[Anti-rabies vaccines applied in the Russian Federation and perspectives for their improvement].

Rabies is almost ubiquitous (except in certain areas) and poses a significant danger to both animals and humans. Every year around 55,000 people die from this disease worldwide. In the Russian Federation alone 400,000- 450,000 patients annually apply for anti-rabies treatment. In the absolute majority of cases human infection is caused by contact with infected animals. In RF, a number of cultured inactivated anti-rabies vaccines for medical and veterinary purposes have been developed, registered and used for specific prevention of rabies. These vaccine preparations have shown high effectiveness in preventing infection in domestic and farm animals. At the same time, the main reservoir of the rabies virus (Mononegavirales: Rhabdoviridae: Lyssavirus) (RV) are wild carnivores (Mammalia: Carnivora). For the purpose of their oral immunization, live virus vaccines from attenuated (fixed) strains of RV that are little resistant in the external environment are used. In Western Europe and North America there is successful experience with recombinant anti-rabies vaccine preparations containing a viral glycoprotein gene (G-protein). Such vaccines are safe for humans and animals. In Russia also had been developed a vector anti-rabies vaccine based on adenovirus (Adenoviridae), which can be used to combat this infection. Currently, in addition to classical rabies, diseases caused by new, previously unknown lyssaviruses (Lyssavirus) are becoming increasingly important. Bats (Mammalia: Microchiroptera) are their vectors. Cases of illness and death after contact with these animals have been described. In the near future, we should expect the development of new vaccines that will provide protection not only against RV, but also against other lyssaviruses.

[Production of the monoclonal antibodies to the rabies virus nucleoprotein].

Five hybridomas secreting monoclonal antibodies (MAbs) for the nucleocapsid protein of the rabies virus were obtained through the fusion of the SP2/0 murine myeloma cells with splenocytes of BALB/c mice immunized with fixed rabies virus (CVS strain). All hybridomas secret MAbs of the IgG class that display different specificity to the nucleocapsids of rabies and rabies-related viruses. MAbs 2ell showed the specificity for the prevalent in Russia rabies viruses that are similar to commercially available anti-rabies conjugate.

[Genetic effects induced by nickel sulfate in germline and somatic cells of WR mice].

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (LD50) on the frequency of dominant lethal mutations and two-strand DNA breaks (TSBs) in germline cells and on an increase in frequency in gene mutations W(y) in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD50, while the lowest observable adverse effect level (LOAEL) was 1/100 LD50.

[Estimation of genetic effects of chronic exposure to low-dose rate gamma-radiation by cytogenetic methods and DNA-comet assay]. / Otsenka geneticheskikh éffektov khronicheskogo vozdeistviia nizkointensivnogo gamma-izlucheniia tsitogeneticheskimi metodami i metodom DNK-komet.

The study of genetic effects in CBA/lac mice exposed for 1 year to constant low dose-rate gamma-radiation at a dose-rate 63 cGy/year has been carried out. We have shown the significant increase in the DNA breaks' level in spleen lymphocytes by comet-assay beginning from the total absorbed dose of 20 cGy. It is possible that the DNA breaks' level increase resulted from the structural rearrangement of chromatin or induction of lymphocyte proliferation. The results obtained by micronucleus test have proved that the mutagenic effect of chronic low dose-rate gamma-radiation depends on cell type and respectively on cell proliferation rate, cell differentiation, etc. So, by the end of experiment the significant increase in the frequency of PCE with micronuclei (MN) was observed. However, in contrast, the frequency of NCE with MN was not increased. No significant increase in the percent of lung cells with MN was registered.

[The estimation of molecular and cytogenetic effects in mice exposed to chronic low dose gamma-radiation]. / Otsenka molekuliarnykh i tsitogeneticheskukh éffektov khronicheskogo vozdeistviia nizkointensivnogo gamma-izlucheniia u myshei.

Molecular and cytogenetic parameters were estimated in male CBA/lac mice exposed to chronic low dose-rate gamma-radiation (62 cGy/year) for 40, 80, 120, 210, and 365 days. After 40 days of exposure (6.7 cGy), spleen lymphocyte susceptibility to hydrogen peroxide was shown to increase. However, beginning from the day 120 of the treatment (20.4 cGy), the opposite effect was observed. An increase in number of the DNA-protein crosslinks was recorded in spleen lymphocytes only on day 40 of the experiment. The number of DNA breaks increased significantly beginning from day 120 of the experiment, as shown by the DNA-comet method. On the day 210 of irradiation, the frequency of abnormal sperm heads in the mice significantly increased. The number of normochromatic micronucleated erythrocytes of the peripheral blood remained unchanged.