PREPARATION, CHARACTERIZATION AND STUDIES OF PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES OF DRUGS COATING LACTOSE IN FLUIDIZED BEDS

Objective: Study physicochemical properties and activity of biotechnological drugs coating lactose particles in fluidized beds for the development of a prospective approach of their identification. Methods: Lactose monohydrate as pharmaceutical excipient; affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma as a drug substance; Pilotlab fluid bed apparatus was used for lactose powder saturation with solutions of pharmaceutical substances to the point of granulation (pelletizing); inverse light scattering method (2D-LS) for analysis of micron vibrations frequency spectra of samples surfaces for light intensity distribution in time by values of d1, d2, d3 primary descriptors; low angel and dynamic laser light scattering (LALLS, DLS) methods for distribution of lactose-water (LW) supramolecular complexes into volume fractions (micron "size spectra"), using the Master Sizer 2000 instrument and Zeta Sizer Nano ZS instrument in the nanoscale; Spirotox method for research of biological activity to determine the activation energy (Ea) values of cell death in solutions of tested samples. Results: Changes in 2D-LS scattering time on sample surfaces, described by topological descriptors, made it possible to clearly differentiate the intact lactose from fluidized samples by specific corridors in coordinates di=F(t). The calculated activation energy (Ea) values of cell biosensor death process in solutions of drugs coating lactose allow to characterize the biological activity of it in the initial (by Ea increase) and activated state (by Ea decrease) after the creation of intra-laboratory transmucosal conditions. A unique dimensional spectrum of LW complexes in the nanoscale range was obtained by DLS. The differences between samples in the distribution of LW complexes in the size range from 1 µm to 125 µm was showed by LALLS. Conclusion: The developed approach, including Сhemometrics, laser and biotesting methods can be used for qualitative the analysis tasks as well as for analytical control of the fluidization process in cases where identifiable pharmaceutical substances are not distinguishable by traditional analytical methods

Innovative quality improvements in hotel services

The paper is devoted to the development of approaches for the improvement of quality of hotel services on innovative basis. It has been established that in the market of hotel services, innovations are being introduced successfully for the purpose of attracting as many customers as possible. All this ensures development of new technologies of constructing hotels, appearance of new market segments satisfying a diverse demand of visitors. It has been proved that to improve the quality of hotel services, it is necessary to develop a strategy and tactics of development of hotel business on innovative basis. It has been determined that introduction of innovations must be realised both at the level of the state and at the level of separate hotels. Further innovative growth will allow improving the quality of hotel services in the world market of hotel real estate. However, this is possible in case of normalization of the economic and political situation in the country and creation of conditions for investment attractiveness in hotel business.peer-reviewe

Strong 3D correlations in vortex system of Bi2212:Pb

The experimental study of magnetic flux penetration under crossed magnetic fields in Bi2212:Pb single crystal performed by magnetooptic technique (MO) reveals remarkable field penetration pattern alteration (flux configuration change) and superconducting current anisotropy enhancement by the in-plane field. The anisotropy increases with the temperature rise up to $T_m = 54 \pm 2 K$. At $T = T_m$ an abrupt change in the flux behavior is found; the correlation between the in-plane magnetic field and the out-of-plane magnetic flux penetration disappears. No correlation is observed for $T > T_m$. The transition temperature $T_m$ does not depend on the magnetic field strength. The observed flux penetration anisotropy is considered as an evidence of a strong 3D - correlation between pancake vortices in different CuO planes at $T < T_m$. This enables understanding of a remarkable pinning observed in Bi2212:Pb at low temperatures.Comment: 8 pages, 9 figure

ASCORBIС ACID DEGRADATION IN N, N-DIMETHYLFORMAMIDE SOLUTIONS

Objective: Investigate the mechanisms of L-ascorbic acid&nbsp;transforтmation and formation of coloured enamines in&nbsp;N, N-dimethyl-formamide&nbsp;solutions. Methods: An automatic polarimeter Atago POL-1/2 was used for polarimetric investigation. Electronic spectra were recorded by UV-spectrometer Cary 60 (Agilent). The statistical analysis was carried out using the OriginPro 9.1 packages. Results: The Biot’s law violation was found in below 0.1% solutions of&nbsp;L-ascorbic acid (AA)&nbsp;in&nbsp;N,&nbsp;N-dimethylformamide (DMF).&nbsp;During the day, the specific rotation&nbsp; &nbsp;of 1% AA solution varied from+37 to-1.0. Gradually, the solution acquired the red colour, and its intensity depended on the AA concentration. Spectrophotometrically, it was shown that after 15 min AA was absent in the n·10-3% solutions. The decomposition followed the first-order kinetics (k1=1.83·10-2с-1). At the same time, new absorption bands appeared at 273, 390, 533 nm. Model solutions containing dimethylamine (DMA) had a similar spectrum, and the intensity of the absorption bands increased in proportion to the concentration of DMA. Conclusion: The results show that the first step in the decomposition of ascorbic acid AA in DMF follows first-order kinetics. Numerous decomposition products are optically active compounds and reverse the sign of the optical rotation of the solution. The water resulting from the decomposition of AA is involved in the hydrolysis of the solvent. The hydrolysis product, the secondary amine DMA, interacts with the carbonyl groups of the AA decomposition products to form coloured enamines. Magnesium (II) accelerates the formation of coloured products

