Role of Ebola Virus vp24 Protein in Inhibition of Interferonogenesis.

The effects of recombinant analog of natural Ebola virus protein vp24 in configurations virulent (vp24-ad) and avirulent (vp24-w) for guinea pigs on interferonogenesis were studied in vivo and in vitro. Amino acid differences were determined by His186 substitution in avirulent (nonlethal) configuration for Tyr in the virulent (lethal) one. Recombinant analogs vp24-w and vp24-ad inhibited interferonogenesis in vivo and in vitro. Inhibition by the two protein configurations was virtually the same.

[Experimental and clinicolaboratory evaluation of complex therapy efficacy in arboviral infections].

Search for drugs efficient in prophylaxis and treatment of dangerous infections (especially arboviral ones) is rather actual, since no specific therapy is available. Many-year investigations of interferon inductors showed that they had immunomodulating, antiviral and antiinflammatory effects and were low toxic. The present study demonstrated that the protective effect was the following: Venezuelan equine encephalitis (VEE)--cycloferon > amixin = ridostin, Rift Valley fever (RVF)--cycloferon > amixin > ridostin, predator pox (PP)--cycloferon > amixin = ridostin, that was obvious that cycloferon was the most active agent in the treatment of VEE, RVF and PP, thus making it possible to acknowledge its priority in prophylaxis and therapy of dangerous viral infections (DVI). Ribavirin in combination with cycloferon solution or cycloferon tablets provided shorter periods of the fever, minimized the intoxication syndrome, promoted earlier resolution of hemorrhagic eruption and lowered the frequency of complications, which was in favour of the disease prognosis.

[Experience in the use of present day immunomodulators for prophylaxis of exacerbations of chronic adenoiditis and development of pharyngeal tonsil hypertrophy in poor health children]. / Opyt primeneniia sovremennykh immunomoduliatorov dlia profilaktiki obostrenii khronicheskogo adenoidita i razvitiia gipertrofii glotochnoi mindaliny u chasto boleiushchikh detei.

Children having frequent acute respiratory infections and chronic adenoiditis were given immunomodulators (ridostin, IRS-19, polyoxidonium). As a result of such prophylaxis, respiratory infections and exacerbations of chronic adenoiditis occurred in poor-health children 2-2.5 times less frequently. Their local immunity and nonspecific resistance improved. Thus, modern immunomodulators can be used in poor-health children with chronic adenoiditis to prevent acute respiratory viral infection and development of pharyngeal tonsil hypertrophy as well as to treat them.

Interferon system in women with genital papillomavirus infection receiving immunomodulatory therapy.

The interferon system was studied in women with genital papillomavirus infection. In most patients the interferon system was activated, while the ability of lymphocytes to respond to inductors decreased. Laserotherapy and immunomodulatory therapy with larifan, ridostin, and viferon for 1 month normalized blood interferon concentration (39.4% patients) and interferon-gamma production by lymphocytes in response to inductors (87.9% patients). After laser monotherapy these parameters returned to normal only in 13.2 and 7.6% patients, respectively. Correlation and regression analyses showed that changes in the interferon system were synchronized after immunomodulatory therapy. These data indicate that immunomodulatory therapy produces a complex effect on the interferon system. Measurements of blood interferon level can be used to predict the effect of further treatment with interferon-gamma inductors.

[Combined use of killed vaccines and immunomodulator ridostin for urgent prevention of epidemic stomatitis, Aujeszky disease and carnivore plague in experiment]. / Sochetannoe ispol'zovanie ubitykh vaktsin i immunomoduliatora ridostina dlia ékstrennoi profilaktiki iashchura, bolezni Aueski i chumy plotoiadnykh v éksperimente.

Results of experimental studies of mice and pigs infected with foot-and-mouth disease virus, minks infected with Aujeszky's disease virus, and dogs infected with canine distemper virus are described. In animals with foot-and-mouth disease and Aujeszky's disease, combined treatment with killed vaccine and immunomodulator Ridostin by the scheme of urgent prophylaxis (3 days before infection) caused 75% (foot-and-mouth disease) and 100% (Aujeszky's disease) prevention of animal death and development of generalized infection. The use of Ridostin by the scheme of urgent prophylaxis in a canine distemper infection focus arrested clinical symptoms of the disease in 50% of animals received immunomodulator. Clinical symptoms of canine distemper in the other dogs treated with immunomodulator were manifested in a mild form, and their appearance was delayed to 23-25 days after contact with infected animal.

