envenomation

Envenomation
  • 文章类型: Journal Article
    蛇咬伤被认为是一个重大的健康问题。目前的抗蛇毒血清含有多克隆抗体,它们对不同毒液成分的特异性不同。开发和表征下一代抗蛇毒血清,包括针对眼镜蛇的纳米抗体是本研究的主要目的。将粗毒液注入SephadexG50过滤凝胶色谱柱中,然后获得有毒级分。然后将相应的级分注射到HPLC柱中并鉴定毒性峰。将N.najaxiana毒液注射到骆驼中,并使用噬菌体展示技术针对毒性峰进行特定的纳米抗体筛选。获得的结果表明,在获得的12个克隆中,N24纳米抗体能够中和从HPLC色谱获得的毒性最强的峰P1。P1的分子量用质谱仪测量,发现为约7kDa。用N24纳米抗体中和试验结果表明,250μg重组纳米抗体可中和小鼠20μg的毒性作用,相当于LD50×10的粗毒液。研究结果表明,开发的纳米抗体具有作为新型抗蛇毒血清疗法的潜力。
    Snakebites are considered a significant health issue. Current antivenoms contain polyclonal antibodies, which vary in their specificity against different venom components. Development and characterization of next generation antivenoms including nanobodies against Naja naja oxiana was the main aim of this study. Crude venom was injected into the Sephadex G50 filtration gel chromatography column and then toxic fractions were obtained. Then the corresponding fraction was injected into the HPLC column and the toxic peaks were identified. N. naja oxiana venom was injected into a camel and specific nanobodies screening was performed against the toxic peak using phage display technique. The obtained results showed that among the 12 clones obtained, N24 nanobody was capable of neutralizing P1, the most toxic peak obtained from HPLC chromatography. The molecular weight of P1 was measured with a mass spectrometer and was found to be about seven kDa. The results of the neutralization test of crude N. naja oxiana venom with N24 nanobody showed that 250 μg of recombinant nanobody could neutralize the toxic effects of 20 μg equivalent to LD50 × 10 of crude venom in mice. The findings indicate the potential of the developed nanobody to serve as a novel antivenom therapy.
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  • 文章类型: Case Reports
    随着景观变得更加城市化,蛇咬伤越来越成为新加坡急诊部门的罕见表现,而导致严重毒液的蛇咬伤则更为罕见。在这个案例报告中,我们讨论了一名55岁的男子,他从ShorePitViper(TrimeresurusPurpureomaculatus)中产生了明显的毒液,并成功接受了血液毒性多价抗蛇毒血清(HPAV)治疗。他最初表现出疼痛,他的伤口肿胀出血.由于他的凝血功能恶化,他接受了两剂HPAV,通常只用于蛇类。在服用抗毒液后,患者的凝血状况有所改善,毒液的局部软组织效应得以解决。他没有表现出任何不利影响,并且在蛇咬伤后约72小时顺利出院。在这种情况下,HPAV对ShorePitViper(TrimeresurusPurpureomaculatus)毒液的交叉中和潜力表明,各种蛇种的毒液蛋白之间可能存在共同的潜在化学结构和病理生理学。鉴于Trimeresurus特异性抗蛇毒血清在大多数国家不可用,在类似情况下,这种交叉中和策略值得进一步考虑和评估。
    As the landscape becomes more urbanized, snakebites have increasingly become uncommon presentations to the emergency departments in Singapore, while snakebites causing significant envenomation are even rarer. In this case report, we discuss a 55-year-old man who had significant envenomation from a Shore Pit Viper (Trimeresurus Purpureomaculatus) and who was successfully treated with haemato-toxic polyvalent antivenom (HPAV). He initially presented with pain, swelling and bleeding over his wound. Due to a deterioration in his coagulation profile, he was given two doses of HPAV which is typically reserved for viperid snakes instead. Following administration of the anti-venom, the patient\'s coagulation profile improved, and the local soft tissue effects of the venom resolved. He did not manifest any adverse effects and was discharged uneventfully about 72 h after the snakebite. The cross-neutralization potential of HPAV for Shore Pit Viper (Trimeresurus Purpureomaculatus) venom in this case study suggests that there may be a possible common underlying chemical structure and pathophysiology among the venom proteins of various snake species. Given that Trimeresurus-specific antivenom is unavailable in most countries, this cross-neutralization strategy deserves further consideration and evaluation in similar circumstances.
