色甘酸二钠类的研究进展与临床应用

色甘酸二钠是肥大细胞膜稳定剂,能抑制肥大细胞及嗜碱细胞释放过敏介质,还能抑制迷走神经反射,调节一些其他类型的反射性支气管痉挛及降低支气管对非特异刺激的敏感性。主要用于各种类型的支气管哮喘、过敏性鼻炎、过敏性结膜炎、春季卡他性结膜炎,还用于与过敏或刺激有关的咳嗽、食物过敏。还可试用于溃疡性结肠炎等病症。     

地塞米松对哮喘大鼠肺组织Muc5ac蛋白和P物质的影响

目的:研究大鼠支气管哮喘(简称哮喘)模型肺组织Muc5ac蛋白和P物质的分布及地塞米松对其影响。方法:30只清洁级Wistar大鼠随机分成对照组、哮喘组和地塞米松治疗组(简称治疗组),采用免疫组化SP法和计算机图象分析技术检测肺组织中Muc5ac蛋白和P物质的分布。结果:哮喘组肺组织Muc5ac蛋白和P物质(分别1.5100±0.4149,0.39±0.11)表达均较对照组(分别为1.0639±0.2550,0.24±0.19)明显增加(P<0.01),地塞米松治疗后二者均降低(分别为1.1700±0.1947,0.25±0.01),和哮喘组相比(P<0.05)有统计学意义。结论:反复抗原刺激引起气道过敏性炎症,导致气道粘蛋白和P物质的大量产生,加重哮喘气道炎症和气道阻塞,地塞米松可下调Muc5ac蛋白和P物质,对气道粘蛋白高分泌有明显的治疗作用,并能逆转哮喘大鼠气道SP-IR神经纤维到正常分布。     

P物质对哮喘大鼠神经内分泌功能的调节

目的探讨哮喘大鼠脑内P物质在哮喘发作中的作用。方法以大鼠腹腔注射含百日咳和氢氧化铝的卵蛋白溶液制备哮喘动物模型,免疫组织化学方法(SABC)检测哮喘大鼠脑内c-fos蛋白,放射免疫法检测下丘脑室旁核(para-ventricular nucleus,PVN)内P物质(substance P,SP)的含量及正中隆起(ME)中促肾上腺皮质激素释放激素(cortico-tropin-releasing hormone,CRH)和外周血中促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticoster-one,CORT)含量,PVN内分别微量注射外源性SP、SP受体拮抗剂S0145,观察其对哮喘大鼠肺功能与下丘脑-垂体-肾上腺皮质功能轴(hypothalamus-pituitary-adrenal axis,HPA轴)活动的影响。结果哮喘大鼠发作时PVN内SP含量升高;正中隆起CRH与外周血中ACTH、CORT含量均降低(P<0.05),呼/吸时程比和气道阻力增加,膈肌放电积分、肺顺应性减小(P<0.01)。PVN内微量注射SP后哮喘大鼠的肺通气功能进一步下降,CORT、ACTH、CRH含量进一步降低(P<0.01)。SP受体阻断剂S0145则可逆转哮喘发生时大鼠肺功能与HPA轴的改变。结论哮喘大鼠下丘脑室旁核内SP可影响HPA轴的功能,参与哮喘发作。     

P物质和神经降压肽对胃肠道的作用

五十多年前Euler和Gaddum在马肠和脑提取物中首次发现了P物质(SP)。经部分纯化的这种物质能明显降低血压,并收缩胃肠道平滑肌。1970年,Chang 等在牛下丘脑提取物中再次发现SP,并将其看作是一种催涎物质(Sialagogic substances),经纯化发现,它是一种11个氨基酸组成的多肽,具有如表1所示的氨基酸序列。SP 的C-端序列及其生物活性与其它统称为“速激肽”(Tachykinins)的肽类相似。除了存在于章鱼唾液腺中的章鱼涎肽(Eledoisin)外,其它肽主要从两栖类的皮中分离而得。在纯化SP 的过程中,发现另一种能产生皮肤血管舒张和发绀的物质,其化学性质     

