Фармакологічна безпечність комбінованого засобу для корекції плацентарної дисфункції у вагітних

Topicality. Along with the pronounced pharmacological effectiveness, high requirements for the safety are applied to new medicines. To obtain the necessary information regarding the safety of a potential drug and predict the risk of further side effects, a preclinical study of possible toxic effects, primarily acute toxicity, is performed.Aim. To study the acute toxicity of a new pharmaceutical composition for the correction of placental dysfunction in pregnant women.Materials and methods. The study object was the pharmaceutical composition in the form of solid gelatinous capsules containing active pharmaceutical ingredients from basic therapeutic group of drugs used for fetoplacental dysfunction in pregnant women. The acute toxicity was determined according to the methodological guidelines “Preclinical studies of drugs” edited by A. Stefanov, in outbreed female rats weighing 200-250 g in compliance with the “European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes” (Strasburg, 1985).Results and discussion. The study of the pharmaceutical safety has been performed by the acute toxicity criterion under the condition of short-term influence of a new pharmaceutical composition combining the required pharmaceutical ingredients in well-balanced doses affecting different chains of pathogenesis of placental dysfunction. Under the condition of the acute experiment a new combined composition (intraperitoneal introduction in the dose of 5000 mg/kg of the body weight) does not cause changes in the rat’s organism. It has been determined that this pharmaceutical composition belongs to practically nontoxic substances – Toxicity Class V according to the generally accepted classification system.Conclusions. The data for the preclinical safety assessment of a new combined composition for the correction of placental dysfunction in pregnant women have been obtained.Актуальность. К новым лекарственным препаратам наряду с выраженной фармакологической эффективностью предъявляются высокие требования в отношении их безопасности. Для получения необходимой информации о безопасности потенциального средства и прогнозировании риска возникновения в дальнейшем побочного действия проводится доклиническое изучение возможных токсических эффектов, в первую очередь острой токсичности.Цель. Целью данной работы является исследование острой токсичности комбинированного препарата для коррекции плацентарной дисфункции у беременных.Материалы и методы. Объектом исследования была фармацевтическая композиция в форме твердых желатиновых капсул, которая содержит активные ингредиенты из групп базовой терапии фетоплацентарной дисфункции у беременных. Исследование ее острой токсичности проводилось согласно методическим рекомендациям «Доклинические исследования лекарственных средств» под редакцией Стефанова А. В. на беспородных крысах-самках массой тела 200-250 г с соблюдением основных положений Конвенции Совета Европы об охране позвоночных животных, используемых в экспериментах и в других научных целях.Результаты и их обсуждение. Проведено исследование фармацевтической безопасности согласно критерия острой токсичности в условиях кратковременного влияния нового комбинированного препарата, который содержит в одной лекарственной форме необходимые активные фармацевтические ингредиенты в сбалансированном количестве, влияющие на несколько звеньев патогенеза плацентарной дисфункции. В условиях острого эксперимента новый комбинированный препарат (внутрижелудочное введение в дозе 5000 мг/кг массы тела) не вызывает изменений в организме крыс. Установлено, что фармацевтическая композиция согласно общепринятой класификации токсичности относится к классу практически нетоксичных веществ – V классу токсичности.Выводы. Получены данные в отношении доклинической оценки безопасности нового комбинированного препарата для коррекции плацентарной дисфункции у беременных.Актуальність. До нових лікарських препаратів поряд із вираженою фармакологічною ефективністю висувають підвищені вимоги щодо їх безпечності. Для отримання необхідної інформації про безпечність потенційного засобу та прогнозування ризику виникнення негативної дії в подальшому проводять доклінічне вивчення можливих токсичних ефектів, насамперед гострої токсичності.Мета. Метою нашої роботи є дослідження гострої токсичності комбінованого засобу для корекції плацентарної дисфункції у вагітних. Матеріали та методи. Об’єкт дослідження становила фармацевтична композиція у формі твердих желатинових капсул, що містить активні інгредієнти з груп базової терапії фетоплацентарної дисфункції у вагітних. Визначення її гострої токсичності здійснювали згідно з методичними рекомендаціями «Доклінічні дослідження лікарських засобів» за редакцією Стефанова О. В. на безпородних щурах-самицях масою тіла 200-250 г із дотриманням основних положень Конвенції Ради Європи про охорону хребетних тварин, які використовуються в експериментах та в інших наукових цілях.Результати та їх обговорення. Проведено дослідження фармацевтичної безпечності за критерієм гострої токсичності в умовах короткочасного впливу нового комбінованого засобу, що об’єднує в одній лікарській формі необхідні активні фармацевтичні інгредієнти в збалансованій кількості, які можуть впливати на декілька ланок патогенезу плацентарної дисфункції. За умов гострого експерименту новий комбінований засіб (внутрішньошлункове введення в дозі 5000 мг/кг маси тіла) не викликає змін в організмі щурів. З’ясовано, що фармацевтична композиція за загальноприйнятою класифікацією токсичності належить до практично нетоксичних речовин – до V класу токсичності.Висновки. Отримано дані щодо доклінічної оцінки безпеки нового комбінованого засобу для корекції плацентарної дисфункції у вагітних

