对花生四烯酸人皮肤炎症模型和咪唑斯汀抗炎作用的研究

目的探讨咪唑斯汀对花生四烯酸(AA)人体皮肤炎症模型的抗炎作用。方法以20%、4%浓度的AA在25名健康志愿者前臂屈侧做点刺试验,并在其服用抗过敏药(咪唑斯汀/氯雷他定)前1h及服药后1h、2h进行AA点刺试验,分别记录点刺试验30min后的红斑面积和风团面积。用氯雷他定作为对照组。结果20?人体皮肤点刺试验中,服用咪唑斯汀前与服用后1h红斑面积及风团面积变化显著(P<0.01),显著优于氯雷他定组(P<0.05);服用咪唑斯汀前与服用后2h红斑面积及风团面积变化显著(P<0.01),显著优于氯雷他定组(P<0.01);4%点刺试验中,咪唑斯汀组用药前与服用后2h风团面积存在显著性差异(P<0.05),显著优于氯雷他定组(P<0.01);咪唑斯汀2h抗炎效果优于1h。结论咪唑斯汀具有明显的拮抗AA引起的人体皮肤炎症反应作用。     

Effect of Mizolastine on Release of Inflammatory Mediators in Sensitized Mice

Mizolastine is widely prescribed for acute allergic cutaneous diseases because of its powerful antihistamine activity. Moreover, it has been recently put forward that mizolastine might also be effective on other inflammatory and refractory disorders such as atopic dermatitis and psoriasis. The aim of the present study is to investigate the effect of mizolastine on the release of two kinds of inflammatory mediators and cytokines （Leukotriene B4 and Interleukin-5）, which play pivotal roles not only in chronic allergic diseases but also in inflammatory diseases. The study was performed using epidermis from mice stimulated by intradermal injection of substance P and splenocytes from mice sensitized by intraperitoneal administration of ovalbumin （OVA）. Competitive enzyme-linked immunosorbent assay （ELISA） method was applied to examine the effects of mizolastine and the control drugs （chlorpheniramine, rolatadine and dexamethasone） on the release of Leukotriene B4 （LTB4） and Interleukin-5 （IL-5）. Mizolastine inhibited the release of LTB4 and IL-5 in epidermis as well as in splenocytes. The inhibitory effect was dose-dependent. Neither chlorpheniramine nor rolatadine showed inhibitory effects release from epidermis and splenocytes by mizolastine was not as strong as that by dexamethasone. Nevertheless, the results showed inhibitory effect of mizolastine over leukotriene and Th2 cytokines other than its anti-histamine effect. Thus, mizolastine seems to regulate on the release of inflammatory mediators and to have the potential to reorientate the T-cell response toward a balance between Th1 and Th2, which might have implications for the treatment of other inflammatory and chronic disorders.     

Study of cardiac repolarization in healthy volunteers performed with mizolastine, a new H1-receptor antagonist

AIMS: The occurrence of serious dysrhythmias, such as torsades de pointes, with terfenadine and astemizole had led to a reexamination of the potential effect of H1 antihistamines on cardiac repolarization. Mizolastine is a potent, selective, nonsedating peripherally acting H1-receptor antagonist which is registered for rhinitis and urticaria at a recommended dose of 10 mg once daily. The present study was carried out to investigate the effects of therapeutic and supratherapeutic doses of mizolastine, on ventricular repolarization in healthy volunteers. METHODS: Twenty-four healthy young volunteers participated in a double-blind, placebo-controlled, randomised study with three parallel groups. Each group consisted of 2 way cross-over 7 day treatment periods where mizolastine (10, 20 or 40 mg) and placebo were randomly administered. On day 1 and day 7, 12-lead ECG recordings were performed prior and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 20 h after dosing and from day 2 to day 6, before dosing and 1, 2, 3, and 4 h after. RESULTS: Whatever the analysis used (raw data, changes from baseline, incidence of individual out-of-range values) no significant differences were observed at any dose level vs placebo, on any of ECG parameters (HR, PR, QRS, QT, and QTc). In particular, no effect of mizolastine vs placebo was shown on QT and QTc although 95% CIs were wide. The only subject who exhibited a QTc>/=450 ms received placebo for 7 days. CONCLUSIONS: This study found no evidence of an effect of mizolastine up to 40 mg (four times the therapeutic dose) on ventricular repolarization in healthy volunteers.     

4种抗组胺药对体外培养鼻息肉组织炎症因子表达影响的比较

目的 比较多种药物对鼻息肉体外培养组织中趋化因子表达的影响.方法 咪唑斯汀、氯雷他定、西替利嗪、非索非那定、地塞米松、环孢素A等抗炎药物和鼻息肉组织体外共同培养,同时加入组胺、花生四烯酸致炎刺激物,培养24 h后逆转录PCR法测定上述药物作用后鼻息肉组织中MCP-1、MCP-3、RANTES、eotaxin等趋化因子mRNA表达,ELISA法测定培养上清液中细胞因子IL-4、IL-5和TNF-α等炎症介质的含量,观察不同药物对其影响的情况.结果 咪唑斯汀组中MCP-3基因的表达显著低于氯雷他定、西替利嗪组(P＜0.05);MCP-1基因的表达显著低于氯雷他定、非索非那定组(P＜0.05);Eotaxin的表达显著低于西替利嗪组;而RANTES表达显著低于氯雷他定、非索非那定组(P＜0.05);培养上清液中的IL-4含量显著低于氯雷他定和西替利嗪组,IL-5的含量显著低于西替利嗪、氯雷他定组(P＜0.05),TNF-α的含量与其他拮抗药物组均无统计学差异(P＞0.05).结论 比较不同的抗组胺药,咪唑斯汀显示有较强的抗炎症作用.     

