[Efficacy of combined administration of ridostin and oseltamivir (tamiflu) for therapy and prophylaxis of experimental infection induced by influenza virus A (H5N1) in mice].

AIM: Study of possibility of treatment-prophylaxis effect increase during combined administration of ridostin and tamiflu in experiments in mice infected with highly pathogenic influenza virus strain A/chicken/Kurgan/05/2005 (H5N1). MATERIALS AND METHODS: Balb/c line mice infected intranasally with influenza virus at 100 and 10 LD50 doses received ridostin and tamiflu as monopreparation or the combined variant before or after the infection. The mice were observed for 16 days, lethality rate, protection coefficient and average life span were evaluated. Virus concentration in lungs was determined by using titration in MDCK cell line. RESULTS: Combined administration ofridostin and tamiflu after the infection increased survivability of the animals when compared with the control group, and reduced influenza virus concentration in lungs. CONCLUSION: Treatment effect during combined administration of ridostin and tamiflu after influenza virus infection increased.

[Biological properties of a prolonged action interferon inductor].

AIM: Evaluation of composite formulation of yeast double stranded RNA with polyglucinum (dsRNA-PG) effect on non-specific antiviral resistance factors in mice in comparison with commercial formulation Ridostin. MATERIALS AND METHODS: dsRNA and Ridostin formulations were injected intramuscularly once at the dose of 5 mg/ml, polyglucinum--at the dose of 3.75 mg/ml. 3, 5, 24, 48 and 72 hours after the injection serum interferon levels, neutrophil oxidation-reduction activity parameters, peritoneal macrophage phagocyte activity levels were analyzed in mice blood samples. RESULTS: New dsRNA and polyglucinum containing composite formulation is a non-specific resistance system stimulator. dsRNA-PG effect on interferon synthesis and mice phagocyte activity was higher than with Ridostin and developed earlier. Neutrophil function activation by the formulation had a prolonged effect. A possible explanation for increased activity of dsRNA and polyglucinum composite formulation is a modulating effect by the polysaccharide component. CONCLUSION: The new formulation may have a more intensive and prolonged protective effect against influenza virus in comparison with Ridostin.

[Antitumor properties of a liposomal form of a differentiation factor HLDF fragment in cultured cells].

Cytotoxic properties of a liposomal form of the HLDF6 hexapeptide, representing an HL-60 cell differentiation factor fragment, have been studied on a murine primary lymphosarcoma cell culture. It is established that the liposomal HLDF6 peptide is capable of inhibiting proliferation and enhancing death of the cells of both LS and RLS lymphosarcoma strains distinguished by their sensitivity to cytostatic agents. The effect of the preparation is determined by its antiproliferative and apoptogenic actions on the cells. Free HLDF6 peptide showed a lower cytotoxic activity with respect to the tumor cells as compared to the liposomal preparation.

Pharmacokinetics and antitumor effects of the drug containing TNF-α in nanoparticles.

Antitumor activity of TNF-α incorporated in nanoparticles (VLP-TNF-α) and dynamics of its accumulation and elimination from the blood and tumor tissue were studied in ICR mice. The VLP-TNF-α preparation exhibited higher antitumor activity compared to free TNF-α, presumably due to longer circulation of the cytokine in the blood and its more intensive accumulation by tumor tissue.

Antitumor and immunomodulating effects of a fragment of HL-60 cell differentiation factor in mice with lewis pulmonary carcinoma.

A six-member HLDF6 peptide, fragment of HL-60 cell differentiation factor, exhibited antimetastatic and immunomodulating effects.

[Investigation of antitumor activity of the hexamer fraction of HLDF-6 peptide as a differentiation factor in hemoblastoma-bearing mice].

A study of antitumor properties of HLDF-6 was carried out in DBA/2 mice with transplantable ascites lympholeukemia P-388 as well as in tumor cell culture. Immunomodulating characteristics were evaluated. Five-fold administration of HLDF-6 peptide to tumor-bearing mice inhibited tumor growth thus extending survival. As a result metabolic activity decreased which was followed by longer survival of lympholeukemia P-388 cells and enhanced cytological effect of peritoneal macrophages on tumor cells of the same strain.

Effect of granulocyte colony-stimulating factor on myocardium recovery in postinfarction period.

The effect of Neutrostim (preparation of granulocytic colony-stimulating factor) on recovery of myocardial tissue after acute myocardial infarction was studied in rats. A course of Neutrostim after ligation of the left coronary artery led to normalization of electrocardiographic and morphological parameters of the myocardium after one month.

[Effects of the dsRNA interferon inducer on the interaction between macrophages and Mycobacterium tuberculosis in vitro]. / Vliianie induktora interferona na osnove dvuspiral'noi RNK n vzaimodeistvie makrofagove i Mycobacterium tuberculosis in vitro.

