国产环孢素A合并小剂量皮质类固醇激素治疗狼疮性肾炎的临…

使用国产小剂量环孢素Ａ（ＣｙＡ）合并小剂量皮质类固醇激素治疗６例狼疮性肾炎取得较满意的临床和免疫学疗效。与进口ＣｙＡ对照，两组间无统计学显著差异。     

环孢素A治疗严重银屑病：临床及血清细胞因子研究

报告了小剂量环孢素Ａ（ＣｙＡ）治疗严重银屑病的临床和血清细胞因子研究情况。６例严重的银屑病患者经ＣｙＡ治疗４－８周后临床症状基本消失。血清细胞因子研究结果如下：（１）银屑病患者的血清ｓＩＬ－２Ｒ，ＩＬ－２及ＴＮＦ－α水平明显升高（２）ＣｙＡ治疗银屑病症状缓解后血清ｓＩＬ－２Ｒ，ＩＬ－２水平明显降低，其中ＩＬ－２降至正常水平，ＳＩＬ－２Ｒ明显降至正常水平以下，血清ＴＮＦ－α仍明显高于正常水平。分析表     

国产环孢素A对郎格罕细胞及接触过敏的影响

环孢素Ａ（ＣｙＡ）作为非细胞毒免疫抑制剂，近年来广泛应用于某些皮肤病的治疗并取得较好的疗效。主要认为ＣｙＡ能抑制ＣＤ＋４Ｔ淋巴细胞及角朊细胞的增殖，但其全部作用机理尚未明了。最近研究发现ＣｙＡ对银屑病患者郎格罕细胞、中性粒细胞、内皮细胞等亦产生影响［１］。郎格罕细胞作为皮肤抗原提呈细胞在接触过敏反应中起关键作用。有作者［２，３］分别报道ＣｙＡ在体内、外均有减少和影响ＡＴＰａｓｅ＋ＬＣ数量及抗原提呈功能的作用。我们采用国产ＣｙＡ对小鼠表皮ＬＣ及ＣＨＳ两方面结合进行研究，观察其影响。一、资料和方法１…     

环孢素A及雷公藤内酯醇对CD4^＋T细胞,角质形成细胞和Hela细 …

目的 比较环孢素Ａ（ＣｙＡ）和雷公藤提取物Ｔ０对ＣＤ４＾＋Ｔ细胞，角质形成细胞和Ｈｅｌａ细胞增殖的影响。方法 采用人外周血单一核细胞（ＰＢＭＣ），人表皮角质形成细胞和Ｈｅｌａ细胞培养，＾Ｈ－ＴｄＲ掺入法测定药物对细胞ＤＮＡ合成的影响，结果Ｔ０和ＣｙＡ都能抑制ＣｏｎＡ诱导的人外周血Ｔ淋巴细胞增殖。Ｔ０在体外可抑制生长于低无血清角质形成细胞培养基中的正常人角持形成细胞和Ｈｅｌａ细胞株的生长，而ＣｙＡ     

增列细胞核抗原,细胞周期素E及细胞周期蛋白依赖性激酶抑制 …

目的 探讨细胞周期相关因子增殖细胞核抗原（ＰＣＮＡ）、细胞周期素Ｅ（ｃｙｃｌｉｎＥ）、ｐ２１（ＷＡＦ１／ＣＩＰ）、ｐ２７在ＨＰＶ６／１１相关尖锐湿疣（ＣＡ）病变中的各种变化及其意义。方法 应用原位杂交技术诊断ＨＰＶ６／１１相关ＣＡ,采用ＳＰ免疫组化染色技术检测５０例ＨＰＶ６／１１阳性ＣＡ患者皮损、２５例正常人皮肤（包 皮）中ＰＣＮＡ、ｃｙｃｌｉｎＥ及ｐ２１、ｐ２７的表达及分布。结果 ①ＣＡ皮损中Ｐ     

