[Effect of pharmacological stimulation of melatonin receptors on renal function in aging.]

The aim of the study was to study ion exchange, as well as water and nitrogen excretion function of the kidneys in rats under the influence of pharmacological stimulation of melatonin receptors. The experiment was conducted on male rats, which were divided into 2 groups. The first group was a control group (n=35) and was kept in standard vivarium conditions. Animals of the second group received melatonin along with drinking water throughout their lives (n=35). The study was conducted in compliance with the international principles of the Helsinki Declaration on Humane Treatment of Animals. According to the blood and urine analysis, water consumption, the volume of diuresis, the content of creatinine, urea, sodium and potassium ions in urine and blood were determined. Based on the data obtained, the parameters of water-salt metabolism were calculated. The data obtained as a result of the study were subjected to statistical processing. As a result of the experiment, a decrease in the functional abilities of the kidneys was noted in rats both in the control group and in the group of animals treated with melatonin. However, data analysis shows that rats treated with melatonin had higher values of indicators of water-releasing, ion-regulating and nitrogen-releasing kidney functions compared with intact animals. Thus, long-term use of exogenous melatonin led to more stable functioning of the kidneys and water-salt metabolism in old animals compared with the control group.

[Prevalence of calcium deficiency in the hair in people at different age and sex living in the European North.]

Calcium is one of the most important elements in the human body, while its deficiency is common among residents throughout the world. The reasons for the deficiency are the lack of calcium in food and water, which is especially important for the North territories belonging to the biogeochemical provinces. The surface waters of the Republic of Karelia are ultra-fresh and low-mineralized. The purpose of this study was to determine the calcium level in the hair of the European North (Republic of Karelia) residents with an assessment of the deficiency prevalence in different sex and age groups. Atomic emission spectrometry and mass spectrometry with inductively coupled argon plasma were used for elemental analysis of hair. A 4-point scale corresponding to the range of deviation of the calcium content from reference values was used to estimate the data obtained. A Ca deficiency was established in 78,43% of individuals who participated in the study. The 4th degree of deviation from the norm towards a decrease in the concentration of the element in the hair was most often observed (43,15%). Calcium deficiency was equally typical for persons aged 20-25 years (84,45%) and 60-87 years (73,69%). It was more common in men (88,88%) than in women (72,73%), p<0,05. However, women were significantly more likely to be diagnosed with grade 4 calcium deficiency. From the foregoing, we can conclude that calcium deficiency in the Republic of Karelia is caused not only by age and gender characteristics, but it is connected with the natural, environmental and social conditions extent of the region. Residents of the North territories need an additional intake of calcium as part of mineral complexes, while the composition of such a complex should have a higher calcium content than for residents of central part of Russia.

[The effectiveness of BIFIFORM KIDS in the prevention of the incidence of acute respiratory infections in children].

