A model of tick-borne encephalitis in BALB/c mice was used to investigate the protective anti-viral effect of an interferon inducer, poly(G).poly(C), and specific gamma-globulin administered to the animals together or separately in small doses 24 hours before or after virus inoculation. Administration to the animals of poly(G).poly(C) alone or gamma-globulin alone was shown to produce a poor protective effect. Simultaneous administration of both preparations resulted in a significant decrease of mouse mortality after infection. As a result of the pretreatment of chick embryo cell cultures with poly(G).poly(C) before inoculation and the addition of specific immune serum to the agar overlay after the Sindbis virus inoculation, its multiplication was inhibited much more than after treatment of the cells with interferon inducer alone or antibody alone. Possible mechanisms of the observed additive antiviral effects of the interferon inducer and antibody, including those associated with the influence on the virus-induced interferon production, as well as the possibility of their combined use for the prevention and treatment of viral infections are discussed.

Animals↗

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[Thermoactivation of poly(G).poly(C): a description of the effect and its hypothetical mechanism].

Heating of poly(G).poly(C) complex solutions at a temperature about 100 degrees C was shown to overcome a decrease in the antiviral and interferon-inducing activity of the preparations which were obtained at relatively high concentrations of polynucleotides from poly(G) stored in solution, or were stored frozen themselves. These unfavourable conditions contributed to stabilization of the poly(g) secondary structure and decrease in the degree of regularity of the complex molecules. The results suggest that thermal activation of such poly (G). poly(C) preparations occurred in 2 stages by melting residual free regions of poly(G) and their subsequent interaction with poly(C) with formation of a more regular complex.

Animals↗

PubMedDate not supplied

[Effect of different polyribonucleotide interferonogens on acute and latent viral infections in mice].

Poly(G) . poly(C) and poly(I) . poly(C) complexes administered soon after the viral challenge induced a high survival rate in mice with experimental tick-borne encephalitis. The protective effect was still noted when the treatment was given 24 hours after the infection. If the therapy was conducted at the end of the incubation period, at the peak of the virus reproduction in the mouse brain, poly(I) . poly(C) intensified the infection development and increased the animal death rate, while poly(G) . poly(C) had no such effect. Poly(I) . poly(C) injected 12 hours after the peak of the virus-induced interferonogenesis led to death of 80% animals inoculated with non-pathogenous Newcastle disease virus. The action of various samples of poly(I) . poly(C) was diverse. Poly(G) . poly(C) failed to effect the outcome of latent viral infection. The death of infected mice induced by polyribonucleotide complexes was not connected with their anti-viral interferonogenous activity, but correlated with the level of their toxicity for the intact animals. The results of the study have confirmed the risk of using poly(I) . poly(C) for the therapy of viral infections, especially during their clinical manifestation, and proved the safety of application of poly(G) . poly(C) and of some other polyribonucleotide interferonogens.

Animals↗

PubMedDate not supplied

[Induction of plant resistance to the tobacco mosaic virus with a double-stranded poly(G)-poly(C) complex].

Inoculation of double-stranded polyribonucleotide poly(G) . poly(C) complex in a concentration of 50-200 micrograms/mg into tobacco and thornapple leaves was found to produce resistance of the plants to subsequent infection with tobacco mosaic virus (TMV) manifested in decreased number and size of local virus lesions. The induced resistance may spread over the plant and be found in the upper untreated leaves. The level of systemic resistance, however, is much lower than that of the resistance demonstrated in the injected leaves. Actinomycin D (5 micrograms/ml) had no significant effect on the number but stimulated the growth of lesions developing in leaves injected with poly(G) . poly(C) as well as increased their number in the upper leaves of the same plants proximal to the treated ones. Development of tobacco resistance to TMV was accompanied by changes in the activity of terminal oxidases, particularly peroxidase. Possible mechanisms of formation of induced resistance are discussed.

Plant Diseases↗

PubMedDate not supplied

[Laboratory and clinical study of biological activity of poly G-poly C complex].

Poly(G).poly(C) inoculated intravenously to mice in a dose of 100 microgram induced interferon in the blood in amounts comparable to those induced by poly(I).poly (C). In contrast to rapid accumulation (within 2 hours after induction) and rapid disappearance of interferon in response to poly(I).poly(C) inoculation, the interferon induced by poly(G).poly(C) reached the maximum titer by 6 hours and remained at a high level for 24 hours after inoculation. When given to human volunteers intranasally in a dose of 6 mg, the poly(G).poly(C) complex induced interferon in the blood serum in 70% of the subjects in a titer of 85 units/ml within 24 hours.

Administration, Intranasal↗

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[Biological activity of the poly(G).poly(C) complex, modified by divalent platinum compounds].

Modification of poly(G).poly(C) with cys-diaminodichloroplatinum (cys-DDP) at the level of rb = 0.02 increased the in vivo antiviral and interferon-inducing activity of the complex, in contrast to the data reported for complex poly(G).poly(C). Antiinfluenza activity in this case depends on the method of modification and increases more intensively when a ready complex is treated with cys-DDP, as against treatment of poly(G) alone before the formation of a complex with poly(C). If rb is increased, the activity reduces again. Modification with trans-DDP at rb = 0.02 also leads to an increase of antiinfluenza activity of poly(G).poly(C), but mainly after pretreatment of poly(G).

Animals↗

PubMedDate not supplied

[A method of determination of cholesterol contents on the surface of the human skin and prospects of its use. I. Atherosclerosis].

Proceeding from published data on lipid content and composition in human skin and on the possible relationship between cholesterol level in skin biopsy specimens and status of blood vessels, the authors measured cholesterol content in skin layers available for external extraction in patients with atherosclerosis with different types of dyslipoproteinemias. Effective conditions of extraction were developed permitting after external rapid atraumatic treatment extraction of the maximally possible amount of cholesterol, 1.5 to 1.6 mkg from 1 cm2 of the palm skin surface, this being a constant value for each examinee (coefficient of variations after 3-4 repetitions 5%). Though slight, but statistically reliable increase of the amount of surface-extractable cholesterol was observed in atherosclerosis patients. This parameter did not correlate with the blood serum concentration of lipid components. A correlation (r = 0.54, p < 0.001) was observed with an only serum lipoprotein parameter, the so-called dyslipoproteinemia coefficient representing the sum of "atherogenic" parameters (cholesterol+triglycerides) divided by alpha-lipoprotein cholesterol. Measurements of surface-extractable skin cholesterol may be used as an available discriminant of atherosclerosis; the method seems to find application in other diseases as well.

Arteriosclerosis↗

PubMedDate not supplied

[Cation permeability of liver mitochondrial membranes during Ca+-dependent anoxic damage in vitro].

Ca2+ ions are responsible for impairment of oxidative phosphorylation in rat liver mitochondria under anoxia in vitro. The decrease in this function is due to inhibition of electron transport over respiratory chain and to uncoupling. The increase in membrane permeability for H+, K+ and Na+ was observed on incubation of mitochondria under anoxic condition together with Ca2+. Uncoupling of phosphorylation depends on the increased permeability of the membranes for H+. The increased permeability of membranes for Na+ and K+ under energy liberation and in presence of penetrating anions led to active swelling of organelles and to secondary (osmotic) impairment. Ca2+-activated mitochondrial phospholipase A2 appears to participate in the organelle impairment under anoxia.

Animals↗