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Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan
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作者 Yiqiao Gao Wei Li +5 位作者 Jiaqing Chen Xu Wang Yingtong Lv Yin Huang Zunjian Zhang Fengguo Xu 《药学学报:英文版》 CSCD 2019年第1期157-166,共10页
Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, wh... Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan(CPT-11),and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually,two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine. 展开更多
关键词 IRINOTECAN Individual differences Complicating TOXICITY PREDICTION Metabolomics GASTROINTESTINAL TOXICITY Biomarkers DIARRHEA
和中降逆贴穴位贴敷治疗大肠癌mFOLFOX6方案毒性反应临床观察 预览
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作者 董皖辉 孙庆明 《安徽中医药大学学报》 2019年第1期44-47,共4页
目的观察和中降逆贴穴位贴敷减轻大肠癌化学治疗所致毒性反应的效果。方法将72例大肠癌化学治疗患者随机分为观察组和对照组,每组36例。对照组患者单纯采用mFOLFOX6化学治疗方案(5-氟尿嘧啶+亚叶酸钙+奥沙利铂),观察组患者采用mFOLFOX6... 目的观察和中降逆贴穴位贴敷减轻大肠癌化学治疗所致毒性反应的效果。方法将72例大肠癌化学治疗患者随机分为观察组和对照组,每组36例。对照组患者单纯采用mFOLFOX6化学治疗方案(5-氟尿嘧啶+亚叶酸钙+奥沙利铂),观察组患者采用mFOLFOX6方案化学治疗联合中药穴位贴敷。化学治疗第1、3、6天,分别观察两组患者消化道毒性反应、白细胞毒性反应及口腔黏膜毒性反应。结果化学治疗第1、3、6天,对照组消化道毒性反应分级比较,差异无统计学意义(P >0.05),观察组消化道毒性反应分级比较,差异有统计学意义(P<0.05);两组3个时点白细胞毒性分级比较,差异均有统计学意义(P<0.05);两组3个时点口腔黏膜毒性反应分级比较,差异均无统计学意义(P >0.05)。两组化学治疗第6天和第1天消化道毒性反应分级变化比较,差异有统计学意义(P<0.05),两组白细胞毒性分级变化、口腔黏膜毒性反应分级变化比较,差异均无统计学意义(P >0.05)。结论和中降逆贴穴位贴敷可有效缓解大肠癌患者因mFOLFOX6化学治疗方案所致的消化道症状。 展开更多
关键词 穴位贴敷 大肠癌 化学治疗 毒性 不良反应
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栀子与淡豆豉配伍减毒机制的研究 预览
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作者 杜玉青 袁美杰 王鑫国 《河北中医》 2019年第1期91-95,共5页
目的 探讨栀子与淡豆豉配伍减毒作用的机制。方法 将50只Wistar大鼠随机分为空白对照组(等容积蒸馏水)、栀子中剂量组(1.4 g生药/kg)、栀子高剂量组(2.8 g生药/kg)、栀子中剂量+淡豆豉中剂量组(各1.4 g生药/kg)、栀子高剂量+淡豆豉高剂... 目的 探讨栀子与淡豆豉配伍减毒作用的机制。方法 将50只Wistar大鼠随机分为空白对照组(等容积蒸馏水)、栀子中剂量组(1.4 g生药/kg)、栀子高剂量组(2.8 g生药/kg)、栀子中剂量+淡豆豉中剂量组(各1.4 g生药/kg)、栀子高剂量+淡豆豉高剂量组(各2.8 g生药/kg),连续灌胃给药7 d后,腹主动脉取血,测定大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,将大鼠脊椎脱臼处死取出肝脏,计算肝脏指数并观察肝脏病理变化。结果 与空白对照组比较,栀子中剂量组、栀子高剂量组、栀子中剂量+淡豆豉中剂量组、栀子高剂量+淡豆豉高剂量组ALT、AST升高(P<0.05);栀子高剂量组ALT、AST高于栀子中剂量组(P<0.05);栀子中剂量+淡豆豉中剂量组、栀子高剂量+淡豆豉高剂量组与栀子中剂量组、栀子高剂量组比较ALT、AST均降低(P<0.05);栀子高剂量+淡豆豉高剂量组与栀子中剂量+淡豆豉中剂量组比较ALT、AST降低(P<0.05)。与空白对照组比较,栀子中剂量组、栀子高剂量组、栀子中剂量+淡豆豉中剂量组、栀子高剂量+淡豆豉高剂量组肝脏指数均升高(P<0.05);栀子高剂量组肝脏指数高于栀子中剂量组(P<0.05);栀子高剂量+淡豆豉高剂量组与栀子中剂量+淡豆豉中剂量组比较肝脏指数降低(P<0.05);与栀子中剂量组、栀子高剂量组比较,栀子中剂量+淡豆豉中剂量组、栀子高剂量+淡豆豉高剂量组肝脏指数均降低(P<0.05)。结论 栀子与淡豆豉配伍使用,能够大大降低肝毒性。 展开更多
关键词 栀子 淡豆豉 毒性 中药配伍
