Effects of Chronic Oral Administration of Midazolam on Memory and Circadian Rhythms in Rats

Studies have shown the ability of benzodiazepine drugs to cause memory loss in animals and humans. Midazolam is a benzodiazepine commonly administered intravenously during surgical procedures because it reacts rapidly, causes anterograde amnesia, and has few side effects. It has also been used in palliative medicine where, among others, an oral route has been employed for chronic administration of the drug. The current study evaluated the effects of chronic orally administered midazolam on spatial working memory and procedural memory in control and experimental female rats over a threeweek experimental period utilizing the Morris water maze. Sample and test run times to a submerged platform in the maze were recorded daily. In addition, activity wheels attached to each cage were employed to monitor daily circadian activity of the animals. Spatial working memory was not impaired in either group. However, procedural memory amnesia occurred in animals receiving the drug indicative of a consolidation or retrieval problem. Concerning circadian rhythms, a phase-shift was noted in experimental animals possibly indicating that time of day of drug administration is important. The findings of the present study could shed insight into altered reactions observed in humans who have received midazolam as a component of treatment in palliative medicine

The Role of the Gene-Gene and Gene-Environment Interactions of Polymorphic Loci of Matrix Metalloproteinases in Forming the Risk of Ischemic Stroke on the Background of Arterial Hypertension in Men

To analyze the role of genetic polymorphisms of matrix metalloproteinase (MMP) genes and their gene-gene and gene-environment interactions in the formation of ischemic stroke (IS) in men with arterial hypertension (AH

Clinical significance of sensitization to house dust mite allergens using flow cytometry-based basophil activation test

Respiratory allergy takes a significant place among allergic diseases. Similar clinical manifestations occur in sensitized patients in response to various airborne allergens. Accordingly, the allergen testing by means of in vivo and in vitro techniques is necessary to identify a causally significant allergen. The main laboratory assay to estimate sensitization to the airborne allergens is based on detection of specific immunoglobulin E (sIgE). However, clinical manifestations cannot be always confirmed by this test. The aim of this work was to evaluate the potential of basophil activation test (BAT) using flow cytometry, in order to confirm sensitization to house dust mite allergens. The BAT was carried out with allergens from Dermatofagoides in 34 volunteers, 130 patients were examined at the Russian Centre of Emergency and Radiation Medicine (33 people with household and 97 people with polysensitization), and 10 patients with allergy to house dust mites confirmed by skin testing. The sensitization was assessed using two laboratory kits (Allergenicity and BD FastImmune). The total IgE and sIgE to house dust mites, as well as concentrations of eosinophilic cationic protein, were determined. Specificity of the BAT with Allergenicity kit for the house dust mites was 94%. The sensitivity was 88% in the patients with household sensitization, thus being comparable with skin testing results available from the literature. An absolute correlation was found between positive results of skin testing and the BAT. In patients with household sensitization, sIgE levels > 0.35 UA/mL were detected in 39% of cases. A positive correlation was shown between the indices of basophil activation in response to testing allergens, and total immunoglobulin E and sIgE concentrations. High degree of correlation was found between the results of Dermatofagoides sensitization testing with both BAT kits. It was shown that the use of H1 histamine receptor blockers had no effect on BAT results. A decrease in sensitivity assay for airborne allergens was revealed upon therapy with glucocorticosteroids. Due to the proven clinical significance of the basophil activation test for diagnosing sensitization to inhaled allergens, one may require to supplement the range of approved assays in Russian Clinical Guidelines with BAT testing to prove sensitization in patients with allergic rhinitis and bronchial asthma, thus contributing to better diagnosis of causally significant allergens and, accordingly, administration of proper therapy

SOCIO-ECONOMIC DAMAGE BY ACUTE CORONARY SYNDROME IN RUSSIAN FEDERATION

Aim. To estimate the economic damage by acute coronary syndrome (ACS) in Russia in 2006-2009. Material and Methods. Direct costs and economic losses associated with ACS were estimated. The structure of direct costs includes the costs of hospitalization, medical emergencies, out-patient visits, high-tech medical care, as well as drug therapy in outpatient treatment. Losses in the economy associated with ACS include loss of gross domestic product due to death in working-age, temporary disability and payments of disability benefits. Estimation of economic damage by cardio-vascular diseases was based on analysis of Russian Ministry of Health official statistics. Results. Approximately 520,000 cases of ACS are registered annually (36,4% - myocardial infarction, 63,6% - unstable angina). Trend to increased mortality from myocardial infarction, especially among women, was found during the analyzed period. From 2000 to 2009 this index rose from 34.9 to 41.1 per 100,000 of population among women, and from 52.3 to 55.9 per 100,000 of population among men. Total direct costs of health care for patients with ACS in 2009 amounted to almost 21 billion rubles, and indirect – 53.5 billion rubles. The total economic damage by ACS in Russia in 2008-2009 exceeded 70 billion rubles per year. Conclusion. ACS in Russia is connected with significant social and economic damage. Most part of this damage is indirect losses in economy due to premature mortality of working aged men

