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Methods: Male Wistar rats were suckled in litters with six or 12 pups (L6 and L12 groups). Animals swam at postnatal days (P) 8–23, or P60–P75 (early-exercised or late-exercised groups, respectively), or remained no-exercised. Behavioral tests (open field – OF and object recognition – OR) were conducted between P77 and P80. Between P90 and P120, ECoG was recorded for 2 hours. After this ‘baseline’ recording, CSD was elicited every 30 minutes over the course of 2 hours.
Results: Early swimming enhanced the number of entries and the percentage of time in the OF-center (P?<?0.05). In animals that swam later, this effect occurred in the L6 group only. Compared to the corresponding sedentary groups, OR-test showed a better memory in the L6 early exercised rats, and a worse memory in all other groups (P?<?0.05). In comparison to baseline values, ECoG amplitudes after CSD increased 14–43% for all groups (P?<?0.05). In the L6 condition, early swimming and late swimming, respectively, reduced and enhanced the magnitude of the post-CSD ECoG potentiation in comparison with the corresponding L6 no-exercised groups (P?<?0.05).
Discussion: Our data suggest a differential effect of early- and late-exercise on the behavioral and electrophysiological parameters, suggesting an interaction between the age of exercise and the nutritional status during lactation. 相似文献
In this study, total body clearance (CLt), volume of distribution at steady state (Vss) and plasma concentration–time profiles in humans of model compounds were predicted using chimeric mice with humanized livers.
On the basis of assumption that unbound intrinsic clearance (CLUint) per liver weight in chimeric mice was equal to those in humans, CLt were predicted by substituting human liver blood flow and liver weights in well-stirred model. Vss were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SFKp) in chimeric mice estimated from a difference between the observed and predicted Vss. These physiological approaches showed high prediction accuracy for CLt and Vss values in humans.
We compared the predictability of CLt and Vss determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method.
Simulation of human plasma concentration–time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CLUint and SFKp obtained from chimeric mice.
Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.