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Comprehensive Application of Graphene: Emphasis on Biomedical Concerns
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作者 S.Syama P.V.Mohanan 《纳微快报:英文版》 CAS CSCD 2019年第1期101-131,共31页
Graphene, sp~2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalys... Graphene, sp~2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional(2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a sca old for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications. 展开更多
关键词 GRAPHENE BIOMEDICAL BIOPRINTING Toxicity PHOTOTHERMAL therapy
Physical and toxicological profiles of human IAPP amyloids and plaques
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作者 Aleksandr Kakinen Yunxiang Sun +9 位作者 Ibrahim Javed Ava Faridi Emily H.Pilkington Pouya Faridi Anthony W.Purcell Ruhong Zhou Feng Ding Sijie Lin Pu Chun Ke Thomas P.Davis 《科学通报:英文版》 SCIE EI CSCD 2019年第1期26-35,共10页
Although much has been learned about the fibrillization kinetics,structure and toxicity of amyloid proteins,the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologica... Although much has been learned about the fibrillization kinetics,structure and toxicity of amyloid proteins,the properties of amyloid fibrils beyond the saturation phase are often perceived as chemically and biologically inert,despite evidence suggesting otherwise.To fill this knowledge gap,we examined the physical and biological characteristics of human islet amyloid polypeptide (IAPP)fibrils that were aged up to two months.Not only did aging decrease the toxicity of IAPP fibrils,but the fibrils also sequestered fresh IAPP and suppressed their toxicity in an embryonic zebrafish model.The mechanical properties of IAPP fibrils in different aging stages were probed by atomic force microscopy and sonication,which displayed comparable stiffness but age-dependent fragmentation,followed by self-assembly of such fragments into the largest lamellar amyloid structures reported to date.The dynamic structural and toxicity profiles of amyloid fibrils and plaques suggest that they play active,long-term roles in cell degeneration and may be a therapeutic target for amyloid diseases. 展开更多
关键词 IAPP AMYLOID PLAQUE Self assembly Toxicity
石墨烯量子点在生物医学中的应用:进展与挑战 预览
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作者 赵贤贤 陈菲(综述) 罗阳(审校) 《国际检验医学杂志》 CAS 2019年第5期513-517,共5页
与其他纳米材料相比,以石墨烯量子点为基础的复合纳米材料,具有许多独特的理化性质,因此,在多个应用研究领域特别是在生物医学方面得到了高度关注。本篇综述中,笔者主要着眼于石墨烯量子点在生物传感器、体内外成像以及疾病治疗等领域... 与其他纳米材料相比,以石墨烯量子点为基础的复合纳米材料,具有许多独特的理化性质,因此,在多个应用研究领域特别是在生物医学方面得到了高度关注。本篇综述中,笔者主要着眼于石墨烯量子点在生物传感器、体内外成像以及疾病治疗等领域的研究进展,并讨论了石墨烯量子点尚未解决以及在生物医学应用中有争议的话题,展望了石墨烯量子点为基础的纳米材料在生物医学方面的应用前景。 展开更多