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

POLARIMETRIC RESEARCH OF PHARMACEUTICAL SUBSTANCES IN AQUEOUS SOLUTIONS WITH DIFFERENT WATER ISOTOPOLOGUES RATIO

Objective: Methodology development for quality control of optically active pharmaceutical substances based on water isotopologues. Methods: Solutions of L-ascorbic acid, glucose, galactose and valine stereoisomers were prepared using deuterium depleted water (DDW-«light» water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), heavy water (99.9% D2O). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. The size distribution of giant heterogeneous clusters (GHC) of water was recorded by low angle laser light scattering (LALLS) method. Results: The infringement of Biot's Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation Â&nbsp;at a concentration of below 0.1%, depends on the D/H ratio. The inequality was established in absolute values of optical rotation for L-and D-isomers of valine in solutions with different ratios of hydrogen isotopologues. The mutarotation of glucose confirmed the first-order kinetics, and the activation energies were statistically distinguishable for BD and DDW. The mutarotation of the natural galactose D-isomer proceeded with a lower energy consumption compared to the L-isomer. In heavy water, the mutarotation of monosaccharides had different kinetic mechanisms. Polarimetric results correlated with the number and size of GHC, which confirmed the possibility of chiral solvent structures induction by optically active pharmaceutical substances. Conclusion: In the optically active pharmaceutical substances quality control there should be considered the contribution of induced chiral GHC of water to the optical rotation value that depends on the isotopic D/H ratio, the substance nature and the form of its existence at a given pH

Малые ледники плато Путорана на фоне климатических перемен

The characteristic feature of the Putorana Plateau is that the glaciological objects here are mostly represented by small glaciers and perennial snow patches. Their regime and morphology have so much common features that separation of these two categories of nival glacial formations from one another is extremely difficult problem. The distinctions between results of earlier studies carried out in the 1970s (the USSR Glacier Inventory estimated local resources at 22 glaciers with a total area of 2.5 km2) and at the beginning of the current century (in 2005, V.A. Sarana identified 61 glaciers with a total area of 7 km2) are too large to make any reliable conclusions about the current trends of the Putoran glaciation. In such conditions, the materials of rare field monitoring work performed on individual nival-glacial bodies become very valuable. Three expedition seasons of 2002–2004 included thorough geodetic and mass-balance measurements on 3 reference objects on the northern ledge of Lama Mts. – Prives (No. 30) Glacier, Marlborough (No. 31) Glacier and Strudoms snow patch. Similar field monitoring was repeated in summer’2019. The change in their configuration according to digital photography data, including the results of the analysis of satellite images, make possible to reveal that interannual fluctuations in the area of each glacier occur due to different vector displacements of its different sections along their entire perimeters. In 2019, the somewhat unexpected good budget state of all 3 monitored objects was detected. It manifested itself in growth of their areas and increased fraction of firn basin as well as in larger water equivalent of the firn residue as this followed from results of snow surveys. This fact contradicts the previous conclusion about the steady trend of deglaciation on the Putorana Plateau. The favourable condition for small glaciers occurred here in 2019 was mainly caused by reduced ablation owing to the weakened insolation that resulted from tremendous forest fires in Siberia, remarkable by their abnormal intensity in this year.По итогам экспедиционных исследований снежников и ледников Ламских гор на плато Путорана в 2002–2004 и 2019 гг. для суждений об их современном состоянии получены новые сведения о режиме и эволюции малых форм оледенения на фоне климатических тенденций последних лет. В условиях неблагоприятных климатических перемен малые ледники плато Путорана демонстрируют большую устойчивость по сравнению с крупными ледниками и малыми формами оледенения, существующими в тёплой фирновой зоне льдообразования

Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD

Background: Lack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer’s disease (AD). Recent studies showed that ACD can also be reduced in the early stages. Methods: We described different trends of evolution of ACD over 3 years in a cohort of memory-complainers and their association to amyloid burden and brain metabolism. We studied the impact of ACD at baseline on cognitive scores’ evolution and the association between longitudinal changes in ACD and in cognitive score. Results: 76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a steadily heightened ACD and were comparable to those with accurate ACD in terms of demographic characteristics and AD biomarkers. 4.25% constantly showed low ACD, had significantly higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution and no association between longitudinal changes in ACD and in cognitive scores. Conclusions: ACD begins to decrease during the preclinical phase in a group of individuals, who are of great interest and need to be further characterized. Trial registration: The present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42