Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury

Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.     

我国首例由丁酸梭菌引起婴儿E型肉毒中毒实验室诊断研究

目的对一起疑似婴儿肉毒中毒进行实验室诊断研究。方法对1例疑似婴儿肉毒中毒病例的粪便、食用过的食品和生活环境涂抹共计30份标本/样品进行梭菌分离鉴定及肉毒毒素检测,对分离菌株进行产毒试验。结果将患儿粪便标本培养物上清液腹腔注射小鼠后可致小鼠出现典型肉毒毒素中毒表现(竖毛、呼吸困难并出现典型的蜂腰、四肢麻痹),继而死亡,且培养物上清液经胰酶处理后毒性增强,表现为小鼠出现中毒及死亡时间较未处理组明显缩短。但培养物上清液经100℃加热处理后再次染毒动物,小鼠未出现中毒和死亡。混合型肉毒毒素诊断血清及单价抗E型肉毒毒素诊断血清可对小鼠起到保护作用。从患儿的粪便标本中分离到G~+芽胞杆菌,该菌在哥伦比亚血平板上呈不规则半透明扁平菌落,边缘根状生长,并携带E型肉毒毒素产毒基因,16S rRNA将其鉴定为丁酸梭菌,产毒试验结果显示该菌株可产E型肉毒毒素。结论该起婴儿中毒事件是由感染产E型肉毒毒素的丁酸梭菌引起。     

Improved bio-hydrogen production by overexpression of glucose-6-phosphate dehydrogenase and FeFe hydrogenase in Clostridium acetobutylicum

Clostridium acetobutylicum is an attractive industrial microorganism for biochemical production, but there have been few attempts for bio-hydrogen production based on metabolic engineering. In this study, metabolically engineered C. acetobutylicum carrying glucose-6-phosphate dehydrogenase (zwf) and FeFe hydrogenase (hydA) were constructed as recombinant strains CA-zwf(pIMP-zwf) and CA-hydA(pMTL-hydA), respectively, to improve hydrogen productivity. The results showed that the engineered strains produced 1.15 and 1.39-fold higher hydrogen yield, respectively, than the wild type. Furthermore, when pH and glucose concentration were optimized for the CA-hydA strain, enhanced hydrogen productivity of 25.8% was achieved in 7 L jar scale fermentation. This result provides an insight into the future direction for metabolic engineering of C. acetobutylicum for improved hydrogen production.     

外送餐引起产气荚膜梭菌食物中毒流行病学调查分析

目的查明发生在某工厂的食源性疾病暴发的可疑食品、致病因子及危险因素等,并对事件调查过程中暴露出的问题进行探讨,为今后类似事件的防控和调查提供参考依据。方法病例定义为于2019年3月3日～3月4日期间在M工厂加班职工中发生腹痛、腹泻(≥3次/24 h)或呕吐症状之一者,运用描述性和分析性流行病学方法开展病例访谈和回顾性研究。收集病例的粪便标本、剩余食品和相关环境样品进行病原分离和采用聚合酶链式反应(PCR)检测阳性菌株的毒素基因。结果检索到病例106名,罹患率为73.6%(106/144),临床症状以腹泻(78.3%,83/106)、腹痛(78.3%,83/106)为主,部分半腹部胀气、胀痛(9.4%,10/106),无发热;流行曲线为点源暴露模式,潜伏期为2～22 h,可疑餐次为2019年3月3日的午餐;单因素分析和Logistic回归分析结果显示,发病与红烧鱼块[相对危险度(RR)=1.55, 95%置信区间(95%CI):1.29～1.85]、蒜苗肉丝(RR=1.26, 95%CI:1.01～1.57)和雪菜烧鸭血(RR=1.47, 95%CI:1.16～1.87)有关;在3份肛拭子、3份环境样品中检出产气荚膜梭菌,菌株和2份剩余食品均检测出α毒素和产气荚膜梭菌肠毒素(CPE)基因。送餐的D企业在加工经营中存在着被细菌污染并繁殖的条件。结论本次事件是因食用某供餐企业提供的配送餐引起的产气荚膜梭菌食物中毒,外送餐做好后应迅速冷却、低温储存,不能立即进食的,在食前要充分加热。     