痛啡肽抑制豚鼠气道兴奋性非肾上腺素能非胆碱能反应

目的:研究痛啡肽(Nociceptin,NC)及U-50488H对豚鼠离体支气管环的非肾上腺素能非胆碱能兴奋(eNANC)所致收缩的抑制作用。方法:记录电场刺激及辣椒素引起标本eNANC反应的收缩张力,了解NC及U-50488H的作用。结果:NC 0.001-0.1μmol·L~(-1)可抑制标本的eNANC收缩。与对照组相比,NC 0.01μmol·L~(-1)抑制收缩达(43±31)％;预用纳洛酮0.1μmol·L~(-1)后,NC仍抑制收缩达(46±28)％。IC_(50)(95％可信限)是6.12(3.8-9.9)nmol·L~(-1)。U-50488H 0.01 -1μmol·L~(-1)可抑制eNANC收缩,其IC_(50)(95％可信限)为1.08(0.5-2.2)μmol·L~(-1),但是U-50488H 0.1μmol·L~(-1)的抑制作用可被纳洛酮0.1μmol·L~(-1)完全取消。辣椒素0.01-1μmol·L~(-1)可引起eNANC收缩,NC 0.01μmol·L~(-1)和U-50488H 0.1μmol·L~(-1)均不能明显影响辣椒素的作用。外源性神经激肽A 0.01μmol·L~(-1)引起的收缩不受NC和U-50488H 0.1μmol·L~(-1)的影响。结论:NC非纳洛酮敏感地抑制电场刺激引起的豚鼠气道eNANC反应;U-50488H通过激动阿片受体而抑制电场刺激引起的豚鼠气道eNANC反应。     

长期低剂量大环内酯类抗生素的抗哮喘作用

以红霉素为代表的大环内酯类抗生素在感染性疾病中应用相当广泛,疗效确切。经过长期的药理研究和临床实践,人们发现此类抗生素除具有抗感染作用外,对支气管哮喘亦有一定作用。近年来国内外对其研究逐渐增多,笔者就大环内酯类抗生素在哮喘治疗中的机理及疗效作一综述。     

丙卡特罗扩张支气管的作用时间

目的：了解丙卡特罗扩支气管的作用时间。方法：支气管哮喘１４５例（男性８７例，年龄４１±１４ａ，女性５８例，年龄３９±２０ａ），口服丙卡特罗５０μｇ，每２ｈ测定最大呼气流速值。结果，服药后４ｈ和１２ｈ改善呼吸困难的总有效率为８７．５％和６６．１％，改善哮鸣音的总有效率为９４．７％和８１．３％，ΔＰＥＦ％≥１５％有７４．５％和３２．４％，结果：丙卡特罗时间可达１２ｈ。     

特殊类型的支气管哮喘诊治分析

据支气管哮喘的定义我们一般所指的典型的支气管哮喘为反复的喘息、气急、胸闷、咳嗽，多与接触变应源、冷空气、物理、化学刺激、病毒感染、运动等有关。以咳嗽为唯一症状者称咳嗽变异性哮喘；运动时出现的胸闷、咳嗽和呼吸困难者称运动型哮喘。近来有学者报道以胸痛为主的哮喘后引起了笔者的注意，经回顾及随访有6例以胸痛为主的病例。     

Disodium cromoglycate: a novel gastric antiulcer agent?

The influence of oral pretreatment with disodium cromoglycate (2.5 or 5 mg/kg X 9 doses) on the 4-h gastric effects of i.p. injected reserpine (5 mg/kg) was examined in rats. Disodium cromoglycate markedly prevented reserpine-induced ulceration, mucosal mast cell degranulation and superficial mucosal microcirculatory changes in the glandular portion of the stomach wall. These interesting results points to the possibility that disodium cromoglycate may also have gastric antiulcer effects in man.     

Section 3 Introduction

Summary

Ibuprofen is now an established drug in the treatment of rheumatic diseases. In this section is presented a number of papers providing new information to help us in our use of the product.     

Comparison of 1 mg and 5 mg sodium cromoglycate metered dose inhalers in the treatment of asthma: A 12-week double-blind,parallel group trial

Summary

A double-blind, parallel group trial of a 1?mg sodium cromoglycate metered dose inhaler, a 5?mg formulation and a placebo aerosol was undertaken in 139 asthmatic patients with extrinsic allergic asthma. None of the patients had previously been treated with sodium cromoglycate and few (15%)were familiar with the use of a pressurized aerosol device. Each test treatment was taken at a dose of 2 ‘puffs’ 4-times per day for a period of 12 weeks. Response to treatment was assessed by analysis of symptom scores, medication usage and 3-times daily home measurements of PEFR recorded on diary cards, and by assessment of asthma severity and lung function in the clinic at the beginning and end of a 2-week baseline period and at intervals of 3 weeks throughout the trial. Analysis of patient-generated data (symptom scores and PEFR)demonstrated statistically significant differences in favour of each active treatment compared with placebo treatment. Clinic assessments of asthma severity and the investigator's opinion of treatment also showed the superiority of each sodium cromoglycate treatment regimen over placebo. These differences were statistically significant after 9 weeks (high dose)and 12 weeks (both doses). No statistically significant differences were demonstrated between the two active treatment groups in the clinic assessments of asthma severity, or in the home or clinic measurements of PEFR. There was, however; a consistent trend in favour of the higher dose formulation with respect to diary card symptom scores. In general, improvement in the low-dose sodium cromoglycate treatment group was slower than in the high-dose group suggesting an advantage for the 5?mg sodium cromoglycate inhaler in terms of onset of therapeutic response. The results indicate that sodium cromoglycate administered by pressurized aerosol at a dose of 2×1?mg or 2×5?mg 4-times daily is effective in the treatment of asthma and suggest that the higher dose formulation may provide more rapid control of symptoms.     

