[A new approach to postexposure treatment of rabies by complex of immuno- and chemotherapy in belarus].

A method for preventive treatment of rabies with a complex of immuno- and chemotherapeutics was developed. Rifampicin was used a an etiotropic drug. In the experiments on laboratory animals infected with fixed and street strains of rabies virus it was shown to prolong the incubation period and to increase the survival rate. The protective mechanisms of rifampicin against rabies should be associated with inhibition of RNA transcription, as well as immunomodulating function of macrophages, dendritic cells, B- and T-cells. Since 1992, after the approval of the Ministry of Health of Belarus rifampicin is used in complex with antirabic vaccine for postexposure treatment of rabies in people after severe bites by infected animals (wolves, foxes, dogs). For an 18-year period (1992-2009) of integrated application of chemo- and immunotherapy in Belarus there was not registered any case of hydrophobia in people even after the heaviest wolf bites, incompatible with life (penetrating injuries of the skull, scalping, multiple bites).

[Photodynamic inhibition of infection caused by herpes simplex virus type 1 in the cultured cells, by using 5-aminolevulinic acid-induced porphyrins].

On simulating infection caused by different herpes simplex virus type 1 (HSV-1) variants responsive and unresponsive to the drugs acyclovir and phosphonoacetic acid in the cultured Vero and C6 cells has revealed the higher ability of target cells to accumulate 5-aminolevulenic acid (ALA)-induced endogenous porphyrins, which determines the selectivity of their photo damages. Optimal conditions have been defined for all the studied HSV-1 variants to show a virus-inhibiting effect upon photodynamic exposure of infected and ALA-treated cell cultures.

Virologic and serologic investigations of West Nile virus circulation in Belarus.

In 1985-1994 virologic and serologic investigations were performed for the purposes of West Nile (WN) virus circulation establishment on the territory of Belarus. Blood-sucking mosquitoes, midges, wild small mammals, birds as well as blood and cerebrospinal samples from patients with nondifferentiated fevers and from healthy individuals were under studies. Four virus strains were isolated in Belarus for the first time, namely: 1--from birds (48-WN Tremlya); 2--from Aedes mosquitoes (319 and 2438); 1--from a febrile patient (Win). Their antigenic and biological properties were examined in cell cultures and laboratory animals. The isolates turned to be identical with each other and closely related to reference Egypt strain Eg 101, that is a topotype for the African virus group. One more WN virus strain (8891) was isolated from Anopheles mosquitoes in 1999. Specific antibodies to the virus in human blood sera were identified by immunological and serologic assays in 1.7% of Belarusian population. In Gomel and Brest Regions the percentage of seropositive individuals reached 5.8 and 15.4, respectively. WN virus antibodies prevailed in 0.6-5.8% of cattle, in 2.9-6.8% of wild small mammals and in 6.5-16.7% of birds. Thus, the conclusion was made on the existence of favourable conditions for the virus spread throughout the whole country and in the south in particular. Blood-sucking mosquitoes and birds are principle vectors in WN virus circulation in Belarus. 16 serologically confirmed cases of WN encephalitis were revealed in patients with fever of obscure etiology. In the view of the given data, reports on the reemergence of the pathogen in different countries and the tendency in global warming WN virus monitoring should become a subject of concern for Belarusian public medical care services.

[Experience in the use of chemical compounds for the primary identification and differentiation of enteroviruses]. / Opyt ispol'zovaniia khimicheskikh soedinenii dlia pervichnoi identifikatsii i differentsiatsii énterovirusov.

Data on the usage of chemical inhibitors nifan and belvtazid, which possess a selective and antienteroviral effect, in the primary identification of enteroviruses and their differentiation into polio- and non-poliomyelytic ones isolated from human clinical materials or the environment by using the cell culture are presented in the article. The method is recommended for the practical use by the virology service in the diagnostics of enteroviral infections and in the identification of cytopathic agents isolated from the enviroment.

[Water-borne outbreak of serous meningitis caused by Echovirus-30 in Belarus]. / Vodnaia vspyshka seroznogo meningita, vyzvannaia virosom Echo-30, v Belarus.

In recent years outbreak of enterovirus infections caused by Echovirus-30 were rather frequently registered in different European countries. A major outbreak caused by this virus took place during the summer-autumn period of 1997 in the city of Gomel, Belarus. Sanitary epidemiological and molecular epidemiological studies made it possible to determine that the outbreak was water-borne. The sequence analysis of Echovirus-30 strains isolated from water and the cerebrospinal fluid of patients revealed a minor divergence between them (0.2%) indicative of their practical identity. The comparison of the Belorussian isolates with the strains isolated in Europe in 1994-1998 also showed a small percentage of differences in their genomes, which showed that the outbreak of Echovirus-30 infection was probably brought to Belarus from the territories of European countries.

