盐酸米诺环素软膏治疗干槽症的临床观察

目的:比较盐酸米诺环素与碘仿纱条在治疗干槽症中的疗效。方法:对42例确诊为干槽症的患者经过常规清创后,分别采用牙槽窝注射盐酸米诺环素(21例)或者填塞碘仿纱条(21例)的方法治疗,借以控制或缓解临床症状,随访比较其疗效。结果:两种治疗方法的总有效率没有明显差异,但是盐酸米诺环素组的疗效评价为良好的比例明显高于碘仿纱条组(P<0.05)。结论:盐酸米诺环素牙用软膏辅助治疗干槽症是一种行之有效的方法。     

盐酸米诺环素复合明胶海绵治疗干槽症的临床研究

目的:比较盐酸米诺环素复合明胶海绵与碘仿纱条治疗干槽症的疗效。方法:58例确诊为干槽症的患者经常规清创后,随机均分为2组。实验组牙槽窝内置入盐酸米诺环素复合明胶海绵;对照组填塞碘仿纱条,随访比较其疗效。结果:组间比较[实验组/对照组:优(例)23/16;良(例)6/11;可(例)0/2],Kruskal-Wallis检验法检验,疗效评价等级为"优"的实验组病例数多于对照组(P<0.05)。结论:盐酸米诺环素复合明胶海绵对干槽症的疗效优于碘仿纱条。     

盐酸米诺四环素软膏对慢性牙周炎龈沟液中硫化物的影响

目的：分析慢性牙周炎病人局部应用盐酸米诺四环素（minocycline HCl，MINO）后，不同牙周状态下龈沟液（GCF）中硫化物（suleus sulphide level，SUL）浓度变化及其与临床指标的关系。方法：采用金刚牙周探测仪对盐酸米诺四环素治疗前后龈沟液中硫化物浓度及其临床指标进行测定。随机单盲法选择慢性牙周炎病人21例，61个患牙。用药组（T）34个患牙，204个位点，基础治疗后将盐酸米诺四环素软膏置牙周袋内；对照组（C）卯个患牙，162个位点，以单纯基础治疗为主。于基线前两周完成全口龈上洁治、口腔卫生宣教。基线时测定相应位点龈沟液中硫化物浓度，龈沟出血指数（SBI），牙周袋探诊深度（PPD），牙周临床附着丧失水平（CAL）；然后行龈下刮治术，用药组龈沟内放药，对照侧不放药。第2周各项指标检查同上。结果：用药组（T）龈沟液中硫化物浓度与其基线时和对照组相比明显下降（P〈0．05），其临床指标用药组（T）与对照组（C）相比改善明显（P〈0．05），龈沟液中硫化物的浓度与临床指标间具有相关性。结论：盐酸米诺四环素软膏（MINO）辅助治疗牙周炎，能有效降低龈沟液中硫化物浓度，改善牙周组织状况；椅旁龈沟液硫化物浓度变化可间接反映对牙周袋内细菌的杀灭、抑制作用。     

派丽奥与牙康治疗牙周炎的疗效比较

目的　比较派丽奥(2%盐酸米诺环素软膏)与牙康(甲硝唑棒)治疗牙周炎的临床疗效及对牙周可疑致病菌的清除作用。方法　选取11例慢性牙周炎患者的26颗牙周炎患牙为研究对象。患牙要求:①牙周袋探诊深度≥4 mm,且探诊后出血;②左右对称。26颗患牙随机分成实验组(派丽奥治疗组)13颗,对照组(牙康治疗组)13 颗。观察用药前及用药后7 d和14 d,患牙的牙周临床指标菌斑指数(PLI)、牙龈指数(GI)、探诊深度(PD)、探诊出血(BOP)的变化和龈下附着菌斑中螺旋体、球菌、杆菌的百分比,以及非附着菌斑中牙龈卟啉单胞菌、中间普氏菌、二氧化碳噬纤维菌等牙周可疑致病菌百分比的变化。结果　实验组和对照组患牙在用药前各项牙周临床指标和微生物学指标均无显著性差异(P>0.05)。用药后,两组患牙绝大部分牙周临床指标和微生物学指标均较用药前明显改善(P<0.05),但两组间无显著性差异(P>0.05)。结论　派丽奥与牙康均是治疗牙周炎有效、安全的局部治疗药物,两者的疗效无显著性差异。     

Open-label Extension Study Evaluating Long-term Safety and Efficacy of FMX103 1.5% Minocycline Topical Foam for the Treatment of Moderate-to-Severe Papulopustular Rosacea