关键词 石墨烯量子点 传感器 成像 药物传递 毒性
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Osteocyte viability and bone density in cadmium chloride-induced osteoporosis ameliorated with Pilostigma thonningii stem bark-extracted D-3-O-methy-chiroinositol 预览
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作者 Edwin Aihanuwa Uwagie-Ero Clifford Nwabugwu Abiaezute +4 位作者 Chinaka O.Nwaehujor Theophilus Okafor Nnaji Eugene Amienwanlen Odigie Oyetunde Kazeem Ekeolu Ohiemi Benjamin Ocheja 《动物模型与实验医学(英文)》 CSCD 2019年第1期25-33,共9页
Background:T his study examined the ameliorative effect of D-3-O-m ethylchiroinositol,isolated from the stem bark of Piliostigma thonningii,on cadmium chloride-induced osteoporosis in male Wistar rats.Methods:T hirty-... Background:T his study examined the ameliorative effect of D-3-O-m ethylchiroinositol,isolated from the stem bark of Piliostigma thonningii,on cadmium chloride-induced osteoporosis in male Wistar rats.Methods:T hirty-s ix rats were assigned to three treatment groups(n=12).Group A(2 mL distilled water),group B:(2.5 mg/kg b.w.CdCl 2)and group C:(2.5 mg/kg b.w.CdCl 2 and D-3-O-methyl-chiroinositol 2 mg/kg b.w.).Bone ash,calcium,phosphate,magnesium,and zinc content,as well as bone histological changes were determined at the end of months 1,2,and 3.Results:T here were significant differences(P≤0.05)in the weight of the cervical,tibia,and femoral bones in all groups.The serum concentration of CdCl 2 was significantly different across the three groups with time.There was significant variation(P<0.005)in the mean bone ash across groups.The concentration of OH-proline was significantly different(P<0.0001)across groups.There were significant differences(P<0.0001)in bone calcium,magnesium,zinc,and phosphorus concentrations.Histology revealed high levels of bone mineralisation in the CdCl 2-treated group,indicative of osteoporosis with hypertrophied osteocytes,while the femur of Wistar rats treated with D-3-O-methyl-chiroinositol showed bone trabeculae and viable osteocytes.Conclusion:T he study concluded that D-3-O-m ethyl-c hiroinositol extract from Piliostigma thionningii stem bark ameliorated cadmium chloride-induced osteoporosis in male Wistar rats. 展开更多
关键词 cadmium chloride D-3-O-methyl-chiroinositol OSTEOCYTES OSTEOPOROSIS toxicity AMELIORATION
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机体保护多肽对大鼠重复给药毒性研究 预览