[Effectiveness of the interferon inducers ridostin and camedon in prevention and treatment of experimental alpha- and flavivirus infections]. / Effektivnost' induktorov interferona ridostina i kamedona v profilaktike i lechenii éksperimental'nykh al'fa- i flavivirusnykh infektsii.

Antiviral activity of rybamidil (virasol) and interferon inducers ridostine and camedone developed in Russia and introduced in practical medicine has been studied in mice with experimentally induced arboviral infections, flavivirus (tick-borne encephalitis-TBE, and yellow fever-YF) and alphavirus ones (Western and Eastern equine encephalomyelitis-WEE and EEE). Rybamidil injected subcutaneously proved to be ineffective both for prevention and treatment of these infections. Early interferon inducers ridostine and camedone (larifan) with a peak of interferon production 4 hours after injection, when used in doses of 5 and 150 mg/ kg, respectively, had a clear-cut prophylactic antiviral effect if injected 24 or 4 hours before infection. Ridostine had a distinct antiviral effect, providing up to 40% protection from TBE, YF, and WEE.

[The efficacy of the emergency prophylactic and therapeutic actions of immunomodulators in experimental filovirus infections]. / Effektivnost' ékstrenno-profilakticheskogo i lechebnogo deistviia immunomoduliatorov pri éksperimental'nykh filovirusnykh infektsiiakh.

The study of the preventive and therapeutic action of some immunomodulators (ridostin, reaferon and polyribonate) used alone and in combinations was conducted on laboratory animals infected aerogenically by Marburg or Ebola virus. It was found that special preventive intranasal and intramuscular administration of ridostin provided protection of the animals infected by Marburg virus (p = 0.1) and an increase in their mean lifespan by 2.4 days (p = 0.15). In the Ebola infection combined administration of ridostin and reaferon caused an essential increase in the mean lifespan of the animals by 2.9 days (p = 0.04). None of the tested drugs had any significant positive effect when used in various combinations according to the treatment schemes in Marburg and Ebola infections in guinea pigs.

[The efficacy of the therapeutic and prophylactic actions of immunomodulators in experimental infection due to the causative agent of Venezuelan equine encephalomyelitis]. / Effektivnost' lechebno-profilakticheskogo deistviia immunomoduliatorov pri éksperimental'noi infektsii, vyzvannoi vozbuditeliami venesuél'skogo éntsefalomielita loshadei.

The investigation of the prevention and treatment action of some immunomodulators (ridostin, reaferon and polyribonate) used alone and in combinations was conducted on laboratory animals infected aerogenically by Venezuelan equine encephalitis (VEE) virus. A lower death rate of the aerogenically infected mice (10-30 respiratory LD50) was observed after intramuscular injection of ridostin. The preventive affect of ridostin and ridostin + reaferon administered intranasally and intramuscularly was achieved in the aerogenically infected guinea pigs (10 respiratory LD50). The results of the study on the early virus reproduction in the animals were used for the choice of the treatment scheme. The immunomodulators had no effect when the treatment was started 1 day after the VEE virus infection.

[The natural killer activity and indices of the interferon status of patients with recurrent genital herpes being treated with ridostin]. / Aktivnost' estestvennykh killerov i pokazateli interferonovogo statusa u bol'nykh retsidiviruiushchim gerpesom genitalii pri lechenii ridostinom.

