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Reactions of indolo[2,3-a]furano[3,4-c]carbazole-5,7-diones with hydrazine hydrate, hydroxylamine hydrochloride, and formyl hydrazine produced the corresponding N-6-substituted indolopyrrolocarbazole glycosides with the carbohydrate residues L-arabinose, D-galactose, D-xylose, and D-ribose. The obtained compounds were studied in vitro and in vivo and showed significant antiproliferative activity against HCT-116 cells (IC50 = 10–6 – 10–7 M) and high antitumor effects on Ehrlich ascites tumor and P-388 lymphocytic leukemia models. The lifespan increase of animals in the first model ranged from 540 – 495% to 172 – 132%; in the second model, from 80 – 83% to 120 – 93%.

According to modern healthcare requirements, it is necessary to increase workforce capacity of primary care practice, therefore, improving the specialist training is one of the high-priority problems of medical education. Not enough attention is paid to paramedic education and their role in Russian healthcare. The presented analysis of the paramedic profession history and the current state of high-quality healthcare in Russia shows the need to create a regulatory basis for the training of paramedics in the higher education system — a bachelor’s degree.

Background. The addition of active metabolites (in particular, amino acids) to the molecule affects the physicochemical and prodrug properties of derivatives of indolocarbazoles. Using computed chemoinformatics, probability antitumor activity of amino-acid derivatives of glycosides of indolocarbazol (AADGI) is predicted with low probability of their cytotoxic activity in vitro. Based on these data, a study of these compounds in vivo is conducted. Objective: the assessment of AADGI as potential antitumor medications. Materials and methods. Research antitumor activity of AADGI was done using murine tumor models - cervical cancer CC-5. Investigated compounds were injected to mice СВА abdominally 5-times daily with interval of 24 h. Observation of animals were continued till their death. Antitumor effect of compounds was assessed by criteria of tumor growth inhibition and increase in life expectancy of mice comparing to control animals. Results. The optimal dose for these series of compounds was titrated and this dose is 100 mg/kg. Antitumor activity of AADGI was assessed on CC-5. Conclusions. Based on data received we suggest an extended study in vivo of antitumor qualities of selected 5 leader AADGI.

Objective: to study the cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with antipyrine (AP), caffeine (caf) and 1,10-phenantroline (phen) in comparison with that of free ligands, zinc (II) and cadmium (II) iodides in vitro. Materials and methods. The cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with AP, caf and phen in comparison with that of free ligands, zinc (II) and cadmium (II) iodides was investigated by methylthiazole tetrazolium assay using 5 human tumor cell lines. Results. It has been found that all 3 cadmium complexes demonstrate cytotoxic activity towards all 5 cell lines with concentration of inhibition of 50 % cell growth 5.5-84.0 mkM. Cytotoxicity of the most active diiodo(1,10-phenantroline)cadmium was slightly above than that of the respective ligand. One zinc-containing complex (diiodo(1,10-phenantroline)zinc) demonstrated significant activity towards 3 cell lines. The Jurkat cells were the most sensitive to studied compounds. Conclusion. It seems that zinc (II) and cadmium (II) iodide complexes with organic ligands are promising ones as potential antitumor drugs for further investigations both in vitro and in vivo.

The dynamics of the endogenous production of NO metabolites, nitrites, nitrates, and volatile nitrosamines, has been investigated in the body, a tumor tissue, and peritoneal macrophages of mice F1 (C57Bl × CBA), Balb/c and BDF with subcutaneously transplanted tumors: Ehrlich carcinoma (EC) and Lewis metastatic lung carcinoma (LC). It has been shown that during the first three weeks, growth of EC is accompanied by a statistically significant increase in the total concentration of NO metabolites (NOx; nitrites + nitrates) up to levels (7.3 ± 3.49) × 10−6−(7.8 ± 2.57) × 10−5 mol/kg in the tumor tissue and a sharp increase in NOx excretion with urine. At the same time, in the LC tumor tissue the maximal level of NOx (3.6 ± 0.46) × 10−5 mol/kg was registered on day 7, and later it decreased demonstrating negative correlation with the tumor mass. At the stage of intensive LC growth (14, 21 days) there was significant inhibition of nitrite secretion by peritoneal macrophages. In all the controlled time-intervals the EC tumor tissue contained carcinogenic N-nitrosodimethylamine and N-nitrosodiethylamine; however, their concentrations significantly varied. Thus, the ability of the tumor tissue to produce NO metabolites was more pronounced in EC than in LC and depended on the time parameters of tumor growth.

