DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function.

Background: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm.

Methods: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function.

Proportional pulse pressure relates to cardiac index in stabilized acute heart failure patients.

Aims: In chronic heart failure, proportional pulse pressure (PPP) is suggested as an estimate of cardiac index (CI). The association between CI and PPP in acute heart failure (AHF) has not been described.

Methods: This was examined using hemodynamic measurements (from a trial using serelaxin) in 63 stabilized AHF patients.

A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.

Aims: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF).

Methods And Results: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.

PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity.

Recombinant interferon-β1b (IFN-β1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation.

A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure.

Aims: The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF).

Methods And Results: This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg, systolic blood pressure (BP) ≥ 115 mmHg, and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m(2) to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization.

Electrocardiographic markers predict left ventricular wall motion improvement in patients with acute myocardial infarction receiving thrombolysis.

Background: In patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolysis, prediction of early left ventricular wall motion changes is important for prognosis.

Materials And Methods: In 106 patients with STEMI treated with thrombolysis, we analyzed the degrees of total and maximal ST-segment resolution at 3 hours and changes in sums of T-wave amplitudes in leads with ST elevation 3 and 48 hours after thrombolysis as the predictors of the echocardiographic left ventricular wall motion score index (WMSI) improvement.

Results: Wall motion score index improvement was best predicted by total ST-segment resolution of more than 44% in anterior infarctions (sensitivity, 81%; specificity, 62%) and more than 59% in nonanterior infarctions (sensitivity, 100%; specificity, 42%) and by difference in sums of T-wave amplitudes between electrocardiograms at 48 hours and baseline less than -28 mm (sensitivity, 68%; specificity, 76%).

N-terminal region of Saccharomyces cerevisiae eRF3 is essential for the functioning of the eRF1/eRF3 complex beyond translation termination.

Background: Termination of translation in eukaryotes requires two release factors, eRF1, which recognizes all three nonsense codons and facilitates release of the nascent polypeptide chain, and eRF3 stimulating translation termination in a GTP-depended manner. eRF3 from different organisms possess a highly conservative C region (eRF3C), which is responsible for the function in translation termination, and almost always contain the N-terminal extension, which is inessential and vary both in structure and length. In the yeast Saccharomyces cerevisiae the N-terminal region of eRF3 is responsible for conversion of this protein into the aggregated and functionally inactive prion form.