Conotoxins That Could Provide Analgesia through Voltage Gated Sodium Channel Inhibition

Chronic pain creates a large socio-economic burden around the world. It is physically and mentally debilitating, and many sufferers are unresponsive to current therapeutics. Many drugs that provide pain relief have adverse side effects and addiction liabilities. Therefore, a great need has risen for alternative treatment strategies. One rich source of potential analgesic compounds that has emerged over the past few decades are conotoxins. These toxins are extremely diverse and display selective activity at ion channels. Voltage gated sodium (Na_V) channels are one such group of ion channels that play a significant role in multiple pain pathways. This review will explore the literature around conotoxins that bind Na_V channels and determine their analgesic potential.     

A型肉毒毒素注射治疗眉间纹的高频超声研究

【摘要】 目的 研究A型肉毒毒素治疗眉间纹引起的皮肤及其下肌层的厚度改变。方法 收集北京协和医院2017年8月至2018年2月注射A型肉毒毒素治疗的26例中重度眉间纹受试者，于注射前及注射后4周、16周，采用50 MHz高频超声检测注射部位皮肤的真皮层厚度，20 MHz高频超声检测皮肤全层和肌层厚度。采用单组重复测量资料的方差分析、配对t检验及Bonferroni法比较受试者注射治疗前后3个时间点超声检测的组织厚度。结果 注射前，真皮层、皮肤全层和肌层厚度分别为（2.01 ± 0.48）、（4.32 ± 0.73）、（4.51 ± 0.67） mm。注射前、注射后4及16周真皮层厚度差异无统计学意义（F = 1.94，P = 0.199），而皮肤全层厚度、肌层厚度差异均有统计学意义（F = 6.28、24.19，P = 0.020、 < 0.001）。与注射前相比，注射后4周皮肤全层厚度显著增加（4.88 ± 0.93 mm，t = 3.72，P = 0.004），而肌层厚度显著降低（3.82 ± 0.79 mm，t = 4.65，P = 0.001）。与注射前和注射后4周相比，注射后16周时皮肤全层厚度（4.61 ± 0.73 mm）和肌层厚度（4.38 ± 0.90 mm）差异均无统计学意义（均P > 0.0167）。结论 注射A型肉毒毒素可改变皮下组织和肌层厚度，高频超声可用于A型肉毒毒素注射治疗眉间纹的疗效评价及随访。     

Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra)

The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A₂, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A₂, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6–27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A₂ are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms.     

卒中后肢体痉挛治疗的研究进展

痉挛是卒中后常见的并发症之一，严重的肢体痉挛不仅会导致关节活动度的受限、灵活性 和姿势的异常，还可引起不可逆的关节挛缩、肢体功能丧失及残疾，极大地影响着患者的生活质量， 并增加照护者的负担。目前对卒中后肢体痉挛的治疗方案仍未达成共识。近年来，痉挛治疗的药物 和非药物研究也有了一定的进展，尤其是非药物治疗手段，如采用非侵入性经颅或外周电、磁刺激技 术以及基于肌动图和肌电图的多源信息采集整合分析技术等新型康复治疗手段，在痉挛治疗过程中 表现出更加精准、有效以及可重复性高等优点。现就卒中后肢体痉挛治疗的研究进展进行综述。     

肉毒毒素注射引起的不良反应

肉毒毒素注射引起的不良反应,是药物本身的组成成分引起的与用药目的无关的有害反应,与医生注射方式和注射技术无关。尽管肉毒毒素生产厂家的药品说明书上也有提示,但其所提供的信息不够全面,也未必能引起医生的足够重视。目前文献上多为散发病例。为此作者对过去20年有关肉毒毒素注射引起的过敏反应、肉瘤样肉芽肿、眼睑水肿、流感样症状等相关不良反应的临床表现、发病机制与治疗方法进行综述。