Motivation as an element of medical help quality management at socially important diseases

The present article deals with the problem of some aspects of motivation as an element of management activity of health protection managers of different levels in order to improve medical help quality including early diagnostics of socially important diseases. Researches have been held with the help of questionnaire method, 129 managers of different level of primary and specialized section have taken part in it. The role of individual motivating factors in managing working staff and achieving the tasks set have been studied. It has been found out that the overwhelming majority of managers share the opinion that it is necessary to use different incentives in work to improve its efficiency. Money reward, convenient working schedule and available social quarantees are considered to be the most important from this point of view. Corporative measures, as concerns the opinion of the interviewed, are the least important.В настоящей статье рассмотрены некоторые аспекты мотивации как элемента управленческой деятельности руководителей здравоохранения разного уровня в целях повышения качества медицинской помощи, в том числе при ранней диагностике социально значимых заболеваний. Исследование проводилось методом анкетирования, в котором приняли участие 129 руководителей различного уровня первичного и специализированного звена. Изучена роль отдельных мотивирующих факторов в управлении трудовым коллективом и достижении поставленных целей. Установлено, что подавляющее большинство руководителей считает необходимым применять различные стимулы в работе для повышения ее эффективности. Наиболее значимыми с этих позиций признаны материальное вознаграждение, удобный график работы и наличие социального пакета. Наименьшей мотивирующей силой, по мнению опрошенных, обладают корпоративные мероприятия

Homologs of the rolC gene of naturally transgenic toadflaxes Linaria vulgaris and Linaria creticola are expressed in vitro

Agrobacterium mediated transformation is the most common way for obtaining transgenic plants in laboratory conditions. At the same time, there are species inside the genera Nicotiana, Linaria and Ipomoea that contain homologs of agrobacterial T-DNA genes as a result of genetic transformation of their ancestral forms in natural conditions. Such plants are called naturally transgenic plants, and T-DNA in their genomes is called cellular (cT-DNA). It is proposed that in the evolution of these genera, the introduced sequences played an important role. This idea is confirmed by the data on the expression of some T-DNA genes in Nicotiana and Ipomoea. Until the last moment, the expression of cT-DNA genes in Linaria has not been documented. However, the analysis of the nucleotide sequence indicates the functionality of rolC gene in L. vulgaris Mill., L. acutiloba Fisch. ex Rchb., L. genistifolia (L.) Mill. In this research work, we have sequenced the rolC homolog in one more toadflax species (Linaria creticola Kuprian). The in silico analysis of this gene has shown that it can encode a full-length peptide. Using the real time RT-PCR method, we have demonstrated that the rolC homolog is expressed in vitro in shoots, roots and calli of L. vulgaris Mill., as well as in shoots of L. creticola Kuprian. The results obtained are an important argument in favor of the fact that cT-DNA is functional and that its fixation in genomes played a certain role in the evolutionary process. However, the level of expression of the gene studied is quite low. A similar trend was observed in other naturally transgenic species. This can explain the absence of explicit morphological differences of species containing cT-DNA from their non-transgenic relatives

Features of molecular mechanisms of insulin resistance pathogenesis in various tissues in obesity

Obesity is a chronic pathology, which experts of theWorld Health Organization regard as an epidemic, based on the high rates of annual growth in the proportion of the overweight population in almost all countries of the world. Obesity is the leading cause of tissue insulin resistance and type 2 diabetes mellitus. This disease is fraught with serious complications: the onset and aggravation of cardiovascular pathology, non-alcoholic fatty liver disease, the appearance of certain types of malignant neoplasms and dysfunctions of the reproductive system. Adipose tissue, skeletal muscle and liver play unique roles in maintaining metabolic homeostasis of the whole organism. These differences are due to the tissue-specificity of the intracellular signaling  pathways of insulin. This review presents the current literature data on the features of the molecular mechanisms responsible for disturbances in the conduction of regulatory insulin signals at the intracellular level in its main target organs in obesity. The data on the nature of disturbances  in interorgan metabolic flows caused by the growth of adipose tissue mass and their participation in the formation of insulin resistance in the liver and muscles are presented. The importance of  further in-depth study of the tissue features of the mechanisms of insulin resistance pathogenesis  for the development of new targeted pharmaceuticals that will serve to improve the complex drug correction of metabolic disorders in patients with type 2 diabetes is discussed

A Revised Design for Microarray Experiments to Account for Experimental Noise and Uncertainty of Probe Response

