Impact of optimal therapy for noncommunicable diseases on the course and outcome of COVID-19 inpatients

Aim. To carry out a comparative analysis of the impact of optimal and suboptimal therapy for noncommunicable diseases (NCDs) at the prehospital stage on the severity and outcomes of coronavirus disease 2019 (COVID-19).Material and methods. The study included 158 patients hospitalized with a diagnosis of COVID-19 and having one or more concomitant NCDs. Patients were divided into two groups depending on the quality of initial therapy for NCDs: group 1 — patients receiving treatment that does not meet modern clinical guidelines, taking drugs not regularly or not taking them at all (n=100; 63%), and group 2 — patients receiving treatment in accordance with current clinical guidelines, taking regularly prescribed therapy (n=58; 37%). The primary endpoint was inhospital death, while secondary endpoints — duration of fever, length of intensive care unit (ICU) stay, length of hospital stay.Results. Inhospital mortality was significantly higher in the 1st group of patients compared with the 2nd group (18,0% vs 1,7%, p=0,002). Analysis of secondary endpoints revealed that patients of the 1st group (nonoptimal therapy), in comparison with the 2nd group (optimal therapy), had significantly longer period of fever (10 [7; 12] vs 9 [7; 10] days, p=0,03), longer ICU (0 [0; 3] vs 0 [0; 0] days, p<0,001) and hospital stay (10 [8; 14] vs 8 [7; 11] days, p=0,001).Conclusion. Patients who received standard NCD therapy before admission to the infectious disease hospital, in accordance with current clinical guidelines and who regularly take drugs, have a more favorable course of COVID-19 at the hospital stage and a lower inhospital mortality rate than patients with suboptimal therapy who are not adherent to treatment or not receiving drugs, but having indications for taking them

Белковый состав и функциональные показатели мембран эритроцитов при трансплантации печени и почки

