[The interferon-inducing and immunomodulating action of bonafton in chronic diseases of the oral mucosa]. / Izuchenie interferonindutsiruiushchego i immunomoduliruiushchego deistviia bonaftona pri khronicheskikh zabolevaniiakh slizistoi obolochki polosti rta.

The immunocorrective activity of bonaphthon, an antiviral agent, was studied in 27 patients with chronic diseases of the buccal mucosa (recurrent aphthous stomatitis, lichen ruber planus, Melkersson-Rosenthal's syndrome). Bonaphthon therapy resulted in quite a number of patients in elevation of serum interferon titer and of the titer of specific antiherpetic antibodies. These results evidence that, besides the antiviral effect, bonaphthon is characterized by an immunomodulating effect and is conducive to fortification of the defense potential of the body in patients with stubborn chronic diseases of the buccal mucosa.

[Interferon-inducing and immunostimulating activity of bonafton in an experiment]. / Izuchenie interferonindutsiruiushchei i immunostimuliruiushchei aktivnosti bonaftona v éksperimente.

It was shown for the first time that the antiviral drug bonafton administered orally to nonlinear albino mice in single doses of 5, 12.5 and 25 mg/kg induced production of interferon in the animal blood serum. The maximum interferon titer of 160-320 IU/ml was observed 18 hours after the drug administration in a dose of 12.5 mg/kg. In low doses of 5 to 12.5 mg/kg bonafton increased the nonspecific resistance of the mice to experimental viral infections when administered orally in single doses not earlier than 2 weeks prior to the contamination. The ability of the drug to stimulate the host protective forces probably plays a certain role in the mechanism of its therapeutic action in severe viral infections of man such as severe recurring ophthalmic herpes, genital herpes, Behçet's disease, Melkersson-Rosenthal syndrome and others.

[Optimization of the schemes for using interferon inducers]. / Optimizatsiia skhem ispol'zovaniia induktorov interferona.

The results of study on 2 Soviet interferon inductors, i.e. the synthetic polyguacyl polynucleotide and natural double-strand phage RNA or dsRNA were studied. It was shown that the time course of accumulation and period of circulation of interferon depended on the route of the inductor administration. The antiviral activity of polyguacyl and dsRNA in experimental influenza and tick-borne encephalitis is described. The maximum protective effect with respect to experimental influenza was observed with intranasal administration of the drugs 4 hours before inoculation. A pronounced protective effect with respect to tick-borne encephalitis was observed with intraperitoneal administration of the inductors or their use in the form of aerosols. Direct correlation between interferon production and the final protective effect was found.

[Trial of polyguacyl safety and tolerance]. / Ispytanie bezvrednosti i perenosimosti poliguatsila.

The results of studies of the antiviral and interferon-inducing activity of the synthetic interferon inducer polyguacyl in white mice as well as the results of the study of safety and tolerance of this drug given to human subjects as aerosol and intranasally are presented. Both modes of administration to mice induced production of endogenous interferon, although after intranasal inoculation high interferon titres in the blood serum of the animals were observed for longer periods of time, whereas after aerosol administration interferon disappeared more rapidly. Significant antiviral protection was achieved only by the intranasal administration of the inducer resulting in 84.0% survival of the animals challenged with the mouse-adapted influenza A/Aichi virus. Clinical trials of polyguacyl in human volunteers demonstrated the safety and good tolerance of this drug given both as aerosol and intranasally.

[Interferon-inducing and protective action of polyguacyl in an experimental influenza infection]. / Izuchenie interferonindutsiruiushchego i zashchitnogo deistviia poliguatsila pri éksperimental'noi grippoznoi infektsii.

A comparative study of the interferon-inducing and anti-influenza activity of polyguacyl, an interferon inducer, given to human volunteers intranasally and as an aerosol, was carried out. The induction of endogenous interferon in the blood to 100-127 units/ml was observed only after intranasal administration of 5 mg polyguacyl. By both routes of administration the inducer did not diminish the implantation of the virus and development of postvaccination reactions in volunteers to intranasal administration of live influenza A (H1N1) vaccine.

