Blockade of the human cardiac K+ channel Kv1.5 by the antibiotic erythromycin

Erythromycin administration has been associated with a prolongation of cardiac repolarization in certain clinical settings. This could be due to blockade of voltage-dependent K⁺ channels in the human heart. For this reason we examined the effects of erythromycin on a rapidly activating delayed rectifier K⁺ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells. When examined using the whole-cell patch clamp technique, erythromycin (100 μM) blocked Kv1.5 current in a time-dependent manner but required prolonged exposure to do so. However, when we examined Kv1.5 current using inside-out macropatches, erythromycin applied to the cytoplasmic surface rapidly (within 1-2 min) inhibited Kv1.5 current with an IC₅₀ value of 2.6 x 10^-5M (1.7 - 3.9 x 10^-5M, 95% C.L.). The main effect of erythromycin was to accelerate the rate of Kv1.5 current decay thereby reducing the current at the end of a prolonged voltage-clamp pulse. Erythromycin also blocked Kv1.5 current in both a voltage- and frequency-dependent manner but had little effect on the activation kinetics, deactivation kinetics, or the steady-state inactivation properties of Kv1.5. These data suggest that erythromycin acts as a blocker of an activated state of the Kv1.5 channel and that it may access its binding site from the intracellular face of the channel. This study is the first to examine the effects of erythromycin on a cloned human cardiac K⁺ channel. It is concluded that erythromycin blocks Kv1.5 at clinically relevant concentrations. Blockade of voltage-dependent K⁺ channels in the heart could contribute to the alterations in cardiac repolarization that have been observed with erythromycin. Received: 22 November 1996 / Accepted: 26 February 1997     

有机氮源对红霉素发酵影响的具体分析

红色糖多孢菌的摇瓶培养基中使用不同有机氮源时红霉素的效价明显不同。通过对不同有机氮源所含营养成分的逐步回归分析,我们得到有机氮源中的苏氨酸为影响红霉素效价的主要因子。最后向对照培养基中添加苏氨酸,则使红霉素的效价比对照培养基提高了22.85%。     

红霉素硬化疗法在非感染性疾病中的应用现状

红霉素的化学刺激作用一直被视为药物不良反应 ,近年通过对这一副作用进行深入的实验研究和临床验证 ,成功地用于许多难治性疾病的硬化治疗 ,取得了较好的效果。现就红霉素的硬化治疗新用途的国内外现状加以介绍。     

小剂量红霉素联合孟鲁司特钠治疗儿童哮喘临床疗效

目的：研究小剂量红霉素联合孟鲁司特钠治疗儿童哮喘的临床疗效。方法：选取河南科技大学第一附属医院2020年1月至2022年6月诊治的90例哮喘患儿,采用随机对照方法分为观察组和对照组,各45例。对照组采用孟鲁司特钠治疗,观察组采用小剂量红霉素联合孟鲁司特钠治疗,比较两组患儿疗效、并发症、肺功能、儿童哮喘控制测试(C–ACT)评分、血清炎症因子及T淋巴细胞的差异。结果：观察组患儿治疗总有效率高于对照组,差异具有统计学意义(P <0.05);观察组患儿消化道症状、肝肾功能损伤、嗜睡及心率失常发生率高于对照组,但差异无统计学意义(P> 0.05);观察组患儿治疗后用力肺活量(FVC)、第1秒用力呼气量(FEV1)、呼气流量峰值(PEF)及C–ACT评分均高于对照组,差异具有统计学意义(P <0.05);观察组患儿治疗后血清白三烯D4(LTD4)及肿瘤坏死因子–α(TNF–α)、CD3⁺、CD4⁺及CD8⁺均低于对照组,差异具有统计学意义(P <0.05)。结论：小剂量红霉素联合孟鲁司特钠可改善哮喘患儿肺功...     

应用威布尔分布函数研究红霉素微囊的溶出度

本文测定了红霉素微囊在人工肠液中的溶出度，并用威布尔分布函数求出了溶出百分率与时间的关系。     

Effect of erythromycin on the oro-caecal transit time in man

Summary Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility, 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA, 2-acetyl erythromycin stearate) 800 mg in a double-blind trial. The orocaecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H₂-peak (ppm) in end-expiratory breath by two methods, t₁ representing the front and t₂ the bulk of lactulose reaching the colon.t₁ was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p < 0.05, ES vs placebo). t₂ was 74 min, 64 min, and 46 min, respectively (p < 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication.It was concluded that erythromycin shortens the orocaecal transit time in man and that EA affects the transit time slightly less than ES.     

