ABSTRACT
Carboxylesterase(CES), the most abundant hydrolase in humans and animals, participates in the metabolism of various endogenous and exogenous compounds and drugs. The distribution and activity of CES have obvious species differences in hu mans and animals, which are closely related to the pharmacokinetics(PK), pharmacodynamics(PD)and toxic side effect of drugs. Therefore, this paper summarizes the effects of the difference in the classification, distribution, induction and inhibition of CES as well as the effects of species difference in plasma, liver, small intestine and skin on the metabolism of ester prodrugs, so as to provide a reference for the correct selection of experimental animals in preclinical studies of new drugs to accurately predict the clinical PK, PD and toxicological effects.
ABSTRACT
With the continuous progress of virtual simulation technology, medical surgery visualization system has been developed from two-dimensional to three-dimensional, from digital to network and intelligentization. The visualization system with mixed reality technology will also be used in all stage of medical surgery, such as case discussion, surgical planning, intraoperative guidance, post-operative evaluation, rehabilitation, so as to further promote high intelligence, high precision of medical surgery, and consequently improve effectiveness of treatment and quality of medical service. This paper discusses the composition and technical characteristics of medical operation visualization system based on mixed reality technology, and introduces some typical applications of mixed reality technology in medical operation visualization, which provides a new perspective for the application of mixed technology in medical surgery.
ABSTRACT
Nobiletin is a kind of polymethoxyflavonoid with many pharmacological effects, such as antiinflammatory and antioxidation activities. This study was carried out to investigate the inhibitory effects of nobiletin on P-glycoprotein (P-gp) in vitro and in vivo. The molecular mechanism for structure-inhibition relationships of nobiletin with P-gp was investigated. Nobiletin exhibited significant inhibition (IC50=2.21 μmol·L-1) on P-gp in MDR1-MDCKⅡ cells. In the cell toxicity test, the paraquat-treated cell viability was decreased with nobiletin by inhibiting P-gp activity. In the rats PK study, the AUC0-t of digoxin was increased 2.02 folds while the Cmax of digoxin was increased 3.29 folds, when nobiletin was used in the pretreatment of SD rats. Molecular docking analysis elucidated that the formation of Pi-Pi bonds with Phe974 was the key factor for P-gp inhibition. The research findings provide important guideline for prediction of potential interaction between nobiletin and P-gp.