Acute Coronary Syndrome during the Pandemic New Coronavirus Infection

The experience of managing patients with COVID-19 around the world has shown that, although  respiratory symptoms predominate  during the manifestation of infection, then many patients can develop serious damage  to the cardiovascular system. However, coronary artery disease (CHD) remains the leading cause of death worldwide. The purpose of the review is to clarify the possible pathogenetic links between COVID-19 and acute coronary syndrome (ACS), taking into account which will help to optimize the management of patients with comorbid  pathology. Among the body's responses to SARS-CoV-2 infection, which increase the likelihood of developing  ACS,  the role of systemic inflammation, the quintessence  of which is a "cytokine storm" that can destabilize  an atherosclerotic  plaque is discussed.  Coagulopathy, typical for patients with Covid-19, is based on immunothrombosis, caused by a complex  interaction between neutrophilic  extracellular  traps and von Willebrandt  factor in conditions  of systemic inflammation. The implementation  of a modern strategy  for managing patients with ACS,  focused on the priority of percutaneous interventions (PCI), during  a pandemic is experiencing great  difficulties  due to the formation  of time delays  before  the start of invasive  procedures  due to the epidemiological situation. Despite this, the current European,  American and Russian recommendations for the management of infected patients with ACS confirm the inviolability of the position of PCI as the first choice for treating patients with ACS and the undesirability  of replacing  invasive treatment with thrombolysis

Особенности метаболического обеспечения респираторного взрыва нейтрофилов крови и мокроты у больных внебольничной пневмонией

The aim of the study was to investigate relationships between the respiratory burst in blood and sputum neutrophils and intracellular enzyme activity in patients with pneumonia. Methods. The study involved 82 patients with moderate to severe community-acquired pneumonia (CAP). The chemiluminescent assay was used to investigate synthesis of primary and secondary reactive oxygen species (ROS). The bioluminescent method was used to examine NAD(P)-dependent dehydrogenase activity in neutrophils. Results. Low-intensity respiratory burst in blood neutrophils and its predominant relations to the state of mitochondrial metabolism and malic enzyme activity were observed in healthy subjects. Blood neutrophils in patients with CAP were activated; the anaerobic respiration and mitochondrial metabolism increased in the cells. Additionally, intensity of the respiratory burst was related to terminal glycolysis reactions and the key reaction of the pentose phosphate cycle. Sputum neutrophils in patients with CAP were also activated. Conclusion. Abnormalities of metabolic support of the respiratory burst, such as decreased production of primary and secondary ROS, could appear under unfavorable conditions. Peroxidation increased in the cells, the intensity of terminal glycolysis reactions decreased, and substrates transferred from the citric acid cycle to amino acid exchange reactions. Under these conditions, malic enzyme remained the only substrate that stimulated the respiratory burst in sputum neutrophils, while substrate transfer from the tricarboxylic acid cycle inhibited synthesis of the secondary ROS.Целью исследования явился сравнительный анализ зависимости состояния «респираторного взрыва» нейтрофилов крови и мокроты у больных пневмонией от уровней активности внутриклеточных ферментов. Материалы и методы. Обследованы больные (n = 82) внебольничной пневмонией (ВП) средней и тяжелой степени. С помощью ХЛ-анализа определены уровни синтеза первичных и вторичных активных форм кислорода (АФК). С помощью биолюминесцентного метода исследованы уровни активности никотинамидадениндинуклеотидфосфат (НАДФ)-зависимых дегидрогеназ в нейтрофилах. Результаты. Установлено, что у здоровых людей наблюдается низкий уровень «респираторного взрыва» нейтрофилов крови и его зависимость преимущественно от состояния митохондриального метаболизма и активности малик-фермента. У больных ВП нейтрофилы крови находятся в активированном состоянии, в клетках возрастает активность анаэробного дыхания и метаболизма митохондрий. Дополнительно появляется зависимость уровня респираторного взрыва от активности терминальных реакций гликолиза и ключевой реакции пентозофосфатного цикла. Нейтрофилы мокроты при пневмонии также находятся в активированном состоянии. Заключение. Продемонстрировано, что в условиях неблагоприятного окружения наблюдается нарушение механизмов метаболического обеспечения «респираторного взрыва», что проявляется в снижении уровня синтеза первичных и вторичных АФК. В клетках возрастает уровень перекисных процессов, выявляется снижение интенсивности терминальных реакций гликолиза и отток субстратов с лимонного цикла на реакции аминокислотного обмена. На этом метаболическом фоне малик-фермент остается единственным, стимулирующим респираторный взрыв нейтрофилов мокроты, в то время как отток субстратов с цикла трикарбоновых кислот ингибируют синтез вторичных АФК