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  • 文章类型: Journal Article
    在2023年,一组专家提出在所有蛇咬伤试验中使用药物抗凝患者的大出血定义。这包括导致死亡的出血,危及生命,导致慢性后遗症,或者消耗主要的医疗资源,包括出血到主要区域或血红蛋白浓度降低≥20g/L我们假设,在我们的亚利桑那响尾蛇咬伤患者人群中,血红蛋白浓度下降≥20g/L是常见的,但临床上很少有意义。
    从2018年到2022年人类响尾蛇咬伤的毒物中心记录进行了回顾性审查,并根据上述标准评估了大出血。
    四百八十一名患者符合纳入标准,其中265人(55.1%)的血红蛋白浓度降低≥20g/L。没有病人死亡,没有证据表明有一个重要器官出血.3名患者(1.1%)接受了输血。血红蛋白浓度降低≥20g/L对于确定主要出血相关结局是100%敏感的;然而,特异性仅为45.2%.在血红蛋白浓度降低≥20g/L的患者中,医疗保健利用和慢性后遗症的措施更高。
    血液毒性的实验室表现在该人群中很常见,但出血很少见.虽然超过一半的患者符合血红蛋白浓度下降≥20g/L的主要出血标准,只有1.1%的患者因接受红细胞输血而有可能危及生命的出血.没有人死亡或出血到关键区域。虽然对大出血是非特异性的,血红蛋白浓度的下降与更严重的毒化严重程度相关:这些患者接受了更多的抗蛇毒血清,有更高的医疗费用,住院时间更长,并且不太可能在90天报告完全恢复。
    血红蛋白浓度降低≥20g/L不应被用作亚利桑那响尾蛇毒血症研究中大出血的证据,但它可能是毒气严重程度的间接标记。
    UNASSIGNED: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients.
    UNASSIGNED: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria.
    UNASSIGNED: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L.
    UNASSIGNED: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days.
    UNASSIGNED: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity.
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  • 文章类型: Journal Article
    了解环境因素如何影响捕食者的表现,可以从进化和生态角度以及每个分类单元的全球分布模式为捕食者与猎物的相互作用提供深刻的见解。几乎所有有毒的捕食者都是异温动物,肌肉收缩特性取决于温度。对于具有由肌肉收缩驱动的毒液运输系统的捕食者,温度可能对猎物捕食的捕毒性能有相当大的影响。这里,我们使用摄像和酶联免疫吸附试验来检查毒蛇的捕食性对毒液运动学和毒液消耗的热效应,MamushiGloyydiusblomhofii,在野外和实验室实验条件下,在不同的体温下,它的主要啮齿动物猎物。出乎意料的是,我们发现,在几乎整个生态相关的温度范围内(从13.2°C到26.2°C),对麻醉性能的热效应都受到限制。尽管温度在统计上显着影响野外条件下注射的毒液的质量,温度仅解释了毒液支出变化的一小部分。这些发现表明,Mamushi能够在很宽的温度范围内保持猎物的征服性能,这对放热捕食者非常有利。进一步的研究应该检查有限的热效应的潜在机制及其在有毒捕食者中的普遍性。
    Understanding how environmental factors affect the performance of predators can provide profound insights into predator-prey interactions from evolutionary and ecological perspectives and the global distributional patterns of each taxon. Almost all venomous predators are ectotherms, with muscle contraction properties depending on temperature. For predators having venom transportation systems driven by muscle contraction, temperature may have quite large effects on envenomation performance for prey subjugation. Here, we used videography and enzyme-linked immunosorbent assay to examine thermal effects on envenomation kinematics and venom expenditure in predatory strikes of a venomous snake, the Mamushi Gloydius blomhoffii, to its main rodent prey at various body temperatures under both field and laboratory experimental conditions. Unexpectedly, we found that the thermal effects on envenomation performance are limited over nearly the entire ecologically relevant range of temperature (from 13.2°C to 26.2°C). Although temperature statistically significantly affected the mass of venom injected under field conditions, temperature explained only a minor proportion of the variation in venom expenditure. These findings suggest that the Mamushi is able to maintain prey subjugation performance across a wide range of temperatures, which is highly advantageous for ectothermic predators. Further studies should examine the underlying mechanisms of the limited thermal effects and their ubiquity across venomous predators.
