紫外导数光谱法测定依托咪酯注射液的含量

依托咪酯是一种新型非巴比妥类静脉全麻药,该药临床广泛用于手术时麻醉。本文根据依托咪酯紫外吸收光谱特征及微分原理,拟定了一阶导数光谱法,排除了丙二醇及其它物质对依托咪酯含量测定的影响。 1 仪器与试剂:仪器:日立330型分光光度计。试剂:依托咪酯(自行提取精制,mp115℃);依托咪酯注射液(市售品);丙二醇(分析纯)。依托咪酯标准液的配制:精密称取60℃干燥至恒重的依托咪酯50mg,置50ml量瓶中,加水溶解并稀释至刻度,摇匀,备用。丙二     

依托咪酯对机械通气患者相对肾上腺皮质功能不全和死亡率的影响

目的:研究依托咪酯对机械通气患者相对肾上腺皮质功能不全(RAI)和死亡率的影响。方法:将机械通气患者随机分成依托咪酯组和丙泊酚组,2组均在治疗原发病基础上给予机械通气和镇静治疗,依托咪酯组给予依托咪酯镇静,丙泊酚组给予丙泊酚镇静。比较两组RAI和死亡率的差异。结果:依托咪酯组RAI发生率(62.99%)和死亡率(38.98%)均显著高于丙泊酚组(分别为46.85%和27.95%),差异均有统计学意义(P<0.05);依托咪酯组RAI和死亡率的相对危险度分别为丙泊酚组的1.34倍和1.39倍;在调整年龄、性别和急性生理学及慢性健康状况评分后,依托咪酯组RAI和死亡率的相对危险度分别为丙泊酚组的1.26倍和1.30倍。结论:依托咪酯可增加机械通气患者RAI发生率和死亡率。     

丙泊酚注射液与依托咪酯注射液的配伍稳定性考察

目的:考察丙泊酚注射液与依托咪酯注射液的配伍稳定性。方法:取丙泊酚注射液和依托咪酯注射液一定量按20 mg∶2mg的比例混合,分装成5份后分别在37℃恒温水浴箱中放置0、4、8、12、24 h,采用核磁共振波谱(NMR)法检测二者混合后是否生成新的物质,使用二甲基亚砜(DMSO)-d6溶剂溶解后分别进行H1-NMR的图像采集。结果:通过与标准品谱图对比及对不同水浴时间下混合样品间谱图峰面积积分可知,丙泊酚、依托咪酯二者混合后在上述条件下表现出良好的化学稳定性。结论:所建方法简便、快速、准确;丙泊酚注射液与依托咪酯注射液混合后无化学性质的变化,配伍稳定,可在临床联合应用。     

依托咪酯联合丙泊酚用于老年患者无痛胃肠镜检查的麻醉效果及对患者认知功能的影响

目的:探讨依托咪酯联合丙泊酚用于老年患者无痛胃肠镜检查的麻醉效果及对患者认知功能的影响。方法:90例行无痛胃肠镜检查的老年患者随机分为丙泊酚组(30例)、依托咪酯组(30例)和联合组(30例)。丙泊酚组患者给予芬太尼注射液1μg/kg+丙泊酚注射液1.5 mg/kg;依托咪酯组患者给予芬太尼注射液1μg/kg+依托咪酯注射液0.3 mg/kg;联合组患者给予芬太尼注射液1μg/kg+丙泊酚注射液1 mg/kg+依托咪酯注射液0.15 mg/kg。观察3组患者不同时间点的收缩压(SBP)、舒张压(DBP)、心率(HR)、平均动脉压(MAP)、血氧饱和度(SpO_2),检查、麻醉诱导、苏醒和定向力恢复时间,神经行为认知状态检查(NCSE)情况,不同时间点的简易精神状态检查表(MMSE)评分及不良反应发生情况。结果:丙泊酚组患者检查时SBP、DBP、MAP、SpO_2均显著低于同组麻醉前、检查后及联合组,差异均有统计学意义(P<0.05),但丙泊酚组检查后与同组麻醉前比较,差异均无统计学意义(P>0.05)。联合组患者苏醒、定向力恢复时间均显著短于丙泊酚组和依托咪酯组,差异均有统计学意义(P<0.05),但依托咪酯组与丙泊酚组间比较,差异均无统计学意义(P>0.05)。联合组患者记忆能力、计算能力、定向力检查通过例数占比均显著高于丙泊酚组,差异均有统计学意义(P<0.05),但联合组与依托咪酯组、依托咪酯组与丙泊酚组间比较,差异均无统计学意义(P>0.05)。联合组患者不同时间点的MMSE评分比较,差异无统计学意义(P>0.05);丙泊酚组患者麻醉后15、30 min及依托咪酯组患者麻醉后15 min MMSE评分均显著低于同组麻醉前及联合组,差异均有统计学意义(P<0.05),但丙泊酚组麻醉后1 h、依托咪酯组麻醉后30 min及1 h与同组麻醉前比较,差异均无统计学意义(P>0.05)。呼吸暂停、低血压、注射痛发生率联合组、依托咪酯组<丙泊酚组,体动反应、肌阵挛、恶心呕吐发生率联合组、丙泊酚组<依托咪酯组,心动过缓发生率联合组<丙泊酚组,差异均有统计学意义(P<0.05)。结论:依托咪酯联合丙泊酚用于老年患者无痛胃肠镜检查的麻醉效果较好,可减少检查后认知功能障碍,缩短苏醒时间,且未增加不良反应的发生。     

