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Acrolein scavenger dimercaprol offers neuroprotection in an animal model of Parkinson’s disease:implication of acrolein and TRPA1 被引量:1
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作者 Liangqin Shi Yazhou Lin +5 位作者 Yucheng Jiao Seth AHerr Jonathan Tang Edmond Rogers Zhengli Chen Riyi Shi 《Translational Neurodegeneration》 2021年第2期151-165,共15页
Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously... Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key factor.We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat model.As such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral benefits.Methods:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats.The acrolein levels and related pathologies were measured by immunohistochemistry.Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test.Pain was assessed using mechanical allodynia,cold hypersensitivity,and plantar tests.Finally,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.Results:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and cortex.DP also mitigated both motor and sensory deficits typical of PD.In addition,DP lowered acrolein and protected DA-like cells in vitro.Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.Conclusions:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD.Considering the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health. 展开更多
关键词 Oxidative stress Parkinson’s disease NEUROINFLAMMATION ACROLEIN TRPA1 dimercaprol
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血液灌流联合二巯基丙醇救治急性毒鼠强中毒的临床研究 被引量:5
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作者 郑大伟 张在其 +7 位作者 黄泽亮 彭巍 吴德华 谢登荣 杨华喜 刘仁水 李永亮 邓顺莲 《中国血液净化》 2006年第1期21-23,40,共4页
目的研究血液灌流(HP)联合二巯基丙醇救治急性毒鼠强中毒的临床疗效及患者血清β-内非肽(β-EP),内皮素(ET),一氧化氮(NO),肿瘤坏死因子(TNF)在病程中的变化。方法将湖南省怀化市第二人民医院急诊科1996年6月~2004年12月收治的56例患... 目的研究血液灌流(HP)联合二巯基丙醇救治急性毒鼠强中毒的临床疗效及患者血清β-内非肽(β-EP),内皮素(ET),一氧化氮(NO),肿瘤坏死因子(TNF)在病程中的变化。方法将湖南省怀化市第二人民医院急诊科1996年6月~2004年12月收治的56例患者分为A、B、C三组。①C组(常规+药物+HP)(n=20)与B组(常规+药物)(n=19)急性毒鼠强中毒39例患者,分别在入院后即刻、HP或入院后1、3、5、7、9、11d从外周静脉抽血2ml,测定β-EP、ET、NO与TNF。②A组(常规组)(n=17)为既往采用安定、苯巴比妥抗惊厥等一般救治措施;B组采用在A组治疗基础上加用二巯基丙醇治疗;C组在B组治疗基础上采用HP联合治疗。结果①C组和B组35例治愈者中,β-EP、ET、NO与TNF在C组均于入院后即刻达高峰,在B组均于入院后1d达高峰,随后均缓慢下降。C组和B组35例治愈者治疗后β-EP、ET、NO与TNF对应指标比较,C组较B组均有显著性降低。②C组和B组患者治愈率比A组均有显著性提高。C组中的安定和苯巴比妥用量、止惊时间比B组、A组均有显著性减少;B组中的安定和苯巴比妥用量、止惊时间比A组均有显著性减少。结论HP联合二巯基丙醇救治急性毒鼠强中毒临床疗效优于单纯二巯基丙醇和常规救治措施,可以明显降低患者β-EP、ET、NO与TNF水平,可作为治疗急性鼠毒强中毒的一种较为理想方案。 展开更多
关键词 毒鼠强 中毒 血液灌流 二巯基丙醇 β-内非肽 内皮素 一氧化氮 肿瘤 坏死因子
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大豆多酚氧化酶、过氧化物酶的酶学特性研究 被引量:6
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作者 李笑梅 马永强 王金凤 《食品科学》 EI CAS CSCD 北大核心 2001年第6期32-35,共4页