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作者 阮苗苗 岳鹏 +3 位作者 沈姣 李楚 刘晶 戴一凡 《蚌埠医学院学报》 CAS 2019年第2期141-145,共5页
目的:检测机体保护多肽(HuBPP)对大鼠产生的毒性反应,为临床提供无毒性反应剂量,从而为临床更安全地用药以及不良反应的监控提供参考信息。方法:80只SD大鼠单次静脉和肌内注射给药以确认给药剂量。选择0.2mg/kg、1mg/kg和4mg/kg为本次... 目的:检测机体保护多肽(HuBPP)对大鼠产生的毒性反应,为临床提供无毒性反应剂量,从而为临床更安全地用药以及不良反应的监控提供参考信息。方法:80只SD大鼠单次静脉和肌内注射给药以确认给药剂量。选择0.2mg/kg、1mg/kg和4mg/kg为本次实验的低、中、高剂量,并设置溶媒对照组,每组30只大鼠,雌雄各半。连续肌内注射给药一个月,实验期间观察大鼠质量、摄食量等指标,给药末期和恢复期采血检测各临床指标,病理学检测各主要脏器毒性变化。结果:急性毒性实验表明,20mg/kg给药剂量下,实验组与对照组相比各观察指标未发现明显改变。长期毒性实验结果表明,与对照组相比,各剂量组大鼠质量、摄食量、主要脏器指标均未发现明显毒性反应(P>0.05)。长期毒性实验给药结束后,高剂量组雌鼠MCHC高于溶媒对照组,MPV低于溶媒对照组(P<0.01和P<0.05);中剂量对照组雌鼠TG高于溶媒对照组,Na+浓度低于溶媒对照组(P<0.05);雄鼠高、中剂量组活化部分凝血活酶时间显著低于溶媒对照组(P<0.05),高剂量组Cl-浓度显著高于溶媒对照组(P<0.05)。恢复期结束后高剂量组雄鼠红细胞体积分布宽度值低于溶媒对照组(P<0.05),低剂量组雌鼠丙氨酸氨基转移酶、血糖、三酰甘油显著高于溶媒组(P<0.05~P<0.01),但均处于文献报道正常变化范围内;其他指标差异无统计学意义。结论:在本实验条件下,HuBPP对大鼠的相对安全剂量为4mg/kg及其以下剂量。 展开更多
关键词 机体保护多肽 单次给药 重复给药 毒性 大鼠
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基于模式生物斑马鱼的款冬叶肝肾毒性比较研究
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作者 段亚辉 张云 +2 位作者 王雪 韩利文 李震宇 《中草药》 CAS CSCD 北大核心 2019年第3期669-674,共6页
目的采用斑马鱼模型比较款冬叶、花的肝脏、肾脏毒性,为款冬叶的资源利用提供实验依据。方法取3 dpf(day post fertilization)健康AB系及转基因系斑马鱼,将款冬叶、款冬花以及款冬叶、花分别与紫菀配伍后的4个样品溶于斑马鱼培养用水,... 目的采用斑马鱼模型比较款冬叶、花的肝脏、肾脏毒性,为款冬叶的资源利用提供实验依据。方法取3 dpf(day post fertilization)健康AB系及转基因系斑马鱼,将款冬叶、款冬花以及款冬叶、花分别与紫菀配伍后的4个样品溶于斑马鱼培养用水,分别以0.5、1.0、1.5 mg/mL给药,以培养用水为对照,处理72 h后观察各组样品对斑马鱼肝、肾形态及各指标的影响,以斑马鱼肝脏的荧光面积和肝脏丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平评价药物对肝脏的毒性,以斑马鱼表型变化结合培养液蛋白量评价药物的肾脏毒性。结果与对照组比较,各给药组对斑马鱼肝脏生化指标无显著影响,但在1.5 mg/mL剂量下,款冬花及款冬花+紫菀组斑马鱼的肝脏荧光面积减小。各药物处理组斑马鱼表型及培养液蛋白量无显著差异。结论款冬花及款冬花配伍紫菀在高剂量时对肝脏产生一定的毒性,而款冬叶及款冬叶配伍紫菀未表现出明显的肝肾毒性,即款冬叶入药的安全性风险不高于款冬花。研究结果为款冬叶的资源利用奠定了基础。 展开更多
关键词 款冬叶 款冬花 斑马鱼 毒性 资源利用
Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook 预览
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作者 Yue Gao Aihua Liang +3 位作者 Xiaohui Fan Limin Hu Feiran Hao Yubo Li 《工程(英文)》 2019年第1期76-82,共7页
Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adve... Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics;methods to identify dose–toxicity relationships in TCM;and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae. 展开更多
关键词 TRADITIONAL Chinese MEDICINE SAFETY METHODS and technical platform TOXICITY Mechanism
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微塑料对微藻的毒性效应研究进展
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作者 王素春 刘光洲 +2 位作者 张欢 黄天媛 刘菲菲 《海洋环境科学》 CAS CSCD 北大核心 2019年第2期192-197,共6页