Special surfaces based on titanium dioxide are developed for prevention of nosocomial infections. The reactive oxygen species (ROS) have been generated by the surfaces after their UV-irradiation. ROS caused destruction of bacteria. However, effectiveness of bactericidal activity of ТiO 2-films depends on several factors. Influence of time of UV irradiation, thermal (annealing) and chemical (benzene) treatment of films on the bactericidal activity, as well as the bactericidal effect against suspended and lyophilized bacteria have been studied. Three clinical isolates Staphylococcus aureus 956, Staphylococcus epidermidis 1061, Escherichia coli 321-5 have been used. Viability of the suspended bacteria has been determined with use of the classical method of counting CFU, viability of lyophilized bacteria has been determined with use of the method of estimation of coefficients of bactericidal extinction of control and test samples. It has been shown that the bactericidal effect of thin films against all strains increased with an increase in the flow of UV exposure. dermal and chemical treatment caused bactericidal activity recovery which was lost during the initial incubation of the bacterial suspension on the surface. Absence of fluid in the system increased the bactericidal activity of TiO 2-films.

Synthesis of lupane C28-imidazolides, contained 3-oxo-, 3-oximino- and 2-cyano-2,3-seco-4(23)-en-frag ments in cycle A was carried out. The most antitumor activity at. in vitro testing showed 3-oximino-lup- 20(29)-en-28-yl-1H-imidazole-1-carboxylate; which inhibited the growth or induced apoptosis of non-small lung cancer, colon cancer, breast cancer, CNS cancer, ovarian cancer, prostate cancer, leucosis, melanoma cells. In experiments in mice its moderate antitumor activity against grafted breast adenocarcinoma Ca 755 and adenocarcinima of colon was observed.

A decline in CFU of gram-positive and gram-negative bacteria on the surface of UV illuminated TiO2 films (wavelength of 380 nm) is shown. A 29, 45, and 47% decrease in bacterial viability of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli, respectively, was seen following a 12-min exposition. It was first discovered that the reuse of TiO2 films to test a bacterial suspension for viability removes UV-induced bactericidal activity. However, annealing of TiO2 at a temperature above 400 degrees C restores the photoinduced bactericidal activity to its initial state.

The endogenous formation of metabolites of NO - nitrite (NI), nitrates (NA) and volatile nitrosamines in the body, tumor tissue and by abdominal cavity by macrophages for dynamics was investigated in mice F1(C57BlxCBA), Balb/c and BDF with subcutaneous transplanted tumors (Erlich carcinoma - EC and metastatic Lewis lung carcinoma - LLC). It was shown that growth of EC was accompanied by a statistically significant increase in the concentrations of NI and NA in tumor tissue to (7.3±4.67)'10-6 - (7.8±2.57)'10-5 (mol/kg) for the first three weeks and a sharp increase in urinary excretion of NI and NA. The maximum total concentration of NI and NA - (3.,6±0.46)'10-5 in tissue LLC was registered during the early stage of the tumor growth (7 days); it later declined, negatively correlating with the mass of the tumor. NI secretion by abdominal cavity macrophages demonstrated statistically significantly decrease at the stage of intensive growth LLC (14, 21 days). The tissue of EC contained varied concentration of cancerogenic N-nitrosodimethylamine and N-nitrosodiethylamine at all investigated time points. Thus, the ability of different gistogenesis tumor tissue to synthesize metabolites NO depended on time parameters and was more pronounced for EC, than LLC.V issledovaniiakh na myshakh F1(C57BlxCBA), Balb/c i BDF s podkozhno perevitymi opukholiami (kartsinoma Érlikha – KÉ i metastaziruiushchaia kartsinoma legkikh L'iuisa – KL) izuchena dinamika éndogennogo obrazovaniia metabolitov NO – nitritov (NI), nitratov (NA), letuchikh nitrozaminov v organizme, v opukholevoĭ tkani i peritoneal'nymi makrofagami. Pokazano, chto rost KÉ v techenie pervykh trekh nedel' soprovozhdaetsia statisticheski znachimym uvelicheniem summarnoĭ kontsentratsii NI+NA v opukholevoĭ tkani do urovneĭ (7,3±4,67)´10-6 – (7,8±2,57)´10-5 (mol'/kg), a takzhe rezkogo uvelicheniia vydeleniia NI+NA s mochoĭ. V to zhe vremia, v opukholevoĭ tkani KL maksimal'nyĭ uroven' kontsentratsii NI+NA (3,6±0,46kh10-5) registrirovali na 7-e sutki, v dal'neĭshem on snizhalsia, otritsatel'no korreliruia s massoĭ opukholi. Na étape intensivnogo rosta KL (14, 21 sutki) obnaruzheno dostovernoe podavlenie sekretsii NI peritoneal'nymi makrofagami. Na vsekh kontroliruemykh srokakh razvitiia opukholevaia tkan' KÉ soderzhala kantserogennye N-nitrozodimetilamin i N-nitrozodiétilamin, kontsentratsiia kotorykh sushchestvenno var'irovala. Takim obrazom, sposobnost' opukholevoĭ tkani sintezirovat' metabolity NO bolee vyrazhena u KÉ, po sravneniiu s KL i zavisit ot vremennykh parametrov rosta opukholeĭ.

