Phenomenological model of mechanoelectric transformations in rocks

A phenomenological model is proposed on the example of the rock destruction development in underground mines. The characteristics of the electromagnetic signal generated due to the appearance and change of the dipole moment of cracks, whose beads are charged when the discontinuity is disturbed, are analytically investigated. The model is constructed using the theory of reliability and percolation theory, which allows to take into account the non-synchronism of the mechanical converters

POST-COVID-19-syndrome in young healthy women: myth or reality?

Aim. To assess the incidence and severity of new persistent symptoms in somatically healthy young women with and without a history of COVID-19. Materials and methods. The main study group included patients who had PCR-confirmed COVID-19 in JulyOctober 2021 (n=181); the comparison group included women without COVID-19 during this period (n=71). Inclusion criteria: female sex, age 1835 years, no pregnancy, overweight/obesity, diabetes mellitus, chronic hypertension, premenstrual syndrome, and other somatic and/or chronic infectious diseases. Post-COVID syndrome (PCS) was diagnosed based on symptoms absent before COVID-19, appeared 4 weeks from the disease onset, and lasted at least 2 months, which could not be explained by alternative diagnoses. We used primary medical records and interviewed patients using a special questionnaire to develop a statistical database. The severity of symptoms was assessed using a 10-point scale. Results. New persistent symptoms during the pandemic in young, initially somatically healthy women with and without COVID-19 were reported with similar frequency: 96.1 and 93.0%, respectively (odds ratio OR 1.88, 95% confidence interval CI 0.586.14; p2=0.327). Only patients with COVID-19 reported cough (43.6%), shortness of breath (26.5%), chest pain (18.2%), weight loss (18.8%), hair loss (60.8%); in the comparison group, these symptoms were not reported; p20.001. Patients with PCS were more likely to experience memory impairment 49.2% vs 12.7% (OR 6.66, 95% CI 3.1314.21; p20.001); headache 43.1% vs 11.3% (OR 5.96, 95% CI 2.713.17; p20.001); depression 19.9% vs 8.5% (OR 2.69, 95% CI 1.086.7; p2=0.029); myalgia 31.5% vs 8.5% (OR 4.98, 95% CI 2.0412.17; p20.001). Patients of both groups showed similar frequency of fatigue (69.0% vs 71.8%; p2=0.66), drowsiness (54.9% vs 43.6%; p2=0.11), palpitations (19.7% vs 29.8%; p2=0.1), menstrual cycle changes (22.5% vs 21.0%; p2=0.865), and skin manifestations (2.8% vs 6.6%; p2=0.24). COVID-19 survivors had a more pronounced memory impairment (4.0 vs 1.0 points; p0.001), headache (5.0 vs 3.0 points; p=0.001), myalgia (5.0 vs 1.0 points; p0.001) and less severe insomnia (3.0 vs 5.0 points; p=0.004). Conclusion. The PCS symptoms are common in initially somatically healthy women of early reproductive age. Similar symptoms in women with no history of COVID-19 may be due to post-traumatic stress anxiety disorder. Further interdisciplinary research is needed to identify the pathophysiological mechanisms for the occurrence of new persistent symptoms in different age and social groups during the COVID-19 pandemic

Determination of Folic Acid in Multivitamin Preparations by Reversed Phase HPLC

A great variety of components in multivitamin preparations containing folic acid, and a variety of test methods and conditions of folic acid determination proposed by manufacturers, require alignment of test procedures for products with similar composition.The aim of the study was to compare the results of experimental verification of folic acid determination procedures which use reversed phase high-performance liquid chromatography (RP HPLC) with isocratic elution mode. Materials and methods: The Agilent 1260 Infinity II LC system with a diode array detector (280 nm), isocratic elution mode, C8- and C18-bonded silica gel chromatographic columns, model mixtures containing folic acid, cyanocobalamin, ferrous sulfate, and potassium iodide, were used in the study.Results: The lowest relative standard deviation of the folic acid peak area (RSD=0.09%), and the lowest asymmetry factor (As=1.04) for folic acid were observed for the model mixture “ferrous sulfate+folic acid+cyanocobalamin” and the following test conditions. Column: 250×4.0 mm, silica gel for chromatography, octylsilyl (C8), endcapped; mobile phase:  methanol‒phosphate buffer (12:88), pH 6.6; column temperature: 25ºС. The study demonstrated the feasibility of using these conditions for determination of pteroic acid impurity with simultaneous precipitation of interfering ferrous ions, using ethylenediaminetetraacetic acid solution, pH 9.5, as a solvent.Conclusions: RP HPLC can be recommended as an optimal aligned test procedure for determination of folic acid in combination products. It is recommended to use a solution containing folic and pteroic acids for system suitability testing

Современные подходы к разработке проектов общих фармакопейных статей и фармакопейных статей на препараты крови человека

