The Pharmacokinetics of Pancuronium in Infants,Children and Adults

研究观察年龄对潘库溴铵药代动力学的影响。选择２４例施择期整形外科手术的患者，根据年龄分成三组：１组为５例婴幼儿，年龄０．７５～２．９５岁；２组为１３例儿童，年龄４～１４岁；３组为６例成人，年龄１６～２７岁。静注潘库溴铵１００μｇ／ｋｇ后用改良荧光法测定其血浓度。潘库溴铵的体内过程能用二室开放模型完整描述，年龄愈小，分布容积愈大，血浆清除率愈高，潘库溴铵的血药浓度愈低。Ｖ１（中央室分布容积）、Ｖ２（周边室分布容积）、Ｖｄｓｓ（稳态分布容积）、Ｃｌ（血浆清除率）和ＡＵＣ（曲线下面积）在三组间有明显差别。１组的Ｔ１／２β和ＭＲＴ明显比２、３组长，但Ｔ１／２α和Ｋ２１在三组间无明显差别。     

阿曲库铵和维库溴铵量—效关系和恢复时相的比较性研究

比较性观察阿典库铵和维库溴铵量－效关系和恢复时相特征,选择60例ASA I级,年龄17－50岁,施择期整形外科手术的中国患者,分层随机平均分成阿曲库铵组和维库溴铵组,用60％NO2－O2－硫喷妥钠－芬太尼维持麻醉,用加速度仪监测神经肌肉功能,采用TOF刺激方式,以T1抑制的百分比为研究指标。用累计给药方法建立阿曲库铵和维库溴铵的量－效关系曲线,根据用最小二乘法建立的量－效关系曲线,阿曲库铵的神经肌肉阻滞作用强度仅为维库溴铵的17％,两药的ED50,ED90和ED95均有明显差别。应用等效剂量（1．5xED95)后,两药的高峰时间,临床肌松时间,恢复时间和体内作用时间均无明显差别,结论：阿曲库铵是一弱效能的肌松药,而维库溴铵为一强效能肌松药,阿典库铵和维库溴铵的作用强度经为1／6,应用等效剂量后,两药的恢复时相无明显差别。     

噻托溴铵治疗慢性阻塞性肺疾病随机双盲双模拟对照临床试验

目的 评价噻托溴铵治疗慢性阻塞性肺疾病（COPD）的疗效和安全性。方法 用双盲双模拟随机对照方法，观察了COPD病人吸人噻托溴铵（21例，18μg，qd）与异丙托溴铵（23例，40μg q6h）的支气管扩张作用及安全性。结果 用药后，噻托溴铵组病人第1秒用力呼气容积（FEV1）和用力肺活量（FVC）均显著增加（P〈0．001）；2，3h时，FEV1的增加较异丙托溴铵组有显著性差异（P〈0．05）；治疗2，4周时，噻托溴铵组病人FEV，谷值明显上升（P〈0.01），较异丙托溴铵组分别高0．14，0．05L。2组药物不良反应发生率无统计学差异。结论 噻托溴铵是治疗COPD病人有效和安全的支气管扩张药物，疗效和用法均优于异丙托溴铵。     

维库溴铵对糖尿病患者神经肌肉阻滞的影响

目的研究维库溴铵对2型糖尿病患者神经肌肉阻滞的时间效应。方法需在全身麻醉下进行手术的患者30例，治疗组和对照组各15例，治疗组患者均为2型糖尿病患者，对照组患者均无糖尿病。两组患者的麻醉诱导均给予异丙酚2 mg·kg^-1，芬太尼2 μg·kg^-1，维库溴铵0.1 mg·kg^-1。用异丙酚＋芬太尼维持麻醉，复合吸入异氟烷。给予4个成串刺激，检测两组患者能够引起最大反应（T0）的平均最大刺激量以及静脉注射维库溴铵后T1、T2、T3、T4出现的时间。结果给予维库溴铵后，治疗组平均最大刺激量［（50.5±14.1） mA］明显高于对照组［(33.4±6.1) mA］(P＜0.01)。治疗组T1和T4恢复时间均明显长于对照组（P＜0.01）。给予维库溴铵 80～120 min后，治疗组T1/T0值明显低于对照组(P＜0.05)。结论治疗组T1、T2、T3、T4恢复时间明显长于对照组。糖尿病患者最大刺激量明显高于非糖尿病患者。给予维库溴铵后，糖尿病患者神经阻滞时间明显延长。     

阿曲库铵和维库溴铵量──效关系和恢复时相的比较性研究(英)

比较性观察阿曲库铵和维库溴铵量-效关系和恢复时相特征。选择60例ASAI级,年龄17～50岁,施择期整形外科手术的中国患者,分层随机平均分成阿曲库铰组和维库溴铵组。用60％NO2-O2-硫喷妥钠-芬太尼维持麻醉。用加速度仪监测神经肌肉功能,采用TOF刺激方式,以T1抑制的百分比为研究指标。用累计给药方法建立阿曲库铵和维库溴铵的量-效关系曲线。根据用最小二乘法建立的量-效关系曲线,阿曲库铵的神经肌肉阻滞作用强度仅为维库溴铵的17％。两药的ED50、ED90和ED95均有明显差别。应用等效剂量（1.5×ED95）后,两药的高峰时间、临床肌松时间、恢复时间和体内作用时间均无明显差别。结论：阿曲库铵是一弱效能的肌松药,而维库溴接为一强效能肌松药。阿曲库按和维库溴铵的作用强度比率为1／6。应用等效剂量后,两药的恢复时相无明显差别。     

艾司洛尔对颅脑外科全麻插管和安置头架期脑电双频指数和循环的影响

目的：探讨艾司洛尔应用于颅脑外科手术全麻插管和安置头架时的临床效果及可能机制。方法选择择期颅脑手术患者40例，年龄20～55岁，ASAⅠ～Ⅱ级，随机分为对照组（ A组）和艾司洛尔组（ B组），每组30例。患者入室安静5 min后记录脑电双频指数（ BIS）、收缩压（ SBP）、舒张压（ DBP）、平均动脉压（ MAP）、心率（ HR）基础值。 A组采用咪达唑仑0．1 mg／kg，舒芬太尼0．3μg／kg，依托咪酯0．3 mg／kg，维库溴铵0．1 mg／kg静脉注射快速诱导并插管，B组诱导前静脉注射艾司洛尔1 mg／kg，然后以200μg· kg－1· min－1的速度维持，其余同A组。记录2组给予艾司洛尔前（T0）、诱导前（T1）、诱导后（T2）、插管即刻（T3）、插管后1 min（T4）、安置头架前（T5）、安置头架后（T6）的BIS、SBP、DBP、HR值。结果2组患者T0、T1、T2、T5各项指标差异无统计学意义（ P ＞0．05）；T3、T4、T6各时间点HR、MAP均升高，但A组明显高于B组（ P ＜0．01）；T3、T4、T6各时间点BIS值与T2比较，A组明显升高（ P＜0．05），B组无明显变化（ P ＞0．05）。结论艾司洛尔可以抑制气管插管及安置头架引起的BIS值变化，同时减轻心血管反应。     

信必可联合噻托溴铵吸入治疗中重度稳定期 COPD 患者疗效观察

目的：观察信必可（布地奈德／福莫特罗粉吸入剂）联合噻托溴铵治疗中重度稳定期慢性阻塞性肺疾病（ COPD）的临床疗效。方法将150例中重度稳定期COPD患者随机分为A、B、C组各50例。3组患者均给予一般性综合治疗措施,在此基础上A组给予信必可吸入治疗,B组患者给予噻托溴铵吸入治疗,C组给予信必可联合噻托溴铵吸入治疗。比较3组患者治疗前后第1秒用力呼气容积（FEV1）,6min步行距离（6－MWD）、圣乔治呼吸问卷得分（ SGRQ）变化。结果治疗3个月后,3组FEV1和6－MWD均较治疗前有所增加,SGRQ得分较治疗前有所降低,差异均有统计学意义（P＜0．05）;且C组患者FEV1和6－MWD均大于A组和B组,SGRQ得分小于A组和B组,差异均有统计学意义（P＜0．05）。结论信必可联合噻托溴铵较两药单独使用可明显改善中重度稳定期COPD患者的肺功能和生活质量。     

2型糖尿病患者非酶糖基化蛋白与性激素含量的研究

目的：研究老年性糖尿病患者体内性激素的分泌和蛋白非酶糖基化反应的改变及临床意义。方法：检测老年性糖尿病患者48例，年龄60－72岁（男31，女17）和正常对照组15例，年龄60－69岁（男9，女6）的血糖、血浆胰岛素、非酶糖基化蛋白（血浆果糖胺、糖化血红蛋白）和性激素（血浆睾酮、雌二醇）的含量。结果：1、糖尿病患者血浆胰岛素（Ins)含量与正常对照无显著差异；其血糖（Glu)、血浆果糖胺FA及糖化血红蛋白（GHb)含量显著高于正常对照。2、男性糖尿病患者血浆睾酮（T）含量显著低于正常对照，雌二醇（E2）含量和雌二醇与睾酮的比值（E2／T）均高于正常对照；女性糖尿病患者睾酮含量明显高于正常对照，而雌二醇含量和E2／T均低于正常对照。结论：老年性糖尿病患者体内存在性激素分泌功能紊乱。2型糖尿病患者的血浆果糖胺和糖化血红蛋白含量显著高于正常对照组。     

老年与青壮年瑞芬太尼药代动力学差异比较

目的探讨老年与青壮年手术患者瑞芬太尼药代动力学参数差异。方法 ASAⅠ或Ⅱ级择期全麻老年及青壮年患者各8例,老年患者年龄62～81岁,青壮年患者年龄18～60岁,全麻诱导时静脉注射瑞芬太尼5μg/kg,于瑞芬太尼注射后1、2、3、5、7、10、15、20、25、30、45、60min分别采集动脉血1.0ml。采用液-液萃取毛细管气相色谱质谱法测定瑞芬太尼血药浓度。结果老年及青壮年患者主要药代动力学参数分别为：t1/2β：（20±9）min、（12±7）min,表现分布容积：（56±17）L、（44±10）L,血浆清除率：（2.7±0.4）L/min、（4.0±0.5）L/min。结论老年与青壮年患者瑞芬太尼药代动力学均符合二房室模型,消除半衰期、表观分布容积、清除率二者明显不同,提示老年与青壮年患者间瑞芬太尼群体药代动力学可能存在差异。     

大剂量甲氨蝶呤治疗急性淋巴细胞白血病患儿群体药动学研究

目的建立儿童急性淋巴细胞白血病（ALL）患儿静脉使用大剂量甲氨蝶呤（HDMTX）稀疏点血药浓度数据库,估算群体药动学参数,结合Bayesian反馈法,估算个体药动学参数。方法132例ALL患儿接受HDMTX（3g·m^-2）静脉滴注后,不同时间点采血样,用荧光偏振免疫法（FPIA）测定MTX的血浆浓度,收集24—68h左右稀疏血药浓度数据510个。用NONMEM软件进行模型拟合和PPK参数的估算,并定量分析患儿年龄、性别、体重、身高、ALT、AST、CREA、UA等固定效应参数对甲氨蝶呤PPK参数的影响,得到最终拟合药动学模型。结果PPK模型为：中央室清除率CLli（L·h^-1·kg^-1）=5．84×10^0.017·（age-9.2）＋0．0150×WT^10685×e^CLli,周边室清除率CL2i（L·h^-1·k^-1）=0．265×10^0.029＊（age-10）＋0．00067×WT^1.178×e^CLli,中央室表观分布容积Vli（L·kg^-1）=2．42×10（WT-1.47）＋15．45×10^0.0046＊（age-4.8×e^VIi,外周室表观分布容积V2i（L·kg^-1）=1．85×10^0.063＊（148-Height）＋0．042×10（WT＋0.32×e^V2i;其中建模型组CL1、V1、CL2、V2的群体间标准值（个体问RSD）分别为6．272L·h^-1·kg^-1（17．62％）,1．136L／kg（7．39％）,0．28L·h^-1·kg^-1（7．5％）,3．453L／kg（25．98％）;年龄、体重对CL的影响具有统计学意义（P〈0．05）;预测MTX达到0．1μmol／L的时间是46．85h,个体间标准差（RSD）为5．19％。结论本实验模型拟合情况较好,该模型可用于临床制定个体化给药方案。     

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.     

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.