Twenty-four rosettes (proliferative epidermal units) in epithelial tissue are united into morphofunctional zones, where cambial cells proliferate with the formation of maternal and daughter cells and these latter ones differentiate under the influence of electrical field generated by 12 maternal cells. The number of cambial cells in morphofunctional zone of a malignant tumor is reduced at least 2-fold. Hence, the number of maternal cells is reduced to 6, which is insufficient for electric field generation and stimulation of daughter cells differentiation. The percentage of cambial cells in a benign tumor decreases 1.5 times. Daughter cells are differentiated in an electric field whose strength is below optimal, but above the threshold value at which cells do not differentiate; hence, differentiation is incomplete.

The basal layer of mouse skin epidermis consists of special structures - rosettes functionally arranged in zones including about 20 rosettes. The rosette contains a central cambial cell; after division of this cell the mother cell remains in the center of the rosette and the daughter cell migrated to the center of a free rosette. The mother and daughter cells are dipole cells (sources of electric field). If the disposition of mother cells is unidirectional and they predominate over daughter cells, the latter cells transform into other cells, i. e. are differentiated.

Studies of mouse ear epidermis showed that proliferative activity of basal epidermal cells has two active and two passive phases throughout 24 h. Active phases consist of two subphases: long (proliferation of cambial cell descendants) and very short (cambial cell proliferation). Cambial cells proliferate at the boundary between active and passive phases; this results in an increase in the counts of epidermal melanocytes and Langerhans cells resultant from division of epidermal cambial cells. The count of Langerhans cells almost 2-fold surpasses melanocyte count, because melanocytes gradually transform into epidermal basal cells.

A decline in CFU of gram-positive and gram-negative bacteria on the surface of UV illuminated TiO2 films (wavelength of 380 nm) is shown. A 29, 45, and 47% decrease in bacterial viability of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli, respectively, was seen following a 12-min exposition. It was first discovered that the reuse of TiO2 films to test a bacterial suspension for viability removes UV-induced bactericidal activity. However, annealing of TiO2 at a temperature above 400 degrees C restores the photoinduced bactericidal activity to its initial state.

In recent years, considerable effort of researchers has been devoted to studying the cellular signal systems, that is, the pathways of information transfer inside the cell. A significant role in this process is played by the transport of K, Na, Ca, Mg and some other ions. In connection with this, it is interesting to study ionophores – compounds with a special molecular structure that renders them capable of carrying small ions through lipid barriers. Ionophores are stable both chemically and biologically. These compounds either contain macrocyclic structural fragments or are capable of forming such structures by means of hydrogen bonds. Macrocyclic ionophores of natural origin can be considered as prototypes of crown compounds [1]. As is known, actinomycin D forms complexes with Na analogous to those formed by crown compounds [2, 3]. The crown groups can be introduced into the structure of a DNA complexon [4], but the effect of such groups upon the antitumor activity of such complexes has not been systematically studied. It was suggested that the complexation of actinomycin D with Na is related to the properties of cyclopeptide groups of this antibiotic, which are composed predominantly of N-alkylamino acids [5, 6]. We suggested that introducing crown groups free of cationoid centers into the amide groups of actinocin amides would lead to new compounds with properties close to those of actinomycin D. In this context, we have synthesized actinocin derivatives containing benzo-15-crown-5 and benzo-18-crown-6 groups attached via amide bonds. We studied both compounds with the crown fragments introduced immediately in the amide groups of actinocin diamides [7] and those in which with the fragments were separated from the amide groups by amino acid residues (glycine, -alanine, and 6-aminocaproic acid) [8]. The compounds studied were synthesized as described previously [7, 8].

Epidermis and dermis form an integral morphofunctional area, where cambial cells proliferate and their first-division daughter cells differentiate. An important feature of this area is different rates of the development of daughter cells (fibroblasts) in the dermis and epidermis, which is greater in the epidermis. This asymmetry results in the prevalence of first epidermal daughter cells and, hence, their effect on cambial cells, and then of stromal daughter cells and their effects on cambial cells. The regulator factors of epidermal daughter cells promote unblocking of the major polarity axis of cambial (mother) cell, while stromal cells (fibroblasts) induce their polarization along the major axis and the onset of mitosis. In the dermis and epidermis, division of cambial cells is asymmetric; a prominent role in the formation of mother and daughter cells is given to the basal membrane as an elastic support. Mother and daughter cells form ring-like structures generating electric field that can promote differentiation of the daughter cells.