Evaluation of cytotoxic action of antihistamines – desloratadine and loratadine – using bulls spermatozoa as a test object

Antihistamines with active ingredients of loratadine and desloratadine are produced by Ukrainian pharmaceutical industry. According to the law, ther are assessed for their potential danger to human health and the environment, including alternative test objects. Evaluation has been carried out with regard to cytotoxic effect of pharmacological substances (loratadine and desloratadine) using the bull sperm suspension as test objects, standardized and highly sensitive to toxic substances. Sperm was divided into the control sample (dissolved by phosphate-buffered saline) and the investigated sample. Loratadine was added to phosphate-buffered saline in doses of 1/500 LD50 (12.3 mg), 1/100 LD50 (61.5 mg) and LD50 (6150 mg). Desloratadine doses were 1/500 LD50 (1.25 mg), 1/100 LD50 (6.25 mg) and LD50 (625 mg). Survival of spermatozoa was defined until termination of rectilinear forward movement in sperm intacted at +2…+5 °C. Respiratory activity (ex tempore) was defined in 1.0 ml thermostated cell (temperature of 38.5 °C) by polarography with the automatic registration of process flow by potentiometer; restorative activity was defined potentiometrically, using the open microelectrodes that were inserted in thermostated polarographic cell. Survival of spermatozoa in the sperm under the impact of loratadine in doses of 1/500 LD50 and 1/100 LD50 is respectively 136.0 ± 26.2 hours and 144.0 ± 19.6 hours. Adding LD50 dose of loratadine reduced survival to 112.0 ± 26.2 hours, which is lower than the control (160.0 ± 26.1 hours), respectively, by 10.0–15.0 and 30.0%. Loratadine reduces the respiratory activity of sperm: in the dose of 1/500 LD50 by 20.5%, in the dose of 1/100 LD50 – by 43.6%, and that of 100 LD50 – by 61.5% compared to the control. Restorative sperm activity under the impact of the loratadine reduced by 84.0% (dose of 1/500 LD50), 98.0% (dose of 1/100 LD50), 80.0% (dose LD50) compared to controls. The survival of spermatozoa in the sperm under desloratadine action in the dose of 1/500 LD50 is 144.0 ± 19.6 hours (10.0% reduction compared with the control – 152.0 ± 23.6 hours), in the dose of 1/100 LD50 – 136.0 ± 26.1 hours (15.0% reduction), in the dose of LD50 – 72.0 ± 19.6 hours (30.0% reduction). The intensity of oxygen consumption by sperm reduced by 16.2% when adding desloratadine in the dose of 1/500 LD50, by 38.8% in the dose of 1/100 LD50 and by 80.7% – in the dose of LD50, compared with the control. Inhibition of respiratory activity is accompanied by decreasing in the transport of protons and electrons from spermatozoa into the extracellular medium, that manifests decreasing of reconstructive activity when the dose of desloratadine is 1/500 LD50 (by 12.0%), 1/100 LD50 (by 40.0%) and LD50 (by 60,0%) compared with the control

Promising directions for vaccine development to prevent shigellosis

Shigellosis (bacterial dysentery) is an acute infectious disease caused by Shigella spp., members of the Enterobacteriaceae family. The disease has the highest mortality rate amongst bacterial enteric infections. A considerable proportion of Shigella infections occur in children under the age of five. In 2017, WHO included Shigella spp. strains into the list of “priority pathogens” that are resistant to most antibiotics and pose a threat to global public health. This provided a stimulus for the development of new antibiotics to treat shigellosis. Apart from the creation of new antimicrobial therapies for Shigella infections, an important role in fighting against shigellosis belongs to the preventative measures set out in WHO’s Immunisation Agenda 2030. These include sanitation, hygiene, consumption of clean water, and vaccination. The development of Shigella vaccines has been a priority of the WHO programme for more than 20 years. The aim of the study was to analyse promising approaches to Shigella vaccine development. According to the analysis of literature, only one vaccine against shigellosis has been approved so far—Shigellvac, the Russian polysaccharide dysentery vaccine against Shigella sonnei. This study covers a number of vaccine candidates (whole-cell, polysaccharide, polysaccharide conjugate, protein antigen-based vaccines, etc.) that are at different stages of clinical trials. The importance of researching combination (multivalent) vaccines against Shigellа spp. and other enteric pathogens is noted. However, the authors consider subunit vaccines based on Ipa proteins, providing broad cross-protection against Shigellа spp., and conjugate polyvalent vaccines for children under 5 the most promising for further development

