盐酸右美托咪定对单肺通气患者炎症反应的影响

目的:探讨盐酸右美托咪定对实施食管癌根治术患者单肺通气时炎症反应的影响.方法:选择择期行食管癌根治术的42例患者,采用完全随机法分为盐酸右美托咪定组(D组)和对照组(C组),各21例.D组于麻醉诱导前10min经静脉输注盐酸右美托咪定1.0μg/kg,然后按0.5μg/(kg· h)的速率继续输注至术毕前30min;C组经静脉给予等容量生理盐水.分别于麻醉诱导前(T0)、单肺通气即刻(T1)、单肺通气开始30min(T2)、90min(T3)、双肺通气即刻(T4)和术毕(T5)时间点采用ELISA法检测患者血浆中TNF-α和IL-6的浓度,并测定中性粒细胞核蛋白NF-κB活性.结果:与C组相比,D组在T2～T5时刻血浆中TNF-α和IL-6的浓度和中性粒细胞核蛋白NF-κB活性均下降,差异有统计学意义(P＜0.05).结论:围手术期持续静脉输注盐酸右美托咪定可抑制食管癌根治术患者单肺通气时NF-κB活性,从而减轻炎症反应.     

右美托咪定对肢体缺血再灌注诱发肺损伤的影响

目的:评价右美托咪定对肢体缺血再灌注诱发肺损伤的影响。方法:择期行择期行下肢手术患者40例,性别不限,年龄40~65岁,体质量50~85 kg,ASA分级Ⅰ或Ⅱ级。采用随机数字表法,将其分为2组(n=20):对照组(C组)和右美托咪定组(D组)。麻醉诱导后气管插管,机械通气,采用静吸复合麻醉。麻醉诱导后,D组静脉输注右美托咪定1 μg·kg^-1(加入100 ml生理盐水),C组给予生理盐水,于止血带充气前滴注完毕。于麻醉诱导前(T₁)、止血带充气(T₂)、60 min(T₃)、90 min(T₄)时,止血带放气后5 min(T₅)、30 min(T₆)时采集桡动脉血样,行血气分析,计算氧合指数和呼吸指数。测定血浆白介素6(IL-6)、丙二醛(MDA)及细胞间黏附分子(ICAM-1)的浓度。结果:与C组相比,D组T_2~5时RI升高(P<0.05),而OI差异无统计学意义(P>0.05);D组T_2~6时血浆IL-6、MDA及ICAM-1的浓度降低(P<0.05)。结论:右美托咪定可减轻肢体缺血再灌注诱发的肺损伤,其机制与抑制炎性反应有关。     

右美托咪定对肢体缺血再灌注后患者肺换气的影响

目的:观察右美托咪定对上肢止血带诱发肢体缺血再灌注后肺换气的影响。方法:前臂或者手部需要止血带进行手术的患者40例,采用随机数字表法,将患者分成两组（n=20）:对照组（C组）,右美托咪定组（D组）。D组患者在完成肌间沟臂丛神经阻滞后静脉泵注右美托咪啶负荷剂量1μg/kg,持续10 min,随后以0.5μg·kg-¹·h^-1速率直到手术结束;C组患者相同方法静脉泵注等量生理盐水。待麻醉起效后上止血带,分别在上止血带即刻（T₀）、上止血带后1 h（T₁）、松止血带后0.5 h（T₂）、2 h（T₃）、6 h（T₄）和24 h（T₅）取动脉血进行血气分析和测定血浆超氧化物歧化酶（SOD）和丙二醛（MDA）浓度,记录动脉血二氧化碳分压（Pa CO₂）、动脉血氧分压（PaO₂）,按照公式计算肺泡动脉血氧分压差（PA-a DO₂）、呼吸指数（RI）和动脉血/肺泡氧分压比值（a/A比值）。结果:与T0比较,两组患者T4时Pa O2、a/A比值下降,PA-a DO₂、RI比值上升,D组上升幅度比C组大。与T0比较,C组T_3-5时血浆MDA浓度升高、SOD浓度降低,D组仅在T₄时血浆MDA浓度升高、SOD浓度降低,MDA浓度增加幅度明显低于C组,SOD浓度降低幅度明显低于C组。结论:右美托咪定改善肢体缺血再灌注后患者的肺换气功能,其可能的机制是右美托咪定可以增加体内氧自由基清除剂（SOD）从而减少体内脂质过氧化反应（MDA）,减少肢体缺血再灌注过程中脂质过氧化损伤。     

