Sclerostin antibodies as novel anabolic therapy for osteoporosis

Osteoporosis medications are dividedinto two groups: those inhibiting bone resorption and formation (bisphosphonates and denosumab), and those stimulating bone formation i.e. having an anabolic effect. The latter include teriparatide, parathyroid hormone 1-84 and abaloparatide, all of which stimulate bone resorption as well as bone formation, which limits their anabolic effect. The discovery of sclerostin the key inhibitor of bone formation has led to development of the concept that inhibition of this protein could stimulate bone formation. Romosozumab is a human monoclonal antibody to sclerostin that binds to sclerostin and enables Wnt-signaling pathway ligands and their co-receptors to interact with each other, which, in turn, leads to increased bone formation and bone mineral density. Unlike classical anabolic drugs in osteoporosis treatment, romosozumab stimulates bone formation and inhibits bone resorption. In clinical trials, romosozumab showed marked increase in lumbar spine and hip bone mineral density. Presented article contains information about pre-clinical and clinical studies of romosozumab

Comparative analysis of the DNA isolated from thyme leaves using different methods

Background. The base for a molecular analysis is DNA of high quality. For DNA isolation, different kits or classical methods are used. For mass analysis, isolation with kits is a very expensive process. So, the objective of our investigation was to find a cheap method for high-quality DNA isolation from leaves of various thyme cultivars.Materials and methods. Leaves cut from thyme accessions (Thymus mastichina L. cv. ‘Svetliachok’, T. striatus Vahl. cv. ‘Jubileiniy’, T. vulgaris L. cv. ‘Fantasia’, and T. vulgaris cv. ‘Jalos’.) maintained ex situ in the collection of the Nikita Botanical Gardens were used as the material for the analysis. Light microscopy was used to study leaf anatomy and localize essential oil on leaf cross sections. Essential oil was extracted on Ginsberg devices, and phenolic content was measured with The Folin–Ciocâlteu reagent (FCR). Commercial kits (DiamondDNATM, PureLink® Plant Total DNA Purification Kit) and classical methods (CTAB, CTAB with 2% polyvinylpyrrolidone) were used for DNA isolation. DNA quality was evaluated spectrophotometrically, with electrophoresis (horizontal, automated system Agilent 4200 TapeStation) and PCR.Results. The analysis showed that the leaf blade mesophyll of four thyme cultivars had inclusions with essential oil. The content of essential oil and phenolic compounds was measured biochemically. Since the plants were characterized by the presence of secondary metabolites, DNA was isolated by different methods. Spectrophotometry demonstrated that the classical CTAB method and CTAB with 2% PVP provided the best results. Using an automated electrophoresis system, the presence of high-molecularweight DNA (more than 52000 bp) in significant amounts was detected in the samples isolated with DiamondDNATM kit and CTAB + 2% PVP.Conclusion. Among the tested kits and methods, CTAB + 2% PVP provided thyme DNA suitable for PCR and, presumably, for genome library preparation. The low cost of reagents for this technique makes it applicable for future mass analysis of plant material

Reference materials of catalytic activity as a means of ensuring the metrological traceability of measurement results. KATAL

Introduction. The article considers the problems of metrological support of catalytic activity measurements. The paper gives certain characteristics of the State Primary Special Measurement Standard for the unit of catalytic activity – KATAL and examines the role of reference materials (RMs) in ensuring the metrological traceability of measurement results.Materials and methods. A method for measuring the concentration of the recombinant protective antigen of Bacillus anthracis and the recombinant GP-protein of the Ebola virus, which means in using «sandwich» enzyme-linked immunosorbent assay, was certified by FGUP «VNIIMS» as a measurement procedure. The following RMs tested by FGUP «VNIIMS» can be used for the development and production of appropriate control samples when performing measurements for comparisons: the RM for the mass concentration of the recombinant protective antigen of Bacillus anthracis in phosphate-saline solution, the RM for the mass concentration of the recombinant GP-protein of the Ebola virus, and the RM for the mass concentration of recombinant Clostridium Difficile toxin.Results. The paper presents the main reactions of the method for measuring the catalytic activity of catalysts for heterogeneous processes, which are also used to carry out exhaust gas cleaning processes.Discussion and conclusions. Thus, conditions have been created for building hierarchies of calibrations of in-demand objects established on the basis of the List of Critical Technologies of the Russian Federation, state programs for the development of industrial sectors

PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY OF THE NEW ANTIVIRAL SUBSTANCE

Objective: To develop a set of quality control procedures for the promising antiviral pharmaceutical substance L-histidyl-1-adamantylethylamine dihydrochloride monohydrate, a derivative of rimantadine. Methods: Substances and solvents: synthesized in laboratory L-histidyl-1-adamantylethylamine dihydrochloride monohydrate (H-His-Rim•2HCl•H2O), rimantadine hydrochloride (Rim•HCl), 99%, ethanol 96%, N, N-dimethylformamide (DMF) anhydrous, 99.8% and n-hexane anhydrous, 95%, deionized high-resistance water (18.2 MΩ•cm at 25 °C, Milli-Q system), silver nitrate. Infrared (IR) Spectroscopy–Cary 630 Fourier Transform IR Spectrometer, elemental analysis–elemental composition analyzer CHNS-O EuroEA3000, ultraviolet (UV) spectrometry–Cary-60 spectrophotometer, polarimetry–POL-1/2 polarimeter with an external Peltier module, granulometric analysis by optical microscopy (Altami BIO 2 microscope) and low-angle laser light scattering (LALLS)–Master Sizer 3600, measurement of potential for hydrogen–potentiometer PB-11, Spirotox method–the study of temperature dependences of Spirostomum ambiguum lifetime to characterize the biological activity of the studied compounds. Results: The substance H-His-Rim•2HCl•H2O is an amorphous yellowish powder, slightly soluble in water, soluble in ethanol, freely soluble in N, N-dimethylformamide, and practically insoluble in n-hexane. A study of the elemental composition has confirmed the authenticity of H-His-Rim•2HCl•H2O. Comparison of the spectral characteristics of H-His-Rim•2HCl•H2O and Rim•HCl by IR spectroscopy and UV spectrometry confirmed the authenticity of the substance. The racemic form of the substance Rim•HCl with an insignificant amount of impurity of the levorotatory enantiomer was proved polarimetrically: α =-0.0126±0.0003 (1% aqueous solution, 20±0.5 °С). The specific optical rotation of 1% aqueous solution H-His-Rim•2HCl•H2O . In 1% ethanol solution -10.32±0.12. Using the method of laser light diffraction for a substance H-His-Rim•2HCl•H2O, the dimensional spectra «fraction of particles, %-d, μm» were characterized, the maximum of which in hexane is in the region of 40–50 μm. Arrhenius’s kinetics on the Spirotox model established statistically significant differences in ligand-receptor interactions, which are characterized by values of observed apparent activation energy °bsEa, kJ/mol: 132.36±1.55 for H-His-Rim•2HCl•H2O and 176.15±0.48 for Rim•HCl. Conclusion: The developed set of methods for assessment of physical and chemical properties and biological activity of a new antiviral substance H-His-Rim•2HCl•H2O is the basis for establish of regulatory documentation

Synthesis and properties of novel polyurethanes based on amino ethers of boric acid for gas separation membranes

© The Royal Society of Chemistry. Herein we present the structural and mechanical properties of polyurethanes synthesized from amino ethers of boric acid for gas separation. The polymers were characterized by light scattering methods, conductivity measurements, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and atomic force microscopy. Additionally, the permeability of ammonia and carbon dioxide, as well as the selectivity for their diffusion and resultant impurity are presented. The results illustrate the steric hindrance, resulting in a branched architecture borate formation, leads to intermolecular complexation which may assist the polymer in ammonia diffusion selectivity

First description of a type v osteogenesis imperfecta clinical case with severe skeletal deformities caused by a mutation p.119C> T in IFITM5 gene in Russia

