Ciguatera Poisoning

Ciguatera 中毒
  • 文章类型: Journal Article
    海鲜中毒在全球范围内很常见,但临床医生和公众对此并不了解,可能与其他原因混淆。本文讨论了两种常见的海鲜中毒病例-雪卡菌和scombuid中毒-并提供了建议的护理注意事项。
    UNASSIGNED: Seafood poisoning is common worldwide but is relatively unknown by clinicians and the general public and can be confused with other causes. This article discusses two common seafood poisoning cases-ciguatera and scombroid poisoning-and offers recommended nursing considerations.
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  • 文章类型: English Abstract
    Ciguatera中毒(CP)是全球最常见的海鲜中毒之一。CP结果来自鱼肉的消耗,这些鱼肉积累了主要的毒素,称为雪茄毒素(CTX),它主要发生在热带和亚热带地区。在日本,据报道,CP事件主要来自亚热带地区的冲绳和Amami群岛。同时,内地也有零星的报道。由于鱼肉中的CTX含量极低,需要通过LC-MS/MS的高灵敏度检测方法。但目前报道的检测方法仅适用于特定设备,许多实验室难以应对CP。在这项研究中,为全国CP的风险做准备,我们研究了一种基于LC-MS/MS的CTXs通用分析方法。使用补充有氢氧化锂和甲酸的水/乙腈流动相产生稳定的[MLi]离子的突出峰。由于[M+Li]+离子即使在高碰撞能量下也不产生有效的产物离子,将每个类似物的[M+Li]+离子设定为前体离子和产物离子([M+Li]+>[M+Li]+),并在多反应监测(MRM)模式下监测。通过上述方法,对9种CTX同源物进行了分析。检测限(LOD,S/N>5)和定量(LOQ,S/N>10)估计为0.005-0.030ng/mL和0.010-0.061ng/mL,分别。当从5克鱼组织中制备1毫升提取液时,LOD和LOQ将为0.001-0.006μg/kg和0.002-0.012μg/kg,分别。该结果表明,我们可以在鱼肉中检测到所需的0.175μg/kgCTX1B当量水平,建议在日本安全食用。该方法被认为是不依赖于特定设备的通用分析方法。因此,它可能有助于改善全国实验室的CP调查。
    Ciguatera poisoning (CP) is one of the most frequent seafood poisonings across the globe. CP results from the consumption of fish flesh that has accumulated principal toxins known as ciguatoxins (CTXs), and it mainly occurs in tropical and subtropical regions. In Japan, incidents of CP have been reported primarily from Okinawa and Amami Islands in the subtropical area. Meanwhile, there have also been reports from Mainland sporadically. Since the amount of CTXs contained in fish flesh is extremely low, a highly sensitive detection method by LC-MS/MS is required. But the currently reported detection method is applicable only to specific equipment, and many laboratories have difficulty to respond CP. In this study, to prepare for the risk of nationwide CP, we researched a universal analytical method for CTXs based on LC-MS/MS. Using a water/acetonitrile mobile phase supplemented with lithium hydroxide and formic acid gave rise to prominent peaks of the stable [M+Li]+ions. As the [M+Li]+ions did not produce valid product ions even with high collision energy, the [M+Li]+ions of each analog were set for both precursor and product ions ([M+Li]+>[M+Li]+) and monitored under the multiple reaction monitoring (MRM) mode. With the method described above, analyses of nine CTX congeners were carried out. The limit of detection (LOD, S/N>5) and quantitation (LOQ, S/N>10) were estimated as 0.005-0.030 ng/mL and 0.010-0.061 ng/mL, respectively. When the 1 mL of extract solution is prepared from 5 g of the fish tissue, the LOD and LOQ will be at 0.001-0.006 μg/kg and 0.002-0.012 μg/kg, respectively. This result indicates that we could detect the required level of 0.175 μg/kg CTX1B equivalent in fish flesh which is recommended for safe consumption in Japan. This method is considered to be a universal analytical method without depending on the specific equipment. Thus it could contribute to improving the CP investigations in nationwide laboratories.
