Biomedical subjects
F R Nelson
Publications and source records attributed to F R Nelson.
Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity.
Seven aromatic polycyclic hydrocarbons (PCHs) were investigated for their toxic effects on respiratory mucosa: benzo(e)pyrene (BeP), pyrene, anthracene, benz(a)anthracene(BaA), dibenz(a,c)anthracene(DBacA), benzo (a)pyrene (BaP), and dimethylbenz(a)anthracene (DMBA). The compounds were chosen because they comprise a spectrum of PCHs ranging from noncarcinogens, to initiators, to weak and strong carcinogens. All of them except DMBA are environmentally relevant chemicals. The chemicals were tested over an 8-week period. Heterotopic tracheal transplants were continously exposed and the histopathologic effects induced by the various PCHs were periodically assessed semiquantitatively. All PCHs exhibited varying degrees of toxicity for respiratory epithelium and submucosa. BeP clearly showed the least toxicity followed by pyrene and anthracene. BaA and DBacA caused marked epithelial and submucosal changes. In addition to epithelial hyperplasia, undifferentiated epithelium and squamous metaplasia developed. Marked mononuclear infiltration occurred in the subepithelial connective tissue. With BaP the epithelial and submucosal changes were similar but were much stronger. DMBA was the most toxic substance, causing epithelial necrosis followed by generalized keratinizing squamous metaplasia; the subepithelial changes consisted of an early acellular exudate and, later (at 8 weeks), marked condensation and hyalinization of the lamina propria. The toxic response pattern of the tracheal mucosa to carcinogenic agents was characterized by the chronicity of epithelial and connective tissue damage, as opposed to the short-lived hyperplastic and inflammatory response elicited by the noncarcinogens and weak initiators.
Development of a system for controlled release of benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and phorbol ester for tumor induction in heterotopic tracheal grafts.
Explore the source record for details and available documents.
Two-wheeled shopping cart. An inexpensive aid to ambulation.
Explore the source record for details and available documents.
Disposition of acrivastine in the male beagle dog.
Three male beagle dogs were given 10 mg/kg iv and oral doses of [14C]acrivastine, a novel nonsedating antihistaminic agent, in a nonrandomized crossover experiment. Urine and feces were collected for 72 hr after dosing. After iv dosing, a mean of 34% was recovered in the urine, and 63% was recovered in the feces. After po dosing, a mean of 29% of the radiocarbon was recovered in the urine, and 63% was recovered in the feces (dose adjusted for 14% lost in vomitus). Acrivastine and three major metabolites were detected in the excreta. The metabolites were identified as a side-chain-reduced analog of acrivastine (metabolite 3, 270C81), a gamma-aminobutyric acid analog of 270C81 (metabolite 2), and a benzoic acid analog of 270C81 (metabolite 1). After iv dosing, 34% of the dose was excreted as parent drug, 21% as metabolite 3, 15% as metabolite 2, and 6% as metabolite 1, while after po dosing, 35% of the dose was excreted as parent drug, 18% as metabolite 3, 11% as metabolite 2, and 7% as metabolite 1. Pharmacokinetic analysis of acrivastine plasma concentration-time curves after both routes of administration indicated a mean total body clearance of 17.3 ml/min/kg, a Vss of 0.93 liter/kg, a terminal half-life of 0.7 hr, and an oral bioavailability of 40%. The apparent plasma half-life of the metabolite, 270C81, was 1.5 hr. Analysis of AUC values indicated that greater amounts of 270C81 than acrivastine circulated in plasma after both iv and po dosing, and that first-pass metabolism of acrivastine to 270C81 occurred. The results indicated that acrivastine was extensively metabolized in the dog to 270C81 and suggested that 270C81 itself underwent further metabolism to metabolites 1 and 2.