MONOCYTE SUBSETS IN HEALTHY ADULTS AND SEPSIS PATIENTS

Monocytes play a key role in the development of immune response in bacterial infection, because of their phagocytic, antigen-presenting and secretory functions. There are three subpopulations of monocytes: “classical” CD14+CD16-, “intermediate” CD14+CD16+, and “nonclassical” CD14+dimCD16+. These monocyte subtypes have different phenotypes and functions. The ratio of appropriate subpopulations varies with development of the antibacterial response. The aim of the present research was to study phenotypes of the monocyte subpopulations in the patients with sepsis, and changes in the monocyte subpopulation ratio, depending on the presence of bacteria in circulating blood of the patients, as well as to estimate contribution of the monocyte subpopulations to the cytokine production. We observed 16 patients with sepsis (10 men and 6 women; mean age, 58±14 years, SOFA 9.4±2.1; a total of 44 blood samples) examined in dynamics. The control group included healthy adults (n = 23, 12 men and 11 women; mean age, 51±13 years). Laboratory studies included bacteriological cultures, determination of absolute and relative numbers of subpopulations of classical, intermediate and non-classical monocytes and their expression of HLA-DR and CD64, determination of IL-6, TNFα, IL-1β, IL-10 concentration in blood serum. Absolute number of monocytes was increased in the sepsis patients, the ratio of classical monocytes was also increased, like as relative and absolute numbers of  intermediate cells. Meanwhile, the subpopulation of non-classical monocytes did not change significantly. The monocyte subpopulation ratio depended on the presence of bacteria in blood, i.e., a higher proportion of intermediate cells was observed in the samples positive for bacteria in blood cultures. The ratio of subpopulations was restored after elimination of bacteria from the circulation. The expression density of LPS receptor (CD14), IgG receptors (CD16 and  CD64) was found to be increased, especially in the subpopulations of intermediate and nonclassical monocytes. In all subpopulations of monocytes, expression of HLA-DR is reduced, most notably in classical monocytes, least in intermediate cells. There was a significant increase in serum levels of IL-6, IL-1β, TNFα and IL-10 cytokines. Direct correlation between the absolute number of classical monocytes and IL-6 concentration was revealed, as well as intensity of multiple organ dysfunction. Increase in absolute amount of classical monocytes and IL-6 concentration might serve as an indirect criterion for evaluation of endothelial activation, an active producer of IL-6 and myeloid cell growth factors. A direct correlation between the percentage of CD14+CD16+ cells and IL-10 concentration in blood serum indicates to an important role of intermediate monocytes in IL-10 production. IL-10 suppresses the antigen-presenting function of intermediate cells, namely, expression of HLA-DR molecules, as suggested by inverse correlation between the IL-10 concentration and HLA-DR expression density on CD14+CD16+ cells. We have also determined an inverse correlation between the degree of multi-organ dysfunction  and relative amount of HLA-DR+ monocytes. The larger was a classical monocyte subpopulation, the more noticeable was a decrease of this index. The studies in ratios of monocyte subpopulations help to understand the mechanisms of antibacterial protection in sepsis. Monitoring of classical monocyte numbers and serum concentrations of IL-6 is necessary for a comprehensive assessment of inflammatory response in sepsis. Determination of HLADR expression on monocytes allows us to evaluate the intensity of immune suppression in critically ill patients

Epistemological models in understanding cultural and civilizational specificity

The article proposes a methodology for linking the formation-evolutionary, cultural-civilizational, ethnological, and cultural-anthropological models in understanding the changes of complicated sociocultural system

Дослідження антимікробної активності данофлоксацину проти збудників бактеріальних інфекцій у кіз

