Influence of injected metoprolol and high-dosage statin therapy on some markers of early myocardial remodeling in acute coronary syndrome

Aim of the study was to evaluate of the effect of intravenous metoprolol tartrate administered before percutaneous coronary intervention (PCI), in combination with long-term use of high-dose atorvastatin, on dynamic changes in biochemical and ultrasound markers, as well as on the outcomes of early myocardial remodeling in patients with ST-segment elevation acute myocardial infarction (MI). Material and methods. A prospective randomized clinical trial included 136 patients with MI. The terms of the study were 35 ± 5 (from 30 to 40) days from the moment of admission to the hospital. The first group (control) included patients who received standard interventional and drug treatment at the hospital and outpatient post-infarction stages. The second group (exposure) included individuals who received a single intravenous injection of metoprolol tartrate before PCI, followed by a switch to oral metoprolol succinate on a systemic basis. These patients, as well as in the first group, regularly received all components of the basic drug therapy, including atorvastatin at a dose of 80 mg per day for one month from the onset of MI. On the 1st-2nd day of MI and a month later, plasma levels of biochemical biomarkers were assessed in patients; on the 1st, 10th day and one month later, ultrasound markers were evaluated using echocardiography. Upon the follow-up clinical outcomes of post-infarction myocardial remodeling were analyzed. Results. We confirmed that the use of a single intravenous injection of metoprolol tartrate (5–15 mg) in acute myocardial infarction before PCI against the background of high-dose atorvastatin (80 mg/day) for one month from the onset of myocardial infarction demonstrated convincing efficacy in relation to the prevention of early myocardial remodeling, which we assessed by the dynamics of ultrasound markers, as well as by the plasma activity of all three key biochemical markers in comparison with the control group of patients. Conclusions. The use of a single intravenous injection of metoprolol tartrate in the acute phase of MI against the background of high-dose atorvastatin for one month from the onset of MI is a highly effective pharmacological method for preventing the formation of early postinfarction myocardial remodeling

Distinguishing Acute from Chronic Hepatitis C Virus (HCV) Infection Based on Antibody Reactivities to Specific HCV Structural and Nonstructural Proteins▿

Currently available serological assays for detection of antibodies to hepatitis C virus (HCV) cannot reliably discriminate acute from chronic HCV infection. We developed a multiplexed, flow-cytometric microsphere immunoassay to measure anti-HCV-IgG reactivities to the core, NS3, NS4, and NS5 HCV recombinant proteins and applied it to 99 serum samples from 24 anti-HCV seroconverters and 141 anti-HCV-IgG and HCV RNA-positive plasma specimens from chronically infected people. Differences in the geometric means or means of signal/cutoff ratios between the two sample sets were statistically significant for all the antigens tested. A multivariate logistic regression model correctly classified the samples in two groups, with a cross-validation accuracy of 90.8% for the acute group and 97.2% for the chronic group. The immunoassay described has the potential to distinguish acute from chronic HCV infection

Properties of Fluorescent Far-Red Anti-TNF Nanobodies

Upregulation of the expression of tumor necrosis factor (TNF-α, TNF) has a significant role in the development of autoimmune diseases. The fluorescent antibodies binding TNF may be used for personalized therapy of TNF-dependent diseases as a tool to predict the response to anti-TNF treatment. We generated recombinant fluorescent proteins consisting of the anti-TNF module based on the variable heavy chain (VHH) of camelid antibodies fused with the far-red fluorescent protein Katushka (Kat). Two types of anti-TNF VHH were developed: one (BTN-Kat) that was bound both human or mouse TNF, but did not neutralize their activity, and a second (ITN-Kat) that was binding and neutralizing human TNF. BTN-Kat does not interfere with TNF biological functions and can be used for whole-body imaging. ITN-Kat can be evaluated in humanized mice or in cells isolated from humanized mice. It is able to block human TNF (hTNF) activities both in vitro and in vivo and may be considered as a prototype of a theranostic agent for autoimmune diseases

Phenotypic Changes in T and NK Cells Induced by Sputnik V Vaccination

A highly effective humoral immune response induced by the Sputnik V vaccine was demonstrated in independent studies, as well as in large-scale post-vaccination follow-up studies. However, the shifts in the cell-mediated immunity induced by Sputnik V vaccination are still under investigation. This study was aimed at estimating the impact of Sputnik V on activating and inhibitory receptors, activation and proliferative senescence markers in NK and T lymphocytes. The effects of Sputnik V were evaluated by the comparison of PBMC samples prior to vaccination, and then three days and three weeks following the second (boost) dose. The prime-boost format of Sputnik V vaccination induced a contraction in the T cell fraction of senescent CD57+ cells and a decrease in HLA-DR-expressing T cells. The proportion of NKG2A+ T cells was down-regulated after vaccination, whereas the PD-1 level was not affected significantly. A temporal increase in activation levels of NK cells and NKT-like cells was recorded, dependent on whether the individuals had COVID-19 prior to vaccination. A short-term elevation of the activating NKG2D and CD16 was observed in NK cells. Overall, the findings of the study are in favor of the Sputnik V vaccine not provoking a dramatic phenotypic rearrangement in T and NK cells, although it induces their slight temporal non-specific activation