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. Main clinical manifestations include recurring pathological fractures and progressive skeletal deformation. Five types of OI are distinguished based on clinical symptoms. In most cases, the disease is caused by mutations in the COL1A1 and COL1A2 genes, leading to a defect of type 1 collagen synthesis, which is the main component of the bone matrix. Up to 5% of patients with OI have a mutation in IFITM5 gene, which leads to the development of OI type V. Approximately 150 cases of the OI type V are described in the literature, and mutation c.-14C T in IFITM5 gene is found in most of the cases. Only 5 patients have a c.119C T: p.S40L.mutation. Pathogenesis of OI type V is not fully understood. It is assumed that mutations in the IFITM5 gene cause impaired osteoblastogenesis, decreased bone mineral density and multiple low-traumatic fractures. There is probably a phenotype-genotypic correlation in cases with different mutations of the IFITM5. However, it is currently difficult to assess the relationship in view of the variability of the characters and the low prevalence of the OI type V. We present the first description in Russia of the clinical case of an adult patient with OI type V due to a rare mutation p.119C T: p.S40L in the IFITM5 gene

Стандартные образцы каталитической активности как средство обеспечения метрологической прослеживаемости результатов измерений. КАТАЛ

Introduction. The article considers the problems of metrological support of catalytic activity measurements. The paper gives certain characteristics of the State Primary Special Measurement Standard for the unit of catalytic activity – KATAL and examines the role of reference materials (RMs) in ensuring the metrological traceability of measurement results.Materials and methods. A method for measuring the concentration of the recombinant protective antigen of Bacillus anthracis and the recombinant GP-protein of the Ebola virus, which means in using «sandwich» enzyme-linked immunosorbent assay, was certified by FGUP «VNIIMS» as a measurement procedure. The following RMs tested by FGUP «VNIIMS» can be used for the development and production of appropriate control samples when performing measurements for comparisons: the RM for the mass concentration of the recombinant protective antigen of Bacillus anthracis in phosphate-saline solution, the RM for the mass concentration of the recombinant GP-protein of the Ebola virus, and the RM for the mass concentration of recombinant Clostridium Difficile toxin.Results. The paper presents the main reactions of the method for measuring the catalytic activity of catalysts for heterogeneous processes, which are also used to carry out exhaust gas cleaning processes.Discussion and conclusions. Thus, conditions have been created for building hierarchies of calibrations of in-demand objects established on the basis of the List of Critical Technologies of the Russian Federation, state programs for the development of industrial sectors.Введение. В данной статье рассматриваются вопросы метрологического обеспечения измерений каталитический активности. Приведены характеристики Государственного первичного специального эталона единицы каталитической активности – КАТАЛ. Рассмотрена роль стандартных образцов в обеспечении метрологической прослеживаемости результатов измерений.Материалы и методы. Метод измерений концентрации рекомбинантного протективного антигена Bacillus anthracis и рекомбинантного белка GP вируса Эбола, заключающийся в использовании «сэндвич» варианта иммуноферментного анализа, аттестован ФГУП «ВНИИМС» в качестве методики измерений. Испытанные ФГУП «ВНИИМС» стандартные образцы массовой концентрации рекомбинантного протективного антигена Bacillus anthracis в фосфатно-солевом растворе, массовой концентрации рекомбинантного белка GP вируса Эбола и массовой концентрации рекомбинантного токсина Clostridium Difficile могут применяться для разработки и производства соответствующих контрольных образцов, при проведении измерений для сличений.Результаты исследования. Приведены основные реакции метода измерений каталитической активности катализаторов гетерогенных процессов, которые применяются и для осуществления процессов очистки выхлопных газов.Обсуждения и заключения. Таким образом, созданы условия для построения иерархий калибровок востребованных объектов, установленных на основе Перечня критических технологий Российской Федерации, государственных программ развития отраслей промышленности

THE EFFECT OF AIR TEMPERATURE AND DURATION OF SOLAR ILLUMINATION ON ANTHOCYANIN ACCUMULATION IN CHERRY PLUM FRUITS WITH VARIOUS MATURATION PERIODS

The article presents the data of a long-term research on the effect of air temperature and sunshine duration on the increase in anthocyanin content in the fruits of cherry plum varieties with different maturation periods and on their coloration degree. It is shown that the duration of sunshine is inversely associated with anthocyanin accumulation, which indicates the possibility of biosynthesis of these pigments under reduced illumination. Correlations between the accumulation of anthocyanins and daytime, night, and total air temperatures were absent