[CLINICAL EFFICACY OF TREATMENT OF STAPHYLOCOCCAL INFECTION BY COMPOSITION OF NANOSTRUCTURED SILICON DIOXIDE AND FOSFOMYCIN.]

Clinical efficacy of a composition of nanostructuared silicon dioxide and fosfomycin in treating the skin abscess induced by Staphylococcus aureus inoculation in rabbits has been studied. It is established that the proposed composition of silicon dioxide nanoparticles and fosfomycin exhibits higher therapeutic potential in treating local purulent-septic process in skin of test animals. The therapy with this composition reduced the number of abscesses in the skin by 50% after two days of application and by 80 - 90% after five days of therapy as compared to therapy with application of chloramphenicol liniment (15.0 vs. 4.0 and 7.0 vs. 2.0, respectively).

[Cytokine synthesis in the healthy volunteer's blood mononuclear cells under the influence of an indolyl-thio-alkanecarboxylic acid derivative with selective immunosuppressant properties].

The influence of BM-7-02 compound on the production of cytokines in the culture of healthy volunteers' blood cells. This compound suppresses the production of main cytokine (gamma-IFN, IL-2 and IL-4) synthesized by CD4+ Th1 and Th2 cells, stimulates the production of TNF-alpha and IL-6, and does not change the production of IL-1 beta.

[Screening of new derivatives of arylheteroalkanecarboxylic acid on the immune system].

The screening of 13 original compounds from the group of derivatives of arylheteroalkanecarboxylic acid on immunity were performed. The compounds exhibit strong myelostimulating/myelosuppressive property, increased or decreased influence on the: PFC (IgM and IgG), DTH at the sheep erythrocytes in CBF1 in vivo. In contrast, in vitro the compounds had no effect or inhibited the spontaneous, ConA or PWM induced proliferation of the splenocytes from normal mice. The problems of the universal methods of the screening of immunoactive properties of compounds are discussed.

[In vitro synthesis of immunoglobulins caused by an inactivated Ebola virus]. / Sintez immunoglobulinov in vitro pod vliianiem inaktivirovannogo virusa Ebola.

An in vitro model Ebola infection was used to study the humoral response of human mononuclear cells to stimulation by purified inactivated Ebola virus antigen. Inactivated Ebola virus was cocultivated with human mononuclear cells in the presence or absence of B-cell mitogen LPS E. coli: B5. An increase in the rate of synthesis of immunoglobulins (both IgG and, to a less extent, other classes) was observed. The Ebola virus proteins were suggested to exert no suppression effect on B-cells. The IgM/IgG synthesis was evaluated by EIA in supernatants after 7 days of cultivation. It was concluded that Ebola fever is accompanied by active humoral immune response, which provides a promising basis for further search of the methods of treatment of this disease.

Russian Academy of Medical Sciences (RAMS), Siberian Branch, activity in solving the medical problems of Russian Circumpolar regions.

RAMS, Siberian Branch, has been actively participating for the last 25 years in elaboration and realization of numerous scientifically applied programs aimed at improving diagnosis, treatment, and prophylaxis of the most widespread diseases among the Native and newcoming populations of the Russian Far North (Taimyr, Yakutia, and Chukotka). The medical researchers of different RAMS, Siberian Branch, institutes, based on long-term investigations, have obtained a number of largely new data on etiology, pathogenesis, and epidemiology of cardiovascular, infectious, and cancer disease; diabetes; alcohol addiction; trauma; etc., and have developed practical recommendations for public health institutions on improvement of people's health.

[Functional activity of T-, B-lymphocytes, and macrophages during suppression of expression of the env gene from an endogenous retrovirus genome]. / Funktsional'naia aktivnost' T-, B-limfotsitov i makrofagov v usloviiakhpodavleniia ékspressii gena env éndogennogo retrovirusnogo genoma.

Incubation of murine spleen cells with antisense oligonucleotide complementary to initiation site of this gene highly increased RNA synthesis relative to the normal T- and B-lymphocytes from spleen. In macrophages, inhibition of gene env expression stimulated phagocytosis and IL-1 production. Under these conditions, the level of expression of proviral envelope transmembrane p15E protein, which in infectious type C retroviruses is known to be immunosuppressive, decreased in spleen cells. Antisense oligonucleotide stimulatory effect on murine spleen cell RNA synthesis is presumably related to the reduced production of endogenous p15E.

Endogenous retroviral envelope peptide expression is involved in a regulation of lymphocyte and hematopoietic precursor activity.

