Neurotoxin

神经毒素
  • 文章类型: Journal Article
    破伤风是由破伤风梭菌神经毒素(TeNT)的作用引起的毒素性疾病,导致受感染的哺乳动物和鸟类部分或全身肌肉僵硬。由于猫对毒素的先天抵抗力,这种疾病很少在猫中报道。这项多中心回顾性研究旨在描述诊断为破伤风的大量猫并报告其信号。临床和神经体征,诊断结果,治疗,和结果。从2005年7月至2023年4月,对欧洲11个转诊中心的医疗记录进行了回顾性搜索,发现了27例猫破伤风病例。将这些病例与兽医文献中先前报道的病例进行了进一步比较。幼猫比老年猫更常见,平均年龄为4岁。临床体征最初以跛脚和/或僵硬的肢体为特征,靠近主要损伤部位,在17/26(65%)猫中。这项研究的21/27(78%)猫的症状是局灶性或多灶性的,一个典型的症状是无法弯曲受影响最严重的四肢。电诊断研究揭示了特征性变化,例如激动剂和拮抗剂肌肉的连续自发运动单位放电。此类研究在局灶性和多灶性病例中特别有用,应进行以进一步支持诊断。在一种情况下,使用小鼠生物测定法成功鉴定了毒素。在大多数情况下,治疗包括抗生素治疗(甲硝唑),肌肉松弛剂,适当的护理和潜在并发症的处理。总的来说,结果似乎是积极的,只有1/27(3.7%)的猫由于经济限制而被安乐死。23/25(92%)的猫在25天的中位延迟内恢复了所有肢体的独立行走能力。据报道,八只猫(30%)有轻度至中度的长期后遗症。这项多中心研究是第一个将如此大量的破伤风猫聚集在一起的研究。这种疾病在猫中的表现与在人类和狗中观察到的不同,大多数猫在当地受到影响。与以往的破伤风报道相比,这一系列猫总体上有更好的结果,特别是对于患有全身破伤风的猫。
    Tetanus is a toxigenic illness caused by the action of Clostridium tetani neurotoxin (TeNT), which results in partial or generalized muscle stiffness in infected mammals and birds. The disease is rarely reported in cats due to their innate resistance to the toxin. This multicentric retrospective study aimed to describe a significant population of cats with a diagnosis of tetanus and report their signalment, clinical and neurological signs, diagnostic findings, treatment, and outcome. A retrospective search through medical records from 11 referral centers in Europe resulted in the identification of 27 cases of feline tetanus from July 2005 to April 2023. These cases were further compared with previously reported cases in the veterinary literature. Young cats were more commonly represented than older cats, with a median age of 4 years. Clinical signs were initially characterized by a lame and/or stiff limb, near the primary injury site, in 17/26 (65%) cats. Signs were focal or multifocal in 21/27 (78%) cats of this study and one typical sign was the inability to flex the most severely affected limbs. Electrodiagnostic studies revealed characteristic changes, such as continuous spontaneous motor unit discharges in both agonist and antagonist muscles. Such studies are particularly useful in focal and multifocal cases and should be performed to further support the diagnosis. The toxin was successfully identified in one case using the mouse bioassay. Treatment included antibiotherapy (metronidazole) in most cases, muscle relaxants, appropriate nursing cares and handling of potential complications. Overall, the outcome appeared to be positive, with only 1/27 (3.7%) cats being euthanized due to financial restrains. 23/25 (92%) cats returned to an independent ambulatory capacity on all limbs within a median delay of 25 days. Mild to moderate long-term sequelae were reported in eight (30%) cats. This multicentric study is the first to bring together such a large number of cats affected with tetanus. Presentation of the disease in cats differs from that observed in humans and dogs, with most cats being locally affected. Compared to previous reports of tetanus, this series of cats had a better outcome overall, especially for cats affected with generalized tetanus.
