In vitro effects of sporobacterin probiotic on the function of donor granulocyte-macrophage cells.

The effects of sporobacterin probiotic (Bakoren Company) on oxidative activity of donor granulocyte-macrophage cells (GMC) were studied in vitro by luminol-dependent chemiluminescent method, and the effects of the probiotic on the production of pro- and anti-inflammatory cytokines were evaluated by ELISA. The probiotic dose-dependently stimulated spontaneous production of free radicals by GMC; combined treatment with immunomodulators likopid, polyoxydonium, and IFN-α2a produced a more potent effect. Sporobacterin stimulated the production of pro- and anti-inflammatory cytokines in cell cultures. These data confirmed the immunomodulatory effect of sporobacterin, an important component in the phagocytic system cells.

[Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis].

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.

[Perinatal transmission of hepatitis C virus].

The perinatal transmission of hepatitis C virus (HCV) is the major route of infection in infants. The understanding of the risk factors of perinatal infection and the continuation of studies in this area allow one to propose immunological algorithms of prediction and to work outa follow-up strategy of infected children. The authors have made virological and Immunological studies of infants born to mothers with HCV infection.

[Transgenerational genomic instability in children of liquidators of the accident at the ChNPP (cytogenetic and immunogenetic characteristics)].

A complex of cytogenetic and of immunogenetic study of the state of the lymphocyte genomes in the liquidators of the ChNPP accident and their unirradiated children has been carried out for the first time. Increased frequencies of the chromosome aberrations, of gene mutations (TCR mutations) and of predictors of apoptosis (cells with CD95+ immunophenotype) have been revealed in both generations. The analysis of correlations between the parameters under study has demonstrated distinctive features characteristic of induction of genomic instability in the organism of unirradiated children as compared to their fathers--liquidators directly exposed to radiation. Individual variability of genome destabilization were observed by all criteria used and manifested themselves in the diverse spectrum of transgenerational mutational effects and in different levels of their expression. The results obtained demonstrate the necessity of integral evaluation of the state of the genome using several genetic criteria to reveal transgenerational genomic instability in children of a special category--the offsprings of irradiated parents.

[Effect of vector potential variations on monocyte/macrophage system parameters in mice in laboratory conditions].

The effect of 30-min vector potential variation on the phagocytosis of macrophages from laboratory mice was investigated. It was found that the effect changes the characteristics of mice immunity: the quantity and percentage of neutrophils and lymphocytes in the blood, the activity of capture, degranulation, the splitting of bacterial agents, and the dynamics of formation of reactive oxygen species.

[Transposition of autologous cultivated bone marrow cells promotes prevention and treatment of immunodependent complications in cardiosurgical patients].

Coronary artery bypass grafting (CABG) has been made in two groups of patients with chronic heart failure (CHF) with further estimation of the rate of postoperative organic dysfunctions and pyoseptic complications. In group 1 (n = 50) CABG was combined with intracoronary or intramyocardial injection of autologous precultivated for 7-8 days mononuclear cells of the bone marrow (1 x 10(9) cells). In group 2 (n = 479) the intraoperative injection of the above cells was not made. It was found that autologous cultivated mononuclear bone marrow cells prevent organic dysfunction and reduce frequency of infectious-septic complications especially in patients with preoperative focuses of chronic infections.

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas. The data obtained suggest a systemic character of dysgenomic effects, the reality of induction of genome instability in the growing organism of children exposed to low-intensity radiation at low doses the expression of which is determined by individual genotypic features of the organism. Biological significance of the phenomenon of the post-radiation genome instability, its relation to the state of health and the pathogenetic role in the development of somatic pathology are postulated.

[Immuno-modulating properties of a macrolide antibiotic "Z-factor"]. / Immunomoduliruiushchie svoistva makrolidnogo antibiotika "Zi-faktor".

Zi-Factor is a trade mark of azithromycin made in Russia by ZAO Veropharm. The in vitro modulating action of Zi-Factor (ZF) on neutrophil functional activity and production of immunity mediators was studied. The direct modulating effect of ZF in a concentration of 50 mcg/ml corresponding to the single therapeutic dose of 500 mg/70 kg body weight on the neutrophil oxidase activity evident from increased production of active oxygen and higher myeloperoxidase activity was shown. The immunomodulating effect of ZF on modulation of intracellular oxidative metabolism depended on the initial state of the phagocyte system (secondary insufficiency or activation). When the neutrophil oxidase system is exhausted and there is no response to the antigen stimulus, it is advisable to combine the use of ZF with immunomodulating therapy.

