12 research outputs found

    Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

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    Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

    The measurement of adhesion forces in the system «cell-cell» by using atomic force microscope

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    The last decades in the world are characterizedby a steady increase in the number of naturaland man-made emergencies. The Republic ofKazakhstan is not an exception to the global patterns ofemergency situations. In the period from September 4 toOctober 6, 2017, a comprehensive study of the state ofhealth of 551 cardiovascular Rescuers in Almaty (Kazakhstan)was carried out according to reports on registereddiseases, their outcomes and causes of temporary disabilityfor 2012-2017, and the need for rehabilitation basedon a specially designed questionnaire. The study showsthe need to develop effective measures for the organizationof medical and psychological rehabilitation of cardiovascularRescuers

    Structure of purinergic P2Y12 receptors and some aspects of their biochemistry

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    The goal of this study is to develop a more rigorous understanding of the P2Y12 receptor first described in blood platelets where it plays a central role in the complex processes of activation and aggregation. P2Y12 receptors are 7-membrane-spanning proteins coupled to G proteins, which are activated by nucleotides, extracellular signaling molecules that are released from damaged cells or secreted via non-lytic mechanisms during inflammatory, ischemic, and hypoxic conditions. It is the drug targets for inhibition of platelet aggregation. We paid attention to structure and properties that provide essential insights for the development of improved P2Y12R ligands and allosteric modulators as drug candidates

    ANALYSIS OF DYNAMICS OF ANTIBIOTIC RESISTANCE OF PATHOGENS IN PATIENTS WITH DIABETIC FOOT SYNDROME UNDERGOING IN-PATIENT TREATMENT

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    Persistent ulcers in patients with diabetic foot syndrome in 85% of cases lead to amputation because of secondary infection and growing gangrene that significantly worsen the prognosis. In the course of our study, the data were obtained on the role of the staphylococcus, Pseudomonas aeruginosa infections, Enterobacteriaceae isolates, and, in a small percentage of cases, Candida fungus in diabetic foot syndrome. It was shown that in case of incomplete eradication of the pathogen the structure of pathogens and its sensitivity to antibiotics undergo changes. In this case, methicillin-resistant staphylococci and Pseudomonas aeruginosa are detected. In this paper we discuss the approaches to the choice of antibiotic therapy, subject to the sensitivity of these microorganisms to antibiotic therapy in the surgical department of St. Joseph Belgorod Regional Clinical Hospital. The obtained data state that III-IV generation pseudomonas cephalosporins and fluoroquinolones can be used for empirical therapy. And, in case of staphylococcal infections, - vancomycin

    STUDY OF THE ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY OF A NEW NON-OPIOID ANALGESIC BASED ON A SELECTIVE INHIBITOR OF TRPA1 ION CHANNELS