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  • 文章类型: Journal Article
    响尾蛇(Crotalusspp.,Sistrurusspp.)美国西南部的咬伤与显著的发病率有关。这项研究旨在描述向亚利桑那毒物和毒品信息中心报告的25年响尾蛇遭遇,以确定易受攻击的人群和情况,以创建公共教育以减少未来的叮咬。
    分析了1999年至2023年之间在亚利桑那州报告给亚利桑那州毒物和药物信息中心的疑似响尾蛇遭遇案例,以确定与遭遇相关的人群和情况。
    对3,808例病例进行了总体分析和年龄亚组分析。大多数相遇发生在男性中(69.9%),晚上(16:00-21:59;49.2%),夏季(41.9%),离家近(38.2%)。大多数咬伤发生在下肢(51%)。在农村地区,0至12岁的儿童比13岁及以上的儿童有更多的遭遇(27.7%对14.8%;P=0.005),春季(31.8%对22.3%;P=0.0005),和晚上(64.4%对48.1%;P<0.001)。
    响尾蛇和人类行为模式重叠时遇到响尾蛇。许多人在夏天的晚上在外面度过时光,和食物等宝贵资源,水,可以在人们花费大量时间的房屋附近找到庇护所。大多数年龄组都有类似的遭遇情况,但0至12岁儿童的遭遇在一天中的时间不同,季节,与13岁及以上的人相比,城市化水平更高。这项研究的局限性包括对相遇的漏报,不完整的案例细节,潜在的报告偏见,潜在的蛇错误识别,和毒物中心的地理覆盖范围。
    通过减少遭遇来预防响尾蛇叮咬是减少痛苦和医疗费用的最有效方法。未来的步骤包括使用收集的数据创建和传播有针对性的公共卫生教育。
    UNASSIGNED: Rattlesnake (Crotalus spp., Sistrurus spp.) bites in the southwestern United States are associated with significant morbidity. This study aims to describe 25 years of rattlesnake encounters reported to the Arizona Poison and Drug Information Center to identify vulnerable populations and circumstances where encounters occur to create public education to reduce future bites.
    UNASSIGNED: Cases of suspected rattlesnake encounters in Arizona reported to the Arizona Poison and Drug Information Center between 1999 and 2023 were analyzed to identify populations and circumstances associated with encounters.
    UNASSIGNED: A total of 3,808 cases were analyzed overall and by age subgroups. Most encounters occurred in men (69.9%), during the evening (16:00-21:59; 49.2%), in summer (41.9%), and close to home (38.2%). Most bites occurred to the lower extremity (51%). Children 0 to 12-years-old have more encounters than those 13-years-old and older in rural zip codes (27.7% versus 14.8%; P = 0.005), during spring (31.8% versus 22.3%; P = 0.0005), and during the evening (64.4% versus 48.1%; P < 0.001).
    UNASSIGNED: Rattlesnakes are encountered when rattlesnake and human behavior patterns overlap. Many people spend time outside during evening hours in the summer, and valuable resources like food, water, and shelter can be found near houses where humans spend much of their time. Most age groups have similar encounter circumstances but encounters among children 0 to 12-years-old differ in time of day, season, and urbanization level than encounters of those 13-years-old and older. Limitations of this study include underreporting of encounters, incomplete case details, potential reporting bias, potential snake misidentification, and geographic coverage of the poison center.
    UNASSIGNED: Prevention of rattlesnake bites by reducing encounters is the most effective way to reduce suffering and healthcare costs. Future steps include creating and disseminating targeted public health education using the data collected.
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  • 文章类型: Journal Article
    蛇咬伤在世界上许多热带和亚热带国家是一个被忽视的公共卫生问题。每年约有540万例蛇咬伤,导致每年180万到270万例毒液。据报道,在实验动物中注射毒液后3-6小时,肝脏标志物会升高。本研究旨在生化评估ALT,AST和GGT水平作为咬伤后6小时在JUTH综合健康中心Zamko出现的蛇咬伤受害者的Echisocellatus毒液的生物标志物,并与被无毒蛇咬伤的值进行比较。
    该研究是一项比较横断面研究,其中血清AST水平,比较研究组和对照组的ALT和GGT。
    在150名受访者中,每个研究组75人,男性90人(60.0%),女性60人(40.0%),男女比例为1.5:1。最主要的年龄组是20-29岁57(38.0%),平均年龄是39岁。最主要的职业是农业82(54.7%)。大多数82人(54.7%)具有中等教育水平。91(60.7%)已婚。123(82.0)的绝大多数人将基督教作为他们的宗教。我们发现,与AST(25.88IU/L)相比,研究组的AST(47.45IU/L)和GGT(61.62IU/L)水平显着增加,对照组的GGT(29.61IU/L)在p<0.05时,而两组的ALT水平在p>0.05时相似。
    这意味着AST和GGT的血清水平可用于诊断蛇咬伤患者的毒液。
    UNASSIGNED: Snake bite is a neglected public health issue in many tropical and subtropical countries of the world. About 5.4 million snakebites occur each year, resulting in 1.8 to 2.7 million cases of envenomation yearly. Hepatic markers have been reported to rise 3-6 hours after injection of venom in experimental animals. This study aims to biochemically assess ALT, AST and GGT levels as biomarkers of Echis ocellatus envenomation in victims of snake bite presenting at JUTH Comprehensive Health Centre Zamko 6hours post-bite and compare with values in those bitten by non-venomous snakes.