Blood products were first represented in the State Pharmacopoeia of the USSR IX and X editions (1961 and 1968) by a single monograph "Gamma globulin for the prevention of measles". During the next 50 years there were no general monographs (GM) or individual monographs (IM) in the State Pharmacopoeia of the Russian Federation that laid down regulatory requirements for the quality of human blood products. In this regard, there came a need to develop GMs and IMs on human blood products taking into account modern approaches, specific features of a complex multi-level production technology and modern harmonized requirements for blood products, ensuring their quality, efficacy and safety in humans. The Order of the Ministry of Health of the Russian Federation "On the adoption of general monographs and individual monographs” No. 768 of 21.11.2014 brought into effect 32 GMs and IMs on blood products, including 11 GMs and 5 IMs that have been introduced into the national pharmacopoeial texts for the first time. The monographs were developed with due regard to modern pharmacopoeial methods of analysis that account for a high level of quality control of this type of products.Впервые препараты крови были представлены одной фармакопейной статьей в Государственных фармакопеях СССР IX и Х изданий (1961 г. и 1968 г.) под названием «Гамма-глобулин для профилактики кори». В дальнейшем, на протяжении 50 лет ОФС и ФС, регламентирующие требования к качеству препаратов крови человека не были представлены в Государственных фармакопеях РФ. В связи с этим, назрела необходимость разработки ОФС и ФС на препараты крови человека с учетом современных подходов, особенностей сложной многоуровневой технологии производственного процесса и современных гармонизированных требований к препаратам крови, обеспечивающих гарантированность их качества, эффективность и безопасность для человека. Приказом МЗ РФ «Об утверждении общих фармакопейных статей и фармакопейных статей от 21.11.2014 г. № 768. утверждены 32 ОФС и ФС по препаратам крови, из них 11 ОФС и 5 ФС впервые введены в практику отечественного фармакопейного анализа. Статьи составлены с учетом с использования современных методов фармакопейного анализа, обуславливающих соответствующий уровень оценки качества данной группы препаратов

Анализ фолиевой кислоты в поливитаминных препаратах методом обращенно-фазовой ВЭЖХ

A great variety of components in multivitamin preparations containing folic acid, and a variety of test methods and conditions of folic acid determination proposed by manufacturers, require alignment of test procedures for products with similar composition.The aim of the study was to compare the results of experimental verification of folic acid determination procedures which use reversed phase high-performance liquid chromatography (RP HPLC) with isocratic elution mode. Materials and methods: The Agilent 1260 Infinity II LC system with a diode array detector (280 nm), isocratic elution mode, C8- and C18-bonded silica gel chromatographic columns, model mixtures containing folic acid, cyanocobalamin, ferrous sulfate, and potassium iodide, were used in the study.Results: The lowest relative standard deviation of the folic acid peak area (RSD=0.09%), and the lowest asymmetry factor (As=1.04) for folic acid were observed for the model mixture “ferrous sulfate+folic acid+cyanocobalamin” and the following test conditions. Column: 250×4.0 mm, silica gel for chromatography, octylsilyl (C8), endcapped; mobile phase:  methanol‒phosphate buffer (12:88), pH 6.6; column temperature: 25ºС. The study demonstrated the feasibility of using these conditions for determination of pteroic acid impurity with simultaneous precipitation of interfering ferrous ions, using ethylenediaminetetraacetic acid solution, pH 9.5, as a solvent.Conclusions: RP HPLC can be recommended as an optimal aligned test procedure for determination of folic acid in combination products. It is recommended to use a solution containing folic and pteroic acids for system suitability testing.Поливитаминные препараты, содержащие фолиевую кислоту, значительно различаются по своему составу. Предлагаемые производителями методы и условия анализа фолиевой кислоты также различаются, в связи с чем необходима унификация методик анализа фолиевой кислоты для близких по составу препаратов.Цель работы: сравнение результатов апробации методик анализа фолиевой кислоты в поливитаминных препаратах методом обращенно-фазовой высокоэффективной жидкостной хроматографии в изократическом режиме подачи подвижной фазы.Материалы и методы: хроматограф жидкостный Agilent 1260 Infinity II LC с диодно-матричным детектором, аналитическая длина волны 280 нм. Колонки хроматографические с неподвижной фазой на основе силикагеля с привитыми группами С8 и С18. Режим подачи подвижной фазы – изократический. Модельные смеси, содержащие фолиевую кислоту, цианокобаламин, железа сульфат и калия йодид.Результаты: наименьшие значения относительного стандартного отклонения площади пика фолиевой кислоты (RSD = 0,09%) и фактора асимметрии пика (As = 1,04) отмечены при анализе модельной смеси «железа сульфат+фолиевая кислота+цианокобаламин» на колонке 250×4,0 мм с силикагелем октилсилильным (С8) эндкепированным с использованием в качестве подвижной фазы смеси метанол – фосфатный буферный раствор pH 6,6 (12:88) при температуре 25 ºС. Показана возможность одновременного определения примеси птероевой кислоты в данных условиях анализа и осаждения мешающих ионов железа при использовании в качестве растворителя пробы раствора, содержащего этилендиаминтетрауксусную кислоту, с рН 9,5. Выводы: при выборе оптимальной унифицированной методики анализа фолиевой кислоты в комплексных препаратах можно рекомендовать метод обращенно-фазовой высокоэффективной жидкостной хроматографии. Для проверки пригодности хроматографической системы рекомендуется использовать раствор, содержащий фолиевую и птероевую кислоты

