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Proteomic and toxicological analysis of the venom of Micrurus yatesi and its neutralization by an antivenom 野鼠毒液的蛋白质组学和毒理学分析及抗蛇毒血清的中和作用
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-03-01 DOI: 10.1016/j.toxcx.2022.100097
Gianni Mena , Stephanie Chaves-Araya , Johelen Chacón , Enikő Török , Ferenc Török , Fabián Bonilla , Mahmood Sasa , José María Gutiérrez , Bruno Lomonte , Julián Fernández

Coralsnakes belong to the family Elapidae and possess venoms which are lethal to humans and can be grouped based on the predominance of either three finger toxins (3FTxs) or phospholipases A2 (PLA2s). A proteomic and toxicological analysis of the venom of the coralsnake Micrurus yatesi was performed. This species, distributed in southeastern Costa Rica, was formerly considered a subspecies of M. alleni. Results showed that this venom is PLA2-rich, in contrast with the previously studied venom of Micrurus alleni. Toxicological evaluation of the venom, in accordance with proteomic data, revealed that it has a markedly higher in vitro PLA2 activity upon a synthetic substrate than M. alleni. The evaluation of in vivo myotoxicity in CD-1 mice using histological evaluation and plasma creatine kinase release also showed that M. yatesi venom caused muscle damage. A commercial equine antivenom prepared using the venom of Micrurus nigrocinctus displayed a similar recognition of the venoms of M. yatesi and M. nigrocinctus by enzyme immunoassay. This antivenom also immunorecognized the main fractions of the venom of M. yatesi and was able to neutralize its lethal effect in a murine model.

珊瑚蛇属于蛇科,拥有对人类致命的毒液,可以根据三指毒素(3FTxs)或磷脂酶A2 (PLA2s)的优势进行分组。对珊瑚蛇的毒液进行了蛋白质组学和毒理学分析。该种分布在哥斯达黎加东南部,以前被认为是M. alleni的一个亚种。结果表明,该毒液中含有丰富的pla2,与之前研究的Micrurus alleni毒液不同。根据蛋白质组学数据,该毒液的毒理学评估显示,它在合成底物上具有明显高于M. alleni的体外PLA2活性。用组织学评价和血浆肌酸激酶释放对CD-1小鼠的体内肌毒性评价也表明,斑胸草毒引起肌肉损伤。一种用黑尾马蛇毒制备的商业马抗蛇毒血清通过酶免疫测定显示出对雅氏马和黑尾马毒液相似的识别能力。该抗蛇毒血清也免疫识别的主要部分的叶氏分枝杆菌毒液,并能够中和其致命作用的小鼠模型。
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引用次数: 6
A review of chemical defense in harlequin toads (Bufonidae: Atelopus) 丑角蟾蜍(蟾科)化学防御研究进展
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-03-01 DOI: 10.1016/j.toxcx.2022.100092
Kannon C. Pearson, Rebecca D. Tarvin

Toads of the genus Atelopus are chemically defended by a unique combination of endogenously synthesized cardiotoxins (bufadienolides) and neurotoxins which may be sequestered (guanidinium alkaloids). Investigation into Atelopus small-molecule chemical defenses has been primarily concerned with identifying and characterizing various forms of these toxins while largely overlooking their ecological roles and evolutionary implications. In addition to describing the extent of knowledge about Atelopus toxin structures, pharmacology, and biological sources, we review the detection, identification, and quantification methods used in studies of Atelopus toxins to date and conclude that many known toxin profiles are unlikely to be comprehensive because of methodological and sampling limitations. Patterns in existing data suggest that both environmental (toxin availability) and genetic (capacity to synthesize or sequester toxins) factors influence toxin profiles. From an ecological and evolutionary perspective, we summarize the possible selective pressures acting on Atelopus toxicity and toxin profiles, including predation, intraspecies communication, disease, and reproductive status. Ultimately, we intend to provide a basis for future ecological, evolutionary, and biochemical research on Atelopus.