[Multiple organ failure as a manifestation of immune dysregulation of reparative processes in the organs during critical states]. / Poliorgannaia nedostatochnost' kak proiavlenie immunnoi disreguliatsii reparativnykh protsessov v organakh pri kriticheskikh sostoianiiakh.

The authors claim that the specific clinical symptoms of multiple organ failure (MOF) are explained by impaired interactions of two functionally related systems: the immune system (IS) responsible for regeneration and the reticuloendothelial system (RES) responsible for inflammation. Organ regeneration during MOF is suppressed as a result of suppressed morphogenetic function of lymphocytes, imbalanced macrophage-lymphocyte interactions, and RES hyperactivation. For prevention and treatment of MOF, the authors recommend stimulation of reparative processes in the organs by splenic therapy: assisted xenospleen, infusion of splenic perfusate or xenosplenic peptides. Xenospleen therapy is preferable to other methods of immunocorrection due to more expressed morphogenetic activity of splenic T lymphocytes and their cytokines.

[Plasmapheresis in combined treatment of acute rejection crises after kidney transplantation]. / Primenenie plasmafereza v kompleksnoi terapii ostrykh krizov ottorzheniia posle peresadki pochki.

The aim of the study was assessment of effectiveness and safety of extracorporeal procedures (plasmapheresis) in prevention and combined treatment of acute rejection crises (ARC) after kidney transplantation in patients at high risk to develop acute immunological conflicts in early postoperative period. 94 patients aged 21-56 years after allotransplantation of cadaver kidney (ATCK) entered the study. They were divided into two groups: group 1 patients (n = 47) received plasmapheresis procedures in combined preventive and therapeutic treatment of ARC; matched group 2 patients (n = 47, retrospective) received the same therapy but plasmapheresis. In both groups there were many patients with a high titer of pre-existing antibodies and massive hemotransfusions in the past. The analysis covered also recipients with the second ATCK (9 and 4 patients, respectively). After ATCK both groups received three-component immunosuppressive treatment (neoral, prednisolone, azatioprin and/or sell-cept). The analysis of the transplant and recipient 11-month survival has estimated that it was 93.6 and 91.5% for the recipients, respectively, and 91.5 and 76.5% for the transplanted kidney for group 1 and 2, respectively. The conclusion is that plasmapheresis in combined prevention and treatment of ARC by humoral type in sensitized patients (high titer of the pre-existing antibodies, repeat transplantations, hemotransfusions) is pathogenetically grounded and lowers the percentage of irreversible episodes of acute transplant rejection early after surgery.

[The immune and dental status of women who have given birth to infants with intrauterine growth retardation]. / Immunnyi i stomatologicheskii status zhenshchin, rodivshikh detei s vnutriutrobnoi zaderzhkoi razvitiia ploda.

Secondary immunodeficiency was detected in women who gave birth to small-for-date newborns. This state was one of the causes of periodontal and hard dental tissue involvement. Women with small-for-date fetuses are at risk of dental diseases.

[The enhancement of treatment efficacy in chronic liver failure by using hemoperfusion across donor hepatocytes and spleen fragments]. / Povyshenie éffektivnosti lecheniia khronicheskoi pechenochnoi nedostatochnosti s pomoshch'iu gemoperfuzii cherez donorskie gepatotsity i fragmenty selezenki.

Hemoperfusion via donor hepatocytes and splenic fragments is an effective adjuvant method of treatment of hepatic insufficiency, especially in patients with autoimmune disease. Hemoperfusion effect occurs due to normalization of mesenchymoinflammatory and immunological indices as a result of positive action of hepatotropic and immunotropic factors of the spleen. The highest effectiveness of the above hemoperfusion is reached in its early use, that is before the disease becoming chronic.

[The use of xenogeneic splenic perfusates for treating suppurative-septic diseases]. / Ispol'zovanie ksenosplenoperfuzatov dlia lecheniia gnoino-septicheskikh zabolevanii.

It was shown in experiments on a model of fatal staphylococcal sepsis in 200 mice and 15 dogs that the perfusate of a pig's spleen obtained by perfusion of the isolated organ with a dextran solution (rheopolyglucin, polyglucin) is capable of preventing the animals' death. Intravenous infusion of 400-500 ml of a xenospleen perfusate at an interval of 1-3 days, which was included in the complex of postoperative treatment of 45 patients with destructive diseases of the abdominal organs complicated by peritonitis and sepsis, contributed to reduction of lethality and the terms of recovery. It is shown that the main effect, besides detoxification, is based on immunomodulation at the cost of biologically active substances produced by the cells of a xenospleen and contained in the perfusate. The best results were produced with the use of the perfusate of a xenospleen in the early periods after radical operation and thorough cleansing of the source of the infection.

