What is the role of andexanet alfa in the reversal of anticoagulant effects?

Although using direct oral anticoagulants increases patient risk for hemorrhagic events, FDA-approved options for reversing anticoagulant effects are limited. This article discusses one of the more recent FDA-approved antidotes, andexanet alfa, and provides guidelines for its safe and effective use.

Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo.

The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor hexa-D-arginine amide delays anthrax toxin-induced toxemia both in cells and in live animals, suggesting that furin inhibition may represent a reasonable avenue for therapeutic intervention in anthrax.

The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo.

The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-D-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-D-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.

The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view.

Intrapituitary adenoviral administration of 7B2 can extend life span and reverse endocrinological deficiencies in 7B2 null mice.

The prohormone convertase PC2 requires the aid of a helper protein, known as 7B2, for production of active enzyme. Deletion of 7B2 results in a lethal phenotype resembling Cushing's disease. In this study, we have investigated the effect of a single low dose of recombinant adenovirus vector encoding 7B2 and delivered directly to the pituitary of 7B2 nulls on pituitary ACTH, plasma ACTH, corticosterone, alpha MSH and glucose, and survival time.