自1989年巴西医生Raia开展人类首例活体肝移植（living donor liver transplantation, LDLT）以来，LDLT受体的优良预后及供体的安全性逐步得到了公认，加之“脑死亡”供肝的严重匮乏，LDLT技术迅速发展并被公认为是缓解供肝来源匮乏最有效的方法之一［1，2］。LDLT技术的发展大致经历了三个阶段： ①成人→儿童间活体肝移植（简称儿童活体肝移植，pediatric living donor liver transplantation, PLDLT）； ②成人→成人间活体肝移植(adulttoadult living donor liver transplantation, ALDLT)； ③急诊活体肝移植(emergency or highurgency living donor liver transplantation, ELDLT )。LDLT技术发展的每一阶段均是对前一阶段技术的总结和升华，技术难度和复杂性也逐步增加。
ObjectiveTo explore the effects of several immunosuppressants on the proliferation of pheochromocytoma 12 (PC12) and L929 cells. 〖WTHZ〗Methods Different concentrations of methylprednisolone(10-3,10-4, 10-6and 10-8 mol/L), cyclosporin A(CsA,10-5 ,10-6 , 10 -7and 10-8 mol/L) and FK506 (10-6 ,10-7 , 10-8and 10-9mol/L)were administrated to the PC12 and L929 cells, while control group was given no drugs. At 24, 48 and 72 hours after administration, the cell proliferationwasmeasured with MTT methods respectively. The results were compared and analyzed statistically. Results High concentration methylprednisolone (10-3 mol/L) and low concentration CsA (10-8-10-7mol/L) could promote the proliferation of PC12 cells within 48 hours after administration, after that, the proliferation effects were no longer significant. There were no promotion effects for different concentrations of FK506. Under high concentrations, both CsA (10-6 -1×10-5 mol/L) and methylprednisolone (10-3 mol/L) could significantly inhibit the proliferationof L929 cells after 24 hours of administration. And high concentration (10-6mol/L) FK506 could promote the proliferation of L929 cells transitorily (only for 48 hours after administration). Conclusion 10-3 mol/L methylprednisolone and 10-8 -10-7mol/L CsA can promote the proliferation of PC12 cells for a short period of time. Both 10-3 mol/L methylprednisolone and 10-6-10-5mol/L CsA can significantly inhibit proliferation of L929.
Objective To explore the effects of several immunosuppressants on the cell numbers of cultured rat macrophages and Schwann’s cells. Methods The macrophages and Schwann’s cells were cultured from the newborn Wistar rats. Different concentrations of methylprednisolone(10-3, 10－4,10－6 and 10－8 mol/L), CsA(10－5, 10－6, 10－7 and 10－8 mol/L) and FK506(10-6, 10－7, 10－8 and 10－9 mol/L) were administrated to the cells, while control group was given no drugs. Twentyfour, 48 and 72 hours after administration, the cells from different concentrations were measured with MTT methods respectively. Theresults were compared and analyzed statistically. Results Only high concentration methylprednisolone (10-4 mol/L) and a certain range of concentrations of CsA (10-6，10-7 and 10-8 mol/L) and FK506 (10-7,10-8 and 10-9 mol/L) can provide protection to culturedrat macrophages. Under most concentrations, CsA and FK506 had no effects onthe cell number of cultured rat Schwann’s cell. Only with high concentration CsA (10-5 mol/L) and methylprednisolone (10-3 mol/L) could significantly decreased the cell number of Schwann’s cell. Long time (72 hours) and low dosage (10-8 mol/L) administration of methylprednisolone could significantlyprotect Schwann’s cell. Conclusion High concentration methylprednisolone and some certain concentration CsA and FK506 can protect cultured rat macrophages. But high concentration CsA and methylprednisolone prohibit the proliferation of Schwann’s cells. Only long time and low dosage methylprednisolonecan protect cultured rat Schwann’s cells.
OBJECTIVE: To sum up the clinical results of allogeneic humeral transplantation with vascular anastomosis, and evaluate the clinical significance. METHODS: From September to November 1979, 1 case with humeral shaft defect of 10 cm in length and 2 cases with tibia shaft defect of 12 cm in length were repaired by allogeneic humeral transplantation with vascular anastomosis. Azathiopurine and prednisone were applied for 3 months postoperatively. All cases were followed up for 20 years. RESULTS: Case 1 recovered well with good bone union and reconstruction after operation, and could work normally. In case 2, five chronic rejections were occurred during 3 years after operation, and recovered after treatment, the allograft bone was fractured after 2 years of operation, and unioned by autogeneous iliac bone transplantation. In case 3, the distal part of allograft bone was fractured after 46 months, and unioned by autogeneous iliac bone transplantation. The middle part of allograft bone was non-unioned after 20 years follow-up in case 3, but the patient could still work normally. CONCLUSION: The clinical results of allogeneic long bone transplantation can be improved by rational tissue matching test, application of effective immunosuppressive drugs in a certain period according to the principles of modern transplantation immunology.
