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Based on the study of actual nutrition and availability of macroelements there was found that adult population of the city of Omsk was established to refer to the group at risk for the development of micronutrient deficiency associated with low content of a set of essential elements (copper, zinc, calcium, selenium) in the ration, being prior for correction.There was executed the hygienic substantiation developed the fermented acid milk bioproduct of a functional purpose "Bifidin" enriched with micronutrients, prior for the population of the Omsk region. Introduction of this bio-product into the ration allows to effectively correct disorders of the mineral status, that was manifested in a decline in the proportion of patients with insufficiency of calcium (from 37.9 to 24.1%; p = 0.013), copper (from 51.7 to 25.9%; p = 0.004), selenium (from 96.6 to 84.5%; p = 0.026), zinc (from 58.6 to 48.3% of the subjects; p = 0.264). Upon the completion of the prophylactic course (intake "Bifidin" of 200 ml for 60 days), there was noted the gain in the concentration in hair: calcium (by 24.4%; p=0.441), zinc (by 8.0%; p=0.0008), copper (by 8.8%; p < 0.001), selenium (by 41.5%; p < 0.001). There was established the efficacy of the use of bio-product "Bifidin" enriched with micronutrients for the improvement of the structure of nutrition and element status of the adult population of the city of Omsk. There was justified the extensive use of dairy products enriched with micronutrients both for the reduction of the prevalence of microelementoses and the improvement of the nutritional status.

The pilot controlled study proved the effectiveness of enriched fermented milk product "Prolacta" as means of the primary prevention of nutrition-associated anemia, firstly, at the stage of latent iron deficiency. The study included 166 adult residents of the city of Omsk. Among examined patiens there were 48 (30%) men and 118 (70%) women aged from 18 to 59 years (mean age: 29.2 ± 0.84 years). Experimental group (79 persons) over two months took 1 glass (200 ml) of bioproduct "Prolacta" daily. The control group (87 people) no received this product neither used supplements or other vitamins and minerals. The groups were matched by gender and age. As criteria for the deviation from the normal settings there were accepted following values: the concentration of hemoglobin (Hb)--less than 130 g/l in men and less than 120 g/l in women; serum iron level--less than 12.5 µmol/L, serum ferritin in men less than 95 µg/l, in women--less than 30 µg/l. The proportion of persons from the main study group with latent iron deficiency decreased from 41.8% to 25.3% (p < 0.05), the proportion of subjects with normal iron supply increased significantly (from 26.6 to 41.8%; p < 0.05). Regular consumption of fermented milk enriched with bio "Prolacta" as a means of preventing the deficiency of micronutrients and nutrition-related anemia in large extent is recommended to persons from groups at-risk (athletes, children and adolescents, and women of reproductive age). Preventive effects of this product are combined with the nutritional benefits of dairy products, its use improves the structure of nutrition of the population

There was performed the study of the activity of the antioxidant system of glutathione under regular taking of enriched with micronutrients dairy products "Bifidin " and "Prolacta" in conditions ofsimulation of xcessive exercise loads. Target of research: white outbred male rats weighing 180-200 g (n = 68). Research methods and equipment: information retrieval, biochemical, and statistical. In the subacute experiment there was established that in conditions of excessive exercise loads (CEEL) the body of the rat meets with significant oxidative stress, causing the suppression of the activity of glutathione system: the number of reduced glutathione and the activity of selenium-dependent glutathione-peroxidase decline. Regular taking of dairy products "Bifidin" and "Prolacta" in conditions of CEEL (active training process) allows effectively to neutralize lipid peroxidation processes and normalize indices of the system of glutathione. There is established an increase in the activity ofglutathione-S-transferase in the homogenates of liver tissue in the simulation CEEL in combination with the use ofproduct "Bifidin".

The aim of the study--the assessment of the prevalence of hypovitaminoses B9 (folic acid) and B12 in the population of the city of Omsk and the determination of the possibility of their nutritional prevention. The subject of study--the adult population (18-59 years). The actual nutrition was studied by method of analysis of the frequency of food consumption. Prevalence of hypovitaminoses B9 and B12 was estimated upon the results of laboratory tests of blood by immunochemiluminiscent methods. Established prevalence of hypovitaminoses B (folic acid) and B12 in the population of the city of Omsk accounted for 63.2 ± 5.8% and 13.2 ± 4.1%, respectively. There was shown the possibility of correction of supply with vitamins by means of regular taking offermented dairy product "Prolacta". The serum content of vitamin B12 after a 2-month course of daily use of the product was increased by 17.8%, and the serum folate content--by 29.1%. The proportion of cases with insufficient content ofvitamin B9 in the experimental group decreased from 80.0 ± 6.8% to 38.7 ± 8.7%.

