Onium Salts of Sulfur-Containing Oxyanions Resulting from Reaction of Sulfur(IV) Oxide with Aqueous Solutions of 1,2-Diamines and Morpholine

Reaction products have been isolated from SO2–L–H2O–О2 systems (L = ethylenediamine, N,N,N',N'-tetramethylethylenediamine, piperazine, and morpholine) as onium salts [H3NCH2CH2NH3]SO4, [(CH3)2NHCH2CH2NH(CH3)2]SO4, [(CH3)2NHCH2CH2NH(CH3)2]S2O6 ⋅ H2O, [C4H8N2H4]SO3 ⋅ H2O, [C4H8N2H4]S2O6, [C4H8N2H4]SO4 ⋅ H2O, [O(C2H4)2NH2]2SO4 ⋅ H2O. The prepared compounds have been characterized by X-ray diffraction analysis, X-ray powder diffraction, IR and mass spectroscopy

Assessment the equivalence of the bioanalogue insulin lizpro biphasic 25 (Geropharm-bio, Russia) and Humalog® Mix 25 (Lilly France, France) using the euglycemic hyperinsulinum clamp method on healthy volonters

Background: Modern medicine requires use of effective antidiabetic drugs that can imitate the natural profile of insulin in the body of patients with diabetes mellitus. Examples of such preparations include biphasic insulin lispro, which is a mixture of insulin lispro ultra-short action and insulin lispro protamine suspension with prolonged effect. The clinical trials (CT) program for biosimilar insulins contains pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety studies. Aims: To demonstrate Biphasic Insulin Lispro 25, suspension for subcutaneous administration, 100 U/ml (GEROPHARM-Bio, Russia) and Humalog® Mix 25, suspension for subcutaneous administration, 100 U/ml (Lilly France, France) have comparable pharmacokinetic profiles under conditions of hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers. Materials and methods: The study was conducted on 48 healthy men aged between 18 to 50 years. This was a double-blind, randomized, crossover study of comparative pharmacokinetics of drugs. The investigational products (IP) were administered before the clamp in a single dose of 0.4 U/kg subcutaneously in the abdominal wall. Regular blood sampling was performed during the study. The insulin concentrations in the samples were determined using an ELISA method. The results of the determination were used to calculate the PK parameters and construct the concentration-time curves. Adjust glucose infusion rates were based on blood glucose measurements. These data were used to calculate the PD parameters. Results: Our results demonstrated that Biphasic Insulin Lispro 25 and Humalog® Mix 25 have comparable PK and PD profiles under conditions of HEC in healthy volunteers. The confidence intervals for the ratio of the geometric mean for Cins.max and AUCins.0–12 were 87.75–99.90% and 83.76–96.98% respectively, which were well within 80–125% limits for establishing comparability. Conclusions: Biphasic Insulin Lispro 25 and Humalog® Mix 25 are equivalent based on this CT applying the HEC technique in healthy volunteers

Применение модульно-рейтинговой технологии обучения математике студентов Алтайского государственного аграрного университета

