Treating COPD Patients with Inhaled Medications in the Era of COVID-19 and Beyond: Options and Rationales for Patients at Home.

COVID-19 has affected millions of patients, caregivers, and clinicians around the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads via droplets and close contact from person to person, and there has been an increased concern regarding aerosol drug delivery due to the potential aerosolizing of viral particles. To date, little focus has been given to aerosol drug delivery to patients with COVID-19 treated at home to minimize their hospital utilization.

Polymicrobial sepsis and endotoxemia promote microvascular thrombosis via distinct mechanisms.

Background: We reported recently that endotoxemia promotes microvascular thrombosis in cremaster venules of wild-type mice, but not in mice deficient in toll-like receptor 4 (TLR4) or von Willebrand factor (VWF).

Objective: To determine whether the clinically relevant model of polymicrobial sepsis induced by cecal ligation/perforation (CLP) induces similar responses via the same mechanisms as endotoxemia.

Methods: We used a light/dye-injury model of thrombosis in the cremaster microcirculation of wild-type mice and mice deficient in toll-like receptor-4 (C57BL/10ScNJ), toll-like receptor 2 (TLR2), or VWF.

Differential role of von Willebrand factor and P-selectin on microvascular thrombosis in endotoxemia.

Objective: Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet-microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia.

Methods And Results: A light/dye-induced thrombosis model was used in cremaster microvessels of saline or LPS-injected mice (wild-type, P-selectin-deficient, vWF-deficient, or littermate controls).

Transendothelial flow inhibits neutrophil transmigration through a nitric oxide-dependent mechanism: potential role for cleft shear stress.

Endothelial cells in vivo are well known to respond to parallel shear stress induced by luminal blood flow. In addition, fluid filtration across endothelium (transendothelial flow) may trigger nitric oxide (NO) production, presumably via shear stress within intercellular clefts. Since NO regulates neutrophil-endothelial interactions, we determined whether transendothelial flow regulates neutrophil transmigration.