AIM:Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice.MATERIALS AND METHODS:Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens.RESULTS:MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days).CONCLUSION:Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.

The experimental study of macrophage-activating chemotactic peptide N-f-met-leu-phe-gly (chemotaxic peptide), as well as its liposomal form, on the proliferation and migration of colony-forming precursor cells in mice was carried out. The study revealed that the subcutaneous injection of chemotaxic peptide into mice in a dose of 20 Mg led to a pronounced, but short-term increase in the proliferation of such precursor cells in the marrow: as shown by the hydroxyurea "suicide" method, a day after the injection almost 50% of hematopoietic stem cells entered the S-phase of the cellular cycle; in addition, an increase in the content of colony-forming precursor cells in the peripheral blood and the spleen was observed. The injection of chemotaxic peptide, incapsulated into liposomes, led to a considerable increase in the duration of the stimulating effect, manifested by the maintenance of a stable proliferative state of the pool of hematopoietic stem cells during 4 weeks (the term of observation). This effect could be attributed to the formation of the liposomal "depot" and the gradual liberation of chemotaxic peptide from it.

The main causes of failures during allogenous bone marrow transplantation is the development of graft versus host reactions. The methods of its prevention and treatment are the use of large doses of human toxic cytostatics and immunosuppressants aimed against donor immunocompetent cells. A way of preventing the adverse effects of cytostatics are targeted transport of long-acting cytostatic dosage forms to an organ or target cell through carriers, such as liposomes, microcapsules, microspheres and their conjugates with monoclonal antibodies. For this purpose, the study used gelatin and gum arabic microspheres containing the immunosuppressive cytostatic adriamycin. To enhance the efficiency of cytostatic depositing at the site of transplantation, the procedure of intraosseous transplantation of allogenous bone marrow transplantation with long-acting adriamycin depositing was developed. With this approach, the authors could not only deposit the agent, but could substantially increase the proportion of donor cells kept at the site of grafting as compared to the intravenous and intraosseous infusion of donor cells. The main advantage of the new technique of allogenous bone marrow transplantation in combination with a long-acting cytostatic dosage form is that acute and chronic graft versus host reactions can be inhibited long by using adriamycin in subtherapeutic dosages.

Many microorganisms are capable of prolonged persistence in the marrow. In this study, carried out by the method of negative selection based on the treatment of mouse marrow cells with specific antimicrobial sera and complement, Mycoplasma arthritidis and L-forms of group B streptococci were found to be capable of persisting in the marrow in close association with the late category of clonogenic precursor cells, CFU-7, as well as, to a lesser extent, with late erythroid precursors, CFUe. Early colony-forming cells, CFUs-12 and PFUe, as well as granulocyto-macrophagal precursors, CFUgm, did not practically express antigens to the given infective agents on their surface.

A method for the evaluation of bacterial persistence in the bone marrow in association with particular clonogenic target cells was developed. The method was based on the negative selection of cells expressing microbial antigens after treatment with hyperimmune antiserum specific to a given infective agent and the subsequent quantitation of target cells thus eliminated in appropriate assays. Using this approach, we demonstrated that Mycoplasma arthritidis and L-forms of Streptococcus strain L-406 were capable of persisting in murine bone marrow in close association with CFUs-7 (a subpopulation of hematopoietic stem cells) for at least several months after experimental infection. Francisella tularensis was also found to be capable to express on the CFUs-7 membranes. Persisting microorganisms enhanced both proliferation and migration of CFUs-7.