Pathophysiology of acetaminophen overdosage toxicity: implications for management.

Acute acetaminophen intoxication was studied in the dog to characterize pathogenesis and in the mouse as a model for antidotal research. In the dog, overt toxicity was manifested principally by cyanosis, facial and paw edema, gastrointestinal disturbance, and coma. Typical laboratory findings were methemoglobinemia, hemoconcentration, leukocytosis, and hepatic centrolobular necrosis. In the mouse, physical signs of acetaminophen overdose appeared to be central in origin; sequelae included anemia, leukopenia, thrombocytopenia, and hepatic centrolobular necrosis. The antidotal profile of acetylcysteine in mice was characterized. When acetylcysteine therapy was instituted early (one hour after acetaminophen overdose), it conferred dose-related protection from lethality coupled with hepatoprotection, as judged from transaminase activity. When acetylcysteine therapy was instituted relatively late (4 1/2 hours after acetaminophen overdose), its beneficial effect on survival persisted but was unaccompanied by distinct hepatoprotection, indicating that SGPT activity was an unreliable prognostic indicator. Acetylcysteine was well tolerated in mice even when administered in the presence of preexisting acetaminophen-induced liver damage.

Possible ion-pair-mediated absorption of mixidine II: plasma levels and histology.

Plasma intact 14C-mixidine levels in rats increased when the drug was administered intraduodenally with 1:3 and 1:5 molar ratios of 2-naphthalenesulfonic acid. Upon histological examination of the duodenums, similar doses of mixidine combined with 2-naphthalenesulfonic acid produced no dose-related lesions. These and previous observations demonstrate that mixidine absorption may be enhanced by ion-pair formation.

Morphogenesis and histogenesis of the cartilaginous tracheal rings in the domestic fowl (gallus domesticus).

The morphogenesis, histogenesis and growth pattern of the tracheal rings were studied in chick embryos and in chickens up to 4 months of age. The blastemas representing the earliest ring primordia are seen to arise in the embryo in the cranial portion of the tracheal tube on the 10th day of incubation, and to extend rapidly caudalwards. They form first in the anterior wall of the tracheal tube and expand successively laterally and posteriorly. The mesenchymal blastemas that have acquired the shape of complete rings differentiate into precartilage and then into typical hyaline cartilage. During growth, the tracheal rings undergo striking changes in both shape and position. In the embryo, an active growth rate in a craniocaudal direction prevails, and after hatching each ring outstretches cranially and caudally into two long expansions (winglike projections). Moreover, these rings, which in early embryos were regularly aligned in a longitudinal row, are seen to become alternately located with their higher halves on an inner plane and their lower halves on a more superficial plane. Such a peculiar ring displacement on two different planes may reasonably be assumed to obey spatial requirements, since ring growth rate according to a craniocaudal direction is far more vigorous than growth, in the same direction, of the tracheal wall housing them.