[Characterization of the Lipopolysaccharides of Pseudomonas chlororaphis].

Lipopolysaccharides (LPS) from two strains ot Pseudomonas chlororaphis subsp. aureofaciens,UCM B-111 and UCM B-306, were isolated and characterized. The LPS preparations exhibited low toxicity, high pyrogenicity and high antiviral activity. Mild acid hydrolysis was used to obtain the O-specific polysaccharides. Their structures were established by monosaccharide analysis and determination of absolute configurations, as well as by 1D and 2D NMR spectroscopy. The O-polysaccharides were shown to contain the linear tri- or tetrasaccharide repeating units. Both O-polysaccharides were structurally heterogeneous: P. chlororaphis subsp. aureofaciens UCM B-111--> 4)-αD-GalpNAc6Ac-(1 --> 3)-ß-D-QuipNAc-(1 --> 6)-αD-GlcpNAc-(l --> ßD-GlcpNAc-(l --> 3)] GalNAc -60%; degree of the non-stoichiometric 6-O-acetylation of GalNAc -60%; P. chlorophis subsp. aureofaciens UCM B-306 --> 3)-α-D-Rhap-(1 --> 4)-α-D-GalpNAcAN-(1 --> 3)-αD-QuipNAc4NAc-(1 -->, where GalNAcAN is 2-acetamido-2-deoxy-D-galacturonamide, the degree of non-stoichiometric amidation of the GalNAcA residue -60%.

[Influence of chemically different antiviral substances on the expression of IFNα, PKR, OAS1a and RNAse L genes].

The aim of the study was to determine the ability of several chemically different antiviral substances to induce the expression of interferon α(IFNα), PKR, OAS1a and RNAse L genes in the rat liver. The investigated substances included Amizon, Altabor and Proteflasid, which are already used in practical medicine, and 3',7-dimethylquercetin extracted from Proteflasid, the mixture of synthesized trimethyl- and tetramethylquercetin and Sialospecific lectin from persimmon, which are at the stage of preclinical trial and experimental research respectively. The content of corresponding mRNAs in total RNA was detected with the help of reverse transcription and polymerase chain reaction in real time. The results have shown that all investigated substances induce the expression of genes α, PKR, OAS RNAse L in specific manner. The combination of 3',7-dimethylquercetin + lectin from persimmon had the highest stimulating effect exceeding the effect of each component of the mixture and the influence of Heberon (recombinant IFNα2b) and PolyI-polyC as the standard inducers of IFNα and its target genes. The ability of all substances to specifically induce the expression of IFNa and its target genes, the absence of correlation between the levels of IFNα and its target genes expression as well as between target genes themselves indicate that the mechanism of antiviral activity of the investigated substances is connected not only with up-regulation of IFNα and potential IFNα mediated effects.

[The role of the interferon system in pathogenesis of endothelial dysfunction in patients with metabolic syndrome].

We have studied the serum interferon activity and its relation to the endothelial dysfunction. Atherosclerosis development in patients with metabolic syndrome is followed by significant increase in interferon activity. Close relation presents between activity of the serum interferon and indexes of structural and functional changes of arterial vessels compromised with atherosclerosis process.

[Anti-HIV effect of soy products and possibility of their usage as medicinal and prophylactic nutrition].

An anti-HIV effect of soy products (emulsion, flour) has been revealed in vitro experiment. The unique properties of biologically active components of soy products made from the whole soybeans justify their usage in HIV/AIDS treatment as an additional treatment and prophylactic nutrition.

[Effect of probiotic lactic acid bacteria strains on virus infection].

The effect of probiotic lactic acid bacteria strains on viral infection was studied in experiments in vivo. It was shown that in investigations microbial substance based on living cells of L. plantarum and S. salivarius subsp. thermophilus strains manifested antiinfluenzal activity under administration of 0.3 ml of cultural medium per os at a dose of 3 x 10(8)/CFU mouse and antiherpetic activity at a dose of 0.3 x 10(9)/CFU mouse. The probiotic effectiveness was shown on the model of genital herpes of guinea-pigs at concentration of 1 x 10(9) cells/g.p. It was statistically established, that the lactic acid bacteria inhibited reproduction of HIV at a dose of cells of 0.1 x 10(9)/CFU ml.

[Reversion of antibiotic-sensitivity of lactic acid bacteria in grafted cultures of lymphoblastoid human cells].

The reversion of the antibiotic sensitivity of lactic acid bacteria: Streptococcus salivarius subsp. thermophilus, Enterococcus faecium, Lactobacillus plantarum have been studied. The phenomenon of the reversion has been fists studied in lactic acid bacteria of different taxonomic groups at their interactions with lymphoblastoid human cells. It is shown that resistance of lactobacteria to antibiotics can change depending on the terms of cultivation, genus and strain specificity. Most often the reversion of antibiotic sensitivity was observed with respect to fuzidin (26%) and cefepim (23%), most rarely--with respect to cephazolin, erithromicin, cefamandol, tobramicin and oxacillin.