性传播疾病

２００１１２７３人乳头瘤病毒１６型Ｅ６／Ｅ７基因对人角质形成细胞生长及ＣｙｃｌｉｎＡ，ＣｙｃｌｉｎＤ１和ｃｄｋ４的影响／马翠玲（四军大西京医院皮肤科）…／／第四军医大学学报．－２０００，２１（９）．－１１５６～１１５８ 为了研究 １６型人乳头瘤病毒（ＨＰＶ）Ｅ６／Ｅ７对人角质形成细胞周期素（ＣｙｃＣｌｉｎＡ，ＣｙｃｌｉｎＤ１）及细胞周期素依赖性激素（ｃｄｋ４）的影响。采用Ｌｉｐｏｆｅｃｔａｍｉｎｅ介导法将ＰＬＸＳＮ１６Ｅ６／Ｅ７质粒转染逆转录病毒包装细胞ＰＡ３１７，挑选Ｇ４１８抗性克隆，检测病毒滴…     

环孢素A与雷公藤对IL-1α诱导的人外周血单核细胞IL-6和IL-8 mRNA表达的影响

用重组人ＩＬ１α在体外诱导人外周血单核细胞表达ＩＬ６和ＩＬ８，并用ＲＴＰＣＲ检测环孢素Ａ（ＣｙＡ）及雷公藤提取物Ｔ０对ＩＬ６和ＩＬ８ｍＲＮＡ表达的影响，以探讨这两种细胞因子作为抗银屑病药物作用靶位的病理意义及雷公藤治疗银屑病的作用原理。结果显示Ｔ０能降低ＩＬ６和ＩＬ８ｍＲＮＡ水平，ＣｙＡ明显下调ＩＬ８ｍＲＮＡ水平，而对ＩＬ６ｍＲＮＡ表达仅在０１和１０μｇ／ｍｌ浓度有抑制作用，且只有０１μｇ／ｍｌ组有统计学意义。研究表明，Ｔ０的效价和作用较ＣｙＡ高和强。该研究为两药的抗银屑病作用提供了一定的药效学依据。     

环孢素A与雷公藤对IL—1α诱导的人外周血单核细胞IL—6和IL—8m …

用重组人ＩＬ－１α在体外诱导人外周血单核细胞表达ＩＬ－６和ＩＬ－８,并用ＲＴ－ＰＣＲ检测环孢素Ａ（ＣｙＡ）及雷公藤提取物Ｔ０对ＩＬ－６和ＩＬ－８ｍＲＮＡ表达的影响,以探讨这两种细胞因子作为抗银屑病药物作用靶位的病理意义及雷公藤治疗银屑病的作用原理。结果显示Ｔ０能降低ＩＬ－６和ＩＬ－８ｍＲＮＡ水平,ＣｙＡ明显下调ＩＬ－８ｍＲＮＡ水平。     

短期使用环孢素A治疗天疱疮五例

１９９３年以来我科用环孢素Ａ（Ｃｙｃｌｏｓｐｒｉｎ－Ａ，ＣｙＡ）治疗５例天疱疮，现报道如下。一、临床资料５例均为我科住院患者，全部经普通病理和直接免疫荧光检查确诊。男３例，女２例；年龄２６～６０岁；寻常型３例，红斑型２例；２例为皮损＜体表面积２０％的...     

环孢菌素A治疗几种免疫性皮肤病41例临床分析

环孢菌素Ａ治疗几种免疫性皮肤病４１例临床分析周桦，佟菊贞中山医科大学附属第一医院皮肤科（邮政编码５１００８０）环孢菌素Ａ（ＣｙｃｌｏｓＰｏｒｉｎ－Ａ，ＣｓＡ）是一种非细胞毒性的免疫抑制药。本文对１９ｇＺ年以来应用该药治疗的免疫性皮肤病４１例进行分析，...     

Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis

We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1–2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.     

