Diversity of comorbid conditions in young and middle-aged patients with psoriatic arthritis

Aim. The aim of the study was to investigate the prevalence of comorbid conditions in young and middleaged patients with psoriatic arthritis. Material and methods. We analyzed data from the case reports of 84 patients with psoriatic arthritis for 2018-2020, among whom 39 (47,6%) were men and 45 (52,4%) were women, in a course of a cross-sectional observational study. The mean age of the patients was (42,8±10,1) years, DAPSA-18,1 (10,2; 26,7), PASI-5,3 (1,5; 10,8). Results and discussion. Comorbid conditions were observed in 68 (80,9%) patients; the mean number of comorbid conditions was 3 (1; 4). More than one comorbid condition was observed in 69% of the patients. Among transnosological conditions, cardiovascular diseases were the most frequent (40,5%), with high frequency of arterial hypertension (36,9%), atherosclerosis (20,2%), and combined cardiovascular diseases in 17,9% of patients. Osteoporosis and osteopenia (11,9%), obesity (26,2%) was also observed. Waist circumference was higher than normalvalues in 34,5% of patients, and waist-to-hip ratio was higher than normal in 57,1% of patients. Among the extra-articular manifestations, uveitis (1,2%) and Crohn’s disease (1,2%) were observed. Among chronic conditions there was a high frequency of gastrointestinal diseases (41,6%) - inflammatory diseases of upper gastrointestinal tract (27,4%), abnormality of gallbladder, biliary tract and pancreas (21,4%), alcoholic liver disease, toxic liver damage, nonalcoholic fatty liver disease (14,5%). Other musculoskeletal and connective tissue diseases unrelated to psoriasis were noted in 27,6% of patients (gout, osteoarthritis). Endocrine system diseases occurred in 19% of patients (type II diabetes mellitus, thyroid gland diseases). In 62,5% of the cases, type II diabetes mellitus was combined with increased body weight and obesity. Diseases of urogenital system were registered in 13,9% of patients, respiratory diseases such as chronic bronchitis, and bronchial asthma - in 3,6% of patients. Conclusion. A high incidence of combination of psoriatic arthritis with concomitant diseases, especially with lesions of the cardiovascular system and gastrointestinal tract diseases, has been revealed. This significantly aggravates the course of psoriatic arthritis, worsens the response to therapy, and in some cases (due to the existing contraindications) reduces the possibility of prescribing adequate therapy

A 3D MOF based on Adamantoid Tetracopper(II) and Aminophosphine Oxide Cages: Structural Features and Magnetic and Catalytic Properties

This work describes an unexpected generation of a new 3D metal-organic framework (MOF), [Cu4(μ-Cl)6(μ4-O)Cu(OH)2(μ-PTA=O)4]n·2nCl-EtOH·2.5nH2O, from copper(II) chloride and 1,3,5-triaza-7-phosphaadamantane 7-oxide (PTA=O). The obtained product is composed of diamandoid tetracopper(II) [Cu4(μ-Cl)6(μ4-O)] cages and monocopper(II) [Cu(OH)2] units that are assembled, via the diamandoid μ-PTA=O linkers, into an intricate 3D net with an nbo topology. Magnetic susceptibility measurements on this MOF in the temperature range of 1.8-300 K reveal a ferromagnetic interaction (J = +20 cm-1) between the neighboring copper(II) ions. Single-point DFT calculations disclose a strong delocalization of the spin density over the tetranuclear unit. The magnitude of exchange coupling, predicted from the broken-symmetry DFT studies, is in good agreement with the experimental data. This copper(II) compound also acts as an active catalyst for the mild oxidation and carboxylation of alkanes. The present study provides a unique example of an MOF that is assembled from two different types of adamantoid Cu4 and PTA=O cages, thus contributing to widening a diversity of functional metal-organic frameworks. © 2021 The Authors. Published by American Chemical Society

Enthesopathy in spondyloarthritis: The literature review

The article presents data on epidemiology, pathogenesis, clinical manifestations, diagnosis and therapy of enthesopathy in spondyloarthritis. The approaches to assessment of this pathology are examined and detailed, modern clinical and ultrasound indices are given. The features of enthesopathy in diseases that included in the group of spondyloarthridies are described

