[Extracellular vesicles for diagnosis and therapy of gliomas: problems and opportunities]. / Vnekletochnye vezikuly v diagnostike i terapii gliom: problemy i perspektivy.

Glioblastoma is a primary brain tumor and one of the most aggressive malignant neoplasms. The prognosis remains poor with a short survival period after diagnosis even in the case of timely detection and early treatment with the use of advanced chemotherapy, radiation therapy and surgical treatment. In this regard, the research of the main pathogenetic links in the glioblastoma development continues. The current focus is on studying the molecular characteristics of tumours, including the analysis of extracellular vesicles, which play an essential role in intercellular communication processes. In this review, in order to provide up-to-date information on the role of extracellular vesicles in the diagnosis and therapy of gliomas, the analysis of the achieved results of Russian and foreign research related to this area has been carried out. The main goal of this review is to describe the features of extracellular vesicles as the containers and glioma marker transporters, as well as nucleic acids used in diagnosis and therapy.

Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1ß in the Lung Tissue and Blood Serum of Mice with Experimental Influenza.

We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1ß levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 µg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. The results of studying the dynamics of the cytokine levels in the infected animals in general support the previous hypothesis that, in repeated dosing, tilorone enhances the IFN response (compensates for its deficiency) at the early stages of acute respiratory viral infections and suppresses (damps) excessive production of IFN and proinflammatory cytokines at the later stages.

Non-magnetic shell coating of magnetic nanoparticles as key factor of toxicity for cancer cells in a low frequency alternating magnetic field.

This work is devoted to studying the effects of non-magnetic shell coating on nanoparticles in a low frequency alternating magnetic field (LF AMF) on tumor cells in vitro. Two types of iron oxide nanoparticles with the same magnetic core with and without silica shells were synthesized. Nanoparticles with silica shells significantly decreased the viability of PC3 cancer cells in a low frequency alternating magnetic field according to the cytotoxicity test, unlike uncoated nanoparticles. We showed that cell death results from the intracellular membrane integrity failure, and the calcium ions concentration increase with the subsequent necrosis. Transmission electron microscopy images showed that the uncoated silica nanoparticles are primarily found in an aggregated form in cells. We believe that uncoated nanoparticles lose their colloidal stability in an acidic endosomal environment after internalization into the cell due to surface etching and the formation of aggregates. As a result, they encounter high endosomal macromolecular viscosity and become unable to rotate efficiently. We assume that effective rotation of nanoparticles causes cell death. In turn, silica shell coating increases nanoparticles stability, preventing aggregation in endosomes. Thus, we propose that the colloidal stability of magnetic nanoparticles inside cells is one of the key factors for effective magneto-mechanical actuation.

[Prospects of Pharmacogenetic Testing for Design of Algorithms for Personalized Treatment of Tuberculosis of Respiratory Organs in the Astrakhan Region].

In spite of the availability of many antituberculosis drugs all over the world the morbidity of tuberculosis does not lower. Often the tuberculosis therapy schemes are adapted to every particular patient which is mainly due to the therapy unfavourable effects requiring discontinuation of the drugs used. Polymorphism of the detoxication genes, as predictors of the response to the drug therapy, was shown to be of certain significance. The experimental data would allow to substantiate personalized management of tuberculosis patients and to increase its efficacy and safety.

[Regulation of insulin-like growth factors and NF-kappaB by proteasome system in endometrial cancer].

Insulin-like growth factors and the nuclear factor kappaB (NF-kappaB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity ofproteasomes and IGF-I, IGF-II and NF-kappaB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in unaltered endometrium. Negative correlations between the 26S proteasome activity and NF-kappaBp50 level as well as between the 26S and 20S proteasome activities and IGF-I level were found. The data obtained indicate a possible proteasome regulation of growth and transcription factors. As it is considered that the major pool of IGF-I is located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of IGF-I content. The positive correlation between IGF-I level and PAPP-A metalloproteinase gives evidence that this proteolytic enzyme is another important regulator of growth factor level, which provides proteolysis of IGF-I binding proteins and increasing IGF-I concentration in tissues. The present data show possibility of proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.

