[New promising natural immunocorrective agents].

The influence of Sorbus sibirica, Calendula officinalis and Althaea officinalis extracts on the humoral immune response and nonspecific resistance of mice to immunosuppression by cyclophosphan was studied. It was shown that these extracts are not inferior to Echinacea purpurea tincture in terms of stimulation of humoral immune response, phagocytic and bactericidal activity of peritoneal macrophages but exceed effect of E. purpurea on phagocytic activity of peripheral blood neutrophils.

[Effect of Filipendula ulmaria extract on immune system of CBA/CaLac and C57Bl/6 mice].

Extract of Filipendula ulmaria (L.) Maxim administered intragastrically in doses 10, 50, 150 and 500 mg/kg stimulated both inductive and productive phases of the humoral immunity response in CBA/CaLac and C57BL/6 mice. The extract also exhibited pronounced antiinflammatory effect, which was manifested by a decrease in the synthesis of interleukin-2 by splenocytes and by suppression of proinflammatory cytokines production in delayed-type hypersensitivity reaction. At the same time, Filipendula ulmaria extract did not influence the functional activity of peritoneal macrophages.

[Evaluation of homeostatic disorders induced by radiation exposure].

Possibilities of correction and prophylaxis. The authors presented results of study covering workers of radiation-dangerous plants of Siberian Chemical Enterprise, who underwent long-term exposure to outer and inner radiation in "low" doses range during the occupational activity. Target-systems for radiation effects were proved to be lipid peroxidation and antioxidant defence systems, cell energy metabolism--severity of disorders in which is correlated with degree of radiation exposure.

[Reactogenicity, safety and immunogenicity of a recombinant bivaccine against smallpox and hepatitis B in limited clinical trials]. / Reaktogennost', bezopasnost' i immunogennost' rekombinantnoi bivaktsiny protiv ospy i gepatita B v ogranichennykh klinicheskikh ispytaniiakh.

The reactogenicity of the embryonic live recombinant variola and hepatitis B bivaccine as tablets (Revax-BT) as well as its safety and immunogenicity were evaluated in clinical trials made in volunteers who had previously immunized or not with variola vaccine. A preliminary conclusion was made on a lack of side effects and drug safety in primary vaccination and been revaccination with low and high doses. Primary immunization of volunteers and as bivaccination with high doses stimulated the most pronounced immune response to the vaccine virus versus such effect observed in immunization of volunteers with low vaccine doses. Humoral immune response to HBs was observed in 75% of volunteers of both groups after as bivaccination. Such response was most pronounced in examinees immunized with low vaccine doses versus those who received high bivaccine doses. At the same time, no protective levels of humoral immunity response to HBs Ag were observed in volunteers first vaccinated.

[Efficacy of therapeutic and prophylactic actions of ultralow doses of antibodies to gamma-interferon in experimental murine model of herpes virus]. / Izuchenie éffektivnosti lechebno-profilakticheskogo deistviia sverkhmalykh doz antitel k gamma-interferonu na éksperimental'noi myshinoi modeli gerpesvirusnoi infektsii.

The process of the disease due to herpes simplex virus types 1 and 2 (HSV-1 and 2) was studied on white uninbred mice weighing 10 to 12 g. The animals were infected intracerebrally or intraperitoneally. Intraperitoneal contamination of the animals with MS strain of HSV-2 was used for the experimental model of the herpes simplex infection. The prophylactic antiherpes action of ultralow doses of the human gamma-interferon antibodies (ULD of anti-IFN-gamma) at a course of its intragastral administration was evaluated. The preparation was shown to have a significant (p < 0.05) protective effect in a dose of 10 LD50, evident from a 10-fold decrease of the HSV-2 accumulation in the brain, a lower percentage of the animal deaths and an increase of the average lifespan of the animals by 3.3 days. The study of the therapeutic action of ULD of anti-IFN-gamma at a course of its intragastral administration showed that the preparation had no significant positive effect on the disease process in the animals infected with HSV-2 in a dose of 10 LD50. However, a positive effect associated with delayed virus replication in the brain was observed in the study on the therapeutic effect of ULD of anti-IFN-gamma after its intragastral administration to the mice infected with a sublethal dose of the virus.

[Antiviral activity of oral ultralow doses of antibodies to gamma-interferon: experimental study of influenza infection in mice]. / Protivovirusnaia aktivnost' sverkhmalykh doz antitel k gamma-interferonu pri peroral'nom vvedenii: éksperimental'noe issledovanie grippoznoi infektsii u myshei.

