The study of Raddeanin A cerebrovascular endothelial cell trafficking through P-glycoprotein.

As one of the natural triterpenoids isolated from Anemone Raddeana Regel, Raddeanin A (RA) has been confirmed to possess therapeutic effects against multiple tumorigeneses, especially for the onset of glioblastoma and growth in human brains. However, the mechanism by which this happens remains poorly understood in terms of the vascular endothelium trafficking routine of RA through the brain-blood barrier (BBB). To seek such answers, human brain microenvironment endothelial cells (HBMECs) were used to stimulate the microenvironment in vitro, and to explore the intracellular accumulation of RA. The results of this experiment illustrated that RA has a relative moderate transport affinity for such cells. The kinetic parameter Km was 37.01 ± 2.116 µM and Vmax was 9.412 ± 0.1375 nM/min/mg of protein. Interestingly, protein downregulation of P-glycoprotein (P-gp, ABCB1/MDR1) significantly activated RA transmembrane activity, which proves that P-gp is responsible for RA cellular trafficking. In addition, the selective non-specific inhibitor, LY335979 increased either RA or the classical substrate of P-gp, digoxin, intracellular accumulation by restricting the transporter's function but without jeopardizing cytomembrane proteins. Moreover, a decrease in the expression or activity of P-gp triggered RA drug resistance to HBMECs. In summary, our data showed that both the expression and function of P-gp are all necessary for RA transmembrane trafficking through cerebrovascular endothelial cells. This study provides significant evidence for the presence of a connection between RA transport and P-gp variation during drug BBB penetration. It is also suggesting some vital guidance on the RA pharmacodynamic effect in human brains.

[The impact of human serum immunoglobulin treatment of refractory immune thrombocytopenic purpura. Analysis].

AIM: To observe the impact of human serum immunoglobulin treatment of refractory immune thrombocytopenic purpura in clinical efficacy. METHODS: 220 patients met the diagnostic criteria of refractory immune thrombocytopenic purpura, patients were randomly divided into treatment group and control group, 110 patients in each group. Groups were given prednisolone tablets 1 mg/ (kg x d), 2 times/d, oral, taking for 2 weeks, and than gradually reducing, the maintenance to be suspended; all-trans retinoic acid, each 10 mg, 3 times a day, oral. On this basis, the treatment group increases the employing blood immunoglobulin 400 mg/ (kg x d) infusion qd for 7 days. The two groups are 4 weeks for the course of treatment, a therapeutic effect after treatment. RESULTS: The total effective treatment group and control group were 94.56%, 80.91%, statistically significant differences between two groups (P < 0.05). Treatment serum IL-2, IFN-gamma, IL-4, IL-10, TGF-beta1, significant differences compared to other indicators (p < 0.05). Platelet counts after treatment, the rates of increase, effective hemostasis time of the treatment group compared with the control group, significant difference (p < 0.05). CONCLUSION: The impact of human serum immunoglobulin treatment of refractory immune thrombocytopenic purpura significantly shorten the bleeding time, platelet and platelet rise-time return to normal time.