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

INVESTIGATION OF SORPTION CHARACTERISTICS OF POLYMERIC MINERAL-FILLED COMPOSITES FOR MEDICINE

The polymer compositions on the base of acrylic derivatives and bentonite particles modified by silver ions with various share and dispersion are received and studied by radical polymerization in the water. Partially neutralized acrylic acid, acrylamide and methylene-bis-acrilamide and particles of bentonite with fraction 0 - 0,05 mass.% are chosen as initial substances. The influence of bentonite concentration on absorbing characteristics of polymer materials in the distilled water is shown. It is demonstrated that the increase of bentonite fraction up to 5 mass.% leads to the rise of degree of equilibrium swelling by 1,5 – 2 times in comparison with an unfilled polymer matrix. The acrylic nanocompositions with a mass fraction of bentonite equal to 0,01 mass.% possess the greatest kinetic characteristics. Kinetic dependences of new composite materials swelling in physiological solution from a filler dispersion part are investigated. It is shown that in high dispersion (with particle size less than 0,25 mm) a part of mineral–containing filler equal to 1 mass.% leads to significant increase in values of equilibrium swelling degree in comparison with an unfilled sample (by 1,5 times). The effect of polyelectrolyte suppression of polymer composition swelling in physiological solution is studied. It results in values reduction of equilibrium swelling degree in comparison with these values in the distilled water. Application prospects for the received compositions are shown at bandages creation for wounds treatment of various etiologies. Research results are recommended for usage in medical practice for optimization of wound process march

Эффективность распределённого внесения азота на луке репчатом (Allium cepa L.) в однолетней культуре

Relevance. Onions in Russia in 2021: Cultivation area – 56.3 thousand hectares; Productivity – 28.6 t/ha; Production – 1608.6 thousand tons; Import from the volume of consumption – 10.7%. Modern varieties and hybrids and plant protection products make it possible to obtain high yields in the conditions of the Non-chernozem zone. The aim of the research is to optimize the parameters and terms of technological operations for the cultivation of onion in an annual crop on alluvial meadow soils of the Non-Chernozem Zone.Materials and methods. The nutrition system of onion plants was tested through distributed nitrogen application during the growing season: Option 1 – (N160P160K160) presowing – (Ca40N10 + K40N20 + K40N20) during the growing season; Option 2 – (N110P110K110) presowing + (Ca40N20 + K40N40 + K40N40) during the growing season. Experience in the use of the microbiological preparation Bisolbi-Plant (Bacillus pumilis) BIS88 together with the 1% humic preparation "Rostok" at a rate of one liter per hectare each to stimulate active growth.Results. At the end of the growing season in the second variant of the nitrogen experiment, the growing season was extended by 7-10 days. The excess yield under the second option for 2021-22 years of research amounted to more than 20.0 t/ha and is significant. The difference in the options for applying the Bisolbi-Plant preparation in 2.8 t/ha with HCP05 – 8.2 t/ha was not significant. The advantage of the variant with the biological preparation is higher plant density by 71.0 thousand units/ha and the absence of signs of bacteriosis. Thus, the distributed application of nitrogen (N110P110K110) presowing + (Ca40N20 + K40N40 + K40N40) during the growing season with irrigation water was significantly more effective than (N160P160K160) presowing + (Ca40N20 + K40N20 + K40N20) during the growing season. There was a tendency to increase the yield and quality of products with the double application of Bisolbi-Plant (BIS88) at a rate of (1.0 + 1.0) l/ha.Актуальность. Репчатый лук в России в 2021 году: Площадь возделывания – 56,3 тыс. га; Урожайность – 28,6 т/га; Производство – 1608,6 тыс. тонн; Импорт от объёма потребления– 10,7%. Современные сорта и гибриды и средства защиты растений дают возможность получить высокие урожаи в условиях Нечернозёмной зоны. Целью исследований является оптимизации параметров и сроков технологических операций по возделыванию лука репчатого в однолетней культуре на аллювиальных луговых почвах Нечерноземной зоны.Материалы и методы. Была проведена отработка системы питания растений лука посредством распределённого внесения азота в период вегетации: Вариант 1 (N160P160K160) предпосевное +(Ca40 N10 + K40N20 + K40N20) в процессе вегетации; Вариант 2 (N110P110K110) предпосевное +(Ca40 N20 + K40N40 + K40N40) в процессе вегетации. Опыт по применению микробиологического препарата Бисолби-Плант (Bacillus pumilis) BIS88 совместно с гуминовым 1% препаратом «Росток» нормой один литр на гектар каждого для стимуляции активного роста.Результаты. В конце вегетации во втором варианте опыта по азоту имело место продление срока вегетации на 7-10 дней. Превышение урожайности по второму варианту за 2021-22 годы исследований составило более 20,0 т/га и является существенным. Разница по вариантам внесения препарата Бисолби-Плант в 2,8 т/га при НСР05= 8,2 т/га не явилась достоверной. Преимущество варианта с биопрепаратом в более высокой на 71,0 тыс. шт/га густоте стояния растений и отсутствие признаков бактериоза. Таким образом, распределённое внесение азота (N110P110K110) предпосевное +(Ca40N20 + K40N40 + K40N40) в процессе вегетации с поливной водой достоверно оказалось более эффективным, чем (N160P160K160) предпосевное +(Ca40N20 + K40N20 + K40N20) в процессе вегетации. Зафиксирована тенденция увеличения урожайности и качества продукции при двойном внесении препарата Бисолби-Плант (BIS88) нормой (1,0 + 1,0) л/га