Introduction. New requirements are put forward for the organization of educational process, and improving the quality of training of graduates. Purpose setting. Therefore, teachers are faced with the need to apply modular-rating training technology which instantly reacts to changes in the situation in the labor market and can adjust the specialist model. It is democratic in its principles, content, and organization of the educational process. Modular-rating technology provides individualization of educational programs and the ways of their assimilation depending on the abilities and interests of students. Methodology of the study. The authors carried out modular structuring of the “Mathematics” course; methodological support (tests, individual tasks, etc.) of the modular-rating program was developed. A special role in the technology of modular-rating education is assigned to control over the knowledge of students, the authors used current, midterm and fi control. The quality of knowledge and skills of students in mastering the module was determined by various control methods: oral and written survey, control work, individual task, calculate and graphic work, etc. In addition, a testing method was used. To assess the effectiveness of student educational activities, a rating is used which is determined by points set in a selected unifi scale with a clear gradation of the level of theoretical knowledge, practical skills and abilities. The rating is formed during the entire period of the student training. Results. In modern conditions, higher education is faced with the tasks of forming a specialist with stable incentives for further professional self-improvement, activation and development of student cognitive abilities, differentiation of training content and individualization of pedagogical infl in accordance with the level of student training. Conclusion. The authors conclude that one of the effective ways to solve these problems is to train students according to the modular-rating system.Введение. В настоящее время предъявляются новые требования к организации учебного процесса, повышению качества подготовки выпускников. Постановка задачи. В связи с этим перед преподавателями возникает необходимость применять модульно-рейтинговую технологию обучения, которая мгновенно реагирует на изменения ситуации на рынке труда и может корректировать модель специалиста. Она отличается демократичностью принципов, содержания, организации учебного процесса. Модульно-рейтинговая технология обеспечивает индивидуализацию образовательных программ и путей их усвоения в зависимости от способностей и интересов студентов. Методика и методология исследования. Авторами осуществлено модульное структурирование курса «Математика»; разработано методическое обеспечение (тесты, индивидуальные задания и т. п.) модульно-рейтинговой программы. Особая роль в технологии модульно-рейтингового обучения отводится контролю за знаниями студентов; авторы использовали текущий, рубежный и итоговый контроль. Качество знаний и умений студентов при овладении модулем определялось различными методами контроля: устный и письменный опрос, контрольная работа, индивидуальное задание, расчетно-графическая работа и т. д. Кроме этого применялся метод тестирования. Для оценки результативности учебной деятельности студентов используется рейтинг, который определяется баллами, выставленными в выбранной единой шкале с четкой градацией уровня теоретических знаний, практических умений и навыков. Рейтинг формируется в течение всего периода обучения студента. Результаты. В современных условиях перед высшей школой стоят задачи формирования специалиста с устойчивыми побудительными мотивами к дальнейшему профессиональному самосовершенствованию, активизации и развития познавательных способностей студентов, дифференциации содержания обучения и индивидуализации педагогического воздействия в соответствии с уровнем подготовки обучаемых. Выводы. Авторами делается вывод о том, что одним из эффективных путей решения поставленных задач является обучение студентов по модульно-рейтинговой системе

Influence of hyperinsulinemic – hypoglycemic clamp on induced platelet aggregation, activity of physiological anticoagulants and von Willebrand factor in patients with type I diabetes

Background. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. Aims. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemichypoglycaemic clamp. Materials and methods. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 5.6 years, A1C 9.7 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. Results. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin23.9%, ADP30.6%, arachidonic acid30.9%, collagen69.4% and ristocetin70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. Conclusions. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemichypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation

Evaluation of biosimilarity of RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) using the euglycemic hyperinsulinemic clamp technique in patients with type 1 diabetes: double-blind randomized clinical trial

Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research.Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016.Materials and methods: The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters.Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUCins0-T, and 85.43% - 115.64% for the PD-parameter AUCGIR0_T, which fall within the specified limits of 80% - 125% to establish comparability between drugs.Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®

The effect of platinum compounds on the viability of cultured malignant neoplasm cells

The aim of the study – to study the effect of cycloplatinated complexes on the viability of tumor cells and the detection of chemical compounds for the creation of new antitumor drugs.Цель исследования – изучить влияние циклоплатинированных комплексов на жизнеспособность опухолевых клеток и синтезировать химические соединения для создания новых противоопухолевых препаратов

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

Background: Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival.Results: By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems.Conclusions: Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.Financial support was provided by grants BFU2009-12895-C02-01/BMC (Ministerio de Ciencia e Innovación, Spain), the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 212894 and Prometeo/2009/092 (Conselleria d’Educació, Generalitat Valenciana, Spain) to A. Moya. Work in the FdlC laboratory was supported by grants BFU2008-00995/BMC (Spanish Ministry of Education), RD06/0008/1012 (RETICS research network, Instituto de Salud Carlos III, Spanish Ministry of Health) and LSHM-CT- 2005_019023 (European VI Framework Program). Dr. González-Domenech was supported by grant from the University of Granada. LD, thanks to financial support from Facultad de Ciencias, Universidad Nacional Autónoma de México

КООРДИНАЦІЙНІ СПОЛУКИ РІЗНИХ СОЛЕЙ МІДІ(ІІ) З 4-ФЕНІЛСЕМІКАРБАЗИДОМ

Синтезовано комплекси хлориду, нітрату, сульфату, валерату, бензоату, оксалату та фталату міді(ІІ) з 4-фенілсемікарбазидом. Добуті сполуки охарактеризовані методами хімічного аналізу, 14 спектроскопії та термогравіметрії

