Ramatroban for chemoprophylaxis and treatment of COVID-19: David takes on Goliath.

Introduction: In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB ≫ PGE > PGD in the lungs, and 11-dehydro-TxB, a TxA metabolite, in the systemic circulation. While TxA stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA/TP and PGD/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.

Uptake and reduction of alpha-lipoic acid by human erythrocytes.

Objectives: The reducing capacity of erythrocytes has been used clinically as to estimate resistance to oxidant stress. In this work we targeted the antioxidant capacity of pyridine nucleotide disulfide reductases of these cells by measuring their ability to reduce the disulfide alpha-lipoic acid.

Methods: Erythrocyte reduction of alpha-lipoic acid and related disulfides was measured as reduction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) outside the cells.

Cellular disulfide-reducing capacity: an integrated measure of cell redox capacity.

To assess the disulfide reduction capacity of intact cells, EA.hy926 endothelial cells were incubated with alpha-lipoic acid in the presence of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Alpha-lipoic acid was reduced within cells to dihydrolipoic acid, which could be quantified upon efflux from the cells as reduction of DTNB.

Effective attenuation of endotoxin-induced acute lung injury by 2,3-diacetyloxybenzoic acid in two independent animal models.

The pathology of acute lung injury (ALI) is often modeled in animal studies by the administration of lipopolysaccharide (LPS), which results in an endotoxemia with sequelae similar to that seen in acute respiratory distress syndrome (ARDS). Here we report the results of two studies designed to examine the efficacy of a novel agent, 2,3-diacetyloxybenzoic acid (2,3-DABA), in the treatment of LPS-induced ALI. In two separate animal models, 2,3-DABA was effective in significantly reducing lung microvascular permeability, a condition commonly seen in ARDS, which results in pulmonary edema and respiratory insufficiency.