他扎罗汀凝胶治疗寻常型银屑病的临床观察

他扎罗汀是一种新型的受体选择性维A酸类药物犤1犦。其治疗银屑病的主要作用机制是调节角质形成细胞(KC)的分化异常,改善KC的过度增殖,促进炎症消退犤2犦。为进一步验证他扎罗汀凝胶治疗寻常型银屑病的疗效及安全性,笔者用他扎罗汀凝胶(重庆华邦制药有限公司)治疗了115例寻常型银屑病患者,并进行了临床观察,疗效满意,现报告如下。1对象与方法1.1观察对象为2001年10月～2002年1月在上海市12家医院就诊的寻常型银屑病患者,共115例。病人平均年龄45岁(18～65岁),病程6个月～20年。皮损面积占整个体表的2%～30%。靶皮损基线评分:斑块肥厚程度…     

加巴喷丁胶囊治疗疱疹后神经痛的多中心临床观察

Objective To observe the clinical efficacy and safety of gahapentin in the treatment of postherpetic neuralgia. Methods A multicenter, randomized, double-blind, placebo-controlled, parallel design, 6-week study was performed. Patients with postherpetic neuralgia were recruited into this study and randomly divided into two groups to receive gabapentin or placebo 1800 mg daily in three divided doses with a forced titration schedule, respectively. The primary efficacy measure was change in the pain score based on a visual analogue scale from baseline to the final week of therapy, and secondary measure was the improvement in sleep quality scored on a 5-point severity scale. Efficacy and safety evaluation was performed at baseline, and 1, 3, and 6 weeks atter the treatment. Results One hundred and forty-one patients were recruited in four clinical centers, and 125 patients completed the trial, of whom 66 were in the treatment group and 59 in the control group. An improvement was observed in both pain scores and sleep scores on week 1, 3 and 6 in both two groups, and the improvement was greater in gabapentin-treated group than that in the control group. The response rate was 29.58% and 57.75%, respectively in gabapentin-treated group on week 1 and 3, com-pared to 13.04% and 40.58%, respectively, in the control group (t = 5.94, 4.12, respectively, both P ＜0.05).Gabapentin was well tolerated, and the most common adverse events were dizziness, vertigo, somnolence and transient abnormality of hepatic function. Conclusion Gabapentin could markedly reduce pain intensity and improve sleep quality with a low incidence of adverse events in patients with postherpetic neuralgia.     

烟酸缺乏症1例

患者男，３８岁。因“纳差、乏力１年，双手背暗红斑４月，面部色素沉着及黄色颗粒１月余”于２００１年６月２７日入院。患者自３年前开始嗜酒，每日１．５kg黄酒。近１年来渐出现纳差、消瘦、乏力、全身发抖、不能坐立、双下肢麻木、心慌、心悸，失眠、记忆力减退、急躁、自言自语、容易紧张，于２０００年９月以“进行性消瘦伴纳差”收治笔者所在医院内分泌科。多次空腹血糖、糖耐量试验、T３、T４、脑CT、脑电图等检查均无异常，肌电图示四肢神经传导速度减慢。半年前双足侧缘及足跖部出现暗红斑，无自觉症状。２００１年４月双手背及…     

银屑病外周血中转化生长因子β1水平的动态观察

采用ELISA方法对银屑病患者外周血中TGF-β1浓度的改变与PASI评分、病情变化、治疗、预后及复发有无关联进行了比较研究。结果治疗前银屑病患者外周血中TGF-β1平均血清浓度为7.94±1.09(ng/mL),正常人TGF-β1的平均血清浓度为11.10±0.97(ng/mL),两者相比P<0.001;患者PASI评分越高,TGF-β1的血清浓度越低;且TGF-β1的血清浓度随病情及治疗好转而升高,病情复发而降低,复发时基本降至治疗前水平。银屑病患者外周血中TGF-β1的血清浓度可能与PASI评分、治疗、预后与复发有一定的关系。     

砷剂对角质形成细胞CDK2、CDK4和Cyclin-E蛋白表达的影响

目的：研究砷剂对角质形成细胞细胞周期调控因子蛋白表达的影响。方法：以体外培养的角质形成细胞株为对象，一定浓度砷剂处理细胞后，用免疫印迹方法研究HaCaT细胞周期蛋白依赖激酶2（CDK2）、周期蛋白依赖激酶4（CDK4）和细胞周期蛋白E（Cyclin—E）的表达情况及砷剂对其表达的影响。结果：未受到砷剂处理的对照组细胞稳定表达CDK2、CDK4和Cyclin—E，当1nmol／L三氧化二砷处理24h后，HaCaT细胞表达CDK4、Cyclin—E水平升高，但CDK2的表达水平无明显变化。结论：一定浓度砷剂可刺激角质形成细胞增殖，可能与其升高细胞周期调控因子CDK4、Cyclin—E蛋白表达，导致S期细胞比例升高有关。     

Effects of α-melanocyte-stimulating hormone on the production of TNF-α and IL-10 by peripheral blood mononuclear cells from patients with psoriasis