Treatment of pyoderma gangrenosum with cyclosporin A

Two patients with recalcitrant pyoderma gangrenosum were treated with oral cyclosporin A (5 mg/kg body-weight/day). Healing of the lesions was achieved in Patient 1 within 1 month of starting treatment, but new areas of ulceration appeared when the dose was reduced to 3 mg/kg body-weight/day. The ulcers showed marked improvement by 3 weeks after the start of treatment in Patient 2 and remained inactive at a maintenance dosage of 100 mg/day, but there was no change in the associated seronegative arthritis. A steroid-sparing effect of CyA was evident in both patients. It is suggested that a lower dose of cyclosporin A than doses used previously in the treatment of pyoderma gangrenosum may be equally effective.     

Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis

Cyclosporin is a second-line modality for the treatment of psoriasis. The long-term efficacy of cyclosporin and potential adverse side-effects, however, are a concern to patients. Therefore, a cyclosporin microemulsion (Neoral), which is steadily absorbed at an ultra-low dosage (1-2 mg/kg per day) or low dosage (2-3 mg/kg per day), is currently recommended. The dose must be calculated based on patient bodyweight and the blood concentration monitored regularly, which is time-consuming. Furthermore, the concentration is related to the safety profile, but not to efficacy. We examined whether a fixed-dose cyclosporin microemulsion (100 mg/day) is effective for treating psoriasis. Enrolled patients (n = 40) were given either 100 mg cyclosporin emulsion once daily (group A) or 50 mg twice daily (group B), regardless of patient weight and condition, before meals in a randomized controlled study. Patient bodyweight ranged 50-80 kg. We assessed the serum cyclosporin concentration 1 h after administrating the medicine (C1 score), Psoriasis Area and Severity Index (PASI) score, quality of life, and the results of regular blood examinations. The improvement rate was 69.4 ± 4.8% in group A and 73.4 ± 4.3% in group B. PASI-50 was achieved by 82% in group A and 84% in group B. At 6 weeks, the number of patients with PASI-50 was significantly higher in group A than in group B. PASI-75 and -90 were also achieved in both groups with no significant difference between groups. Administration of a fixed-dose cyclosporin microemulsion (100 mg/day) is practical for second-line psoriasis treatment.     

Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial

BACKGROUND: The identification of a highly potent immunosuppressive/antiproliferative agent with an acceptable toxicity profile has long been a goal for the management of severe plaque psoriasis. OBJECTIVES: To investigate the efficacy and safety of sirolimus (Rapamune) for severe psoriasis when given alone or in association with cyclosporin. METHODS: In a randomized, double-blind, eight parallel group, pilot study in 24 out-patient centres in seven European countries, 150 patients, 18 years and older, with severe chronic plaque psoriasis were given sirolimus 0.5, 1.5 and 3.0 mg m(-2) daily for 8 weeks, either alone or in association with a subtherapeutic dose of cyclosporin (1.25 mg kg(-1) daily). Cyclosporin 5 mg kg(-1) daily was the positive control and cyclosporin 1.25 mg kg(-1) daily the negative control. The primary efficacy variable was the mean percentage reduction in Psoriasis Area and Severity Index (PASI). Safety assessments included monitoring of adverse events, clinical laboratory parameters and sirolimus/cyclosporin blood concentrations. RESULTS: The greatest mean percentage decreases in PASI were seen with cyclosporin 5.0 mg kg(-1) daily (70.5%) and with sirolimus 3.0 mg m(-2) daily + cyclosporin 1.25 mg kg(-1) daily (63.7%). Both groups demonstrated significantly better results than cyclosporin 1.25 mg kg(-1) daily (mean decrease 33.4%). Serum creatinine levels were significantly lower for groups with sirolimus alone and sirolimus plus reduced-dose cyclosporin when compared with cyclosporin 5.0 mg kg(-1) daily. Adverse events associated with sirolimus included thrombocytopenia (5%), hyperlipidaemia (9%), aphthous stomatitis (9%) and acne (13%), whereas adverse events associated with cyclosporin included hot flushes (12%), hyperlipidaemia (9%) and increased serum creatinine (9%). CONCLUSIONS: The concomitant administration of sirolimus with a subtherapeutic dose of cyclosporin in severe psoriasis may permit a reduction in their respective toxicities, notably cyclosporin-induced nephrotoxicity.     

