Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Polyphenolic compounds (flavonoids) of lyophilized aqueous extracts from Caragana jubata (Pall.) Poir. raw material from 2010 and 2015 were studied using modern HPLC-DAD-MS. Primarily mono- and diglycosides of O-hydroxylated (myricetin, quercetin, kaempferol) and O-methylated flavonols (isorhamnetin, laricitrin, syringetin) were identified. Long-term storage of dried raw material under standard conditions had little effect on the quantitative content of polyphenolic compounds. Acute toxicity studies of C. jubata extract showed no toxicity.

© 2013-2018 Federal Scientific Center for Medical and Preventive Health Risk Management Technologies. Yessotoxin (YTX) is a polyether. There are more than 90 known derivatives of yessotoxin. YTX was excluded from diarrhea toxins group as it, unlike okadaic acid, doesn't cause diarrhea. YTX chemical structure is similar to that of brevetoxins and ciguatoxins that influence functioning of calcium-sodium pump and trans-membrane ion channels. So, YTX can exert influence on functioning of all the organs and systems in a body. YTX is known to promote apoptosis in the cerebral tissues. Average lethal dose LD50 for YTX and its analogues varied from 100 μg/kg to 500-750 μg/kg; the figures were obtained in various experiments performed on mice. Safe YTX level for acute impact (acute reference dose) amounts to 25 μM/kg of body weight. Nowadays toxicity parameters for YTX and some of its analogues are determined; its basic action mechanisms and a role it plays in promoting apoptosis are well-known. In spite of more and more data on biological effects produced by YTX on a warm-blooded organism, experts are still unable to describe its action mechanisms precisely. Our research goal was to examine YTX toxicity in experiments in vivo in doses that were lower than the detected acute reference dose. The experiment was performed on 72 male Wistar rats with initial body weight being equal to 100±10 g. Animals were given dry balanced feedstuffproduced by "Laboratortakorm" LLC (Russia) and had free access to it. We used YTX preparation produced by "National Research Council Canada" (Canada) in our experiment; the preparation was a methanol solution (YTX content was equal to 4.3 μmol). We determined mass of internal organs, biochemical and hematological blood parameters, apoptosis of brain cells, malonic dialdehyde level in the brain and reduced glutathione in the liver. We showed that YTX doses (2μM/kg, 8μM/kg and 12μM/kg) lower than ARfD=2μM/kg can exert toxic impacts on a warm-blooded organism. The obtain data prove it is necessary to additionally assess risks of an increase in maximum permissible YTX contents in shellfish from 1 mg/kg to 3.75 mg/kg.

© 2018 Russian Transplant Society. All rights reserved. Heart transplantation is the «gold standard» of treatment severe heart failure. Patient survival after heart transplantation has improved dramatically since the availability of calcineurin inhibitor (CNIs). However, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction and reduces long-term patient survival. Use mTOR inhibitor in immunosuppressive therapy may improve renal function when everolimus is administered associated with a progressive reduction of CNIs. The purpose of our report is to demonstrate the successful case of conversion of the recipient after heart transplantation to everolimus and to evaluate the effectiveness of this drug during the observation year after heart transplantation.

© 2018 GEOTAR-Media Publishing Group. Yessotoxin and its derivatives (about 90) are isolated from algae belonging to the species Protoceratium reticulatum, Gonyaulax cf. Spinifera, Lingulodinium polyedrum and from invertebrate organisms that feed on these algae. Previously yessotoxin have been associated with the group of diarrheal toxins. Later studies of the possible impact of yessotoxin on the activity of alkaline phosphatase allowed to exclude them from this group. Yessotoxin causes a violation of calcium entry in the cells, which, in turn, effects the calcium-calmodulin system and thus influences into homeostasis of the organism as a whole. It was shown that yessotoxin induces a biphasic change in the concentration of adenosine monophosphate, an initial increase with a subsequent relative decrease, within some minutes after adding the toxin to the lymphocytes cell culture. Yessotoxin has effects on immune system; which is manifested in an increase of cytokines level, by inducing the expression of the genes encoding them. Yessotoxin have impact into processes of cell adhesion via E-cadherin and, thus, could be an important factor in the development of Alzheimer's disease. It has been established that yessotoxin caused the development of apoptosis. In those cases all three mechanisms of cell death took place - apoptosis, paraptosis and autophagy. Yessotoxin's acute toxicity doses according to different data are from 100 to 500-750 μg per 1kg of body weight. Yessotoxin's acute reference dose (ARfD) - 25 μg/kg of body weight per day. The results of the analysis of yessotoxin level in shellfish meat showed that none of the studied samples contained more than 3.75 mg yessotoxin equivalents/kg shellfish meat. This level has been adopted by the European Union as the maximum acceptable level of yessotoxin in shellfish meat (EU Regulation N 786/2013). Presented data on the mechanism of action, toxicity and prevalence of yessotoxins make it necessary to establish regulations of their content in seafood, placed on the markets of the Eurasian Economic Union.

