Введение. Поиск биологических маркёров индивидуальной радиочувствительности человека остаётся чрезвычайно актуальной проблемой современной радиационной медицины. Цель - провести оценку аберраций числа копий ДНК (copy number aberration - CNA) в лимфоцитах крови работников, подвергшихся хроническому профессиональному радиационному воздействию. Методы. Обследовано 20 условно здоровых работников Сибирского химического комбината, подвергшихся внешнему радиационному воздействию. Всем обследованным лицам провели стандартный цитогенетический анализ. Выделенная ДНК из образцов крови исследована с использованием микроматрицы «CytoScan HD Array» («Affymetrix», США). Для обработки результатов микрочипирования использовали программу «Chromosome Analysis Suite 4.3» («Affymetrix», США). Результаты. У 4 из 20 работников обнаружено 4 CNA различных типов: 3 мозаичные амплификации, 1 мозаичная делеция. Заключение. Обнаруженные 4 CNA, кандидата на происхождение de novo, не индуцированы хроническим низкоинтенсивным облучением, так как не показали ассоциацию с ним. В данном исследовании, предположение о связи возникших de novo CNA с радиочувствительностью индивидов не подтвердилось. Необходимы дальнейшие исследования механизмов сохранения хромосомных аберраций с целью обнаружения маркёров индивидуальной радиочувствительности. Introduction. The search for biological markers of individual radiosensitivity remains an extremely urgent problem of modern medicine. Aim: to evaluate of the copy number aberrations in the blood lymphocytes of workers exposed to occupational radiation exposure. Methods. The object of the study was the blood of 20 relatively healthy workers of the Siberian Chemical Combine, exposed to external radiation. A standard cytogenetic analysis was performed for all the examined individuals. The blood DNA was examined using a «CytoScan HD Array» microarray («Affymetrix», USA). To process the results of microchipping, a program was used «Chromosome Analysis Suite 4.3» («Affymetrix», США). Results. For4 workers found out 4 CNA: 3 mosaic amplifications, 1 mosaic deletion. Conclusion. The detected 4 candidates for the origin of de novo CNA were not induced by chronic low-intensity radiation, as they did not show an association with radiation. In this study, the assumption about the connection of de novo CNA with the radiosensitivity of individuals was not confirmed. Further studies of the mechanisms of XA preservation are needed in order to detect markers of individual radiosensitivity.
Aim To study the association between concentrations of endothelial dysfunction (ED) markers and arterial hypertension (AH) in people who were exposed to long-term action of "low-dose" ionizing radiation.Material and methods The study subjects were men of middle age (45-55 years) who were workers of the Siberian Integrated Chemical Plant with the length of service on the shop floor of at least 5 years. The subjects were divided into the main group (n=96) consisting of workers with grade 1-2 AH and the control group (n=48) consisting of arbitrarily healthy workers. Both groups contained workers who had been exposed to long-term occupational low-intensity irradiation (γ-radiation) and those not exposed to this irradiation. The study evaluated risk factors for cardiovascular diseases, presence of concomitant diseases, blood biochemistry (concentrations of glucose, high-sensitivity C-reactive protein (hsCRP), total cholesterol, low-density lipoproteins, high-density lipoproteins, triglycerides, creatinine, and ED markers, including endothelin, angiotensin II, von Willebrand factor, C-type natriuretic peptide, tissue plasminogen activator, tumor necrosis factor α (TNF-α), and homocysteine, major clinical data, total dose of external irradiation, and the content of 239Pu in the body.Results AH was associated primarily with excessive body weight and severity of atherogenic dyslipidemia and homocysteinemia. Higher plasma concentrations of TNF-α and a tendency to increasing hsCRP in the AH group, as distinct from the control group of arbitrarily healthy men, indicated a proinflammatory shift. The ED markers were related with clinical data of AH patients and associated with the lipid profile and increased blood concentrations of inflammatory mediators. The radiation exposure did not change the ED marker array in AH patients, which did not allow recommendation of the studied plasma indexes for detection of vascular endothelial injury in workers with AH of the Siberian Integrated Chemical Plant.Conclusion The study results evidenced the absence of adverse effects of long-term occupational exposure to low-intensity radiation on the vascular endothelium as evaluated by ED markers. In men aged 45-55 years, AH was associated primarily with excessive body weight, homocysteinemia, and atherogenic dyslipidemia.
