Aldehyde oxidase and its contribution to the metabolism of a structurally novel, functionally selective GABAA alpha5-subtype inverse agonist.

(3-Tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d] [1,2,4]triazine was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5-containing receptors, which enhances performance in animal models of cognition. The routes of metabolism of this compound in rat, dog, rhesus monkey and human in vitro systems, and in vivo in rat, dog and rhesus monkey have been characterized. The current study demonstrates that both a cytosolic oxidative reaction and cytochrome P450 play important roles in the metabolism of the compound. Chemical inhibition studies showed the oxidation in human cytosol to be catalysed predominantly by aldehyde oxidase rather than the related enzyme, xanthine oxidase. The aldehyde oxidase-mediated metabolites were present in vitro and in vivo in both rat and rhesus monkey, and also in vitro in man. They were absent both in vitro and in vivo in dog.

Youth's recreation and drug sensations: is there a relationship?

Adolescents' social behaviors remain a mystery to parks and recreation providers. Adolescence is a "high-risk" time for all youth in terms of experimenting with potentially health-compromising behavior, whether alcohol, drugs, or sex. Most of these antisocial behaviors occur during adolescents' leisure time. These inferences gave impetus to this research effort. The study was designed to ascertain information on adolescents' preferences for pleasure: drugs or recreation. Data were collected from a sample of 100 high school students from a medium-sized college town, and 100 students from a rural town in Florida. Findings revealed four statistically significant associations in the motives or pleasures sought in recreation and in drug behaviors: "enhancement of popularity," "provision of a means for self-discovery," "achievement of personal goal," and means to rebel against parents. In reference to the latter motive, findings revealed that neither drugs nor recreation were used to rebel against parents. Findings also provide documentation of the value of recreation in insulating adolescents against many of the stressors of contemporary life.

An insect cell line persistently infected with a baculovirus-like particle.

A persistent infection by a baculovirus-like particle was found in the established lepidopteran (Heliothis zea) cell line, IMC-HZ-1. The virus caused CPE in less than 1% of the IMC-HZ-1 cells, as measured by phase-contrast and electron microscopy. Transmission tests showed that four lepidopteran cell lines were susceptible to the persistent virus (designated as IMC-HZ-I-NOV). In inoculated TN-368 cell cultures, 90--100% infection was achieved. The ultrastructure and development of IMC-HZ-I-NOV in cell cultures were similar to known baculoviruses, and it is probable that this persistent virus is a member of the family Baculoviridae. Two lepidopterous species (Estigmene acrea and H. zea) inoculated with IMC-HZ-1-NOV by intrahemocoelic injection and/or per os feeding of larvae were not susceptible.