Probiotics are widely used as a means of dietary correction of the intestinal microbiota in patients not only with alimentary, but also with allergic and inflammatory diseases. They have systemic effects on the human organism. However, the diversity of the composition of probiotic complexes complicates the determination of the beneficial effects of specific microorganisms on the human body. These circumstances call for more research. Investigation of the effect of probiotic intake on the levels of various cytokines may explain the mechanisms of the beneficial effect of probiotic intake on the functioning of the immune system. Objective - to study the effectiveness of the probiotic Bifiform Kids for the prevention of respiratory infections in children with recurrent respiratory infections with gastrointestinal allergy symptoms. Material and methods. The prospective randomized controlled trial included 92 children aged from 4 to 5 years who suffers from more than 5 episodes of respiratory infections per year with gastrointestinal allergy symptoms. Patients from the main group (n=46) were prescribed 2 chewable tablets Bifiform Kids (Lactobacillus rhamnosus GG not less than 1×109 CFU, Bifidobacterium animalis spp. lactis not less than 1×109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg in each) twice per day within 21 days. Patients from the control group (n=46) were prescribed no probiotics during the study period. The study included the measurement of blood serum levels of immunoglobulins A, M, G (by immunoturbodimetry) and E, as well as the concentration of cytokines IL-17, IL-10 (by enzyme immunoassay). Measurements were performed at the 1st day of the study, at the 21st day of the study, and 6 months after the study initiation. The microbiota composition was determined by sequencing the bacterial 16S rRNA genes in DNA preparations isolated from stool samples collected at the start of the study and after 21 days. The Shannon index was calculated for the species of detected bacteria to determine the diversity of the microbiome. The effectiveness of disease prevention was measured by calculating the prevention index and the efficiency coefficient based on the incidence of respiratory infections in both groups during the observation period (6 months). Results. In the main group, the volume of the commensal flora decreased 3 weeks after the study initiation: Enterobacter from 18.3±19.3 to 10.5±18.1%; Enterococcus from 8.7±16.1 to 3.1±10.0%; Clostridium from 3.1±8.1 to 0.5±2.2%. There was a statistically significant increase in the proportion of representatives of the genus Bifidobacterium by 2.2 times (from 16.9±26.4 to 36.5±31.5%, p=0.0017) and a decrease in the Shannon index from 1.1±2.1 up to 0.4±1.1 (p<0.05). In the control group, there were no statistically significant changes in the microbiota content. In the main group, after 21 days, the blood IL-10 level increased from 11.3±15.4 to 15.7±13.4 pg/ml, and the IL-17 concentration decreased from 8.9±7.7 to 6.5±7.1 pg/ml (p=<0.05) while maintaining this trend by the 6th month of observation. There were no changes in these indicators in children from the control group. The main group demonstrated a significant (р=<0.05) decrease in the level of IgE from 184±121 to 104±67 and 114±54 kU/l, and a significant increase in IgA from 0.73±0.45 to 1.33±0.65 and 1.21±0.57 g/l after 3 weeks and at the end of the probiotic intake, respectively. The level of IgA in the main group remained higher during the study compared to the control group. The main group demonstrated a 3-fold decrease in the incidence of respiratory infections in comparison with the control group. The efficiency index was 3.21, the therapeutic response was 69%. Conclusion. The results of the study show the effectiveness of the complex probiotic for the respiratory infections prevention in children with gastrointestinal allergy symptoms.

[Blood pressure telemonitoring and remote counseling in uncontrolled hypertension].

Telehealth is a useful adjunct in hypertension (HTN) management. Despite obvious short-term clinical benefit, long-term social impact and cost-effectiveness have not been fully investigated. AIM: Predictive modeling of long-term clinical and social outcomes and the cost-effectiveness analysis of blood pressure (BP) telemonitoring and remote counseling (BPTM) in patients with HTN. MATERIALS AND METHODS: A Markov cohort-based (1000 patients in each study arm) model was developed and adopted a 10-year time horizon with 12-month time cycles. Cost and outcome data collected from the three-month study of 240 patients (160 in BPTM group and 80 controls, 48 y.o.). All patients started at a non-complicated HTN well state with a certain possibility of disease progression in a number of health states over a discrete time period. BPTM was compared with usual care in terms of 10-year healthcare costs, quality adjusted life years (QALY) using a Ministry of Health of Russian Federation perspective. RESULTS: In the long-term run when compared with usual care BPTM was more effective in terms mortality (67 versus 91 patients lost and 9.6 versus 9.71 life years gained) and costs (cost of illness 102 508 000 RUR versus 145 237 700 RUR). Taking quality of life measures into account, the effect of BPTM was also more pronounced (8.31 versus 7.82 QALYs gained). The resultant incremental cost-utility ratio for BPTM was 275 178.98 RUR/1 QALY gained/1 patient (134 837.70 RUR/0.49 QALY/1 patient). CONCLUSION: According to the results of predictive modeling, implementation of BPTM into clinical practice is likely lead to reduced cardiovascular morbidity and mortality in a cost-effective way.

[Assessment of the clinical efficacy of telemonitoring and distant counseling in patients with uncontrolled hypertension].