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  • 文章类型: Journal Article
    可注射神经毒素和填充剂是跨性别/非二元患者面部性别确认的潜在选择。然而,获取的最大障碍是成本/保险范围。
    本文的目的是评估《平价医疗法案》(ACA)白银计划和医疗补助政策涵盖性别确认可注射神经毒素和填充剂程序的程度。
    从2021年6月22日至8月15日对所有ACA白银计划和医疗补助政策进行了横断面研究。特定计划的承保范围证书,保险公司的临床保单,和医疗补助文件进行了评估。
    共审查了915项计划(864项ACA白银计划和所有51项医疗补助政策)。没有可能涵盖神经毒素。只有72个(71个ACA和1个医疗补助)可能覆盖的填充剂,特别是胶原蛋白注射和脂肪填充。覆盖范围需要证明医疗必要性或与患者经验性别的身体外观有明显差异。然而,在71个ACA计划中,69概述了化妆品的排除,可能会取消这种报道。
    数据来自2021年公开的在线信息。此外,我们无法与保险公司确认这些程序的明确承保范围。
    大多数ACA白银和医疗补助计划没有涵盖性别确认神经毒素或填充程序,限制获得这种确认性别的护理。
    UNASSIGNED: Injectable neurotoxins and fillers are potential options for facial gender affirmation for transgender/nonbinary patients. However, the largest barrier to access is cost/insurance coverage.
    UNASSIGNED: The purpose of this article is to assess the extent to which Affordable Care Act (ACA) silver plans and Medicaid policies cover gender-affirming injectable neurotoxin and filler procedures.
    UNASSIGNED: A cross-sectional study of all ACA silver plans and Medicaid policies was performed from June 22 to August 15, 2021. Plan-specific certificates of coverage, clinical policies of insurance providers, and Medicaid documents were evaluated.
    UNASSIGNED: A total of 915 plans were reviewed (864 ACA silver plans and all 51 Medicaid policies). None potentially covered neurotoxins. Only 72 (71 ACA and 1 Medicaid) potentially covered fillers, specifically collagen injections and lipofilling. Coverage required demonstration of medical necessity or significant variation of physical appearance from the patient\'s experienced gender. However, of the 71 ACA plans, 69 outlined cosmetic exclusions, possibly nullifying this coverage.
    UNASSIGNED: Data were sourced from publicly available online information in 2021. Additionally, we were unable to confirm explicit coverage of these procedures with insurance companies.
    UNASSIGNED: The majority of ACA silver and Medicaid plans did not cover gender-affirming neurotoxin or filler procedures, limiting access to this gender-affirming care.
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  • 文章类型: Randomized Controlled Trial
    背景:经皮乳腺切除术在变性人中越来越受欢迎。然而,术后伤疤是不可避免的后果。最近,肉毒杆菌神经毒素A(BoNT-A)在预防疤痕方面显示出积极作用。这项研究的目的是研究BoNT-A在预防瘢痕方面的有效性。
    方法:纳入了15例接受皮下乳房切除术的患者。手术后14天,将incoBoNT-A或安慰剂注射到每一侧的疤痕中。主要结果评估使用温哥华疤痕量表(VSS)和患者和观察者疤痕评估量表(POSAS)测量疤痕的严重程度。次要结果评估使用标准测量设备评估疤痕的颜色。进行结果评估直至手术后6个月。
    结果:在研究结束时,BoNT-A组的VSS评分明显低于安慰剂组(7.43±0.26vs.8.82±0.26,p<0.001)。客观评估显示,在3个月和6个月时,与安慰剂相比,BoNT-A组的发红值在统计学上显著降低。
    结论:BoNT-A通过降低术后瘢痕形成的严重程度和改善整体瘢痕外观,在预防瘢痕方面已证明有效。
    Subcutaneous mastectomies in transmen have been gaining popularity. However, post-operative scars are an inevitable consequence. Recently, Botulinum neurotoxin A (BoNT-A) has shown positive effects in scar prevention. The objective of this study is to investigate the effectiveness of BoNT-A in scar prevention.
