In vitro immune cell monitoring as a guide for long-term immunosuppression in adult liver transplant recipients

BACKGROUNDS/AIMS: We evaluated the clinical usability of immune cell monitoring in adult liver transplantation (LT) recipients. METHODS: This study was composed of two parts as using calcineurin phosphatase (CNP) activity assay and ImmuKnow assay independently as in vitro monitoring tools of immune cell function in adult LT recipients. RESULTS: There was a rough correlation between CNP activity and tacrolimus concentration in 33 patients. This association was evident in patients who were only administered tacrolimus, but disappeared after the co-administration of mycophenolate. In 118 healthy individuals, the mean proportion of helper T-cells was 37.4+/-8.1%. According to ImmuKnow assay, their immune responses were strong in 12 patients (10.2%), moderate in 92 patients (78.0%), and low in 14 patients (11.9%). In 85 patients waiting for LT, there was a rough correlation between the ImmuKnow ATP level and age. Their immune responses were strong in 0 patients (0%), moderate in 8 patients (9.4%), and low in 77 patients (90.6%). There was a difference in the ImmuKnow ATP levels between healthy individuals and patients with liver disease. In 137 LT recipients, there was no correlation between the ImmuKnow ATP levels and tacrolimus concentration. This trend did not change after grouping the patients according to co-administration with mycophenolate. Eight recipients experienced acute rejection, but none showed strong immune response. CONCLUSIONS: We think that both CNP activity assay and ImmuKnow assay are too limited to objectively determine the level of immunosuppression. Further studies should be performed to identify other methods for immune function monitoring.

Protection of Angelica sinensis extract against left ventricular hypertrophy of rats / 中草药

Objective: To investigate the protection of Angelica sinensis extract on the left ventricular hypertrophy (LVH) of rats and explore the possible mechanisms. Methods: Male SD rats were randomly divided into Sham, model, and low-, mid-, and high-dose A. sinensis extract (25, 50, and 100 mg/kg), and L-arginine (200 mg/kg) positive control groups. Except for Sham group, the rats with LVH were induced by abdominal aorta coarctation and were administered from the next day after surgery once daily for consecutive 21 d. Changes of cardiac hypertrophy parameters and hemodynamic indexes of rats were observed. Left ventricular myocardial fiber diameter (MD) was determined. Electron microscopy was used to observe the ultrastructure of myocardial tissue. RT-PCR was used to determine the mRNA expression of atrial natriuretic factor (ANF) and calcineurin phosphatase (CaN). Western blotting was used to determine the expression of α-subunit of calcineurin phosphatase (CnA). Results: Compared with Sham group, the left ventricular hypertrophy index (LVHI), the left ventricular weight/right ventricular weight (LVW/RVW), and MD were remarkably increased, the expression of ANF, CaN mRNA, and CnA protein was obviously elevated. A. sinensis extract could remarkably decrease LVHI, tend to or significantly decrease LVW/RVW, improve the indicators of systolic and diastolic function, and down-regulate the expression of ANF, CaN mRNA and CnA protein. Conclusion: A. sinensis extract has the protection against LVH induced by abdominal aorta coarctation in rats, and the mechanism may be related to its inhibitory effects on CaN signaling pathway.

Effect of Anti-tuberculosis Therapy on Plasma Concentration of Calcineurin Phosphatase Inhibitors in Renal Transplant Recipients / 中国药房

OBJECTIVE:To discuss the effect of anti-tuberculosis therapy on plasma concentration of calcineurin phosphatase inhibitors in renal transplant recipients.METHODS:The change in plasma concentration of calcineurin phosphatase inhibitors in 2 renal transplant recipients who were complicated with tuberculosis infection before or after renal transplantation was analyzed.The patients were routinely treated with cyclosporine(CsA)or tacrolimus(FK506)+ mycophenolate mofetil(MMF)+ prednisolone(Pred).Monoclone fluorescence polarization immunoassay(FPIA)was employed to determine the concentration of CsA or FK506 in different time point before and after administration of antituberculosis drugs.RESULTS:Plasma concentration of CsA was down-regulated significantly by Rifampicin,and the daily dose of CsA has to be increased to more than 3 times the previous concentration before meeting the target concentration.The concentration of FK506 was slightly down-regulated by rifapentine.CONCLUSION:The concentration of CsA or FK506 and the adverse effect of antituberculotic drugs should be closely monitored for renal transplant recipients complicated with tuberculosis infection.