Fluoroquinolones are critical antimicrobials for both human and veterinary medicine. Due to their unique mechanism of antimicrobial action and good pharmacokinetic properties, they are often the first choice drugs in the treatment of bacterial infections in animals. The purpose of the investigation was to study the antimicrobial activity of a third-generation fluoroquinolone antibiotic of danofloxacin against bacteria, pathogens of respiratory and intestinal infection in goats. The samples of the nasal outflows (respiratory infection) and fecal masses (intestinal infection) were collected from clinically ill goats for microbiological studies. The sensitivity test of the microflora of the biomaterial, carried out by the disco-diffusion method, showed that the microorganisms of all the samples were sensitive to danofloxacin. Bacteria Streptococcus pneumonia (n = 10), Staphylococcus aureus (n = 4) and Escherichia coli (n = 2) were isolated and identified from nasal exudate samples (n = 10). Pathogenic strains of Escherichia coli were isolated from all faecal samples (n = 12). The degree of bacteriostatic activity of danofloxacin was determined by establishing its minimum inhibitory concentration (MIC) for bacterial isolates by sequential dilutions in a liquid nutrient medium. The average MIC of danofloxacin for Streptococcus pneumoniae isolates was 0.26 ± 0.13 μg/ml and for Staphylococcus aureus isolates – 0.25 ± 0.075 μg/ml. For Escherichia coli strains isolated from faeces of goats suffering from coli infection, the average MIC of danofloxacin was 0.38 ± 0.12 μg/ml (range 0.2 to 0.8 μg/ml). Antimicrobial sensitivity testing have shown a high level of bacteriostatic activity of danofloxacin against bacteria, pathogens of respiratory and intestinal infections in goats. This may be the argument for the use of danofloxacin-based chemotherapeutic agents in the treatment of bacterial infections in goats, especially for the empirical approach to therapy.Фторхінолони є критично важливими антимікробними речовинами як для гуманної, так і для ветеринарної медицини. Завдяки унікальному механізму антимікробної дії та добрим фармакокінетичним властивостям, вони часто служать препаратами першого вибору при лікуванні бактеріальних інфекцій у тварин. Метою дослідження було вивчення антимікробної активності фторхінолонового антибіотика третього покоління данофлоксацину щодо бактерій, збудників респіраторної та кишкової інфекції у кіз. Для мікробіологічних досліджень від клінічно хворих кіз відбирали зразки носових виділень (респіраторна інфекція) і калових мас (кишкова інфекція). Тест на чутливість мікрофлори біоматеріалу, проведений диско-дифузійним методом, показав, що мікроорганізми усіх зразків були чутливими до данофлоксацину. Зі зразків носового ексудату (n = 10) були виділені та ідентифіковані бактерії Streptococcus pneumoniae (n = 10),  Staрhylococcus aureus (n = 4) і Escherichia coli (n=2). З усіх зразків калових мас (n = 12) були виділені патогенні штами Escherichia coli. Ступінь бактеріостатичної активності данофлоксацину визначали шляхом встановлення його мінімальної інгібуючої концентрації (МІК) для бактерій-ізолятів методом послідовних розведень у рідкому поживному середовищі. Середнє значення МІК данофлоксацину для ізолятів Streptococcus pneumoniae становило 0,26 ± 0,13 мкг/мл, а для ізолятів Staрhylococcus aureus – 0,25 ± 0,075 мкг/мл. Для штамів Escherichia coli, виділених з фекалій кіз, хворих на коліінфекцію, середнє значення МІК данофлоксацину становило 0,38 ± 0,12 мкг/мл (діапазон від 0,2 до 0,8 мкг/мл). Дослідження антимікробної чутливості показало високий рівень бактеріостатичної активності данофлоксацину щодо бактерій, збудників респіраторної та кишкової інфекцій у кіз. Це може служити підставою для застосування хіміотерапевтичних засобів на основі данофлоксацину в лікуванні бактеріальних інфекцій у кіз, особливо при емпіричному підході до терапії

Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response

Biochemical indicators of sports achievements in highly qualified wrestlers

Objective: to conduct comparative analysis of blood biochemical parameters (urea, ALT, AST, creatinkinase, cortisol, testosterone and testosterone / cortisol ratio) in groups of high­class wrestlers with different levels of sports achievements.Materials and methods: male athletes (n = 78), members of the Russian national team in one of the types of wrestling (the average age is 25.2 (21.5–28.9) years, the average weight is 76.9 (68.4–83.4) kg) were recruited to this study. The examined athletes were divided into two groups according to their sporting achievements. The first one — SHA group (super­high achievements) which included athletes (n = 19) who had victories and prizes at the largest international competitions (European, World, Olympic Games), and the second group — MNT group (members of the national team) which included athletes that did not have similar achievements (n = 59). The following biochemical parameters were studied: urea, creatine kinase, ALT, AST, testosterone, cortisol, anabolic index (AI).Results: the absolute values of all metabolites in the examined athletes were within the reference intervals. Statistically significant differences in most of the biochemical parameters were revealed between the compared groups in terms of the level of sports achievements. The SHA group showed a statistically significant shift in relation to MNT group, in direction of increasing the level of metabolites that characterize the predominance of anabolic processes — ALT, testosterone, AI. Metabolite levels, increase which reflects catabolic processes activity and inadequate or insufficient adaptation processes, in the SHA group were significantly lower than in the MNT group. The above changes of the absolute values of biochemical parameters were confirmed by correlation analysis.Conclusions: the obtained results allow us to state the optimal adaptation of this sport, the adequacy of metabolic processes in the group of highly qualified athletes