    Fifteen patients who had undergone subcutaneous mastectomy were included. At 14 days post-surgery, either incoBoNT-A or a placebo was injected into the scar on each side. The primary outcome assessment measured the scar\'s severity using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The secondary outcome assessment evaluated the scar\'s color using a standard measurement device. Outcome assessments were conducted until 6 months post-surgery.
    There were significantly lower VSS scores in the BoNT-A group compared to the placebo at the end of the study (7.43 ± 0.26 vs. 8.82 ± 0.26, p < 0.001). The objective assessment revealed a statistically significant decrease in redness values in the BoNT-A group compared to the placebo at 3 and 6 months.
    BoNT-A has demonstrated effectiveness in scar prevention by reducing the severity of postoperative scar formation and improving overall scar appearance.
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  • 文章类型: Journal Article
    Domoicacid(DA)是一种由假硝化硅藻产生的天然存在的海洋神经毒素。成年加州海狮(Zalophuscalifornianus)可以经历多种暴露后综合征,包括急性中毒和慢性癫痫。此外,建议在子宫内暴露的加利福尼亚海狮(CSL)出现延迟发作的癫痫综合征。此简短报告探讨了一例CSL发展为成年发作性癫痫并伴有进行性海马神经病理学。相对于脑大小的初始脑磁共振成像(MRI)和海马体积分析是正常的。大约7年后,评估新发展的癫痫综合征的MRI研究显示单侧海马萎缩。虽然不能完全排除单侧海马萎缩的其他原因,该病例可能是CSL中成人发作的癫痫样DA中毒的体内证据.通过估计子宫内DA暴露时间,从对实验室物种的研究中推断出来,该病例为子宫内暴露与成人发病疾病相关的神经发育解释提供了间接证据.妊娠暴露于自然发生的DA的继发疾病发展延迟的证据对海洋哺乳动物医学和公共卫生具有广泛的意义。
    Domoic acid (DA) is a naturally occurring marine neurotoxin produced by Pseudo-nitzschia diatoms. Adult California sea lions (Zalophus californianus) can experience multiple post-exposure syndromes, including acute toxicosis and chronic epilepsy. Additionally, a delayed-onset epileptic syndrome is proposed for California sea lions (CSL) exposed in utero. This brief report explores a case of a CSL developing adult-onset epilepsy with progressive hippocampal neuropathology. Initial brain magnetic resonance imaging (MRI) and hippocampal volumetric analyses relative to brain size were normal. Approximately 7 years later, MRI studies to evaluate a newly developed epileptic syndrome demonstrated unilateral hippocampal atrophy. While other causes of unilateral hippocampal atrophy cannot be completely excluded, this case may represent in vivo evidence of adult-onset epileptiform DA toxicosis in a CSL. By estimating in utero DA exposure time period, and extrapolating from studies conducted on laboratory species, this case provides circumstantial evidence for a neurodevelopmental explanation correlating in utero exposure to adult-onset disease. Evidence of delayed disease development secondary to gestational exposure to naturally occurring DA has broad implications for marine mammal medicine and public health.