Destabilization signs in behavioral and somatovegetative parameters of rats selected for catatonia

The article presents data on destabilization signs in response to selection for catatonia at an organismal level. Experiments were conducted with the unique GC (genetic catatonia) rat strain selected for long passive-defensive freezing. The goal of this study was to detect destabilization signs in the behavioral and somatovegetative parameters of GC rats emerging in response to selection. The destabilization manifested itself as changes in rat attitudes towards humans, as became apparent from the glove test. Altered hormone levels in GC rats were detected: corticosterone concentrations were reduced in feces and increased during handling. The metabolic system showed a decrease in energy stored accompanying the fast (glucose level) and slow (triglyceride level) responses. However, the strains did not differ in the concentration of insulin, which affects glucose transport through the cell membrane. Nor did we find differences between Wistar and GC rats in cholesterol level. This lipid is important for both energy and constructive metabolism. A side effect of selection for catatonia was the worse pelage status in GC rats. The overall physical condition of catatonic rats involved reduced body weight in both neonates and adults. All these changes point to the modification of behavioral and somatovegetative patterns and intensification of the passive-defensive component of selection in GC rats

Expression of catecholaminergic genes in the midbrain and prepulse inhibition in rats with a genetic catatonia

The GC rat strain (from the words "genetic" and "catatonia") was created by selection for predisposition to passive-defensive reaction of catatonic freezing in response to stressing stimuli. Rats of the GC strain have previously demonstrated a number of biochemical and behavioral properties similar to those of patients with schizophrenia and depression. Prepulse inhibition (PPI) is widely explored as an important indicator, a decrease of which may be indicative of psychopathology, including schizophrenia. It has been established that the brain noradrenergic system influences the manifestation of PPI, in particular through the activation of central alpha-adrenoreceptors. Also known is the association between PPI and expression of catechol-O-methyltransferase. This study focuses on the reaction of prepulse inhibition in rats of the inbred GC strain, being considered as a hypothetical model of schizophrenia, as well as on the relation of prepulse inhibition to mRNA expression of tyrosine hydroxylase, catechol-O-methyltransferase, alpha1A- and alpha2Aadrenergic receptors in the midbrain of GC rats. For the first time, a decrease of PPI in GC rats compared with WAG rats was shown, both with a prepulse power of 75 dB and at 85 dB, which may indicate a violation of filtration of sensorimotor information into the central nervous system in GC rats. Real-time PCR showed a decrease in mRNA level of Adra1A in intact rats with genetic catatonia when compared to control WAG rats. There was observed no correlation between the expression of mRNA of the Adra1A, Adra2A, Th, and Comt genes in the midbrain and the PPI reaction in GC rats. The reduction of prepulse inhibition in GC rats indicates functional similarity of this genetic model of schizophrenic psychopathology with a prototype. © AUTHORS, 2017.Russian Foundation for Basic Research, RFBR: 16­04­013250324­2016­0002This study was supported by the Russian Foundation for Basic Research, project 16­04­01325, and State Budgeted Project 0324­2016­0002

Перспективные направления разработки вакцинных препаратов для профилактики шигеллеза

