Coherent lidars based on intracavity heterodyning of echo signals

The development and technical realization of the method of laser sounding of the atmosphere based on the effects of mixing of reference and external fields of scattering inside a laser cavity are presented. An approximate theory of the method was developed on the basis of the investigations using the model of a three-mirror laser. The nonlinear effect of a wideband laser on frequency-dependent external influences of the atmosphere was investigated. The field measurements of gaseous composition of the atmosphere were performed on the basis of a given method of coherent reception using a tunable CO2 laser

Применение метода электротомографии для изучения внутреннего строения каменных глетчеров Алтая

Internal structure of rock glaciers was investigated at two key sites in Altai by means of electric tomography. It had been found that the rock glaciers of the same type, located at different altitude levels, differ in electric resistances of ice nuclei and the degree of consolidation of the ice material inside of them. Typical characteristics of the ice core of a rock glacier in the high-mountain area are the following: electrical resistivity is about 1000–2000 kOhm∙m and a high degree of the ice consolidation, while the same for the mid-mountain region: the electrical resistivity is 150–300 kOhm∙m and the presence of the talik zones within the glacier body. Using the method of electric tomography for investigation of the internal structure of the rock-glaciers makes possible to reveal presence of frozen soils and ice and to find the upper boundary of occurrence of them from anomalously high specific electric resistance. However, it is not always possible to determine a thickness of the rock-ice formation, and to estimate a degree of its consolidation that does not allow calculating the ice content volume. Limitations of this technology can be overcome by the use of electric tomography in combination with other geophysical methods.На двух ключевых участках территории Алтая выполнено исследование внутреннего строения каменных глетчеров с использованием метода электротомографии. Установлено, что каменные глетчеры, располагающиеся на различных высотных уровнях, отличаются по удельному электрическому сопротивлению и степени консолидации ледяного материала. Для каменно-ледяного ядра каменного глетчера в высокогорье характерны удельное электрическое сопротивление 1000– 2000  кОм∙м и высокая степень консолидации льда, а для каменного глетчера в среднегорье эта величина равна 150–300 кОм∙м, а в теле каменного глетчера присутствуют таликовые зоны

CORRECTION OF INTERFERON-α-INDUCED DENDRITIC CELL DYSFUNCTIONS IN IMMUNOCOMPROMISED PATIENTS

The correction of impaired functions of in vitro generated interferon-alpha-induced dendritic cells (IFN-DCs) in patients with malignant brain tumors (n = 8), malignant lymphomas (n = 14) and pulmonary tuberculosis (n = 26) was analyzed in the present study. The principal possibility of restoring reduced functional activity of patient DCs was shown. The addition of recombinant human IL-2, complex of pro-inflammatory cytokines, double-stranded human DNA or polyoxidonium to IFN-DC cultures at the stage of maturation could significantly increase the allostimulatory activity of DCs in patients with malignant lymphomas and pulmonary tuberculosis, as well as enhance the cytotoxic activity of cancer patient DCs against NK- and TRAIL-resistant tumor cell line HEp-2. These findings offer new approaches to the correction of DC dysfunctions in the pathology and justify ways of improving the treatment of infectious diseases and cancer using dendritic cell vaccines

INTERLEUKIN-10 REGULATES PD-1-B7-H1-MEDIATED CYTOTOXIC ACTIVITY OF DENDRITIC CELLS

In this investigation the phenotypic and functional properties of healthy donor and patient with pulmonary tuberculosis (PT) dendritic cells (DCs) were characterized. We also studied the influence of IL-10 on the phenotype and apoptosis-inducing activity of healthy donor DCs. 60 patients with pulmonary tuberculosis with different proliferative response to antigens of M. tuberculosis (purified protein derivative, PPD) and 40 healthy donors were enrolled in this study. It was revealed that DCs, generated in vitro from PT patient's blood monocytes with GM-CSF+IFN-α, were characterized by increased B7-H1 expression, up-production of IL-10 and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). The endogenous IL-10 production by DCs was correlated with expression of B7-H1 in the general group of persons. It was revealed that addition of IL-10 to semi-mature DCs of healthy donor results in increasing of B7-H1 expression, diminishing of allostimulatory activity and enlargement of pro-apoptogenic activity of DCs

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 SIGNALING AS A NOVEL MECHANISM OF T CELL SUPPRESSION IN TUMOR NEOANGIOGENESIS

