菊叶三七致肝小静脉闭塞1例报告及文献复习

目的 了解菊叶三七导致肝小静脉闭塞病的临床特征,以加强对该病的认识。方法 回顾分析1例因服用菊叶三七致肝小静脉闭塞病的临床及影像学表现,并进行文献复习。结果 该患者临床表现主要为腹水、右上腹胀痛、肝脏增大,并伴不同程度肝功能异常。腹部增强CT扫描:肝内弥漫性低密度影,与正常密度肝实质相间,伴大小不等片状异常强化,下腔静脉内径缩窄,肝静脉轮廓模糊。发病前1个月服用菊叶三七病史。结合患者症状、体征以及腹部CT,可诊断为肝小静脉闭塞病。停用菊叶三七并给予抗凝、改善循环等治疗后病情逐渐缓解。结论 长期大量服用菊叶三七可致肝小静脉闭塞病。腹部增强CT扫描典型特征基本可对肝小静脉闭塞病行临床诊断。抗凝、改善循环治疗有一定疗效。     

菊三七致肝损伤及其毒性机制的研究进展

目的:为深入研究菊三七的毒性机制提供参考。方法:以"菊三七""毒性机制""肝损伤""肝窦阻塞综合征""Gynura segetum""Toxicity mechanism""Liver damage""HSOS"等为关键词,在中国知网、万方数据、PubMed等数据库中组合查询2000年1月-2019年1月发表的中英文相关文献,对菊三七致肝损伤及其毒性机制研究进展进行综述。结果与结论:共检索到文献70 922篇,最终纳入有效文献42篇。菊三七致病的靶器官为肝脏,而菊三七诱发肝功能衰竭的毒性机制尚不明确,目前较多研究者普遍认为菊三七致肝损伤是与其所含的吡咯里西啶类生物碱(PAs)经肝代谢后生成的毒性成分有关系。不饱和型PAs、PAs毒性代谢物及细胞色素P450酶3A在菊三七诱发肝毒性的发生和发展中起重要作用。细胞分子学水平的研究表明,不饱和型PAs可使细胞器受损、内皮细胞损伤、细胞凋亡等,进而产生较强的肝细胞毒性;且PAs诱导的肝损伤与谷胱甘肽的减少和细胞外基质降解也有密切关系。代谢组学的相关研究则从机体的整体角度出发证明了胆汁酸和氨基酸等代谢异常亦可能与其肝毒性有关。但目前对于菊三七致肝损伤的研究多集中于从毒性代谢物和细胞分子毒性的角度来研究,大多仅通过对某一两个毒性成分从某个单一角度采用多种分析方法进行中药毒性及其机制的探究,而对于菊三七致肝损伤的系统性和整体性研究较少。因此,今后研究者可应用系统生物学和生物信息科学,采用系统的、综合的研究思路和手段从整体水平上动态的对一个体系加以阐述探究。     

土三七致肝小静脉闭塞病1例报告及文献复习

【】 目的 了解土三七导致肝小静脉闭塞病的临床特征,以加强对该病的认识。方法 回顾分析1例因服用土三七致肝小静脉闭塞病的临床及影像学表现,并进行文献复习。结果 该患者临床表现主要为腹水、右上腹胀痛、肝脏增大,并伴不同程度肝功能异常。腹部增强CT扫描：肝实质内不均匀强化,呈高低密度相间的斑片状,腔静脉肝段变扁,肝静脉显示不清。发病前1个月服用土三七病史。结合患者症状、体征以及腹部CT,可诊断为肝小静脉闭塞病。停用土三七并给予抗凝、改善循环等治疗后病情逐渐缓解。结论 长期大量服用土三七可致肝小静脉闭塞病。腹部增强CT扫描典型特征基本可对肝小静脉闭塞病行临床诊断。抗凝、改善循环治疗有一定疗效。     

植物土三七致肝小静脉闭塞病1例的中西医结合治疗

肝小静脉闭塞病(hepatic veno-occlusive disease,HVOD)是一种罕见病,国内文献报道,其常见致病因素为植物土三七。由于发病机制复杂、缺乏特效治疗药物,HVOD的误诊、漏诊率高,预后差。笔者对中西医结合治疗土三七所致肝小静脉闭塞病的病例进行了报道,并通过回顾性分析和文献复习,总结治疗经验,为临床诊治HVOD提供参考。     

野百合碱致肺动脉高压相关机制研究进展

吡咯里西啶类生物碱(pyrrolizidine alkaloids,PAs)分布十分广泛,3%的有花植物中含有PAs,其中含量较多的为紫草科、菊科、豆科及兰科植物[1]。含PAs的中药应用广泛,如中国药典2005年版一部即收录了佩兰(菊科)、紫草(紫草科)、款冬花(菊科)等多种含有该类生物碱的植物。野百合碱(monocrotaline,MCT)是来自于豆科猪屎豆     

