Pharmacokinetics of mycophenolic acid in Chinese patients with liver transplant / 药学学报

<p><b>AIM</b>To investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.</p><p><b>METHODS</b>Thirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.</p><p><b>RESULTS</b>The plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.</p><p><b>CONCLUSION</b>In view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.</p>

Clinical Research of Blood CsA C2 Level Monitoring in Renal Allograft Recipients / 上海第二医科大学学报

Objective To decrease the incidence of acute rejection in renal allograft recipients by monitoring of cyclosporine A (CsA) concentration at 2-hour after dosing(C2). Methods The CsA C2 and CsA trough concentration(C0) were assayed in renal allograft recipients.All patients were followed up for at least 1 year.The correlation of C0 and C2 monitoring with clinical outcomes was analyzed. Results At 1 week and 1 month post-transplantation,the incidence of acute rejection in patients with C2 in target level was 4.41% and 10.29%, respectively,but the incidence of acute rejection in patients with C2 in lower level was 42.37% and 36.20%,respectively. ConclusionBy reflecting the drug exposure of CsA more accurately,C2 monitoring is beneficial for decreasing the incidence of acute rejection after renal allograft transplantation.

Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways act as potent immunoregulatory cells in vitro and vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer.</p><p><b>METHODS</b>Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator. Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells. The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested. For in vivo studies, anergic cells were intravenously injected into 3.0-Gy gamma-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation. To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy [1 mg.day(-1).kg(-1)].</p><p><b>RESULTS</b>Anergic cells strongly suppressed the proliferation of naicaron;ve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naicaron;ve BALB/c splenocytes against the third-party (C57BL/6J) stimulator. The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2. In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8.6 +/- 1.1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11.8 +/- 1.9) days, which was slightly longer than that of the untreated mice. The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29.6 +/- 4.4) days].</p><p><b>CONCLUSIONS</b>Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro, and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy. This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed.</p>

Expression of fractalkine and its receptor in acute cardiac allografts rejection / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of fractalkine (FKN) and its receptor CX3CR1 in cardiac allografts and the effect of Cyclosporin A (CsA).</p><p><b>METHODS</b>Three groups of rats underwent heterotopic cardiac transplantation, 45 cases in each group and 5 cases in control group: SD to SD regarded as isograft group (group A), Wistar to SD divided into CsA untreated allograft group (group B) and CsA treated allograft group (group C), normal SD rats as control group. The FKN mRNA expression was detected by one-step RT-PCR method and the expression of FKN and CX3CR1 protein was detected by standard ABC immunohistochemical technique.</p><p><b>RESULTS</b>The expression of FKN mRNA and protein was weak in both isografts and normal heart specimens. The changes of FKN mRNA expression were correlated with the process of acute allograft rejection. The peak of FKN mRNA expression (0.8 +/- 0.26) appeared on the seventh day after transplantation, which could be down-regulated by CsA significantly (t = 2.390, P < 0.05). FKN protein was located in endothelia cells and its receptor CX3CR1 was located in infiltrating mononuclear cells in allografts.</p><p><b>CONCLUSIONS</b>Upregulation of FKN and its receptor was significantly correlated with the trafficking of mononuclear cells which play an important role in acute allograft rejection. It may be one of the important mechanisms of CsA to intervene the acute rejection by inhibiting the activation of the FKN-CX3CR1 pathway.</p>