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We studied molecular mechanisms of changes in oxidative metabolism under conditions of experimental lipopolysaccharide-induced endotoxemia. Generation of reactive nitrogen and oxygen species in mice increased 18 h after treatment with lipopolysaccharide. These changes contributed to inactivation of enzymes and enzyme complexes (ribonucleotide reductase, NADH-ubiquinone oxidoreductase, and cytochrome c oxidase), dysfunction of the mitochondrial electron transport chain, and development of oxidative stress. Plaferon LB protected mice from the toxic effect of lipopolysaccharide.

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Free radical oxidation plays important role in the radiation-induced cell and tissue damage. Numerous studies evidence a decrease in body antioxidant system activity and changes in nitric oxide levels during irradiation. It has been demonstrated that in the process of radiation damage NO may play either radioprotective or radiotoxic role depending on body redox status. Hence, the search for effective radioprotectors is an urgent issue of the contemporary radiology. We applied vitamin C and plaferon LB as radioprotectors. Plaferon LB has antioxidant, antihypoxic, immunomodulating and antiapoptotic effects. Our study aimed to evaluate effectiveness of correcting action of plaferon LB on oxidative -- reducing balance of the body subjected to ionizing radiation. There have been studied changes in catalase, SOD, GR and ceruloplasmine activities as well as blood NO levels, superoxide and lipoperoxide radical levels in rats being subjected to gamma-radiation and treated by above mentioned preparations. As a result of our study we can conclude that preliminary and postradiation application of antioxidants at irradiation has a protective effect.

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Oxidative damage of biological membranes plays critical role in the process of radiation-induced damages in tissues and cells. It involves reactive oxygen species generated under ionizing radiation. Development of radiation-induced oxidative stress facilitates the intensification of lipid peroxidation and fatty acid reorganization, which, in its turn, results in decreased lipid matrix fluidity, changes in biophysical properties of membranes, increased rigidity of membrane lipid-protein surface. Radiation-induced damage of cellular and subcellular membrane structures results in cellular metabolism disorder, which facilitates farther dysfunction of tissues and changes in homeostasis of whole organism. Hence, the search for effective protection is of actual interest of contemporary radiology. Our study aimed to determine membrane protective properties of Plaferon LB under radiation. On the basis of obtained results we can conclude that intensification of free radical oxidation, accompanying radiation damage, facilitates the activation of lipolysis in a body and functional and structural disorders of erythrocytes revealed by lowered deformability of erythrocytes and accumulation of methaemoglobin. Both vitamin C and Plaferon LB were found ineffective for correction of lipid metabolism at early stage of post radiation damage; although facilitating a decrease in oxidation intensity in blood, they provided retention of erythrocyte deformability and thereby, partial retention of rheological properties of blood. It should be mentioned that in contrast with vitamin C, Plaferon LB, apart from its ability to restrict reactive oxygen formation, revealed ability to stabilize erythrocyte membranes and thereby to prevent hemolysis.

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The proliferation activity of monolayer culture of Madin Darby Canine Kidney (MDSK) cells is suppressed by a thermostable protein factor of renal tissue of white rats and of humans. Under the influence of renal factors (RF), a decrease in cell number, and suppression of DNA synthesis and mitotic activity in MDCK cells occur. The inhibition of proliferative activity of cultured cells under the influence of RF was substantiated also by MTT assay. It was established that the inhibitory influence of RF is stipulated by suppression of RNA synthesis. It follows that RF may inhibit division of MDCK cells via suppression of gene expression in G1-phase. Similar factors were obtained from renal cells of different systematic groups of organisms (snail, frog, fish, pigeon, guinea pig, swine).

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The effect of plaferon on the local cerebral blood flow and brain tissue oxygen tension during transient incomplete ischemia and following recirculation, was studied. The difference revealed between experimental and control data is, probably, due to vasodilatory action of the vasoactive neuropeptides and the effect on the systems of phosphorylation.

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The immunogenic potency of an experimental vaccine against rotavirus infection of cattle was studied under production conditions. Cows with calves were vaccinated in the second period of pregnancy once, twice and three times. The study showed the schedule of immunization of pregnant cows including three vaccinations at 50-40, 30-20, and 15-10 days before delivery to be technological, providing a high protective effect in newborn calves.

