The effect of various acrylonitriles and related compounds on prostaglandin biosynthesis.

We have studied the effect of nearly 90 arylacrylonitrile derivatives, and several related compounds, on the biosynthesis of prostaglandins from bovine seminal vesicle microsomes. This effect was compared to that of triarylacrylonitrile derivatives known for their inhibiting properties. Several arylacrylonitrile derivatives have also proved good inhibitors, especially certain N-trisubstituted compounds: trans (dimethylamino-4 phenyl)-3 (methoxy-4' phenyl)-2 acrylonitrile was the best inhibitor of the group, with an IC50 of 0.

Influence of new hydroxylated triphenylethylene (TPE) derivatives on estradiol binding to uterine cytosol.

Twelve homologous triphenyl acrylonitrile derivatives with a p-OH or p-CH3 group on one or more of the phenyl rings were synthesized in order to assess the relative influence of each position on binding to the estrogen receptor (ER) and on inhibition of prostaglandin synthetase (PGS). Their relative binding affinities (RBAs) for [3H]estradiol (E2)-labeled ER were compared at 0 and 25 degrees C in mouse and rat uterus cytosol with those of tamoxifen derivatives, cyclofenil and diethylstilbestrol. RBAs in both species were closely correlated (r = 0.

Fine-structural changes in the midgut of old Drosophila melanogaster.

Variations of the mitochondrial structure with increasing age are of particular interest because the production of ATP is necessary for most cellular activities. Therefore, a senescent decrease of mitochondrial activity could jeopardize cell survival and function. We combined a statistical with a morphological approach to investigate these changes in mitochondrial size and structure of Drosophila melanogaster.

[Myocardial infarction before the age of 35. Clinical and coronarographic aspects].

Myocardial infarction under the age of 35 is no longer a rarity. A series of 22 patients exhibited all the usual epidemiological, clinical and angiographic features of the disease: risk factors, predominantly excessive smoking associated with dyslipoproteinaemia in 50% of the cases; onset during exercise in one quarter of the cases, more frequently than in elderly people; and absence of significant lesions at angiography in one third of the cases. Angiography of the coronary arteries, performed in the early stages of infarction in 5 patients, demonstrated the presence of several factors in the pathogenesis of arterial occlusion in young people, i.

Inhibition of prostaglandin synthetase by di- and triphenylethylene derivatives: a structure-activity study.

The syntheses of new di- and triphenylethylene derivatives are described along with their X-ray analysis and NMR study, which have helped to establish their conformation. Screening of over 50 derivatives for inhibition of prostaglandin synthetase (PGS) activity in bovine seminal vesicle microsomes has revealed that many of the triphenylethylene derivatives are potent inhibitors of PGS. Several even show marked activity at the extremely low concentration (IC50) of about 4 X 10(-8) M, which is two orders of magnitude lower than the active concentration of the majority of known nonsteroidal antiinflammatory agents (IC50 approximately equal to 10(-6) M).

[Are calcium inhibitors useful in the treatment of effort angina pectoris].

Effort angina is the result of acute myocardial ischemia on exercise due to an imbalance between myocardial oxygen demand and supply. During exercise, ischemia is provoked by an increase in myocardial oxygen needs (tachycardia, increased blood pressure, etc.) which cannot be met by increased coronary blood flow.

Role of metabolic rate and DNA-repair in Drosophila aging: implications for the mitochondrial mutation theory of aging.

The respective roles of respiration rate and DNA repair in determining the life-span of Drosophila melanogaster have been investigated in three wild strains (Oregon R, Domodedov 32, & Swedish C) and two mutants (w/w & w/mei-41 D5). In agreement with the rate of living theory, there was an inverse relation between oxygen consumption and median life-span in flies having normal DNA repair. In contrast, w/mei-41 D5, showed an abnormally low life-span as compared to the controls.

Effects of simulated increased gravity on the rate of aging of rats: implications for the rate of living theory of aging.

Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g.

Thiazolidine-4-carboxylic acid, a physiologic sulfhydryl antioxidant with potential value in geriatric medicine.

Thiazolidine-4-carboxylic acid (TC) is a cyclic sulfur amino acid, a condensation product of cysteine and formaldehyde. The chemistry, biological effects and clinical use of TC are reviewed. Extensive animal experiments and studies on human subjects carried out in Europe indicate that a combination of TC and folic acid, 'Folcysteine', has revitalizing effects on age-related biochemical variables of blood and tissues.

Antioxidants, metabolic rate and aging in Drosophila.

In line with the (metabolic) rate-of-living theory of aging, previous work from this laboratory showed that the life-prolonging effect of the antioxidant thiazolidine carboxylic acid (TCA) in Drosophila was paralleled by a similar reduction of the oxygen consumption rate of the flies. To assess the generality of this phenomenon, several life-prolonging antioxidants were dietarily administered to the flies (in standard medium with 1% w/v of tocopherol-stripped corn oil) and their effects on metabolic rate and life span were determined. Respiration rate of groups of continuously agitated flies was measured in the Gilson respirometer.