Protective effect of FK506 in the reperfusion model after short-term occlusion of middle cerebral artery in the rat: Assessment by autoradiography using [125I]PK-11195

Abstract

The protective effect of the immunosuppressant agent FK506 in the regerfusion after short-term occlusion of the middle cerebral artery in the rat model was evaluated using [¹²⁵I]PK-1 1195 autoradiography. FK506 0.5 mg kg^-1 day^-1 was administered intramurally to Wistar rats weighing 260-300 g from one day prior to ischemia to seven days after ischemia. Reperfusion was performed after 30 or 60 min occlusion. Infarct area was evaluated by [¹²⁵l]PK-l 1195 autoradiography on the seventh day following occlusion. FK506 significantly reduced the infarct area in the caudate nucleus following 30 and 60 min occlusion, but significantly reduced the infarct area in the cortex only following 60 min occlusion. These results suggest that FK506 has a protective effect against reperfusion after short-term occlusion of the middle cerebral artery. [Neurol Res 2000; 22: 630–633]     

Implant treatment followed by living donor lung transplant: A follow-up case report

PatientsDental implant treatment in patients with complicated systemic disease has been discussed, especially in the context of achieving osseointegration. However, some patients with no pre-existing systemic disease develop it later, during their implant maintenance periods. Organ transplants, and the lifelong administration of immunosuppressants that follows, are also of relevance to post-implant oral health. Thus, strategies to maintain the health of peri-implant tissue in these patients should be considered. Here, we present the case of a patient receiving a living-donor lung transplant during her implant follow-up period. The condition of the lung is affected by that of the oral cavity, so the maintenance is of utmost importance. Throughout the follow-up period, we provided periodical professional maintenance care.Discussion and conclusionThe patient experienced no complications, alterations in her radiographic findings, or worsening of periodontal indices, despite being extensively medicated with immunosuppressants, steroids and bisphosphonate.     

肝肾联合移植28例临床分析

目的 总结肝肾联合移植治疗终末期肝脏合并肾脏疾病的体会.方法 对28例肝肾联合移植的临床资料进行回顾分析,并对手术适应证的选择、手术方式、免疫制剂方案的应用以及预后情况进行了分析整理和总结.结果 肝肾联合移植各种适应证中,肝肾功能衰竭占78.6 %(22/28),肝肾综合征占14.3 %(4/28),高草酸盐尿症及多囊肾合并多囊肝各占3.6 %(各1/28).所有受者均先行肝移植,再行肾移植.肝移植采用背驮式者4例,采用经典非转流式者24例,供肾植入位置首选右侧髂窝.术后随访5个月至7年8个月,受者1年存活率为92.9 %(26/28),3年存活率为78.3 %(18/23).28例受者中,围手术期发生移植肾功能不良4例,其中3例经保守治疗病情好转,1例死亡.1例因移植肝并发症于术后3个月再次行肝移植治疗,后好转,期间肾功能未受影响.术后发生肺部感染11例,其中1例死亡,其余10例经治疗后痊愈.无一例发生急性排斥反应.结论 肝肾联合移植是治疗终末期肝脏合并肾脏疾病的有效手段,术前应严格控制手术适应证,把握适当的手术时机.

Abstract：

Objective To summarize the experience of treating the end stage of liver disease complicated with renal failure using combined liver-kidney transplantation.Methods The clinical data of 28 cases receiving combined liver-kidney transplantation were retrospectively analyzed, including the inclusion criteria of surgical indications, modus operandi, protocol of immunosuppression and the prognosis post-operation.Results Among these 28 cases in our study, 22 cases suffered from liver and renal failure, accounting for 78.6%; 4 cases were diagnosed as having hepatorenal syndrome, accounting for 14.3%; and 1 case had hyperoxaluria and polycystic liver with polycystic kidney. As for the modus operandi we used, piggy-back procedure was adopted for 4 patients and classic procedure without bypass was used for the rest. Donor kidneys were all put in the right iliac fossa. During the follow-up period of 5 months to 7 years, one-and 3-year survival rate of the recipients was 92.9% and 78.3% respectively. Among these 28 recipients, 4 cases had the graft renal dysfunction early post-operation: One died and 3 recovered through consecutive therapy. One case received re-transplantation of the liver 3 months after the first due to the relevant complications and then recovered. During this period, no impact on the renal function occurred. Eleven cases had pulmonary infection post-operation, and 1 died. No acute rejection occurred.Conclusion Combined liver-kidney transplantation is the effective treatment to the patients with end stage liver disease complicated with renal dysfunction. Suitable case selection and perfect operation timing were the key points to the success of combined liver-kidney transplantation.     

肺移植术后稳定状态受者T淋巴细胞亚群的动态变化分析

目的  分析肺移植术后稳定状态受者1年内T淋巴细胞亚群的动态变化及影响因素。方法  收集行同种异体肺移植手术且术后处于稳定状态的41例受者的临床资料。采用流式细胞术检测受者术前、术后2周及每个月（术后1年内）外周血T淋巴细胞亚群绝对值和比值。分析受者年龄、性别、体质量指数（BMI）、手术方式、原发性移植物功能障碍（PGD）发生情况及原发病对T淋巴细胞绝对值的影响。结果  肺移植术后1年内,CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺T淋巴细胞绝对值及CD4⁺/CD8⁺比值随时间变化差异有统计学意义（均为P < 0.001）。与术前相比,术后12个月CD3⁺、CD3⁺CD4⁺T淋巴细胞绝对值差异均无统计学意义（P=0.659、0.109）,CD3⁺CD8⁺T淋巴细胞绝对值升高（P=0.02）,而CD4⁺/CD8⁺比值下降,差异有统计学意义（P < 0.001）。肺移植受者的年龄、性别、BMI、手术方式以及术后是否出现PGD对CD3⁺CD4⁺、CD3⁺CD8⁺T淋巴细胞绝对值的动态变化无影响（P > 0.05）。肺移植术前原发病对CD3⁺CD4⁺T淋巴细胞的变化无影响,但感染性肺疾病受者术后CD3⁺CD8⁺T淋巴细胞绝对值较高（P < 0.05）。结论  肺移植术后稳定状态受者CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺T淋巴细胞绝对值在术后早期较低,随后逐渐恢复,术后6个月后达到稳态。其动态变化与受者年龄、性别、BMI、手术方式以及术后是否出现PGD无关。     