土三七致肝小静脉闭塞病2例

肝小静脉闭塞病（HVOD）是指肝小叶中央静脉和小叶下静脉损伤导致管腔狭窄或闭塞而产生的肝内窦后性门静脉高压。近年来,我院诊治2例服用土三七后发生的HVOD。现回顾分析其临床资料,以了解土三七致肝小静脉闭塞病的临床特点,提高对该病的认识,报道如下：     

利托那韦对菊三七致大鼠肝毒性的保护作用

大量体外研究表明,吡咯里西啶生物碱(pyrrolizidine alkaloids, PAs)肝毒性与细胞色素酶P450 (cytochrome P450, CYP) 3A4密切相关,但尚未在整体水平得到证实。因此,本研究利用大鼠探讨CYP3A4化学抑制剂利托那韦对菊三七致肝损伤的影响。实验方案经上海中医药大学实验动物福利与伦理委员会审查,符合实验动物福利与伦理相关规范。大鼠单次灌胃菊三七提取物(8 g·kg^-1)造成肝损伤模型,并设利托那韦(30 mg·kg^-1)干预组、溶剂对照组和利托那韦对照组。结果表明,利托那韦对菊三七致大鼠肝损伤有明显的保护作用:利托那韦可明显降低肝损伤大鼠血清转氨酶活性及总胆汁酸水平,肝窦淤血、肝组织坏死等病理状态均有所缓解。进一步测定菊三七提取物给药后10 min～24 h内PAs致肝毒性生物标识物吡咯-蛋白结合物含量及主要胆汁酸的含量,发现利托那韦可明显降低血清吡咯-蛋白结合物含量,修复胆汁酸代谢紊乱。本研究表明,利托那韦可明显改善菊三七致大鼠肝损伤的情况,与抑制PAs代谢活化及调节胆汁酸代谢密切相关。研究结果...     

猜屎豆属和千里光属植物提取物与环磷酰胺对实验性肿瘤的协同作用

从猪屎豆属的响铃豆(Crotalaria albida)和菽麻(C.juncea)以及千里光属的菊状千里光(SenecioChrysanthemoides)、密花千里光(S.densiflorus)、雅古山千里光(S.jacquemontianus)和红脉千里光(S.ru finervis)6种植物中以石油醚和甲醇连续提取得到6种相应提取物。实验结果表明,这6种提取物与环磷酰胺(CTX)联合应用均可增强CTX 的抗癌作用,延长实验性腹水癌S 180小鼠存活期。菊状千里光、密花千里光和雅古山千里光植物甲醇提取物的增效作用近     

菊叶三七致肝小静脉闭塞病35例临床分析

目的 分析菊叶三七(土三七)导致肝小静脉闭塞病(HVOD)的临床特点、诊治方法和预后。方法 回顾性分析35例因服用土三七所致肝小静脉阻塞病的临床资料。结果 HVOD临床表现为腹水(91%)、腹胀(86%)、纳差(71%)、乏力(71%)、肝肿大(66%)等。彩超可见肝大、腹水、肝内“豹纹状”、“斑片状”低回声区等,增强CT可见特征性“地图状”不均匀强化影。出院后随访1周至3年,失访3例,死亡13例,治愈/好转19例;死亡组病人白细胞计数、凝血酶原时间、血肌酐、尿素氮水平较治愈/好转组病人相对较高(P＜0.05)。结论 HVOD病程相对较短,诊治困难,预后较差。     

五味子醇甲对千里光碱致小鼠肝损伤的改善作用

菊三七含千里光碱(senecionine, SEN)等大量吡咯里西啶生物碱(pyrrolizidine alkaloids, PAs),其所导致的肝毒性问题成为最受关注的中药药源性肝损伤之一,但尚无有效的临床治疗药物。本课题组前期研究表明CYP3A4抑制剂利托那韦可有效抑制SEN代谢活化并降低其肝毒性。保肝中药五味子含大量木脂素类活性成分,可通过影响药物代谢酶改善药源性肝损伤。因此,本研究探讨了五味子主要木脂素类化合物五味子醇甲(schisandrol A,SoA)对SEN致小鼠肝损伤的改善作用,并初步探讨其对千里光碱代谢的影响。所有动物实验经上海中医药大学实验动物伦理委员会审查(PZSHUTCM210604002),符合实验动物伦理相关规范。小鼠单次灌胃SEN (150μmol·kg^-1)造成肝损伤模型,并设SoA (116μmol·kg^-1)干预组、溶剂对照组和SoA对照组。结果表明, SoA可明显降低SEN致肝损伤小鼠血清转氨酶活性,缓解肝细胞坏死、肝窦淤血等病理状态。进一步测定小鼠血清中SEN代谢产物的含量,结合体外肝微粒体代谢研究,...     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.