Effect of Benzo(a)pyrene on the Expression of miR-483-3p in Hepatocyte Primary Culture and Rat Liver.

Here, we suggested that the epigenetic mechanism of benzo(a)pyrene (BP) action might be based on the aryl hydrocarbon receptor (AhR)-mediated transcription of the target genes, including miRNAs, that have the dioxin response element (DRE) in their promoters. The effect of BP on the expression of the oncogenic miR-483-3p, its host gene IGF2, and target gene IGF1 in primary hepatocytes and in the liver of Wistar female rats was investigated. The activation of AhR was confirmed using selective AhR inhibitor CH-223191 and by evaluating expression of the target CYP1A1 gene. The lack of coordination between the expression of miR-483-3p and its host gene IGF2 was revealed, which may be due to the presence of the binding site for the estrogen receptor alpha (ERα), which is a negative expression regulator. Our results confirm the existence of the AhR-mediated pathway in the regulation of expression of miR-483-3p, IGF1, and IGF2 under BP exposure, which is of considerable interest for understanding the epigenetic mechanisms of the carcinogenic effect of BP.

The pre-exponential voltage-exponent as a sensitive test parameter for field emission theories.

For field electron emission (FE), an empirical equation for measured current I m as a function of measured voltage V m has the form I m = CV m k exp[-B/V m], where B is a constant and C and k are constants or vary weakly with V m. Values for k can be extracted (i) from simulations based on some specific FE theory, and in principle (ii) from current-voltage measurements of sufficiently high quality. This paper shows that a comparison of theoretically derived and experimentally derived k-values could provide a sensitive and useful tool for comparing FE theory and experiment, and for choosing between alternative theories. Existing methods of extracting k-values from experimental or simulated current-voltage data are discussed, including a modernized 'least residual' method, and existing knowledge concerning k-values is summarized. Exploratory simulations are reported. Where an analytical result for k is independently known, this value is reliably extracted. More generally, extracted k-values are sensitive to details of the emission theory used, but also depend on assumed emitter shape; these two influences will need to be disentangled by future research, and a range of emitter shapes will need examination. Other procedural conclusions are reported. Some scientific issues that this new tool may eventually be able to help investigate are indicated.

[Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs]. / Vliianie benz[a]pirena na ékspressiiu AhR-reguliruemykh mikroRNK v legkikh samok i samtsov krys.

Smoking is the main risk factor for lung cancer, mainly due to presence of nitrosamines and polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP) in tobacco smoke composition. The genotoxic effect of BP is based on the high DNA-binding ability of its metabolites, while the epigenetic effects are mediated by a change in the expression of cancer related genes or regulatory RNAs. It has been shown that women have a higher risk to develop lung cancer upon smoking rather than men. We hypothesized that crosstalk between signaling pathways activated by BP and estrogens could underlie the sex-dependent differences in miRNAs expression. To test this hypothesis, male and female rats were subjected to short-term or long-term BP exposure. Using in silico analysis, miRNAs containing the ER- and AhR-binding sites in the promoters of the genes (or host genes) were selected. During chronic exposure of BP the expression of miR-22-3p, -29a-3p, -126a-3p, -193b-5p in the lungs of male rats were significantly increased, while the level of miRNA-483-3p were decreased. Expression of miRNA-483-3p was up-regulated during chronic BP exposure in the lungs of female rats and the levels of other studied miRNAs were unchanged. In turn, changes in the expression of miRNAs were followed by changes in the expression of their target genes, including PTEN, EMP2, IGF1, ITGA6, SLC34A2, and the observed changes in female and male rat lungs were varied. Thus, our results suggest that sex-dependent epigenetic effects of BP may be based on different expression of AhR- and ER- regulated miRNAs.

[Clinical and neuroimmunoendocrine effects of doxasosine in treatment of benign hyperplasia of the prostate in elderly people].

