玉屏风颗粒联合泼尼松和环孢素治疗特发性膜性肾病的临床研究

目的 分析玉屏风颗粒联合泼尼松和环孢素治疗特发性膜性肾病的临床疗效。方法 选取河池市中医医院在2020年3月—2022年7月收治的90例特发性膜性肾病患者,随机分为对照组和治疗组,每组各45例。对照组口服醋酸泼尼松片,起始剂量为1 mg/(kg∙d),共服用4周,此后每周减量10 mg维持;同时口服环孢素胶囊,剂量为3～5 mg/(kg∙d),1次/12 h。治疗组在对照组方案基础上口服玉屏风颗粒,5 g/次,3次/d。两组患者治疗3个月。观察两组患者临床疗效,比较治疗前后两组患者中医证候积分,肾功能指标24 h尿蛋白定量（24 h UP）、血尿素氮（BUN）、血清肌酐（Scr）和血清白蛋白（Alb）,及Th17/Treg免疫平衡指标。结果 治疗后,治疗组临床有效率为（91.11%）明显高于对照组（73.33%,P＜0.05）。治疗后,两组患者中医症候积分均有降低（P＜0.05）;治疗组主要中医证候积分均明显低于对照组（P＜0.05）。治疗后,两组患者24 h UP、BUN、Scr、Th17、Th17/Treg明显低于治疗前,而Alb和Treg高于治疗前（P＜0.05）,且治疗组肾功能指标和免疫指标明显好于对照组（P＜0.05）。结论 玉屏风颗粒联合泼尼松和环孢素治疗特发性膜性肾病临床疗效显著,可改善患者主要中医症候和肾功能指标,调节Th17/Treg免疫平衡态,治疗安全性较好。     

Treatment of pure red-cell aplasia and aplastic anaemia with ciclosporin: long-term clinical effects

6 patients with pure red-cell aplasia were treated with Ciclosporin (Cyclosporine A; CS) alone or combined with prednisolone for a period of 9-46 (median 27) months. Prior to study, 5 cases had refractory disease, steroids were contraindicated in 1, and 4/6 patients, including 2 cases with congenital disease, had a disease duration exceeding 11 years. A complete haematological response was obtained in 5/6 subjects, and a partial response in 1. When the pre-treatment Hb levels (mean +/- S.D. = 64 +/- 13 g/l, range 41-80) for all 6 PRCA patients were compared with the Hb levels after 6 months of CS therapy (104 +/- 17 g/l, 80-125), a significant improvement was registered (p less than 0.005). In half of the patients, remission is maintained with CS as single drug in a dose-dependent manner. We also treated 5 patients with refractory severe aplastic anaemia with CS (1 case) or CS plus prednisolone (4 cases) for 3-27 (median 10) months. Only 1 patient responded. In this case, a complete haematological remission was induced with CS alone, and remission has been maintained for 27 months. Side effects of CS therapy were common but were dose-dependent and reversible, with the exception of persistent nephrotoxicity in 1 patient with pure red-cell aplasia. Based on our present results and a survey of the literature, we conclude that CS therapy is effective and indicated in refractory pure red-cell aplasia. In severe aplastic anaemia resistant to conventional immunosuppression, the response rate is lower, but a small proportion (around 15%) of patients may benefit from CS therapy. Longer treatment periods may, however, be needed to evaluate the role of CS in aplastic anaemia.     

Manejo práctico de inmunosupresores en dermatología

The treatment of inflammatory and autoimmune diseases is challenging because of their frequency and complexity. Treatment of these diseases is based on the suppression of the patient's immune system using corticosteroids, corticosteroid-sparing immunosuppressive agents, and biologic drugs, making an understanding of the management of immunosuppressive therapy essential.Before an immunosuppressive agent is prescribed, a study must be carried out to identify contraindications, detect latent infections, and determine the most appropriate dose. During treatment, regular monitoring is required to detect adverse effects. The clinician must be familiar with the time lag between start of treatment and onset of the immunosuppressive effect as well as the maximum recommended duration of treatment and cumulative dose for each drug. As dermatologists we are accustomed to using these immunosuppressive agents, but we should have a good knowledge of the guidelines for their use and the monitoring required in each case if we are to reduce variability and avoid potentially serious adverse effects.     

Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy

De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed.
We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients.     