Shigellosis (bacterial dysentery) is an acute infectious disease caused by Shigella spp., members of the Enterobacteriaceae family. The disease has the highest mortality rate amongst bacterial enteric infections. A considerable proportion of Shigella infections occur in children under the age of five. In 2017, WHO included Shigella spp. strains into the list of “priority pathogens” that are resistant to most antibiotics and pose a threat to global public health. This provided a stimulus for the development of new antibiotics to treat shigellosis. Apart from the creation of new antimicrobial therapies for Shigella infections, an important role in fighting against shigellosis belongs to the preventative measures set out in WHO’s Immunisation Agenda 2030. These include sanitation, hygiene, consumption of clean water, and vaccination. The development of Shigella vaccines has been a priority of the WHO programme for more than 20 years. The aim of the study was to analyse promising approaches to Shigella vaccine development. According to the analysis of literature, only one vaccine against shigellosis has been approved so far—Shigellvac, the Russian polysaccharide dysentery vaccine against Shigella sonnei. This study covers a number of vaccine candidates (whole-cell, polysaccharide, polysaccharide conjugate, protein antigen-based vaccines, etc.) that are at different stages of clinical trials. The importance of researching combination (multivalent) vaccines against Shigellа spp. and other enteric pathogens is noted. However, the authors consider subunit vaccines based on Ipa proteins, providing broad cross-protection against Shigellа spp., and conjugate polyvalent vaccines for children under 5 the most promising for further development.Шигеллез (бактериальная дизентерия) — острое инфекционное заболевание, вызываемое возбудителями Shigellа spp. семейства Enterobacteriaceae, характеризуется наибольшим показателем смертности населения от бактериальных кишечных инфекций. Значительная доля случаев заболевания приходится на детей в возрасте до 5 лет. В 2017 г. штаммы Shigellа spp. были включены в опубликованный ВОЗ список устойчивых к действию большинства антибиотиков «приоритетных патогенов», представляющих угрозу мировому здравоохранению, что послужило стимулом к разработке новых противомикробных препаратов для терапии шигеллезов. Наряду с созданием антимикробных средств против Shigellа spp. важную роль в борьбе с шигеллезами играет комплекс превентивных мер, изложенный в программе иммунизации ВОЗ 2030, в который, помимо санитарии, гигиены и потребления чистой воды, входит вакцинация. Разработка вакцины против шигеллеза остается одним из приоритетных направлений программы ВОЗ уже более 20 лет. Цель работы — анализ перспективных направлений разработки вакцинных препаратов против шигеллеза. Проведенный анализ данных литературы показал, что в настоящее время на мировом рынке зарегистрирована только одна вакцина против шигеллеза — российская вакцина Шигеллвак, полисахаридная дизентерийная вакцина против шигелл Зонне. Рассмотрен ряд вакцинных препаратов (цельноклеточные, полисахаридные конъюгированные и неконъюгированные, препараты на основе белковых антигенов и др.), находящихся на различных этапах клинических испытаний. Отмечено, что важным направлением является создание комбинированных мультивалентных препаратов против инфекций, вызываемых Shigellа spp. и другими кишечными патогенами. Сделан вывод о том, что наиболее перспективными являются разработки субъединичных вакцин на основе Ipa-белков, обеспечивающих перекрестную защиту против Shigellа spp., а также конъюгированных поливалентных вакцин, предназначенных для детей в возрасте до 5 лет

Evolution of climate, glaciation and subglacial environments of Antarctica from the deep ice core and Lake Vostok water sample studies (Key results of implementation of the Russian Science Foundation project, 2014–2016)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores

Брюшнотифозные вакцины. История создания и современные вакцинные препараты

Typhoid fever is an acute infectious disease caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi), which is still extremely common in endemic low- and middle-income countries of Asia and Africa. Industrialised countries may also be affected by typhoid fever outbreaks due to booming international tourism, and natural disasters. Given S. Typhi progressive resistance to antibiotics, high epidemiological burden, and lack of adequate sanitation and hygiene in a number of regions, the introduction of new treatment protocols and the improvement of preventive vaccination are critical tasks in global healthcare. The aim of the study was to highlight the main historical aspects of the typhoid vaccine development, to summarise data on the licensed vaccines and promising approaches to the development of new typhoid vaccines. The paper describes the current epidemiological situation of typhoid fever globally and in the Russian Federation. It dwells upon the global experience in typhoid vaccine development from the production of an inactivated vaccine to the development of conjugated vaccines. The paper summarises data on Russian and foreign-made typhoid fever vaccines currently available in the global pharmaceutical market. It outlines the main trends in the development of vaccines against the disease caused by S. Typhi. The paper demonstrates the need for improving the efficacy of existing vaccines and development of new typhoid combination vaccines.Брюшной тиф — острое инфекционное заболевание, вызываемое возбудителем Salmonella enterica subsp. enterica серотип Typhi (S. Typhi), по-прежнему является одной из основных причин заболеваемости населения в эндемичных экономически средне- и слаборазвитых странах Азии и Африки. Индустриальные страны могут быть подвержены вспышкам брюшного тифа ввиду стремительно развивающегося международного туризма, а также стихийных бедствий. В условиях прогрессирующей резистентности S. Typhi к антимикробным препаратам, высокой эпидемиологической нагрузки и невозможности обеспечения удовлетворительных санитарно-гигиенических условий в ряде регионов, наряду с внедрением новых протоколов лечения заболевания, актуальной задачей мирового здравоохранения является развитие вакцинопрофилактики брюшного тифа. Цель работы — освещение основных аспектов истории создания брюшнотифозных вакцин, систематизация данных о лицензированных вакцинных препаратах и перспективных направлениях разработки новых вакцин. В статье описана эпидемиологическая картина брюшного тифа в мире и в Российской Федерации. Изложен мировой опыт создания вакцинных препаратов от момента получения убитой брюшнотифозной вакцины до этапа производства конъюгированных вакцин. Приведена информация об отечественных и зарубежных вакцинах, представленных на мировом фармацевтическом рынке. Обозначены основные тенденции в сфере разработки вакцинных препаратов против заболевания, вызываемого S. Typhi. Сделан вывод о необходимости повышения эффективности ранее разработанных вакцин, а также создания новых, комбинированных вакцинных препаратов против брюшного тифа

