The Mode of Action of Certain 3- and 5-Nitropyridines and Pyrimidines. IV. Development of Drug-Resistance by Trichomonas vaginalis.

SYNOPSIS. Certain 5-nitropyridines and pyrimidines are growth inhibitory to Trichomonas vaginalis in vitro. Populations were made resistant either to 2-amino-5-nitropyrimidine, or 2-amino-5-nitropyridine, or 2-hydroxy-5-nitropyridine, by growth in gradually increasing concentrations of one of these inhibitors. After resistance was maximal, clonal lines were established. The development of resistance to any one of these inhibitors was accompanied by resistance to the other two. Since cross-resistance was complete, these inhibitors act at the same locus. This in vitro resistance persisted in vivo.
Resistance was accompanied by an increase in the generation time and a decrease in the maximal obtainable population. These growth parameters were unique for each resistant clone. The growth of the clone made resistant to 2-amino-5-nitropyridine was the closest to the normal clone. Its metabolic capacity, as measured by conventional Warburg techniques, was less than half of the parent strain and anaerobically was the same as had been previously found for non-resistant cells which had been grown for 3 hr with inhibitor. The mechanisms of killing by the inhibitor and the development of drug resistance are the same. The inhibitor kills the cells by holding them in an early metabolic sequence. Some of them succeed in growing by using this metabolic sequence and reinforcing it with an alternate aerobic route.     

Effect of L-Dopa on the Locomotor Activity of Rats pretreated with 6-Hydroxydopamine

LARGE doses of 3,4-dihydroxyphenylalanine (dopa) cause increased locomotor activity in rats and mice pretreated with a peripherally acting decarboxylase inhibitor^1–3. The effect of dopa is enhanced in animals pretreated with a mono-amine oxidase inhibitor^4–7 and reduced when the decarboxylation of dopa in the brain is inhibited¹. Consequently, the increase in motor activity is thought to be due to the formation of catecholamines in the brain.     

Femoral ontogeny and locomotor biomechanics of Dryosaurus lettowvorbecki (Dinosauria, Iguanodontia)

Ontogenetic changes in femoral morphology and locomotion were analysed in the iguanodontian dinosaur Dryosaurus lettowvorbecki using cross-sectional data and applying principles of beam theory. The results presented here suggest that locomotor ontogeny in D. lettowvorbecki was more complicated than has generally been recognized. The percentage cortical area (a measure of the relative amount of bone) increases abruptly over a relatively short period during early ontogeny and then remains uniform during subsequent increases in body size. Modifications in cross-sectional shape also occur with increasing size, as demonstrated by differences in second moment of area ratios. The patterns of change in these properties indicate that the orientation of mechanical loadings acting on the femur of D. lettowvorbecki differed at various stages of growth and development. It is suggested that the alterations in femoral architecture described here reflect a shift from quadrupedality to bipedality early in the ontogeny of this animal.