微塑料(MPs)污染已经成为全球的持久性污染问题,引起了世界范围内的广泛关注。目前的研究表明,微塑料对水环境中的初级生产者微藻具有一定的毒害作用,同时,微塑料与其他污染物结合还可能产生更为严重的联合毒性效应,进而影响水体中食物... 微塑料(MPs)污染已经成为全球的持久性污染问题,引起了世界范围内的广泛关注。目前的研究表明,微塑料对水环境中的初级生产者微藻具有一定的毒害作用,同时,微塑料与其他污染物结合还可能产生更为严重的联合毒性效应,进而影响水体中食物链的稳定性,并对生态系统的健康带来潜在的风险。因此,开展微塑料对微藻毒性效应的研究十分必要。本文介绍了已公开发表的相关研究及成果,总结了微塑料对微藻的机械损伤、遮蔽效应、氧化损伤、吸附和团聚等致毒机理,并对未来微塑料对微藻毒性的研究方向做了简要分析与展望。 展开更多
关键词 微塑料 微藻 污染物 毒性
基于斑马鱼毒/效同步评价的壮骨关节丸促骨骼发育作用与初步安全性研究
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作者 时克 王茉 +1 位作者 景莉君 韦英杰 《中国现代应用药学》 CAS CSCD 北大核心 2019年第2期164-167,共4页
目的用斑马鱼毒/效同步法评价壮骨关节丸的促骨骼发育作用及初步安全性。方法将受精后3d(3daypost fertilization,3 dpf)的斑马鱼幼鱼暴露于25μmol·L-1泼尼松龙(prednisolone,PN),壮骨关节丸溶液及含PN的壮骨关节丸溶液(12.5,25,5... 目的用斑马鱼毒/效同步法评价壮骨关节丸的促骨骼发育作用及初步安全性。方法将受精后3d(3daypost fertilization,3 dpf)的斑马鱼幼鱼暴露于25μmol·L-1泼尼松龙(prednisolone,PN),壮骨关节丸溶液及含PN的壮骨关节丸溶液(12.5,25,50,100,200,300和400μg·mL-1)中,0.5%DMSO胚胎培养基为空白对照,于28℃培养至8 dpf,隔天换一半药液。采用茜素红对8 dpf的斑马鱼幼鱼头部骨骼染色,定量分析骨骼染色区域;给药期间每天同步观察鱼死亡及脏器中毒情况。结果在8dpf时,100μg·mL-1及以上浓度的壮骨关节丸健康鱼组和含PN的壮骨关节丸模型鱼组斑马鱼死亡率>80%,未进行骨骼染色。壮骨关节丸健康鱼组(12.5,25,50μg·mL-1)的斑马鱼头骨矿化面积和累积光密度值IOD与PN组比较显著增加(P<0.01或<0.05),而含PN的壮骨关节丸模型鱼组(12.5,25,50μg·mL-1)斑马鱼的头骨矿化面积或IOD结果显示阻止PN致骨丢失的趋势,但均低于健康鱼组。给予壮骨关节丸后,PN模型鱼的死亡速度和死亡率较健康鱼高,鱼死亡率与给药浓度和时间呈依赖性;PN模型鱼的6dpf和8dpf半数致死浓度值(63.92,63.92μg·mL-1)均低于健康鱼(94.66,87.84μg·mL-1)。结论斑马鱼毒/效同步法快速评价了壮骨关节丸对健康鱼和模型鱼的骨骼发育作用及初步安全性。壮骨关节丸对健康鱼和模型鱼的作用及毒性有差别。 展开更多
关键词 斑马鱼 壮骨关节丸 毒性 骨质疏松
自乳化给药系统对雷公藤甲素的减毒作用研究
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作者 章瑾 谢明华 +1 位作者 蔡鑫君 游剑 《中国现代应用药学》 CAS CSCD 北大核心 2019年第2期168-171,共4页
目的考察自乳化给药系统对雷公藤甲素的肝肾毒性影响。方法构建荷人胃癌细胞株MGC80-3的裸鼠肿瘤模型,分为模型对照组、雷公藤甲素原料药组和雷公藤甲素自微乳组,灌胃给药,每2天1次,连续23 d,末次给药24 h后,各组裸鼠采血收集血清,检测... 目的考察自乳化给药系统对雷公藤甲素的肝肾毒性影响。方法构建荷人胃癌细胞株MGC80-3的裸鼠肿瘤模型,分为模型对照组、雷公藤甲素原料药组和雷公藤甲素自微乳组,灌胃给药,每2天1次,连续23 d,末次给药24 h后,各组裸鼠采血收集血清,检测各裸鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素、肌酐、总蛋白、白蛋白、球蛋白及血尿酸;动物死亡后称重,解剖取肝、肾,观察形态,计算肝、肾指数;取各组裸鼠肝、肾组织病理切片,HE染色后,在生物显微镜下观察各组织形态学变化。结果雷公藤甲素自微乳组与雷公藤甲素原料药组相比,给药后裸鼠血清AST和ALT极显著下降(P<0.01);总蛋白显著升高(P<0.05),白、球蛋白比值极显著升高(P<0.01);血肌酐有下降趋势,但无统计学意义;尿素显著下降(P<0.05);尿酸极显著下降(P<0.01)。雷公藤甲素自微乳组肝细胞轻微肿胀,少见炎细胞灶状浸润;雷公藤甲素原料药组肝组织出现脂肪变形,肝细胞细胞核增大,碎片状坏死,中重度纤维化。2组动物的肾脏组织均无明显病理特征。结论雷公藤甲素自微乳的肝肾毒性明显小于雷公藤甲素原料药。 展开更多
关键词 雷公藤甲素 自乳化给药系统 毒性
转铁蛋白-金纳米簇荧光分子探针小鼠体内急性毒性研究 预览
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作者 李建伟 王芳 +2 位作者 蔡芳震 黄思淮 孙建国 《牡丹江医学院学报》 2019年第1期9-12,共4页
