect. Possible mechanisms of the protective effect of LCAT on LDL peroxidative modification are discussed.

Accumulation of cholesteryl esters in macrophages incubated with human lipoprotein-antibody autoimmune complex.

The interaction of mouse peritoneal and human pericardial macrophages with lipoprotein (LP)-antibody (Ab) immune complex isolated from the serum of ischemic heart disease (IHD) patients has been studied. It is shown that the Ab of the autoimmune complex belongs to IgG class, and the antigen is the LP with d less than 1.063 g/ml. Incubation of mouse peritoneal macrophages with such complex led to the activation of [14C]oleic acid incorporation into cholesteryl esters by 2.5-2.8-fold, in comparison with the experiments where macrophages were incubated with free apoprotein (apo) B-containing LP isolated from the same serum. Incubation of human pericardial macrophages with autologous LP-Ab immune complex led to the transformation of macrophages into foam cells. These data lead to the conclusion that formation of LP-Ab autoimmune complexes may play an important role in the formation of atherosclerotic lesions of the arteries.

[Antioxidant effect of high-density lipoproteins in the peroxidation of low-density lipoproteins]. / Antioksidantnyi éffekt lipoproteidov vysokoi plotnosti pri perekisnom okislenii lipoproteidov nizkoi plotnosti.

It has been shown that in the solution of low density lipoproteins (LDL) during their incubation at 37 degrees C the turbidity and concentration of malondialdehyde was increased, as compared to that observed at 4 degrees C. Both parameters were slowed down by the addition of high density lipoproteins (HDL) into the medium. The protective effect of HDL depended on the time of incubation and the concentration of HDL added. Delipidated HDL had no effect. Similar action of HDL was established in the experiments where the peroxidation in LDL was induced by the xanthine-xanthine oxidase. The data obtained demonstrate that HDL possess an antioxidant property that may play an important role in their antiatherogenic action.

Lipoprotein-antibody immune complexes. Their catabolism and role in foam cell formation.

Immune complexes consisting of human [125I]LDL or [125I]VLDL and anti-apo B IgG were prepared in vitro. After intravenous administration of these complexes or free LDL to normal rabbits the elimination rate for complexes was 2-3-fold higher than for free lipoproteins. The liver/spleen radioactivity ratio after administration of immune complexes was 34% less than after administration of free lipoproteins. Investigations carried out on the cell cultures have shown that during 4-h incubation the uptake of [125I]LDL-anti-apo B IgG complex by human lung fibroblasts was lower than uptake of free [125I]LDL, whereas mouse peritoneal macrophages took up immune complex more actively than free LDL. During 3 days of incubation of macrophages with LDL-anti-apo B IgG the transformation of macrophages into foam cells was observed. This process was accompanied by almost a 60-fold increase of cholesteryl ester content in the cell. It is suggested that excessive uptake of lipoprotein-antibody complexes by macrophages leading to formation of foam cells may play an important role in atherogenesis.

[Capture of native and in vivo modified 125I-low density lipoproteins by fibroblasts and macrophages. Effect of high density lipoproteins on this process]. / Zakhvat nativnykh i modifitsirovannykh in vivo 125I-lipoproteidov nizkoi plotnosti fibroblastami i makrofagami. Vliianie lipoproteidov vysokoi plotnosti na étot protsess.

Unspecific interaction was analyzed between native 125I-lipoproteins of low density (LDL) as well as 125I-LDL, maintained in rabbit circulation during 4 hrs, and fibroblasts and macrophages. Alterations in properties of the LDL, occurred in blood, were accompanied by an increase in their affinity towards macrophages and a decrease in the affinity to fibroblasts. In vivo effect of HDL on catabolism of LDL was manifested as inhibition of extracellular modification of LDL and elimination of them from circulation, and in vitro--as inhibition of the native LDL capture by fibroblasts and, especially, by macrophages. In vivo inhibitory effect of HDL on modification of LDL, which are captured by cells (including arterial endothelial cells) by means of unspecific endocytosis, appears to be one of mechanisms in the antiatherogenic action of HDL.

Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins.

A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human [125I]LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for [125I]LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to [125I]LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells.

[Ultrastructural characteristics of macrophage transformation in foam cells in in vitro experiments]. / Ul'trastrukturnye osobennosti transformatsii makrofagov v penistye kletki v opytakh in vitro.

Ultrastructural features of lipid vacuole formation in foam cells were studied in a mouse macrophage culture on the use of aggregated low density lipids (a-LDL) and fibroblast-modified LDL (fm-LDL). Modification of LDL properties is a factor which induces rapid transformation of macrophages to foam cells. Catabolism of a-LDL and fm-LDL and lipid vacuole formation is carried out in two ways: with and without involvement of lysosomes. In the former case membraneless lipid vacuoles are formed, in the latter one, lipid vacuoles surrounded by a membrane.

[Effect of high-density lipoproteins on the permeability of the rabbit aorta for low-density lipoproteins]. / Vliianie lipoproteidov vysokoi plotnosti na pronitsaemost' aorty krolikov k lipoproteidam nizkoi plotnosti.

After administration of high doses of high density lipoproteins (HDL) into control rabbits the index of aorta permeability for 125I-low density lipoproteins (LDL) was decreased by about 19%. This index was decreased by 45% if HDL was administered into animals with hypercholesterolemia. Historadiographic assays showed that presence of 125I-LDL in circulation simultaneously with the exogenous HDL caused a decrease in the vessel wall permeability for LDL both in control rabbits and, especially, in hypercholesterolemic animals. As shown in experiments with human embryonal lung fibroblasts, under conditions of mainly unspecific interaction of LDL with cells, HDL inhibited the 125I-LDL absorption by 28%. High molar excess of HDL appears to inhibit the LDL penetration via intact endothelial layer into the arterial wall due to ability of HDL to compete with LDL at the sites of low affinity on the endothelial cells surface.

[Nonreceptor interaction of low-density lipoproteins with human fibroblasts]. / Neretseptornoe vzaimodeistvie lipoproteidov nizkoi plotnosti s fibroblastami cheloveka.

An analysis was made of catabolism of low density lipids (LDL) labeled in the protein or lipid moieties with cultivated human fibroblasts under inhibition of receptor-mediated endocytosis of LDL. The results have shown that under these conditions, only part of LDL uptaken by the cells are catabolized in the cells for 24 h. A considerable part account for a slow-metabolized intracellular pool. LDL of the latter may leave the cells by exocytosis (regurgitation), appearing in the culture medium. On the whole, the data obtained agree with the basic regularities of LDL transport in the cell within the structure of uncoated vesicles.

[Changes in the size and properties of lipoprotein particles in the extracellular medium during incubation of low density lipoproteins with human fibroblasts]. / Izmenenie razmera i svoistv lipoproteidnykh chastits vo vnekletochnoi srede pri inkubatsii lipoproteidov nizkoi plotnosti s fibroblastami cheloveka.

Electron microscopy, disc electrophoresis in polyacrylamide gel, and microzonal electrophoresis on acetate cellulose were used to examine the changes in the properties of low density lipoproteins (LDL) in extracellular medium during incubation with human fibroblasts. It was established that as a result of LDL interaction with fibroblasts there appeared lipoprotein particles less in size, with higher aggregation ability and electrophoretic mobility. The data obtained indicate that LDL undergo physicochemical changes due to non-specific interaction with fibroblasts.