Course intragastric administration of ultralow doses of human gamma-interferon antibodies (ULD anti-IFN-gamma) to intact mice resulted in an increase of endogenous IFN-gamma production by the animal lymphocytes. Oral prophylactic administration of ULD anti-IFN-gamma significantly lowered the influenza virus concentration in the animal lungs at the initial stage of the aerogenous infection: in 2 (p = 0.05) and 3 (p = 0.07) days after the contamination. The therapeutic antiviral effect of ULD anti-IFN-gamma in mice with influenza was evident from a significant decrease of the influenza virus concentration in the lungs of the animals on the 4th (p = 0.05) and 5th (p = 0.07) days after the contamination. The antiviral effect of ULD anti-IFN-gamma after the prophylactic and therapeutic use is likely provided by induction of endogenous IFN-gamma.

[Preclinical toxicologic study of a Baikal aconite tincture (bayacon)]. / Doklinicheskoe toksikologicheskoe izuchenie nastoiki akonita baikal'skogo (Baiakona).

The safety of bayacon, a new drug based on Baikal aconite intended for the treatment of inflammation-proliferative dermatitis (psoriasis), was studied on a preclinical level. With respect to a single introduction in rats and mice, the drug is classified as a low-toxicity substance. However, a 3-month oral administration of bayacon (0.25, 0.5, and 2.5 mg/kg) in rats showed a number of dose-dependent functional and morphological changes. A dose of 2.5 mg/kg induced weak hyporegenerative anemia, neutrophile leukocytosis, and dystrophic changes in the stomach mucosa, heart, liver, and kidneys. All these symptoms disappeared within two weeks after abolition of the drug. Oral administration of bayacon (0.1 and 0.5 mg/kg) in rabbits produced no pathological morphofunctional changes in the organs and tissues studied. In rats, bayacon 2.5, 0.5, and 0.25 mg/kg doses of bayacon led to dose-dependent changes in some characteristics of the reproduction system. The drug did not influence the expression of allergic reactions and showed no immunotoxicity and mutagenicity manifestations.

[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.

[The allergenic and immunotropic properties of the preparation pantohematogen]. / Izuchenie allergennykh i immunotropnykh svoistv preparata pantogematogen.

Experiments on CBA/Ca Lac mice showed that pantohematogen, a drug prepared from whole blood of Siberian deer, wapiti, and deer, when administered in a course in doses under study and in chosen conditions of the experiment does not possess allergenic and immunotoxic properties. The immunomodulating properties of the drug were characterized by marked stimulation of macrophage phagocytic activity and, under definite conditions, by activation of formation of antibody-producing cells in the spleen of mice immunized with sheep erythrocytes.

[Parameters of cellular immunity in lung cancer patients with different types of adaptation reactions during polychemotherapy]. / Pokazateli kletochnogo immuniteta u bol'nykh rakom lëgkogo s razlichnymi tipami adaptatsionnykh reaktsii v protzesse provedeniia polikhimioterapii.

A relationship between cellular immunity and general adaptation syndrome in the course of CAM polychemotherapy has been investigated. The results point to a lack of lymphopenia, lower levels of T-suppressors and higher instability of immunological indices in patients showing increased activation reaction and maximum antitumor resistance during cytostatic therapy, unlike in those in stress. This opens an opportunity for correction.

[Interleukin-1 production by exudate and bone marrow macrophages in experimental acute infectious peritonitis]. / Produktsiia interleikina-1 makrofagami éksudata i kostnogo mozga pri éksperimental'nom ostrom infektsionnom peritonite.

The model of acute infectious peritonitis in mice has been used to show that inflammation is attended by a marked phasic increase in interleukin-1 (IL-1) production by macrophages of exudate and bone marrow. The increased IL-1 production by macrophages of exudate proceeds earlier than that by macrophages of the bone marrow. This indicates that activation of the bone marrow macrophages may be a result of the effect of OL-1 and other haemopoietic factors released by macrophages on the inflammatory focus.

[The production by bone marrow cells of humoral factors in extreme exposures of different origins]. / Produktsiia kostnomozhgovymi kletkami gumoral'nykh faktorov pri ékstremal'nykh vozdeistviiakh razlichnogo geneza.