免疫抑制剂对合并或不合并移植后糖尿病肾移植患者自测健康的影响

目的:研究环孢素、他克莫司对合并或不合并移植后糖尿病肾移植患者自测健康的影响。方法:根据是否合并有移植后糖尿病和服用的主要免疫抑制剂,将门诊肾移植患者分为合并糖尿病组、不合并糖尿病组、环孢素组、他克莫司组,应用自测健康评定量表(SRHMS)进行调查。结果:合并有移植后糖尿病肾移植患者生理、心理、社会健康比不合并糖尿病组明显偏低,二者有显著性差异(P<0.01);环孢素、他克莫司对合并移植后糖尿病的肾移植患者生理、心理、社会健康的影响无显著性差异;他克莫司对不合并移植后糖尿病的肾移植患者生理健康的身体症状与器官功能维度、心理健康的正向情绪维度方面较环孢素组得分高,二者有显著性差异(P<0.05)。结论:移植后合并糖尿病明显影响肾移植患者的自测健康;对不合并移植后糖尿病肾移植患者,服用他克莫司的比服用环孢素的有更好的生理健康和心理健康。     

Retrospective evaluation of the efficacy and safety of belatacept with thymoglobulin induction and maintenance everolimus: A single‐center clinical experience

Belatacept use has been constrained by higher rates of acute rejection. We hypothesized that belatacept with low‐dose rATG and initial mycophenolate maintenance with conversion to everolimus at 1 month post‐transplant ± corticosteroids would improve efficacy and maintain safety. Retrospective single‐center analysis of the first 44 low immunologic risk kidney transplant recipients treated with this regimen. The cohort was 59% male, mean age at transplant of 57 years. Diabetes was the most common cause of ESRD (39%). The mean 1‐year eGFR was 61.4 (SD 18.4) mL/min/1.73 m². There were five acute cellular rejections (11.4%) that occurred in patients who had changed from everolimus to mycophenolate mofetil due to side effects. Thirty‐two percent developed BK viremia and 12% developed CMV viremia. There were no cases of PTLD. A novel belatacept regimen with rATG induction and maintenance everolimus demonstrated a low acute rejection rate and maintained an excellent 1‐year eGFR.     

溃疡性结肠炎的治疗现状及前景

溃疡性结肠炎是结、直肠慢性非特异性炎症性疾病,多呈反复发作的慢性病程。本病治疗难度大,与结肠癌的发病有关,被WHO列为现代难治病之一。目前溃疡性结肠炎的治疗手段多样,出现了许多新技术如生物靶向治疗、干细胞移植等,现将近年来溃疡性结肠炎现代医学研究进展进行综述。     

前列地尔治疗反应指导CNI类免疫抑制剂减量的作用

目的探讨前列地尔应用于肾移植术后患者的治疗反应,指导钙调神经蛋白抑制剂（calcineurin inhibitor,CNI）类药物减量的临床应用价值。方法回顾性分析42例同种异体肾移植术后〉1年,肌酐140～250 mmol/L,环孢素或他克莫司血药浓度正常,因肌酐升高于2010年6月至2011年5月在我科住院患者,应用前列地尔治疗效果指导CNI类药物减量,改善移植肾功能的有效率。结果 42例患者经前列地尔治疗后肌酐均有不同程度的下降,其中38例肌酐下降〉20%,平均下降率为23.8%,减少CNI类药物用量后,肌酐稳定出院;2例肌酐分别下降18.7%、14.5%,CNI减药后发生急性排斥反应;2例肌酐分别下降11.9%、16.5%,免疫抑制方案未予调整,停用前列地尔后肌酐稳定出院;前列地尔治疗反应指导CNI类药物减量改善移植肾功能的有效率为95.0%。结论利用前列地尔治疗反应指导CNI类药物减量是一种简便、有效的方法,弥补了血药浓度监测调整CNI类药物用量存在局限性的不足,在临床上有一定的实用价值。     

广东地区98家医院2007-2011年免疫抑制剂利用分析

目的:了解广东地区医院免疫抑制剂的应用情况及趋势。方法:收集广东地区98家医院2007-2011年免疫抑制剂的应用数据,对其名称、用量、销售金额等进行统计、分析。结果:该地区医院免疫抑制剂的销售金额和用量呈逐年上升趋势,2008年比2007年分别增长24.2%、20.9%,2009年比2008年分别增长23.8%、13.9%,2010年比2009年分别增长17.5%、11.7%,2011年比2010年分别增长12.0%、8.0%。从剂型方面看,片剂、胶囊及注射液的用量在近5年均排在前3位;单品种用量排序列前3位的分别是醋酸泼尼松、甲泼尼龙、雷公藤多苷。结论:免疫抑制剂在该地区医院的用量和销售金额均呈上升趋势,开发高效、不良反应少、价廉、新型的免疫抑制剂具有重要意义。     

Inhibitory actions of HERG currents by the immunosuppressant drug cyclosporin a

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC(50) value and a Hill coefficient of 3.17 μM and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.