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    The aim is to study the analgesic and anti-inflammatory activity of an innovative molecule under the ZC02-0012 laboratory code belonging to the group of selective blockers of the TRPA1 ion channel.Materials and methods. The study of the ZC02-0012 analgesic activity was carried out by the hot plate and acetic acid writhing tests. The hot plate test was performed on white laboratory mice. ZC02-0012 substance was administered in doses of 1, 3 and 9 mg/kg. Ketorol at a dose of 3.48 mg/kg was chosen as the reference drug. To study the analgesic effects in the hot plate test, intact white laboratory mice were placed on a preheated at 55°C plate to determine the base level of pain sensitivity. Then the test substances were administered to the animals divided into groups, and the hot plate test was repeated after 30, 60, 90 and 120 minutes. To study the analgesic effects in the test of acetic acid writhing, white laboratory rats were injected with the ZC02-0012 substance at doses of 0.46, 1.38, and 4.15 mg/kg. Ketorol at a dose of 1.6 mg/kg was chosen as the reference drug. 30 minutes after intramuscular injection and 60 minutes after intragastric administration, the intraperitoneal administration of a 0.75% solution of acetic acid was carried out at the rate of 1 ml per 100 g of animal weight. Counting the number of writhings started 15 minutes after the injection of acetic acid and continued for 30 minutes. The anti-inflammatory effects of the ZC02-0012 substance were studied using a model of acute exudative inflammation in response to the subplantar introduction of 0.02 ml of 2% formaldehyde aqueous solution into the right hind paw of the mouse. 4 hours after the phlogistic introduction, the mass of the edematous paw was evaluated. ZC02-0012 substance at doses of 1, 3 and 9 mg/kg and the Diclofenac reference drug at a dose of 13.91 mg/kg were administered intragastrically or intramuscularly 45 minutes before the introduction of phlogistic. The presence and severity of anti-inflammatory activity was judged by the inhibitory effect, expressed in percentage.Results. The analgesic activity of ZC02-0012 is found to exceed that for Ketorol in both the intramuscular and intragastric ways of administration according to the results of hot plate tests in doses of 3 and 9 mg/kg and acetic acid writhing in doses of 1.38 and 4.15 mg/kg, while the anti-inflammatory activity of ZC02-0012 at doses of 3 and 9 mg/kg is shown to be comparable to that of Diclofenac. Conclusion. The innovative molecule under the ZC02-0012 laboratory code is established to exhibit a pronounced analgesic and anti-inflammatory activity, thus being prospective for further research.Conflict of interest: the authors declare no conflict of interest

    The influence of non-selective arginase inhibitors on some reparative regeneration indexes of experimentally resected liver

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    The impact of L-norvaline, a non-selective arginase inhibitor, on the state of the resected liver of Wistar strain white male rat, was evaluated. The resection of the liver was made on the second day of the experiment to the extent of 70%. L-norvaline ("WIRUD JmgH", Hamburg) was intragastrically administered, at a daily dose of 18mg/kg for the first seven days of the experiment, every 48 hours. The effect of the drug on the state of the resected liver was assessed according to the mortality rate, time of the volume recovery, the structure and functions of the organ. The mortality rate was being assessed in the experimental animal groups for the first ten days after the surgery. The animals were withdrawal from the experiment on the second, seventh, fourteenth, twenty-first, and twenty-eight days after the surgery. The cytolysis degree was assessed according to the AlAT, AsAT, and LDH indexes in the blood of the experimental animals, by an ultraviolet kinetic method. The synthesis function of the liver was evaluated according to the coagulogram indexes (APPT, INR, fibrinogen). The level of microcirculation in the liver was determined by laser doppler fluorometry. The morphological study was performed on the material of the standard liver sites taken after the animal had been withdrawal from the experiment. It was shown, that the non-selective arginase inhibitor, L-norvaline, stimulates liver regeneration after resection, which is manifested by decreased lethality, a significant decrease in the post-resection liver failure in comparison with the control group; significant earlier restoration of the volume, structure, and functions of the resected organ compared with the control group

    PRECLINICAL STUDY OF THE ALLERGENIC PROPERTIES OF CARBAMYLATED DARBEPOETIN

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    The article presents the results of a study of allergenicity of a new drug from the group of erythropoietin, carbamylated darbepoetin. The study was performed according to the Russian manual of pre-clinical studies and carried out through the following tests: the reaction of active cutaneous anaphylaxis, systemic anaphylactic reaction and delayed type reaction. The results of the reaction of active cutaneous anaphylaxis showed that the drug had caused a stain at the injection site 2.87 ± 0.17 of size, not significantly differenced from the size of the stain caused by placebo solution — 2.74 ± 0.10even tenfold dose. The systemic anaphylactic reaction has not produced any symptoms, classified according to the Weigle index. In the delayed type reaction in mice the relative size of the edema paw after administration of the shocking dose of the drug was 0.18±0.04, and did not exceed the control results — 0.16±0.03. Thus, the standard tests prove the absence of allergenic actions of carbamylated darbepoetin. Key words: carbamylated darbepoetin, allergenicity
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