爪蟾属蟾蜍的化学防御是由内源性合成的心脏毒素(蟾二烯内酯)和可能被隔离的神经毒素(胍生物碱)的独特组合组成的。对爪蟾小分子化学防御的研究主要关注于识别和表征这些毒素的各种形式,而在很大程度上忽视了它们的生态作用和进化意义。除了描述关于爪蟾毒素结构、药理学和生物来源的知识范围外,我们还回顾了迄今为止用于爪蟾毒素研究的检测、鉴定和定量方法,并得出结论,由于方法学和采样的限制,许多已知的毒素谱不太可能全面。现有数据的模式表明,环境因素(毒素可得性)和遗传因素(合成或隔离毒素的能力)都会影响毒素的特征。从生态学和进化的角度,我们总结了可能的选择压力作用于爪蟾的毒性和毒素谱,包括捕食,种内交流,疾病和生殖状态。为今后对爪足类的生态学、进化和生化研究提供基础。
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引用次数: 4
Heterologous expression of four recombinant toxins from Panamanian scorpions of the genus Tityus and Centruroides for production of antivenom 四种巴拿马蝎属重组毒素的异源表达及抗蛇毒血清的制备
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-03-01 DOI: 10.1016/j.toxcx.2021.100090
Marcos H. Salazar , Herlinda Clement , Ligia L. Corrales-García , Jairo Sánchez , John Cleghorn , Fernando Zamudio , Lourival D. Possani , Hildaura Acosta , Gerardo Corzo

Background

The development of more effective antivenoms remains a necessity for countries where scorpionism is a public health problem. Also, the regionalization of antivenoms may be important for some countries with special scorpionism characteristics.

Objective

Production of antibodies capable of neutralizing the lethal effect of the venom of three scorpion species from Panama.

Methods

The primary structures of two neurotoxins from T. pachyurus, one from T. cerroazul and another from C. bicolor were elucidated using N-terminal amino acid degradation and Sanger gene cloned sequencing. The obtained mRNA transcripts were cloned and expressed using E. coli vectors. Different bacterial expression conditions were tested and the best culture conditions for each expressed protein is reported. The expressed scorpion toxins were purified by chromatographic methods and used as immunogens in rabbits.

Results

The antibodies produced under the reported immunization scheme show better neutralization (ED50) than other reported commercial antivenoms used to neutralize similar species scorpion venoms under similar LD50 conditions.

Conclusion

The information reported here shows the proof of concept for selecting recombinant immunogens with the ability to produce antibodies for neutralizing the lethal effects of the most important medical species of scorpions in Panama.

发展更有效的抗蛇毒血清对于那些蝎子病是公共卫生问题的国家来说仍然是必要的。此外,抗蛇毒血清的区域化可能对一些具有特殊蝎子病特征的国家很重要。目的制备能中和巴拿马三种蝎子毒液致死作用的抗体。方法采用n端氨基酸降解和Sanger基因克隆测序的方法,对两种不同神经毒素的主要结构进行分析。将获得的mRNA转录本克隆并利用大肠杆菌载体进行表达。试验了不同的细菌表达条件,并报道了每种表达蛋白的最佳培养条件。表达的蝎毒素经层析纯化后作为免疫原用于家兔。结果在相同的LD50条件下,该免疫方案产生的抗体比其他已报道的商业抗蛇毒血清具有更好的中和效果(ED50)。结论选择重组免疫原能够产生抗体来中和巴拿马最重要的药用蝎子的致死效应,这一概念得到了证明。
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引用次数: 3
Access to antivenoms in the developing world: A multidisciplinary analysis 发展中国家抗蛇毒血清的获取:多学科分析
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100086
Julien Potet , David Beran , Nicolas Ray , Gabriel Alcoba , Abdulrazaq Garba Habib , Garba Iliyasu , Benjamin Waldmann , Ravikar Ralph , Mohammad Abul Faiz , Wuelton Marcelo Monteiro , Jacqueline de Almeida Gonçalves Sachett , Jose Luis di Fabio , María de los Ángeles Cortés , Nicholas I. Brown , David J. Williams

Access to safe, effective, quality-assured antivenom products that are tailored to endemic venomous snake species is a crucial component of recent coordinated efforts to reduce the global burden of snakebite envenoming. Multiple access barriers may affect the journey of antivenoms from manufacturers to the bedsides of patients. Our review describes the antivenom ecosystem at different levels and identifies solutions to overcome these challenges.