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  • 文章类型: Journal Article
    肉毒杆菌毒素A(IncoBoNT-A)可有效预防紫外线B(UVB)诱导的色素沉着过度。这个未来,随机化,对照研究旨在评估IncoBoNT-A对15名志愿者UVB诱导的色素沉着的治疗效果。基线时,腹部局部UVB诱发了五个色素沉着过度正方形(2×2cm)。在第7天,每个部位随机接受不治疗(对照),生理盐水,或以1:2.5、1:5和1:7.5稀释度(12、6和4个单位,分别)。平均亮度指数(L*),由盲症皮肤科医生评估的色素沉着过度改善评分,在第21、28和35天获得参与者满意度评分。在第21天,平均L*改善为1:2.5、1:5和1:7.5IncoBoNT-A处理,盐水处理,控制地点为14.30%,12.28%,6.62%,0.32%,4.98%,分别(p=0.86)。在第28天,IncoBoNT-A治疗组的平均L*改善优于其他组。在色素沉着过度改善评分方面,与其他部位相比,12名参与者(80%)使用IncoBoNT-A注射部位的结果更好。IncoBoNT-A,特别是在较高的浓度下,对治疗UVB引起的色素沉着有一定的积极作用。这可以作为UVB加重的色素沉着症的辅助治疗。
    Incobotulinum toxin A (IncoBoNT-A) is effective in preventing ultraviolet B (UVB)-induced hyperpigmentation. This prospective, randomized, controlled study aimed to evaluate the effect of IncoBoNT-A on the treatment of UVB-induced hyperpigmentation in 15 volunteers. Five hyperpigmentation squares (2 × 2 cm) were induced by local UVB on the abdomen at baseline. At Day 7, each site was randomized to receive no treatment (control), normal saline, or intradermal IncoBoNT-A injection with 1:2.5, 1:5, and 1:7.5 dilutions (12, 6, and 4 units, respectively). The mean lightness index (L*), hyperpigmentation improvement score evaluated by blinded dermatologists, and participant satisfaction scores were obtained at Days 21, 28, and 35. At Day 21, improvements in mean L* of 1:2.5, 1:5, and 1:7.5 IncoBoNT-A-treated, saline-treated, and control sites were 14.30%, 12.28%, 6.62%, 0.32%, and 4.98%, respectively (p = 0.86). At Day 28, the improvement in mean L* in IncoBoNT-A-treated groups was superior to that in the other groups. In terms of the hyperpigmentation improvement score, 12 participants (80%) experienced better outcomes with the IncoBoNT-A-injected site compared with the other sites. IncoBoNT-A, especially at higher concentrations, showed some positive effects on the treatment of UVB-induced hyperpigmentation. This may serve as an adjuvant treatment for hyperpigmentary conditions that are aggravated by UVB.
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  • 文章类型: Journal Article
    抑郁症可能是非运动症状,一个风险因素,甚至是帕金森病(PD)的合并症。无论哪种情况,抑郁症严重影响PD患者的生活质量。不幸的是,目前,大量的临床和基础研究集中在PD的病理生理机制和运动症状的预防和治疗上。尽管人们越来越关注与PD相关的抑郁症,很难做到早期发现和早期干预,因为临床指南主要是指在运动障碍后或伴有运动障碍后出现的抑郁症。为什么会有这样的困境?这是因为没有合适的临床前动物模型来研究抑郁症与PD之间的关系,在PD临床前模型中评估抑郁行为也是一项非常具有挑战性的任务,因为它并非没有运动障碍的混杂因素。作为模拟PD症状的常用方法,神经毒素诱导的PD模型已被广泛使用。研究发现,神经毒素诱导的PD模型动物可以表现出抑郁样行为,有时比运动障碍更早表现出来。因此,已经尝试通过神经毒素诱导建立PD相关抑郁模型.然而,由于缺乏统一的协议,报告的结果多种多样.为了进一步促进动物模型的改进和优化以及PD相关抑郁症的研究,我们根据现有文献和我们自己的研究经验,回顾了目前PD相关抑郁动物模型的建立和评估策略,并讨论了可能的机制和干预措施,以期为今后这方面的研究提供参考。
    Depression can be a non-motor symptom, a risk factor, and even a co-morbidity of Parkinson\'s disease (PD). In either case, depression seriously affects the quality of life of PD patients. Unfortunately, at present, a large number of clinical and basic studies focused on the pathophysiological mechanism of PD and the prevention and treatment of motor symptoms. Although there has been increasing attention to PD-related depression, it is difficult to achieve early detection and early intervention, because the clinical guidelines mostly refer to depression developed after or accompanied by motor impairments. Why is there such a dilemma? This is because there has been no suitable preclinical animal model for studying the relationship between depression and PD, and the assessment of depressive behavior in PD preclinical models is as well a very challenging task since it is not free from the confounding from the motor impairment. As a common method to simulate PD symptoms, neurotoxin-induced PD models have been widely used. Studies have found that neurotoxin-induced PD model animals could exhibit depression-like behaviors, which sometimes manifested earlier than motor impairments. Therefore, there have been attempts to establish the PD-related depression model by neurotoxin induction. However, due to a lack of unified protocol, the reported results were diverse. For the purpose of further promoting the improvement and optimization of the animal models and the study of PD-related depression, we reviewed the establishment and evaluation strategies of the current animal models of PD-related depression based on both the existing literature and our own research experience, and discussed the possible mechanism and interventions, in order to provide a reference for future research in this area.