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  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

Перинатальные факторы программирования девиаций физического развития преждевременно родившихся младенцев

The analysis of obstetric anamnesis and indicators of heart rate variability in the neonatal period in prematurely born children who had deviations of somatometric parameters from reference values at the age of 12 months was carried out. Excessive due to various reasons, the level of adrenomimetics supplied with maternal blood caused an increase in the intensity of metabolism in the fetal body and inhibition of the activity of sympathoadrenal systems. The insufficient provision of the fetal and newborn organism with energy and plastic materials that arose under these conditions initiated perinatal metabolic programming of deviations in the physical development of prematurely born infants.Материалы и методы. Проводился анализ акушерского анамнеза и показателей вариабельности сердечного ритма в неонатальном периоде у преждевременно родившихся детей, имевших отклонения соматометрических показателей от референсных значений в возрасте 12 месяцев.Результаты. Избыточный вследствие различных причин уровень адреномиметиков, поступавших с материнской кровью, вызывал в организме плода повышение интенсивности метаболизма и ингибирование активности симпатоадреналовых систем. Возникавшее в этих условиях недостаточное обеспечение организма плода и новорожденного энергетическими и пластическими материалами инициировало перинатальное метаболическое программирование девиаций физического развития преждевременно родившихся младенцев

ОСОБЕННОСТИ АНЕСТЕЗИОЛОГИЧЕСКОГО ПОСОБИЯ ПРИ ПРОВЕДЕНИИ ОПЕРАЦИЙ С НЕЙРОМОНИТОРИНГОМ ВОЗВРАТНЫХ ГОРТАННЫХ НЕРВОВ В ТИРЕОИДНОЙ ХИРУРГИИ

The literature review describes the specifics of anesthesia when performing surgeries on the thyroid and parathyroid glands with neuromonitoring of recurrent laryngeal nerves. This technique has been described, the rationale of its use and role of the anesthesiologist in the provision of full functioning of neuromonitoring have been investigated. The article describes the anesthesia techniques (choice of neuromuscular relaxant, hypnotic and analgesic agents), method of endotracheal tube insertion, electrode positioning, causes of potential failures and ways of their management. В обзоре литературы рассмотрены особенности анестезии при проведении операций на щитовидных и паращитовидных железах с использованием нейромониторинга возвратных гортанных нервов. Приведено описание метода, изучены актуальность его применения и роль анестезиолога в обеспечении полноценного функционирования нейромониторинга. Освещены методики анестезии (выбор миорелаксантов, гипнотиков и анальгетиков), техника установки эндотрахеальной трубки, позиционирования электрода, причины возможных неудач и способы их исправления.

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

Бактериальные инфекции у пациентов детского и подросткового возраста после трансплантации аллогенных гемопоэтических стволовых клеток: этиология, структура, факторы риска

155 children and adolescents who had been diagnosed oncohematological diseases and had undergone allogeneic hemapoetic stem cell transplantation were examined. In post-transplant period 80% of patients developed different bacterial complications. Main risk factors of bacterial infections were acute leukemia (73%), acute «graft versus host disease» (61%), severe infectious complications before HSCT (30%), cytomegaloviral reactivation (51%). Main causative agents were Kl. pneumoniae (15%), Escherichia coli (8%), Enterobacter sp. (7%), Pseudomonas sp. (6,5%), Enterococcus sp. (16,5%), S.еpidermidis (13,5%). Most frequent involved sites are urinary tract (30,6%), lungs (22,5%) and bacteriemia (38,7%). Rise in ciprofloxacin resistans among Entorobactri, aerobic and Gram-positive cocci. General survival rate of patients with bacterial complications was 36,3% (p<0,001). Number of infectious episodes and their severity were statistically significant (both p<0,001) deteriorating factor for general surviral rate.Обследовано 155 пациентов детского и подросткового возраста со злокачественными заболеваниями системы крови после трансплантации аллогенных гемопоэтических стволовых клеток (алло-ТГСК). У 80% больных на разных этапах после алло-ТГСК развились бактериальные осложнения различной степени тяжести. Основными факторами риска бактериальных инфекций были диагноз острого лейкоза (73%), развитие острой «реакции трансплантат против хозяина» (61%), тяжелые инфекционные осложнения в анамнезе до трансплантации (30%), реактивация цитомегаловирусной инфекции (51%). Основные возбудители: Kl. pneumoniae (15%), Escherichia coli (8%), Enterobacter sp. (7%), Pseudomonas sp. (6,5%), Enterococcus sp. (16,5%), S. еpidermidis (13,5%). Наиболее часто возникает поражение мочевыводящих путей (30,6%), легких (22,5%) и бактериемия (38,7%). Отмечен рост резистентности к ципрофлоксацину среди энтеробактерий, аэробной и грам-положительной кокковой флоры. Общая выживаемость больных с развившимися бактериальными осложнениями составила 36,3% (p<0,001). Статистически значимо ухудшает показатели общей выживаемости больных с бактериальными инфекциями количество инфекционных эпизодов (p<0,001) и их тяжесть (p<0,001)

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD)