盐酸羟考酮与芬太尼分别复合丙泊酚对喉显微手术患者麻醉效果的比较

目的：比较盐酸羟考酮与芬太尼分别复合丙泊酚对喉显微手术的麻醉效果。方法：喉显微手术患者120例,年龄22～65岁,体重42～85 kg,ASA分级Ⅰ～Ⅱ级,随机均分2组（n=60例）。所有病人均采用全凭静脉麻醉。常规去氮给氧依次静注丙泊酚2.0 mg·kg^-1+芬太尼3.0 μg·kg^-1（F组）或丙泊酚2.0 mg·kg^-1盐酸羟考酮0.1 mg·kg^-1（O组）,以1.0 mL·s^-1的速率静脉推注芬太尼或盐酸羟考酮后,观察1 min内患者的呛咳反应,然后再给予米库氯胺2.0 mg·kg^-1,待肌松完全后行气管插管。记录入室前（T₀）、静注芬太尼或盐酸羟考酮后1 min（T₁）、插管后1 min（T₂）、插管后5 min（T₃）、拔管后3 min（T₄）,记录平均动脉压（MAP）、心率（HR）并采集静脉血用放免法检测皮质醇（Cor）、用高效液相色谱-电化学法测定去甲肾上腺素（NE）、用己糖激酶法测定血糖（Glu）,同时记录麻醉诱导时两组患者呛咳反应（FIC）发生率;麻醉苏醒和离开手术室时间及恶心呕吐、呛咳躁动、咽喉疼痛、呼吸抑制等不良反应发生率。结果：F组、O组在T₂、T₃、T₄时点NE、Cor、Glu、MAP、HR虽有所升高,但与T₀相比,差异无统计学意义（P＞0.05）;在T₁时点,F组MAP明显升高、HR明显加快,NE、Cor、Glu分泌水平也明显增加,O组T₀与T₁时点相比,差异有明显的统计学意义（P＜0.05）;F组患者FIC的发生率18例（30%）明显高于O组的0例（P＜0.05）;术后呼吸抑制F组发生率6例（10%）明显高于O组的1例（1.7%）（P＜0.05）;恶心、呕吐发生率F组10例（16.7%）明显高于O组的2例（3.3%）（P＜0.05）;两组清醒时间、离开手术室时间差异无统计学意义;两组咽喉疼痛、苏醒期呛咳躁动等不良反应发生率差异无统计学意义（P＞0.05）。结论：盐酸羟考酮（0.1 mg·kg^-1）作为全麻诱导辅助药可以增强心血管稳定性、降低围手术期的应激反应,避免FIC的发生,降低了不良反应的发生。     

间硝苯地平在Beagle犬体内的药代动力学

目的用反相高效液相色谱法研究间硝苯地平(m-nifedipine，m-Nif)在Beagle犬体内的药代动力学特征。方法正交设计优化色谱分离条件，Beagle犬分别iv给予m-Nif 0.288 mg·kg^-1和ig m-Nif 1.152，3.456，10.370 mg·kg^-1。用反相高效液相色谱法分析血浆中原型药物浓度，血浆药物浓度-时间数据用3P97药代动力学软件分析。结果Beagle犬iv m-Nif，其体内过程符合二室模型，T_1/2β为116.8 min；ig给予m-Nif 后在Beagle犬体内的代谢符合一室模型，其中低剂量(1.152 mg·kg^-1)组C_max为20 μg·L^-1， T_1/2(k_e)为147 min；中剂量(3.456 mg·kg^-1)组C_max为36 μg·L^-1，T_1/2(k_e) 为122 min；高剂量(10.37 mg·kg^-1)组C_max为69 μg·L^-1，T_1/2(k_e)为144 min。结论Beagle犬ig和iv m-Nif 后，血浆中药物消除迅速，口服绝对生物利用度较低。     

溴泰君(W198)在大鼠和比格狗体内的药代动力学

目的研究溴泰君(W198)在大鼠和比格狗的药代动力学。方法采用HPLC紫外检测方法测定大鼠及比格狗注射W198后血清药物浓度。结果大鼠iv W198 10,20和40 mg·kg^-1 3个剂量的T_1/2β分别为6.60,7.36和6.77 h,AUC_0-24h分别为3.797,7.371和15.192 mg·h·L^-1,V_d分别为7.14,4.33和4.13 L·kg^-1,CL分别为2.83,2.60和2.71 L·(kg·h)^-1。大鼠im W198 20 mg·kg^-1后T_1/2β为11.61 h,AUC_0-24h为4.191 mg·h·L^-1,im的生物利用度为56.9%。比格狗iv W198 5 mg·kg^-1,T_1/2β为11.72 h,AUC_0-24h为12.646 mg·h·L^-1,V_d为0.70 L·kg^-1,CL为0.46 L·(kg·h)^-1。W198与人血浆蛋白的结合率平均为78.0%。结论W198 im的T_1/2β比iv的略长,其生物利用度为56.9%。在10～40 mg·kg^-1剂量内的吸收呈现一级动力学特征。     

雷公藤内酯醇在Beagle犬体内的药代动力学

雷公藤内酯醇(triptolide，TP)是雷公藤的主要有效成分之一。研究不同剂量TP在Beagle犬灌胃给药时的绝对生物利用度和药代动力学， 可望为其临床研究提供参考。以泼尼松龙作内标， 用乙酸乙酯液液萃取， 建立LC-APCI/MS选择性离子监测方法测定血浆TP浓度。Beagle犬分别静脉注射TP 0.05 mg·kg^-1、 灌胃TP 0.05，0.08和0.1 mg·kg^-1进行药代动力学和绝对生物利用度研究。结果表明， TP在1～200 ng·mL^-1呈良好线性关系(r=0.999 7)，批内和批间精密度RSD均小于10%，准确度在95.0%～105.0%，提取回收率大于75%。静注0.05 mg·kg^-1 TP后，T_1/2β为(2.5±0.8) h。3个剂量灌胃组，T_max，T_1/2α和T_1/2β，经检验无统计学差异。AUC和C_max与剂量之间线性相关。灌胃0.05 mg·kg^-1后，TP在Beagle犬体内绝对生物利用度为(75±17)%。可见，LC-APCI/MS法灵敏、可靠、专属性强，可用来测定Beagle犬血浆TP的浓度；TP在Beagle犬体内消除较快，灌胃给药生物利用度较高。     

静脉注射利多卡因对丙泊酚麻醉下阿芬太尼抑制人流手术患者体动反应的半数有效剂量的影响

目的 研究静脉注射利多卡因对丙泊酚麻醉下阿芬太尼抑制人流手术患者体动反应的半数有效剂量（ED₅₀）的影响。方法 择期人工流产手术患者，年龄18~40岁，美国麻醉医师协会分级I~II级。随机分成2组，利多卡因联合阿芬太尼组（LA组）与阿芬太尼组（A组）。LA组患者静脉注射利多卡因1.0 mg·kg^-1后，缓慢注射丙泊酚2.0 mg·kg^-1及阿芬太尼（初始剂量为15.5 μg·kg^-1），A组患者则静脉注射0.1 mL·kg^-1生理盐水后，再依次缓慢注射丙泊酚2.0 mg·kg^-1与阿芬太尼。待患者意识消失后，消毒铺巾，观察患者置入宫颈探条的体动反应。采用序贯法计算阿芬太尼的剂量，若在置入宫腔探条时，发生体动阳性反应，则下一例患者剂量增加20%，反之则剂量降低20%。直至出现 ≥ 6个阳性反应和阴性反应的交替点，结束试验。采用概率单位回归分析法计算阿芬太尼抑制人流患者体动反应的ED₅₀、95%有效剂量（ED₉₅）及其95%可信区间（CI），记录术中生命体征，静脉注射痛，术后10 min、术后30 min、出院时疼痛评分及不良反应等指标。结果 LA组ED₅₀为6.55 μg·kg^-1（95%CI，2.10~8.07 μg·kg^-1），A组ED₅₀为8.24 μg·kg^-1（95%CI，6.75~9.75 μg·kg^-1），2组阿芬太尼的ED₅₀有差异；与A组比较，LA组术后10 min、术后30 min、出院时疼痛评分更低，差异有统计学意义（P<0.000 1或P<0.05）；LA组静脉注射痛发生率下降（减少44.2%），差异有统计学意义（P<0.01）；2组呼吸抑制发生例数、清醒时间与恶心呕吐等比较差异无统计学意义。结论 静脉注射利多卡因可显著降低阿芬太尼用于人流手术的ED₅₀，减少静脉注射痛发生率，缓解术后短期急性疼痛。     

蛇床子素在兔体内药物代谢动力学

目的研究蛇床子素在兔体内的药物代谢动力学。方法用高效液相色谱法,以丹皮酚为内标,以甲醇-水(80∶20)为流动相,测定兔血液中蛇床子素(iv,10 mg·kg^-1)的含量。采用3P87程序计算药物代谢动力学参数。结果蛇床子素iv药代动力学符合二房室开放模型,T_1/2α=5.81 min,T_1/2β=42.2 min,K21=0.036 0·min^-1,K₁₂=0.045 0·min^-1,K₁₀=0.054 0·min^-1,AUC=235 mg·min·L^-1,CLs=0.043 0 L·min^-1·kg^-1,V_C=0.780 L·kg^-1。结论蛇床子素在兔体内分布及消除较快     