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  • 文章类型: Journal Article
    Ciguateric综合征是与食用某些鱼类有关的食物中毒,这些鱼类在其组织中积累了雪茄毒素(CTX)。该综合征的影响与神经失衡一起发生,这已经描述了很长一段时间,并在几个世纪的航海文学中被提及。在过去的十年里,研究一直集中在毒素鉴定的分析方法的实施和CTXs的作用模式的研究,以设计有效的治疗。然而,一个重要的方面是确定CTX在受影响个体的器官中造成的损害。在这项工作中,在小鼠组织中观察到的损伤,主要在小肠,进行了分析。以低于中位致死剂量(LD50)10倍的浓度饲喂受CTX污染的鱼肌肉,持续10周。对来自口腔治疗的组织的分析导致Paneth细胞的发生率增加,存在浸润粘膜的淋巴组织和小肠粘膜层中的纤维性病变。观察到用毒性肌肉喂养的动物的体重下降。
    Ciguateric syndrome is a food poisoning associated with the consumption of some species of fish that have accumulated ciguatoxins (CTXs) in their tissues. The effects of the syndrome occur with nervous imbalances which have been described for quite some time, and mentioned in sailing literature for centuries. In the last decade, research has been focused on the implementation of analytical methods for toxin identification and the study of action modes of CTXs to design effective treatments. However, an important aspect is to determine the damage that CTXs caused in the organs of affected individuals. In this work, the damages observed in tissues of mice, mainly in the small intestine, were analyzed. The animals were fed with CTX-contaminated fish muscle at concentrations 10-times below the median lethal dose (LD50) for 10 weeks. The analysis of tissues derived from the oral treatment resulted in an increased occurrence of Paneth cells, presence of lymphoid tissue infiltrating the mucosa and fibrous lesions in the mucosal layer of the small intestine. A decreasing weight in animals fed with toxic muscle was observed.
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  • 文章类型: Systematic Review
    雪卡中毒患者通常表现为胃肠道和神经系统症状,但其心脏毒性在很大程度上尚未被认识。本系统综述首次总结了有关雪茄中毒引起的心脏毒性的临床特征的证据,为临床医生提供了疾病脚本和相关知识。在系统评价和荟萃分析声明的首选报告项目之后,我们在MEDLINE和EMBASE中搜索了所有同行评审文章,这些文章使用的关键词包括"ciguatera"和"心脏毒性",从文章开始到2024年1月.我们收录了20篇文章,包括148例,在这个系统的审查。在包括的案件中,中位年龄为54岁,男性占优势(62.2%).根据世界卫生组织的指定,68.5%来自西太平洋区域。常见症状包括低血压(75.0%)和心动过缓(67.6%),胸痛或晕厥较不常见(2.7%和1.4%,分别)。窦性心动过缓是最常见的心电图异常(35.9%),其次是房室传导阻滞(15.4%)。阿托品等对症治疗,多巴胺,肾上腺素是常用的,只有4.1%需要入住重症监护室。由于雪卡病毒的心脏毒性,没有过期。这篇综述总结了当前的证据和卡卡菌心脏毒性的特征。尽管目前尚未认识到ciguatera的心脏毒性,提高临床医师对病情的认识是至关重要的,因为只要早期发现和干预,患者的临床结局可能是良性的.