Effects of the IFN inducer, yeast dsRNA, produced on the interaction between mouse macrophages and phagocytized mycobacteria were experimentally studied in vitro. Mycobacteria were shown to reproduce in macrophages in their initial infection at a ratio of 1:1.25, 1:2.5, 1:5 and 1:10, which was confirmed by an increased insertion of 5.6-[3H]-uracil in M. tuberculosis H37Rv; they also had a destructive impact on macrophages as verified by a higher release of lactic dehydrogenase (LDG) from macrophages. The dsRNA preparation, 40.0, 80.0 and 120.0 microg/ml, was demonstrated to decrease the insertion amount of labeled uracil in phagocytized mycobacteria at a macrophage:mycobacteria ratio of 1:10 and 1:100. The effect depended on a preparation dose and infection degree of macrophages. A decreased release of specific LDG from infected macrophages was shown under the same conditions. The dsRNA affects the interplay of macrophages and phagocytized mycobacteria through inhibiting the vitality of intracellular mycobacteria and through enhancing the stability of macrophages. Special studies denoted that dsRNA, 40.0 microg/ml and 120 microg/ml, activated the production of peroxidation compounds by neutrophils, which phagocytized the sheep erythrocytes. Finally, a possible mechanism of dsRNA impact on the interaction between macrophages and mycobacteria phagocytized by them is under discussion.

[Designing of a liquid serum panel containing or not class IgG antibodies specific to human cytomegalovirus]. / Konstruirovanie zhidkoi paneli syvorotok, soderzhashchikh i ne soderzhashchikh antitela klassa IgG k tsitomegalovirusu cheloveka.

Designing of a liquid serum panel for the determination of class G antibodies specific to human cytomegalovirus (HCMV) is under discussion. Sera were selected by ELISA for antibodies to HCMV and by PCR for CMV DNA. The serum panel comprises samples of positive and negative sera with high and low titers. Sera were stabilized by a stabilization solution. The panel shelf life was evaluated by routine methods and by the "accelerated aging" technique. Sera selected for a standard panel containing or not antibodies to HCMV preserve their properties and stability for as long as 1 year at 4 degrees C.

[Results of Befnorin clinical trails in healthy volunteers]. / Rezul'taty klinicheskogo ispytaniia preparata benforina na zdorovykh dobrovol'tsakh.

Clinical trails of Befnorin based on the human recombinant TNF-beta elaborated at the Research Design and Technology Institute of Biologically Active Substances, "Vector" State Research Center of Virology and Biotechnology, were carried out on healthy volunteers in compliance with a decision passed by the Committee of Medical and Immunobiological Preparations, Russia's Health Ministry. Single Befnorin doses of 5-10(4) U, 10(5) U, 5-10(5) U, and 10(6) U were administered as intramuscular injections. Clinical, biochemical and immunological parameters were registered for 7 days after a single dose. The drug had an impact on the below immunity indices: Fc-phagocytosis of monocytes, migration index and migration inhibition index. The dose of 10(5) U was proven to be most effective and safe. Supposedly, the drug can be effective in the treatment of herpetic diseases.

[Outlooks for using the interferon inducers in the treatment and prevention of influenza and acute respiratory viral diseases]. / Perspektivy ispol'zovaniia induktorov interferona v lechenii i profilaktike grippa i ORVI.

The methods of treatment by using the stimulators of the non-specific resistance system have been growing even more topical. Drugs based on interferon (INF) and its inducers belong to the group. IFN is of key importance in the regulation of antiviral immunity. The use of IFN inducers can be referred to as the most promising approach to enhancing and activating the body resistance mechanisms. The advantages of IFN inducers before IFN drugs, a wide spectrum of antiviral effects, compatibility with many pharmaceuticals, good tolerability by patients and effectiveness in different administration modes served as a basis for designing a new class of antiviral drugs--IFN inducers. A lot of experimental medical-and-biological research was made to evaluate the efficiency of IFN inducers in influenza. They were shown to possess a pronounced therapeutic-and-preventive action in experiment and clinical trials. Synthetic and natural dsRNA belong to IFN inducers. Multiple research made in cell culture and with experimental animals demonstrated a high interferon-inducing and antiviral activity of double-stranded RNA against influenza virus. A number of dsRNA-based IFN inducers are permitted for clinical use. Data obtained in clinical trials of such inducers are indicative of their pronounced therapeutic-and-clinical effect. Hence, the IFN inducers having different structures and origins can be regarded as promising in the treatment and prevention of influenza and acute respiratory viral diseases.

[The impact of compound of double-stranded RNA and hyaluronic acid on the parameters of non-specific resistance in mice]. / Vliianie kompozitsii dvuspiral'nykh RNK i gialuronovoi kisloty na pokazateli nespetsificheskoi ustoichivosti myshei.

The effect of yeast double-stranded RNA (dsRNA) and of hyaluronic acid (HA) compositions produced on the interferon synthesis, peritoneal phagocytic activity of macrophages and on the hematological parameters were studied in an experiment with white noninbred mice. HA was shown to enhance the dsRNA-induced interferon synthesis, to inhibit the leukopenic reaction and to produce no effect on the phagocytosis-stimulating activity. The data obtained are indicative of that HA is a promising preparation regarding its use within the interferon-inducing compositions based on dsRNA.