目的评估转铁蛋白-金纳米簇荧光分子探针的体内急性毒性。方法以转铁蛋白为模板,氯金酸为原料,合成转铁蛋白-金纳米簇荧光分子探针。利用透射电镜和粒度分析仪测定所合成纳米粒子的形貌、水合粒径;利用紫外-可见光和荧光分光光度计检测... 目的评估转铁蛋白-金纳米簇荧光分子探针的体内急性毒性。方法以转铁蛋白为模板,氯金酸为原料,合成转铁蛋白-金纳米簇荧光分子探针。利用透射电镜和粒度分析仪测定所合成纳米粒子的形貌、水合粒径;利用紫外-可见光和荧光分光光度计检测其光学特性。经小鼠尾静脉注射转铁蛋白-金纳米簇溶液,分时取血检测血常规、生化指标和急性时相反应蛋白。结果本研究制备的金纳米簇粒径为(1.8±0.2)nm,转铁蛋白-金纳米簇水合粒径为(48.7±8.6)nm,在波长280nm的有特征性蛋白吸收峰,最大荧光发射峰位于波长700nm处。白细胞数、急性时相反应蛋白在给药后会一过性升高,但均可在短时间内恢复至正常水平。结论采用模板法制备转铁蛋白-金纳米簇分子探针,方法简单高效,所制备的分子探针具有毒性低,生物相容性好等优点。 展开更多
关键词 转铁蛋白 金纳米簇 合成方法 毒性试验 体内 小鼠
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Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210 预览
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作者 Xuelian Chen Lanying Ma +7 位作者 Xi Wang Hongnan Mo Dawei Wu Bo Lan Dong Qu Hongtu Zhang Jing Huang Binghe Xu 《癌症生物学与医学:英文版》 CAS CSCD 2019年第1期173-180,共8页
Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangio... Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces;84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events. 展开更多
关键词 REACTIVE capillary HEMANGIOMAS SHR-1210 skin TOXICITY ANTI-TUMOR efficacy
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Iron toxicity resistance strategies in tropical grasses:The role of apoplastic radicular barriers
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作者 Advanio Inácio Siqueira-Silva Camilla Oliveira Rios Eduardo Gusmao Pereira 《环境科学学报:英文版》 SCIE EI CAS CSCD 2019年第4期257-266,共10页
The revegetation of mined areas poses a great challenge to the iron ore mining industry.The initial recovery process in degraded areas might rely on the use of Fe-resistant grasses.Tropical grasses, such as Paspalum d... The revegetation of mined areas poses a great challenge to the iron ore mining industry.The initial recovery process in degraded areas might rely on the use of Fe-resistant grasses.Tropical grasses, such as Paspalum densum and Echinochloa crus-galli, show different resistance strategies to iron toxicity;however, these mechanisms are poorly understood.The Fe-resistance mechanisms and direct iron toxicity as a function of root apex removal were investigated. To achieve this purpose, both grass species were grown for up to 480 hr in a nutrient solution containing 0.019 or 7 mmol/L Fe-EDTA after the root apices had been removed or maintained. Cultivation in the presence of excess iron-induced leaf bronzing and the formation of iron plaque on the root surfaces of both grass species, but was more significant on those plants whose root apex had been removed. Iron accumulation was higher in the roots, but reached phytotoxic levels in the aerial parts as well. It did not hinder the biosynthesis of chloroplastidic pigments. No significant changes