Pharmacokinetics of glaucine after intravenous and oral administrations and detection of systemic aporphine alkaloids after ingestion of tulip poplar shavings in horses.

Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( t 1 / 2 α ) and beta ( t 1 / 2 ß ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( AUC 0 ∞ iv ) was 45.4 (34.7-52.3) h*ng/ml, and the volume of distribution of the central (Vdc ) and peripheral (Vdp ) compartments was 2.7 (1.3-4.6) and 4.9 (4.3-8.2) L/kg, respectively. A one compartment model best described the oral administration of glaucine with absorption ( t 1 / 2 ka ) and elimination ( t 1 / 2 kel ) half-lives of 0.09 (0.05-0.15) and 0.7 (0.6-0.8) h, respectively. The area under the curve ( AUC 0 ∞ PO ) was 15.1 (8.0-19.5) h·ng/ml. Bioavailability following oral administration was 17%-48%. Following ingestion of shavings, glaucine and liriodenine were detectable in plasma for up to 16 and 48 h, respectively. Glaucine was quantifiable briefly in the urine from two horses. Liriodenine was quantifiable in urine for 12-20 h in four horses and for 48 h in two horses. The presence of liriodenine indicates ingestion of tulip poplar tree parts, however, does not rule out co-administration of purified glaucine in horses.

Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.