Differential Mitochondrial, Oxidative Stress and Inflammatory Responses to SARS-CoV-2 Spike Protein Receptor Binding Domain in Human Lung Microvascular, Coronary Artery Endothelial and Bronchial Epithelial Cells.

Recent evidence indicates that the SARS-CoV-2 spike protein affects mitochondria with a cell type-dependent outcome. We elucidate the effect of the SARS-CoV-2 receptor binding domain (RBD) on the mitochondrial network and cristae morphology, oxygen consumption, mitoROS production, and inflammatory cytokine expression in cultured human lung microvascular (HLMVECs), coronary artery endothelial (HCAECs), and bronchial epithelial cells (HBECs). Live Mito Orange staining, STED microscopy, and Fiji MiNa analysis were used for mitochondrial cristae and network morphometry; an Agilent XFp analyser for mitochondrial/glycolytic activity; MitoSOX fluorescence for mitochondrial ROS; and qRT-PCR plus Luminex for cytokines.

Contractions Induced in Human Pulmonary Arteries by a HS Donor, GYY 4137, Are Inhibited by Low-Frequency (20 kHz) Ultrasound.

The present study aimed to investigate the effect of a HS donor, GYY 4137, on human pulmonary arteries and whether low-frequency ultrasound (20 kHz, 4 W/cm) inhibits GYY 4137 contractions. Functional studies were conducted on human and rat pulmonary arteries mounted on microvascular myographs. We placed an ultrasonic gadget in the tissue organ bath to insonate the arteries with low-frequency ultrasound.

The Glomerular Filtration Rate Estimators in the Pharmacokinetic Modelling in Acute Kidney Injury: An Observational Study.

The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI.

Low-Frequency (20 kHz) Ultrasonic Modulation of Drug Action.

We tested the effect of low-frequency ultrasound (LUS, 20 kHz, 4 W/cm) on the function of rat mesentery and human pulmonary arteries with wire myography. The vessels were induced to contract with either noradrenaline or physiologic saline solution (PSS) with a high potassium concentration (KPSS) and then incubated with capsaicin (2.1 × 10 M, TRPV1 [transient receptor potential vanilloid 1] activator), dopamine (1 × 10 M, dopamine and α-receptor activator), or fenoldopam (dopamine receptor agonist, 1 × 10 M) with and without glibenclamide (1 μM, KATP [adenosine triphosphate {sensitive potassium channel (ATP)}-sensitive potassium channel] inhibitor and α-receptor modulator), and insonated.