A biological function of endogenously expressed MuLV p15E-related proteins for lymphocyte and hematopoietic precursor activity in mice was examined. A high level of endogenous p15E-related peptide expression in spleen cells of mice with hemolytic anemia rendered by phenylhydrazine (PHZ) treatment was observed, detected by hyperimmune rabbit antisera against amino acid sequence which compose the immunosuppressive domain (ISD) of exogenous viral transmembrane (TM) p15E protein. The conditioned medium of these cultured cells (PHZ/CM) was inhibitory for lymphocyte blastogenesis and granulocyte-macrophage (GM) precursor activity, but stimulatory for the erythroid colony growth. When added to PHZ/CM, anti-ISD/p15E antibodies were capable to abrogate these effects. These antibodies bound 14K and 48K structural peptides contented in PHZ/CM as presumably smaller components of env gene products. Given together, the results indicate that erythroid immature cells produce proteins appearing in cell culture medium which exert p15E-related properties. These peptides are suggested to exert a down regulation for both lymphocyte and GM precursor activities, and the colony-promoting effect towards erythroid compartment cells.

The growth of human HIV-1 infected U937 cells in immune-deprived mice.

We report in vivo growth of human promonocytic cells infected with HIV-1 presented in new mouse model. Cloned U937 cells chronically infected with HIV-1 were grafted in (CBA*C57B1/6)F1 mice deprived of immunity by thymectomia and total body irradiation with subsequent marrow reconstitution. Nine weeks after cell inoculation, HIV-1-positive cells were found only in mice that received an additional single dose of cyclophosphamide (100 mg/kg bw) prior to transplantation, whereas, in mice without further immune deprivation, the complete elimination of cells bearing viral antigen occurred already on the seventh day after transplantation. The approach described may be suitable for in vivo development of antiviral drugs against latent infection in macrophage-like cells which represent a serious problem in therapy of AIDS in humans.

Antisense oligonucleotide complementary to endogenous retroviral MCF env gene inhibits both BFU-E and CFU-S colony formation in mice.

A possible biologic activity of endogenously expressed env sequence of retroviral mink cell focus-forming virus (MCF) genome for hematopoietic colony formation was studied in mice. Antisense 20-mer complementary to MCF env sequence was used to detect the result of blockage of this gene translation on the potency of marrow cells to form colonies of erythroid (BFU-E), myeloid granulocyte-macrophage (CFU-GM), and stem cell (day 11 CFU-S) hematopoietic compartments. A large relative decrease in BFU-E number was found in bone marrow cell cultures preincubated with antisense oligonucleotide during 4 h, whereas CFU-GM colonies remained unaffected. A marked reduction of CFU-S colony formation was also registered under antisense oligomer influence. Following a decreased proliferation of erythroid progenitors, we suggest the mechanism by which antisense oligonucleotide could cause the loss of colony formation. Taken together, these data allow to propose that the expression of this gene is naturally significant for hematopoietic progenitor activity exerting some property of env gene products to regulate the growth of erythroid and multilineage hematopoietic precursors.

The influence of synthetic peptide from retroviral transmembrane protein p15E on murine spleen cell proliferation and bone marrow hemopoietic precursor colony formation.

The retroviral transmembrane p15E peptide is known to suppress a wide variety of immune cell functions, suggesting a role for immunosuppression associated with retroviral infection. The 10-amino acid sequence from the highly conserved portion of p15E (CKS-10) is capable of reproducing this inhibitory activity. In this study we set out to determine the influence of this decapeptide on murine spleen cell mitogen-induced proliferation and hematopoietic granulocyte-macrophage and erythroid precursor colony formation in vitro. A dose- and time-dependent suppression of spleen cell blastogenic response was produced by the CKS-10 peptide. When bone marrow cells were incubated with decapeptide, the significant decrease of CFU-GM colony number was also dose-dependent. In contrast, the same doses of CKS-10 peptide which induced a most significant inhibition of CFU-GM colony formation caused a marked increase of BFU-E colonies. A most pronounced effect of the peptide on bone marrow hematopoietic progenitor activity was produced by prolonged exposure to the peptide. Given the results of this study, it seems likely that, in addition to the cytopathic effect of retroviruses on the lymphocytes, viral peptide-mediated hematopoiesis disorders may also play an important role in the pathogenesis of immunodeficiency associated with retroviral infections.

[Proliferative activity of the hematopoietic stem cell in antigenically stimulated splenectomized mice]. / Proliferativnaia aktivnost' stvolovoi krovetvornoi kletki u splenéktomirovannykh myshei pri antigennom vozdeistvii.

Proliferative activity of hemopoietic bone-marrow stem cells has been studied in splenectomized mice in response to sheep red blood cells (2 X 10(8], pneumococcal polysaccharide (100 micrograms) and lipopolysaccharide E. coli (100 micrograms) injections. Spleen and its lymphoid cellular elements were shown to be of great importance for the regulation of the functional activity of hemopoietic stem cells under the antigenic influence.

Colony-forming activity of pluripotent stem cells in tolerant mice following antigen exposure.

The effect of sheep red blood cells (SRBC) and human red blood cells (HRBC) on the number of CFU-S in the bone marrow and spleen of (CBA X C57BL/6)F1 mice tolerant to SRBC was examined. The number of bone marrow and spleen CFU-S in SRBC tolerant mice was increased after injection of HRBC. After challenge with SRBC, CFU-S number was elevated in the spleen but not in the bone marrow. Thus, the mechanism of CFU-S activation in response to antigen exposure is different in the bone marrow and spleen.