The aim of the study was to investigate the mathematical correlation of the clinical efficacy of blood pressure telemonitoring and distant counseling (BPTM) in patients in uncontrolled hypertension (HTN). Telehealth tools are widely used in HTN management. However clinical efficacy of such interventions assessed mainly in groups investigated without its populational and attributable impact. Materials and methods. The total of 240 patients were included, then randomized in 2:1 manner to BPTM group (n=160, median age 47 y.o.) and control group (n=80, median age 49 y.o). The user - friendly and secure telehealth software was provided with mobile application (patients) and desktop (doctors) platforms which allowed storage and analysis of self-BP monitoring data and remote consultations. A three - month surveillance was designed with mandatory baseline and final face - to - face visits with the assessment of office systolic BP (oSBP). Mathematical evaluation was based on target SBP rates achieved in comparator groups and included the absolute efficacies (AE), the attributable efficacy (AtE), the relative efficacy (RE) and the population attributable efficacy (PAtE). Results. BPTM group characterized by larger decrease in SBP level compared with controls (-16.8±2.9 mm Hg versus -7.9±3.9 mm Hg; p.

[The role of constant light exposure in various periods of postnatal ontogenesis in the development of pathology and mortality in male rats.]

The purpose of the experimental work was to study the effect of constant light, depending on the time of the onset of light exposure (from the age of one month or from fourteen months), on the development of age-related pathology and oncology in male rats. The results of the study show that decreased functional activity of the epiphysis due to the influence of constant light from the age of one month increases the incidence of inflammatory, non-tumor and tumor genesis diseases, and leads to the rapid development of age-related pathology. On the contrary, the onset of constant light exposure in male rats from the age of 14 months slows the development of age-related pathology, reduces the incidence and development of malignant tumors.

[The influence of light deprivation and luzindol on ovulatory function of rats].

The age dynamics of ovulatory function of rats which were kept in conditions of light deprivation and receiving luzindol (a blocker the melatonin receptors) is investigated in this research. Cytological research of an estrous cycle was conducted quarterly within two years. It is defined that the age changes of an ovulatory cycle in the mode of light deprivation came later and were less expressed in comparison with similar changes at control rat females kept in the conditions of standard lightning. In case of the blockade of melatonin receptors by luzindol, the dynamics of aging of reproductive system corresponded to the one in the control group kept in standard lightning mode.

[Analysis of the efficiency of antimicrobial treatment for community-acquired pneumonia in clinical practice]. / Analiz éffektivnosti antimikrobnoi terapii vnebol'nichnoi pnevmonii v klinicheskoi praktike.

AIM: To analyze actual drug consumption based on the defined daily dose (DDD analysis) and to analyze the utilization of drugs based on their proportion of the total defined daily doses (DU90% analysis) for the antimicrobial therapy of community-acquired pneumonia (CAP) in clinical practice at a hospital in Russia. MATERIAL AND METHODS: The investigation materials were the data of 117 case histories of male (51.3%) and female (48.7%) patients hospitalized with CAP at Nizhny Novgorod City Clinical Hospital Five in 2015. The investigation enrolled all the patients admitted to the hospital over the analyzed period. DDD analysis and DU90% analysis were used as study methods. RESULTS: DDD analysis and DU90% analysis of antimicrobial therapy for CAP were carried out at the hospital in clinical practice during a year. The annual number of defined daily doses (NDDD) for antimicrobial drugs, the number of defined daily doses per 100 bed-days (NDDD/100 bed-days), and a drug load (g) per 1000 CAP patients per day and per CAP patient per year were determined. The largest NDDD/year for CAP treatment with ceftriaxone was 376 g, or 43.43 NDDD/100 bed-days, which is much higher than that with other antimicrobial agents. The daily drug load of ceftriaxone per 1,000 CAP patients was 8.8 g, which exceeds that of moxifloxacin by 18.7 times, azithromycin and levofloxacin by 5 times, and ampicillin/sulbactam by 2.3 times. The daily drug load of ceftriaxone per CAP patient was 3.2 g, which exceeds that of of ampicillin/sulbactam by 2.3 times, levofloxacin and azithromycin by 5 times, and moxifloxacin by 19 times. CONCLUSION: It may be recommended that the proportion of cephalosporins as drugs that promote the rise of resistance in microbes and their production of extended-spectrum ß-lactamases should be further limited, the proportion of penicillins be extended, and the administered ampicillin/sulbactam be added, for example, by amoxicillin/clavulanate. Penicillins contribute to the rise of resistance to a lesser degree, and the use of two different penicillin molecules specified in the guidelines for the treatment of CAP will be able to slow the process further. By the same reasoning, it is also advisable to use cefuroxime (second-generation cephalosporins) along with ceftriaxone in patients in stable condition, without impairing vital functions.