[Influenza virus sensitivity to interferon and its inducer]. / Chuvstvitel'nost' virusov grippa k interferonu i ego induktoru.

The results of the study on influenza virus sensitivity to interferon of two kinds (human and chicken) and its inducer, poly(G) . poly(C) are presented. Differences in this characteristic among human and animal influenza viruses were demonstrated. There was a correlation between sensitivity to poly(G) . poly(C)-induced interferon and sensitivity to chicken interferon. Comparative studies of sensitivity to interferon in parent viruses and recombinants demonstrated that recombinants derived this property from one of the parental strains.

[Combined use of isoprinosine and an interferon inducer in experimental viral infection]. / Kombinirovannoe primenenie izoprinozina i induktora interferona pri éksperimental'noi virusnoi infektsii.

It was shown for the first time that isoprinosine has an antiviral effect in treatment of experimental forest-spring encephalitis. The combined use of isoprinosine with mouse interferon in treatment of the infected albino mice potentiated antiviral effect as compared to the effect of substances used alone. In addition, the combined use of isoprinosine and interferon inductor in minimum nontoxic amounts resulted in a 4--8 fold increase in the titers of the serum interferon and a statistically significant increase in the mouse resistance to the viral infection. It was found that the efficacy of the combined use of isoprinosine and mouse interferon or interferon inductor increased, when the interval between the drug administrations was prolonged up to 24 hours. The maximum effect providing 75 per cent protection of the animals from the viral infection and an increase in the average life span of the mice from 7.9 to 17.4 days was observed with the combined use of isoprinosine and interferon inductor.

[Aerosol method of using interferon inducers]. / Aérozol'nyi sposob primeneniia induktorov interferona.

A method for aerosol use of interferon inducer in laboratory animals employing an ultrasonic aerosol generator is described. Formules and a table of calculations of an inhalation dose of interferon inducer in solution when atomized in a chamber, as well as in the use of individual masks for monkeys are presented. The aerosol administration of interferon inducer (replicative from RNA of phage f2) was found to be effective in inducing interferon production in mice and monkeys. Prophylactic administration of the inducer 4 and 24 hours before inoculation protected from 50% to 75% of mice against a fatal influenza infection.

[Biological activity of a new Soviet natural inducer, double-stranded RNA]. / Biologicheskaia aktivnost' novogo otechestvennogo prirodnogo induktora--dvunitevoi RNK.

Antiviral activity of a two-spiral RNA (ts RNA), a new natural interferon inductor was studied. It was shown that ts RNA extracted from a phage infected E. coli culture was an active inductor of interferon and resistance to infection with the forestspring encephalitis virus experimental animals. In experiments on 10-12 g mice ts RNA administered in a dose of 50 micrograms/mouse 6 hours after the infection induced up to 1280 units/ml of the serum interferon. When the inductor was administered repeatedly, the experimental animals developed hyporeactivity resulting in a marked decrease in interferon production after the 3rd subsequent injection. The most pronounced effect with respect to the forest-spring encephalitis virus was observed when the inductor was administered intraperitoneally in a dose of 20 micrograms/mouse 4 hours before the infection. The protective effect was less pronounced when the inductor was administered 24 and 48 hours before the infection. A two-fold administration of the inductor did not increase the antiviral effect. When the inductor was administered in a dose of 100 micrograms 14 days before the infection, the animals showed an increase in the nonspecific resistance to the infection resulting in a marked antiviral effect.

[Comparative antiviral and interferonogenic activity of natural and synthetic interferon inducers in vitro and in vivo]. / Sravnitel'naia protivovirusnaia i interferonogennaia aktivnost' prirodnogo i sinteticheskogo induktorov interferona in vitro i in vivo.