BACKGROUND: Efficacy and safety of FMX103 1.5% for papulopustular rosacea were previously demonstrated in two 12-week, Phase 3 studies. OBJECTIVE: We sought to evaluate the safety and efficacy of FMX103 1.5% foam for up to 52 weeks of treatment. METHODS: Following the completion of two 12-week, double-blind, vehicle-controlled, Phase 3 studies, subjects were invited to enter a 40-week open-label extension study in which all subjects applied FMX103 1.5% once daily. Efficacy endpoints were the reduction in inflammatory lesions and the rate of IGA treatment success from the double-blind baseline. Safety assessments included adverse events, vital signs, laboratory tests, and facial tolerability signs and symptoms. RESULTS: The favorable safety profile of FMX103 1.5% observed in the double-blind studies was maintained over extended treatment lasting up to one year. There were no serious treatment-related adverse events. Long-term treatment with FMX103 1.5% was associated with a greater than 82-percent reduction in inflammatory lesions from baseline and with over 79 percent of subjects achieving treatment success. At the end of the open-label treatment period, over 82 percent of subjects indicated they were overall “satisfied” or “very satisfied” with FMX103 1.5%. All facial local tolerability symptoms improved through Week 52. LIMITATIONS: Due to the nature of the open-label study, lacking a vehicle-treated control, no statistical comparisons can be made. CONCLUSION: FMX103 1.5% demonstrated a favorable safety and tolerability profile for up to 52 weeks. Long-term efficacy was demonstrated by progressive reductions in inflammatory lesions and increasing IGA treatment success, suggesting that FMX103 1.5% may be a suitable option for the treatment for papulopustular rosacea.     

Critical data‐based re‐evaluation of minocycline as a putative specific microglia inhibitor

Minocycline, a second generation broad‐spectrum antibiotic, has been frequently postulated to be a “microglia inhibitor.” A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to “inhibition” of microglia. It is, however, unclear how this “inhibition” is achieved at the molecular and cellular levels. Here, we weigh the evidence whether minocycline is indeed a bona fide microglia inhibitor and discuss how data generated with minocycline should be interpreted. GLIA 2016;64:1788–1794     

Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II

Introduction: Efforts in basic research have clarified mechanisms involved in spinal cord injury (SCI), and resulted in positive findings using experimental treatments including cell transplantation and drug administration preclinically. Based on accumulated results, various clinical trials have begun for human SCI.

Areas covered: In this review, the authors focus on five investigational drugs: riluzole, minocycline, Rho protein antagonist, magnesium chloride in polyethylene glycol formulation, and basic fibroblast growth factor. All drugs have established safety and tolerability from Phase I clinical trials, and are now in Phase II. They have been proven to have neuroprotective and/or neuroregenerative effects in animal models of SCI.

Expert opinion: To date, diverse drugs have been translated into clinical trials, but none have reached clinical application. A key gap was the lack of reliable biomarkers for SCI to fast-track Phase I/II trials. Furthermore, problems were often due to lack of adequate outcome assessments for both animal models and SCI patients. In order to advance clinical trials more quickly and with greater success, more clinically relevant animal models should be used in basic research. Clinically, it is indispensable to use appropriate outcome measurements and to construct a wide network among clinical centers to validate the efficacy of drugs.     

米诺环素对5-LOX通路及动脉粥样硬化中炎症反应的抑制作用

目的米诺环素对5-LOX通路及动脉粥样硬化(atherosclorosis,AS)中炎症反应的抑制作用。方法以高脂喂养Apo E-/-小鼠建立AS模型,同时给予米诺环素或辛伐他汀治疗12周。比较各组小鼠的血脂水平,5-LOX的表达及其代谢物LTB4的含量;测定小鼠主动脉AS斑块的面积及斑块组成(脂质、胶原和巨噬细胞含量);PCR方法比较小鼠主动脉中相关炎症因子TNF-α、IL-6、VCAM-1、MMP-2、MMP-9 m RNA的含量。结果米诺环素能显著减少主动脉中5-LOX的表达及血液中LTB4的含量;降低小鼠主动脉中相关炎症因子TNF-α、IL-6、VCAM-1、MMP-2、MMP-9 m RNA的含量。在AS斑块的形成和发展中,米诺环素显著降低了Apo E-/-小鼠AS斑块的面积,减少斑块中巨噬细胞的含量并增加胶原的含量,提高斑块的稳定性。但是米诺环素没有改变Apo E-/-小鼠的血脂水平。结论米诺环素有抗AS的作用,其作用可能与其对5-LOX通路及炎性细胞和炎症介质的抑制作用有关。     

ERK1/2通路介导米诺环素促进PC12细胞氧糖剥夺后血红素加氧酶-1的表达

目的：探讨米诺环素（minocycline, MC）对大鼠肾上腺嗜铬细胞瘤细胞（PC12）缺氧缺糖（oxygen glucose deprivation, OGD）损伤的保护作用及其机制。方法采用氧糖剥夺6 h方法建立PC12细胞缺氧缺糖损伤模型,并将细胞随机分为正常对照组、模型组、米诺环素组及MEK1/2抑制剂组,在OGD/复氧24 h后,采用MTT比色法测定PC12细胞的存活率,Western blotting法检测血红素加氧酶-1（HO-1）及胞外信号调节蛋白激酶1/2（ERK1/2）的磷酸化水平。结果 OGD组PC12细胞存活率显著低于正常对照组,米诺环素（0.1~10μmol/L）能缓解OGD损伤导致细胞存活率的下降,同时上调HO-1蛋白的表达及增加ERK1/2的磷酸化水平,其中1μmol/L浓度最佳。其次,ERK1/2上游激酶MEK1/2特异性抑制剂U0126（10μmol/L）能阻断米诺环素诱导HO-1蛋白表达的增加。结论米诺环素可减轻OGD导致PC12细胞的损伤并上调抗氧化蛋白HO-1的表达,其作用机制可能与激活ERK1/2信号通路有关。