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The nucleotide sequence of the cDNA encoding one of the neutralizing proteins VP7 of the new porcine strain K is determined. The deduced VP7 amino acid sequence of the K strain showed a high homology (93%) and a lower homology (75%) to those of the Gottfried and OSU strains, respectively. This finding suggests that strain K is more closely related to the Gottfried strain serotype 4.

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Thermophilic clones of lymphoblastoid cell cultures Namalwa were generated and found to be capable of life and reproduction at a temperature of 60 degrees C. The reproductive dynamics, cytology, and ultrastructure of these clones were studied.

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Using controlled pore glass chromatography and immunoaffinity chromatography on monoclonal antibodies NK-2 immobilized on Sepharose 4B, the electrophoretically homogeneous interferons alpha N and alpha I1 were isolated from the biomass of gene-engineered Pseudomonas sp. strains. In terms of specific activity on human fibroblast diploid cells, interferon alpha I1 does not differ from interferon alpha A, whereas the specific antiviral activity of interferon alpha N is as low as 2.10(7) JU/mg. The procedures for immunometric assay of interferons alpha N and alpha I1 have been elaborated. Various monoclonal antibodies to interferon alpha A and to natural leucocyte interferon were analyzed; among those the antibodies specifically interacting with interferons alpha N and alpha I1 (but not with interferon alpha A) were identified.

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The authors presented some data on the investigation of the interferon system in patients with dilatation cardiomyopathy (DCM) and viral myocarditis (VM). Diagnosis was verified according to the WHO criteria. Altogether 10 DCM patients and 24 VM patients with a grave course were investigated. Antibodies to Coxsackie B virus and influenza were detected in the VM patients. A decrease in the alpha- and gamma-interferon activity was shown in all DCM patients. The VM patients with a grave course also demonstrated a decrease in the alpha- and especially gamma-interferon (immune) activity. Methods of immune correction in such patients were discussed.

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The effect of combined application of thymalin and plaferon in the prophylaxis and treatment of traumatic syndrome has been investigated in rats. The survival rate was taken as the criterion of efficiency, the mechanism of the effect obtained being estimated at the level of immunological protective factors. Traumatic shock was induced by Kennon's method in Wistar male rats weighing 200-250 g. Post-traumatic syndrome has been observed within 7 days. The combined application of thymalin and plaferon has increased the survival rate twice within the first 7 days. Immunomodulating effect of the combined application of thymalin and plaferon on the 7th day of traumatic syndrome was most marked at the level of total T-lymphocyte population, theophylline-sensitive T suppressors and lysozyme blood serum activity.

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Interleukin-2 (IL-2) was isolated from donor peripheral blood lymphocytes and from JURKAT T-lymphoma cells. The purification procedure including gel filtration on DEAE and CM-Sephadex resulted in a 400-fold increase of the enzyme specific activity. It was shown that optimal proliferation of T-lymphocytes occurs upon consecutive treatment of cells with phytohaemagglutinin and IL-2 as well as in the presence of a serum. The properties and procedure of isolation of the long proliferating line of IL-2-dependent T-cells B-5 were described. Proliferation of B-5 cells completely depended on the presence of IL-2 in the medium, although long-term proliferation occurred upon periodic stimulation of cells with the antigen (allogenic lymphocytes). In the absence of IL-2 B-5 cells decay within 36 hours. The perspective uses of IL-2 prepared from the cultural fluid of human peripheral blood lymphocytes for adoptive immunotherapy of tumours and the applicability of IL-2-dependent B-5 cells for testing the activity of IL-2 preparations from various sources are discussed.

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The possibility of generating large quantities of highly active interferon from human placenta amniotic membrane (plaferon) has been demonstrated. Plaferon is innocuous and nonreactogenic in experimental models and has an antiviral effect of wide spectrum. The activity is resistant to DNase, RNase, lipase, and stable at pH 2. A polyclonal serum to human leukocyte interferon and monoclonal NK-2 antibody did not inhibit the antiviral activity of plaferon. The level of hormones in plaferon and leukocyte interferon preparations was practically similar. In diploid cultures of human fibroblasts the antiviral condition under the effect of plaferon developed slower than under the effect of leukocyte interferon.

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The antiproliferative activity of placenta interferons (amniotic, chorional) prepared at the Institute of Experimental Morphology, Academy of Sciences of the Georgian SSR, was studied. Amniotic interferon was found to be most active in tumor cell cultures of human origin. Placenta interferons showed lower antiproliferative activity in continuous monkey and hamster kidney cell cultures and primary human embryo fibroblast cultures.

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