Objective To investigate the effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on the production of tumor necrosis factor-alpha (TNF-alpha) and intedeukin-10 (IL-10) by peri-pheral blood monohuclear cells (PBMCs) from patients with psoriasis vulgaris. Methods Heparinized peri-pheral blood was obtained from 20 patients with psoriasis vulgaris and 10 healthy human controls. PBMCs were isolated, cultured in complete medium, and stimulated with phytohemagglutinin (PHA) alone, the com-bination of PHA and various concentrations of alpha-MSH, or nothing. After another 48-hour culture, ELISA and real-time PCR were performed to measure the secretion levels of TNF-alpha and IL-10 in the super-natants of cultured PBMCs as well as the mRNA expression levels of TNF-alpha and IL-10 in PBMCs. Results The secretion level of TNF-alpha in the supematants of patient-derived PBMCs stimulated by nothing or PHA alone was significantly higher than that from normal control-derived PBMCs (329.87 ± 99.33 ng/L vs 116.95 ± 37.15 ng/L, 1756.01 ± 183.60 ng/L vs 1287.30 ± 152.36 ng/L, both P<0.01). alpha-MSH of all tested concentrations (10-13, 10-11, 10-7,mol/L) could inhibit the secretion of TNF-alpha by PBMCs com-pared with PHA alone (all P < 0.01), and the maximum effective concentration was 10-13 mol/L. On the con-Wary, a significant decrease was observed in the secretion level of IL-10 in the supematants of patient-derived PBMCs stimulated by nothing or PHA alone compared with normal control-derived PBMCs (P <0.05 or 0.01). Moreover, the secretion of IL-10 by PBMCs was promoted by alpha-MSH of all tested con-centrations (P < 0.01 or 0.05), with the maximum effective concentration being 10-13 mol/L (P < 0.01). The alpha-MSH of 10-13 mol/L down-regulated the mRNA expression of TNF-alpha (P < 0.001), but up-regnlated that of IL-10 (P < 0.001) in PHA-stimulated PBMCs from patients. Conclusion alpha-MSH can regulate the production of TNF-alpha and IL-10 by PHA-stimulated PBMCs from patients with psoriasis vulgaris.     

黄芩甙影响人成纤维细胞诱导型一氧化氮合酶蛋白表达研究

目的 研究成纤维细胞诱导型一氧化氮合酶(iNOS)蛋白表达情况，以及细胞因子和黄芩甙对其表达的影响，探讨黄芩甙治疗银屑病机制。方法 体外培养的成纤维细胞，通过TNF-α、IFN-γ和IL-8刺激，用免疫组化方法研究成纤维细胞表达iNOS情况，并观察黄芩甙对其表达的影响。结果 未受到细胞因子刺激时成纤维细胞不表达iNOS；TNF-α(终浓度1000U／mL)、IFN-γ(200U／mL)、IL-8(200pg/mL)单独或分别组合后刺激成纤维细胞24h后的蛋白分析显示：单独TNF-α能够刺激成纤维细胞表达较弱iNOS，而IFN-γ或IL-8处理未显示该效应，联合TNF-α、IFN-γ和IL-8显示增强的诱导iNOS表达作用，免疫组化有强染色区，位于胞浆近胞核处；50μg／mL黄芩甙能够抑制细胞因子诱导成纤维细胞表达iNOS。结论黄芩甙能够抑制细胞因子刺激成纤维细胞的iNOS蛋白表达，减少NO的产生，发挥抗炎和治疗银屑病的作用。     

自然杀伤T细胞及其在银屑病发病机制中的作用

自然杀伤T细胞是一种通过分泌一些可溶性细胞因子来影响机体免疫系统平衡的免疫细胞，具有特殊的免疫功能，在多种自身免疫性疾病的发病机制中有重要作用，文中就自然杀伤T细胞在银屑病发病机制中的作用进行综述。     

伏立康唑、氟康唑和两性霉素B体内抗克柔念珠菌活性的比较研究

目的比较伏立康唑、氟康唑和两性霉素B在体内对克柔念珠菌的抗真菌活性。方法在克柔念珠菌深部感染的免疫抑制豚鼠模型上,对感染豚鼠分组给予口服伏立康唑10mg/kg,2次/d;伏立康唑5mg/kg,2次/d;氟康唑20mg/kg,2次/d;两性霉素B1mg/kg隔日1次腹腔注射;安慰剂对照组给予生理盐水0.5ml,2次/d口服。均连续7天。观察比较各组的死亡率及脏器组织载菌量。结果安慰剂对照组豚鼠的所有受检脏器都受到了严重的感染。5个处理组中,伏立康唑10mg组的组织载菌量与死亡率(0%)均最低;与对照组相比,该方案使念珠菌在肺、肝、肾、脑四种脏器中的组织载菌量都减少了约99%(P<0.01)。伏立康唑5mg组的组织载菌量和豚鼠死亡率均与安慰剂对照组相近,无显著性差异。氟康唑组的组织载菌量与对照组相近,其死亡率(40%)仅略低于对照组,两组间无显著性差异(P>0.05)。伏立康唑10mg组与两性霉素B组相比,在组织载菌量和死亡率方面均较为接近,较之安慰剂对照组均有显著差异(P<0.01)。结论伏立康唑在免疫抑制豚鼠体内能有效地抑制感染脏器中克柔念珠菌的生长,其作用明显优于氟康唑,与两性霉素B作用相近,但两性霉素B常有严重的不良反应。伏立康唑在体内可能以剂量依赖的形式显示其抗真菌活性。     

MAPK信号转导通路与银屑病

银屑病是一种表皮角质形成细胞过度增殖及异常分化、炎症细胞浸润、真皮血管增生性慢性复发性疾病,其皮损中MAPK及其活化因子表达异常,针对MAPK信号途径异常已开发出多种治疗银屑病的生物制剂。现就MAPK信号转导与银屑病相关性方面做一综述。