[Proteasome activity in tumors of female reproductive system].

Proteasomes (multiproteinase protein complexes) are known to play an important role in cancer pathogenesis, however, few information about their activity in human tumor tissues is available so far. We studied chymotrypsin-like activity of proteasomes in tissues of breast cancer (BC) and endometrial cancer (EC). The chymotrypsin-like total proteasome activity and the 20S and 26S proteasome activity in malignant tissues were shown to be significantly higher in malignant tumors than in normal tissues. No increase in proteasome activity was registered with larger tumor size in both BC and EC, whereas proteasome activity was changed with respect to the extent of tumor involvement. In breast cancer tissues, significant reductions in the total and the 26S proteaome activities were observed in tumors with regional lymph node metastases as compared to tumors without metastases. In endometrial cancer tissues, the total proteasome activity and the 20S and 26S proteasome activities were increased as the depth of myometrial invasion. The data obtained indicate that the proteasome acyivity is significantly changed in the process of cancerogenesis and further study is needed to develop new additional prognostic criteria and effective anti-tumor agents in molecular-directed therapy.

[Study on phenotypical activity of isoenzyme CYP3A4 in children].

The urine levels of cortisol and 6-beta-hydroxycortisol in 30 healthy children were determined with high performance liquid chromatography. The activity of cytochrome P450 isoenzyme CYP3A4 was estimated by the ratio of 6-beta-hydroxycortisol and cortisol. Differences in the CYP3A4 activity depended on the age sex. At the age of 4 to 9 years the value of the ratio was 9.21 +/- 0.67 which in fact was statistically higher than that in the children at the age of 0 to 3 years (p<0.001). In the female children at the age of 0 to 3 years the value of the isoenzyme CYP3A4 activity was actually lower (p<0,05) vs. the female children of the higher ages and the male children at the age of 0 to 3 years. The results are useful for further researches on improvement of drugs dosing and prevention of adverse reactions.

[The value of neopterin in etiological diagnosis of endogenous uveitis].

Neopterin concentration in blood serum and tear fluid was estimated in 94 patients with endogenous uveitis and 28 healthy subjects. Neopterin concentration was found to be elevated in blood serum of patients with herpetic (12,31+1,1 micromol/L), tubercular uveitis (17,77+4,18 18 micromol/L) and uveitis associated with systemic conditions (12,31+1,1 micromol/L). Neopterin concentration in blood serum of healthy subjects was 8,45+0,61 micromol/L. Dynamics of neopterin concentration in blood serum of patients with uveitis varies depending on etiology. Neopterin concentration in tear fluid of healthy subjects appeared to be higher as compared with blood serum and was as high as 14,52+1,61 micromol/L (p < 0.05). Due to wide range of neopterin concentration in tear fluid, absence of significant correlation with blood serum concentration, apparently because of additional "local" production, authors propose to use only blood serum neopterin concentration for etiologocal diagnosis and control of treatment efficacy.

[Plasmapheresis combined with cell mass ozonation in endogenous uveitis treatment].

Authors propose a new method of uveitis treatment based on plasmapheresis in combination with cell mass ozonation. Analysis of treatment results of 3 patient groups (179 patients, 209 eyes) showed advantage of this original modification of plasmapheresis. In our opinion the effectiveness of proposed treatment option is associated with immunomodulatory effect of plasmapheresis and ozone therapy as well as bactericidal, antiviral and fungicidal effects of ozone therapy. Some sanogenetic mechanisms of the new treatment are disclosed in the study such as correction of T-cell immunodeficiency, decrease of circulating immune complexes and others.

[Human dirofilariasis in the Tula region].

The paper describes cases of dirofilariasis in the residents of Tula and the Tula Region. One of the cases does not fit into the traditional concepts. On excising a tumor in an adolescent, two live actively moving nonencapsulated helminths: a male and a female Dirofilaria repens worms were removed, which were identified at the parasitology laboratory, Center of Hygiene and Epidemiology in the Tula Region.

2-(4-Chloro-benzo-yl)-1-(diamino-methyl-ene)hydrazinium chloride monohydrate.