    Patients with ciguatera poisoning commonly present with gastrointestinal and neurologic symptoms, but its cardiotoxicity has been largely unrecognized. This systematic review is the first to summarize the evidence regarding clinical characteristics of cardiotoxicity from ciguatera poisoning to provide the illness script and pertinent knowledge for clinicians. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including \"ciguatera\" and \"cardiotoxicity\" from their inception to January 2024. We included 20 articles, including 148 cases, in this systematic review. Among the included cases, the median age was 54 years with male predominance (62.2%). Based on the WHO designation, 68.5% were reported from the Western Pacific Region. Common symptoms included hypotension (75.0%) and bradycardia (67.6%), and chest pain or syncope were less commonly reported (2.7% and 1.4%, respectively). Sinus bradycardia was the most common electrocardiogram abnormality (35.9%), followed by atrioventricular blocks (15.4%). Symptomatic treatments such as atropine, dopamine, and epinephrine were commonly used, and only 4.1% required intensive care unit admission. None expired due to cardiotoxicity from ciguatera. This review summarizes the current evidence and the characteristics of cardiotoxicity from ciguatera. Although ciguatera cardiotoxicity is currently underrecognized, increased awareness of the condition in clinicians is crucial because the clinical outcomes of the patients could be benign as long as it is identified and intervened early.
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  • 文章类型: Journal Article
    Ciguatera中毒(CP),由雪卡毒素(CTX)引起,是最常见的食源性疾病之一,每年影响超过5万人。在大多数情况下,CP通过对症和支持性治疗来管理,并且没有设计出具体的治疗方法。在这项研究中,为了开发CP的治疗性抗体,我们检查了人源化小鼠抗CTX3C抗体10C9(m10C9),在体外和体内均表现出对雪茄毒素的中和活性。将互补决定区移植到与m10C9具有高序列同一性的人种系序列上,并检查回复突变以维持结合亲和力。优化的人源化抗体,选择。h10C9Fab,显示与CTX3C的强结合亲和力,高亲和力(KD=19.0nM),并且框架区中ArgL46和CysH94的仅两个回复突变参与确定抗原结合亲和力。
    Ciguatera poisoning (CP), caused by ciguatoxins (CTXs), is one of the most common food-borne diseases, affecting more than 50,000 people each year. In most cases, CP are managed with symptomatic and supportive remedies, and no specific treatment has been devised. In this study, toward the development of therapeutic antibodies for CP, we examined to humanize mouse anti-CTX3C antibody 10C9 (m10C9), which exhibited neutralizing activity against ciguatoxin in vitro and in vivo. The complementarity determining regions were grafted onto a human germline sequence with high sequence identity to m10C9, and the backmutations were examined to maintain the binding affinity. The optimized humanized antibody, Opt.h10C9Fab, showed a strong binding affinity to CTX3C with a high affinity (KD = 19.0 nM), and only two backmutations of ArgL46 and CysH94 in the framework regions were involved in determining the antigen binding affinity.
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  • 文章类型: Journal Article
    Ciguatera中毒(CP)是一种与食用被海洋环境中发现的有效天然毒素污染的鱼类有关的疾病,通常称为雪茄毒素(CTX)。由于这些天然毒素的广泛扩展,CP的风险表征已成为全世界关注的问题。CTX的鉴定受到缺乏市售参考材料的阻碍。这种局限性阻碍了在开发分析工具和进行毒理学研究方面的进展,这些研究对于建立控制的监管水平至关重要。这项研究的重点是描述加那利群岛(西班牙)最近发生的CP病例的一名警察的CTX特征,位于大西洋东海岸。毛细管液相色谱与高分辨率质谱联用(cLC-HRMS)提供了卓越的灵敏度,这是加那利群岛第一次被污染的鱼类,最近在加勒比海的G.silvae和G.caribeaus中发现了藻类毒素的痕迹。该藻毒素的结构特征在于cLC-HRMS最初被鉴定为C-CTX5。CTXs的总毒素浓度比美国食品和药物管理局提出的指导水平(0.1ngC-CTX1/g鱼组织)高八倍,以C-CTX1和17-羟基-C-CTX1为主要CTX。
    Ciguatera Poisoning (CP) is an illness associated with the consumption of fish contaminated with potent natural toxins found in the marine environment, commonly known as ciguatoxins (CTXs). The risk characterization of CP has become a worldwide concern due to the widespread expansion of these natural toxins. The identification of CTXs is hindered by the lack of commercially available reference materials. This limitation impedes progress in developing analytical tools and conducting toxicological studies essential for establishing regulatory levels for control. This study focuses on characterizing the CTX profile of an amberjack responsible for a recent CP case in the Canary Islands (Spain), located on the east Atlantic coast. The exceptional sensitivity offered by Capillary Liquid Chromatography coupled with High-Resolution Mass Spectrometry (cLC-HRMS) enabled the detection, for the first time in fish contaminated in the Canary Islands, of traces of an algal ciguatoxin recently identified in G. silvae and G. caribeaus from the Caribbean Sea. This algal toxin was structurally characterized by cLC-HRMS being initially identified as C-CTX5. The total toxin concentration of CTXs was eight times higher than the guidance level proposed by the Food and Drug Administration (0.1 ng C-CTX1/g fish tissue), with C-CTX1 and 17-hydroxy-C-CTX1 as major CTXs.