Ca2+ dependence of motilide-induced contractions in rabbit duodenal muscle strips in vitro

Summary Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called motilides. We have investigated the Ca²⁺-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydro-erythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin.Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca²⁺-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC₅₀ of 26 ± 5 nM for ME-34 (n = 7), and 27 ± 5 nM for EM-5231 (n = 16) and maximal responses of respectively 88 ± 4% and 80 ± 3%. Like motilin, both compounds induced an extra-contraction in depolarized tissues. The EM-523 response in 140 mM K⁺under isotonic conditions was 84 ± 3% (n = 5) at 10^–5 M, with an EC₅₀ that was shifted to 65 ± 18 nM. Similar figures were obtained for ME-34. When Ca²⁺ was added to Ca²⁺-depleted strips, half-maximal Ca²⁺ values (in mM) were 1.10 ± 0.11 (n = 9) for EM-523 and 1.13 ± 0.12 (n = 3) for ME-34, as compared with 1.12 ± 0.13 (n = 7) for motilin and 2.8 ± 1.1 (n = 9) for K⁺. Both ME-34 and EM-523 also induced a transient contraction in Ca⁺-free solutions under isometric conditions. The response to EM-523 (5 × 10^–6 M) was 49 ± 15% (n = 4) after 3 min. A maximal EM-523 -stimulation reduced a subsequent ACh response by 78 ± 7%, whereas EM-523 and ME-34 could not induce a contraction after ACh.We conclude that motilides depend upon external Ca²⁺ to a similar extent to motilin. Like motilin, they are also able to mobilize intracellular Ca Z + stores. Our results support the hypothesis that motilides act on motilin receptors. Send offprint requests to T. L. Peeters at the above address     

红霉素、阿奇霉素联合短程治疗小儿支原体肺炎临床研究

目的探讨红霉素、阿奇霉素联合短程和红霉素、阿奇霉素常规治疗小儿肺炎支原体肺炎,是否具有相同的疗效,并比较两种方案的安全性。方法180例肺炎支原体肺炎患儿随机分为两组,观察组80例,静脉滴注红霉素30mg·kg-1·d-1后同时口服阿奇霉素10mg·kg-1·d-,连续3天。对照组100例静脉滴注红霉素30mg·kg-1·d-1,连续7天后改为口服阿奇霉素10mg·kg-1·d-,连续3天。详细记录症状、体征、X线等及复查肝功能。结果观察组与对照组在治疗后3天,两组均能较好地控制发热、咳嗽等症状,治疗2周后X线检查病灶均基本吸收,疗效无显著差异(P>0.05)。结论对小儿肺炎支原体肺炎,红霉素、阿奇霉素联合短程与红霉素、阿奇霉素常规治疗疗效无差异,安全性相同。但前者既可缩短患者住院时间,减少用药频率,同时可减轻患儿家庭经济负担。     

红霉素环11,12-碳酸酯与罗红霉素双盲双模拟随机对照治疗细菌性感染的临床及细菌学评价

目的 评价红霉素环11，12—碳酸酯治疗呼吸系统和皮肤细菌性感染的安全性与有效性。方法 采用多中心、区组随机化、双盲双模拟对照试验设计，选用罗红霉素作对照药。试验药：红霉家环ll，12—碳酸酯片剂，250～500mg/次，每日2次。对照药：罗红霉素片剂，150～300mg/次，每日2次，疗程均为5～10d。结果 实验组28例(呼吸系统感染17例，皮肤软组织感染ll例)与对照组29例(呼吸系统感染17例，皮肤软组织感染12例)临床总有效率分别为85．71％与82．76％，细菌清除率分别为76％与83．33％，细菌敏感百分率分别为89．36％与72．34％，不良反应发生率分别为12．1％与12．5％，两组比较无统计学差异。结论 红霉素环11，12—碳酸酯治疗细菌性感染安全有效。     

中性粒细胞对红霉素内在化的特殊意义

为了解红霉素被中性粒细胞(PMN)内在化浓聚的规律及其后续意义。采用体外PMN与红霉素共孵育的方法，检测共孵育过程中及刺激活化后细胞内外红霉素浓度比的时相动力学改变。免疫荧光法检测PMN浓聚红霉素后细胞膜表面炎性表征膜结合弹力酶的基础水平及刺激活化后的改变。检测下呼吸道感染大鼠循环注入浓聚红霉素的PMN后，支气管肺胞灌洗液中红霉素浓度与正常大鼠的差异。结果显示，PMN可迅速浓聚红霉素，60min细胞内／外浓度比达高峰16／1，而此时膜表面弹力酶水平则明显下降。刺激活化浓聚红霉素的PMN，可导致细胞内／外浓度比下降，而此时膜表面弹力酶表达上升，但上升幅度低于正常PMN。接受浓聚红霉素PMN注射的下呼吸道感染大鼠，其气道中红霉素浓度明显高于正常大鼠。研究结果提示红霉素可在PMN中迅速浓聚，这种浓聚可导致PMN基础活化水平的降低以及刺激活化反应的抑制。刺激活化可导致浓聚红霉素的部分释放，此特性有助于浓聚于PMN的红霉素向感染部位的定向释放。