The immunomodulatory activity of vascular endothelial growth factors (VEGFs) reveals a new role of neoangiogenesis in tumor development. Most of VEGF effects on T cells are mediated through the VEGF-R2 receptors. Placental growth factor (PlGF) belongs to the VEGFs family and is a selective ligand for VEGF-R1. In order to study the role of VEGF-R1-signaling in the regulation of T-cell functions, the effect of PlGF on the proliferation of donor T cell has been investigated. PlGF has been shown to inhibit the proliferation of T-lymphocytes in cultures of anti-CD3-stimulated mononuclear cells in a wide dose range, suppressing the proliferative response of both CD4 + and CD8 + T cells. The suppressive effect of PlGF was mediated through the direct interaction with VEGFR-1 on T-cells that was evidenced by the expression of VEGFR-1 by T-lymphocytes (especially after their activation) and by blocking the suppressive effect of PlGF with neutralizing anti-VEGFR-1 antibodies. Given the increased levels of PlGF in many tumors, this factor may play an important role in immunomodulation during tumor growth, mediating its effect through the VEGFR-1 signaling pathway

CYTOTOXIC ACTIVITY OF DENDRITIC CELLS AGAINST ACTIVATED CD4+ AND CD8+T-LYMPHOCYTES IN THE CULTURE IN VITRO

The aim of the present study was a comparative assessment of the cytotoxic activity of IFNα-induced dendritic cells (IFN-DCs) and IL-4-induced DCs (IL4-DCs) against allo-MLC- activated CD4+ and CD8+T-lymphocytes. It was shown the level of AnnexinV+/PI- cells corresponding to early apoptosis among CD4+T-lymphocytes was lower in cultures with IFN-DCs compared with IL4-DCs. At the same time the relative number of AnnexinV+/ PI+ cells (late phase of apoptosis/necrosis) among CD4+T-lymphocytes activated by allogenic IFN-DCs and IL4-DCs increased in an equal degree. It was demonstrated that IFN-DCs possesed similar ability to induce apoptosis of CD3+CD8+T-lymphocytes

SPONTANEOUS AND LPS-INDUCED PRODUCTION OF 26 CYTOKINES SECRETED BY BLOOD CELLS OF PATIENTS WITH LIVER CIRRHOSIS DURING OF CELL THERAPY

The objective of the present study was to assess the level of 26 cytokines secreted by peripheral blood cells of the patients with liver cirrhosis (LC; n = 20) during the cell therapy (CT). All the patients were administered with intravenously injected autologous bone marrow-derived mononuclear cells (MNCs) in a dose of 1.3±0.3 × 109 (Ме 1.0 × 109 ) followed by 14 days later intravenous injection of ex vivo generated mesenchymal stromal cells (MSCs) in a dose of 22.3±5.0 × 106 (Ме 16.0 × 106 ). The patients were examined before the CT, 2-3 days after the administration of MNCs and, then, 2-3 days after the introduction of MSCs. Cytokine-secretory function of peripheral blood cells was evaluated in a 24-hour whole blood cultures both in the absence of any stimulation and in response to lipopolysaccharide (LPS). The control group consisted of 10 healthy donors. The administration of patients’ bone marrow cells (both MNCs and MSC) was safe and well tolerated and caused no any adverse (toxic or allergic) events. Compared with donors, LC patients (especially, with class B+C by Child-Pugh) differed by an initially increased production of several cytokines and chemokines. Actually, there was a statistically significant increase of the spontaneous production of IL-9, MIP-1β, and IP-10, as well as a distinct trend to an increase in TNFα, IL-1ra, IL-4, IL-5, IL-6, IL-13, of MCP-1, MIP-1α, RANTES and Eotaxin. Moreover, the blood cells of LC patients were susceptible to the stimulatory effect of LPS, and the LPS-induced production of 11 out of 26 cytokines (IL-1ra, IL-6, IL-9, IL-15, IL-17, IL-7, IL-8, IP-10, MIP-1α, MIP-1β, Eotaxin) significantly exceeded the normative values. Transplantation of bone marrow MNCs had minimal impact on cytokine production. Meanwhile, the MSCs introduction resulted in a significant decrease in spontaneous and LPS-induced production of, respectively, 20 and 18 analytes including pro-/anti-inflammatory and immunoregulatory cytokines, chemokines and growth factors. The normalization of cytokine-secretory function following transplantation of MSCs revealed in the patients with LC indicates the weakening of an inflammatory activity of circulating blood cells and the decrease in their reactivity to endotoxin. MSC suppressive effect on cytokine production was dose-dependent, and most pronounced in patients with decompensated LC (class B+C by Child-Pugh) of viral etiology