Organ transplantation is an effective treatment for many end-stage diseases. However, reperfusion injury constitutes a major complication of transplantation, which is associated with microcirculatory disorders and aggregation of blood corpuscles. Red blood cells (RBC) play an essential role in maintaining hemodynamic and rheological properties of the blood. Moreover, the study of mechanisms of changes in RBC functional indices is an urgent task. The main indicator of RBC functioning is the stability of RBC membrane structure. The issue of RBC membrane modification in organ transplantation has not been studied so far. Objective: to study the protein composition of RBC membranes, their aggregation and electrokinetic parameters in liver and kidney recipients, as well as in related kidney and liver fragment donors before and after operation. Research materials. Blood of 12 kidney recipients and 5 related kidney donors, 8 liver recipients and 4 related liver fragment donors – 1–2 hours before surgery, 1 week, 1, 2, 7, 10, 12 months after surgery. The control group consisted of 8 healthy volunteers. Research methods. Protein separation was done by Laemmli electrophoresis. RBC electrophoretic mobility, which characterizes the electrokinetic properties of cells, was measured by microelectrophoresis. Aggregation was calculated microscopically by counting unaggregated RBCs. Obtained values were compared by Mann-Whitney U test. Results. Examination of the RBC membrane of kidney recipients revealed a significant decrease in the amount of Band 3 protein and glycophorin before and after transplantation. Band 3 protein levels reduced at 1 month, glycophorin reduced at 7 months after surgery, with a maximum decrease in these protein fractions by more than 50% by 7 days compared with control values. There was also a decrease in spectrin content for 2 months after surgery with a maximum decrease of 30% by 1 month. In liver recipients, analysis of RBC membrane proteins revealed a decrease in the amount of glycophorin before surgery and further decrease at 2 months of post-transplant period. The maximum decrease in this index was 72% by 7 days after surgery. In addition, there was a fall in spectrin and Band 3 protein levels at 1 month by more than 60% relative to the control values. In donors, there were changes in the protein fraction of RBC membranes in the long-term post-operative period: spectrin and Band 3 protein levels reduced by 2 times at month 2 in kidney donors, while glycophorin levels reduced by 2.3 times at month 1 after operation in liver donors. Similarly, both groups of donors had increased actin levels at month 1 after surgery. The revealed changes in protein levels in the protein phase of RBC membranes were combined with functional indices of RBCs. In kidney recipients, decreased RBC electrophoretic mobility and increased aggregation were detected at 2 months. In liver recipients, the changes in these indicators were at 1 month. A decrease in RBC electrophoretic mobility was detected in donors of both groups. Conclusion. Changes in RBC membrane electronegativity are associated with changes in glycophorin and Band 3 protein levels, whereas in RBC aggregation process in liver/kidney recipients, the structural and functional disorders in the interrelationships of such membrane proteins as spectrin, Band 3 protein, and glycophorin, are significant factors. Alteration of actin determines inhibition of RBC aggregation growth in donors.Трансплантация органов является эффективным методом лечения пациентов с терминальными стадиями ряда тяжелых заболеваний. Однако серьезным осложнением при трансплантации являются реперфузионные повреждения, которые связаны с микроциркуляторными нарушениями и агрегацией форменных элементов крови. Эритроциты играют существенную роль в поддержании гемодинамических и реологических свойств крови, и изучение механизмов изменения их функциональных показателей является актуальной задачей. Основным показателем функционирования эритроцита служит стабильность структуры мембраны. Вопрос о модификации эритроцитарной мембраны при трансплантации органов на сегодняшний день не исследован.Цель: изучение белкового состава мембран эритроцитов, их агрегационных и электрокинетических показателей у реципиентов печени и почки, а также родственных доноров почки и фрагмента печени до и в динамике послеоперационного периода.Материалы исследования. Кровь 12 реципиентов почки, 5 родственных доноров почки, 8 реципиентов печени и 4 родственных доноров фрагмента печени во временной динамике – за 1–2 часа до операции, через 1 неделю, 1, 2, 7, 10, 12 месяцев после операции. Группу контроля составили 8 здоровых добровольцев.Методы исследования. Разделение белков проводили методом электрофореза по Лэммли. Электрофоретическую подвижность эритроцитов, характеризующую электрокинетические свойства клеток, измеряли методом микроэлектрофореза. Агрегацию рассчитывали микроскопически, путем подсчета неагрегированных эритроцитов. Сравнение полученных величин проводили по U-критерию Манна–Уитни.Результаты. Исследование мембраны эритроцитов крови реципиентов почки выявило значимое снижение количества белка полосы 3 и гликофорина до и после проведения трансплантации. Уровень белка полосы 3 был снижен в течение 1 месяца, гликофорина – в течение 7 месяцев после операции с максимальным уменьшением данных фракций белков более чем на 50% к 7-м суткам относительно значений контроля. Также регистрировалось снижение содержания спектрина в течение 2 месяцев после операции с максимальным снижением на 30% к 1 месяцу. У реципиентов печени анализ белков мембраны эритроцитов выявил снижение количества гликофорина до операции и дальнейшее его уменьшение в течение 2 месяцев посттрасплантационного периода. Максимальное снижение показателя – на 72% – было отмечено к 7-м суткам после операции. Кроме того, наблюдалось снижение количества спектрина и белка полосы 3 в течение 1 месяца более чем на 60% относительно значений контроля. У доноров изменения в белковой фракции эритроцитарных мембран регистрировались в отдаленный период после операции: у доноров почки снижение в 2 раза количества спектрина и белка полосы 3 отмечалось на 2-й месяц, у доноров печени снижение гликофорина в 2,3 раза – к 1-му месяцу после операции. Также в обеих группах доноров регистрировался рост концентрации актина к 1-му месяцу после операции. Выявленные изменения количества белков в белковой фазе эритроцитарных мембран сочетались с функциональными показателями эритроцитов. У реципиентов почки снижение ЭФПЭ и увеличение агрегации наблюдалось в течение 2 месяцев, у реципиентов печени изменения данных показателей зафиксированы в течение 1 месяца. У доноров обеих групп было выявлено уменьшение ЭФПЭ.Заключение. Совокупность полученных результатов показала, что изменение электроотрицательности мембран эритроцитов сопряжено с изменением содержания гликофорина и белка полосы 3, тогда как в процессе агрегации эритроцитов у пациентов после трансплантации печени/почки значимыми факторами являются структурно-функциональные нарушения взаимосвязей таких мембранных белков, как спектрин, белок полосы 3, гликофорин. Изменение актина определяет сдерживание роста агрегации эритроцитов у доноров

Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors

Type 2 internal ribosomal entry sites (IRESs) of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV) and other picornaviruses comprise five major domains H-L. Initiation of translation on these IRESs begins with specific binding of the central domain of initiation factor, eIF4G to the J-K domains, which is stimulated by eIF4A. eIF4G/eIF4A then restructure the region of ribosomal attachment on the IRES and promote recruitment of ribosomal 43S pre-initiation complexes. In addition to canonical translation factors, type 2 IRESs also require IRES trans-acting factors (ITAFs) that are hypothesized to stabilize the optimal IRES conformation that supports efficient ribosomal recruitment: the EMCV IRES is stimulated by pyrimidine tract binding protein (PTB), whereas the FMDV IRES requires PTB and ITAF45. To test this hypothesis, we assessed the effect of ITAFs on the conformations of EMCV and FMDV IRESs by comparing their influence on hydroxyl radical cleavage of these IRESs from the central domain of eIF4G. The observed changes in cleavage patterns suggest that cognate ITAFs promote similar conformational changes that are consistent with adoption by the IRESs of comparable, more compact structures, in which domain J undergoes local conformational changes and is brought into closer proximity to the base of domain I