[Luzindol accelerates the aging of estrous function of female rats].

In this paper, we investigated the dynamics of aging of the estrous function of female rats kept in the conditions of standard vivarium lighting and receiving luzindol - the blocker of melatonin receptors. Every three months, daily, for two weeks, vaginal smears were taken from the animals and cytological examination of the vaginal contents was conducted. Despite different mechanisms of the development of melatonin system failure (a decreased production of melatonin and a blockade of melatonin receptors), the effects of the influence on the ovulatory function are similar. In case of the blockade of melatonin receptors, the appearance of premature signs of aging of the reproductive function in rats was observed. It was manifested by an increased duration of ovulatory cycle; a decrease in the number of regular cycles; the emergence of irregular cycles; a decrease in the number of short estrous cycles and an increase of long cycles; the early development of persistent estrus.

[The concept of risk factors in assessing the impact of smoking on an exacerbation of chronic obstructive pulmonary disease].

AIM: By using the risk concept, to determine a quantitative relationship between smoking in patients with chronic obstructive pulmonary disease (COPD) and the development of an exacerbation. SUBJECTS AND METHODS: Case history data were studied in 166 patients admitted for a COPD exacerbation in 2009 to 2012. There were 2 exacerbations for a year or longer. The patients were divided into 2 groups: smokers (n=110) and nonsmokers (n=56). The concept for estimating the risks was based on the calculation of absolute risk in the exposed and unexposed groups, attributable risk, relative risk, and population attributable risk and on the determination of standard errors for each type of risk and confidence interval. RESULTS: The methodological aspects of determining the quantitative relationship between smoking in patients with COPD and the development of its exacerbations (twice or more per year) were considered on the basis of the statistical concept of risk factors. A risk factor concept-based analysis has shown that the impact of smoking is directly related to the worsening of COPD. The frequency of exacerbations is 71.8% in the group of smoking patients and 32.1 % in that of nonsmoking patients; the risk factor increases the likelihood of this event by 39.7%. CONCLUSION: Smoking leads to a 2.2-fold increase in the frequency of COPD exacerbations. The potential hazard index was 2.5.

[Features of the Udmurt mitochondrial gene pool in relation to tribal structure].

We present novel data on mitochondrial DNA polymorphism in the Udmurt population, which represents a Finno-Ugric ethnos residing in the Volga-Ural region. Our analysis of the Udmurt mtDNA polymorphisms have shown that neighboring ethnoses had almost no effecton formation of the Udmurtian intraethnic diversity. These results strongly indicate that genetic differences in the Udmurtian population are determined by their tribal structure rather than their geographic location.

[Genetic diversity of Besermyan based on mitochondrial DNA polymorphism].

The first data on mtDNA diversity in Besermyan, the Finno-Ugric ethnic group, related to Udmurts, are presented. An analysis of mtDNA polymorphism showed that Besermyan stood out from the other populations of Volga-Ural region due to the presence of a large proportion of the mongoloid component. The sample of Besermyan contained East Eurasian haplotypes not detected in ethnic populations of the Volga region and Cisurals, while they were detected in South Siberia, mostly among Turkic-speaking populations. An analysis of the genetic distances between Besermyan and the neighboring ethnic groups showed that Besermyan were distant from other populations of Volga-Ural region and close to Turkic-speaking populations of South Siberia. Thus, the data obtained favor the suggestion on the mixed Udmurto-Turkic origin of Besermyan.

[Migration rates as inferred from the 2002 Russian census].

Migration rates in the modern Russian population have been studied on the basis of the results of the 2002 census. The migration rate at the population level corresponding to a city or rural administrative district is m = 0.443. The migration rate for women (m(F) = 0.463) is 11% higher than for men (m(M) = 0.418); the migration rate for urban populations (m(U) = 0.459) is 15% higher than for rural populations (m(R) = 0.398). The geographic variation of migrations has been studied; the geographic distributions of the migration rates for rural, urban, male, and female populations are presented. Comparison of migrations in the rural population of Russia at two temporal cross-sections (1970 and 2002) has shown that the geographic structure of migrations has remained the same in many respects. The ecological factor has remained the main determinant of the migration geography, which is expressed in the relationship of the settled way of life with the forest-steppe and broad-leaved forest landscapes.