Biological activities of the RNA replicative form of phage f2, a natural interferon inductor and poly-I -- poly-C, a synthetic polyribonucleotide complex were studied comparatively. Differences in the comparative interferonogenic and antiviral activity of the inductors were as dependent on the type of the cell system. It was shown that DEAE-dextran increased the interferon-inducing activity of RFf2 in the cell culture by 4 to 8 times. The dynamics of the interferonogenic and antiviral activity of RFf2 in the L-929 cell culture was studied. Interferon appeared in the culture fluid in 6--8 hours and reached its maximum titers (128 IU50/ml) by the 24th hour, the maximum protection of the cells being also developed by the 12th--24th hour, reaching on an average 51 g PFU/ml. It was shown in the experiments with green marmosets that administration of RFf2 in the form of aerosol in a dose of 2.3 mg/kg induced interferon production in the blood serum the titers of which amounted to 80--160 IU50/ml 24 hours after the administration.

[Comparative experimental studies of the combined use of vaccines, interferon and interferon inducers in neurovirus infections]. / Sravnitel'nye issledovaniia po éksperimental'nomu izucheniiu sochetannogo primeneniia vaktsin, interferona i induktorov interferona pri nekotorykh neirovirusnykh infektsiiakh.

Comparative investigations of the combined use of vaccines and interferon in tick-borne encephalitis, herpes, and acute encephalomyelitis of man showed that up to 78% of animal protection against 10--50 LD50 of intraperitoneally inoculated viruses could be achieved. Vaccination alone provided up to 56% survival of the infected mice, while administration of interferon subcutaneously or intraperitoneally in a dose of 800 units (53,300 units per 1 kilo body weight) 18--20 hours before virus gave a survival rate of 36%. The use of vaccine in combination with an interferon inducer, phage of f2 RNA, in tick-borne encephalitis gave up to 75% survival of the infected mice. Four hours after administration, interferon could be detected in mouse sera in a concentration up to 640 units/ml which in immune mice accumulated more rapidly and remained at a higher level 18 hours after inoculation of the inducer.

[Effect of a natural interferon inducer (RFf2) on the formation of vaccinal immunity to tick-borne encephalitis]. / Vliianie prirodnogo induktora interferona (RFf2) na formirovanie vaktsinal'nogo immuniteta k kleshchevomu éntsefalitu.

The effect of the interferon inductor of the natural origin (RFf2) on formation of vaccinal immunity to vernal encephalitis was studied. A single intraperitoneal administration of the preparation in a dose of 10 gamma per a mouse 2 hours after the first injection of the vaccine resulted in increased resistance of the mice to the lethal dose of the infecting virus which was introduced 14 days after the vaccination completion. The production dynamics of interferon induced by RFf2 and its level in the serum of the immunized mice were the same as those in the non-vaccinated animals. An increased number of the vaccine injections, up to 3 did not result in a significant increase in the immunity with respect to either the level of the antiviral resistance or the level of the virus-neutralizing antibody accumulation.

[Interferonogenic and antiviral activity of the double-stranded replicative form of phage f2 RNA in tissue culture and on animals]. / Interferonogennaia i protivovirusnaia aktivnost' dvunitevoi replikativnoi formy RNK faga f2 v kul'ture tkani i na zhivotnykh.

Biological activity of a new natural interferon inductor, the replicative RNA form of phage f2 (RFf2) was studied. A possibility of using RFf2 for production of highly active interferon under conditions of superinduction providing an increase in the interferon yield by to 256--512 times as compared to the control samples was shown. The protective interferonogenic and antiviral effect of RFf2 in mice infected with Semliki forest virus (SFV) and tickborne encephalitis virus (TBEV) was studied on administration of the inductor by various routes. It was found that intraperitoneal administration of RFf2 in a dose of 10 gamma per a mouse protected the infected animals from death. It was accompanied by production of up to 1280 units/ml of interferon in the blood serum of the animals. Maximum protection of the animals from death under conditions of the experiment (80 per cent on infection with SFV and 65 per cent on infection with TBEV) was observed when the preparation was administered twice: 4 hours after the infection. Combined use of RFf2 with chemotherapeutics (rimantadine) increased the protective effect both in the tissue culture and in vivo.