Benign hyperplasia of prostate is a very important not only medical but also social problem. The clinical and neuroimmunoendocrine status of elderly patients with benign hyperplasia of prostate treated by 1-blocker doxasosine is described in this article. Intercellular interactions were examined for tumor necrosis factor a (TNF-alpha), proinflammative interleukine-6 (IL-6), soluble intercellular molecule of adhesion (sICAM). The positive role of doxasosine is demonstrated.

[Medical and social problems in gerontology and geriatrics: the acknowledgment of patients and medical personnel].

The positions of patients and medical personnel are described in this article. The problems of prevention in elders and medical education of patients are investigated.

[Development of rat spleen organotypic culture under the influence of aminoacids and antibodies against nerve growth factor receptors].

Effect of each of 20 L-aminoacids on spleen organotypic culture of 3 month-old rats was studied in the presence of monoclonal antibodies against low-affinity nerve growth factor (NGF) receptors NGFRp75, which are known to induce apoptosis. It was shown that the action of aminoacids lysine, asparagine and glutamic acid stimulating explant proliferative activity, was independent on NGFRp75. On the contrary, the action of hydrophobic aminoacids, which, if applied separately, inhibited the explant growth, was canceled in the presence of antibodies against NGFRp75. Thus, this group of aminoacids may mediate their proapoptotic effect on lymphoid tissue by means of low-affinity receptors to NGF.

[Endothelial changes in cardiovascular pathology in the elderly. Part 2. Signal molecules and the pathogenesis of atherosclerosis].

This article is a continuation of the review on the issue of the interaction between the endothelium and numerous biologically active substances, secreted by endotheliocytes and their environment--the so called signal molecules--in the most prevalent cardiovascular pathology in the elderly. For example tumor necrosis factor plays a pathogenetic role as an immunomodulator, possesses anti-inflammatory and pro-atherogenic properties, provokes endothelial dysfunction, and stimulates the expression of other pro-inflammatory cytokines. Other signal molecules are described as well. The article also presents data from studies directed towards the perfection of atherosclerosis therapy via affecting signal molecules: depression of the expression of interleukins and their receptors, inhibition of atherogenic interleukins, neutralization of pro-inflammatory interleukins, and introduction of interleukin receptor antagonists.

[Changes of the endothelium in cardiovascular pathology in the elderly. Part I. Signal molecules and endothelial functions].

The review discusses the issue of the interaction between the endothelium and numerous biologically active substances, secreted by endotheliocytes and their environment--the so called signal molecules - in the most prevalent pathology in the elderly. In the elderly, signal molecules are synthesized by endothelial cells less intensively by comparison to young and middle-age people because a range of morphological features of endotheliocytes at elderly age: a hyperchromic nucleus; a smaller number of ribosomes, which leads to the inhibition of protein synthesis; a bigger number of lysosomes; structural changes in myofibrils; alterations in the mitochondrial structure such as crista death as well as the swelling and destruction of some organellas, which disturb the process of energosynthesis. At the same time, the main regulatory functions of the endothelium--vasomotor, antithrombocyte, anticoagulatory, thrombolytic, antiinflammatory, antioxidative, and antiproliferative ones--are the same in the healthy elderly and at earlier stages of ontogenesis. Disturbances in one or another endothelial function, especially at elderly age when the peculiarities of endothelial functioning under normal conditions are formed together with age-related morphological changes, result in fast development and progress of cardiovascular diseases.

[Effect of amino acids on cell proliferation and apoptosis in organotypic tissue culture of young and old rats].

There was studied in brain cortex, spleen and liver organotypic tissue culture the effect of effective concentrations (0.05 ng/ml) of 20 amino acids on the development of proliferative activity and apoptosis in peripheral fields of explants of rats of various age: 1 month and 18 months old. In the young tissues, the most frequent activity (3 times) was found while using the histidine, asparagine acide, valine, threonine, proline, leucine, tyrosine, methionine, and the less frequent (1 time)--while using lysine, glutamine, cysteine. Almost half number of the amino acids (11) was active in the old tissue cultures, as compared to the young tissues (19). The summary effectiveness of the amino acids was greater in young tissues (42), as compared to the old tissues (11). The data obtained suggest, that the bioregulator peptides should be necessary used to correct the less sensitivity of the tissues to the amino acids in old age.