Influence of ganglioside GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity.

The influence of ganglioside GM3 and some of its breakdown products on phytohemagglutinin-induced blast transformation of human lymphocytes and concanavalin-A-induced T-suppressor activity was studied. The structures of two major hydrolysis products of GM3 were established by negative-ion fast-atom-bombardment mass spectrometry as neuraminyllactosylsphingosine (NeuLacSph) and neuraminyllactosylceramide (NeuLacCer). Both substances were shown to be potent inhibitors of mitogen-induced lymphoblastic transformation whereas their acetylation products NeuAcLacSphAc and GM3 did not affect the proliferative response of lymphocytes to phytohemagglutinin. On the other hand, only GM3 and NeuLacSph were able to enhance concanavalin-A-induced T-suppressor activity. On the basis of these data, it is suggested that the effects of GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity must rest on different mechanisms and that N-deacylation of GM3 appears to be an essential step in conversion of the ganglioside into an inhibitor of lymphocyte blast transformation.

[Hemoperfusion via cryopreserved tissue fragments of xenogeneic spleen in suppurative-septic states in urology]. / Gemoperfuziia cherez kriokonservirovannye fragmenty tkani ksenoselezenki pri gnoino-septicheskikh sostoianiiakh v urologii.

Hemoperfusion through cryopreserved fragments of porcine xenospleen tissue was used in combined treatment of 42 patients with pyoseptic urologic diseases: urosepsis, purulent intoxication due to acute pyelonephritis, pyoinflammatory scrotal and prostatic lesions (in 15, 19, 8 patients, respectively). Indications and contraindications are specified. Altogether 57 sessions were performed. Seventeen patients underwent the perfusion pre- and postoperatively, twenty-five in combination with chemotherapy. After the removal porcine spleen was dissected, treated with cryoprotective mixture (-196 degrees C) and placed into liquid nitrogen. One-year viability of the tissue retained in 82-93% of the samples. Duration of the hemoperfusion was 40-80 min, the rate--30-40 ml/min. Two-four columns with cryopreserved tissue were utilized which were alternately connected with the circuit. Heparinization reached 12,000-15,000 units. All the patients survived. Positive clinical and laboratory findings were obtained for 38 patients (90%). Urine and blood samples appeared sterile on day 7-12. The improvement of the severe condition of the patients is attributed to detoxication, immunostimulation and immunocorrective effects.

Immunomodulatory effects of human placenta gangliosides.

The immunomodulatory properties of the major gangliosides of human placenta were studied. All the gangliosides investigated suppressed the cytotoxic activity of human natural killer cells. The magnitude of the inhibitory effect depended on ganglioside structure. Gangliosides GM1, GM3, and GD3 were the most effective suppressors. Some of the placental gangliosides (GD3, GD1a, IV3NeuAc-nLc4Cer, VI3NeuAc-nLc6Cer) also inhibited lymphoblastic transformation, and one of them (GM3) strongly stimulated the Con-A-induced T-suppressor activity of human lymphocytes. It is suggested that the combined action of the placental gangliosides on maternal effector cells may be involved in the defence of the human embryo against the maternal immune system.

[Ganglioside GM3 derivatives and their immunomodulating effect]. / Proizvodnye gangliozida GM3 i ikh immunomoduliruiushchii éffekt.

The derivatives of ganglioside GM3-NeuLacCer. NeuLacSph and NeuAcLacSphAc-were obtained and their immunomodulating properties studied. These substances are shown to inhibit lymphocyte blast-transformation independently of their ceramide structure. On the contrary, the stimulation by the above GM3-derivatives of Con A-induced T-suppressor activity depends significantly on the structure of their ceramide moiety.

[Selective action of chorionic gonadotropin on lymphocyte subpopulations]. / Izbiratel'noe vliianie khorionicheskogo gonadotropina na subpopuliatsii limfotsitov.

Influence of chorionic gonadotropin on induction and formation of specific T-suppressors, TDTH-effectors and spontaneous killer cells, depending on its doses and schema of injections was studied. It is shown that chorionic gonadotropin has a stimulating effect on precursors of T-suppressors, not affecting the mature specific T-suppressors, causes damage to the TDTH-effectors and spontaneous killer cells, that permits chorionic gonadotropin to be recognized as an immunomodulating agent.