Р-стереогенні діамандоїдні фосфіни

Despite diamondoid phosphines have found many synthetic applications and are even available commercially the chemistry of chiral diamondoid phosphines remains largely unexplored.Aim. To develop the convenient preparative method for the preparation of sterically-congested P-stereogenic secondary diamodoidyl phosphines as potential organocatalysts and ligands in the asymmetric synthesis.Results and discussion. A convenient method for the synthesis of P-stereogenic diamondoid phosphines with high yields through the phosphorylation of hydroxydiamondoids in trifluoroacetic acid followed by the reduction of the corresponding asymmetric chlorophosphonates has been proposed. The secondary phosphines obtained form stable complexes with borane that can be used to separate diamondoid phosphines into enantiomers.Experimental part. The experimental procedures for the preparation of 1- and 4-diamantyl-1-adamantyl- and phenylphosphines were developed; the structures of new compounds were confirmed by NMR and HRMS spectral data.Conclusions. A number of P-stereogenic mixed diamondoidylaryl phosphines and the secondary phosphines containing exclusively diamondoid substituents has been prepared. A degree of steric bulkiness is determined by the combination of diamondoid substituents around a phosphorus atom where 1-diamantyl derivatives are the most sterically-congested. The compounds obtained are potential ligands in asymmetric catalysis.Received: 31.03.2020Revised: 24.06.2020Accepted: 27.08.2020Незважаючи на те, що діамандоїдні фосфіни широко використовуються в органічному синтезі і навіть доступні комерційно, хімія хіральних діамандоїдних фосфінів залишається не дослідженою.Мета. Розробити зручний препаративний метод синтезу стереоускладнених Р-стереогенних вторинних діамандоїдних фосфінів, які можуть бути використані як ліганди в асиметричному синтезі, а також як органокаталізатори.Результати та їх обговорення. Запропоновано зручний метод синтезу P-стереогенних діамандоїдних фосфінів шляхом фосфорилювання гідроксипохідних діамандоїдів у трифтороцтовій кислоті з подальшим відновленням відповідних асиметричних хлорофосфонатів з високими виходами. Одержані таким чином фосфіни утворюють стійкі комплекси з бораном, які розглядаються як проміжні сполуки для подальшого розділення енантіомерів.Експериментальна частина. Був розроблений препаративний метод синтезу 1- і 4-діамантил-, 1-адамантил- і фенілфосфінів, структури яких підтверджено мас-спектрометричними і ЯМР-спектральними даними.Висновки. Одержано ряд Р-стереогенних змішаних діамандоїларилфосфінів та вторинних фосфінів, які містять виключно діамандоїдні замісники. Ступінь стеричного навантаження сполук визначається комбінацією діамандоїдних замісників навколо атома фосфору, де похідні 1-діамантилу найбільш стерично ускладнені. Одержані сполуки є потенційними лігандами в асиметричному каталізі.Received: 31.03.2020 Revised: 24.06.2020 Accepted: 27.08.202

CLINICAL AND CHEST X-RAY FEATURES OF PNEUMONIA IN INJECTING-DRUG USERS

On an example of a clinical case in a patient with drug addiction, the reviewed clinical and chest X-ray features of community-acquired pneumonia, the diagnostic algorithms and the differential diagnostics are based on the recommendations of the Ukrainian Association of Pulmonology. The treatment strategy of the patient in the conditions of an ambulatory are described

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

Introduction: The left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms. Methods: We investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl2 AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca2+]i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay. Results: AF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM. Discussion: Thus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF. 2023 Butova, Myachina, Simonova, Kochurova, Mukhlynina, Kopylova, Shchepkin and Khokhlova.Russian Science Foundation, RSF: 22-75-10134This research was supported by the Russian Science Foundation #22-75-10134. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.This research was supported by the Russian Science Foundation #22-75-10134. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript

Analysis of Mechanical Alternans in Single Cardiomyocytes in Atrial Fibrillation

Atrial fibrillation (AF) has a significant impact on the contractile function of the heart in the form of alternans activity in atrial cardiomyocytes. In this study, we designed a method for evaluating mechanical alternans in atrial cardiomyocytes in AF.Работа выполнена при поддержке государственной темы ИИФ УрО РАН № 122022200089-4

Type 1 Diabetes Impairs Cardiomyocyte Contractility in the Left and Right Ventricular Free Walls but Preserves It in the Interventricular Septum

Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca2+ concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca2+ sensitivity. A decrease in the thin-filament velocity was associated with increased expression of β-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the Russian Science Foundation № 18-74-10059. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology

DEVELOPMENT OF METHOD FOR ANALYSIS OF THE T-TUBULAR SYSTEM IN RAT CARDIOMYOCYTES

The t-system is the highly structured network of membrane invaginations playing an im-portant role in the regulation of cardiac electromechanical coupling and contraction. We de-signed an approach to evaluate the structure of the cardiomyocyte t-tubular system in detail.При поддержке гос.задания ИИФ УрО РАН (тема № AAAA-A19-119070190064-4)

Effectiveness of intravenous isoniazid and ethambutol administration in patients with tuberculosis meningoencephalitis and HIV infection

Effectiveness of intravenous isoniazid and ethambutol administration in patients with tuberculosis meningoencephalitis and HIV infection / Dmytro Butov, Yurii Feshchenko, Mykhailo Kuzhko, Mykola Gumenuik, Kateryna Yurko, Alina Grygorova, Anton Tkachenko, Natalia Nekrasova, Tetiana Tlustova, Vasyl Kikinchuk, Alexandr Peshenko, Tetiana Butova // Tuberculosis and Respiratory Diseases. – 2019. – № 82. – Р. 1-8. – DOI: https://doi.org/10.4046/trd.2019.0021Метою даного дослідження було вивчення ефективності внутрішньовенного введення ізоніазиду (І) та етамбутолу (Е) у пацієнтів з лікарсько-чутливим туберкульозом легень (ТЛ) з позитивним результатом мокротиння, туберкульозним менінгоенцефалітом (ТМ) та вірусом імунодефіциту людини (ВІЛ) у інтенсивній фазі лікеування. При ТЛ/ТМ з ВІЛ внутрішньовенне лікування І та Е було більш ефективним, ніж пероральне лікування І та Е, через 2 місяці інтенсивного лікування в конверсії мокротиння, а також у клінічному поліпшенні, що супроводжується значно вищими середніми концентраціями у сироватці. Крім того, рівень смертності був нижчим при внутрішньовенному лікуванні І та Е порівняно з пероральним лікуванням.The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.Целью данного исследования было изучение эффективности внутривенного введения изониазида (И) и этамбутола (Э) у пациентов с лекарственно-чувствительным туберкулезом легких (ТЛ) с положительным результатом мокроты, туберкулезным менингоэнцефалитом (ТМ) и вирусом иммунодефицита человека (ВИЧ) в интенсивной фазе лечения. При ТЛ/ТМ с ВИЧ внутривенное лечение И и Э было более эффективным, чем пероральное лечение И и Э, через 2 месяца интенсивного лечения в конверсии мокроты, а также в клиническом улучшении, сопровождаемом значительно более высокими средними концентрациями в сыворотке. Кроме того, уровень смертности был ниже при внутривенном лечении И и Э по сравнению с пероральным лечением

Cardioinotropic effects in subchronic intoxication of rats with lead and/or cadmium oxide nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO– NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The work was carried out partly within the framework of the IIF UrB RAS themes No AAA?A18?118020590031?8 and AAAA?A18?118020590135?3. This work was performed using the equipment of the Shared Research Center of Scientific Equipment SRC IIP UrB RAS