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  • 文章类型: Journal Article
    Ciguatera中毒(CP)是全球范围内最常见的海洋生物毒素食物中毒,它是由雪茄毒素(CTX)引起的,鞭毛藻Gambierdiscus和Fukuyoaspp产生的热稳定聚醚毒素。它通常是由食物链上的大型鱼类的消耗引起的,这些鱼类在其肉中积累了CTX。在天然样品中发现了痕量的CTX,它们主要在浓度低至0.2µg/kg的消费者中引起神经毒性作用。根据毒理学数据,美国食品和药物管理局已确定CTX1B的最高允许水平为0.01µg/kg,C-CTX1的最高允许水平为0.1µg/kg。已经鉴定了CTX1B和CTX3C系列的20多种变体,最近需要同时检测痕量的CTX类似物。先前发表的使用LC-MS/MS的作品通过监测CTX的钠加合离子([M+Na]+>[M+Na]+)实现了安全水平。在这项研究中,我们优化了使用钠或锂加合物检测CTX的高灵敏度方法,[M+Na]+或[M+Li]+,通过向流动相中加入碱金属如Na+或Li+。这项工作表明,可以在FDA推荐的低浓度下成功检测到CTX,并使用LC-MS/MS进行良好的色谱分离。它还报告了使用[M+Li]+的方法的新分析条件和准确性。
    Ciguatera poisoning (CP) is the most common type of marine biotoxin food poisoning worldwide, and it is caused by ciguatoxins (CTXs), thermostable polyether toxins produced by dinoflagellate Gambierdiscus and Fukuyoa spp. It is typically caused by the consumption of large fish high on the food chain that have accumulated CTXs in their flesh. CTXs in trace amounts are found in natural samples, and they mainly induce neurotoxic effects in consumers at concentrations as low as 0.2 µg/kg. The U.S. Food and Drug Administration has established CTX maximum permitted levels of 0.01 µg/kg for CTX1B and 0.1 µg/kg for C-CTX1 based on toxicological data. More than 20 variants of the CTX1B and CTX3C series have been identified, and the simultaneous detection of trace amounts of CTX analogs has recently been required. Previously published works using LC-MS/MS achieved the safety levels by monitoring the sodium adduct ions of CTXs ([M+Na]+ > [M+Na]+). In this study, we optimized a highly sensitive method for the detection of CTXs using the sodium or lithium adducts, [M+Na]+ or [M+Li]+, by adding alkali metals such as Na+ or Li+ to the mobile phase. This work demonstrates that CTXs can be successfully detected at the low concentrations recommended by the FDA with good chromatographic separation using LC-MS/MS. It also reports on the method\'s new analytical conditions and accuracy using [M+Li]+.