Purpose. The aim of this study was to ascertain the characteristics of major salivary glands endocrine effect onspermatogenesis.Materials and methods. Mature white outbred male rats (2 months, 153 ± 18 g) consisted of the following groups (each containing 30 rats): intact, control, and group of rats subjected to multiple amputation of incisors. To achieve hypertrophy of major salivary glands multiple amputation of incisors was performed: incisors were cut to a level of 1-2 mm above the gingival margin under ether anesthesia once every 3 days within 2 weeks. Animals of the control group were anesthetized with ether at the same time. Rats were sacrificed by CO2 asphyxia after 2, 3, 4, 6, 8 and 10 weeks after the first amputation of incisors. Fragments of the rat testes were examined on a JEM-1400 “JEOL” (Japan) transmission electron microscope. On electron microscopy images the specific vacuolization of the cytoplasm of Sertoli cells, spermatogonia, spermatocytes and spermatids (standard units) was analyzed by the point counting method. In spermatogenic cells the proportion of mitochondria (%) with morphological signs of swelling was assessed.Results. Transient ultrastructural changes of Sertoli and spermatogenic cells develop in the rats convoluted seminiferous tubules as a result of multiple amputation of the incisors, such as phagosomes and pronounced vacuolization in the Sertoli cells cytoplasm, cytoplasm vacuolization and mitochondrial swelling in spermatogenic cells. Sporadic spermatogenic cells with signs of nuclear (chromatin fragmentation, its condensation on the periphery of the nucleus) and cytoplasm (destruction of membrane organelles) destruction appeared as a result of multiple incisors’ amputation. Ultrastructural changes of Sertoli and spermatogenic cells are most pronounced at 2-3 weeks, decrease at 4 week and are completely leveled by the 6th week of the experiment.Conclusion. Hypertrophy of major salivary glands, caused by multiple amputations of incisors, has similar to sialoadenectomy effect on the spermatogenic epithelium. Multiple incisors’ amputation cause transient depression of granular convoluted cells function. Probably submandibular gland granular convoluted tubules cells endocrine factors make the greatest contribution to the regulation of spermatogenesis in rats.
Sialadenectomy in young rats modifies the development of the spermatogenic and steroidogenic functions of the testes. Sialadenectomy causes ultrastructural changes in spermatogenic cells, sustentocytes, and Leydig cells that disappear by week 8 of the experiment due to realization of compensatory and adaptive mechanisms. The effects of endocrine factors of the greater salivary glands on the spermatogenic cells are realized directly and indirectly via interstitial endocrinocytes and sustentocytes.
The structure of the testicles was studied in adult rats in 120 days after a single intravenous injection of chitosan-modified (magnetic nanospheres) and lipid-modified (magnetoliposomes) nanosized magnetite particles. Perls histochemical reaction detected in the testicular interstitial connective tissue the cells which absorbed and accumulated magnetite nanoparticles. The dynamics of spermatogenesis index and the count of Perls+ cells in the rat testicles were traced throughout the experiment. The studied modified nanosized magnetite particles did not penetrate through the blood-testicle barrier in rats.
OBJECTIVE:To perform immunohistochemical typing of cells as a component of bioprosthetic (BP) heart valves explanted during reoperations for prosthetic valve endocarditis.MATERIAL AND METHODS:The authors investigated 8 models of KemCor and PeriCor artificial heart valves produced by NeoCor Company (Kemerovo, Russia), which were explanted from the mitral position due to infection of xenogeneic implanted material. The following markers: CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD34 and VEGFR2 (endotheliocytes), CD68 (monocytes/macrophages), vimentin (fibroblasts), and α-smooth muscle actin (smooth muscle cells), were used for immunohistochemical typing of cells as a component of the analyzed samples.RESULTS:Recipient cells were found to colonize devitalized BP tissues in infective endocarditis. This process simultaneously involved several types of cells performing their functions in infectious lesion and its initiation of BP remodeling. Macrophages contributed to the sanitation of the foci of infection and destruction of BP xenotissue; endotheliocytes ensured neovascularization and resistance of the implanted valve surface to infection; fibroblasts played a role in the neoplastic transformation of collagen, and smooth muscle cells were likely to take on the role in forming the elastic framework of a leaflet and in ensuring the mechanical properties of the bioprosthesis.CONCLUSION:In the time course of development of prosthetic endocarditis, the recipient cells populate xenovalve leaflets that are a modified extracellular matrix obtained from the porcine aortic valve complex. This process is a consequence of the destruction of the BP surface and deep components. The observed cellular reactions are likely to be adaptive and to be aimed at eliminating microorganisms and regenerating structural damages.