The intensification of cytokine-producing activity by mouse bone marrow cells forming the hemopoiesis-inducing microenvironment (HIM) was demonstrated to be an obligatory component of adaptation processes developing in the body under the influence of different extreme factors (immobilization, inflammation, cytostatics, irradiation). As a rule, the first stress reaction of adhesive and nonadhesive cells consists in interleukin-1 and interleukin-3 secretion with following erythropoietic and colony-stimulating activity induction. For all this, the levels and periods of production of hemopoiesis humoral regulators are comparable under hemopoiesis-stimulating or -suppressing influences. Finally Activation of HIM functional properties expresses the interaction of central and local regulating systems, which favours the formation of an optimal response of the blood system to stress.

[The effect of mast cells on the T-lymphocyte mechanisms of hemopoiesis regulation in inflammation]. / Vliianie tuchnykh kletok na T-limfotsitarnye mekhanizmy reguliatsii gempoéza pri vospalenii.

It was shown on the model of acute infections peritonitis in mice that the inflammation induced in the absence of mast cells was characterized by increased T-lymphocyte accumulation and macrophage-activating factor production and, in case of Thy-1,2(+)-lymphocyte elimination from bone marrow cell suspension, by earlier suppression of colony-stimulating and erythropoietic activity production by adhering and non-adhering myelokaryocytes. The results indicate that the modulatory effect of mast cells on haematopoiesis in inflammation is due in many respects to T-lymphocyte inhibition.

[The effect of the mast cells on interleukin-1 production by exudate and bone marrow macrophages in inflammation]. / Vliianie tuchnykh kletok na produktsiiu interleikina-1 makrofagami ékssudata i kostnogo mozga pri vospalenii.

It was shown on the model of acute infectious peritonitis in mice that the inflammation induced in the absence of mast cells was characterized by an earlier interleukin-1 (IL-1) production by bone marrow macrophages and by the lack of relapsed IL-1 production by macrophages of both exudate and bone marrow. This correlated with the previous data of the authors on the earlier haematopoiesis activation but weaker bone marrow hyperplasia expression in inflammation induced in the absence of mast cell. The results testify to essential role of mast cells in regulation of IL-1 production by macrophages of exudate and bone marrow. The previously established modulatory effect of mast cells on haematopoiesis in inflammation may be mediated by their effect on IL-1 production by macrophages of the inflammatory focus and haematopoiesis-induced microenvironment.

[Influence of mast cells on the regulatory mechanisms of hemopoietic bone marrow in inflammation]. / Vliianie tuchnykh kletok na kostnomozgovye mekhanizmy reguliatsii gemopoéza pri vospalenii.

Acute infectious peritonitis simulated in mice was used to show that previous osmotic deterioration of the abdominal mast cell population significantly influenced the function of hemopoiesis-inducing microenvironment (HIM). The earlier production of the colony-stimulating and erythropoietic activities by the non-adhesive myelokaryocytes and the decreased production of these activities by the adhesive cells have been established. The results obtained evidence that mast cells modulate HIM mediating their influence on hemopoiesis under natural conditions of inflammation.

[Role of humoral factors in the regulation of hemopoiesis in stress]. / Rol' gumoral'nykh faktorov v reguliatsii gemopoeza pri stresse.

The change of 11-1, IL-3, CSA concentrations in adherent and nonadherent bone marrow cells condition medium at stress were investigated. The activation of bone marrow hemopoiesis was registered at mice after immobilization stress. The number of CFU-GM increased on 1, 4 and 5 day after stress. Maximum of CSA in adherent and nonadherent cells conditioned medium was observed on day 4, 6 or 2, 5 respectively. The increasing of 11-3 activity in culture of nonadherent bone marrow cells was registered from day 1 and mount to maximum at 4-5 days. The increasing of 11-1 level in culture of adherent bone marrow cells was found at 1 and 4 days.

[Blood system responses in inflammation and mechanisms of their development]. / Reaktsii sistemy krovi pri vospalenii i mekhanizmy ikh razvitiia.

A model of acute infectious peritonitis in mice demonstrated that the inflammation is attended by marked biphasic activation of bone-marrow granulomonocytopoiesis and that the activation is due in many respects to increased functional activity of elements forming the hemopoiesis-inducing microenvironment. This was suggested by increased colony-stimulating activity of the marrow mononuclear cells and the content of hemopoietic islets in the marrow. The colony-stimulating activity of peripheral blood also increased. It was established that inflammation is also characterized by activation of bone-marrow erythropoiesis, which is linked with increased erythropoietic activity of the hemopoiesis-inducing microenvironment and blood. There was a relation between the hemopoietic changes and the kinetics of leukocytes in the focus of inflammation.