1 Nateglinide, a novel oral hypoglycemic agent, rapidly reaches the maximum serum concentration after oral administration, suggesting that it is rapidly absorbed in the gastrointestinal tract. The aim of this work is to clarify the intestinal absorption mechanism of nateglinide by means of in vitro studies. 2 We examined the transcellular transport and the apical uptake of [ 14 C]nateglinide in a human colon carcinoma cell line (Caco-2). We also examined whether nateglinide is transported via monocarboxylate transport-1 (MCT1) by means of an uptake study using MCT1-expressing Xenopus laevis oocytes. 3 In Caco-2 cells, the transcellular transport of [ 14 C]nateglinide from the apical to basolateral side was greater than that in the opposite direction. The uptake of [ 14 C]nateglinide from the apical side was concentration ± dependent, H + -dependent, and Na + -independent. Kinetic analysis revealed that the Kt and Jmax values of the initial uptake rate of [ 14 C]nateglinide were 448 mM and 43.2 nmol mg protein 71 5 min 71 , respectively. Various monocarboxylates, including salicylic acid and valproic acid, and glibenclamide signi®cantly inhibited the uptake of [ 14 C]nateglinide. 4 The uptake study using MCT1-expressing oocytes showed that nateglinide inhibits the MCT1-mediated uptake of [ 14 C]L-lactic acid, though nateglinide itself is not transported by MCT1. 5 Taken together, these results suggest that the uptake of nateglinide from the apical membranes of Caco-2 cells is, at least in part, mediated by a proton-dependent transport system(s) distinct from MCT1.
Background: Intestinal expression of peptide absorption transporter (PepT1)/Slc15a1 exhibits circadian oscillation, but the mechanism is unknown. Results: During the daily feeding cycle, bile acids accumulated in intestinal cells, thereby suppressing PPAR␣-mediated expression of PepT1/Slc15a1. Conclusion: Time-dependent suppression of PPAR␣ activity by bile acids underlies circadian expression of PepT1/Slc15a1. Significance: Bile acids cause circadian change in the intestinal absorption of peptides.
Background/Aim: To develop and evaluate the accuracy of augmented reality (AR)-based patient positioning systems in radiotherapy. Materials and Methods: AR head-mounted displays (AR-HMDs), which virtually superimpose a three-dimensional (3D) image generated by the digital imaging and communications in medicine (DICOM) data, have been developed. The AR-based positioning feasibility was evaluated. Then, the setup errors of three translational axes directions and rotation angles between the AR and the conventional laser-based positioning were compared. Results: The AR-based pelvic phantom positioning was feasible. The setup errors of AR-based positioning were comparable to laser-based positioning in all translational axis directions and rotation angles. The time necessary for AR-based positioning was significantly longer than that for laser-based positioning (171.0 s vs. 47.5 s, p<0.001). Conclusion: AR-based positioning for radiotherapy was feasible, and showed comparable positioning errors to those of conventional line-based positioning; however, a markedly longer setup time was necessary.
Materials and MethodsThis study, because it involved a phantom experiment, did not require the approval of an institutional review board (IRB).
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