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  • 文章类型: Journal Article
    Ciguatoxins(CTXs)是负责雪卡中毒(CP)的神经毒素,每年影响全球超过50,000人。预防CP的分析方法的发展是一个紧迫的全球问题,N2a测定法是检测CTX最有前途的方法之一。CTX是剧毒的,并且已经提出了在鱼中0.01μgCTX1B当量(eq)/kg的作用水平。期望进一步提高N2a测定中CTX的检测灵敏度以可靠地检测这样的低浓度。电压门控钠通道(NaV通道)的开放和电压门控钾通道(KV通道)的阻断被认为与CTX的毒性有关。因此,在这项研究中,我们开发了一种检测CTX的方法,其灵敏度高于传统的N2a检测方法,使用KV通道抑制剂作为N2a细胞的致敏试剂。向N2a细胞中添加KV通道抑制剂4-氨基吡啶和四乙基氯化铵,除了传统的致敏试剂哇巴因和维拉替丁,将N2a细胞对CTX的敏感性提高约4倍。这也是第一项在基于细胞的测定中证明KV通道对CTX毒性的影响的研究。
    Ciguatoxins (CTXs) are neurotoxins responsible for ciguatera poisoning (CP), which affects more than 50,000 people worldwide annually. The development of analytical methods to prevent CP is a pressing global issue, and the N2a assay is one of the most promising methods for detecting CTXs. CTXs are highly toxic, and an action level of 0.01 μg CTX1B equivalent (eq)/kg in fish has been proposed. It is desirable to further increase the detection sensitivity of CTXs in the N2a assay to detect such low concentrations reliably. The opening of voltage-gated sodium channels (NaV channels) and blocking of voltage-gated potassium channels (KV channels) are thought to be involved in the toxicity of CTXs. Therefore, in this study, we developed an assay that could detect CTXs with higher sensitivity than conventional N2a assays, using KV channel inhibitors as sensitizing reagents for N2a cells. The addition of the KV channel inhibitors 4-aminopyridine and tetraethylammonium chloride to N2a cells, in addition to the traditional sensitizing reagents ouabain and veratridine, increased the sensitivity of N2a cells to CTXs by up to approximately 4-fold. This is also the first study to demonstrate the influence of KV channels on the toxicity of CTXs in a cell-based assay.
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  • 文章类型: Journal Article
    Gambierdiscus属产生一系列生物活性亲水性和亲脂性次生代谢产物,其作用方式和毒性范围。在这项研究中,代谢物指纹图谱绘制了13个甘比尔饼,通过评估56种具有特征的次生代谢产物的产生,有5种Coolia和2种Fukuyoa物种(34种分离株)。Gambierdiscuspolynesiensis是唯一产生太平洋雪卡毒素3B(P-CTX3B)的物种,P-CTX3C,iso-P-CTX3B/C,P-CTX4A,P-CTX4B和iso-P-CTX4A/B.australes产生maitotoxin-1(MTX-1)和MTX-5,螯合链球菌产生MTX-6和G.honu产生MTX-7。在所有Gambierdiscus分离物中观察到普遍产生44-甲基冈比亚酮,有九个物种也生产冈比亚龙。额外的冈比亚龙类似物,包括脱水冈比亚酮(本文暂定),在所有冈比亚铁饼物种中也被检测到,两种Coolia和两种Fukuyoa。在G.lewisii和G.pacificus中检测到Gambieroxide,在10种Gambierdiscus中检测到gambierdic酸A,G.australes(CAWD381)是唯一产生冈比亚酸A-D的分离株。这项研究表明,迄今为止测试的分离株产生已知的CTX或MTX,但不是两者都有,并强调了几种产生“未知”化合物的物种,这些化合物具有环状聚醚的特征,这将是未来化合物发现工作的重点。
    The genus Gambierdiscus produces an array of bioactive hydrophilic and lipophilic secondary metabolites that range in mode of action and toxicity. In this study, the metabolite fingerprint was mapped for thirteen Gambierdiscus, five Coolia and two Fukuyoa species (34 isolates) by assessing the production of 56 characterised secondary metabolites. Gambierdiscus polynesiensis was the only species to produce Pacific-ciguatoxin-3B (P-CTX3B), P-CTX3C, iso-P-CTX3B/C, P-CTX4A, P-CTX4B and iso-P-CTX4A/B. G. australes produced maitotoxin-1 (MTX-1) and MTX-5, G. cheloniae produced MTX-6 and G. honu produced MTX-7. Ubiquitous production of 44-methylgambierone was observed amongst all the Gambierdiscus isolates, with nine species also producing gambierone. Additional gambierone analogues, including anhydrogambierone (tentatively described herein), were also detected in all Gambierdiscus species, two Coolia and two Fukuyoa species. Gambieroxide was detected in G. lewisii and G. pacificus and gambieric acid A was detected in ten Gambierdiscus species, with G. australes (CAWD381) being the only isolate to produce gambieric acids A-D. This study has demonstrated that the isolates tested to date produce the known CTXs or MTXs, but not both, and highlighted several species that produced \'unknown\' compounds displaying characteristics of cyclic polyethers, which will be the focus of future compound discovery efforts.