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  • 文章类型: Journal Article
    Objective The aim of this study was to evaluate the effect of botulinum toxin A (BTX-A) injection on patients with chronic low back pain (CLBP). Design In this open-label prospective study, patients with CLBP who satisfied inclusion and exclusion criteria received 100 units of BTX-A injection. Patients were followed up at four weeks, three months, and six months after injection. Pain and function were assessed with visual analog scale (VAS), Roland-Morris Disability Scale (RMS), and Oswestry Disability Index (ODI) at baseline and subsequent visits. Results A total of 19 participants with a mean age of 41.11 years completed the study. Compared to baseline, a significant improvement in all scores was observed that persisted up to six months post-injection (P<0.001). Only two patients reported transient injection site pain that improved over two to three days without any treatment. Conclusion BTX-A injection is safe and improves pain and function in patients with resistant CLBP. The effects are more beneficial when the population is more homogenous in diagnosis and devoid of negative predictors for the outcome.
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  • 文章类型: Journal Article
    Scorpionism is responsible for most accidents involving venomous animals in Brazil, which leads to severe symptoms that can evolve to death. Scorpion venoms consist of complexes cocktails, including peptides, proteins, and non-protein compounds, making separation and purification procedures extremely difficult and time-consuming. Scorpion toxins target different biological systems and can be used in basic science, for clinical, and biotechnological applications. This study is the first to explore the venom content of the unexplored scorpion species Rhopalurus crassicauda, which inhabits exclusively the northernmost state of Brazil, named Roraima, and southern region of Guyana. Here, we pioneer the fractionation of the R. crassicauda venom and isolated and characterized a novel scorpion beta-neurotoxin, designated Rc1, and a monomeric hyaluronidase. R. crassicauda venom and Rc1 (6,882 Da) demonstrated pro-inflammatory activities in vitro and a nociceptive response in vivo. Moreover, Rc1 toxin showed specificity for activating Nav1.4, Nav1.6, and BgNav1 voltage-gated ion channels. This study also represents a new perspective for the treatment of envenomings in Roraima, since the Brazilian scorpion and arachnid antivenoms were not able to recognize R. crassicauda venom and its fractions (with exception of hyaluronidase). Our work provides useful insights for the first understanding of the painful sting and pro-inflammatory effects associated with R. crassicauda envenomings.
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  • 文章类型: Journal Article
    产生震颤的神经毒素的组织水平升高,Harmane,已在美国和西班牙的特发性震颤(ET)患者中检测到。最近,在法罗群岛进行的一项研究同样指出,在可能和确定的ET病例中,血液中的harmane浓度升高。潜在的机制尚不清楚。可能的机制包括增加饮食消费(尤其是。通过煮熟的肉类),新陈代谢受损,或增加哈曼的内生产量。为了进一步调查这个问题,我们在法罗群岛进行了一项基于人群的研究,以检查ET病例和对照中的肉类消费和肉类烹饪习惯.
