Donna J. Fournier

Variations in ATPase activity in the development of experimental cataracts.

Summary Determinations of Mg ATPase and Na/K ATPase activity in lens epithelium and in decapsulated lenses or lens fibers were made in lenses obtained from rats on normal and galactose diets at 0, 6, 15, and 23 days of the experimental period. Galactose feeding resulted in a marked lowering of Mg ATPase activity in the epithelium after 6 days on the diet. The level of Na/K ATPase activity was markedly decreased in the fibers after 15 days on the diet. The lowering of Na/K ATPase activities in the fibers may provide a possible link between the known decrease in the glutathione early in the cataractogenic process and the known destruction of fiber membranes that is associated with the appearance of mature cataracts.

A Gompertz Age-Specific Mortality Rate Model of Aging, Hormesis, and Toxicity: Fixed-Dose Studies

Based on the proposition that the logarithm of age-specific mortality rate (Gompertzian) is a linear measure of the mean intensity of injury for a homogeneous mammalian population in a uniform environment, a model was developed which characterizes mortality experience resulting from both toxic and hormetic actions. The mortality-reducing component (longevity hormesis) was assumed to be reversible; toxic effects, on the other hand, were assumed to accumulate irreversibly. Following chronic low-dose administration of selected toxic substances, it was demonstrated (in certain cases) that longevity hormesis could enhance lifespan, even in the presence of concomitant toxicity. Even when toxicity was evident, hormesis could ameliorate some of the mortality. The assumption that high-dose chronic toxicity studies can generate realistic estimates of risk at low doses is challenged.

A Gompertz age-specific mortality rate model of aging: modification by dietary restriction in rats

A Gompertz age-specific mortality rate model characterizing actuarial effects of food restriction in rats was developed based on mortality data from the study of Yu et al. (J. Gerontol. 40: 657-670, 1985). Results indicated that in the presence of adequate nutrition, food restriction reduces the aging rate parameter in a consistent manner, regardless of the age at which food restriction is initiated.

Lens regeneration after mature galactose cataract formation.

Summary Following the development of mature cataracts in the lenses of rats, one group of rats was placed on a normal diet and a control group continued on the galactose diet. New healthy lens fibers were formed around a dense opaque nucleus in the lenses of rats on the normal diet. Those that were continued on a galactose diet had lenses that were completely opaque. The implication of this observation for further experimental studies and for the interpretation of the etiology of cataractogenesis is discussed.

Inhibition of [3H]5-HT binding to rat brain membranes by psychotomimetic amphetamines

A number of psychotomimetric amphetamines have been tested for their ability to inhibit specific [3H]5-HT binding to rat brain membranes. Although the compounds studied showed only weak affinities for the specific [3H]5-HT sites, their IC50 values correlated roughly with their rank order in human hallucinigenic potency.

Structure activity correlations in the inhibition of brain synaptosomal3H-norepinephrine uptake by phenethylamine analogs. The role of α-alkyl side chain and methoxyl ring substitutions

alpha-Ethylphenethylamine proved to be a weaker inhibitor of rat brain synaptosomal [3H]norepinephrine ([3H]NE) uptake than amphetamine, while 2-amino-tetralin and 2-amino-1,2-dihydronaphtalene, compounds in which the alpha-side chain ethyl group is tied to the aromatic ring have a similar inhibiting potency as amphetamine. Hallucinogenic polymethoxy substituted phenethylamine analogs have very low inhibitory potencies indicating that inhibition of NE-reuptake in brain noradrenergic neurons is not associated with the drug-induced hallucinogenic syndrome.