The difference between drugs of the same category in the treatment of psoriasis: an economic analysis

Psoriasis is one of the most common chronic dermatosis, which affects from 1 to 5% of the world's population. The article discusses the current views on the pathogenesis, the methods of treatment and drugs necessary for this and the economic analysis of the ratio of prices and effectiveness of treatment.Псориаз - один из самых распространенных хроничеcких дерматозов, которым страдает от 1 до 5 % населения планеты. В статье обсуждаются современные взгляды на патогенез, представлены методы лечения и лекарственные средства, необходимые для этого и проведен экономический анализ соотношения цен и эффективности лечения

EFFECT OF DEXAMETHASONE ON INTERFERON-α-INDUCED DIFFERENTIATION OF MONOCYTES TO DENDRITIC CELLS

Type I Interferons are potent inducers of monocyte’s differentiation into dendritic cells (DCs). However, sensitivity of these DCs to tolerogenic effect of glucocorticoids has not been previously investigated. The aim of this study was to investigate the effect of dexamethasone upon maturation and functions of interferonalpha-induced DCs (IFN-DC) derived from healthy donors. DCs were generated from blood monocytes cultured for 5 days with GM-CSF and IFNα, in absence or with addition of dexamethasone (10-6 M), applied on the 3rd day. Addition of dexamethasone inhibited IFN-DC maturation, which manifested with increasing numbers of CD14+ cells and decreased percentage of CD83+ DCs. Dexamethasone did not significantly influence HLA-DR, CD86 and B7H1 expression. However, it caused a 2-fold increase of tolerogenic TLR-2 molecule expression. Along with suppression of IFN-DC maturation, dexamethasone inhibited production of proinflammatory/Th1 cytokines (TNFα, IL-1, IL-2, IFNγ, IL-12), and some chemokines (MIP-1α, RANTES). Dexamethasone-treated IFN-DCs exhibited a 2-fold lower allostimulatory activity in mixed lymphocyte culture (MLC). Worth of note, the capacity of IFN-DCs to stimulate T cell proliferative response in allo-MLC showed direct correlation with CD83 expression on DCs, and an inverse correlation with CD14 and TLR-2. Evaluation of Th1/Th2-polarizing activity of IFN-DCs showed that dexamethasone exerted a pronounced inhibitory effect upon ability of DCs to stimulate T cells for IFNγ production, along with lowgrade suppressive effect upon ability of DCs to induce IL-6 production, thus being indicative for a dominance of Th2-polarizing activity of IFN-DCs under the influence of dexamethasone. In general, the data obtained show that IFN-DCs are sensitive to tolerogenic action of dexamethasone, and, hence, the IFN-DCs may mediate the immunomodulatory effect of glucocorticosteroids and represent novel candidate cells for the development of therapeutic tolerogenic DC-based vaccines applicable for management of autoimmune disorders

INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS

Dendritic cells (DCs) play a key role in maintaining the peripheral tolerance of lymphocytes to autoantigens. Recovery of immunological tolerance in autoimmune diseases, particularly, in rheumatoid arthritis (RA) is considered a new therapeutic strategy. The aim of this work was to study the effect of dexamethasone-modified DCs generated from monocytes of RA patients in the presence of IFNα (DCsDex), upon autologous T lymphocytes in mixed leukocyte culture (auto-MLC), and to investigate possible mechanisms of the DCsdex tolerogenic effect upon autoreactive T cells. We have shown, that DCsDex from RA patients induce T cell hyporeactivity in auto-MLC. Hyporeactivity of T cells is associated with cell cycle blockage in CD4+T lymphocytes and decreased IFNγ, IL-17, IL-4 and IL-13 production, which indicates the induction of CD4+T cell anergy. In this case, inhibition of Th1/Th17 has been more pronounced than the suppression of Th2 cells producing IL-4 and IL-13. Along with T cell anergy, the decrease of proliferative response in auto-MLC is associated with increased CD3+T lymphocyte apoptosis. In addition, the DCsDex of RA patients suppresses the proliferation of autologous T cells stimulated by unmodified DCs. This effect is associated with enhancement of IL-10-producing CD4+T cells in the auto-MLC, thus being indicative for an ability of DCsDex to induce conversion of CD4+T lymphocytes into regulatory T cells (Tr1). The data obtained characterize a new type of tolerogenic DCs, generated from blood monocytes of RA patients in the presence of IFNα and modified by dexamethasone, thus revealing a mechanism for tolerogenic effect of DCsDex upon T cells that recognize self-antigens in auto-MLC