环孢素联合丙种球蛋白和川芎嗪治疗小儿重型再生障碍性贫血

目的:观察环孢素(CsA)、静脉注射用丙种球蛋白(IVIG)、川芎嗪三者联合治疗重型再生障碍性贫血(SAA)的疗效.方法:观察环孢素联合IVIG和川芎嗪治疗12例SAA临床疗效及实验指标,并与CsA加IVIG治疗10例SAA对照组相比较.结果:CsA、IVIG、川芎嗪三者联用治疗SAA总有效率为83.3%,CsA加IVIG总有效率40%,两者比较有显著性差异(P＜0.05);血象、骨髓象与对照组相比较有统计学差异(P＜0.05);而细胞免疫功能与对照组相比无统计学差异(P＞0.05).结论:CsA、IVIG、川芎嗪三者联用治疗SAA有效、安全,是治疗SAA的有效方案之一.     

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.     

熊去氧胆酸联合胆维他与山莨菪碱治疗环孢素性肝损害比较

目的 观察熊去氧胆酸片联合胆维他片及单独山莨菪碱治疗肾移植术后环孢素性肝损害的疗效,寻找有效的治疗方法.方法 将肾移植术后28例环孢素性肝损害患者分为两组,A组:口服熊去氧胆酸片50 mg,tid胆维片25 mg,tid;B组:山莨菪碱40 mg加入5%葡萄糖注射液中,每天一次静点或10 mg每日4次口服,疗程1～3个月.结果 A组16例中有15例治愈(占93.8%),1例好转(占6.3%);B组12例中3例好转(25.0%),9例无效(占75.0%).结论 熊去氧胆酸与胆维他联合应用肾移植术后环孢素所致肝损害疗效明显优于山莨菪碱.     

钙调神经磷酸酶调控血管升压素诱导大鼠心脏成纤维细胞胶原合成的作用

目的：探讨钙调神经磷酸酶（CaN）信号通路对血管升压素（AVP）诱导新生大鼠心脏成纤维细胞（CF）胶原合成的调控作用。方法：采用胰酶消化法培养新生SD大鼠CF，应用羟基脯氨酸比色法测定细胞培养上清中羟基脯氨酸含量，CaN活性通过分光光度计测定。结果：①CF培养上清中羟基脯氨酸含量随着AVP浓度的升高而增加，其中10^-7mol／LAVP和10^-6mol／LAVP组羟基脯氨酸含量与空白对照组比较有显著性差异（均P〈0．01）；在0．5μg／mlCaN的特异性抑制剂环孢素共同干预下，羟基脯氨酸含量明显减少，并有统计学意义（P〈0．01）。②随着AVP浓度的升高，CF内CaN活性亦随之增高，与空白对照组比较，10^-7和10^-6mol／LAVP组细胞内CaN活性显著增高（P〈0．01）。③在10^-7mol／LAVP作用下，随着细胞内CaN活性的升高，CF培养上清中羟基脯氨酸含量随之增加，两者之间呈显著正相关（r=0．91，P〈0．05）：④在10^-7mol／LVI受体拮抗剂[d（CH2）5-Tyr2（Me）]AVP和10^-7mol／LAVP共同作用下，CF中CaN活性和培养上清中羟基脯氨酸含量与单独10^-7mol／LAVP作用组比较均显著降低，并有统计学意义（均P〈0．01）：结论：CaN信号通路在AVP诱导CF胶原合成过程中起到了重要的调控作用，该通路的激活可能是通过V1受体介导的.     

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.     

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。     

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.     

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.     

Ciclosporin-Monitoring bei Patienten mit chronischer Uveitis

ZusammenfassungHintergrund Ciclosporin (CsA) ist ein häufig verwendetes Medikament in der Behandlung der posterioren Uveitis. Während sich die Visusprognose der Uveitispatienten unter Therapie mit CsA deutlich gebessert hat, steht dem therapeutischen Nutzen das Auftreten von Nebenwirkungen, u.a. Nephrotoxitität und Entwicklung einer Hypertonie, gegenüber. Neuerdings wurde das C₂-Monitoring (CsA-Blutspiegel 2 h nach oraler Einnahme) als neuer sensitiver Parameter in der Transplantationsmedizin eingeführt.Patienten und Methode In die prospektiv angelegte Studie wurden bisher 15 Patienten mit posteriorer Uveitis eingeschlossen. Sie erhielten oral CsA (5 mg/kg KG 2-mal/Tag). Die Abhängigkeit zwischen C₂- und C₀-Blutspiegel wurde analysiert und mit der klinischen Sicherheit und Effektivität korreliert.Ergebnisse Eine große intra und interindividuelle Variabilität der C₀-Spiegel wurde wie erwartet in Abhängigkeit von Faktoren wie Comedikation und intestinaler Resorption beobachtet. Die C₂-Messungen korrelierten gut mit der klinischen Kontrolle der intraokularen Entzündung.Zusammenfassung Das C₂-Monitoring ist eine einfache und akkurate Alternative für das klinische Monitoring von CsA. Es ermöglicht eine Individualisierung der CsA-Dosierung für jeden Patienten und somit eine Verringerung der Nebenwirkungsrate.Der Inhalt des Beitrags wurde auf der 101. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft, 2004 vorgetragen.     

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...