[Interferon induction by lacticacid bacteria in vitro and in vivo experiments].

Interferonogenic acitivity of lacticacid bacteria was studied in experiments in vitro and in vivo. It have been shown, that interferon induction depends both on strain species and on culture medium used for lactobacteria harvesting. Streptococcus thermophilus induces interferon more actively in leucocytes (in vitro)--1280 AU/ml on the bines broth medium, and less actively--320 AU/ml on fermented corn medium. Interferon induction in human leucocytes was not registered in case of L. plantarum 200 strain. In vivo experiments show that E. faecium strain and strain mixture of streptococcus termophilus are active interferon inductors. Induced interferon is recognized as alpha- and gamma-interferon, with domination of alpha-interferon.

Virus-inhibitory effect of a yeast RNA-tilorone molecular complex in cell cultures.

The virus-inhibitory activity of a molecular complex (MC) of tilorone and yeast RNA was studied in vitro on three virus-cell systems: vesicular stomatitis virus (VSV) - murine fibroblast L929 cells, Venezuelan equine encephalittis virus (VEEV) - swine embryo kidney (SEK) cells and encephalomyocarditis virus (EMCV) - established piglet testicular (EPT) cells. In all these systems the MC exerted an antiviral effect similar to that of polynucleotide interferon (IFN) inducers such as poly(I)-poly(C), larifan and ridostin. The antiviral effect of the MC was similar when the compound was applied before or after virus adsorption to cells. The MC may be regarded as a perspective antiviral agent of common use.

[Construction of the immunoenzyme test system "IFA-AtEBV-Strip" for detecting antibodies of the Epstein-Barr virus]. / Konstruiuvannia imunofermentnoï test-systemy "IFA-AtVEB-Strip" dlia vyiavlennia antytil proty virusu Epshteina-Barr.

The first home immunoenzyme test-system for finding antibodies to the Epstein-Barr virus (EBV) has been created. The test-system laboratory prototype was called "IFA-AtEBV-strip". Production technology has been developed for specific components of immunoenzyme test system and all the analysis stage conditions have been optimized: the antigen sorption on plates, its interaction with the studied serum, finding out of the formed immune complex. The test system "IFA-AtEBV-strip" sensitivity made up 96%, specificity--100%.

Biological active acridine derivatives. Part 4: Synthesis and antiviral activity of some bis-acridinylated diamides.

Nine bis-acridine derivatives have been synthesized in search of structures with antiviral properties. Synthesis of target compounds was provided by a standard peptide-like coupling procedure using aliphatic diamines and protected amino acids following protective group removing and acridinylation by means of 9-methoxyacridine. Two out of nine compounds tested demonstrate high protective activity of Vero cells against HSV infection. Antiviral activity was observed only for compounds containing a pentamethylene fragment as a linker. The alanyl-containing derivative was less active than those containing valyl- and phenylalanyl. Most of synthesized compounds were less toxic than N,N'-bis-(acridinyl) hexamethylenediamine.

[Comparative cytotoxic characteristics of the interferon-inducing yeast RNA-tilorone complex]. / Sravnitel'naia kharakteristika tsitotoksichnosti interferon-indutsiruiushchego kompleksa drozhzhevaia RNK-tiloron.

Cytotoxicity of the yeast RNA-tilorona molecular complex (MC) with interferonogenic properties and its influence on the DNA replicative synthesis were studied in experiments with human lymphocytes and 3 cell lines. It was shown that the MC doses of 25, 100 and 250 micrograms/ml were absolutely nontoxic for all the cell lines. The main parameters of the MC toxicity based on the cell viability were calculated. The parameters were found to correlate in the order of their magnitude with those relating to interferonogens of the polynucleotide nature. Within the dose ranges of 10 to 100 micrograms/ml the MC had a stimulating effect on replicative processes in the cells. It was concluded that the use of the MC as an inductor in large-scale manufacture of human and animal interferons of type 1 was promising.

[The toxicity and interferon-inducing activity of the lipopolysaccharides of Cytophaga sp. (strains 81 and 92)]. / Toksichnost' i interferonogennaia aktivnost' lipopolisakharidov Cytophaga sp. (shtammy 81 i 92).

The experiments on mice and cell culture of a kidney of green monkey Vero have shown that lipopolysaccharides (LPS) of the studied strains 81 and 92 of Cytophaga sp. were nontoxic. They were less active as compared to LPS of other Gram-negative bacteria as to interferon-inducing activity. A comparative study of initial and dephosphorylated LPS has shown that phosphate groups were not responsible for the interferon-inducing activity of LPS of Cytophaga genus representatives.

[The biological activity of a lipopolysaccharide from Ralstonia solanacearum ICMP 7859 and of its modified derivative]. / Biologicheskaia aktivnost' lipopolisakharida Ralstonia solanacearum ICMP 7859 i ego modifitsirovannogo proizvodnogo.