[The tissue-specific effect of synthetic peptides-biologic regulators in organotypic tissues culture in young and old rats].

The synthetic peptides--cardiogen, bronchogen, prostamax and pancragen were used to investigate their effect on organotypic tissue culture of explants from heart, lungs, prostatic gland and pancreas of young (3-week old) and aged (18-month old) rats. The peptide effective concentration of 0.05 ng/ml showed a stimulating effect in appropriate tissue cultures as compared to the control explants in all groups of rats. So these bioregulatory peptides can be used in clinic practice for the stimulation of reparative processes in the appropriate tissues while ageing.

[Chemiluminescence in a stimulated polymorphonuclear leukocytes--luminol system: suppression by thiols].

The effect of some scavengers of thiol nature, which eliminate all reactive oxygen species and oxidants with reactive chlorine, on the luminol-enhanced chemiluminescence of polymorphonuclear leukocytes was studied. The use of two scavengers of this type (penetrating and not penetrating into the cell) made it possible to separate the luminescence of cell structures from the luminescence generated by oxidants in the surrounding medium. It was found that about a half of luminol luminescence is due to its oxidation in the medium surrounding the cell, and it is completely inhibited by the nonpenetrating reduced glutathione. The cell itself is a source of a considerable portion of luminescence, and this luminescence is quenched by penetrating sulfhydryl compounds such as dithiothreitol and N-acethyl cysteine. Reduced glutathione, which penetrates into cells and whose action is due only to the sulfhydryl group, is recommended as a candidate for the selective neutralization of extracellular oxidants.

Heterogeneity of smooth muscle cells in embryonic human aorta.

Cellular composition of aortas from 5- to 12-week and 18- to 28-week-old human embryos were investigated using immunocytochemistry, scanning and transmission electron microscopy. The aorta of the 5- to 12-week-old embryos consisted of three sublayers differing in cellular composition. The inner sublayer adjacent to the endothelium contained round and ovoid cells with synthetic phenotype. In the intermediate sublayer, spindle-like cells ultrastructurally similar to smooth muscle cells were found. Cells of the outer sublayer resembled fibroblasts or poorly differentiated mesenchymal cells. There were not definite morphological borders between sublayers. In the 18- to 28-week-old embryo aorta the intima was separated from media by internal elastic lamina. Intimal and innermost medial cells had predominately stellate shape and synthetic phenotype. The outer part of media contained spindle-like cells that had well developed contractile structures. Both the 5- to 12-week-old and the 18- to 28-week-old embryo aortic cells were positively stained for alpha-actin and myosin and negatively stained for macrophage antigens. Thus, the majority of embryo aortic cells appeared smooth muscle cells, however there was a regional difference in shape and synthetic state of these cells.

[Functional morphology of an organotypic liver culture exposed to the peptide livagen]. / Funktsional'naia morfologiia organotipicheskoi kul'tury pecheni pri deistvii peptida livagena.

In this study the results of the tetrapeptide livagen effect on functional morphological characteristics have been produced. Under the data of the immunocytochemical and morphometrical analysis, tetrapeptide stimulates structural and functional homeostasis of cell populations in the liver culture. It was demonstrated that the main activity of investigated peptide had been directed to the stabilisation of morphological safety and reinforcement of the processes of cellular and intracellular forms of regeneration.

[Cellular orientation and form in the elastic-hyperplastic layer of the human aortic intima in the area of the ostia of the intercostal arteries]. / Orientatsiia i forma kletok élastiko-giperplasticheskogo sloia intimy aorty cheloveka v oblasti ust'ev mezhrebernykh arterii.

Using the Hatcher monolayer method, it has been shown that the aortic intimal smooth muscle cells, disposed on the flow divider of an intercostal artery, have predominantly spindle-like shapes to be oriented perpendicularly to the long axis of the vessel. Unlike, in the proximal and lateral sites of the intercostal ostium the intima is represented by stellate cells lacking any orientation. These distinctions may be presumably determined by the irregular distribution of hemodynamic loading on the aortic intima in different regions around the ostium of an intercostal artery.