in gas exchange and chlorophyll a fluorescence occurred in either grass when their roots were kept intact;the contrary was true for plants with excised root apices. In both studied grasses, the root apoplastic barriers had an important function in the restriction of iron translocation from the root to the aerial plant parts, especially in E. crus-galli. Root apex removal negatively influenced the iron toxicity resistance mechanisms(tolerance in P. densum and avoidance in E. crus-galli). 展开更多
关键词 PASPALUM densum ECHINOCHLOA crus-galli Apoplastic BARRIER Iron TOXICITY
截短腐败梭菌α毒素的表达及其免疫原性评价
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作者 彭国瑞 彭小兵 +1 位作者 李旭妮 蒋玉文 《中国兽医科学》 CAS CSCD 北大核心 2019年第2期220-225,共6页
为了获得截短腐败梭菌α毒素并评价其毒性、反应原性和免疫原性,根据腐败梭菌α毒素的结构与功能,设计2对引物分别扩增含有穿孔活性区和受体结合区的α毒素基因csaN和csaC,克隆至pET-28a(+)质粒,构建截短α毒素表达载体,转化大肠杆菌BL2... 为了获得截短腐败梭菌α毒素并评价其毒性、反应原性和免疫原性,根据腐败梭菌α毒素的结构与功能,设计2对引物分别扩增含有穿孔活性区和受体结合区的α毒素基因csaN和csaC,克隆至pET-28a(+)质粒,构建截短α毒素表达载体,转化大肠杆菌BL21(DE3),诱导csaN和csaC表达,鉴定产物的反应原性和毒性,将经过诱导表达的工程菌灭活制成铝佐剂疫苗免疫家兔1次,通过血清中和试验和攻毒保护试验评价免疫效力,设立重组α全毒素rcsa免疫组作为阳性对照。结果显示,2个截短α毒素在大肠杆菌BL21(DE3)中均获得表达,产物能够与腐败梭菌抗毒素血清发生特异性反应,但失去了小鼠致死毒性。免疫家兔血清中和试验结果显示,csaN组血清的中和效价为1 MLD/0.1 mL,达到《中华人民共和国兽药典三部(2015年版)》效力检验的最低标准,csaC组为0,rcsa组为8 MLD/0.1 mL;csaN和csaC组家兔用1 MLD毒素攻击均未获得保护,而rcsa组家兔4/4获得保护。结果表明,截短α毒素与全毒素相比,失去了毒性但保留了反应原性,仅含穿孔活性结构区的截短部分具有较弱的免疫原性。 展开更多
关键词 腐败梭菌 截短α毒素 毒性 免疫原性
Lead?Free Halide Double Perovskite Materials:A New Superstar Toward Green and Stable Optoelectronic Applications
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作者 Liang Chu Waqar Ahmad +5 位作者 Wei Liu Jian Yang Rui Zhang Yan Sun Jianping Yang Xing’ao Li 《纳微快报:英文版》 CAS CSCD 2019年第1期264-281,共18页
Lead-based halide perovskites have emerged as excellent semiconductors for a broad range of optoelectronic applications,such as photovoltaics,lighting,lasing and photon detection.However,toxicity of lead and poor stab... Lead-based halide perovskites have emerged as excellent semiconductors for a broad range of optoelectronic applications,such as photovoltaics,lighting,lasing and photon detection.However,toxicity of lead and poor stability still represent significant challenges.Fortunately,halide double perovskite materials with formula of A2M(I)M(III)X6 or A2M(IV)X6 could be potentially regarded as stable and green alternatives for optoelectronic applications,where two divalent lead ions are substituted by combining one monovalent and one trivalent ions,or one tetravalent ion.Here,the article provides an up-to-date