    对1,328名法罗群岛成年人进行了震颤筛查,确定了27例ET病例。将肉类消费和肉类烹饪实践与200个对照进行了比较。通过问卷调查收集了有关14种肉类的当前肉类消费量和8种肉类的肉类烹饪熟度的详细数据。也有关于血液中harmane浓度的数据。
    在14种肉类中,有12种在ET病例和对照中目前的肉类消费量相似,在任何肉类类型中进行Bonferroni校正后没有观察到差异;按性别分层时没有观察到差异。ET病例和对照组之间的肉熟度没有差异。血harmane浓度与饮食数据无关。
    这是第一个基于人群的关于ET中与harmane相关的饮食因素的研究。研究表明,在ET中观察到的血harmane差异不是由饮食差异驱动的,并且可能是由于其他机制(例如,新陈代谢受损)。
    Elevated tissue levels of the tremor-producing neurotoxin, harmane, have been detected in patients with essential tremor (ET) in the USA and Spain. Recently, a study in the Faroe Islands similarly noted an elevation in blood harmane concentrations in probable and definite ET cases. The underlying mechanism is not understood. Possible mechanisms include increased dietary consumption (esp. through cooked meats), impaired metabolism, or increased endogenous production of harmane. To investigate this issue further, we conducted a population-based study in the Faroe Islands to examine meat consumption and meat cooking practices in ET cases and controls.
    1,328 Faroese adults were screened for tremor and 27 ET cases were identified. Meat consumption and meat cooking practices were compared to 200 controls. Detailed data were collected via questionnaires regarding current meat consumption for 14 meat types and meat cooking doneness for 8 meat types. Data were also available on blood harmane concentrations.
    Current meat consumption was similar in ET cases and controls in 12 out of 14 meat types, with no differences observed after a Bonferroni correction in any meat type; no difference was observed when stratified by gender. No difference was observed in meat doneness between ET cases and controls. Blood harmane concentrations were not correlated with dietary data.
    This is the first population-based study of harmane-linked dietary factors in ET. The study suggests the observed difference in blood harmane in ET is not driven by dietary differences and is likely due to other mechanisms (e.g., impaired metabolism).
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  • 文章类型: Journal Article
    原发性震颤(ET)是最常见的神经系统疾病之一。它的环境决定因素知之甚少。Harmane(1-甲基-9H-吡啶并[3,4-b]吲哚),产生震颤的神经毒素,在纽约和马德里的一些研究中已经与ET联系在一起。水星,也是一种产生震颤的神经毒素,没有在ET中研究过。法罗群岛一直是许多神经系统疾病的流行病学调查的重点。
    在这个以人口为基础的,病例对照研究,我们直接测量了ET病例和对照组的血harmane浓度(HA)和血汞浓度(Hg)。
    总共,筛选了1,328名法罗群岛成年人;确定了26例ET病例,将其(HA)和(Hg)与197例对照进行了比较。
    尽管诊断组之间没有统计学上的显著差异,中位数(HA)比对照组(1.53g-10/mL)高2.7倍(4.13g-10/mL),可能的ET(2.28g-10/mL)高1.5倍。小样本量是一个限制。对于明确的ET与对照,p=0.126。(Hg)组间相似。
    我们证明了明确和可能的ET(HA)略有升高。这些数据与先前发表的数据相似,并可能将这种神经毒素和ET之间的病因联系扩展到第三地区。该研究不支持汞和ET之间的联系。
    Essential tremor (ET) is among the most prevalent neurological diseases. Its environmental determinants are poorly understood. Harmane (1-methyl-9H-pyrido[3, 4-b]indole), a dietary tremor-producing neurotoxin, has been linked to ET in a few studies in New York and Madrid. Mercury, also a tremor-producing neurotoxin, has not been studied in ET. The Faroe Islands have been the focus of epidemiological investigations of numerous neurological disorders.
    In this population-based, case-control study, we directly measured blood harmane concentrations (HA) and blood mercury concentrations (Hg) in ET cases and controls.
    In total, 1,328 Faroese adults were screened; 26 ET cases were identified whose (HA) and (Hg) were compared to 197 controls.
    Although there were no statistically significant differences between diagnostic groups, median (HA) was 2.7× higher in definite ET (4.13 g-10/mL) and 1.5× higher in probable ET (2.28 g-10/mL) than controls (1.53 g-10/mL). Small sample size was a limitation. For definite ET versus controls, p = 0.126. (Hg) were similar between groups.
    We demonstrated marginally elevated (HA) in definite and probable ET. These data are similar to those previously published and possibly extend etiological links between this neurotoxin and ET to a third locale. The study did not support a link between mercury and ET.
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