对大豆氧化还原酶系中的多酚氧化酶和过氧化物酶的酶学特性进行了较深入系统地研究,其中包括酶活力、酶热稳定性、pH值的影响,以及大豆卵磷脂、二巯基丙醇对酶活力的抑制作用。结果表明多酚氧化酶在120℃时,酶活力值已达到不可逆失... 对大豆氧化还原酶系中的多酚氧化酶和过氧化物酶的酶学特性进行了较深入系统地研究,其中包括酶活力、酶热稳定性、pH值的影响,以及大豆卵磷脂、二巯基丙醇对酶活力的抑制作用。结果表明多酚氧化酶在120℃时,酶活力值已达到不可逆失活状态,pH6~7时酶活力最大,当二巯基丙醇的浓度为1.5m mol/L时其酶活力降至6%以下。过氧化物酶具有较高的耐热性,酶活力最适的pH值为5.5左右,大豆卵磷脂浓度达到80mg/L时其酶活力可降至20%左右。 展开更多
关键词 大豆多酚氧化酶 大豆对氧化物酶 酶活力 酶热稳定性
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恒电流库仑分析法测定维生素C等药物 被引量:15
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作者 梁述忠 《理化检验(化学分册)》 CAS CSCD 北大核心 2005年第9期671-673,共3页
以恒电流库仑分析法测定维生素C、安乃近、二巯丙醇等药物的含量,以永停终点法指示库仑滴定终点,方法简便快速,相对误差为0.21%~0.28%,相对标准偏差(n=11)为0.027%~0.034%.
关键词 恒电流库仑分析法 维生素C 安乃近 二巯丙醇
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毒黄素与米酵菌酸中毒的解毒研究 被引量:9
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作者 赵乃昕 马麦生 《潍坊医学院学报》 1990年第3期1-3,15,共4页
酵米面与变质银耳中毒是由椰毒假单胞菌引起的。此菌产生两种毒素:毒黄素和米酵菌酸。本研究显示以含维生素E的饲料饲喂小白鼠7天,可保护动物使之耐受毒黄素2μg/g体重的腹腔注射,使之不发生中毒,而喂正常饲料的小鼠在此毒素剂量攻击下... 酵米面与变质银耳中毒是由椰毒假单胞菌引起的。此菌产生两种毒素:毒黄素和米酵菌酸。本研究显示以含维生素E的饲料饲喂小白鼠7天,可保护动物使之耐受毒黄素2μg/g体重的腹腔注射,使之不发生中毒,而喂正常饲料的小鼠在此毒素剂量攻击下全部死亡。超氧化物岐化酶与触酶只有当静脉注射时才有治疗毒黄素中毒的效果,还原性谷胱甘肽与维生素C则无效。试验了二巯基丙醇与半胱氨酸对米酵菌酸中毒的疗效,前者明显有效,可使腹腔注射米酵菌酸(1.2μg/g体重)的小鼠绝大部分存活,而未治疗的或用半胱氨酸治疗的小鼠则绝大部分死亡。由此提示,此菌中毒可用二巯基丙醇和维生素E来治疗。 展开更多
关键词 毒黄素 米酵菌 酸中毒 解毒 酵米面
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Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms 被引量:3
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作者 Chunfang Xie Julien Slagboom +4 位作者 Laura-Oana Albulescu Govert W.Somsen Freek J.Vonk Nicholas R.Casewell Jeroen Kool 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2020年第10期1835-1845,共11页
Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming.In this study,we investigated the inhibiting effects of the small molec... Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming.In this study,we investigated the inhibiting effects of the small molecules varespladib(nonspecific phospholipase A2 inhibitor),marimastat(broad spectrum matrix metalloprotease inhibitor)and dimercaprol(metal ion chelator)against coagulopathic toxins found in Crotalinae(pit vipers)snake venoms.Venoms from Bothrops asper,Bothrops jararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in parallel.Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study.Anticoagulant venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases.Varespladib was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant toxins.Contrastingly,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins.The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments. 展开更多
关键词 SNAKEBITE ANTIVENOM Varespladib MARIMASTAT dimercaprol CHELATORS Nanofractionation
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