Федеральный дистанционный консультативный центр анестезиологии и реаниматологии на базе Первого МГМУ им. И.М. Сеченова
Background SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of disease presentations. Methods Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins (APPs) by nephelometry, and full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF). Results When compared to controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, α1-acid glycoprotein (AGP), α1-antitrypsin (AAT), ceruloplasmin (CP), haptoglobin (HP), and high-sensitivity C-reactive protein (hs-CRP). The concentrations of α1-antichymotrypsin (ACT), α2-macroglobulin (A2MG) and serum amyloid A (SAA) proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose- and sialylated di-antennary glycans and decreased non-sialylated di-antennary glycan A2G2 in COVID-19 patients compared to controls. Conclusions COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
The structure near polyelectrolyte-coated gold nanoparticles (AuNPs) is of significant interest because of the increased use of AuNPs in technological applications and the possibility that the acquisition of polyelectrolytes can lead to novel chemistry in downstream environments. We use all-atom molecular dynamics (MD) simulations to reveal the electric potential around citrate-capped gold nanoparticles (cit-AuNPs) and poly(allylamine hydrochloride) (PAH)-wrapped cit-AuNP (PAH-AuNP). We focus on the effects of the overall ionic strength and the shape of the electric potential. The ionic number distributions for both cit-AuNP and PAH-AuNP are calculated using MD simulations at varying salt concentrations (0, 0.001, 0.005, 0.01, 0.05, 0.1, and 0.2 M NaCl). The net charge distribution (Z(r)) around the nanoparticle is determined from the ionic number distribution observed in the simulations and allows for the calculation of the electric potential (ϕ(r)). We find that the magnitude of ϕ(r) decreases with increasing salt concentration and upon wrapping by PAH. Using a hydrodynamic radius (R H) estimated from the literature and fits to the Debye-Hü̈ckel expression, we found and report the ζ potential for both cit-AuNP and PAH-AuNP at varying salt concentrations. For example, at 0.001 M NaCl, MD simulations suggest that ζ = −25.5 mV for cit-AuNP. Upon wrapping of cit-AuNP by one PAH chain, the resulting PAH-AuNP exhibits a reduced ζ potential (ζ = −8.6 mV). We also compare our MD simulation results for ϕ(r) to the classic Poisson–Boltzmann equation (PBE) approximation and the well-known Derjaguin–Landau–Verwey–Overbeek (DLVO) theory. We find agreement with the limiting regimeswith respect to surface charge, salt concentration and particle sizein which the assumptions of the PBE and DLVO theory are known to be satisfied.
There is a great need for early verification of the severity of acute pancreatitis (AP). The early stage of pathogenesis of AP is characterized by endothelial dysfunction which could be determined by wavelet analysis of skin temperature (WAST) technique. The aim is to investigate whether the dysregulation of microvascular tone caused by endothelial dysfunction and detected by WAST can be a significant indicator in early differential diagnosis of AP severity. The WAST performed in the frequency range of 0.0095-0.02 Hz during the contralateral cold test. Forty nine patients with AP aged 19-65 participated in this study. The control group included 12 healthy volunteers aged 20-65. Dysregulation of vascular tone during the contralateral cold test was observed in all patients with AP. The basal amplitudes of skin temperature oscillations in patients with AP were much lower than in healthy volunteers and progressively decreased as the disease severity increased. In patients with mild and moderate AP only the vasodilator component is destroyed, but vasoconstriction still operates. In patients with severe AP both mechanisms of endothelial vascular tone regulation are destroyed. Patients with AP have abnormal microvascular reactions related to the endothelial mechanism of vascular tone regulation. Based on the initial values of amplitudes and the indices of vasoconstriction and postcold vasodilatation, the WAST method makes it possible to evaluate two related but different characteristics of the endothelial dysfunction in patients with AP on admission which can be a significant indicator in early differential diagnosis of AP severity.
Aim. In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. Materials and methods. We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. Results. We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). Conclusion. The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.
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