马兜铃酸体内毒性的产生及防治研究进展

马兜铃酸广泛存在于马兜铃科马兜铃属中草药中,具有。肾毒性和致癌致突变性。其在体内经一系列硝基还原酶代谢活化后与DNA共价结合形成加合物而诱发癌变,并通过诱导肾小管上皮细胞凋亡及间质纤维化而导致马兜铃酸肾病。综述马兜铃酸体内毒性产生的分子机制和防治研究进展,探讨相关药物的研发,为马兜铃酸肾病的治疗提供新思路。     

马兜铃酸肾病研究的新进展

根据近年有关研究和报道对含马兜铃酸中药的毒性成分、马兜铃酸的代谢、马兜铃酸肾病的发病机制、临床特征及其诊断方法进行综述,旨在对马兜铃酸的毒理学及马兜铃酸肾病的诊治加深认识。     

马兜铃酸肾病的临床与机制研究进展

含马兜铃酸类成分中药导致的肾损害-马兜铃酸肾病近年受到国内外医药学界的广泛关注,本文根据10年来的临床与药学研究,从马兜铃酸肾病的临床特征、相关药物以及马兜铃酸的代谢过程、毒性作用及致病机制等方面进行了探讨,并提出了今后的研究方向。     

肾小管上皮细胞特异性转运马兜铃酸机制研究进展

因应用不当或饮食污染摄入马兜铃酸I所引起的、以进展性间质纤维化为特征的急慢性肾炎称为马兜铃酸肾病或巴尔干地方性肾病。马兜铃酸I特异性损伤近端小管,而对肾脏其他组织细胞未表现出明显的直接损伤作用。因此,近曲小管上皮细胞通过有机阴离子蛋白1和3特异性摄入马兜铃酸I,是马兜铃酸I发挥特异性肾毒性作用的关键。近年来对肾小管摄取马兜铃酸I的机制已明确,但参与其在肾小管上皮细胞顶膜侧转运的蛋白鲜有报道。通过综述马兜铃酸I在肾小管的消除机制,以期为预防和治疗马兜铃酸肾病提供新靶点。     

马兜铃酸的毒理学现状

目的:介绍马兜铃酸的毒理学研究进展方法:方法:参考国内外相关文献,进行综合、分析、归纳。结果:马兜铃酸具有肾毒性、消化道毒性、致癌性、致突变性和基因毒性。结论:要辨证合理使用含有马兜铃酸成分的中药材。     

马兜铃酸类物质的生物标记物与减毒策略研究进展

马兜铃酸类物质(aristolochic acids,AAs)广泛存在于马兜铃科植物,是马兜铃科中药的重要毒性成分.作为致癌数据库(CPDB)中最强的致癌物之一,AAs能够产生肝毒性、肾毒性、致癌和致突变等毒副作用,在体内能够产生AA-DNA加合物等一系列代谢物,其特异的代谢物可作为生物标志物,用于相关疾病的早期诊断与...     

中药马兜铃酸的研究进展

本文总结了马兜铃酸的化学结构、含马兜铃酸的中草药及中成药、马兜铃酸的药理作用和毒性作用、马兜铃酸肾病。通过本文的综述,使医药人员对马兜铃酸有一个全面、正确的认识,以指导临床安全、合理、规范使用含有马兜铃酸的中药。     

马兜铃属植物与其替代药材的对比分析

马兜铃属植物由于对肾脏的毒性而遭到否定,故寻求替代药材已经成为迫不及待的任务.本文从本草、功效、化学成分、机制等方面将常用马兜铃药用植物与《中国药典》规定的已有替代药材进行比较,探讨其可行性.同时对马兜铃酸肾病的病理表现做一简要的介绍.     

马兜铃酸毒理学性研究与启示

有关马兜铃酸的毒理实验国内外均有报道,尤其国外在毒理学方面做了大量研究.大量的实验提示:马兜铃酸的肾毒性与剂量呈相关性;遗传毒性研究提示马兜铃酸具有致突变作用;在对大鼠和小鼠的长期毒性研究中发现:动物可发生局部和全身肿瘤,且肿瘤的发生与给药时间和剂量呈相关性;并发现动物的主要毒性与人的不良反应有相关性.马兜铃酸的相关实验研究提醒有关方面应重视马兜铃酸问题,使传统中药更好地发挥防病治病作用.     

马兜铃酸肾病的临床病理分析

目的 探讨马兜铃酸肾病的临床病理特点。方法 回顾性分析3例马兜铃酸肾病患者的临床表现及病理资料。结果 2例急性马兜铃酸肾病临床表现为：消化道症状、肾功能减退、尿酶升高、电解质紊乱;病理诊断为急性肾小管坏死。1例慢性马兜铃酸肾病临床表现为：贫血、尿检异常、高血压、肾功能减退,病理诊断为慢性间质性肾炎。结论 含有马兜铃酸的中药有肾损害,可致马兜铃酸肾病,其临床表现病理变化有一定特点。     

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.