Insulin resistance and its possible personal stress moderators

Background. Recently, insulin resistance (IR) has been actively investigated by experts in various fields. Here we aim to study the effect of stress on the development of IR. Objective. To study the associations between IR and personal stress moderators (self-attitude, locus of control and coping strategies) as well as the related performance lifestyles. Methods. The study included 63 patients (16 men; mean age, 48.2 11.7 years). Of these participants, 26 were diagnosed with type 2 diabetes mellitus, 10 with impaired glucose tolerance, 6 with impaired fasting glucose and 21 with normal glucose tolerance. The levels of HbA1c and IR ratio were determined using HOMA. Well-known psychological assessment questionnaires were used to assess the effect of personal stress moderators. Results. There was a significant relationship between IR and personal stress moderators. A positive self-attitude was associated with a lower risk of IR (p 0.05), which can be explained by a decrease in the risk of developing stress. Assertive coping strategies were most pronounced in subjects with a low level of IR (p 0.05). Personal characteristics also determined an individuals lifestyle, which may have an impact on the increase in IR. There was an association between high levels of IR and unhealthy alimentary preferences (p 0.05). Such preferences were also associated with personal characteristics, such as external locus of control, less positive self-attitude and passive coping strategies (p 0.05). People with high IR rarely engage in a regular physical activity; there was a direct correlation between the frequency of physical activity and assertive coping strategies (p 0.01). Married participants had high levels of IR (p 0.05). Conclusion. There were significant relationships between IR and personal stress moderators, such as self-attitude and coping strategies. Besides the direct effects on stress levels, personality traits may also indirectly increase the risk of IR by influencing the individuals lifestyle. There is a need to investigate the fact that married people have higher levels of IR

Proteomic Insights into Starvation of Nitrogen-Replete Cells of Nostoc sp. PCC 7120 under β-N-Methylamino-L-Alanine (BMAA) Treatment

All cyanobacteria produce a neurotoxic non-protein amino acid β-N-methylamino-L-alanine (BMAA). However, the biological function of BMAA in the regulation of cyanobacteria metabolism still remains undetermined. It is known that BMAA suppresses the formation of heterocysts in diazotrophic cyanobacteria under nitrogen starvation conditions, and BMAA induces the formation of heterocyst-like cells under nitrogen excess conditions, by causing the expression of heterocyst-specific genes that are usually “silent” under nitrogen-replete conditions, as if these bacteria receive a nitrogen deficiency intracellular molecular signal. In order to find out the molecular mechanisms underlying this unexpected BMAA effect, we studied the proteome of cyanobacterium Nostoc sp. PCC 7120 grown under BMAA treatment in nitrogen-replete medium. Experiments were performed in two experimental settings: (1) in control samples consisted of cells grown without the BMAA treatment and (2) the treated samples consisted of cells grown with addition of an aqueous solution of BMAA (20 µM). In total, 1567 different proteins of Nostoc sp. PCC 7120 were identified by LC-MS/MS spectrometry. Among them, 80 proteins belonging to different functional categories were chosen for further functional analysis and interpretation of obtained proteomic data. Here, we provide the evidence that a pleiotropic regulatory effect of BMAA on the proteome of cyanobacterium was largely different under conditions of nitrogen-excess compared to its effect under nitrogen starvation conditions (that was studied in our previous work). The most significant difference in proteome expression between the BMAA-treated and untreated samples under different growth conditions was detected in key regulatory protein PII (GlnB). BMAA downregulates protein PII in nitrogen-starved cells and upregulates this protein in nitrogen-replete conditions. PII protein is a key signal transduction protein and the change in its regulation leads to the change of many other regulatory proteins, including different transcriptional factors, enzymes and transporters. Complex changes in key metabolic and regulatory proteins (RbcL, RbcS, Rca, CmpA, GltS, NodM, thioredoxin 1, RpbD, ClpP, MinD, RecA, etc.), detected in this experimental study, could be a reason for the appearance of the “starvation” state in nitrogen-replete conditions in the presence of BMAA. In addition, 15 proteins identified in this study are encoded by genes, which are under the control of NtcA—a global transcriptional regulator—one of the main protein partners and transcriptional regulators of PII protein. Thereby, this proteomic study gives a possible explanation of cyanobacterium starvation under nitrogen-replete conditions and BMAA treatment. It allows to take a closer look at the regulation of cyanobacteria metabolism affected by this cyanotoxin