Vertical incisal disocclusion: etiopathogenesis, classification, clinical and morphological forms, principles of treatment (review of the literature)

The article provides an overview of published data relating to the issues of etiopathogenesis, classification, differences in clinical and morphological forms, as well as the principles of treatment of patients with vertical incisal disocclusion. Particular attention is paid to the combined (orthodontic and surgical) approach in the treatment of adult patients.В статье представлен обзор литературных данных, касающихся вопросов этиопатогенеза, классификации, различий клинико-морфологических форм, а также принципов лечения пациентов с вертикальной резцовой дизокклюзией. Особое внимание уделяется комбинированному (ортодонтическому и хирургическому) подходу в лечении взрослых пациентов

Диагностическое значение биомаркеров при обострении хронической обструктивной болезни легких

An acute exacerbation of chronic obstructive pulmonary disease (COPD) plays an important role in the disease progression and significantly reduces the patients' quality of life. The aim of this review was to summarize published findings about a possible role of biomarkers in diagnosis, management and predicting outcomes in COPD patients. Creactive protein and serum amyloid A are the most investigated biomarkers in this field. Measurement of copeptin and proadrenomedullin may be useful in predicting shortterm outcomes. Biomarkeroriented management of patients with acute exacerbation of COPD could be important for choosing medications.Обострения хронической обструктивной болезни легких (ХОБЛ) играют важную роль в прогрессировании заболевания, значительно снижают качество жизни больных. Целью настоящего обзора явилось обобщение результатов исследований о возможной роли биомаркеров в диагностике, выборе тактики ведения больных, а также прогнозировании исходов обострений заболевания. Наиболее изученными биомаркерами являются Среактивный белок и сывороточный амилоид А. Оценка уровня копептина и проадреномедуллина может быть полезной в прогнозировании краткосрочных исходов. Биомаркернаправленное ведение пациентов с обострениями ХОБЛ имеет большое значение при выборе лекарственных препаратов

COVID-19 и хроническая обструктивная болезнь легких: известное о неизвестном

The article reviews 60 publications and addresses key aspects of concurrent COVID-19 and chronic obstructive pulmonary disease (COPD). It presents data stating that COPD patients have higher expression of the receptor of angiotensin-converting enzyme 2 in the lungs and this may contribute to a greater susceptibility to COVID-19. In COPD, signs of endothelial cell dysfunction and tendency to thrombus formation have been identified which can present the risk of unfavorable outcomes of COVID-19. Cohort study data do not confirm that COPD patients are more susceptible to SARS-CoV-2 infection, but their clinical outcomes of COVID-19 appear to be worse including the need for mechanical ventilation and lethality. There is no clinical evidence about the role of inhaled glucocorticosteroids used to manage COPD in the development and course of COVID-19.Обзор 60 источников литературы посвящен ключевым аспектам, касающимся коморбидности COVID-19 и хронической обструктивной болезни легких (ХОБЛ). Содержит сведения, что у больных ХОБЛ повышена экспрессия рецептора ангиотензин-превращающего фермента 2 в легких, это может способствовать большей предрасположенности к COVID-19. При ХОБЛ выявлены признаки дисфункции эндотелиальных клеток и склонность к тромбообразованию, что может быть риском неблагоприятных исходов COVID-19. Данные когортных исследований не подтверждают, что пациенты с ХОБЛ в большей степени подвержены заражению SARS-CoV-2, но, по-видимому, клинические исходы COVID-19 у них хуже, включая потребность в искусственной вентиляции легких и летальность. Пока не получены клинические доказательства роли ингаляционных глюкокортикостероидов, используемых при ХОБЛ, в развитии и течении COVID-19

Some Aspects of Mast Cells Carboxypeptidase A3 Participation in the Pathogenesis of COVID-19

