米诺环素联合美金刚治疗肌萎缩性脊髓侧索硬化病

目的 观察联合美金刚和米诺环素用药在肌萎缩性脊髓侧索硬化病(ALS)转基因小鼠模型治疗中的协同作用.方法 ALS转基因小鼠被随机分成生理盐水对照组、米诺环素组、美金刚组和米诺环素/美金刚组.对腹腔注射米诺环素和美金刚后ALS小鼠的运动能力、发病时间、生存时间以及腓肠肌重量变化进行定量分析.结果 (1)与对照组发病时间(98.3±4.6)d比较,米诺环素组和美金刚组分别为(117.1 ±7.4)、(114.0±3.5) d(P ＜0.05)；对照组生存期为(129.4±6.2)d,米诺环素组和美金刚组分别为(146.2±5.9)、(141.9±6.3) d(P ＜0.05).联合治疗组发病时间和生存期分别为(126.2±8.4)d和(159.1±3.9)d.与对照组比较,米诺环素组、美金刚组和联合治疗组生存时间分别延长13％、11％和23％.(2)对照组小鼠第16周时腓肠肌重量为(83.5±10.2)mg,米诺环素组和美金刚组分别为(133.7 ±12.5)、(130.1 ±10.3) mg,联合治疗组为(186.3±17.9) mg,与对照组和单一用药组比较,差异有统计学意义(P＜0.05).结论 联合米诺环素和美金刚对治疗ALS小鼠具有协同治疗作用.     

[开放获取] 米诺环素单药或联合小剂量糖皮质激素治疗红斑型天疱疮15例和疱疹样天疱疮9例疗效和安全性回顾分析

【摘要】 目的 探讨米诺环素单药或联合小剂量糖皮质激素（简称激素）治疗红斑型天疱疮（PE）和疱疹样天疱疮（PH）的疗效和安全性及对免疫指标的影响。方法 回顾性纳入2011年6月至2021年6月于北京大学第一医院皮肤科初诊、初治方案为米诺环素单独或联合小剂量激素且随访至少6个月的PE和PH患者。收集基线及不同随访时间点患者病情、自身抗体水平变化，分析疾病严重程度、诊断、自身抗体变化趋势及与疗效间的关系。采用Kaplan-Meier方法分析完全缓解情况，用卡方检验分析不同严重度和疗法下PF患者的疗效。结果 共纳入24例汉族患者，包括15例PE和9例PH，男女比例为1.4∶1，中位年龄68.8岁，中位病程为22.1个月，平均随访时间为21.8个月。24例均获得疾病控制，疾病控制时间M（Q1，Q3）为15.9（12，20.1）周。完全缓解23例 （95.8%），完全缓解时间8.7（6.4， 10）个月。米诺环素单药治疗1年完全缓解率（11/13）与联合小剂量激素疗法（9/11）差异无统计学意义（χ2 = 0.16，P = 0.692）。随访期间复发2例（8.7%），皆处于疾病控制状态，1例调整剂量后于第38周达完全缓解，另1例换用利妥昔单抗，半年后达到完全缓解。轻中度患者间疗效差异无统计学意义（χ2 = 0.28，P = 0.599）。3例发生药物相关不良反应，1例为背部体癣，2例为全身皮肤及牙龈部位色素沉着。结论 米诺环素单药或联合小剂量激素治疗轻中度PE或PH疗效显著，且无严重药物相关不良反应，但该方案的长期疗效、不良反应及患者预后需未来进一步扩大样本量，进行多中心、前瞻性研究。     

耐亚胺培南鲍曼不动杆菌的体外联合药物敏感试验

目的 了解体外联合药物敏感试验对耐亚胺培南鲍曼不动杆菌的效果,为临床抗感染治疗提供依据.方法 收集自2007年3月至2008年2月耐亚胺培南鲍曼不动杆菌27株标本,以E test法和琼脂稀释法测定7种常用抗菌药物的最低抑菌浓度(MIC),以肉汤稀释棋盘法进行联合药物敏感试验,用时间杀菌试验检测米诺环素和头孢哌酮-舒巴坦的协同率.结果 肉汤稀释棋盘法结果提示,米诺环素与头孢哌酮-舒巴坦、阿米卡星、环丙沙星的协同率分别为74.1%、28.0%、48.1%,阿米卡星与头孢哌酮-舒巴坦、环丙沙星的协同率分别为23.1%、37.0%,头孢哌酮-舒巴坦与环丙沙星的协同率为7.1%.米诺环素与头孢哌酮-舒巴坦联合后药物浓度均降至非耐药范围内.时间杀菌试验结果提示,米诺环素和头孢哌酮-舒巴坦的协同率为100%.结论 针对临床上多重耐药鲍曼不动杆菌的感染,推荐使用米诺环素加头孢哌酮-舒巴坦进行联合治疗.     

