Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.

The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays.

Targeted transarterial therapy of Vx-2 rabbit liver tumor with Yttrium-90 labeled ferromagnetic particles using an external magnetic field.

Background: Our goal was to study the efficacy of liver cancer embolization with magnetically targeted Yttrium-90 labeled ferromagnetic particles and establish the biodistribution profile of these particles.

Materials And Methods: Of twenty rabbits, nine underwent transarterial radioembolization of implanted Vx-2 tumor with increasing 90Y-MTC doses, three were treated with carrier particles alone, four remained untreated and four were sacrificed early to document biodistribution. At various intervals, animals were sacrificed and biodistribution, liver cancer viability and toxicity were measured.

Immunomodulatory effect of endotoxin on the development of latex allergy.

Background: Although numerous studies have been conducted delineating the clinical manifestations of latex allergy and characterizing the protein allergens, little is known regarding the natural history of the disease.

Objective: These studies were undertaken to investigate the immunomodulatory role of inhaled endotoxin on the development of latex-specific IgE-mediated responses to natural rubber latex (NRL) proteins by using a mouse model.

Methods: Female BALB/c mice were exposed to 25 microg of NRL proteins with or without increasing concentrations of endotoxin (50-25,000 EU) through the respiratory tract.

Intravesical administration of doxorubicin to swine bladder using magnetically targeted carriers.

Purpose: The feasibility of using magnetic targeted carriers (MTC) to deliver doxorubicin intravesically was studied in normal swine bladder. MTCs are microparticles consisting of metallic iron and activated carbon. Doxorubicin is adsorbed to the activated carbon component of the MTCs (MTC-DOX) while the iron component provides magnetic susceptibility.