Oxime K074 – in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides

Abstract

Oxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074.     

Optical coherence tomography findings in patients with alcohol use disorder and their relationship with clinical parameters

Abstract

Purpose: In our study, we aimed to investigate the ganglion cell-inner plexiform layer thickness (GCIPL), retinal nerve fibre layer thickness (RNFL), mean macular volume (MMV), central macular thickness (CMT), mean macular thickness (MMT), and choroidal thickness (CT) values with optical coherence tomography (OCT) in patients who are diagnosed with alcohol use disorder (AUD).

Materials and methods: The study included 43 patients who were diagnosed with AUD, and 43 healthy controls. Detailed biomicroscopic examinations of all the participants, visual acuity, intraocular pressure, anterior and posterior segment examinations, and then, OCT measurements were carried out.

Results: Although the measured values for RNFL in the superior and temporal quadrant are within normal limits, they were slightly higher compared to those in the control group (p values 0.127 and 0.191 for superior quadrant and temporal quadrant, respectively). The CT measurements in all quadrants were higher than the control group; however, these measurements were not statistically significant (p?>?0.05). When the relation between clinical features and OCT findings of the patients were examined, it was determined that the ages of the patients were statistically significantly and inversely correlated with the temporal CT and also the nasal and temporal quadrants of RNFL.

Conclusions: Our study is the first study that examines the retinal GCIPL and CT with OCT in patients who are diagnosed with AUD. In our results, it was determined that there were no statistically significant differences between the participants in terms of OCT parameters. Further studies with larger sampling groups evaluating neurotransmission findings may provide wider results.     

周围性面神经麻痹的针刺时机探析

周围性面神经麻痹是临床常见的多发病,在治疗上多采用针刺治疗,而针刺的时机异同,会直接影响病患的恢复效果。现代医学研究普遍认为,急性期面瘫,面神经炎症,多发生水肿,不应尽快针刺治疗;而针灸临床多数报道表明,早期给予针刺,能有效提高临床有效率。因此,对于针刺时机则需进一步加强其标准化。本文则主要通过对近几年文献的检索,探索最佳针刺时机在面神经麻痹中的临床应用。     

曲克芦丁脑蛋白水解物联合醒脑静治疗脑卒中的疗效

目的探讨曲克芦丁脑蛋白水解物联合醒脑静注射液治疗急性缺血性脑卒中的临床疗效。方法选取医院2016年6月—2018年10月收治的急性缺血性脑卒中患者96例,治疗方案不同分为观察组(n=48)和对照组(n=48),对照组采用曲克芦丁脑蛋白水解物治疗,观察组于对照组基础上采用醒脑静注射液治疗,疗程结束后,观察分析2组治疗效果,治疗前后神经缺损(NIHSS评分)、生活质量(SS-QOL评分)。结果观察组总有效率91.67%较对照组75.00%高(P<0.05),治疗后观察组SS-QOL评分较对照组高(P<0.05),观察组NIHSS评分较对照组低(P<0.05)。结论曲克芦丁脑蛋白水解物联合醒脑静注射液应用于急性缺血性脑卒中患者治疗中,疗效肯定,并可显著减轻神经缺损,提高生活质量。     

中西医联合治疗糖尿病周围神经病变效果观察

目的研究中西医联合治疗糖尿病周围神经病变患者的临床效果。方法按照随机数字表法将2017年7月-2018年6月期间本院收治的72例糖尿病周围神经病变患者分为两组,对照组36例采用常规西医治疗,观察组36例采用中西医联合治疗。将两组的神经传导速度、临床疗效、用药安全性进行比对。结果观察组糖尿病周围神经病变患者治疗后正中神经、尺神经的MNCV、SNCV均快于对照组,临床总有效率高于对照组,P<0.05;两组的不良反应发生率进行比较差异无统计学意义,P>0.05。结论中西医联合治疗糖尿病周围神经病变患者具有较高的有效性和安全性。     

中医康复护理对中风肢体功能障碍患者的疗效

目的分析脑卒中肢体功能障碍患者应用中医康复护理干预后,上下肢功能、生活品质以及神经功能损伤症状变化情况。方法选取本院2017年3月-2019年3月收治的160例脑卒中肢体功能障碍患者为研究对象,将其随机均分为采用传统康复护理的常规组,与采用中医康复护理的研究组。对比两组患者护理干预前后上下肢力指标、神经功能损伤评估分值以及生活品质评估分值。结果干预前,两组患者上、下肢肌力差异无统计学意义(P>0.05),干预后,两组患者上、下肢肌力全部明显增加,并且研究组增加幅度优于常规组,差异均具有统计学意义(P<0.05);干预后,研究组与常规组脑卒中患者神经功能缺损评分标准(CSS)评估分值均显著降低,且常规组降低幅度低于研究组;两组生活自理能力评估分值全部显著增加,且研究组提升幅度明显高于常规组,差异均具有统计学意义(P<0.05)。结论脑卒中肢体功能障碍患者应用中医康复护理干预,能够显著提高患者肢体肌肉能力以及生活品质,促进神经功能的修复。     

彩色超声引导下针刀治疗肩胛上神经卡压综合征临床疗效观察

目的:观察彩色超声引导下针刀治疗肩胛上神经卡压综合征的临床疗效。方法:选择本院治疗的肩胛上神经卡压综合征患者60例,随机分为观察组和对照组,每组30例。对照组给予小针刀松解治疗,观察组在彩色超声引导下给予小针刀松解治疗。结果:观察组有效率96.7%,对照组有效率86.7%,观察组高于对照组,差异有统计学意义(P<0.05);治疗1周后、1个月后随访,两组VAS评分均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05);治疗1周后、1个月后随访,两组Constant-Murley肩关节评分均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。结论:彩超引导下针刀局部松解治疗肩胛上神经卡压综合征,可减轻患者的疼痛,缩短肩关节活动功能恢复的时间。     

Heterologous fibrin sealant potentiates axonal regeneration after peripheral nerve injury with reduction in the number of suture points

The use of suture associated with heterologous fibrin sealant has been highlighted for reconstruction after peripheral nerve injury, having the advantage of being safe for clinical use. In this study we compared the use of this sealant associated with reduced number of stitches with conventional suture after ischiatic nerve injury. 36 Wistar rats were divided into 4 groups: Control (C), Denervated (D), ischiatic nerve neurotmesis (6 mm gap); Suture (S), epineural anastomosis after 7 days from neurotmesis, Suture + Fibrin Sealant (SFS), anastomosis with only one suture point associated with Fibrin Sealant. Catwalk, electromyography, ischiatic and tibial nerve, soleus muscle morphological and morphometric analyses were performed. The amplitude and latency values of the Suture and Suture + Fibrin Sealant groups were similar and indicative of nerve regeneration.The ischiatic nerve morphometric analysis in the Suture + Fibrin Sealant showed superior values related to axons and nerve fibers area and diameter when compared to Suture group. In the Suture and Suture + Fibrin Sealant groups, there was an increase in muscle weight and in fast fibers frequency, it was a decrease in the percentage of collagen compared to group Denervated and in the neuromuscular junctions, the synaptic boutons were reestablished.The results suggest a protective effect at the lesion site caused by the fibrin sealant use. The stitches reduction minimizes the trauma caused by the needle and it accelerates the surgical practice. So the heterologous fibrin sealant use in nerve reconstruction should be considered.