Cold-induced anesthesia impairs path integration memory in dung beetles

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反毒为药：精准控制河鲀毒素用作局部麻醉药的新进展

钠离子通道阻断剂河鲀毒素(TTX)是致命的毒素之一,却是极具价值的神经生物学和生理学等生命科学研究领域的工具药.近年来,越来越多的研究指出,TTX具有强大的局部麻醉潜能,有望成为替代氨基酯类和氨基酰胺类局部麻醉药、避免阿片类药物滥用的新型麻醉药物.本文综述TTX局部麻醉应用的辅助药物、TTX缓释及控释给药系统等相关研究,旨在为局部麻醉新药研发提供参考并探讨新的思路.     

Genetic Manipulation of the Mouse Developing Hypothalamus through In utero Electroporation

Genetic modification of specific regions of the developing mammalian brain is a very powerful experimental approach. However, generating novel mouse mutants is often frustratingly slow. It has been shown that access to the mouse brain developing in utero with reasonable post-operatory survival is possible. Still, results with this procedure have been reported almost exclusively for the most superficial and easily accessible part of the developing brain, i.e. the cortex. The thalamus, a narrower and more medial region, has proven more difficult to target. Transfection into deeper nuclei, especially those of the hypothalamus, is perhaps the most challenging and therefore very few results have been reported. Here we demonstrate a procedure to target the entire hypothalamic neuroepithelium or part of it (hypothalamic regions) for transfection through electroporation. The keys to our approach are longer narcosis times, injection in the third ventricle, and appropriate kind and positioning of the electrodes. Additionally, we show results of targeting and subsequent histological analysis of the most recessed hypothalamic nucleus, the mammillary body.     

The discovery of potent and selective non-steroidal glucocorticoid receptor modulators,suitable for inhalation

We report the discovery of highly potent and selective non-steroidal glucocorticoid receptor modulators with PK properties suitable for inhalation. A high throughput screen of the AstraZeneca compound collection identified sulfonamide 3 as a potent non-steroidal glucocorticoid receptor ligand. Further optimization of this lead generated indazoles 30 and 48 that were progressed to characterization in in vivo models. X-ray crystallography was used to gain further insight into the binding mode of selected ligands.     

右美托咪定对老年恶性肿瘤全麻手术患者术后细胞免疫功能、认知功能及炎症因子水平的影响

目的:探讨右美托咪定对老年恶性肿瘤全麻手术患者术后细胞免疫功能、认知功能及炎症因子水平的影响。方法:选取2017年2月～2019年6月期间到我院择期行手术治疗的老年恶性肿瘤患者119例,根据随机数字表法将患者分为对照组(n=59)和研究组(n=60),研究组麻醉中输注右美托咪定,对照组麻醉中输注同容量等速率的生理盐水,比较两组患者围术期指标、细胞免疫功能、不良反应、炎症因子指标、简易智力状态量表(MMSE)评分。结果:两组患者术后第3 d的CD4~+/CD8~+、CD3~+、CD4~+较术前下降,CD8~+较术前升高(P0.05);研究组术后第3 d的CD4~+/CD8~+、CD3~+、CD4~+高于对照组,CD8~+则低于对照组(P0.05)。两组术后第3 d的血清高迁移率族蛋白1(HMGBl)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平均升高,但研究组低于对照组(P0.05)。两组手术时间、术中出血量、麻醉时间比较无差异(P0.05)。两组患者术前、术后第1 d、术后第3 d的MMSE评分呈先下降后升高趋势(P0.05),且研究组术后第1 d、第3 d的MMSE评分高于对照组(P0.05)。两组不良反应发生率比较无统计学差异(P0.05)。结论:老年恶性肿瘤全麻手术患者术中输注右美托咪定,可减轻细胞免疫抑制及炎症反应,对术后早期的认知功能下降有一定预防作用。     

非人灵长类个性化麻醉方案的探讨

目的 比较氯胺酮、舒泰、速眠新Ⅱ、戊巴比妥钠等4种全身麻醉药或其组合对非人灵长类的麻醉效果,探寻能替代或者减少氯胺酮使用的个性化麻醉方案。方法 以单独使用氯胺酮麻醉的方案作为对照,另设单独使用舒泰、氯胺酮复合速眠新Ⅱ、舒泰复合速眠新Ⅱ和戊巴比妥钠复合速眠新Ⅱ等麻醉4个实验组,每组选取5只食蟹猴进行实验,记录麻醉后的心率、体温、血氧饱和度、以及麻醉诱导时间和维持时间,以比较各方案的麻醉效果。结果 与单独使用氯胺酮麻醉比较,其他四种麻醉方案在心率、体温、血氧饱和度和麻醉诱导时间上均无显著性差异,不同方案麻醉维持时间分布在30~200min之间。在非人灵长类的全身麻醉中,舒泰可以很好地替代氯胺酮;氯胺酮复合速眠新Ⅱ麻醉可取得较长的麻醉维持时间,并减少氯胺酮的使用量;舒泰与速眠新Ⅱ联用、戊巴比妥钠与速眠新Ⅱ联用的方案也可替代氯胺酮,且麻醉维持时间较长。结论 在一定的麻醉时间内,联合用药可以降低氯胺酮的使用量,不同麻醉方案灵活运用可满足不同实验对麻醉维持时间的需求。     