Progressive muscular atrophy variant of familial amyotrophic lateral sclerosis (PMA/ALS).

Twelve cases of adult-onset progressive muscular atrophy variant of amyotrophic lateral sclerosis (PMA/ALS) were studied in a small rural population of 1500 in the Republic of Belarus (former Soviet Union). The patients were members of three apparently related kindreds, each showing autosomal dominant pattern of disease inheritance. The average age at clinical onset ranged from 26 to 57 years (mean, 40 years). Each patient suffered from skeletal muscle weakness and wasting, starting in the limbs and spreading to the trunk and neck, with very limited bulbar and no upper motor neuron involvement. Death from respiratory failure occurred from 13 to 48 months (mean, 28 months) after first symptoms. Dramatically decreased number of spinal motor neurons was the most characteristic neuropathologic feature in two autopsied cases. Most of the remaining degenerating neurons contained intracytoplasmic hyaline inclusion bodies. A D101N mutation in exon 4 of the SOD1 gene was identified in a PMA/ALS patient and in one of her three unaffected children. Our data support the view that some subtypes of familial ALS associated with SOD1 mutations may present as PMA. Diagnostic criteria of ALS should be accordingly modified to include the PMA variant of familial ALS.

[Change in the sensitivity of influenza virus, replicating in the presence of rimantadine, to antiviral agents]. / Izmenenie chuvstvitel'nosti virusa grippa, razmnozhivshegosia v prisutstvii remantadina, k protivovirusnym preparatam.

A variant obtained by a single passage of the initial FPV in the presence of 25 micrograms/ml rimantadine is more resistant to the drug than the parental virus. Sensitivity to rimantadine is higher in a variant obtained similarly by cell culture infection with rimantadine-resistant FPV. Potentiation of the antiviral effect of a combination of ribavirin (12-25 micrograms/ml) and rimantadine (0.1-6 micrograms/ml) is decreased or null if rimantadine dose is increased to 12-25 micrograms/ml; this phenomenon does not depend on the sensitivity of infective virus to rimantadine. Antiviral effect of drug combination with a high concentration of rimantadine is due to ribavirin alone.

[Use of rapid methods in detection of enteroviruses]. / Ispol'zovanie ékspress-metodov dlia detektsii énterovirusov.

Indirect immunofluorescence (IIF) and RT-PCR were used for rapid diagnosis of enterovirus infection during an outbreak of aseptic meningitis in Gomel. IgM to enterovirus were detected in 93.6% sera by IIF and in 71.4% cerebrospinal fluid specimens by RT-PCR. IIF takes only 1.5-2 h and RT-PCR 6-7 h. The methods are recommended for rapid diagnosis of enterovirus infection.

[Polypeptides from influenza virus, obtained in the presence of high concentrations of rimantadine]. / Polipeptidy virusa grippa, poluchennogo v prisutstvii vysokikh kontsentratsii remantadina.

FPV/Rostock obtained in the presence of remantadine (25 micrograms/ml) is studied. This variant of the virus is characterized by a decreased amount of M1-protein. Its buoyant density in urograffin density gradient is 1.20 gamma/cm3 vs. 1.18 and 1.175 g/cm3 for initial FPV and remantadine-resistant FPV, respectively. Purification and concentration decreases the hemagglutinating activity of the virus 5-10 times more intensely than that of initial and remantadine-resistant FPV. On the other hand, the production of virus-specific proteins and intracellular distribution of hemagglutinin in this virus variant were not changed. The changes associated with a decrease of hemagglutinin and M1-protein content in virions are believed to manifest at a later stage preceding virion release from the cell.

[Suppression of the reproduction of the human immunodeficiency virus (HIV) with a cytokine-like antiviral factor]. / Podavlenie reproduktsii virusa immunodefitsita cheloveka (VICh) tsitokinopodobnym antivirusnym faktorom.

Cytokine-like antivirus factor, obtained from the culture fluid of chick embryo fibroblasts, was found to possess inhibitory activity with respect to HIV-1 (strains 1/Zmb and RF). The treatment of HIV-infected cell culture with cytokine-like factor was accompanied by a decrease in the cytopathic effect of the agent without manifestations of cytotoxicity. The combined use of the cytokine-like factor and azidothymidine at near-threshold concentrations was not accompanied by an increase in the antivirus effect, observed after the use of each preparation separately.

[Features of the antiviral effect of carbocyclic compounds depending on their concentration]. / Osobennosti protivovirusnogo deistviia soedinenii karbotsiklicheskogo riada v zavisimosti ot ikh kontsentratsii.