[Changes in the spatial organization and structure of the smooth-muscle cells of the tunica media of the major arteries during lengthwise stretching in situ]. / Izmenenie prostranstvennoi organizatsii i struktury gladkomyshechnykh kletok srednei obolochki magistral'nykh arterii v usloviiakh prodol'nogo rastiazheniia in situ.

It has been shown that in vivo stretching of the arterial wall leads to the loss of cell-cell contacts between medial smooth muscle cells (SMC), and to the change in the cell cooperation type. It is accompanied by the increase in SMC proliferative activity, and by changes in their shape and phenotype, from the contractile to the synthetic one. The increase in the number of extracellular connective tissue structures occurs in the intercellular space.

[Changes in the orientation of the smooth-muscle cells of the tunica media from major arteries under constant lengthwise stretching in situ]. / Izmenenie orientatsii gladkomyshechnykh kletok srednei obolochki magistral'nykh arterii v usloviiakh postoiannogo prodol'nogo rastiazheniia in situ.

It has been shown that changes in the orientation of arterial smooth muscle cells during a constant longitudinal stretching of the artery in vivo are not similar in different sections of the stretching zone. Cells in the proximal and distal sections keep their orientation but this orientation differs from that of smooth muscle cells in the control arteries. Cells in the central part of the stretching region lose their definite orientation to settle randomly.

[Structural changes in the endothelium of the major arteries under conditions of longitudinal stretching in vivo (based on scanning electron microscopic data)]. / Izmenenie struktury éndoteliia magistral'nykh arterii v usloviiakh prodol'nogo rastiazheniia in vivo (po dannym skaniruiushchei élektronnoi mikroskopii).

The method of scanning electron microscopy was used for studying three-dimensional organization of the endothelium of major vessels under conditions of distraction in vivo. The distraction resulted in an enlargement of the spaces between endotheliocytes without formation of considerable areas of deendothelialized surface. The main mechanism of induction of flattening and division of endotheliocytes in the zone of distraction seems to be the elimination of the contact inhibition resulting from a mechanical distraction.

[Spitz nevus (juvenile nevus) of the penile skin]. / Nevus Spitz ("iuvenil'nyi" nevus) kozhi polovogo chlena.

Compound spindle cell and epithelioid cell nevus (Spitz nevus) at the anterior surface of the penile skin in a 31-year-old patient is described. The histological structure of the tumor is discussed in terms of differential diagnosis.

[Use of impase in the therapy of erectile dysfunction]. / Primenenie preparata impazy v terapii érektil'noi disfunktsii.

Efficacy of impasse in therapy of sexual dysfunctions of vascular genesis was studied in 38 male patients aged 35-68 years. The drug was taken for 2 months. The control was conducted with ultrasonic dopplerography. Impasse showed high efficacy in therapy of vascular sexual dysfunctions especially in the group of patients aged 35-50 years with initial values of maximal systolic speed at least 15 cm/s.

[Application of the preparation "vitamax" in the complex treatment of chronic prostatitis complicated by sexual dysfunction]. / Primenenie preparata "vitamaks" v kompleksnoi terapii khronicheskogo prostatita, oslozhennogo seksual'noi disfunktsiei.

A multivitamin complex Vitamax was given to 65 patients with chronic prostatitis who retained sexual disorders after basic treatment. Mean age of the men was 41 +/- 10 years (25-67 years). The efficacy of the drug was assessed by the data obtained with Male Copulative Function questionnaire. All the patients were found to have mixed sexual dysfunction. Vitamax was taken in a dose 2 capsules a day before a morning meal, a total of 30 capsules a course. After the treatment all the patients improved their copulative function. Thus, Vitamax is an effective drug in sexual dysfunctions related to chronic prostatitis, the efficacy being higher in young men. Side effects were absent.