3种抗组胺药抗组胺及抗花生四烯酸作用的比较研究

目的:比较咪唑斯汀、氯雷他定、西替利嗪3种抗组胺药的抗组胺及抗花生四烯酸的作用。方法:给大鼠左、右爪分别皮下注射花生四烯酸(1.0g/L,0.1mL)和组胺(10g/L,0.1mL)构建鼠爪水肿炎性模型。在注射花生四烯酸和组胺2h前分别给予咪唑斯汀、氯雷他定、西替利嗪(0.6mg/kg)灌胃,注射后应用体积测量仪分别测定给药后鼠爪体积在不同时间点的变化。结果:咪唑斯汀可抑制花生四烯酸所致的鼠爪水肿(P<0.05),西替利嗪、氯雷他定对其无明显抑制作用;咪唑斯汀对组胺所致的鼠爪水肿有抑制作用(P<0.05),抑制作用强于氯雷他定组,但与西替利嗪组比较无统计学差异(P>0.05)。结论:咪唑斯汀具有抗组胺和抗花生四烯酸的作用,且其抗组胺作用强于氯雷他定;与氯雷他定、西替利嗪相比,咪唑斯汀表现出其独特的抗花生四烯酸的作用。     

皿治林治疗荨麻疹临床疗效观察

以皿治林治疗急性荨麻疹的有效率为86·11%;慢性荨麻疹为83·33%。该药的副反应轻微。     

咪唑斯汀抗组胺点刺试验及治疗荨麻疹临床疗效观察

目的：评价咪唑斯汀治疗荨麻疹的疗效及安全性。方法：①对93例急、慢性荨麻疹患者口服咪唑斯汀10mg,每日1次,急性荨麻疹患者首次服药后留观2h,慢陛荨麻疹患者连续用药2周。②选择10名健康志愿者作组胺点刺试验,观察咪唑斯汀对组胺诱导风团的抑制作用。结果：①61例急性荨麻疹患者首次服药后在1h内起效49例(80．3％);32例慢性荨麻疹治疗1周后有效率为90．6％,治疗2周后有效率为100．0％。3例患者出现短暂而轻度的嗜睡反应。②健康志愿者服用咪唑斯汀1、2h后,对组胺诱导风团的抑制率分别为40．19％和83．92％;红晕抑制率分别为49．90％和87．69％。结论：咪唑斯汀治疗急、慢性荨麻疹起效快,作用持久,不良反应少。     

咪唑斯汀和西替利嗪对湿疹的疗效及对患者免疫功能的影响

目的：比较咪唑斯汀和西替利嗪对湿疹的疗效和对患者免疫功能的影响,为临床湿疹的治疗提供参考。方法：收集湿疹患者96例,随机分为咪唑斯汀组和西替利嗪组,各48例,另选40例健康体检者纳入对照组。咪唑斯汀组口服咪唑斯汀10 mg·次-1,1次·d-1;西替利嗪组口服西替利嗪10 mg·次-1,1次·d-1。治疗3周,观察两组患者治疗前后IL-4、IL-5、TNF-α、IFN-γ变化情况及临床疗效。结果：两组患者治疗前IL-4、IL-5、IFN-γ水平明显均高于对照组（P〈0.05）,但两组间差异无统计学意义（P〉0.05）。治疗后两组血清IL-4、IL-5、IFN-γ水平均较同组治疗前明显下降（P〈0.05）,但仍高于对照组（P〈0.05）;咪唑斯汀组患者血清IL-4、IL-5水平明显低于西替利嗪组（P〈0.05）,咪唑斯汀组患者总有效率明显高于西替利嗪组（P〈0.05）,两组不良反应发生率差异无统计学意义（P〉0.05）。结论：临床湿疹的治疗应优先选择那些对Th1/Th2失衡改善作用明显的药物。     

One-year treatment of chronic urticaria with mizolastine: efficacy and safety

AIM: To assess the long-term safety and efficacy of the H1-receptor antagonist mizolastine in the symptomatic treatment of chronic urticaria (CU). BACKGROUND: Mizolastine is a novel second generation antihistamine with additional anti-inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted. METHODS: This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40+/-13 years), with > or = 1 episode/week if untreated. After a 7-day placebo run-in period, patients received mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular attention to QT intervals. RESULTS: The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician's assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug-related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration. CONCLUSION: Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side-effects are associated with its long-term use in the current study.