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  • 文章类型: Journal Article
    Ciguatoxins(CTXs)是引起Ciguatera鱼类中毒(CFP)的主要毒素,是以其特征性的多环醚结构而著称的重要化合物。在以前的报告中,我们通过在使用LC-MS的雪卡毒素-3C(CTX3C)的质谱(MS)/MS光谱中假设三个电荷位点,鉴定了通过均裂片段产生的产物离子的结构。本研究旨在阐明雪卡毒素-3C同源物的均裂片段。我们在天然存在的雪卡毒素-3C同源物的MS/MS光谱中分配了产物离子的详细结构,51-羟基环瓜毒素-3C(51-羟基CTX3C),使用具有大气压化学电离(APCI)源的液相色谱/四极杆飞行时间质谱。在C51上引入羟基取代基可诱导不同的片段化途径,包括涉及消除51-OH和形成烯醇醚的M环的新型裂解机制。因此,新的裂解模式在m/z979(C55H79O15)产生产物离子,439(C24H39O7),149(C10H13O),135(C9H11O),和115(C6H11O2)。此外,在m/z509(C28H45O8)处观察到特征产物离子,491(C28H43O7),481(C26H41O8),463(C26H39O7),439(C24H39O7),421(C24H37O6),171(C9H15O3),153(C9H13O2),141(C8H13O2),和123(C8H11O)。
    Ciguatoxins (CTXs) stand as the primary toxins causing ciguatera fish poisoning (CFP) and are essential compounds distinguished by their characteristic polycyclic ether structure. In a previous report, we identified the structures of product ions generated via homolytic fragmentation by assuming three charge sites in the mass spectrometry (MS)/MS spectrum of ciguatoxin-3C (CTX3C) using LC-MS. This study aims to elucidate the homolytic fragmentation of a ciguatoxin-3C congener. We assigned detailed structures of the product ions in the MS/MS spectrum of a naturally occurring ciguatoxin-3C congener, 51-hydroxyciguatoxin-3C (51-hydoxyCTX3C), employing liquid chromatography/quadrupole time-of-flight mass spectrometry with an atmospheric pressure chemical ionization (APCI) source. The introduction of a hydroxy substituent on C51 induced different fragmentation pathways, including a novel cleavage mechanism of the M ring involving the elimination of 51-OH and the formation of enol ether. Consequently, new cleavage patterns generated product ions at m/z 979 (C55H79O15), 439 (C24H39O7), 149 (C10H13O), 135 (C9H11O), and 115 (C6H11O2). Additionally, characteristic product ions were observed at m/z 509 (C28H45O8), 491 (C28H43O7), 481 (C26H41O8), 463 (C26H39O7), 439 (C24H39O7), 421 (C24H37O6), 171 (C9H15O3), 153 (C9H13O2), 141 (C8H13O2), and 123 (C8H11O).
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