目的通过Buehler试验,观察豚鼠皮肤接触苦参凝胶后的过敏反应,初步评价苦参凝胶的安全性。方法挑选60只雌性健康的SPF级Hartley豚鼠,分为4组:基质组、苦参凝胶低、高剂量组和阳性对照组,基质组和阳性对照组各10只,低剂量组和高剂量组各2...目的通过Buehler试验,观察豚鼠皮肤接触苦参凝胶后的过敏反应,初步评价苦参凝胶的安全性。方法挑选60只雌性健康的SPF级Hartley豚鼠,分为4组:基质组、苦参凝胶低、高剂量组和阳性对照组,基质组和阳性对照组各10只,低剂量组和高剂量组各20只。试验分为两个阶段,第一阶段为诱导期,基质组给予苦参凝胶(基质)0.4 m L/只;低、高剂量组分别给予苦参凝胶0.4 m L/只和0.8 m L/只;阳性对照组给予1%(W/V)2,4-二硝基氯苯0.4 m L/只。于试验第1、8、15日采用经皮涂抹给药,共3次。第二阶段为激发期,在诱导期末次给药后第14日一次激发。除阳性对照组给予0.2%(W/V)2,4-二硝基氯苯,其余3组与诱导期的给药体积均相同,给药途径为经皮涂抹。结果所有豚鼠都存活至激发前,各动物致敏期及激发期详细临床观察均未见明显异常。在致敏后1 h和24 h,各组动物皮肤均未见明显红斑和水肿等过敏反应;激发给药后24小时,各组均未出现皮肤过敏反应;激发给药后48小时,阳性对照组1只动物(1/10例)出现轻微红斑,1只动物(1/10例)出现中度红斑、轻度水肿,2只动物(2/10例)出现轻度红斑、轻度水肿,苦参凝胶低、高剂量组及基质组激发后均正常。结论苦参凝胶皮肤给药对豚鼠无明显致敏作用。展开更多
Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these ...Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these pseudoallergic reactions can be severe or even lethal, it is an important clinical objective to find biomarkers for proneness for C activation by reactogenic nanoparticles that will allow the prediction of in vivo reactions by in vitro assays. With this goal in mind we identified a normal human blood donor who consistently showed high sensitivity to Caelyx-induced C activation in vitro, whose plasma (Caelyx sensitive plasma, CSP) was subjected to proteome profiling with a library of human plasma proteome specific mAbs. The chip (PlasmaScan-380TM) contained 380 non redundant (with respect to epitopes) mAbs. The analysis revealed 8 proteins that were differentially represented in CSP in comparison with Caelyx-insensitive control plasma. These proteins were identified by mass spectrometry and Western blot analyses to represent factor H (decreased in CSP), factor H related protein, serum amyloid P component, fibronectin, complement component C4, Apo B100, prothrombin and alpha-2-HS glycoprotein (all increased in CSP). Some of these protein changes are consistent with proneness for increased C activation, suggesting the potential use of this method in the search for biomarkers for liposome-induced or other types of nanomedicine-induced HSRs.展开更多
奥沙利铂是多种恶性肿瘤治疗的基石药物。超敏反应是奥沙利铂令人困扰的不良反应之一,可能危及患者生命,常迫使医师停用奥沙利铂,转寻其他替代方案,而这些替代方案可能效果更差、耐受性更低和(或)价格更昂贵。奥沙利铂超敏反应主要表现...奥沙利铂是多种恶性肿瘤治疗的基石药物。超敏反应是奥沙利铂令人困扰的不良反应之一,可能危及患者生命,常迫使医师停用奥沙利铂,转寻其他替代方案,而这些替代方案可能效果更差、耐受性更低和(或)价格更昂贵。奥沙利铂超敏反应主要表现为经典的Ⅰ型过敏反应,另外还包含细胞因子释放反应及混合型。临床上最关注的是严重过敏反应的管理以及针对发生超敏反应后奥沙利铂再挑战的问题。因此,本专家组基于国内外循证医学证据,结合临床实践经验,对奥沙利铂超敏反应的定义、临床特征、诊断、分类与分级标准、处理以及再挑战进行充分的评估与讨论,最终形成《奥沙利铂超敏反应全程管理中国专家共识(2024年版)》,以便进一步规范对奥沙利铂超敏反应的全程管理。本共识已在国际实践指南注册与透明化平台(Practice guideline REgistration for transPAREncy,PREPARE)上注册,注册编号为PREPARE-2024CN371。展开更多