[Study of viremia in chronic human herpetic infection]. / Izuchenie virusemii pri khronicheskoi gerpeticheskoi infektsii cheloveka.

Attempts at virus isolation were made on the blood specimens from patients with relapsing herpesvirus infection. Examinations of over 100 blood specimens from patients with various localizations of herpetic lesions yielded II strains of herpesvirus. In all the cases the virus was isolated from a mixture of leukocytes with erythrocytes of the blood of patients. The method of cocultivation of blood leukocytes with cell cultures was most sensitive and yielded 7 herpesvirus isolates. The herpesvirus isolates vary in their biological and antigenic properties.

[Study of the antigenic properties of herpesvirus strains isolated from herpetic lesions at different sites]. / Izuchenie antigennykh svoistv shtammov virusa gerpesa, vydelennykh iz gerpeticheskikh porazhenii razlichnoi lokalizatsii.

The antigenic properties of 15 strains of hepesvirus isolated from herpetic lesions of different localization were studied. The serotype of each strain was established by the neutralization tests with hyperimmune sera to the reference type 1 and 2 strains: the cross-neutralization tests revealed antigenic relationships between the strains of 1 and 2 serotypes. Most strains isolated from lesions of the genitalia belonged to type 2, although one strain isolated in herpes genitalis belonged to type 1, and 2 strains isolated from facial lesions also belonged to type 2. These results confirm the necessity of using inactivated polyvaccine prepared from herpesvirus strains of antigenic types 1 and 2 for relapse control therapy instead of using monovalent type 1 and type 2 vaccines as reported by foreign authors.

[Development and study of an experimental herpesvirus vaccine]. / Razrabotka i izuchenie éksperimental'noi protivogerpeticheskoi vaktsiny

The strains suitable for the development of herpesvirus vaccine were selected as a result of studies on numerous herpes virus strains isolated from patients with relapsing herpes infection of various localizations. Infectious tissue culture antigens were obtained by roller cultivation of chick embryo fibroblast cultures infected with herpesvirus in the presence of 0.2% human serum albumin. A high immunogenic and antigenic activity of the experimental vaccines prepared from these antigens was established. Animal experiments demonstrated the possibility of control of the specific activity of herpesvirus vaccines.

[Interferon production in vitro (by leukocytes) in response to arbovirus infections]. / Obrazovanie interferona in vitro (leikotsitami) pod vliianiem arbovirusnoi infektsii

Experiments on cultivation of Semliki Forest virus in suspensions of the blood from immune and intact white mice and rabbits showed that adsorption of virus of phagocytosis by these cells occurred in the process of cultivation. There was a relationship between the rate of virus adsorption and interferon production: upon rapid virus adsorption by the immune cells interferon production by these cells was more intensive early after inoculation of the inducer. The dynamics of Semliki virus adsorption and of interferon production of leukocytes of white mice was close to that determined in cultivation of the virus in rabbit leukocyte suspension.

[Pathomorphology of experimental infections caused by a virus isolated from a case of encephalomyelopathy]. / Patomorfologiia éksperimental'noi infektsii, vyzvannoi virusom, vydelennym ot bol'noi éntsefalomielopatiei

Experimental infection was produced in white mice, rats, hamsters and rabbits inoculated with a virus isolated from the blood of a patient suffering from encephalopathy. Investigation of the pathomorphology of the experimental infection in white mice with with manifest clinical picture revealed acute meningoencephalomyelitis characterized by marked disorders in the central nervous system. In white rats and rabbits showing no symptoms of disease chronic affection of the CNS was established characterized by signs of encephalomyelopathy pathomorphologically similar to lesions observed in human cases of encephalopathy.