右美托咪定预处理对体外循环下室间隔修补术患儿炎性反应的影响

目的：探讨右美托咪定预处理对体外循环下室间隔修补患儿中炎性反应的影响。方法选取80例需要手术纠治的室间隔缺损患儿,随机分为两组（每组40例）,D组于气管插管后给予右美托咪定,先静脉给予负荷量0.5μg/kg,10min内泵注完毕,继以0.5μg/（kg·h）的速率泵注维持直至体外循环开始;C组则给等量的生理盐水。分别于麻醉诱导后(T0),体外循环结束后即刻(T1),体外循环后4h(T2),手术后12h(T3)经中心静脉抽血测定TNF-α、IL-6、IL-8、丙二醛(MDA)浓度和过氧化物岐化酶(SOD)活性以及CK-MB、cTnI值,并记录患儿术后临床指标。结果 T0时两组各项指标比较无统计学差异（P>0.05）;组内比较,在T1、T2、T3时D组和C组的TNF-α、IL-6、IL-8、MDA、CK-MB、cTnI较T0时增高,而SOD较T0时降低（P<0.05）;组间比较,D组的TNF-α、IL-6、IL-8、MDA、CK-MB、cTnI在 T1、T2、T3时较C组低,SOD较C组高（P<0.05）。结论右美托咪定预处理可以减轻婴幼儿体外循环中炎性反应,产生心肌保护作用。     

不同剂量右美托咪定对OSAHS腭咽成形术患儿苏醒期躁动及血流动力学的影响

目的:探讨不同剂量右美托咪定对阻塞性睡眠呼吸暂停低通气综合征(OSAHS)腭咽成形术患儿苏醒期躁动及血流动力学的影响。方法:选取2019年1月至2021年8月接受腭咽成形术治疗的100例OSAHS患儿,采用随机数表法分为A组(33例)、B组(33例)和C组(34例)。三组患儿均采用全身麻醉,于麻醉诱导前,A组给予0.2μg/kg右美托咪定,B组给予0.4μg/kg右美托咪定,C组给予0.6μg/kg右美托咪定。采用广义估计方程分析两组患儿入室时(T₀)、泵注10 min时(T₁)、拔管时(T₂)、苏醒时(T₃)的血流动力学[平均动脉压(MAP)、心率(HR)、血氧饱和度(SpO₂)]相关指标,比较三组患儿苏醒期相关情况。结果:基于广义估计方程分析,结果显示,T₁时三组患儿HR水平均较T₀时升高,但在T₂时回降,且趋于平稳,但三组患儿各时点之间比较差异无统计学意义(P>0.05);三组患儿MAP、SpO     

右美托咪定镇静复合罗哌卡因骶管阻滞用于新生儿会阴肛门成形术的效果

目的观察右美托咪定镇静复合罗哌卡因骶管阻滞用于新生儿会阴肛门成形术的效果。方法选取择期行会阴肛门成形术患儿80例,根据随机数字表法分为右美托咪定组(D组)和对照组(C组)。D组患儿给予负荷剂量右美托咪定1μg/kg(泵注时间大于10 min),Ramsay评分3～4分时左侧卧位下骶管穿刺注入0.2%罗哌卡因1 m L/kg,术中持续泵注右美托咪定0.2～1μg/(kg·h)维持Ramsay评分3～4分。C组患儿静脉麻醉诱导,气管插管成功后左侧卧位下骶管穿刺,成功后注入0.2%罗哌卡因1 m L//kg。记录2组患儿入手术室时(T₀)、手术开始时(T₁)、肛周固定时(T₂)、手术结束时(T₃)、出手术室时(T₄)心率、平均动脉压和血氧饱和度;记录麻醉时间、手术时间和苏醒时间、手术室内低氧血症发生情况,术中、苏醒期及麻醉复苏室(PACU)停留期间呼吸抑制、呼吸暂停、呛咳、喉痉挛、支气管痉挛及骶管阻滞相关并发症发生情况。结果与C组相比,D组T₁、T_2<...     

单核细胞趋化蛋白1和核因子-κB在右美托咪定注射下的兔脊柱结核免疫应答中的作用

目的 研究单核细胞趋化蛋白1(MCP-1)和核因子-κB(NF-κB)在右美托咪定注射下的兔脊柱结核免疫应答中的作用。方法 新西兰大白兔分成对照组、模型组(脊柱结核模型)、实验低剂量组(脊柱结核模型,2.5μg·kg^-1·h^-1右美托咪定治疗)、实验中剂量组(脊柱结核模型,5μg·kg^-1·h^-1右美托咪定治疗)、实验高剂量组(脊柱结核模型,10μg·kg^-1·h^-1右美托咪定治疗)、阳性组(脊柱结核模型,链霉素、利福平、异烟肼治疗)。用自动血沉分析仪检测红细胞沉降率,用流式细胞仪检测T淋巴细胞亚群,用酶联免疫吸附法检血清中C反应蛋白、MCP-1、肿瘤坏死因子-α(TNF-α)水平,用蛋白质印迹法检测病灶脊柱椎体中NF-κB p65、MCP-1蛋白表达。结果 对照组、模型组、实验低剂量组、实验中剂量组、实验高剂量组、阳性组C反应蛋白分别为(14.83±1.33),(135.10±11.27),(91.01±7.71),(70.47±7.67),(39.58...     