Juvenile generalized circinate pustular psoriasis treated with oral cyclosporin A

We report on a 17-year-old boy presenting with relapsing generalized circinate pustular psoriasis exacerbated by streptococcal angina. Because of the severe course in his case, we started systemic treatment with cyclosporin A and corticosteroids. Corticosteroids could easily be tapered down. Cyclosporin A maintenance therapy was realized with 100 mg/day (1.6 mg per kg body weight and day). Side effects were a temporary increase in blood pressure during initiation with 200 mg cyclosporin A/day. After dose reduction no side effects were seen. The pustular lesions disappeared and the PASI score decreased from 40.7 to 4.8. The treatment was found to be well tolerated and effective.     

Cyclosporin maintenance therapy for severe atopic dermatitis.

Twelve patients with chronic severe atopic dermatitis were treated with cyclosporin A (CsA) in a dose of 5.0 mg/kg/day. All patients except one showed a good therapeutic response. After week six, the CsA dose was reduced until an increased activity of atopic dermatitis was noticed (minimal effective dose). The minimal effective dose fluctuated with the severity of the atopic dermatitis. The mean minimal effective dose was approximately 4.0 mg/kg/day. Maintenance therapy with CsA for atopic dermatitis seems to be effective but may be hampered by side effects in the same way as CsA therapy is hampered by side effects in the treatment of psoriasis.     

The correlation between response to oral cyclosporin therapy and systemic inflammation, metabolic abnormality in patients with psoriasis

Psoriasis is a disease presenting cutaneous, immunological and vascular abnormalities. Oral cyclosporin therapy has been shown to be effective for the disease. Clinical and laboratory findings affecting the response of oral cyclosporin therapy in patients with psoriasis were studied. Forty-seven patients with psoriasis (male:female = 27:20, age 56.7 + 12.6 years) were studied. The response to oral cyclosporin therapy was categorized as excellent, good, fair and poor according to decrease of PASI score and decrease of cyclosporin dose. Clinical and laboratory findings including cyclosporin trough level and high sensitivity-CRP were statistically analyzed. Nine patients showed excellent response, 17 good response, 19 fair response and 2 poor response. High sensitivity-CRP (0.11 +/- 0.02 mg/dl) in fair response patients to oral cyclosporin therapy was significantly lower than those in excellent response patients (0.42 +/- 0.21 mg/dl) (P < or = 0.05). Body mass index (23.4 +/- 0.6 kg/m(2)), HDL-cholesterol (57.1 +/- 3.6 mg/dl) and fasting plasma glucose (105 +/- 5 mg/dl) in fair response patients to oral cyclosporin therapy was significantly lower, higher and lower than those in excellent response patients (25.7 +/- 0.9 kg/m(2); 43.0 +/- 2.8, 140 +/- 20 mg/dl) (P < 0.05, P < 0.05, P < 0.05), respectively. No other clinical and laboratory findings showed statistical significance among excellent, good and fair response patients. These results showed the correlation between response of oral cyclosporin therapy and systemic inflammation, metabolic abnormality in patients with psoriasis.     

Healing of severe ulcerative necrobiosis lipoidica with cyclosporin

A 55-year-old woman with severe, chronic, treatment-resistant ulcerating necrobiosis lipoidica of the shins was commenced on oral cyclosporin at a dose of 2.5 mg/kg/day. Improvement started within 1 week of commencing treatment, and the lesions healed completely over 8 months. Further ulceration occurred 3 months after discontinuing cyclosporin, with improvement on reintroduction of cyclosporin. There have been four previous case reports of healing of treatment-resistant ulcerating necrobiosis lipoidica with cyclosporin.     

Steroid-resistant bullous pemphigoid treated with cyclosporin A

A 70-year-old woman with steroid-resistant bullous pemphigoid, severe osteoporosis, and several crush fractures was given cyclosporin A at a dose of 5 mg/kg/day. Considerable improvement was evident within 4 weeks, and control has been maintained over a period of 14 months allowing reduction of her steroid dose to 4 mg on alternate days.