    UNASSIGNED: The study was a comparative cross-sectional study where serum levels of AST, ALT and GGT were compared between the study group and the control group.
    UNASSIGNED: Of the 150 respondents, 75 from each study group, 90(60.0%) were Male while 60(40.0%) were Female, with a Male to Female ratio of 1.5:1. The most predominant age group was 20-29 years 57(38.0%), the mean age was 39 years. The most predominant occupation was farming 82(54.7%). The majority 82(54.7%) had a secondary level of education. 91(60.7%) were married. A large majority of 123(82.0) had Christianity as their religion. We found a significant increase in the levels of AST (47.45IU/L) and GGT (61.62 IU/L) in the study group compared to AST (25.88IU/L), GGT (29.61IU/L) in the control group at p<0.05, while the level of ALT was similar in both groups at p>0.05.
    UNASSIGNED: This implies that serum levels of AST and GGT can be used to diagnose envenomation in snakebite patients.
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  • 文章类型: Case Reports
    Poecilotheria蜘蛛被认为是临床重要性被低估的治疗方法,这些物种的叮咬会引起严重疼痛和剧烈肌肉痉挛等症状。然而,对这些物种引起的毒液没有特殊的治疗方法,which,虽然原产于印度和斯里兰卡,在世界各地广泛分布。本研究报告了一名31岁男子被Poecilotheriaregalis标本咬伤的病例。患者的临床表现与Latrodectus毒液相似,患者接受了L.mactans抗蛇毒血清治疗。大多数患者的症状得到改善(纤维震颤,疼痛,红斑,和局部肿胀),除了肌肉痉挛.在小鼠上进行的毒理学研究未显示出马卡坦乳杆菌抗蛇毒血清具有中和作用。本报告讨论了Poecilotheria物种的繁殖过程以及L.mactans抗蛇毒血清可能产生的中和作用。
    Poecilotheria spiders are considered theraphosids of underestimated clinical importance, with bites from these species inducing symptoms such as severe pain and intense muscle cramps. However, there is no specific treatment for the envenomation caused by these species, which, while native to India and Sri Lanka, are widely distributed worldwide. The present study reports the case of a 31-year-old man bitten by a Poecilotheria regalis specimen. The patient\'s clinical presentation was similar to Latrodectus envenomation, and patient was treated with an L. mactans antivenom. Most of patient\'s symptoms improved (fasciculations, pain, erythema, and local swelling), except muscle cramps. A toxicological study conducted on mice did not show that L. mactans antivenom has a neutralizing effect on the toxicity of P. regalis. The present report discusses the envenoming process of Poecilotheria species and the possible neutralizing effect exerted by L. mactans antivenom.
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  • 文章类型: Journal Article
    目的:除了描述局部SS的临床表现外,还描述了一个具有典型荨麻疹病变的蝎子刺痛(SS)的年轻患者。
    方法:在主要数据库中对1966年至2021年的文章进行了系统筛选。所有文章都包括SS和荨麻疹之间的关联。新病例报告将添加到发布的列表中。
    结果:文献检索发现5篇文章,29例SS和荨麻疹/过敏反应。我们通过添加我们目前的案例来进行分析,共30例。大多数是男性,他们的年龄从29岁到48岁不等。关于SS严重性,大多数是轻度或中度。在两篇文章中,患者有不止一次刺痛。过敏反应与荨麻疹不同,瘙痒,冲洗,血管性水肿,喘息,鼻漏,打喷嚏,意识改变,以及胃肠道和心血管改变。在5/6(83%)的文章中,患者在研究时间还活着。一名受试者死于过敏性休克。
    结论:本文系统回顾了所有已发表的SS和蝎毒过敏反应的病例。这是一种罕见的关联;大多数患者是男性,处于生产年龄,反应可能从轻度到重度不等,包括死亡。
    OBJECTIVE: To describe a young patient with scorpion sting (SS) with typical lesions of urticaria besides the local SS clinical picture.