At the global level, there is insufficient manufacturing output to meet clinical needs, notably for antivenoms intended for use in regions with a scarcity of producers. At national level, variable funding and deficient regulation of certain antivenom markets can lead to the procurement of substandard antivenom. This is particularly true when producers fail to seek registration of their products in the countries where they should be used, or where weak assessment frameworks allow registration without local clinical evaluation. Out-of-pocket expenses by snakebite victims are often the main source of financing antivenoms, which results in the underuse or under-dosing of antivenoms, and a preference for low-cost products regardless of efficacy. In resource-constrained rural areas, where the majority of victims are bitten, supply of antivenom in peripheral health facilities is often unreliable. Misconceptions about treatment of snakebite envenoming are common, further reducing demand for antivenom and exacerbating delays in reaching facilities equipped for antivenom use.

Multifaceted interventions are needed to improve antivenom access in resource-limited settings. Particular attention should be paid to the comprehensive list of actions proposed within the WHO Strategy for Prevention and Control of Snakebite Envenoming.

获得针对地方性毒蛇品种的安全、有效、有质量保证的抗蛇毒血清产品是最近为减轻全球蛇咬伤负担而进行的协调努力的一个重要组成部分。多重准入障碍可能影响抗蛇毒血清从制造商到患者床边的旅程。我们的综述描述了不同水平的抗蛇毒血清生态系统,并确定了克服这些挑战的解决方案。在全球一级,制造产量不足以满足临床需求,特别是用于生产者稀少地区的抗蛇毒血清。在国家层面,某些抗蛇毒血清市场的资金不稳定和监管不足可能导致采购不合格的抗蛇毒血清。当生产商未能在应该使用其产品的国家寻求其产品的注册,或者在薄弱的评估框架允许在没有当地临床评估的情况下进行注册时,情况尤其如此。蛇咬伤受害者的自付费用往往是抗蛇毒血清的主要资金来源,这导致抗蛇毒血清使用不足或剂量不足,以及不顾疗效而偏爱低成本产品。在资源有限的农村地区,大多数受害者被咬伤,外围卫生设施的抗蛇毒血清供应往往不可靠。对蛇咬伤治疗的误解很常见,这进一步减少了对抗蛇毒血清的需求,并加剧了到达配备抗蛇毒血清使用设施的延误。在资源有限的环境中,需要采取多方面的干预措施来改善抗蛇毒血清的获取。应特别注意世卫组织预防和控制蛇咬伤战略中提出的综合行动清单。
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引用次数: 27
Assessing the practicalities of joint snakebite and dog rabies control programs: Commonalities and potential pitfalls 评估蛇咬伤和狗狂犬病联合控制方案的可行性:共性和潜在的陷阱
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100084
Terence P. Scott , Sanjib K. Sharma , Ryan M. Wallace , Louis H. Nel , Samir K. Adhikari , Bernadette Abela-Ridder , S.M. Thumbi

Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders.

狂犬病和蛇咬伤主要影响全球服务不足和贫困的社区,估计每年有20万人死于这些疾病,非洲和亚洲的负担最重。这两种疾病都被忽视了,因此没有得到适当的优先考虑、支持和干预,并面临着所有被忽视的热带病共同面临的许多挑战。根据最近的被忽视热带病路线图中对在被忽视热带病之间采取综合方法的呼吁,我们试图通过确定蛇咬伤和狂犬病之间的共性,在以前的综合方法概念的基础上,探索综合方法的可行性。虽然确定了多个潜在整合领域,但考虑到每种疾病及其干预计划的细微差别,我们强调了整合狂犬病和蛇咬伤计划的潜在陷阱。我们的结论是,加强卫生系统和能力建设应成为被忽视热带病的任何综合方法的重点,并且通过加强整体卫生系统,狂犬病和蛇咬伤都可以倡导政府和利益攸关方的进一步支持。
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引用次数: 2
Artemia salina as an animal model for the preliminary evaluation of snake venom-induced toxicity 盐渍蒿作为蛇毒毒性初步评价的动物模型
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100082
Mitchel Otieno Okumu , James Mucunu Mbaria , Joseph Kangangi Gikunju , Paul Gichohi Mbuthia , Vincent Odongo Madadi , Francis Okumu Ochola , Mercy Seroney Jepkorir