Characteristics of Populations of the Russian Federation over the Panel of Fifteen Loci Used for DNA Identification and in Forensic Medical Examination.

Seventeen population groups within the Russian Federation were characterized for the first time using a panel of 15 genetic markers that are used for DNA identification and in forensic medical examinations. The degree of polymorphism and population diversity of microsatellite loci within the Power Plex system (Promega) in Russian populations; the distribution of alleles and genotypes within the populations of six cities and 11 ethnic groups of the Russian Federation; the levels of intra- and interpopulation genetic differentiation of population; genetic relations between populations; and the identification and forensic medical characteristics of the system of markers under study were determined. Significant differences were revealed between the Russian populations and the U.S. reference base that was used recently in the forensic medical examination of the RF. A database of the allelic frequencies of 15 microsatellite loci that are used for DNA identification and forensic medical examination was created; the database has the potential of becoming the reference for performing forensic medical examinations in Russia. The spatial organization of genetic diversity over the panel of the STR markers that are used for DNA identification was revealed. It represents the general regularities of geographical clusterization of human populations over various types of genetic markers. The necessity to take into account a population's genetic structure during forensic medical examinations and DNA identification of criminal suspects was substantiated.

[Polymorphism of immunogenetic and biochemical markers in Siberian (Tobol-Irtysh) Tatars].

The polymorphism of immunogenetic and biochemical markers has been studied in nine populations of five ethnic-geographic groups of Siberian (Tobol-Irtysh) Tatars. Data on the frequency distributions of 33 alleles and 6 haplotypes of 14 loci (ABO, RHD, RHC, RHE, P, KEL, HP, C'3, TF, GLO1, ESD, ACP, PGD, and PGM1) in sample of 354 subjects have been obtained. Comparison with other ethnic groups has shown that the gene pool of Tobol-Irtysh Tatars contains an ancient autochthonic genetic stratum similar to that found in the neighboring Ob' Ugrian population. Genetic relationships of various strengths with Central Asian Turks and the ethnic groups of the Volga region have been found, which apparently reflect different stages of the ethnogenesis of the Tobol-Irtysh Tatars.

[Mitochondrial DNA variability in populations and ethnic groups of Tatars of the Tobol-Irtysh basin].

The data on mitochondrial DNA diversity in seven local populations (villages) and four territorial groups of Tatars of the Tobol-Irtysh basin are presented. In the Turkic-speaking populations from the Tobol and Irtysh river basins, high levels of intergroup and interpopulation mtDNA variation were observed. It was demonstrated that genetic diversity of the territorial groups of Tatars of the Tobol-Irtysh basin resulted from various interethnic relationships and different ethnic components integrated into these groups.

[Mitochondrial DNA diversity in Siberian Tatars of the Tobol-Irtysh basin].

Data on the variation of the nucleotide sequence of hypervariable segment I (HVSI) and restriction fragment length polymorphism (RFLP) of the coding region of mitochondrial DNA (mtDNA) have been used to characterize the mitochondrial gene pool of Siberian Tatars of the Tobol-Irtysh basin (N = 218), one of three geographic/linguistic groups of Siberian Tatars. The gene pool of Siberian Tatars has been shown to contain both Asian and European mtDNA lineages at a ratio of 1 : 1.5. The mtDNA diversity of Siberian Tatars is substantially higher than that of other Turkic-speaking populations of North and Central Asia. The position of the mitochondrial gene pool of Tatars of the Tobol-Irtysh basin in the genetic space of northern Eurasia populations has been determined.

[The population gene pool of Yakutia: cartographic analysis based on the polymorphism of immune and biochemical markers].

The gene pool of the indigenous population of Sakha Republic (Yakutia) has been studied within the borders of this republic coinciding with the main area of Yakuts, which was formed by the end of the 19th century and have remained stable until the present time. Maps of the geographic variation of the integrated characteristics of the Yakut gene pool, including the principal components, parameters of genetic diversity, and genetic distances from the "average" Yakut population are presented. It has been demonstrated that ethnographers' reports on intense internal assimilation in modem Yakutia agree with genetic data. The stratification of the Yakut gene pool reflected in the maps of two principal components corresponds to the observed general (H(T)) and interpopulation (FST) gene diversities.