    METHODS: A systematic screening of articles dating from 1966 to 2021 was conducted in the main databases. All articles included the association between SS and urticaria. A new case report is added to the published list.
    RESULTS: The literature search found 5 articles with 29 patients with SS and urticaria/allergic reactions. We performed our analysis by adding our present case, resulting in a total of 30 cases. Most were male, and their ages varied from 29 to 48 years. Regarding SS severity, most were mild or moderate. In two articles, patients had more than one sting. The allergic reaction varied from urticaria, pruritus, flushing, angioedema, wheezing, rhinorrhea, sneezing, consciousness alterations, and gastrointestinal and cardiovascular alterations. In 5/6 (83%) articles, the patients were alive at the study time. One subject died from anaphylactic shock.
    CONCLUSIONS: The present article systematically reviewed all published cases of SS and allergic reactions to scorpion venom. It is an infrequent association; most patients are male and in the productive age, and reaction may vary from mild to severe, including death.
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  • 文章类型: Journal Article
    背景:蛇咬伤毒(SBE)和蝎毒毒(SSE)是严重被忽视的热带病,主要影响发展中国家农村地区的贫困社区。对蛇和蝎子物种及其分布缺乏了解,加剧了SBE和SSE造成的残疾和死亡。在苏丹,特别是在医疗保健资源稀缺的受持续冲突影响的地区,社交媒体平台为解决公共卫生挑战提供了一种具有成本效益的方法。我们在这项研究中的目的是强调在这种环境中使用社交媒体进行数据收集和健康促进的好处。
    方法:我们提出了喀土穆大学有毒生物研究中心(TORC)实施的具有成本效益的沟通和数据收集策略,专注于一个Facebook群组,\"蝎子和蛇的苏丹\",作为我们的主要社交媒体平台。此外,我们讨论了该战略对提高人口健康素养的经验教训和初步影响。
    结果:团体社区由来自14个国家的5000名成员组成。在2023年1月至2024年1月期间,我们收到了417项有关蛇和蝎子的查询,这些蛇和蝎子属于11科,由55种组成。此外,其他53项调查涉及一系列生物及其踪迹(例如,蜘蛛,Skinks,变色龙,狐狸,太阳蜘蛛,蜱,蜥蜴,蛾幼虫,和昆虫痕迹)。苏丹Malpolonmonspessulanus的第一个摄影证据是通过小组活动。稀有物种Telescopusgezirae,蓝色尼罗河猫蛇,还通过组成员的查询记录。认识到公共卫生中社交媒体使用的演变性质,我们还解决了当前的局限性和证据差距,需要解决这些问题,以有效地将最佳实践转化为政策。
    结论:结论:利用Facebook作为机构平台,以简单的阿拉伯语分享科学信息强调了公民的积极作用,科学家,公共卫生利益相关者可以利用社交媒体进行电子健康,意识,和公共卫生倡议。这种方法突出了合作努力的潜力,特别是在危机期间,最大限度地发挥社交媒体在促进公共卫生方面的优势。
    BACKGROUND: Snakebite envenomation (SBE) and scorpion sting envenomation (SSE) are significant neglected tropical diseases that primarily affect impoverished communities in rural areas of developing nations. A lack of understanding about snake and scorpion species and their distribution exacerbates the disabilities and fatalities caused by SBE and SSE. In Sudan, particularly in regions affected by ongoing conflicts where healthcare resources are scarce, social media platforms offer a cost-effective approach to addressing public health challenges. Our aim in this study is to highlight the benefits of using social media for data collection and health promotion in such environments.
    METHODS: We present a cost-effective communication and data collection strategy implemented at the Toxic Organisms Research Centre (TORC) of the University of Khartoum, focusing on a Facebook group, \"Scorpions and Snakes of Sudan\", as our primary social media platform. Additionally, we discuss the lessons learned and the initial impact of this strategy on enhancing population health literacy.