Ca2+-dependent modulation of single human cardiac L-type calcium channels by the calcineurin inhibitor cyclosporine

OBJECTIVE: Activity of single L-type calcium channels (LTCC) is enhanced in human failing myocardium (Circulation 98 (1998) 969.), most likely due to impaired dephosphorylation. Protein phosphatase 2B (calcineurin) has recently been shown to be involved in heart failure pathophysiology. We now focus on the regulation of single LTCC by calcineurin that were prevented by Ca(2+)-free experimental conditions in our previous study. METHODS: Single LTCC currents were recorded in myocytes from human atrium and ventricle. Charge carriers were 70 mM Ba(2+), or a mixture of 30 mM Ca(2+) and 60 mM Ba(2+) to facilitate Ca(2+) permeation through recorded channels. The calcineurin inhibitor cyclosporine (10 microM) was used to reveal a putative role for calcineurin in regulation of LTCC. RESULTS: A mixture of Ca(2+) and Ba(2+) as charge carriers allowed for Ca(2+) permeation through recombinant human embryonic kidney cells and native (atrial and ventricular) human cardiac LTCC. With only Ba(2+) as the charge carrier, activities of both ventricular and atrial LTCC were strongly decreased by cyclosporine. In contrast, channel activity remained constant when Ca(2+) permeation was provided. In the presence of thapsigargin and (S)-BayK 8644, cyclosporine here even increased channel activity. CONCLUSIONS: We propose a dual cyclosporine effect on human cardiac LTCC. A non-specific inhibitory effect prevails with Ba(2+) permeation but can be compensated or overcome by a specific Ca(2+)-dependent stimulation with Ca(2+) permeation. More complete restoration of physiological Ca(2+) movements (e.g., Ca(2+) release from sarcoplasmic reticulum) will help to define even more precisely the involvement of calcineurin in regulation of human cardiac LTCC.     

非洛地平缓释剂治疗肾移植术后高血压患者的中远期疗效观察(附37例报告)

目的 研究非洛地平缓释剂治疗肾移植术后高血压患者的中远期疗效与安全性.方法 74例肾移植患者随机分为非洛地平缓释剂治疗组(研究组)和硝苯地平对照组(对照组)各37例.研究组给予口服非洛地平缓释剂,起始剂量为每次2.5 mg,每日1次;对照组给予口服硝苯地平,起始剂量为每次10 mg,每日3次.根据血压控制情况调整两组的...     

环孢素A与吗替麦考酚酯治疗难治性肾病综合征疗效对比

目的：通过检测临床指标的变化,观察对比环孢素A和吗替麦考酚酯治疗难治性肾病综合征的疗效差异。方法：将本院自2008年1月以来收治的56例原发性难治性肾病综合征患者随机分为CsA、MMF两组,在口服泼尼松0.5mg.kg-1.d-1治疗的基础上,CsA组口服环孢素4mg·kg-1.d-1,MMF组口服吗替麦考酚酯0.75mg2/d,进行1年的随访,在治疗前、治疗3、6、12个月分别记录尿常规、24h尿蛋白定量、肝功能（AST、ALT、Alb）、肾功能（CRE,UA,GLU）、血脂以及环孢素血药浓度等指标的变化,并记录不良反应。结果：从治疗1个月开始,部分患者的尿蛋白定量减轻,血浆白蛋白水平开始有所恢复,前后结果差异有统计学意义（P〈0.05）,两组患者之间差异无统计学意义（P〉0.05）。结论：环孢素A、吗替麦考酚酯均可以有效的治疗难治性肾病综合征,治疗同期两者差异不明显。     

CsA对缺血再灌注心肌高能磷酸化合物代谢的影响

目的：研究环孢素A（CsA）对大鼠心肌缺血再灌注损伤能量代谢的影响。方法：建立大鼠离体心肌缺血再灌注模型,测定心肌梗死面积,使用高效液相色谱（HPLC）法测定心肌组织中高能磷酸化合物ATP、ADP和AMP的含量,测定心肌组织Na^＋-K^＋-ATPase以及乳酸脱氢酶（LDH）活性,观察环孢素A（0．1mg/mL）的保护作用。结果：环孢素A能显著降低缺血再灌注心脏灌流液的LDH水平,提高心肌组织ATP含量和能量物质的储备,降低心肌组织ATPase活性。结论：环孢素A对大鼠心肌缺血再灌注损伤有一定的保护作用。其作用机制可能与增加缺血区心肌能量物质含量,降低ATPase活性,改善能量代谢障碍有关。     

灵芝多糖拮抗环孢素A,氢化可的松及抗肿瘤药的免疫抑制作用

灵芝多糖在50,100和200μg·ml~1时可完全拮抗环孢素A,丝裂霉素C,氟尿嘧啶和阿糖胞苷对小鼠混合淋巴细胞反应(MLR)的轻度抑制(抑制50％以下)作用,部分拮抗氢化考的松对MLR的严重抑制(抑制50％以上)作用。     

In Vitro Model for Ciclosporin Intestinal Absorption in Lipid Vehicles

The influence of lipid vehicles on the intestinal absorption of Ciclosporin was studied in vitro. The effect of the intestinal lipid digestion was considered on the partition of the drug from olive oil or middle-chain triglyceride (MCT) into phases of simulated intestinal content. The phases obtained after ultracentrifugation were analyzed for their Ciclosporin content and characterized for their lipid classes. For both lipid vehicles the presence of lipolysis products did not promote the partition of the drug into the aqueous phase. The absorption in vivo was not related to the drug amount in the aqueous phase and in the oil phase. Therefore, phase quantification in vitro cannot simulate the dynamics of in vivo absorption events following application of a poorly water-soluble drug in a lipid vehicle.