There was performed an experimental study of the influence of regular intake offermented milk enriched by products "Bifidin" and "Prolacta" on indices of iron metabolism in adolescents of 12-17 years, involved in sports (n = 94). In all study participants there was made double blood test (every 60 days), there were determined the levels of hemoglobin, serum iron, serum ferritin, C-reactive protein. The intervention in the main group (n = 68) was in daily intake offermented milk product in a volume of 200 ml (1 Cup) in addition to the normal diet within 2 months, including 35 cases who had used the bioproduct "Bifidin" and 33 persons- bioproduct "Prolacta". The control group was consisted of 26 persons from the adolescents engaged in the same sections, but not taking additional fermented milk drinks. The average values of all studied indices in adolescent athletes of the main and control groups before and after the intervention were consistent with reference values. Latent iron deficiency was detected in 23.4 ± 4.4% of adolescents involved in sports. At the second point of the research in two months of intake of enriched dairy products in the main group there was noticed the gain in levels of serum iron, ferritin, and the decline of the concentration of C-reactive protein. The results of the study allow us to consider enriched dairy products "Bifidin" and "Prolacta" as one of the components of complex measures of prophylaxis of hypovitaminosis and microelementoses in adolescents who are actively involved in sports.

Comparative study of the structural and functional state of cerebral cortex of adult albino rats after intracerebral allo- and xenotransplantation of embryonic nervous tissue and intravenous injection of umbilical cord blood-derived stem cells at different terms after diffuse-focal cerebral trauma revealed the best cerebroprotective effect on day 7 of posttraumatic period in animals receiving embryonic nervous tissue.

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 of haemopoietic factors (IL-1, IL-3, CSA) by adherent and nonadherent cells of lethally irradiated CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoietic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by nonadherent bone marrow elements was realised in a late terms of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells.

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.

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.

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.

Interleukin-1 levels were measured according to S. B. Mizel in 25 patients with pseudotuberculosis and concomitant chronic opisthorchiasis and in 25 ones with pseudotuberculosis alone over the course of the disease and in 3 months after it. The controls were patients with chronic opisthorchiasis and normal subjects. Hyperproduction of interleukin-1 by peripheral blood monocytes was found in chronic opisthorchiasis patients and in pseudotuberculosis patients with concomitant opisthorchiasis over the entire follow-up period. In patients with pseudotuberculosis alone interleukin-1 production was found elevated only at the peak of the disease and during early convalescence, that was followed by a stable normalization of this characteristic.

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.

We studied the condition of CBA mice bone marrow hemopoiesis and functional activity of adherent cells 6 months after a single treatment with vinblastine (VB), doxorubicin (DR) and cyclophosphamide (CP) in LD10 dose (6, 22 and 250 mg/kg, respectively). There was a long-term disorganization of bone marrow cell composition. The damage may be attributed to exhaustion of the pools of stem cells and changes in function of the cells formed by hemopoiesis induction microenvironment.

Cytostatic and cytotoxic activity of peripheral blood lymphocytes was studied in 30 cases of lung cancer. Enhanced cytostatic activity of lymphocytes was initially recorded. The level of natural antitumor resistance was maintained by means of neurovegetative inhibition used to prevent surgical stress.

Cyclophosphamide was injected at a dose of 150 mg/kg once to CBA mice and caused expressed hypoplasia of bone marrow hemopoiesis (decreased myelokaryocyte count, CFU-S and CFU-D) from day 1 of the experiment. The rise of CFU-S (8) and CFU-S (12) to a baseline level was noted on day 4 (the time of intensive regeneration processes), whereas CFU-D levels did not change. It is suggested that cytostatic action may trigger "shunt" hemopoiesis mechanisms which enhance differentiation of primitive hemopoietic cells and proliferative activity of mature hemopoietic elements.

On the model of adriamycine-induced hemopoiesis hypoplasia it has been shown that the accelerated differentiation of hemopoietic precursors regeneration is of great importance in regeneration of hemopoiesis. This differentiation is provided by preceded recovery of bone marrow structural-functional organization. The important role in regeneration of hemopoiesis belongs to hemopoietic microenvironmental elements which express its induced influence by the increase of colony-stimulating and erythropoietic activities, interleukin-1 and interleukin-3 production.