米诺环素对难治性肺炎支原体肺炎的疗效分析

目的探究分析米诺环素对难治性肺炎支原体肺炎(RMPP)的临床疗效。方法选取该院自2010年1月—2011年1月收治的难治性肺炎支原体肺炎患者70例,将其作为临床研究对象。随机分为A、B两组,每组均为35例。A组患者采用大环内酯类抗生素治疗,即为对照组;B组患者在大环内酯类抗生素治疗的基础上加用米诺环素治疗。观察并对比两组患者的疗效。结果治疗后B组患者的发热时间、住院时间及并发症的总发生率均明显少于A组患者,B组的显效人数和总有效率明显高于A组,差异有统计学意义(P<0.05)。结论米诺环素对难治性肺炎支原体肺炎疗效显著,能有效的缓解患者的症状,值得在临床上广泛应用。     

Minocycline inhibits the enhancement of antidromic primary afferent stimulation-evoked vasodilation following intradermal capsaicin injection

Neurogenic inflammation is induced by inflammatory mediators released in peripheral tissue from primary afferent nociceptors. Our previous studies suggest that neurogenic inflammation induced by intradermal injection of capsaicin results from the enhancement of dorsal root reflexes (DRRs), which involve antidromic activation of dorsal root ganglion (DRG) neurons. Numerous studies have reported the important role of glial modulation in pain. However, it remains unclear whether glial cells participate in the process of neurogenic inflammation-induced pain. Here we tested the role of DRG satellite glial cells (SGCs) in this process in anesthetized rats by administration of a glial inhibitor, minocycline. Electrical stimuli (ES, frequency 10 Hz; duration 1 ms; strength 3 mA) were applied to the cut distal ends of the L4–5 dorsal roots. The stimuli evoked antidromic action potentials designed to mimic DRRs. Local cutaneous blood flow in the hindpaw was measured using a Doppler flow meter. Antidromic ES for 10 min evoked a significant vasodilation that could be inhibited dose-dependently by local administration of the calcitonin gene-related peptide receptor antagonist, CGRP8–37. Pretreatment with capsaicin intradermally injected into the hindpaw 2 h before the ES enhanced greatly the vasodilation evoked by antidromic ES, and this enhancement could be reversed by minocycline pretreatment. Our findings support the view that neurogenic inflammation following capsaicin injection involves antidromic activation of DRG neurons via the generation of DRRs. Inhibition of neurogenic inflammation by minocycline is suggested to be associated with its inhibitory effect on SGCs that are possibly activated following capsaicin injection.     

Early-activated microglia play a role in transient forebrain ischemia-induced neural precursor proliferation in the dentate gyrus of mice

Although it has been well established that ischemic insults promote cell proliferation in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), the mechanisms by which this occurs remain unclear. The present study demonstrates that early-activated microglia in the hilus of the DG play an important role in ischemia-induced cell proliferation. Transient forebrain ischemia induced by 20 min of bilateral common carotid artery occlusion (BCCAO) significantly increased cell proliferation in the SGZ of the DG beginning 4 days post-reperfusion. Moreover, BCCAO increased microglial activation in the hilus of the DG from 1 day post-reperfusion and in the CA1 layer from 4 days post-reperfusion. An injection of minocycline (10 or 100 nmol in 0.5 μl) into the DG immediately after reperfusion decreased microglial activation in the hilus of the DG 1 day post-reperfusion, but only a high dose of minocycline (100 nmol) significantly decreased microglial activation in the CA1 layer. Both high and low doses of minocycline significantly decreased the number of BrdU-positive cells at 7 days post-reperfusion. These results suggest that early-activated microglia in the hilus of the DG take part in the cell proliferation induced by transient forebrain ischemia.     

紫外分光光度法测定复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量

目的建立紫外分光光度法测定复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量。方法采用紫外分光光度法,测定波长为352nm。结果米诺环素的检测线性范围为4～24μg/ml,r=0.9999,平均回收率为100.2%。结论本法操作简便,准确性好,适合复方米诺环素过氧化苯甲酰洗剂中米诺环素的含量测定。     

米诺环素在神经病理性疼痛治疗中的最新研究进展

神经病理性疼痛的发病机理复杂,所以其治疗困难。米诺环素是第二代半合成的四环素类药物,近年来的研究显示,此药可以抑制小胶质细胞的激活而减轻神经病理性疼痛以及阻止神经病理性疼痛的发展。本文就迄今为止米诺环素在神经病理性疼痛的研究作一综述。