review on the developments of halide double perovskite materials and their related optoelectronic applications including photodetectors,X-ray detectors,photocatalyst,light-emitting diodes and solar cells.The synthesized halide double perovskite materials exhibit exceptional stability,and a few possess superior optoelectronic properties.However,the number of synthesized halide double perovskites is limited,and more limited materials have been developed for optoelectronic applications to date.In addition,the band structures and carrier transport properties of the materials are still not desired,and the films still manifest low quality for photovoltaic applications.Therefore,we propose that continuing efforts are needed to develop more halide double perovskites,modulate the properties and grow high-quality films,with the aim of opening the wild practical applications. 展开更多
关键词 HALIDE double PEROVSKITE OPTOELECTRONIC APPLICATIONS Efficiency Stability TOXICITY
为什么美国还没有全面禁用APEO 预览
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作者 陈荣圻 《印染助剂》 CAS 北大核心 2019年第3期59-64,共6页
APEO主要是NPEO和OPEO,由于NPEO的急性毒性LD50仅1 600 mg/kg为低毒性,对鱼类LC50为4 mg/L,特别是NPEO9的最初生物降解率只有4%~80%,而且其降解代谢物NPEO1~2和NPEC1~2更毒,因而20世纪80年代欧洲多国限用APEO,21世纪初更有欧盟在纺织品... APEO主要是NPEO和OPEO,由于NPEO的急性毒性LD50仅1 600 mg/kg为低毒性,对鱼类LC50为4 mg/L,特别是NPEO9的最初生物降解率只有4%~80%,而且其降解代谢物NPEO1~2和NPEC1~2更毒,因而20世纪80年代欧洲多国限用APEO,21世纪初更有欧盟在纺织品和印染废水中加以限制和禁用。至今发达国家中仅美国尚无全面禁用APEO的法规。原因是欧洲在实验室内测得的生物降解率与美国从河流中取样测得的数据大相径庭。从生物降解基本原理分析欧盟测得的数据论据不足;而且在纺织品上尚无国际公认的标准测试方法。两种状况是美国至今无APEO禁令之原因。 展开更多
关键词 APEO 生物降解 毒性 测试方法
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三种不同氧化工艺条件下对乙酰氨基酚的降解过程与产物毒性变化研究
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作者 冯天宇 黄艳 +3 位作者 潘旸 金晶 周庆 李爱民 《环境化学》 CAS CSCD 北大核心 2019年第1期23-33,共11页
作为一种典型的药物,对乙酰氨基酚(acetaminophen,ACE)由于其广泛存在和潜在毒性引起重要关注.本研究比较了氯化、紫外/过氧化氢(UV/H2O2)和紫外/氯(UV/Cl)三种工艺对ACE的降解情况.结果表明,3种工艺中,UV/Cl和UV/H2O2工艺均能完全降解A... 作为一种典型的药物,对乙酰氨基酚(acetaminophen,ACE)由于其广泛存在和潜在毒性引起重要关注.本研究比较了氯化、紫外/过氧化氢(UV/H2O2)和紫外/氯(UV/Cl)三种工艺对ACE的降解情况.结果表明,3种工艺中,UV/Cl和UV/H2O2工艺均能完全降解ACE,其中UV/Cl工艺的降解速率更快. UV/H2O2和UV/Cl工艺降解能用准一级动力学模型很好地拟合,它们的反应动力学常数(kobs,ACE)分别为0.1343 min-1和0.0657 min-1(293K,p H=7).通过p H实验发现,酸性条件下UV/Cl工艺效果更好,而p H对UV/H2O2工艺没有显著影响.相比而言,ACE的矿化比降解困难许多,在60 min后其矿化率最高仅为5.60%(UV/Cl工艺).在UV/Cl工艺降解过程中,检测到12种主要的转化产物,其转化途径主要包括羟基化、氯取代、二聚化、脱酰化和氧化反应.通过发光菌实验对溶液毒性进行分析,3种工艺条件下ACE溶液的毒性都会有所升高,其中氯化工艺最为突出.每种工艺中不同的反应活性物质导致了ACE转化产物的不同,最终使得溶液毒性不同程度地升高. 展开更多
关键词 对乙酰氨基酚 氧化工艺 降解动力学 水处理 毒性
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