Coordinational compound of the Ralstonia solanacearum ICMP 7859 lipopolysaccharide (LPS) with germanium was obtained. The derivative has lost to considerable extent its toxicity (as compared to the initial substance) but preserves immunomodulating activity, interferon-inducing one in particular. Lipid A modification has led to complete loss of interferon-inducing activity. Apparently, phosphate at C4' GlcN II can be responsible for interferon-inducing activity of lipid A, while carboxylic groups of core oligosaccharide or 0-specific polysaccharide, are responsible for that in native molecule of LPS.

The effect of trimeric 2',5'-oligoadenylic acid and its epoxy-derivative on human immunodeficiency virus (HIV-1) reproduction and retroviruses reverse transcriptase activity.

The effect of trimeric 2',5'-oligoadenylic acid (2',5' A3) and its epoxy-derivative (2',5'-A2 (RAA) on human immunodeficiency virus (HIV-1) reproduction was studied. An HIV-1 infectivity titer decrease was shown on the model of limphoblastoid cells when the substances under study were used. The interferonogenic effect of both substances was discovered. 2',5'-A2 (RAA) inhibited the activity of retrovirus reverse transcriptase (a C-type).

[The use of carbon carriers for the immunoenzyme diagnosis of viral infections]. / Ispol'zovanie uglerodnykh nositelei dlia immunofermentnoi diagnostiki virusnykh infektsii.

Carbon solid phase for enzyme-linked immunosorbent assay was proposed. This support can be used instead of polysterene plates because the following steps (carbon support incubate with specific and detective reagents) are implemented in arbitrary minimal capacities. The method was tested for detection of the virus antigens (hepatitis B, herpes simplex) and anti-viral (anti-adenovirus, anti-influenza virus) antibodies.

[The reproductive characteristics of human adenovirus type 2 in cultures of lymphoblastoid cells with B and T phenotypes]. / Osobennosti reproduktsii adenovirusa cheloveka tipa 2 v kul'turakh limfoblastoidnykh kletok B- i T-fenotipa.

A comparative characteristic of the reproduction process of type 2 human adenovirus in several lines of lymphoblastoid cells of B- and T-phenotype is presented. Formation of hexone and infectious virus in the cells of Jurkat, MT4, Raji lines was rather intensive and approached to that in the culture of the permissive epithelium cells Hep-2. These indices were much lower in the cultures of cells B 95-8 and MT4/BIII LBK which were chronically infected by VEB and HIV, accordingly and produced them that can evidence for the interference of Ad and VEB or Ad and HIV under superinfection of cells. Cells of SEM line possessing T-phenotype, were apparently semi-permissive for Ad h2, though the low almost unchanged content of hexone and infectious virus remains in them for a rather long time: about 15 days. Thus, obtained data within analyzed series of experiments expand the present ideas about lymphotropicity of Ad as their important property realized at the level of cell and infected macroorganism.

[The combined treatment with prednisolone and recombinant alpha 2-interferon of patients with chronic hepatitis B: the factors influencing the immune response]. / Kombinirovannoe lechenie prednizolonom i rekombinantnym al'fa 2-interferonom patsientov s khronicheskim gepatitom B: faktory, vliiaiushchie na immunyi otvet.

The study included 39 patients with chronic HBeAg and DNA HBV-positive hepatitis B. 18 patients received combined therapy with prednisolone and recombinant interferon. Pretreatment investigations involved assessment of the basic virus replication by HBeAg, IgM anti-HBc, RPSHA titers, of DNA HBV concentration, alanine aminotransferase activity. The serum was examined for antibodies to alpha 2-interferon using enzyme immunoassay. The treatment resulted in disappearance of HBeAg in 70.6% of the examinees, DNA HBV in 66.6% of them. AlAT activity returned to normal in 58.8% of the patients. HBeAg and HBsAg were not registered in 5.6% of the patients. In 2 out of 4 nonresponders antibodies to alpha 2-interferon were absent. It is shown serologically that patients with initially low HBeAg, DNA HBV, high activity of AlAT, high titers IgM anti-HBc, no antibodies to alpha 2-interferon have the most favourable prognosis of the hepatitis.

[Glycopolymers of Clavibacter michiganense and Pseudomonas solanacearum--interferon inducers]. / Glikopolimery Clavibacter michiganense i Pseudomonas solanacearum--induktory interferona.

A polysaccharide, being an active inductor of gamma-interferon, has been found among glycopolymers of Clavibacter michiganense. Lipopolysaccharide of Pseudomonas solanacearum is shown to display an interferonogenic activity which is analogous to that of the classical interferon inductor, lipopolysaccharide of Escherichia coli O55: B5. Besides lipid A, core oligosaccharide also contributes much to the interferonogenic activity of P. solanacearum lipopolysaccharide.

[The use of an immunoenzyme method for detecting enteroviruses]. / Ispol'zovanie immunofermentnogo metoda dlia obnaruzheniia énterovirusov.

It was established as a result of these investigations that the immunoenzymatic method may be used for detection of enteroviruses both in materials from human subjects and from objects of the environment. It is shown that the immunoenzymatic method has advantages as compared with the virological.