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.

It was demonstrated on an experimental model of cytostatic disease induced by a course of injections (1/10 LD50 for 10 days) of antineoplastic agents with various mechanism of action (doxorubicin, vinblastine, cyclophosphamide) that persistent (for 6 months) disorganization of the morphological composition of the thymus and other lymphoid organs is attended by inhibition of the functional activity of the T-cells of the immunity system. It is suggested that the weakened control (on the part of the thymus) due to the effect of the cytostatics may lead to disorders of the processes of proliferation and differentiation of the hematopoietic cells and impairment of the bone marrow morphological composition in late-term periods after cytostatic treatment.

The role of intercellular interactions in regulation of proliferation process in normal and tumor cells has been studied in experiments with mouse hybrids F1 (CBA X C57BL/6). The cytostatic activity to tumor cells has been shown to possess both adherent and nonadherent cells of bone marrow. The adherent cell-effectors inhibit, nonadherent ones stimulate the DNA synthesis in myelokaryocytes of normal bone marrow. During the activation of bone-marrow proliferation (under 10-hour immobilized stress) the cytostatic effect of nonadherent cells to tumor ones grows; the myelokaryocyte proliferation is stimulated on the 4th day after immobilized stress. The cytostatic activity of adherent cell-effectors remains to be low up to 7th day after immobilization. The maximum of depression in cytostatic function of the adherent elements coincides with the peak of bone marrow proliferation activity (6th day). The character of changes in cytostatic activity of adherent cells to tumor and nontumor ones is of the same type. The data obtained testify to the generality of regulation mechanisms in proliferation of tumor and normal cells.

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.

In experiments on Wistar rats the cytotoxic activity of NK on the 1, 2, 10 days after partial hepatectomy (PH) and the application of Rodiola extract (RE) was studied. After 5 injections of RE the NK activity in gut increased by 112%, and after 12 ones (towards the end of experiment) by 222% in the spleen. The decreasing of this index in a first day after PH in lung, liver and gut was shown to restore in these tissues to the end of experiment. The absence of NK cytotoxicity diminishing just after PH in all the tissues was shown in operated animals, receiving RE and the decreasing of this index was found only in the lungs (by 335%).

The role of T-lymphocytes in the regulation of bone marrow haemopoiesis was investigated under conditions of immobilization stress in mice. Development of the general adaptation reaction was accompanied by hyperplasia of the bone tissue at the level both of the committed precursor cells and of the morphologically differentiated haemopoietic cells. The existence of a subpopulation of T-cells expressing the Lyt-1+,Lyt-2+,L3T4-antigens on their surface is demonstrated. T-lymphocytes with this phenotype migrated into the bone marrow of stressed mice and stimulated the proliferation and differentiation of erythroid and granulocyto-macrophagal precursors.

Different cytogenetic effects in bone marrow cells induced by antitumor drugs with different mechanisms of action was studied. The treatment of adriablastine causes the appearance of chromatid deletion, vinblastine-polyploid cells, cyclophosphamide-chromosomal and chromatid aberration in mice. It was shown that bone marrow cells with cytogenetic damage have altered susceptibility to normal spleen cells-effectors cytotoxic action.

It has been shown that at late periods after immobilization stress there is an essential reduction in the cytostatic activity of CBA mice splenocytes detected by inhibition of mastocytoma P 815 cell proliferation in the test with 3H-uridine incorporation. The cytostatic activity returns to normal 5 to 14 days after stress. The changes in the cytolytic and cytostatic activity of mouse splenocytes following stress are correlated and a possible biological value of changes in the immunoassays for the host are discussed.

Cytostatic and cytotoxic activity of mouse spleen cells against normal and tumour target cells has been studied. The comparative analysis of mouse spleen cell cytostatic and cytotoxic activity after exposure to cyclophosphamide has shown that the effectors of natural cytotoxic activity are highly sensitive to cyclophosphamide, while cytostatic effectors are heterogeneous in their sensitivity to cyclophosphamide. Pretreatment of spleen cells with alpha-interferon produced an increase in cytotoxic and cytostatic activity against tumour target cells. The cells of lymphoid organs (spleen, bone marrow, thymus) had greater distinctions in cytotoxic than in cytostatic activity against tumour target cells.

