[A study of possibility to predict the sensitivity of different respiratory tract divisions to influenza].

To predict a potential value of a viral ID50 for a macro-organism of interest (e.g. humans), it is necessary to determine in vitro two parameters of the interaction of the virus with susceptible cells of the host, i.e. the probability of the virus' productive absorption on a susceptible cell and the average virus yield per cell. A different macroorganism (a model animal) and primary cells obtained from it can be used to determine the value of a scale factor, which accounts for the difference between the values of the probability of the virus' absorption measured in vivo and in vitro. An original mathematical model is used to convert the above-mentioned data to ID50 for the macroorganism of interest. It was shown that the method of cultivating influenza virus (A/ Aichi/2/68) in primary suspension culture of respiratory tract cells of rats and two breeds of mice may be used to estimate potential human susceptibility to novel influenza viruses. This work was sponsored by DAPRA, USA, and performed under the contract 450p to the International Science and Technology Center, Moscow.

[Target-cell susceptibility and lung phagocyte activity in mice with influenza virus resistance lowered by glucocorticoidal immunosuppression].

The results of the study showed that subcutaneous kenalog (Kn) lowered the resistance of mice to influenza virus (InV), as was seen by a decrease in 50% lethal dose and an increase in the degree of pulmonary tissue lesion, and the susceptibility of the lungs to InV, seen by the fact that 50% aerogenic infective dose (AID50) was significantly higher in the main group (Kn+InV) than in controls, which received Hanks solution subcutaneously (HS+InV). In vitro, 50% infective doses of InV for suspension of pulmonary and tracheal cells, characterizing their susceptibility to InV, were similar in Kn mice and controls. At the same time, lower resistance and higher degree of pulmonary inflammation noted in Kn mice after receiving a dose of InV that was much higher than an infecting one, was accompanied by the prevalence in the number as well as phagocyte and superoxide-producing activity of neutrophiles (Nph) over the same parameters for alveolar macrophages (AMph) as early as two days after receiving InV dose, vs. InV-infected controls. Evidently, one of the reasons for lower resistance to InV after Kn administration is significant disbalance between the functional activity of AMph and Nph populations. Ineffective AMph clearance of the lungs from InV and excessive number of recruited Nph and products of tissue disintegration may favor the development of respiratory failure and infectious-toxic shock, which leads to lower resistance in animals which receive Kn before InV infection.

[4647-cell culture for preparation of recombinant bivaccine against smallpox and hepatitis B].

The seeding and working banks of a 4647-cell culture have been created. The 4647-cell culture in these banks has a high proliferative activity, as well as the morphology, typical of this line, and the karyotype and the enzymogram, which are characteristic for the cells of an African talapoin (Cercopithecus aethiops). The culture is not contaminated with bacteria, fungi, Mycoplasma, and viruses, including oncoviruses. The deposited 4647 cells have high viral productive properties for the accumulation of the recombinant virus strain b7,5S2-S vaccine and keep the stability of all biological properties during a long-term cultivation. The continuous 4647 cell line was tested at the L. A. Tarasevich State Institute of SK. The seeding and working banks of 4647-cell culture at passages 108 and 128 are recommended as a substrate for cultivation of the strain b7,5S2-S vaccinia, used to prepare a bivaccine against smallpox and hepatitis B.

[The influence of glucocorticoid immunosuppression on the course of experimental influenza pneumonia].

The study demonstrates the effects of kenalog (Kn), a synthetic glucocorticoid hormone, on the course of virus A/Aichi/2/68 influenza in white mice. In doses of 5 and 10 mg/kg, Kn reduced the weight of the adrenal glands, thymus and spleen, which was accompanied by decrease of the resistance to the mentioned virus, judging by LD50 decrease vs. this index in the control infected group. Besides, four days after infecting with 5 LD50 of influenza virus (IV), lung virus and interferon titers were significantly lower in mice pretreated with Kn vs. mice treated with placebo. Lung cell susceptibility to IV in vitro was identical in mice treated with Kn or placebo. In ultrathin lung sections of IV-infected mice, both experimental and control ones, there was virus budding in bronchial epithelium cells and type I and II alveolocytes. Analysis of inflammatory effusion compound in semithin lung sections 6 days after IV infection, found a substantially smaller number of mature alveolar macrophages (AM) and a bigger number of neutrophiles vs. infected controls. The authors reckon that higher mortality of mice pretreated with Kn before infecting, is caused not by enhancement of IV reproduction in target lung cells during influenza development, but by the contribution of other pathogenic factors. One of those may be increase of neutrophilic migration into the lungs; neutrophiles are more able to realize their significant destructive potential under the condition of reduction in the clearing function of AM and IV infection.

[Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region]. / Funktsional'nyi polimorfizm genov p53 i CCR5 u dolgozhitelei Sibirskogo regiona.

The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.

Inactivation and mineralization of aerosol deposited model pathogenic microorganisms over TiO2 and Pt/TiO2.

Air disinfection from bacteria and viruses by means of photocatalytic oxidation is investigated with microorganisms loaded over photocatalysts' films from aerosols. Deposition method and equipment have been developed to load Mycobacterium smegmatis , Bacillus thuringiensis , vaccinia virus, and influenza A (H3N2) virus on slides with undoped TiO(2) and platinized sulfated TiO(2) (Pt/TiO(2)). Inactivation dynamics was measured under UVA irradiation and in the dark. About 90% inactivation is reached in 30 min irradiation on TiO(2) and from 90 to 99.8% on Pt/TiO(2). The first-order inactivation rate coefficient ranged from 0.18 to 0.03 min(-1), over Pt/TiO(2) being higher than on TiO(2) for all microorganisms except Bacillus thuringiensis. The photocatalytic mineralization of Bacillus thuringiensis was performed on TiO(2) and Pt/TiO(2) with different photocatalyst and microorganism loadings. Completeness of mineralization depended on the TiO(2) to bacteria mass ratio. The rate of the photocatalytic carbon dioxide production grows with both the cell mass increase and the photocatalyst mass increase. Pt/TiO(2) showed increased rate of mineralization as well as of the inactivation likely due to a better charge carrier separation in the doped semiconductor photocatalyst. The results demonstrate that photocatalytic filters with deposited TiO(2) or Pt/TiO(2) are able to inactivate aerosol microorganisms and completely decompose them into inorganic products and Pt/TiO(2) provides higher disinfection and mineralization rates.