Natural killer cell activity (NK) in parallel with the interferon (IFN)-alpha and IFN-gamma production as well as with a level of IFN in the blood serum were studied in 15 patients with relapsing herpes genitalis (RHG). Rhidostin, well known as an IFN-alpha inducer, was used in a dose of 2 mg once daily for 3 days subcutaneously up to a total dose of 8 mg of the preparation. The NK cell activity and IFN-alpha production were shown to decrease in RHG more significantly in the stage of remission than during the relapse of the process. As a result of rhidostin therapy the NK cell activity was restored simultaneously with the positive clinical effect of the drug. Rhidostin was found to be an efficient modifier of the IFN system functioning in patients with RHG. The above data allow a conclusion that rhidostin exhibiting an independent antiviral and immunostimulating action might be useful in patients with a remission of RHG for prevention of its relapses.

[The treatment of protracted forms of Flexner dysentery]. / Lechenie zatiazhnykh form dizenterii Fleksnera.

The clinical efficacy of sodium nucleinate (SN) combined with splenin and quercetin given for lingering Flexner's dysentery in a group of 43 patients was compared with that of routine therapy used in a group of the same number of patients. It has been established that the above drug combination favours the elimination of the pathological symptoms of dyspepsia, the arrest of bacterial isolation and normalization of the immune status. Provided the effect of the combined drug treatment is insufficient, the method of choice is the administration of gene engineering alpha 2-interferon (reaferon) in combination with tocopherol acetate and rectal suppositories containing methyluracil.

[Changes of the necrotic area and functional indices of the myocardial microcirculatory bed during the treatment of experimental myocardial infarct with nitroglycerin, alpha-tocopherol and sodium nucleinate]. / Izmeneniia ploshchadi nekroza i pokazatelei sostoianiia mikrotsirkuliatornogo rusla miokarda krys pri lechenii éksperimental'nogo infarkta miokarda nitroglitserinom, al'fa-tokoferolom i natriia nukleinatom.

A new non-injection method was used to study the quantitative values characterizing the condition of the microcirculatory channel of the peri-infarct zones of rat myocardium without treatment and in treatment with nitroglycerin, alpha-tocopherol, and sodium nucleinate. In combined administration of these agents the total number of capillaries per unit of tissue volume increased, with subsequent increase of the capillary diameter, the exchange surface and the capacity of the capillary channel. These changes in the micro-circulatory channel were reflected in reduction of the focus of myocardial infarction. The authors discuss the mechanisms of the limiting effect of the complex of agents on restriction of the focus of affection in the early and late terms of myocardial infarction development.

[Effect of dekaris and sodium nucleinate on the blood antioxidant system of guinea pigs exposed to paprin inhalation]. / Vliianie dekarisa i nukleinata natriia na antioksidantnuiu sistemu krovi morskikh svinok pri ingaliatsionnom vozdeistvii paprina.

The changes of lipid peroxidation, thiol disulfide equilibrium, glucoso-6-phosphate dehydrogenase, catalase and superoxide dismutase activity under influence of immunostimulants during paprin inhalation were studied. Pro-oxidant effect of dekaris has been established. The conclusion on the necessity to estimate the level of antioxidant system under immunocorrection has been made.

[Antiherpetic activity of Soviet-made phosphonic acid derivatives and their combinations with interferon inducers in a model of ophthalmic herpes]. / Protivogerpeticheskaia aktivnost' otechestvennykh proizvodnykh fosfonovoi kisloty i ikh sochetanii s induktorami interferona na modeli oftal'mogerpesa.

A comparative analysis of the effectiveness of national phosphonic acid derivatives (FUK and FMK) and acyclic nucleoside, acycloguanosine (Acg), as well as interferon (INF) inducers, lafarin and ridostin, was carried out on the model of herpetic conjunctivitis in rabbits and guinea pigs. Upon therapeutic-prophylactic administration, lafarin reduced the intensity of eye symptoms 2-fold as compared with the controls (infected but untreated guinea-pigs). In rabbits with herpetic conjunctivitis, the therapeutic schedule of the use of FMK (FUK) and Acg shortened the duration of the disease by 7 and 11 days, respectively, as compared with the control. The combined use of chemical drugs and INF inducers, lafarin or ridostin, reduced the intensity of the disease manifestations 3-fold and shortened the duration of the disease by 8-11 days. The survival rate was 80%-100%. Use of the combination of the two chemical drugs gave an additive effect. The synergistic effect was observed with FMK used in combination with lafarin.