丙泊酚与依托咪酯乳剂在颅脑损伤合并肺部感染患者纤维支气管镜治疗中的镇静效果及安全性评估

目的 观察丙泊酚与依托咪酯乳剂在颅脑损伤合并肺部感染患者纤维支气管镜治疗中的镇静效果及安全性。方法 选取河北医科大学第二医院2019年1月一2021年8月收治的重症医学科（ICU）机械通气颅脑损伤合并肺部感染患者84例为研究对象,按照用药方案不同分为丙泊酚组和依托咪酯组,每组各42例。两组均给予纤维支气管镜治疗,丙泊酚组给予丙泊酚乳状注射液1~2 mg·kg^-1,人工缓慢静推3~5 min。依托咪酯组给予依托咪酯中/长链脂肪乳注射液0.2~0.4 mg·kg^-1,缓慢静推。操作中若患者躁动明显或呛咳剧烈影响进境,或气管壁出血,则追加丙泊酚30mg或依托咪酯6mg。比较两组给药前5 min （T₀）、给药后-入镜即刻（T₁）、入镜后3 min （T₂）、入镜后10 min （T₃）、撤镜即刻（T₄）、术毕5 min （T₅）时脑电双频谱指数（BIS）、心率（HR）、呼吸频率（RR）、平均动脉压（MAP）、血氧饱和度（SpO₂）、脑氧饱和度（rSO₂）差异,比较两组药物平均使用量、追加药物次数、麻醉起效时间、不良反应发生情况及纤维支气管镜操作医生对镇静效果的满意度。结果 T₁、T₄、T₅时两组BIS均低于本组T₀时,T₂、T₃时高于本组T₁时（P<0.05）;T₀、T₂、T₄、T₅时两组BIS差异无统计学意义（P>0.05）;T₁、T₃时丙泊酚组BIS低于依托咪酯组（P<0.05）;T₁、T₂、T₃、T₄时丙泊酚组HR、MAP低于依托咪酯组（P<0.05）;T₀、T₅时两组HR、MAP差异无统计学意义（P>0.05）;T₀、T₁、T₂、T₃、T₄、T₅时两组RR、SpO₂、rSO₂差异无统计学意义（P>0.05）;丙泊酚组药物平均使用量多于依托咪酯组,追加药物次数少于依托咪酯组（P<0.05）;两组麻醉起效时间差异无统计学意义（P>0.05）;依托咪酯组呛咳反应发生率高于丙泊酚组（P<0.05）;两组呼吸抑制发生率、躁动发生率差、纤维支气管镜操作医生对镇静效果满意度差异无统计学意义（P>0.05）。结论 丙泊酚与依托咪酯乳剂在ICU机械通气颅脑损伤合并肺部感染患者行纤维支气管镜治疗中均具有良好镇静效果,其中依托咪酯药物平均使用量较少,对HR、MAP、BIS影响较小,但追加药物频次、呛咳反应发生率较高。     

小檗碱对2型糖尿病大鼠视网膜PPARα/δ/γ表达的影响

糖尿病视网膜病是最常见的糖尿病并发症之一，是导致失明的主要原因，因此有必要寻找新的治疗药物。给大鼠腹腔注射链脲菌素(35 mg·kg^-1) 2周后用高糖高脂饲料喂养14周，之后连续16周每天分别拌食给予小檗碱75、150及300 mg·kg^-1、非诺贝特100 mg·kg^-1和罗格列酮4 mg·kg^-1。用HE染色检查视网膜结构和免疫组化检测过氧化物酶体增殖物激活受体(PPARs) α/δ/γ的表达。结果发现，正常对照组大鼠的视网膜厚度大于其他各组，经小檗碱(150及300 mg·kg^-1)和罗格列酮(4 mg·kg^-1)的治疗能增加糖尿病大鼠视网膜的厚度，但视网膜的结构在各组间无差别；小檗碱(150及300 mg·kg^-1)和罗格列酮(4 mg·kg^-1)能明显降低糖尿病大鼠视网膜中PPARγ蛋白表达，小檗碱(150及300 mg·kg^-1)和非诺贝特(100 mg·kg^-1)能显著增加糖尿病大鼠视网膜中PPARα和PPARδ的表达。小檗碱调控视网膜PPAR α/δ/γ蛋白表达可能是其改善糖尿病视网膜病的机制之一，可能成为比罗格列酮和非诺贝特更有效的用于治疗糖尿病视网膜病的药物。     

复方聚维酮碘片长期给药对大鼠甲状腺功能的影响

目的:观察复方聚维酮碘片(CPI)长期给药对大鼠甲状腺功能的影响。方法:Wistar大鼠每天口腔给予CPI 0.4和4.0mg·kg^-1·d^-1,连续给药30d。采用放射免疫法测定血清甲状腺激素(T₃和T₄)含量。结果:CPI组大鼠的甲状腺指数、血清T₃和T₄水平与对照组比较无显著性差异(P>0.05)。结论:CPI长期口腔给药对大鼠甲状腺功能无明显影响     

反相HPLC法测定兔血浆异钩藤碱浓度及其药物代谢动力学

用ODS柱分离,甲醇—水(95∶5)为流动相,检测波长UV254nm,建立了兔血浆异钩藤碱浓度的HPLC测定方法。结果显示,血药浓度在0016～16μg·ml^-1范围内呈线性关系,血浆最低检测浓度为0.016μg·ml^-1,绝对回收率为80.5%～85.1%。兔iv IRHY 2及5mg·kg^-1,药代动力学过程符合二室开放模型,T_1/2β分别为1.32h和1.25h。兔经十二指肠给2及5mg·kg^-1后,T_1/2β分别为1.75h和1.26h。生物利用度为42.4%～69.4%。此法简便、快速。IRHY在兔体内吸收迅速,消除也较快。     

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.

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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.     

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.     

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.