Antiviral agents and new agents possessing antiviral properties and characterized by a carbocyclic (carcass) structure were shown to differ from other, specifically, heterocyclic compounds, by the presence of a range from the maximally effective to maximally tolerable concentrations, the antiviral effect decreasing in this range of concentrations. This feature was observed in cell cultures, chick embryos, and laboratory animals in experiments with different influenza viruses and RS virus.

[The efficacy of an antiviral factor obtained from infected chick embryo fibroblasts in an experimental herpetic infection]. / Effektivnost' antivirusnogo faktora, poluchaemogo iz infitsirovannykh fibroblastov kurinogo émbriona, pri éksperimental'noi gerpeticheskoi infektsii.

Treatment of mice with an antiviral factor obtained from the culture medium of infected chick embryo fibroblasts protected them against lethal meningoencephalitis caused by herpes simplex virus. The degree of protection varied from 50 to 75% depending on the virus dose, the route of infection, and the mode of the antiviral factor application.

[Virus-induced dyslipidemias as possible risk factors in the development of somatic diseases]. / Virusindutsirovannye dislipidemii kak vozmozhnye faktory riska v razvitii somaticheskikh zabolevanii.

Experimental and clinical studies showed a number of virus infections to be accompanied by lipidemic disorders. Experimentally, dyslipidemias were found in tick-borne encephalitis (TBE) in mice, rotavirus infection in rabbits, and amyotrophic leukospongiosis in guinea pigs. The possibility of correcting the virus-induced lipidemic disorders with an antiviral drug, lincomycin, was demonstrated in TBE in mice. Dynamic study of the lipidemic status of patients with virus hepatitis A revealed marked dyslipidemia of the atherogenic type which was stable and persisted up to the time of clinical recovery. The data obtained supplement the current concepts concerning the pathogenesis of virus infections.

[Dyslipidemia in herpetic infection]. / Dislipidemiia pri gerpeticheskoi infektsii.

Herpes ophthalmicus (HO) patients were examined for lipid spectrum of the serum. The tests revealed dyslipidemia (DLE) with a distinctive rise in the levels of total cholesterol (CS), alpha-CS and beta-CS. The severity of the lipidemic shifts correlated with that of the infection. DLE was more marked in recurrent HO. Clinical evidence was consistent with experimental findings. In rabbit models, herpetic keratoconjunctivitis was characterized by pronounced lipidemic alterations correctable with antiherpetic drug furavir. The results are discussed in terms of herpetic infection pathogenesis and its role in the development of atherosclerosis.

[New properties of trental as an inhibitor of viral activity with a wide range of activity]. / Novye svoistva trentala kak ingibitor virusnoi aktivnosti shirokogo spektra deistviia.

Experimental investigations on the spectrum and degree of the expression of trental antiviral activity were carried out. The investigations were done in cell cultures and laboratory animals using laboratory strains (including drug-resistant ones) of 13 viruses, causative agents of human and animal infections. The drug demonstrated its activity against 8 viruses of 7 families. It was highly active against 5 viruses: herpes simplex virus (including its acyclovir-resistant strain), vaccinia virus (including its methisazone-resistant strain), rotavirus and tick-borne encephalitis virus. As regards other viruses, its activity was less pronounced (hepatitis JA virus) or low (vesicular stomatitis virus, West Nile virus). It was concluded that, being a cardiovascular drug, trental was an effective broad spectrum virus inhibitor.

[The characteristics of thymus involvement in regional and generalized forms of herpetic infection]. / Osobennosti porazheniia timusa pri regional'noi i generalizovannoi formakh gerpeticheskoi infektsii.

The features of thymus involvement in pathologic process in different types of experimental herpetic infection in rabbits were studied using morphologic and immunologic analysis methods. Insignificant features of thymus pathology were revealed in animals with regional manifestations of the infection in the form of ophthalmoherpes, whereas the rabbits with generalized herpes simplex virus (HSV) infection by retrosternal administration showed pronounced structural-functional changes and the presence of virus antigens as well, which may indicate the possibility of HSV reproduction in thymus cells.

[The action of reserpine in experimental rabies infection]. / Izuchenie deistviia rezerpina pri éksperimental'noi rabicheskoi infektsii.

Experimental studies in laboratory animals showed reserpine in doses of 0.01-0.05 mg/kg body weight to inhibit the development of rabies infection in white mice and rabbits by 40.0-83.4% depending on the dose and mode of administration. The inhibiting properties of reserpine were demonstrated for both fixed and street rabies virus strains. The protective effect of the drug was manifested after parenteral and oral administration to the infected animals. The experimental data suggest that reserpine may be used as an antiviral drug for protective treatment of rabies in the incubation period.