Lethality and cytotoxicity assays of snake venoms and their neutralization by antivenom require many mice for the experiments. Recent developments have prompted researchers to seek alternative strategies that minimize the use of mice in line with Russel and Burch's 3Rs philosophy (Replacement, Reduction, and Refinement). Artemia salina is an animal model widely used for toxicity screening. However, its use in snake venom toxinology is limited by a lack of data. The present study compared the toxicity of venoms from Bitis arietans, Naja ashei, and Naja subfulva using mice and Artemia salina. In the Artemia salina test at 24 h and the dermonecrotic test in mice, the toxicity of the venoms was in the order Naja ashei ~ Naja subfulva > Bitis arietans. In the lethality test in mice, the toxicity of the venoms was in the order Naja subfulva > Naja ashei > Bitis arietans. These findings suggest that the toxicity of the venoms in Artemia salina and the dermonecrotic bioassay in mice have a similar trend but differ from the lethality test in mice. Therefore, it may be relevant to further explore the Artemia salina bioassay as a potential surrogate test of dermonecrosis in mice. Studies with more venoms may be needed to establish the correlation between the Artemia salina bioassay and the dermonecrotic assay in mice.

蛇毒的致死性和细胞毒性测定及其抗蛇毒血清中和作用需要许多小鼠进行实验。最近的发展促使研究人员寻求替代策略,以最大限度地减少小鼠的使用,这符合罗素和伯奇的3r哲学(替换、减少和改进)。盐蒿是一种广泛用于毒性筛选的动物模型。然而,由于缺乏数据,它在蛇毒毒理学中的应用受到限制。本研究用小鼠和盐蒿比较了白斑双翅虫(Bitis arietans)、灰翅虫(Naja ashei)和细翅虫(Naja subfulva)毒液的毒性。在24 h盐蒿试验和小鼠皮肤腐蚀试验中,毒液的毒性依次为Naja ashei ~ Naja subfulva >比提arietans。在小鼠的致死试验中,毒液的毒性在Naja subfulva >Naja ashei >比提arietans。这些结果表明,盐蒿毒液的毒性和小鼠皮肤腐蚀生物试验具有相似的趋势,但与小鼠致死试验不同。因此,进一步探索盐蒿生物测定法作为小鼠皮肤坏死的替代试验可能具有重要意义。可能需要更多毒液的研究来确定盐蒿生物测定与小鼠皮肤腐蚀测定之间的相关性。
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引用次数: 11
Local inflammatory mediators alterations induced by Daboia siamensis venom 大鲵毒液诱导局部炎症介质的改变
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100085
Suchitra Khunsap , Kanyanat Promruangreang , Sunutcha Suntrarachun , Jureeporn Noiphrom , Orawan Khow

The ability of Russell's viper (Daboia siamensis) venom (total RVV) and phospholipase A2 (purified PLA2) to induce the local pathological effects were investigated by the local inflammatory events and the release of inflammatory mediators. Both 0.5 μg of total RVV/mouse and 0.15 μg of purified PLA2/mouse were administered via intra-peritoneal injection. After 30 min, 1 h, 2 h, and 4 h incubation time, the peritoneal cavity was flooded with normal saline and the total leukocytes were collected. The eicosanoids (lipid mediators) and the leukocyte expression of cyclooxygenase (COX-1 and COX-2) were investigated by ELISA assay and western blotting, respectively. The amounts of total leukocytes were increased from 30 min to 2 h, then decreased at 4 h, by both total RVV and purified PLA2. Both treatments also induced the expression of COX-2 which was increased at 2 h and then decreased at 4 h, whereas only purified PLA2 induced the expression level of a COX-1 protein which was increased at 30 min, then constantly expressed until 4 h. In addition, total RVV and purified PLA2 caused the release of the eicosanoids; PGE2, TXB2, and LTB4, which reached the peak after 2 h. The findings of this study indicate that purified PLA2 has the potential effects to induce the local inflammation relating the amounts of leukocytes cells, lipid mediators and COX-2 more than the total RVV.