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6;

The history of development of Pharmacopoeia standards quality biological drugs and methods of tests in Russia

The Russian system of standardization of HP including biological medicines is based on the State Pharmacopoeia of the Russian Federation numbering more than the 250th summer history of the development. Requirements of general the farmakopoeia and the farmakopoeia of articles included in the State Pharmacopoeia of the Russian Federation are obligatory for all organizations which are engaged in the territory of the Russian Federation in production, production, quality control, storage and use of medicines. Historical development the farmakopoeia of the quality standards on biological medicines is reflected in article, starting with the first publications of articles editions (1910) and to GF Programme of the Russian Federation editions (2015) in which are provided are included in GF VI of Russia 57 OFS and 56 FS on the biological medicines allowing to provide standardization of requirements to their quality. Further enhancement and development of various directions in the immunobiology, immunobiological technologies which are based on a joint of immunology and molecular biology, and also genetic engineering and as a result of it, development of new BLP requires further development and the standardization of these HP guaranteeing their quality at all stages of lifecycle

Modern approaches to drafting general and individual monographs on human blood products

Blood products were first represented in the State Pharmacopoeia of the USSR IX and X editions (1961 and 1968) by a single monograph "Gamma globulin for the prevention of measles". During the next 50 years there were no general monographs (GM) or individual monographs (IM) in the State Pharmacopoeia of the Russian Federation that laid down regulatory requirements for the quality of human blood products. In this regard, there came a need to develop GMs and IMs on human blood products taking into account modern approaches, specific features of a complex multi-level production technology and modern harmonized requirements for blood products, ensuring their quality, efficacy and safety in humans. The Order of the Ministry of Health of the Russian Federation "On the adoption of general monographs and individual monographs” No. 768 of 21.11.2014 brought into effect 32 GMs and IMs on blood products, including 11 GMs and 5 IMs that have been introduced into the national pharmacopoeial texts for the first time. The monographs were developed with due regard to modern pharmacopoeial methods of analysis that account for a high level of quality control of this type of products

История разработки фармакопейных стандартов качества на биологические лекарственные препараты и методы испытаний в России

The Russian system of standardization of HP including biological medicines is based on the State Pharmacopoeia of the Russian Federation numbering more than the 250th summer history of the development. Requirements of general the farmakopoeia and the farmakopoeia of articles included in the State Pharmacopoeia of the Russian Federation are obligatory for all organizations which are engaged in the territory of the Russian Federation in production, production, quality control, storage and use of medicines. Historical development the farmakopoeia of the quality standards on biological medicines is reflected in article, starting with the first publications of articles editions (1910) and to GF Programme of the Russian Federation editions (2015) in which are provided are included in GF VI of Russia 57 OFS and 56 FS on the biological medicines allowing to provide standardization of requirements to their quality. Further enhancement and development of various directions in the immunobiology, immunobiological technologies which are based on a joint of immunology and molecular biology, and also genetic engineering and as a result of it, development of new BLP requires further development and the standardization of these HP guaranteeing their quality at all stages of lifecycle.Российская система стандартизации ЛС, в том числе, биологических лекарственных препаратов базируется на Государственной Фармакопее Российской Федерации, насчитывающей более чем 250-летнюю историю своего развития. Требованиями общих фармакопейных и фармакопейных статей, включенных в Государственную Фармакопею Российской Федерации, руководствуются организации, занимающихся на территории РФ производством, изготовлением, контролем качества, хранением и применением лекарственных средств. В статье отражено историческое развитие фармакопейных стандартов качества на биологические лекарственные препараты, начиная с первых публикаций статей в ГФ России VI издания и до ГФ РФ XIII издания, в которой представлено 55 ОФС и 54 ФС на биологические лекарственные препараты, позволяющие обеспечить унификацию требований к их качеству. Дальнейшее совершенствование и развитие различных направлений в иммунобиологии, иммунобиологических технологиях, базирующихся на стыке иммунологии и молекулярной биологии, а также генной инженерии и, как следствие этого, разработка новых БЛП требует дальнейшего развития и стандартизации этих ЛС, гарантирующих их качество на всех этапах жизненного цикла