Injuries to the normal killer membrane were studied during contact with tumor cells on isolated tumor cell-lymphocyte conjugates. The properties of the lymphocyte membrane were shown to undergo changes in the area of contact with the tumor cell membrane, manifesting in the increased membrane permeability for ribonuclease molecules. This effect was more pronounced if lymphocytes were used, in which the synthesis of RNA was suppressed.

The effect of exogenous interferon on membrane toxicity and cytotoxicity of mouse tumor cells (MX-II, SA-I, thymomas, IAC) was studied with respect to target IAC-I cells. The treatment with leukocyte interferon made tumor cell membrane toxicity rise by 27-40%, while that with fibroblast one by 30-47%. As a result of the treatment with leukocyte interferon, tumor cell cytotoxicity increased by 26-47%. Antiserum against fibroblast interferon reversed its activation effect on tumor cells. It is assumed that the effect described is linked with the increased resistance of tumor cells as regards normal killers under interferon action.

The effect of the in vivo treatment with synthetic interferon inducer B-58 on natural killer (NK) and cytostatic cell activity was studied in CBA and A/Sn mice. A marked increase in NK cell activity against target cells YAC-1 was observed in the spleen of CBA mice within 4 days after treatment. On the other hand, NK activity in A/Sn mice was not affected by B-58. However, B-58 was shown to enhance cytostatic cell activity both in CBA and A/Sn mice, when tested against target cells P 815.

The phenotypic and functional characteristics of T-lymphocytes detected in bone marrow at stress was studied in experiments on mice. The T-lymphocytes-regulators taking part in hemopoiesis stimulation on 5-7 days after 10-hours immobilization have phenotype by Lyt 1+, 2+, L3T4-.

In experiments on CBA/Lac J mice it was found that the course administration of adriamycin (0.95 mg/kg), vinblastine (0.24 mg/kg) and cyclophosphan (27 mg/kg) in 1/10 LD50.10 causes persistent disturbances of the functional activity of the lymphoid tissue manifesting by inhibition of the proliferative response of the spleen lymphocytes to T- and B-cell mitogens one month and to a lesser extent three months after cytostatic action. The lymphotropic effect of adriamycin is due to the predominant damage of the functional activity of T-lymphocytes. Vinblastin suppresses T- and B-cell link of the immunity system and the inhibitory effect of cyclophosphan is directed mainly to B-cell population.

The paper discusses the status of polymorphonuclear neutrophils (PMN) in untreated patients with stage III and IV lung and stomach cancer. Pronounced increase in peripheral blood neutrophil count was matched by decrease in the level of leukocyte cationic proteins. In vitro cytotoxic activity of PMN against K-562 cells was significantly higher in cancer patients, as compared to healthy controls, and unaccompanied by reaction of neutrophils to stimuli. NBT-test value variation range appeared wider in cancer patients than in controls.

The cytostatic effect of different lymphoid cells on tumour cells was studied in mice. It was shown that the cells differed in their ability to manifest cytostatic and natural cytotoxic activity. The interstrain variations of cytostatic activity levels in murine splenocytes were revealed. The degree of cytostatic action of effector cells on tumour cells depended both on effector-target cells ratio and on the incubation time of effector and target cells. The cytostatic effect of splenocytes and macrophages was demonstrated to be unrestricted by H-2 complex and independent of the tumour type. The data suggest that the cytostatic effector cells are heterogeneous and may be distinct from natural killer cells.

The authors attempted to study which parts of the lipid molecules are most responsible for an increase in the sensitivity of the tumor cell to the cytostatic and membrano-toxic action of natural spleen effectors. Use was made of different combinations of egg phosphatidylcholine, phosphatidylethanolamine, cardiolipin, dipalmitoyl phosphatidylcholine and a mixture of bovine brain gangliosides. Introduction of phosphatidylethanolamine into the membrane of tumor cells increased, that of phosphatidylcholine and cardiolipin did not change whereas introduction of a mixture of brain gangliosides reduced their sensitivity to spleen effectors. Introduction of brain gangliosides together with egg phosphatidylcholine into the membrane of the target cell increased whereas that together with dipalmitoyl phosphatidylcholine reduced its sensitivity to spleen effectors. It is concluded that the increase in the sensitivity of the tumor cell primarily depends on changes in the lipid template of its membrane, induced by unsaturated fatty acids of egg phosphatidylcholine, and to a less degree on the properties of carbohydrate heads of gangliosides.