通过局部炎症事件和炎症介质的释放,研究了罗素蝰蛇毒液(总RVV)和磷脂酶A2(纯化PLA2)诱导局部病理效应的能力。腹腔注射总RVV 0.5 μg /只,纯化PLA2 0.15 μg /只。孵育30 min、1 h、2 h、4 h后,腹腔灌注生理盐水,收集白细胞总数。采用酶联免疫吸附法(ELISA)和免疫印迹法(western blotting)分别检测各组小鼠脂质介质类二十烷酸和白细胞环氧化酶(COX-1和COX-2)的表达。总RVV和纯化PLA2在30分钟至2小时内使白细胞总数增加,然后在4小时时减少。两种处理均诱导COX-2的表达,在2 h时升高,在4 h时降低,而纯化PLA2只诱导COX-1蛋白的表达,在30 min时升高,并持续表达至4 h。此外,总RVV和纯化PLA2均引起类二十烷酸的释放;PGE2、TXB2和LTB4在2 h后达到峰值。本研究结果表明纯化PLA2具有诱导局部炎症的潜在作用,其白细胞、脂质介质和COX-2的数量大于RVV总量。
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引用次数: 0
Assessing a 6-h endpoint observation time in the lethality neutralization assay used to evaluate the preclinical efficacy of snake antivenoms 评估用于评估抗蛇毒血清临床前疗效的致死性中和试验的6小时终点观察时间
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100087
Gina Durán, Gabriela Solano, Aarón Gómez, Daniel Cordero, Adriana Sánchez, Mauren Villalta, Melvin Sánchez, Cecilia Díaz, José María Gutiérrez, Guillermo León

The lethality neutralization assay in mice is the gold standard for the evaluation of the preclinical efficacy and specification fulfillment of snake antivenoms. However, owing to the animal suffering involved, this assay is a candidate to be replaced by in vitro alternatives or, at least, improved by the reduction of the number of animals used per experiment, the introduction of analgesia, and the refinement of the test. Since these tests are usually run for 24 or 48 h, one possibility to refine it is to shorten the endpoint observation time of the assay and so limiting the duration of suffering. To assess the effect of this modification of the standard procedure on the analytical properties of the assay, we compared the median lethal dose (LD50) and median effective dose (ED50) values, estimated through observation times of 6, 24 and 48 h. We used African and Latin American snake venoms and several batches of two polyspecific antivenoms. A significant correlation was found between LD50 and ED50 values estimated at the three observation times. Although some LD50 and ED50 values were significantly different at these time points, results of 6 h were robust enough to be used in the characterization of new antivenoms, the verification of specification compliance, and the parallel comparison of formulations. Our observations support the modification of the standard procedures used for assessing neutralizing ability of antivenoms by carrying out the observations at 6 h instead of 24 or 48 h, with the consequent reduction in the suffering inflicted upon mice during these assays. However, the shortening of the observation time in the lethality tests must be validated for each venom and antivenom before its introduction in the routine procedures.

小鼠致死性中和试验是评价抗蛇毒血清临床前疗效和满足规格要求的金标准。然而,由于所涉及的动物的痛苦,该试验是被体外替代的候选方法,或者至少通过减少每次实验使用的动物数量、引入镇痛剂和改进试验来改进。由于这些测试通常运行24或48小时,一种改进的可能性是缩短试验的终点观察时间,从而限制痛苦的持续时间。为了评估标准程序的修改对分析性质的影响,我们比较了中位致死剂量(LD50)和中位有效剂量(ED50)值,通过观察时间分别为6、24和48小时。我们使用了非洲和拉丁美洲的蛇毒和几批两种多特异性抗蛇毒血清。在三次观测中,LD50和ED50值之间存在显著的相关性。尽管在这些时间点上,一些LD50和ED50值存在显著差异,但6小时的结果足够可靠,可用于新抗蛇毒血清的表征、规格符合性验证以及配方的平行比较。我们的观察结果支持对用于评估抗蛇毒血清中和能力的标准程序进行修改,通过在6小时而不是24或48小时进行观察,从而减少了在这些试验中对小鼠造成的痛苦。然而,在将每种蛇毒和抗蛇毒血清引入常规程序之前,必须对其进行验证,以缩短其在致命性试验中的观察时间。
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引用次数: 5
Promoting co-existence between humans and venomous snakes through increasing the herpetological knowledge base 通过增加爬虫学知识基础,促进人与毒蛇共存
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100081
Anita Malhotra , Wolfgang Wüster , John Benjamin Owens , Cameron Wesley Hodges , Allwin Jesudasan , Gnaneswar Ch , Ajay Kartik , Peter Christopher , Jose Louies , Hiral Naik , Vishal Santra , Sourish Rajagopalan Kuttalam , Shaleen Attre , Mahmood Sasa , Carlos Bravo-Vega , Kris A. Murray