P13K-Akt-HIF-1α信号通路在右美托咪定减轻大鼠呼吸机相关性肺损伤中的作用

目的评价磷脂酰肌醇3-激酶-丝氨酸-苏氨酸蛋白激酶-缺氧诱导因子-1α(P13K-Akt-HIF-1α)信号通路在右美托咪定减轻大鼠呼吸机相关性肺损伤(VILI)中的作用。方法成年雄性SD大鼠60只,体重300~350g,分为4组,每组大鼠15只:对照组(C组)、机械通气组(V组)、机械通气+右美托咪定组(D组)和机械通气+右美托咪定+LY294002组(DL组)。D组和DL组经尾静脉输注右美托咪定负荷剂量1μg/kg(输注时间10min)后调整输注速率至0.5μg/(kg·h);DL组给予右美托咪定前静脉输注LY294002 0.3mg/kg,输注时间为5min。其余注射等容量的0.9%Na Cl。于机械通气前(T0)、机械通气结束时(T1)、机械通气后30min(T2)时采集动脉血样,检测动脉血气,测定呼吸指数(RI)和氧合指数(OI)后处死大鼠,取肺组织,ELISA法检测肺组织TNF-α、IL-6和IL-10的含量,肺组织湿/干重比(W/D)和Western blot法检测磷酸化Akt(P-Akt)和HIF-1α表达。结果与C组比较,其余三组肺组织TNF-α、IL-6、IL-10含量及W/D比升高,T1、T2时RI升高,OI降低,P-Akt表达下调和HIF-1α表达上调(P0.05);与V组比较,D组和DL组肺组织TNF-α、IL-6、IL-10含量升高,W/D比降低,T1、T2时RI升高,OI降低,P-Akt和HIF-1α表达上调(P0.05)。结论右美托咪定可能通过影响P13K-Akt-HIF-1α信号通路进而减轻大鼠呼吸机相关性肺损伤。     

右美托咪定对新辅助化疗后乳腺癌手术患者早期预后的影响

目的 评价右美托咪定对新辅助化疗后乳腺癌手术患者早期预后的影响。方法 将2022年3月～2023年6月在我院进行新辅助化疗后拟手术的40例乳腺癌患者分为对照组(C组)和右美托咪定组(D组),每组20例。两组患者采用相同麻醉方法,其中D组患者于麻醉诱导时外周静脉以0.5μg·kg^-1·h^-1泵注右美托咪定,手术结束前30min停药。分别在麻醉前(T1)、手术结束(T2)、术后第1天(T3)抽取血样,测量血浆肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-10、8-异前列腺素F₂α(8-iso-PGF_2α)的浓度及调节性T细胞(Treg)比例;术后第1、7天进行15项恢复质量(QoR-15)评分;记录术后患者胃肠道恢复时间、术后呕吐、首次补充镇痛时间。结果 两组患者血浆TNF-α、IL-10、8-isoPGF_2α及外周血Treg细胞含量在T2时升高,T3时回落,且T2、T3时与T1时同组内比较,均高于T1时;两组间比较,在T2、T3时D组均低于C组(P<0.05);D组术后...     

右美托咪定对食管癌手术中单肺通气肺损伤的影响

目的观察右美托咪定对食管癌手术单肺通气(OLV)肺损伤是否具有肺保护作用。方法选择40例择期行食管癌切除术的患者,按随机数字表法分为右美托咪定处理组(D组)和对照组(C组),每组20例。D组麻醉诱导前10min静脉输注右美托咪定1μg/kg,后恒速静脉输注0.5μg·kg-1·h-1至术毕前30min,C组采用同样方法静脉输注等容量0.9%氯化钠注射液。其余麻醉方案2组相同。分别于麻醉诱导后5min(T0),OLV开始后1h(T1)及2h(T2),OLV结束后1h(T3)及24h(T4),抽取桡动脉血,测定动脉血气计算呼吸指数(RI)、氧合指数(OI)及动脉肺泡氧分压比(PaO2)/(PAO2),并测定血清肺表面活性物质相关蛋白A(SP-A)浓度。结果 2组患者的性别、年龄、体质量、手术时间、OLV时间等差异无统计学意义(P>0.05)。与T0比较,T1、T2与T3时2组患者的肺功能指标水平皆明显降低(P<0.05),血清SP-A浓度明显升高(P<0.05),T4时恢复至术前水平(P>0.05);与C组比较,D组患者在T1与T2时的肺功能指标水平较高(P<0.05),血清SP-A浓度较低(P<0.05)。结论右美托咪定可减轻食管癌手术患者术后的肺氧合功能下降,减轻肺血管通透性增高和肺泡-毛细血管屏障损伤,对食管癌手术患者术后肺损伤的早期恢复具有积极作用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.