OPTIMIZATION OF PREOPERATIVE ASSESSMENT IN TRANSVAGINAL PELVIC RECONSTRUCTIVE PLASTIC SURGERY FOR THE TREATMENT OF PELVIC ORGANS PROLAPSE

The objective of this study was to optimize the preoperative assessment in transvaginal pelvic reconstructive plastic surgery for the treatment of pelvic organs prolapse. Materials and methods: We conducted the quantitative and qualitative analysis of vaginal biocenosis in 68 female patients before and after administration of Polygynax. It was shown that Polygynax improves vaginal biocenosis owing to the reduction of microbial content. Therefore, the use of Polygynax for the preoperative assessment can be an effective method of prophylaxis of infectious and inflammatory complications and promote tissue regeneration after transvaginal pelvic reconstructive plastic surgery for the treatmentof pelvic organs prolapse

MODERN GENETIC ASPECTS OF PELVIC ORGAN PROLAPS

The review of the russian and foreign literature on pelvic organ prolapse in women and its genetic aspects. According to the literature, an association of pelvic organ prolapse (POP) with a number of single nucleotide polymorphisms (SNPs) on chromosome 9q21, which are involved in the formation of elastic fibers of the connective tissue (CT). The association also polymorphism fibullin – 5 (FBLN5) and lysyl oxidase – like 1 (LOXL1) and theirrelationship to POP. Based on the literature, studies aimed at identifying the genetic nature of the POP, are incomplete and are important for the identification of risk groups who have a predisposition to POP, selecting the optimal policy for patients at risk and the initial stages of POP

Physiology and pathology of extracellular vesicules

This year marks the 50th anniversary of the first publication about blood plasma microparticles. Initially considered as cell fragments or “platelet dust”, extracellular vesicles currently attracted the attention of biochemists, biophysicists, physicians, pharmacists around the world. They are heterogeneous in structure and derived from many cell types, express different antigen and contain variety of biomolecules that determines wide range of biological activity, including procoagulant, regenerative, immunomodulating, and others. They play an important role in the pathophysiology of different diseases and conditions – from infarction, injuries and pregnancies to the “graft versus host” disease. The vesicles as medicaments and their carriers, as well as the drugs that affect them, are a rapidly developing field of research

Electrokinetic, oxidative and aggregation properties of red blood cells in the postoperative period following kidney transplantation

Objective: to study the electrokinetic and aggregation properties, as well as the pro-oxidant and antioxidant processes in red blood cells following kidney transplantation in donors and in recipients in the postoperative period. Materials and methods. Blood from 12 recipients and 5 kidney donors over time – before transplantation, as well as at week 1, months 1, 2, 7, 10 and 12 after surgery, as well as from 8 healthy volunteers who formed the control group. We used microelectrophoresis to measure the electrophoretic mobility of red blood cells, characterizing the electrokinetic properties of cells. Aggregation was calculated microscopically by counting unaggregated red blood cells. Malondialdehyde concentration was measured spectrophotometrically at its absorbance maximum at 530 nm by reaction with thiobarbituric acid. Catalase activity was analyzed by reducing hydrogen peroxide in the sample spectrophotometrically at 240 nm wavelength. The obtained values were compared using the Mann–Whitney U test. Results. Decreased electrophoretic mobility of red blood cells within 2 months after transplantation was associated with increased malondialdehyde concentration and erythrocyte aggregation, decreased catalase activity in kidney recipients, followed by restoration of indicators to the control values. Electrophoretic mobility of red blood cells decreased, while malondialdehyde concentrations increased in donors after surgery. However, the increase was less pronounced than in recipients. The changes indicate that the postoperative period causes changes at the cellular level both in donors and in recipients. This is manifested by decreased stability of erythrocyte membrane structure, which is largely determined by lipid peroxidation processes. At the systemic level, a change in the electrophoretic mobility of red blood cells indicates a stress reaction before and after kidney transplantation in recipients within 2 months after surgery, and in donors in 1–2 months in the postoperative period with gradual increase in the body’s resistance. Conclusion. Kidney transplantation is manifested at the cellular and systemic levels. At the cellular level, there is decreased stability of the membrane structure, which is largely determined by lipid peroxidation processes. At the systemic level, a change in the electrophoretic mobility of red blood cells indicates a stress reaction with gradual increase in the body’s resistance. The data obtained demonstrate changes in the functional properties of red blood cells both in kidney transplant recipients and in donors. These changes need to be taken into account when carrying out therapeutic measures