[Effect of tumor necrosis factor alpha on the efficiency of anti-rabies vaccination]. / Vliianie faktora nekroza opukholi alpha na éffektivnost' vaktsinatsii protiv beshenstva.

Recombinant tumor necrosis factor-alpha (TNF-alpha) improved the survival of random-bred albino mice vaccinated with antirabies vaccine after infection with rabies CVS strain. The agent dose of 0.1 microgram/animal, injected 1 day postvaccination, was the most effective. Improvement of antiviral resistance of non-vaccinated mice under the effect of TNF-alpha suggests that the effect of this factor on nonspecific resistance factors is one of the probable mechanisms of its modulating effect.

[Effect of human recombinant granulocyte colony-stimulating factor on mouse hematopoietic and lymphoid organs]. / Vliianie rekombinantnogo granulotsitarnogo koloniestimuliruiushchego faktora cheloveka na krovetvornye i limfoidnye organy myshei.

Experiments on intact CBA/CALac mice demonstrated that single (1.25 mg/kg) and repeated (0.125 and 1.25 mg/kg, 30 days) injections of recombinant human granulocyte colony stimulation factor lead to reversible dose-dependent granulocyte lineage hyperplasia in bone marrow, regenerative neutrophilic leukocytosis, and thrombocytosis in peripheric blood and to splenic granulo-, erythro-, and thrombocytopoiesis more expressed in males.

[Study of the antiviral activity, pharmacokinetics and toxic properties of liposomal form of human alpha-2b interferon administered topically]. / Izuchenie protivovirusnoi aktivnosti, farmakokinetiki i toksicheskikh svoistv liposomal'noi formy rekombinantnogo alfa-2b-interferona cheloveka pri naruzhnom primenenii.

Human liposomal recombinant alpha 2b-interferon topically applied to laboratory animals was tested for antiviral activity, pharmacokinetics, and toxicity. The interferon was shown to penetrate through the skin and to circulate in the blood of experimental animals longer than its injectable form, and to exhibit its antiviral activity against genital herpes in guinea pigs. It produced no toxic, skin-irritant, or allergic effects in laboratory animals.

[Photoinactivation of microorganisms in the presence of photosensitizers]. / Fotoinaktivatsiia mikroorganizmov v prisutstvii fotosensibilizatorov.

Two photosensitizing preparation for the photodynamic therapy of oncological diseases have been obtained. As revealed in this study, under experimental conditions their action suppresses the growth of Enterococcus faecalis and Staphylococcus aureus, which may be of great importance for the treatment of infections. And in contrast to antibiotic therapy, their use may not affect the development of normal intestinal microflora. The study has shown that their derivatives with the residues of carbonic (or muramic) acids more intensively penetrate microorganisms through their cell walls. This makes in possible to expand the spectrum of action of the preparations. The proposed method permits the rapid analysis of the photochemical activity of preparation for photodynamic therapy in the process of their development.

[The activation of phagocytosis by recombinant human tumor necrosis factor-beta]. / Aktivatsiia fagotsitoza rekombinantnym chelovecheskim faktorom nekroza opukholi beta.

The functional activity of phagocytic cells of various types was studied in white non-inbred mice by administering recombinant human tumor necrosis beta (rhTNF-beta). It was shown that rhTNF-beta increased phagocytic activity of the peritoneal exudate, spleen and liver macrophages as well as blood polynuclears. Stimulation of neutrophils was demonstrated in earlier times after administration of the preparation as compared to macrophages (3 h and 24 h, respectively). The duration of the macrophage activation effect and its expression depended on the dose of the preparation and were the most notable when rhTNF-beta was administered in doses of 10(3)-10(5) U/20 g. The addition of reopolyglucin, the polysaccharide filler, didn't remove a stimulatory effect of rhTNF-beta on macrophages, but influenced its dynamics. Multiple administration of the preparation didn't cause the phagocytosis stimulation effect.

[The immunoregulatory properties of recombinant human tumor necrosis factor-beta in mice opposite-reacting to antigen]. / Issledovanie immunoreguliatornykh svoistv rekombinantnogo faktora nekroza opukholi beta cheloveka u oppozitnoreagiruiushchikh na antigen myshei.

The effect of 10(3)-10(5) E/20 g doses of the recombinant factor of human beta tumor necrosis (rFNT-beta) on formation of the immune response and macrophage functional activity was studied in CBA and C57Bl/6 mice that differ in genetically determined level of the immune response to an antigen (sheep erythrocytes). The rFNT-beta was found to cause a modulating effect on the cell and humoral links of the immune response. The effect of the agent depended on the dose and the genotype of the experimental animals. It is suggested that the interlinear differences in the intensity of the humoral immune response in rFNT-beta administration may be connected with the different sensitivity to the agent of the peritoneal macrophages of mice of the used lines.