Effectiveness of budesonide nebulising suspension compared to disodium cromoglycate in early childhood asthma

ABSTRACT

Objective: The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months.

Research design and methods: 82 infants (mean age 18.0 months [range, 11.6–31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5?mg/2?mL bid or DSCG 20?mg/2?mL tid. Follow-up was at 6 months.

Main outcome measures and results: Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (?p = 0.014), and nights without cough were 89% and 78%, respectively (?p = 0.016). Side-effects were mild and of similar frequency in both groups.

Conclusions: Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6‐month follow-up.     

肌电图仪在周围神经损伤手术中的临床应用

目的探讨肌电图仪在周围神经损伤手术中应用电刺激促进神经再生的监测作用。方法对23例周围神经损伤实施松解手术的患者于术中进行超强电刺激,在肌电图仪的持续监测下分析相应神经在刺激前后的电学变化。结果①电刺激后臂丛神经损伤和尺神经损伤复合肌肉动作电位的潜伏期较刺激前明显缩短,变化有统计学意义(P<0.05)。②电刺激后臂丛神经损伤、正中神经损伤、桡神经损伤的复合肌肉动作电位波幅明显高于刺激前,变化有统计意义(P<0.05)。结论肌电图仪在术中监测到对连续性尚存的损伤神经施行超强电刺激,能有效促进周围神经再生及神经功能恢复。     

Comparison of a lactose-free formulation of sodium cromoglycate and sodium cromoglycate plus lactose in the treatment of asthma

Summary

A double-blind, parallel group, 7-centre trial was carried out to compare the clinical efficacy and patient acceptability of two formulations of sodium cromoglycate for inhalation in patients suffering from asthma. Each single-dose capsule for use in a breath-actuated inhaler contained either a blend of sodium cromoglycate (20?mg) plus lactose (20?mg) or a lactose-free pelletized formulation of sodium cromoglycate (20?mg). Data were summarized from 529 asthmatic patients who had been using the blend formulation for at least 3 months previously. Two hundred and sixty-five patients then received pelletized sodium cromoglycate and 264 patients remained on sodium cromoglycate plus lactose for at least 3 months. Regular assessments were made by patients and clinicians during the trial period of treatment effectiveness. No clinically significant differences were observed between the two formulations after 3 months on test treatment. After a treatment period of 6 months, the pelletized formulation was shown to have some advantages over the blend formulation which were not observed at 3 months, with a significantly higher proportion of ‘very effective’ assessments being recorded by both patients and clinicians. The capsules of pelletized sodium cromoglycate required significantly less inhalations to empty compared to the capsules of the blend. No differences were observed between the two formulations with regard to the incidence of transient cough and throat irritation after inhalation.     

P2X and P2Y Receptors Mediate Contraction Induced by Electrical Field Stimulation in Feline Esophageal Smooth Muscle

It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 (10^-7~10^-4 M), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue (10^-6~10^-4 M), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist α,β-methylene 5''-adenosine triphosphate (αβMeATP, 10^-7~10^-5 M) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5''-[β-thio]diphosphate trilithium salt (ADPβS, 10^-7~10^-5 M) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,N-diethyl-D-β,γ-dibromomethylene 5''-triphosphate triammonium (ARL 67156, 10^-4 M) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.     

舒利迭联合西替利嗪治疗慢性中度哮喘的临床疗效观察

目的分析研究舒利迭联合西替利嗪治疗慢性中度哮喘的临床疗效和安全性。方法将74例患者随机分成治疗组和对照组各37例,治疗组给予舒利迭联合西替利嗪,对照组单用舒利迭治疗,12周为1个疗程。结果治疗组和对照组患者的总有效率分别为91.89%和83.78%,临床症状和肺功能均得到明显改善和提高,其中治疗组患者肺功能改善较对照组明显提高,两组比较差异有统计学意义(P<0.05)。结论应用舒利迭联合西替利嗪治疗慢性中度哮喘能更迅速地改善临床症状和肺功能,且疗效显著,不良反应少,值得在临床上推广应用。