Snakebite incidence at least partly depends on the biology of the snakes involved. However, studies of snake biology have been largely neglected in favour of anthropic factors, with the exception of taxonomy, which has been recognised for some decades to affect the design of antivenoms. Despite this, within-species venom variation and the unpredictability of the correlation with antivenom cross-reactivity has continued to be problematic. Meanwhile, other aspects of snake biology, including behaviour, spatial ecology and activity patterns, distribution, and population demography, which can contribute to snakebite mitigation and prevention, remain underfunded and understudied. Here, we review the literature relevant to these aspects of snakebite and illustrate how demographic, spatial, and behavioural studies can improve our understanding of why snakebites occur and provide evidence for prevention strategies. We identify the large gaps that remain to be filled and urge that, in the future, data and relevant metadata be shared openly via public data repositories so that studies can be properly replicated and data used in future meta-analyses.

蛇咬伤的发生率至少部分取决于相关蛇的生物学特性。然而,对蛇的生物学研究在很大程度上被忽视了,因为人们倾向于人为因素,除了分类,几十年来人们已经认识到它会影响抗蛇毒血清的设计。尽管如此,物种内的毒液变异和抗蛇毒血清交叉反应相关性的不可预测性仍然存在问题。与此同时,可以有助于减少和预防蛇咬伤的蛇生物学的其他方面,包括行为、空间生态学和活动模式、分布和人口统计,仍然缺乏资金和研究。在这里,我们回顾了与蛇咬伤这些方面相关的文献,并说明了人口统计学、空间学和行为学研究如何提高我们对蛇咬伤发生原因的理解,并为预防策略提供证据。我们确定了仍有待填补的巨大差距,并敦促在未来,通过公共数据存储库公开共享数据和相关元数据,以便可以适当地复制研究并将数据用于未来的元分析。
{"title":"Promoting co-existence between humans and venomous snakes through increasing the herpetological knowledge base","authors":"Anita Malhotra ,&nbsp;Wolfgang Wüster ,&nbsp;John Benjamin Owens ,&nbsp;Cameron Wesley Hodges ,&nbsp;Allwin Jesudasan ,&nbsp;Gnaneswar Ch ,&nbsp;Ajay Kartik ,&nbsp;Peter Christopher ,&nbsp;Jose Louies ,&nbsp;Hiral Naik ,&nbsp;Vishal Santra ,&nbsp;Sourish Rajagopalan Kuttalam ,&nbsp;Shaleen Attre ,&nbsp;Mahmood Sasa ,&nbsp;Carlos Bravo-Vega ,&nbsp;Kris A. Murray","doi":"10.1016/j.toxcx.2021.100081","DOIUrl":"10.1016/j.toxcx.2021.100081","url":null,"abstract":"<div><p>Snakebite incidence at least partly depends on the biology of the snakes involved. However, studies of snake biology have been largely neglected in favour of anthropic factors, with the exception of taxonomy, which has been recognised for some decades to affect the design of antivenoms. Despite this, within-species venom variation and the unpredictability of the correlation with antivenom cross-reactivity has continued to be problematic. Meanwhile, other aspects of snake biology, including behaviour, spatial ecology and activity patterns, distribution, and population demography, which can contribute to snakebite mitigation and prevention, remain underfunded and understudied. Here, we review the literature relevant to these aspects of snakebite and illustrate how demographic, spatial, and behavioural studies can improve our understanding of why snakebites occur and provide evidence for prevention strategies. We identify the large gaps that remain to be filled and urge that, in the future, data and relevant metadata be shared openly via public data repositories so that studies can be properly replicated and data used in future meta-analyses.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/b4/main.PMC8426276.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39416934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 18
Analgesic potential of different available commercial brands of botulinum neurotoxin-A in formalin-induced orofacial pain in mice 不同商业品牌肉毒杆菌神经毒素a对福尔马林引起的小鼠口面部疼痛的镇痛潜力
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2021-11-01 DOI: 10.1016/j.toxcx.2021.100083
Thays Crosara Abrahão Cunha , Ana Claudia Gontijo Couto , Eduardo Januzzi , Rafael Tardin Rosa Ferraz Gonçalves , Graziella Silva , Cassia Regina Silva