文摘目的通过Buehler试验,观察豚鼠皮肤接触苦参凝胶后的过敏反应,初步评价苦参凝胶的安全性。方法挑选60只雌性健康的SPF级Hartley豚鼠,分为4组:基质组、苦参凝胶低、高剂量组和阳性对照组,基质组和阳性对照组各10只,低剂量组和高剂量组各20只。试验分为两个阶段,第一阶段为诱导期,基质组给予苦参凝胶(基质)0.4 m L/只;低、高剂量组分别给予苦参凝胶0.4 m L/只和0.8 m L/只;阳性对照组给予1%(W/V)2,4-二硝基氯苯0.4 m L/只。于试验第1、8、15日采用经皮涂抹给药,共3次。第二阶段为激发期,在诱导期末次给药后第14日一次激发。除阳性对照组给予0.2%(W/V)2,4-二硝基氯苯,其余3组与诱导期的给药体积均相同,给药途径为经皮涂抹。结果所有豚鼠都存活至激发前,各动物致敏期及激发期详细临床观察均未见明显异常。在致敏后1 h和24 h,各组动物皮肤均未见明显红斑和水肿等过敏反应;激发给药后24小时,各组均未出现皮肤过敏反应;激发给药后48小时,阳性对照组1只动物(1/10例)出现轻微红斑,1只动物(1/10例)出现中度红斑、轻度水肿,2只动物(2/10例)出现轻度红斑、轻度水肿,苦参凝胶低、高剂量组及基质组激发后均正常。结论苦参凝胶皮肤给药对豚鼠无明显致敏作用。
文摘Complement (C) activation-related hypersensitivity reactions (HSRs) represent an unsolved adverse immune effect of many i.v. administered “nanomedicines”, such as liposomal doxorubicin (Doxil/Caelyx). Because these pseudoallergic reactions can be severe or even lethal, it is an important clinical objective to find biomarkers for proneness for C activation by reactogenic nanoparticles that will allow the prediction of in vivo reactions by in vitro assays. With this goal in mind we identified a normal human blood donor who consistently showed high sensitivity to Caelyx-induced C activation in vitro, whose plasma (Caelyx sensitive plasma, CSP) was subjected to proteome profiling with a library of human plasma proteome specific mAbs. The chip (PlasmaScan-380TM) contained 380 non redundant (with respect to epitopes) mAbs. The analysis revealed 8 proteins that were differentially represented in CSP in comparison with Caelyx-insensitive control plasma. These proteins were identified by mass spectrometry and Western blot analyses to represent factor H (decreased in CSP), factor H related protein, serum amyloid P component, fibronectin, complement component C4, Apo B100, prothrombin and alpha-2-HS glycoprotein (all increased in CSP). Some of these protein changes are consistent with proneness for increased C activation, suggesting the potential use of this method in the search for biomarkers for liposome-induced or other types of nanomedicine-induced HSRs.
文摘奥沙利铂是多种恶性肿瘤治疗的基石药物。超敏反应是奥沙利铂令人困扰的不良反应之一,可能危及患者生命,常迫使医师停用奥沙利铂,转寻其他替代方案,而这些替代方案可能效果更差、耐受性更低和(或)价格更昂贵。奥沙利铂超敏反应主要表现为经典的Ⅰ型过敏反应,另外还包含细胞因子释放反应及混合型。临床上最关注的是严重过敏反应的管理以及针对发生超敏反应后奥沙利铂再挑战的问题。因此,本专家组基于国内外循证医学证据,结合临床实践经验,对奥沙利铂超敏反应的定义、临床特征、诊断、分类与分级标准、处理以及再挑战进行充分的评估与讨论,最终形成《奥沙利铂超敏反应全程管理中国专家共识(2024年版)》,以便进一步规范对奥沙利铂超敏反应的全程管理。本共识已在国际实践指南注册与透明化平台(Practice guideline REgistration for transPAREncy,PREPARE)上注册,注册编号为PREPARE-2024CN371。