The major salivary glands of rats release into the saliva and blood a wide spectrum of bioactive substances, essential for many organs, including the testes. Sialoadenectomy leads to the development of degenerative changes in the cells of the twisted testicular tubules. However, the effects of bioactive factors released by the major salivary glands on the morphology and function of Leydig cells remain little studied. Sialoadenectomy in adult rats led (in 1-4 weeks) to a decrease in the nuclear and cytoplasmatic areas of Leydig cells, violation of the plasmalemma integrity, dilatation of perinuclear space and agranular endoplasmatic reticulum vesicles, and to destruction of the mitochondria. Ultrastructural changes caused by sialoadenectomy completely resolved by week 6 of the experiment at the expense of compensatory activation of the synthesis of the major salivary gland factors by other sources in the organism of rats.
The ultrastructure of nephrocytes of the proximal and distal convoluted tubules, podocytes, mesangial cells, and macrophages of the interstitial connective tissue was studied after single intravenous administration of magnetite nanoparticles modified with chitosan (magnetic nanospheres) or lipids (magnetic liposomes). Transmission electron microscopy showed ultrastructural features of absorption of magnetite nanoparticles. The shape, size, and number of vesicles containing nanoparticles in nephrocytes of convoluted tubules and macrophages after administration of the suspensions of magnetic nanospheres and magnetic liposomes were described.
We studied the effects of single administration of a suspension of magnetomicelles based on carbon-coated iron nanoparticles on the structure of rat lungs within 40 days. Histological analysis revealed a complex of hemodynamic alterations in the lungs. Described changes persisted in the lung stroma from day 1 until day 40, but their intensity decreased by the end of the experiment. Using immunohistochemical Perls reaction we identified cells morphologically corresponding to alveolar and interstitial lung macrophages. The number of Perls+ cells decreased by day 40 of the experiment. Ultrastructural analysis showed endocytosis of modified iron nanoparticles and their accumulation in intracellular digestionorganelles (endoand lysosomes) of mononuclear phagocyte system cells. Accumulation of magnetomicelles in the lungs was not associated with damage to pneumocytes, macrophages, and blood-air barrier.
The review analyses the data on the structure ofsubmandibular (SMG), parotid and sublingualsalivary glands in rodents and on biologically activesubstances produced by them. The evidence ispresented on the mutual influence of rodent majorsalivary glands (MSG) and the testes. Specialattention is paid to gender differences of MSG inrodents, which are more fully apparent in matureindividuals and are most pronounced in SMG.Sexual dimorphism is morphologically manifestedin a larger size of secretory portions, the relativeareas of granular and interlobular excretory ductsof SMG and greater number of granular cells ofstriated ducts of the sublingual glands in males.Biochemically sexual dimorphism is characterizedby different amounts of biologically activesubstances secreted by the epithelial cells ofsecretory portions and granular cells of the ducts.Epidermal growth factor, nerve growth factor,kallikrein and other substances are synthesized ingranular cells of the excretory ducts of all MSG inrodents, however, to the greatest extent — bySMG. The higher content of physiologically activesubstances in MSG saliva in males plays animportant biological role.
Data on volume of the intracellular compartment where the internalized toxin is located and toxin concentration in this compartment have been obtained. Suggestions have been made about a role of toxin molecule aggregates in the translocation of A-chain into cytosol, which leads to cell death.
Effects of multiple intravenous magnetite nanosuspension injections on the structure of rat liver, lungs, kidney, heart and spleen have been studied. Histology of the organs listed have found haemodynamic distortions and necrotic lesions in the parenchyma of these organs. With the help of Pearls histochemical method significant piling of nanoparticles were found in the cells of the mononuclear phagocytes in liver, lungs and spleen of the rats. Only singular Pearls-positive cells were found in kidneys and hearts of the rats.
The aim of this investigation was to study the morphological changes of liver, lung, kidneys and spleen as well as of the cells of mononuclear pahagocyte system in 60 rats 1-40 days after a single intravenous injection of a suspension of magnetite nanoparticles. Moderate hemodynamic disturbances and focal necrotic changes were detected in the hepatic and renal parenchyma. In the lungs and spleen, only hemodynamic disturbances were found. The degree of morphological changes in rat liver, lungs, kidneys and spleen was decreased by day 10. Using Perls histochemical method, the accumulation of nanoparticles was detected in the cells of mononuclear phagocyte system of the organs studied.
Rat liver was examined by transmission electron microscopy after a single intravenous injection of nanosized magnetite suspension (0.1 g (Fe 3 O 4 )/kg body weight). Magnetite particles were found in Kupffer’s cells and hepatocytes. Accumulation of the particles by these two cell types was different. Morphometry of magnetite-containing granules in Kupffer’s cells and nanoparticle agglomerations in hepatocytes was carried out. The ultrastructure of Kupffer’s cell granules was described and the mechanism of penetration of nanosized magnetite particles into the cells was suggested. Nanosized magnetite particles were not completely eliminated over 40 days after a single injection.