ABSTRACT
AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms. METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX.
ABSTRACT
Objective To evaluate the clinical value of speckle tracking imaging in the measurement of two-dimensional strain in patients with myocardial infarction. Methods High frame rate two-dimensional echocardiography were performed in 30 healthy subjects,21patients with anterior myocardial infarction and 15 patients with inferior myocardial infarction. Longitudinal strain (LS), radial velocity (Vs), regional shortening fraction (RFS),radial strain (RS) were measured in the apical two-chamber view and short-axis view(the level of papillary muscle) using two-dimensional strain software. Results Compared with healthy subjects, LS, Vs, RFS, RS decreased in the segments with infarction(P<0.05). LS, Vs, RFS, RS of the two myocardial infarction groups had partly differences(P<0.05). Conclusions Regional wall motion of left ventricle in patients with myocardial infarction can be evaluated accurately with speckle tracking imaging.
