Role of catestatin in development and decompensation of heart failure: a literature review

The current literature review covers the role of sympathetic nervous system activation (SNS) and the significance of a new biomarker catestatin (CST), which is a chromogranin A-derived peptide, for assessing prognosis of patients with heart failure (HF). This review details the works devoted to CST metabolism and its role in clinical conditions with excessive catecholamine production, including the ability to counterbalance the adverse effects of SNS on cardiovascular system. The paper also presents the central results of studies on HF patients and shows the correlation of the CST level with HF functional class and stage. In addition, particular attention is paid on the possibilities and potential benefits of assessing the CST in addition to conventional management of patients hospitalized due to acute decompensated heart failure

Detection of Resistance Mutations to Antivirals Oseltamivir and Zanamivir in Avian Influenza A Viruses Isolated from Wild Birds

The neuraminidase (NA) inhibitors oseltamivir and zanamivir are the first-line of defense against potentially fatal variants of influenza A pandemic strains. However, if resistant virus strains start to arise easily or at a high frequency, a new anti-influenza strategy will be necessary. This study aimed to investigate if and to what extent NA inhibitor–resistant mutants exist in the wild population of influenza A viruses that inhabit wild birds. NA sequences of all NA subtypes available from 5490 avian, 379 swine and 122 environmental isolates were extracted from NCBI databases. In addition, a dataset containing 230 virus isolates from mallard collected at Ottenby Bird Observatory (Öland, Sweden) was analyzed. Isolated NA RNA fragments from Ottenby were transformed to cDNA by RT-PCR, which was followed by sequencing. The analysis of genotypic profiles for NAs from both data sets in regard to antiviral resistance mutations was performed using bioinformatics tools. All 6221 sequences were scanned for oseltamivir- (I117V, E119V, D198N, I222V, H274Y, R292K, N294S and I314V) and zanamivir-related mutations (V116A, R118K, E119G/A/D, Q136K, D151E, R152K, R224K, E276D, R292K and R371K). Of the sequences from the avian NCBI dataset, 132 (2.4%) carried at least one, or in two cases even two and three, NA inhibitor resistance mutations. Swine and environmental isolates from the same data set had 18 (4.75%) and one (0.82%) mutant, respectively, with at least one mutation. The Ottenby sequences carried at least one mutation in 15 cases (6.52%). Therefore, resistant strains were more frequently found in Ottenby samples than in NCBI data sets. However, it is still uncertain if these mutations are the result of natural variations in the viruses or if they are induced by the selective pressure of xenobiotics (e.g., oseltamivir, zanamivir)

Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication

RNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

CATESTATIN AS A NOVEL MARKER OF CARDIOVASCULAR RISK IN SYSTEMIC HYPERTENSION

Review of the key studies on antihypertensive, vasodilatatory, angiogenic and antiapoptotic action of catestatin — a peptide resulting from endogenic protease interaction with chromogranin А. Plasma levels of catestatin correlate negatively with the hypertension phenotype. Pathogenetic role is discussed for catestatin in development of essential hypertension and its possible influence as a marker of cardiovascular risk stratification

The relationship of plasma catestatin and heart rate variability parameters in middle-aged men with primary hypertension

Aim. To study the catestatin plasma level in patients with primary hypertension of different cardiovascular risk and to assess its relationship with heart rate variability (HRV) parameters.Material and methods. One hundred eighty men aged 30-50 years were divided into groups: group 1 (n=28) — hypertensive patients with medium risk of developing cardiovascular complications (CVC), group 2 (n=76) — hypertensive patients with high risk of CVC, group 3 (n=31) — hypertensive patients with very high risk of CVC. The control group consisted of healthy men with normal blood pressure (BP) (n=45). We determined plasma catestatin (ng/ml) and conducted Holter monitoring.Results. A pattern was found to reduce the concentration of catestatin with increasing risk of CVC in hypertensive patients, but there were no significant differences between the studied groups (p>0,05).We determined corrections between catestatin levels and echocardiography thickness of left ventricular posterior wall (r=-0,523; p=0,045) and interventricular septum (r=-0,523, p=0,045) in diastole in group 2; thickness of left ventricular posterior wall (r=0,258; p=0,035) and interventricular septum (r=0,254; p=0,038) in systole in group 3. In patients of group 2, direct correlations of catestatin levels and sympathicotonia LF/HF were revealed during the whole observation period (r=0,301; p=0,019) and during wakefulness (r=0,308; p=0,019); inverse correlations — with parameters of parasympathetic tone: nHF during the whole observation time (r=-0,318; p=0,013) and during wakefulness (r=-0,342; p=0,007), pNN50 in the afternoon (r=-0,270; p=0,037).Conclusion. A decrease in catestatin concentrations in hypertensive patients is associated with the progression of disease and an increase in cardiovascular risk. It is assumed that catestatin is involved in the formation of HRV in patients with primary hypertension

Modeling of aeroelastic composite plates vibrations based on asymptotic theory

The paper is devoted to solving the problem of aeroelastic deformation of multilayer thin composite plates. A theory of aeroelastic deformations of composite plates based on the application of the asymptotic averaging method and piston theory for modeling pressure on the body surface is proposed. The averaged equations of aeroelastic vibrations of composite plates are derived. An example of a numerical solution of the problem of one-dimensional bending vibrations of a composite plate based on the developed theory is given