Formation during glycine-nitrate combustion and magnetic properties of YFe1–xNixO3 nanoparticles

The synthesis of FeO3 and YFe1–xNixO3 (x = 0.1; 0.15; 0.2; 0.3; 0.5) nanocrystals was performed under the conditions of a self-propagating wave of glycine-nitrate combustion and their characterization and determination of the effect of Ni2+ doping of yttrium ferrite on the magnetic properties of nanopowders. The technology for the synthesis of yttrium orthoferrite nanoparticles (with and without doping with Ni2+ ions) by the glycine-nitrate combustion method at a ratio of G/N = 1 and 1.5 without adding a gelling agent to the reaction mixture and using ethylene glycol/glycerol is described. For the characterization of nanopowders based on YFeO3, the following were determined: phase composition and crystal structure (X-ray diffraction (XRD) method); size and structure of nanocrystal particles (transmission electron microscopy (TEM)); elemental composition of the samples (local X-ray spectral microanalysis (LXSMA)); magnetic characteristics (field dependences of specific magnetization). Thermal annealing of the synthesized samples at 800°C for 60 min led to the formation of the о-YFeO3 main phase. Undoped samples of yttrium orthoferrite were characterized by a particle diameter in the range of 5-185 nm, depending on the gelling agent used. YFe1-xNixO3 particles had a predominantly round shape with a size of 24 to 31 nm; the non-monotonic dependence of the average particle diameter on the dopant content was revealed: as the amount of dopant added increased, the average crystallite size tended to decrease. Nanopowders of undoped yttrium orthoferrite exhibit antiferromagnetic behaviour of magnetic susceptibility with temperature. The change in the magnetic properties of the nickel-doped YFeO3 nanocrystalline powders was due to the incorporation of Ni2+ into the Fe3+position, which led to the formation of a material with more pronounced soft magnetic properties at a substitution degree of 0.1. Samples with high degrees of substitution (x = 0.15 and 0.3) were also characterized by paramagnetic behaviour at temperatures above 100 K

Results of Epizootiological Monitoring of Natural Foci for Bacterial Vector-Borne Infections in Caucasian Mineral Waters Region of the Stavropol Territory in 2018–2020

The aim of the study was to assess the epizootiological situation on bacterial vector-borne infections in Caucasian Mineral Waters area of the Stavropol Territory over the period of 2018–2020.Materials and methods. 3494 specimens of ticks (473 pools), 257 specimens of small mammals, 9 regurgitates of birds of prey and mammals, 7 excreta samples of small mammals, and 2 water samples were tested. Laboratory research of the field material was carried out using molecular-genetic, serological, biological methods. Statistical analysis of laboratory results was conducted using Microsoft Excel 2010. The data were mapped using QGIS 2.18 software.Results and discussion. The study revealed that the 44.8 % of collected ticks were positive for tick-borne borreliosis, 21.5 % – for tick-borne rickettsiosis, 10.3% – for human granulocytic anaplasmosis, 2.7 % – for Q fever, 0.84 % – for tularemia. There has been an increase in the percentage of positives for tick-borne borreliosis agent samples (more than three times) and a decrease in this indicator for human granulocytic anaplasmosis (1.5 times) as compared with 2010–2012. Investigation of tick infection with the agents of Q fever and tick-borne rickettsioses has not been previously conducted in the region. During the period under review, 19 pools of ticks had mixed infection, which indicates that there are combined foci of bacterial natural-focal infections with vector-borne transmission in the recreation zone of the Stavropol Territory. This necessitates preventive measures and systematical epizootiological surveys in the Caucasian Mineral Waters region

Эволюция климата, оледенения и подледниковой среды Антарктиды по данным исследований ледяных кернов и проб воды озера Восток (Основные итоги работ по проекту РНФ, 2014–2016 гг.)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores.Изложены основные результаты работ, выполненных Лабораторией изменений климата и окружающей среды ААНИИ по проекту Российского научного фонда в 2014–2016 гг. Показано, что поддержка фонда способствовала получению научных результатов международного уровня в двух приоритетных направлениях антарктических исследований  – реконструкции палеоклимата по ледяным кернам и изучении подледниковой среды Антарктиды