© 2018 Vladimir A. Chistyakov, Alexander V. Usatov, Aleksander I. Klimenko, Maria A. Kolosova, Eugenia V. The abundance of potential genotoxins makes it necessary to improve microbial test systems that allow to identify these substances quickly. At the same time, the methodology of metabolic activation of promutagens in vitro is very important. Microsomal preparations of rodents, which are generally used for that, have significant disadvantages associated with the potential health risks of the inducers of the metabolism of microsomal cytochromes. For the metabolic activation of promutagens, we have developed a protocol of microsomal homogenate fraction (S-9) preparation. We propose to complement the set of methods for quality control of feeds for valuable and rare chicken breeds with the Ames test (Salmonella/microsome) using the activated chicken hepatic S-9 homogenate fraction.

© Izdatel'stvo Meditsina. All rights reserved.  Introduction. Single-walled carbon nanotubes (SWCNTs) can create risks to human health when they enter the body by oral route when used in packaging materials, as promising agrochemicals and pesticides. The aim of the study. Evaluation of the subacute oral toxicity of SWCNT in rats. Material and methods. In the 92-days of the experiment, the SWCNTs were administered to rats along with drinking water at doses of 0 (control); 0.01; 0.1; 1.0 and 10 mg/kg body weight (BW) in the groups 1-5, respectively. Hematological indices of blood, apoptosis of hepatocytes, levels of pro- and anti-inflammatory cytokines in blood plasma and their production by cells of the spleen ex vivo, the content of the main and transient components of the intestinal microbiocenosis in the cecum were studied. There were determined hematological blood counts, hepatocyte apoptosis, levels of pro- and anti-inflammatory cytokines in blood plasma and their production by spleen cells ex vivo, content in the cecum of the main and transient components of the intestinal microbiocenosis. Results. At the SWCNT dose of 0.01 mg/kg BW there was a decrease in the number of neutrophils and basophils, an increase in the number of lymphocytes, and a decrease in the number and volume of platelets. At a dose of 0.1 mg/ kg bw there was noted a decrease in the number of cells in the early stage of apoptosis and the total number of cells in apoptosis, as well as a significant decrease in the levels of cytokines IL-10, IL-2, IL-4, IL-13, chemokine MIP-3a, TGF-β isoform 1; at a dose of 1.0 mg/kg IL-12p70, and TGF-β isoforms 1 and 3. TGF- β 2 level was significantly elevated in group 5. The suppressive effect was noted for SWCNTs on the mold flora in intestinal contents at all doses of nanomaterial used, whereas the number of yeasts increased at 1 mg/kg BW. The immunization of rats with ovalbumin had a clear modulating effect on the immunotropic effects of SWCNTs administered at a dose of 0.1 mg/kg BW in a 28-days experiment. Discussion. The mechanisms of the observed changes development are likely to be associated with both systemic anti-inflammatory effects and with a decrease in the effect of SWCNT on the permeability of the intestinal barrier to protein antigens and microbial toxins. Conclusion. SWCNTs exhibit a number of effects in relation to the studied indices that do not demonstrate a monotonic dependence on the dose of nanomaterial, which, apparently, is related to the processes of aggregation of the SWCNT.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review summarizes the state-of-the-art in the problem of assessment of the safety of domperidone - a prokinetic and anti-emetic drug belonging to those most widely used in clinical practice. Special attention is devoted to the potential cardiotoxicity of domperidone, mechanisms of adverse effects development, and risk factors. For reducing the risk of development of dose-dependent side effects, new drugs have been created and used so as to maintain the active agent concentration in the blood plasma within the therapeutic range. Another method of increasing the efficacy and safety of domperidone treatment is based on the potentiation effect. An example is the use of domperidone in a fixed combination with omeprazole (Omez-DSR), in which a the prokinetic is present in a modified release form, which ensures uniform delivery of the acting agent into blood flow (without drug concentration +AJM-peaks+AJQ-related to increased risk of dose-dependent adverse drug reactions.