Background Although microarrays are analysis tools in biomedical research, they are known to yield noisy output that usually requires experimental confirmation. To tackle this problem, many studies have developed rules for optimizing probe design and devised complex statistical tools to analyze the output. However, less emphasis has been placed on systematically identifying the noise component as part of the experimental procedure. One source of noise is the variance in probe binding, which can be assessed by replicating array probes. The second source is poor probe performance, which can be assessed by calibrating the array based on a dilution series of target molecules. Using model experiments for copy number variation and gene expression measurements, we investigate here a revised design for microarray experiments that addresses both of these sources of variance. Results Two custom arrays were used to evaluate the revised design: one based on 25 mer probes from an Affymetrix design and the other based on 60 mer probes from an Agilent design. To assess experimental variance in probe binding, all probes were replicated ten times. To assess probe performance, the probes were calibrated using a dilution series of target molecules and the signal response was fitted to an adsorption model. We found that significant variance of the signal could be controlled by averaging across probes and removing probes that are nonresponsive or poorly responsive in the calibration experiment. Taking this into account, one can obtain a more reliable signal with the added option of obtaining absolute rather than relative measurements. Conclusion The assessment of technical variance within the experiments, combined with the calibration of probes allows to remove poorly responding probes and yields more reliable signals for the remaining ones. Once an array is properly calibrated, absolute quantification of signals becomes straight forward, alleviating the need for normalization and reference hybridizations

Ледовитость арктических морей и её связь с приземной температурой воздуха в Северном полушарии

The linear relationship between average monthly anomalies of the ice coverage in the Arctic seas and the surface air temperature over the land in the Northern hemisphere in March and September was analyzed for the purpose of finding regions with statistically significant correlations. Possible mechanisms of the revealed interrelations are discussed. Data on the surface temperature and the ice concentration from Met Office Hadley Centre were used in this study. A negative correlation of the sea ice with the temperature in the land regions adjacent to the seas, as well as a number of remote relations was revealed. Specifically, statistically significant relations were found between anomalies of the ice area in the Laptev Sea in September with the temperature anomalies in the Mediterranean region, as well as with the temperature anomalies in Central Asia. In most cases, such relationships may be explained by the influence of atmospheric circulation, including the North Atlantic Oscillation, the Arctic Oscillation, the Pacific Decadal Oscillation, and variability in the intensity of the atmospheric centers of action. Characteristics of seasonal variations of the sea ice coverage and climatic trends together with variability and autocorrelation of the coverage anomalies are considered. The largest reduction in the ice area is observed for the recent decades in the Barents Sea in winter while in the Kara, Laptev and East Siberian seas - in summer.Проанализирована линейная связь среднемесячных аномалий площади морского льда в арктических морях и приземной температуры воздуха над сушей Северного полушария в марте и сентябре. Установлена отрицательная корреляция с температурой в прилегающих к морям регионах суши, а также ряд удалённых связей, которые можно объяснить влиянием атмосферной циркуляции. Наибольшее сокращение площади морских льдов зимой в последние десятилетия наблюдаются в Баренцевом море, в летний – в Карском, Лаптевых и Восточно‑Сибирском морях

Комплексная преемственная реабилитация детей с последствиями перинатального поражения ЦНС

The aim of the study was to estimate the influence of rehabilitation measures on physical growth and cognitive functions in preschool children.We examined 224 children from 4 to 7 years old and in 197 (88%) of them revealed high level of health deviations. The most frequent were cervical insufficiency and bearing abnormality, of general and delicate motions, speech abnormalities. All children underwent cognitive functions checkup. In this connection we tilled the complex of rehabilitation measures for the children with physical growth and cognitive functions abnormalities. The efficacy of rehabilitation measures was estimated 3 years later.Цель исследования — оценить влияние комплекса реабилитационных мероприятий на состояние физического развития и когнитивных функций у детей дошкольного возраста.При обследовании 224 детей от 4 до 7 лет выявлен чрезвычайно высокий уровень отклонений в состоянии здоровья у 197 (88%) человек. Наиболее часто регистрировались цервикальная недостаточность и нарушение осанки, нарушение общей и тонкой моторики, нарушение речи. У всех детей с данными нарушениями проведено исследование  когнитивных  функций.  В  связи с этим разработан комплекс реабилитационных мероприятий для детей с нарушением физического развития и когнитивных функций. По истечении 3 лет проведена оценка эффективности проведенных реабилитационных мероприятий

IN SITU VASCULAR TISSUE REMODELING USING BIODEGRADABLE TUBULAR SCAFFOLDS WITH INCORPORATED GROWTH FACTORS AND CHEMOATTRACTANT MOLECULES