Background: This study aimed to determine the involvement of carboxypeptidase A3 (CPA3) in developing lung damage in patients with COVID-19. Methods and Results: The study included samples of autopsy material from the lungs of patients who died as a result of severe COVID-19 (the main group [MG] and persons who died from external causes (the control group [CG]). Immunohistochemical staining for CPA3 was carried out. A quantitative study of CPA3-positive mast cells (MCs) and the degree of their degranulation was carried out using a ×40 objective lens with an analysis of ≥50 fields of view with further conversion to 1 mm². Significant representation of CPA3-positive MCs per 1 mm2 of CPA3-positive MCs, CPA3-positive MCs with signs of degranulation (SD), and co-adjacent MCs was found in the MG compared to the CG (P=0.01 in all cases). In the main group, positive correlations were identified between the total number of CPA3-positive MCs, CPA3-positive MCs with SD and the blood hemoglobin level shortly before death (r=0.491 [P=0.008] and r=0.521 [P=0.004], respectively). Co-adjacent CPA3-positive MCs were negatively correlated with blood eosinophils at the beginning of hospitalization (r=-0.420 [P=0.023]). Also, the number of separately lying, CPA3-positive MCs negatively correlated with the blood monocyte shortly before death (r=-0.384 [P=0.044]). A positive correlation was established between the total number of CPA3-positive MCs, CPA3-positive MCs with SD, and adjacent CPA3-positive MCs with total blood protein in patients at the beginning of hospitalization (r=0.431 [P=0.020], r=0.449 [P=0.015] and r=0.456 [P=0.013], respectively). In addition, the study demonstrated a positive correlation between CPA3-positive MCs with SD and the total number of CPA3-positive MCs with blood aPTT levels (r=0.304 [P=0.045] and r=0.375 [P=0.045], respectively). A negative correlation was also found between the total number of CPA3-positive MCs and the blood INR level (r=-0.812 [P=0.050]). Finally, in patients at the beginning of hospitalization, a negative correlation was found between CPA3-positive MCs with SD, CPA3-positive MCs without SD, separately located CPA3-positive MCs, adjacent CPA3-positive MCs, and the total number of CPA3-positive MCs with blood amylase (r=-0.550 [P=0.002], r=-0.452 [P=0.045], r=-0.485 [P=0.030], r=-0.622 [P=0.008], and r=-0.590 [P=0.006], respectively). Conclusion: Our study identifies the potential involvement of CPA3 in the pathogenesis of severe COVID-19. However, many aspects of its participation remain unclear and require further study

Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease

Disease models: A reflex reaction A simple reflex in flies can be used to test the effectiveness of therapies that slow neurodegeneration in Parkinson’s disease (PD). Christopher Elliott and colleagues at the University of York in the United Kingdom investigated the contraction of the proboscis muscle which mediates a taste behavior response and is regulated by a single dopaminergic neuron. Flies bearing particular mutations in the PD-associated gene leucine-rich repeat kinase 2 (LRRK2) in dopaminergic neurons lost their ability to feed on a sweet solution. This was due to the movement of the proboscis muscle becoming slower and stiffer, hallmark features of PD. The authors rescued the impaired reflex reaction by feeding the flies l-DOPA or LRRK2 inhibitors. These findings highlight the proboscis extension response as a useful tool to identify other PD-associated mutations and test potential therapeutic compounds

To Be or Not to Be a Flatworm: The Acoel Controversy

Since first described, acoels were considered members of the flatworms (Platyhelminthes). However, no clear synapomorphies among the three large flatworm taxa - the Catenulida, the Acoelomorpha and the Rhabditophora - have been characterized to date. Molecular phylogenies, on the other hand, commonly positioned acoels separate from other flatworms. Accordingly, our own multi-locus phylogenetic analysis using 43 genes and 23 animal species places the acoel flatworm Isodiametra pulchra at the base of all Bilateria, distant from other flatworms. By contrast, novel data on the distribution and proliferation of stem cells and the specific mode of epidermal replacement constitute a strong synapomorphy for the Acoela plus the major group of flatworms, the Rhabditophora. The expression of a piwi-like gene not only in gonadal, but also in adult somatic stem cells is another unique feature among bilaterians. These two independent stem-cell-related characters put the Acoela into the Platyhelminthes-Lophotrochozoa clade and account for the most parsimonious evolutionary explanation of epidermal cell renewal in the Bilateria. Most available multigene analyses produce conflicting results regarding the position of the acoels in the tree of life. Given these phylogenomic conflicts and the contradiction of developmental and morphological data with phylogenomic results, the monophyly of the phylum Platyhelminthes and the position of the Acoela remain unresolved. By these data, both the inclusion of Acoela within Platyhelminthes, and their separation from flatworms as basal bilaterians are well-supported alternatives