ПРОИЗВОДНЫЕ АДАМАНТАНА, СПОСОБНЫЕ ИНГИБИРОВАТЬ РЕПРОДУКЦИЮ РЕЗИСТЕНТНОГО К РИМАНТАДИНУ ШТАММА ВИРУСА ГРИППА A(H1N1)PDM09 (INFLUENZA A VIRUS, ALPHAINFLUENZAVIRUS, ORTHOMYXOVIRIDAE)

Introduction. Adamantanthane-type drugs such as rimantadine and amantadine have long been used to treat diseases caused by influenza A virus. However, as a result of the mutations, influenza viruses have become resistant to aminoadamantans. The target for these drugs was the protein channel M2. Influenza A virus M2 viroporin in the protein shell forms fairly specific ion channels with a diameter of about 11 Å, specializing in transporting protons inside the viral particle (virion). Restoration of the antiviral properties of adamantanthane-type drugs consists in the selection of advanced functional groups bound by the carbocycle to find new sites of binding to the protein target M2. The purpose of the study is to identify the antiviral properties of new adamantanum derivatives to the pandemic strain of influenza A virus in vitro. Material and methods. Compounds of aminoadamantans with amino acids and other organic molecules were obtained by classical peptide synthesis methods. The structure of the compound was tested by means of physical and chemical methods. Antiviral properties of synthetic compounds were studied in vitro on monolayer MDCK cells infected with pandemic strain of influenza A/California/07/2009 virus in two schemes of administration of investigated compounds and virus. Results. The reference strain of the influenza virus A/California/07/2009(H1N1) was sensitive to the compounds under test in varying degrees. The antiviral activity of the compounds was expressed in a 50% inhibitory concentration (IC50) ranging from 0.5 to 2.5 mkM, which is generally a good indicator for the Rimantadine/Amantadine resistant strain. Discussion. The values of the IC50 for compounds introduced two hours before contact with the virus were slightly higher than those for single-moment introduction of the substance and virus. The effect of increasing the inhibitory concentration in the prophylactic scheme of compounds was valid for all compounds of the experiment. Conclusion. The presented synthetic compounds are active against the variant of influenza A virus resistant to Rimantadine and Amantadine preparations. The obtained compounds can be used as model structures for creation of a new drug of direct action against advanced strains of influenza A virus.Введение. Соединения адамантанового ряда, такие как римантадин и амантадин, долгое время применяли для лечения заболеваний, вызванных вирусом гриппа А. Однако в результате возникших мутаций вирусы гриппа приобрели резистентность к аминоадамантанам. Мишенью для этих препаратов служил белковый канал М2. Виропорин М2 в белковой оболочке вируса гриппа А образует достаточно специфичные ионные каналы диаметром около 11 Å, специализирующиеся на транспорте ионов водорода внутрь вирусной частицы (вириона). Восстановление противовирусных свойств препаратов адамантанового ряда заключается в подборе дополнительных функциональных групп, связанных карбоциклом, для поиска новых сайтов связывания с белком мишенью М2. Цель исследования - выявление противовирусных свойств адамантановых производных в отношении пандемического штамма вируса гриппа А in vitro. Материал и методы. Соединения аминоадамантанов с аминокислотами и другими органическими молекулами были получены методами классического пептидного синтеза. Структура соединения подтверждена современными физико-химическими методами. Противовирусные свойства синтетических соединений были изучены in vitro на монослое клеток MDCK, инфицированных пандемическим штаммом вируса гриппа А/California/07/2009 в двух схемах введения исследуемых соединений и вируса. Результаты. Эталонный штамм вируса гриппа A/California/07/2009(H1N1) был в разной мере чувствителен к тестируемым соединениям. Противовирусную активность соединений выражали в виде 50% ингибирующей дозы (ИД50), которая составила от 0,5 до 2,5 мкМ, что в целом неплохой показатель в отношении штамма, резистентного к римантадину/амантадину. Обсуждение. ИД50 для соединений, вносимых за 2 ч до контакта с вирусом, была несколько выше, чем при одномоментном внесении вещества и вируса. Эффект увеличения ингибирующей концентрации в профилактической схеме внесения соединений был справедлив для всех соединений эксперимента. Заключение. Представленные синтетические соединения активны в отношении варианта вируса гриппа А, резистентного к римантадину и амантадину. Полученные соединения могут быть использованы в качестве модельных структур для создания нового препарата прямого действия против современных штаммов вируса гриппа А

Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

Background: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010–2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. Methods: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of oseltamivir and umifenovir was evaluated in a retrospective study conducted in 26 regions of Russia. Results: All tested viruses (n = 36) were susceptible to oseltamivir and umifenovir in vitro. Oseltamivir (10 mg/kg/day) and umifenovir (60 mg/kg/day) significantly increased the survival of mice challenged with A/California/04/2009 (H1N1)pdm09 virus (p < 0.05). Influenza infection was laboratory-confirmed in 442 patients among 1462 patients hospitalized with acute respiratory infections. The treatment of influenza-infected patients within 48 h of symptom onset with oseltamivir and umifenovir was associated with a significant decrease in the duration of illness (2–3 days) and symptoms (p < 0.001). Pneumonia was observed in none of the patients treated with oseltamivir and in 0.3% of the patients treated with umifenovir, compared to 23.7% of patients who did not receive antiviral therapy (p < 0.001). Conclusions: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons

Evolution of pandemic influenza virus A(H1N1)pdm09 in 2009-2016: dynamics of receptor specificity of the first hemagglutinin subunit (HA1)

INTRODUCTION: The new reassortant of the swine flu virus A(H1N1)pdm09, which emerged in 2009, overcame the species barrier and caused the 2009-2010 pandemic. One of the key points required for the influenza virus to overcome the species barrier and adapt it to humans is its specific binding to the receptors on the epithelium of the human respiratory tract. PURPOSE: Studying the dynamics of changes in receptor specificity (RS) of the HA1 subunit of the hemagglutinin of the influenza A(H1N1)pdm09 virus strains isolated during the period 2009-2016 on the territory of the Russian Federation, and an analysis of the possible impact of these changes on the incidence rates of the population of the Russian Federation of pandemic influenza in certain epidemic seasons. MATERIAL AND METHODS: Standard methods of collecting clinical materials, isolation of influenza viruses, their typing and genome sequencing were used. For the study of RS of influenza A virus (H1N1)pdm09, the method of solid phase sialosidenzyme analysis was used. RESULTS: It is shown that the change in the parameter W3/6 , which characterizes the degree of a2-3 receptor specificity (a2-3-RS) of the influenza virus A(H1N1) pdm09 over a2-6-RS, coincides with the change in the incidence rates of the Russian Federation's pandemic flu in separate epidemic seasons. There is a tendency to increase the affinity of the virus A(H1N1)pdm09 to α2-3 analogs of the sialyl-glycan receptors of the human respiratory tract epithelium - α2-3-sialoglycopolymers (α2-3-SGP), and falls to α2-6-SGP, with the virus showing the greatest affinity for sulfated sialoglycopolymers. DISCUSSION: Screening for RS strains of influenza A (H1N1)pdm09 virus isolated on the territory of the Russian Federation in 2009-2016 revealed a decrease in the affinity of viruses for a2-6-sialosides, especially for 6'SL-SGP, which is probably due to the presence of amino acid substitutions in the 222 and 223 positions of RBS HA1 viruses. Previous studies have shown that the presence of such substitutions correlates with an increase in the virulence of the influenza A virus (H1N1)pdm09 [16, 23]. Probably, the pandemic virus has evolved towards the selection of more virulent pneumotropic variants. CONCLUSION: Monitoring of the receptor specificity of a pandemic influenza virus makes it possible to identify strains with altered RS to the epithelium of the human respiratory tract and an increased ability to transfer from person to person. Change in the period 2009-2016 the W3/6 parameter characterizing the degree of α2-3-RS excess of the influenza A(H1N1)pdm09 virus over α2-6-RS, coincides with the change in the incidence rates of the pandemic influenza population of the Russian Federation in certain epidemic seasons