© 2018, Slovak Academy of Sciences. All rights reserved. The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands – ethylenediamine; 1,2-diaminocyclohexane; 2,2’:6’,2’’-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.

© 2018 Bentham Science Publishers. The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years, it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation.

© 2018, The Author(s). Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

© Pushkareva M.V., Shevyreva M.P., Goncharuk N.N., May I.V., Andrishunas A.M., 2018. The article contains information on hazardous chemical wastes, reasons that cause their occurrence and accumulation in the environment as well as issues related to accumulation of persistent organic pollutants (POPs) in the environmental objects. The authors outline specific features of POPs and their possible influence on the environment and a human body; they also dwell on priority activities accomplished in the RF in relation to POPs after Stockholm Convention on Persistent Organic Pollution was ratified. Provisions of international law in the sphere of providing chemical safety are being consolidated now and operating bodies of Basel, Rotterdam, and Stockholm Conventions interact with each other in order to fix concentrations for chemicals which are persistent organic pollutants and to determine their low contents in wastes. The European Union countries and Canada have submitted their proposals on concentrations of 21 various chemicals in wastes for consideration by all the concerned parties. Scientific validity of the proposed concentrations has been analyzed; the analysis results are given in the article. Given the hazards caused by chemicals wastes that contain POPs for people and the environment, the authors suppose that additional research should be performed on substantiation of POPs safe concentrations in wastes. Taking into account national security and common provisions of international laws related to solving global, national, and regional tasks, the authors note that it is necessary to update legislation on state regulation in the sphere of providing chemical safety; they also give grounds and outline conceptual approaches to creation of the Federal Law "On chemical safety". The article gives a basic idea of this law; its purpose; an object of its regulation; people or economic entities whose activities are subject to its force; a place this law, when passed, is going to have in the RF federal legislation and a system of international agreements that are ratified by the RF. It should be noted that when the Federal Law "On chemical safety" is adopted, it will allow to reduce negative effects produced by hazardous chemical wastes on population and the environment and will have both medical and social-economic outcomes.

© 2018 Ima-Press Publishing House. All Rights Reserved. In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". These guidelines were drawn up to improve the use of NSAIDs, our country's most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE. Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world's leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice. The guidelines are intended for physicians of all specialties.

The present study investigates the hepatoprotective effect of a novel zinc-containing drug acyzol in comparison with silymarin, a medicinal extract of milk thistle (Silybum marianum). The hepatoprotective effect was studied in 40 albino nonlinear male rats in a model of toxic liver injury induced by intragastric administration of carbon tetrachloride. Both drugs were diluted in water and administered intragastrically at doses 10 mg/kg (acyzol) and 100 mg/kg (silymarin) for 10 days twice daily, after development of clinical toxic hepatitis. Biochemical and functional indicators of the liver parenchyma demonstrated that both drugs reduced mortality, normalized the body and relative liver weight, reduced intensity of cytolytic, cholestatic, and mesenchymal inflammatory syndromes, and restored liver function. The study demonstrates that acyzol and silymarin have comparable hepatoprotective effect, thus, providing a rationale for the use of acyzol in complex therapy of toxic hepatitis and hepatosis.

Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.

Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.

The present study investigates the hepatoprotective effect of a novel zinc-containing drug acyzol in comparison with silymarin, a medicinal extract of milk thistle (Silybum marianum). The hepatoprotective effect was studied in 40 albino nonlinear male rats in a model of toxic liver injury induced by intragastric administration of carbon tetrachloride. Both drugs were diluted in water and administered intragastrically at doses 10 mg/kg (acyzol) and 100 mg/kg (silymarin) for 10 days twice daily, after development of clinical toxic hepatitis. Biochemical and functional indicators of the liver parenchyma demonstrated that both drugs reduced mortality, normalized the body and relative liver weight, reduced intensity of cytolytic, cholestatic, and mesenchymal inflammatory syndromes, and restored liver function. The study demonstrates that acyzol and silymarin have comparable hepatoprotective effect, thus, providing a rationale for the use of acyzol in complex therapy of toxic hepatitis and hepatosis.