    RESULTS: The group community is composed of ~ 5000 members from 14 countries. During the period from January 2023 to January 2024, we received 417 enquiries about snakes and scorpions belonging to 11 families and composed of 55 species. In addition, 53 other enquiries covered a range of organisms and their tracks (e.g., spiders, skinks, chameleons, foxes, sun spiders, centipedes, lizards, moth larvae, and insect tracks). The first photographic evidence of Malpolon monspessulanus in Sudan was via the group activities. The rare species Telescopus gezirae, the Blue Nile cat snake, is also documented via the group member\'s queries. Recognizing the evolving nature of social media use in public health, we also address the current limitations and evidence gaps that need to be addressed to effectively translate best practices into policy.
    CONCLUSIONS: In conclusion, utilizing Facebook as an institutional platform to share scientific information in simple Arabic language underscores the proactive roles that citizens, scientists, and public health stakeholders can play in leveraging social media for eHealth, eAwareness, and public health initiatives. This approach highlights the potential for collaborative efforts, particularly during crises, to maximize the benefits of social media in advancing public health.
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  • 文章类型: Journal Article
    世界范围内都有寡妇蜘蛛(Latrodectus属)叮咬中毒。疾病,被称为拉丁主义,会导致严重和持续的疼痛,并导致肌肉僵硬,呼吸系统并发症,还有心脏问题.这是一个全球性的健康挑战,尤其是在发展中国家。马血清来源的多克隆抗血清是市售的,可作为治疗latrodness患者的药物。但是血清的使用会带来与其动物来源相关的潜在固有风险。治疗可能会引起人类的过敏反应(血清病),包括过敏性休克.此外,观察到马来源的抗蛇毒血清具有批次间的变异性和较差的特异性,因为它总是一个不确定的混合抗体。因为latrodotism可能非常痛苦,但很少致命,抗蛇毒血清的使用是有争议的,只有一小部分患者得到治疗.在这项工作中,通过噬菌体展示从原始抗体基因库中选择针对欧洲黑寡妇(Latrodectustedecimguttatus)的α-latrotoxin的重组人抗体。将结合α-Latrotoxin(α-LTX)的scFv重新克隆并产生为完全人IgG。开发了一种用于毒液中和的新型alamarBlue测定法,并用于选择中和IgG。人抗体显示出作为单一抗体和抗体组合的体外中和功效。这也通过细胞培养物中神经元活性的电生理测量得到证实。最佳的中和抗体显示纳摩尔亲和力。抗体MRU44-4-A1显示出出色的中和功效和对雷氏乳杆菌α-LTX的亲和力。有趣的是,只有两种中和抗体显示南黑寡妇(Latrodectusmactans)的毒液交叉中和。这是出乎意料的,因为在目前的文献中,α-拉特毒素被描述为高度保守。这里设计的抗体是未来发展的候选药物,作为潜在的治疗和诊断工具,因为他们将首次提供无限制供应的化学上完全定义的具有恒定质量和功效的药物,它也是在不使用动物的情况下制作的。
    Poisoning by widow-spider (genus Latrodectus) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity, respiratory complications, and cardiac problems. It is a global health challenge especially in developing countries. Equine serum-derived polyclonal anti-sera are commercially available as a medication for patients with latrodectism, but the use of sera imposes potential inherent risks related to its animal origin. The treatment may cause allergic reactions in humans (serum sickness), including anaphylactic shock. Furthermore, equine-derived antivenom is observed to have batch-to-batch variability and poor specificity, as it is always an undefined mix of antibodies. Because latrodectism can be extremely painful but is rarely fatal, the use of antivenom is controversial and only a small fraction of patients is treated. In this work, recombinant human antibodies were selected against alpha-latrotoxin of the European black widow (Latrodectus tredecimguttatus) by phage display from a naïve antibody gene library. Alpha-Latrotoxin (α-LTX) binding scFv were recloned and produced as fully human IgG. A novel alamarBlue assay for venom neutralization was developed and used to select neutralizing IgGs. The human antibodies showed in vitro neutralization efficacy both as single antibodies and antibody combinations. This was also confirmed by electrophysiological measurements of neuronal activity in cell culture. The best neutralizing antibodies showed nanomolar affinities. Antibody MRU44-4-A1 showed outstanding neutralization efficacy and affinity to L. tredecimguttatus α-LTX. Interestingly, only two of the neutralizing antibodies showed cross-neutralization of the venom of the Southern black widow (Latrodectus mactans). This was unexpected, because in the current literature the alpha-latrotoxins are described as highly conserved. The here-engineered antibodies are candidates for future development as potential therapeutics and diagnostic tools, as they for the first time would provide unlimited supply of a chemically completely defined drug of constant quality and efficacy, which is also made without the use of animals.
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