The use of botulinum neurotoxin-A (BoNT-A) is an alternative for the management of orofacial pain disorders. Although only Botox has labeled, there are other commercial brands available for use, among them: Dysport, Botulift, Prosigne, and Xeomin. The objective of the present study was to evaluate the possible differences in the antinociceptive effect evoked by different commercially available formulations of BoNT-A in an animal model of inflammatory orofacial pain induced by formalin injection. Male C57/BL6 mice (20–25 g) were submitted to the pre-treatment with five different commercial brands of BoNT-A (Botox, Botulift, Xeomin, Dysport, or Prosigne; with doses between 0.02 and 0.2 Units of Botulinum Toxin, in 20 μL of 0.9% saline) three days prior the 2% formalin injection. All injections were made subcutaneously into the right perinasal area. After formalin injections, nociceptive behaviors like rubbing the place of injection were quantified during the neurogenic (0–5 min) and inflammatory (15–30 min) phases. The treatment using Botox, Botulift, and Xeomin were able to induce antinociceptive effects in both phases of the formalin-induced pain animal model, however, Dysport and Prosigne reduced the response in neither of them. Our data suggest that the treatment using different formulations of BoNT-A is not similar in efficacy as analgesics when evaluated in formalin-induced orofacial pain in mice.

肉毒杆菌神经毒素- a (BoNT-A)的使用是治疗口腔面部疼痛疾病的一种替代方法。虽然只有肉毒杆菌贴了标签,但也有其他商业品牌可供使用,其中包括:Dysport、Botulift、Prosigne和Xeomin。本研究的目的是评估不同市售BoNT-A配方在福尔马林注射引起的炎症性口面部疼痛动物模型中所引起的抗痛感效果的可能差异。雄性C57/BL6小鼠(20-25 g)使用5种不同商业品牌的BoNT-A (Botox、Botulift、Xeomin、Dysport或Prosigne)进行预处理;注射2%福尔马林前3天,在20 μL 0.9%生理盐水中注射0.02 ~ 0.2单位肉毒毒素。所有注射均在右阴部皮下进行。注射福尔马林后,在神经原性(0-5 min)和炎症期(15-30 min),量化摩擦注射部位等伤害性行为。使用肉毒杆菌素、Botulift和Xeomin治疗能够在福尔马林诱导的疼痛动物模型的两个阶段诱导抗伤感受作用,然而,Dysport和Prosigne都没有降低这两个阶段的反应。我们的数据表明,当评估福尔马林诱导的小鼠口腔面部疼痛时,使用不同配方的BoNT-A的治疗效果与镇痛药不同。
{"title":"Analgesic potential of different available commercial brands of botulinum neurotoxin-A in formalin-induced orofacial pain in mice","authors":"Thays Crosara Abrahão Cunha ,&nbsp;Ana Claudia Gontijo Couto ,&nbsp;Eduardo Januzzi ,&nbsp;Rafael Tardin Rosa Ferraz Gonçalves ,&nbsp;Graziella Silva ,&nbsp;Cassia Regina Silva","doi":"10.1016/j.toxcx.2021.100083","DOIUrl":"10.1016/j.toxcx.2021.100083","url":null,"abstract":"<div><p>The use of botulinum neurotoxin-A (BoNT-A) is an alternative for the management of orofacial pain disorders. Although only Botox has labeled, there are other commercial brands available for use, among them: Dysport, Botulift, Prosigne, and Xeomin. The objective of the present study was to evaluate the possible differences in the antinociceptive effect evoked by different commercially available formulations of BoNT-A in an animal model of inflammatory orofacial pain induced by formalin injection. Male C57/BL6 mice (20–25 g) were submitted to the pre-treatment with five different commercial brands of BoNT-A (Botox, Botulift, Xeomin, Dysport, or Prosigne; with doses between 0.02 and 0.2 Units of Botulinum Toxin, in 20 μL of 0.9% saline) three days prior the 2% formalin injection. All injections were made subcutaneously into the right perinasal area. After formalin injections, nociceptive behaviors like rubbing the place of injection were quantified during the neurogenic (0–5 min) and inflammatory (15–30 min) phases. The treatment using Botox, Botulift, and Xeomin were able to induce antinociceptive effects in both phases of the formalin-induced pain animal model, however, Dysport and Prosigne reduced the response in neither of them. Our data suggest that the treatment using different formulations of BoNT-A is not similar in efficacy as analgesics when evaluated in formalin-induced orofacial pain in mice.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.toxcx.2021.100083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39420653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Toxicon: X
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