水中产气荚膜梭菌在不同过滤培养体系中的表型特征的研究

目的比较水中的产气荚膜梭菌在2种不同孔径滤膜和2种培养基上的计数结果,并探讨其机理。方法用0.22μm和0.45μm 2种不同孔径的滤膜过滤添加产气荚膜梭菌的矿泉水后,将滤膜贴在亚硫酸盐-多粘菌素-磺胺嘧啶琼脂培养基(sulfite-polymyxin-sulfadiazine agar,SPS)和胰胨-亚硫酸盐-环丝氨酸琼脂培养基(tryptose sulfite cycloserine agar,TSC)上,36℃±1℃厌氧培养24 h,观察菌落形态并进行菌落计数。用扫描电镜观察0.22μm和0.45μm2种滤膜表面的开口大小。结果水样经过2种不同孔径的滤膜过滤后,产气荚膜梭菌在TSC和SPS上的计数结果无显著性差异(P0.05)。但与SPS相比,产气荚膜梭菌在TSC上更易形成特征性黑色菌落;与孔径为0.22μm滤膜相比,在孔径为0.45μm滤膜上生长的菌落更大。电镜扫描发现,0.22μm滤膜和0.45μm滤膜的平均表面开口分别为2 5μm、4 0μm,后者的表面开口更大。结论水样通过0.45μm孔径滤膜过滤,贴在TSC琼脂上培养,更适用于矿泉水中产气荚膜梭菌的检验。     

Purified Butanol from Lignocellulose – Solvent-Impregnated Resins for an Integrated Selective Removal

In traditional microbial biobutanol production, the solvent must be recovered during fermentation process for a sufficient space-time yield. Thermal separation is not feasible due to the boiling point of n-butanol. As an integrated and selective solid-liquid separation alternative, solvent impregnated resins (SIRs) were applied. Two polymeric resins were evaluated and an extractant screening was conducted. Vacuum application with vapor collection in fixed-bed column as bioreactor bypass was successfully implemented as butanol desorption step. In course of further increasing process economics, fermentation with renewable lignocellulosic substrates was conducted using Clostridium acetobutylicum. Utilization of SIR was shown to be a potential strategy for solvent removal from fermentation broth, while application of a bypass column allows for product removal and recovery at once.     

ORP调控对葡萄糖和果糖混合底物丁醇发酵的影响

采用氧化还原电位(oxidoreduction potential,ORP)调控以模拟菊芋块茎酸解液(葡萄糖和果糖混合糖)为底物进行的丙酮丁醇发酵过程,能够有效控制"酸崩溃"现象的发生。已通过实验确定最佳调控策略为控制整个发酵过程的ORP不低于-460mV。本研究在最佳调控策略下,发酵终点丁醇浓度从3.39g/L提高到11.65g/L,残糖浓度从30.82g/L降低到1.38g/L。对比ORP调控组和对照组发现,ORP调控能够改变发酵过程中细胞内还原力水平,能量状态和代谢流向,因此ORP调控能有效防止"酸崩溃"现象发生,调节菌体生长和溶剂产量。ORP调控策略应用于以葡萄糖和果糖混合糖为底物的丁醇发酵具有操作可行性,是一种简便而有效的工艺优化手段。     

氧化还原电位调控混合糖为底物的丁醇发酵

控制丁醇发酵过程中的氧化还原电位（oxidoreduction potential, ORP）能够大幅提高丁醇产量和果糖利用率,并降低终点有机酸浓度。实验考察了以葡萄糖和果糖混合糖为底物,通过泵入无菌空气控制ORP分别不低于-490、-460、-430及-400 mV丁醇发酵情况。其中,控制ORP不低于-460 mV时,丁醇和总溶剂产量分别达到13.19 g·L^-1及19.71 g·L^-1,相对于不控制ORP的丁醇自然发酵分别提高了139.38%及117.07%,残糖浓度降低至3.20 g·L^-1,糖利用率高达94.18%。该调控策略有效地解决了以葡萄糖和果糖混合糖为底物的丁醇发酵过程中存在的残糖浓度高、丁醇产量低的问题。