In the cation of the title compound, C(8)H(10)ClN(4)O(+)·Cl(-)·H(2)O, the guanidinium group is planar (maximum deviation = 0.0001 Å) and nearly perpendicular to carboxamide group, making a dihedral angle of 87.0 (3)°. The N atoms of the guanidine fragment have a planar trigonal configuration and the N atom of the carboxamide group adopts a pyramidal configuration. In the crystal structure, inter-molecular N-H⋯O, N-H⋯Cl and O-H⋯Cl hydrogen bonds link the cations, anions and water mol-ecules into layers parallel to the bc plane.

[Association of the chromosomal region 2q35 with type 1 diabetes mellitus in the Russian patients from Moscow].

To map human chromosome 2 region associated with type 1 diabetes mellitus, 89 families with concordant and discordant sib pairs were analyzed. Linkage and association with type 1 diabetes were examined using polymorphic microsatellite markers spanning the region of about 4 Mb. The linkage plot was constructed, and association of the five microsatellite markers within the chromosomal region 2q35 was examined. Polymorphic marker D2S137 (Z' = 3.225, p(c) = 0.0048) demonstrated maximum linkage and association with type 1 diabetes.

[Cholera in Kazan. Organization and implementation of cholera control interventions]. / Kholera v Kazani. Organizatsiia i provedenie protivokholernykh meropriiatii.

Data on emergent epidemiological analysis of the cholera outbreak in Kazan are presented. A version of the cholera focus emergence was confirmed, namely water route of transmission as a result of bathing in a water reservoir where sewage waters had penetrated. The outbreak had local and acute character. The complex of cholera control interventions aimed at localization and liquidation of the focus proved to be effective.

[Molecular and epidemiologic characteristics of HIV-infection outbreak in the Irkutsk region]. / Molekuliarno-épidemiologicheskaia kharakteristika vspyshki VICh-infektsii v Irkutskoi oblasti.

The genetic analysis of the variants of human immunodeficiency virus of type 1 (HIV-I) circulating among drug addicts in the Irkutsk region was carried out. The results of serological tests and comparative evaluation of electrophoretic mobility of heteroduplexes (HMA) revealed that all 74 samples under study belonged to subtype A. Genetic differences between these viruses did not exceed 2%. Thus, it was the variant of subtype A prevalent in CIS countries which caused the outbreak of HIV infection among drug addicts in the Irkutsk region, but not viruses of subtypes B, C or A/E typical for this risk group in relatively nearby China.

[Use of heat shock of antigen-presenting cells for functional testing of allospecificity memory T-cells]. / Ispol'zovanie teplovogo shoka antigenprezentiruiushchikh kletok dlia funktsional'nogo testirovaniia allospetsivicheskikh T-kletok pamiati.

For many years, the search for the appropriate method of testing the functional activity of the memory T-cells was an urgent problem and determined progress in the study of immunological memory. We proposed simple methods of functional testing the memory of CD8+ T-cells specific to the H-2Kb alloantigen based on measuring their proliferation in response to heat-treated allogenic splenocytes and cells of allogenic tumors in vitro. Primary proliferative response to the alloantigen was shown not to develop when the allogenic antigen-presenting cells were subjected to an acute (45 degrees C, 1 h) or moderate (42 degrees C, 30 min) heat shock. The block of the primary allogenic response of naive T-lymphocytes to the heated splenocytes could not be abrogated by the addition of exogenous IL-2 and was not due to deletion or suppression of antigen-reactive clones. On the contrary, the long-lived memory CD8+ T-cells induced in the course of the primary in vivo response were capable of proliferation in response to heat-treated allogenic stimulators carrying the same immunizing antigen. The different response of the naive T-cells and memory T-cells to the allogenic stimulators subjected to a heat shock might be due to a strict dependence of the naive T-cells on the inducing co-stimulation provided by the B7 ligand, whose expression was suppressed in the cultures containing the heat-treated stimulator cells. These results probably suggest that a specific immunoregulatory mechanism exists that is based on a disorder in costimulatory functions due to the cellular stress-response induced in the antigen-presenting cells.