硬膜外复合全麻对老年高血压患者腹部手术后并发症的影响

目的：探讨硬膜外复合全麻对老年高血压患者腹部手术后并发生的影响。方法：收集2013 年6 月-2015 年6 月在两家医院 接受腹部手术的老年高血压患者100 例,根据麻醉方法不同分为研究组和对照组。研究组患者给予硬膜外复合麻醉,对照组给予 全凭静脉麻醉。观察并比较两组患者的麻醉时间、药物用量以及术后并发症的发生率。结果：两组麻醉时间比较,差异无统计学意 义（P>0.05）;研究组麻醉药物用量低于对照组,差异具有统计学意义（P<0.05）;两组患者手术时间比较,差异无统计学意义（P>0. 05）;研究组患者术后苏醒时间、拔管时间以及住院时间均短于对照组,差异具有统计学意义（P<0.05）;研究组术后并发症的发生 率低于对照组,差异具有统计学意义（P<0.05）。结论：硬膜外复合全麻用于老年高血压患者腹部手术能够减少麻醉药物用量,降低 术后并发症的发生率,安全性较高。     

老年患者全身麻醉术后认知功能障碍的影响因素分析

目的：探讨分析老年非心脏手术患者全身麻醉术后认知功能障碍(POCD)的影响因素。方法：选择我院80 例老年行非心脏手 术患者,所有患者均给予全身麻醉手术,于术前及术后1、3 d 分别使用简易智能状态检查法（MMSE）评估患者认知功能,同时记 录行不同手术种类患者POCD 发生率并分析其年龄、麻醉时间、术中出血量、并发症情况及受教育程度等指标与POCD发生的相 关性。结果：80 例患者POCD发生率为30.0%,且不同种类手术中的发生率比较差异无统计学意义（P＞0.05）;POCD 组术后1d MMSE 评分为较术前分明显下降,比较差异具有统计学意义（P＜0.05);POCD组术后3 d及非POCD 组术后1、3 d MMSE 评分与 术前比较差异无统计学意义（P＞0.05）;Logistic 回归分析显示,患者年龄、文化程度、麻醉持续时间≥ 3 h、术中出血量≥ 350 mL及 合并高血压与POCD的发生具有显著相关性（P＜0.05）。结论：行全麻手术患者术后POCD 发病率较高,且患者高龄、文化程度 低、高血压合并症及麻醉持续时间长等是引起POCD发生的重要影响因素。     

Monitoring depth of anesthesia using combination of EEG measure and hemodynamic variables

Monitoring depth of anesthesia (DOA) via vital signs is a major ongoing challenge for anesthetists. A number of electroencephalogram (EEG)-based monitors such as the Bispectral (BIS) index have been proposed. However, anesthesia is related to central and autonomic nervous system functions whereas the EEG signal originates only from the central nervous system. This paper proposes an automated DOA detection system which consists of three steps. Initially, we introduce multiscale modified permutation entropy index which is robust in the characterization of the burst suppression pattern and combine multiscale information. This index quantifies the amount of complexity in EEG data and is computationally efficient, conceptually simple and artifact resistant. Then, autonomic nervous system activity is quantified with heart rate and mean arterial pressure which are easily acquired using routine monitoring machine. Finally, the extracted features are used as input to a linear discriminate analyzer (LDA). The method is validated with data obtained from 25 patients during the cardiac surgery requiring cardiopulmonary bypass. The experimental results indicate that an overall accuracy of 89.4 % can be obtained using combination of EEG measure and hemodynamic variables, together with LDA to classify the vital sign into awake, light, surgical and deep anesthetised states. The results demonstrate that the proposed method can estimate DOA more effectively than the commercial BIS index with a stronger artifact-resistance.     

Behavioral and electrophysiological analysis of general anesthesia in 3 background strains of Drosophila melanogaster

General anesthetics achieve behavioral unresponsiveness via a mechanism that is incompletely understood. The study of genetic model systems such as the fruit fly Drosophila melanogaster is crucial to advancing our understanding of how anesthetic drugs render animals unresponsive. Previous studies have shown that wild-type control strains differ significantly in their sensitivity to general anesthetics, which potentially introduces confounding factors for comparing genetic mutations placed on these wild-type backgrounds. Here, we examined a variety of behavioral and electrophysiological endpoints in Drosophila, in both adult and larval animals. We characterized these endpoints in 3 commonly used fly strains: wild-type Canton Special (CS), and 2 commonly used white-eyed strains, isoCJ1 and w¹¹¹⁸. We found that CS and isoCJ1 show remarkably similar sensitivity to isoflurane across a variety of behavioral and electrophysiological endpoints. In contrast, w¹¹¹⁸ is resistant to isoflurane compared to the other 2 strains at both the adult and larval stages. This resistance is however not reflected at the level of neurotransmitter release at the larval neuromuscular junction (NMJ). This suggests that the w¹¹¹⁸ strain harbors another mutation that produces isoflurane resistance, by acting on an arousal pathway that is most likely preserved between larval and adult brains. This mutation probably also affects sleep, as marked differences between isoCJ1 and w¹¹¹⁸ have also recently been found for behavioral responsiveness and sleep intensity measures.