The corticosteroids are the firstline therapeutical agents for noninfectious uveitis patients, but systemic corticosteroids are ineffective for some chronic or recurrent patients, and have many long term usagerelated side effects; these patients may need treatment of immunosuppressive agents and/or biologic agents. However, the mechanism, indication, efficacy and sideeffects of each type of the immunosuppressive agents or biologic agents are not identical. In clinical practice, we should use different and sensitive immunosuppressive agents or biologic agents for different types of uveitis, and watch their efficacy and toxic effects closely. In order to improve the effectiveness of the treatment, the classification, efficacy and existing concerns of commonly used uveitis drugs need to be further clarified.
Objective To assess the effects of different immunosuppressive drugs on proliferation and function of regulatory T cells (Tregs). Methods We searched MEDLINE (1966 to November 2009), EMbase (from inception to September 2009), and The Cochrane Library (Issue 4, 2009) for clinical and basic research about the effects of various immunosuppressive drugs on Tregs. Data were extracted and methodological quality was assessed by two independent reviewers. Outcome measures for clinical research included blood Tregs levels, acute rejection episodes, and graft function. Outcome measures for basic research included percentage of Tregs proliferation, function, Tregs phenotype, and evidence for possible mechanisms. We analyzed data qualitatively. Results Forty-two studies, including 19 clinical trials and 23 basic studies, were included. The immunosuppressive drugs studied were calcineurin inhibitors (CNIs), Rapa, anti-metabolism drugs, IL-2 receptor-blocking antibodies, T-cell depleting antibodies, and co-stimulation blockade antibodies. Most of the studies were on Rapa and CNIs. Eight basic studies on Rapa and CNIs showed that Rapa could promote the proliferation and function of Tregs, while CNIs could not. Five clinical trials involving a total of 158 patients showed that patients taking Rapa had higher blood concentration of Tregs than those taking CNIs, but no differences were found in graft function (6-42-month follow-up). Conclusion There is substantial evidence that Rapa favors Tregs survival and function. However, the larger number of the blood Tregs in the patients treated with Rapa does not show any correlation with better graft function. Large-sample and high-quality clinical studies with longer follow-up are needed to thoroughly assess the efficacy of immunosuppressive drugs on Tregs and to reveal whether a relationship exists between Tregs and graft function.
Objective To evaluate the safety and efficacy of steroid withdrawal in modern triple immunosuppressant (Cycloproine/Tacrolimus, Mycophenolate Mofetil and Steroid) on renal transplantation recipients. Methods We searched MEDLINE (1966-Sep. 2005), OVID (1966-2004), EMBASE (1984-2004), The Cochrane Library (Issue 4, 2005), CBMdisc (1994-2005), and handsearched 7 Chinese Journals. Randomized controlled trials (RCTs) adopting modern triple immunosuppressant, and comparing steroid withdrawal (SW), group and steroid continuing group (SC) were selected. The quality of included studies was evaluated and graded according to Cochrane Reviewer’s Handbook 4.2.5, and meta-analysis was performed by using RevMan 4.2.7 software. Results Nine RCTs including 1 681 patients (845 in SW and 836 in SC) were identified. The average follow-up time was 6-12 months. No significant difference was found in using CsA or Tac in modern triple immunosuppressant. The results of our meta-analysis showed: ① the risk of acute rejection was two times higher in SW than SC (RR 2.05, 95% CI 1.54 to 2.72, P lt;0.000 01), mainly Banff grade I (mild) (RR 1.92, 95% CI 1.16 to 3.17, P =0.01); but no significant differences were found on Banff grade II and III between the two groups. ② the rate of graft and patient survival and chronic rejection were the same between two groups. ③ Steroid withdrawal decreased the incidence of opportunistic infection (mainly caused by simplex herpes virus and Candida) and urinary tract infection. While the incidence of CMV and sepsis infection has no significant difference between two groups. Conclusion Steroid withdrawal within 3 months in modern immunosuppressive regimen ① increases the risk of Banff Grade I rejection reaction, but the moderate and severe rejection are similar between the two groups; ② doesn’t affect the rate of graft, patient survival, and chronic rejection; ③ decreases the incidence of opportunistic and urinary tract infection, but doesn’t improve the CMV infection and sepsis. To prophylaxis serious infection, steroid withdrawal is worth considering under sufficient immunosuppressive regimen. The key point is to balance the benefit and harm for individual recipients.
目的:探讨激素及免疫抑制剂导致乙肝病毒再激活所致的肝损害的危害性及治疗效果，指导临床治疗。方法：总结本院近2年收治的7例慢性乙肝病毒感染者在使用激素及免疫抑制剂致肝炎再激活并加重患者的临床资料进行分析。结果：慢性乙肝病毒感染者因各种原因使用激素及免疫抑制剂所导致的慢性乙肝的复发加重，病情发展迅速，病死率高。结论：抗乙肝病毒治疗是预防肝病复发并恶化的关键，在激素或免疫抑制剂治疗前和治疗中都应使乙肝病毒降至尽可能低的水平。