Background Currently, the search for the bioactive molecules capable of promoting formation of the vascular tissue is still ongoing. We have previously demonstrated that incorporation of the growth factors and chemoattractant molecules into the biodegradable tubular scaffolds can increase their primary patency upon the implantation into rat abdominal aorta. However, further studies are required to investigate tissue remodeling using functionalized vascular grafts with the same diameter as a replaced native vessel. Aim To investigate the specific aspects of de novo vascular tissue formation and calcification employing rat abdominal aorta interposition model and vascular grafts with 1.5 mm diameter with incorporated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor (SDF)-1α. Methods Tubular grafts with a diameter of 1.5 mm were blended of poly(3-hydroxybutyrateco-3-hydroxyvalerate) and poly(ε-caprolactone) (PHBV/PCL). Grafts without growth factors were fabricated using standard electrospinning technique whilst grafts with incorporated growth factors were prepared utilizing emulsion electrospinning. VEGF was incorporated into the inner third, whereas bFGF and SDF-1α were incorporated into the outer two-thirds of the graft. Grafts were implanted into the abdominal aortas of Wistar rats for 1, 3, 6, and 12 months following scanning electron microscopy along with histological and immunofluorescent examination. Results Primary patency of the grafts with VEGF, bFGF, and SDF-1α reached 93% indicative of structural integrity of the vascular tissue. Neither signs of inflammation nor severe calcification was detected. Conclusion As in 2 mm diameter vascular grafts, incorporation of bioactive factors into 1.5 mm diameter grafts increased their long-term primary patency and improved vascular tissue formation in comparison with non-modified grafts.  Background Currently, the search for the bioactive molecules capable of promoting formation of the vascular tissue is still ongoing. We have previously demonstrated that incorporation of the growth factors and chemoattractant molecules into the biodegradable tubular scaffolds can increase their primary patency upon the implantation into rat abdominal aorta. However, further studies are required to investigate tissue remodeling using functionalized vascular grafts with the same diameter as a replaced native vessel. Aim To investigate the specific aspects of de novo vascular tissue formation and calcification employing rat abdominal aorta interposition model and vascular grafts with 1.5 mm diameter with incorporated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor (SDF)-1α. Methods Tubular grafts with a diameter of 1.5 mm were blended of poly(3-hydroxybutyrateco-3-hydroxyvalerate) and poly(ε-caprolactone) (PHBV/PCL). Grafts without growth factors were fabricated using standard electrospinning technique whilst grafts with incorporated growth factors were prepared utilizing emulsion electrospinning. VEGF was incorporated into the inner third, whereas bFGF and SDF-1α were incorporated into the outer two-thirds of the graft. Grafts were implanted into the abdominal aortas of Wistar rats for 1, 3, 6, and 12 months following scanning electron microscopy along with histological and immunofluorescent examination. Results Primary patency of the grafts with VEGF, bFGF, and SDF-1α reached 93% indicative of structural integrity of the vascular tissue. Neither signs of inflammation nor severe calcification was detected. Conclusion As in 2 mm diameter vascular grafts, incorporation of bioactive factors into 1.5 mm diameter grafts increased their long-term primary patency and improved vascular tissue formation in comparison with non-modified grafts

Thermal effects of carbonated hydroxyapatite modified by glycine and albumin

In this work calcium phosphate powders were obtained by precipitation method from simulated solutions of synovial fluid containing glycine and albumin. X-ray diffraction and IR spectroscopy determined that all samples are single-phase and are presented by carbonate containing hydroxyapatite (CHA). The thermograms of solid phases of CHA were obtained and analyzed; five stages of transformation in the temperature range of 25-1000°C were marked. It is shown that in this temperature range dehydration, decarboxylation and thermal degradation of amino acid and protein connected to the surface of solid phase occur. The tendency of temperature lowering of the decomposition of powders synthesized from a medium containing organic substances was determined. Results demonstrate a direct dependence between the concentration of the amino acid in a model solution and its content in the solid phase

Comparative Analysis of Particularly Dangerous Infections Manifestations in the Territory of the Saratov and West-Kazakhstan Regions with a View to Advanced Epidemiological Risk Assessment

On the model of the Saratov and West-Kazakhstan regions carried out is the analysis of the current epidemiological and epizootiological situations in the cross-border territories of the two states: the Russian Federation and the Republic of Kazakhstan. Depicted is not only the common area of natural-focal territories of old-established infections, such as tularemia, but an intense outspread and formation of natural foci of the emerging infectious diseases too: Crimean hemorrhagic and West Nile fevers. This phenomenon assumes a great deal of importance due to dissemination and circulation of previously unknown to these areas infections concurrently in the two neighboring regions. Specified uniformity of epidemiological public risks in the bordering regions testifies to the need for development and implementation of the integrated system for prevention and response to the emergency situations in the sphere of sanitary-epidemiological welfare of the population in the territory of both of them