LC-MS/MS测定Beagle犬血浆中依托咪酯浓度及其在生物等效性评价中的应用

目的：建立液相色谱-质谱联用(LC-MS/MS)分析方法测定Beagle犬血浆中依托咪酯的浓度,并考察2种依托咪酯中/长链脂肪乳注射液的生物等效性。方法：建立LC-MS/MS分析方法检测Beagle犬血浆中依托咪酯含量。12只Beagle犬采用双周期双交叉设计,静脉注射依托咪酯中/长链脂肪乳注射液0.52 mg·kg^–1,检测血浆中依托咪酯的含量,计算药动学参数。结果：Beagle犬血浆中的线性范围为1～200 ng·mL^–1。低中高浓度提取回收率分别为97.4%、100.3%和97.1%,批间/批内精密度和准确度偏差范围在–5.2%～6.1%,变异系数6.5%,均满足分析检测要求。受试制剂与参比制剂AUC_{0–10 h}分别为(171.0±27.1),(176.0±25.3)μg·h·L^–1,C_max分别为(398.0±59.5),(413.0±100.0)μg·L^–1,两者无统计学差异。结论：建立的LC-MS/MS测定方法简便、灵敏、准确,可用于检测血浆中...     

瑞芬太尼复合依托咪酯脂肪乳在无痛胃镜检查中的研究

目的 研究瑞芬太尼和芬太尼复合依托咪酯脂肪乳注射液应用于无痛胃镜的临床效果和安全性.方法 选择进行无痛胃镜术的患者60例,随机分成瑞芬太尼组(R组)和芬太尼组(F组)各30例,R组:瑞芬太尼1.0μg/kg,依托咪酯脂肪乳注射液0.3mg/kg.F组:芬太尼1.0μg/kg,依托咪酯脂肪乳注射液0.3mg/kg.分别记录瑞芬太尼和芬太尼的用量,依托咪酯脂肪乳注射液的追加情况以及血压、心率、血氧饱和度、苏醒时间、定向力恢复时间以及检查术中术后的并发症情况.结果 两组患者的血压、心率、血氧饱和度变化差异无统计学意义,术中F组需追加依托咪酯的例数较R组多(P＜0.05),苏醒时间显著长于R组,不良反应如头晕、乏力发生率比R组高,但两组的恶心、呕吐发生率和对呼吸功能的影响相似.结论 瑞芬太尼复合依托咪酯脂肪乳注射液用于无痛胃镜的安全性与芬太尼相似,但苏醒快,留观时间短,更适于无痛胃镜检查.     

HPLC法测定依托咪酯脂肪乳注射液中依托咪酯的含量

目的建立测定依托咪酯脂肪乳注射液中依托咪酯含量的高效液相色谱法。方法色谱柱:Agilent TC-C18柱(250mm×4.6mm,5μm),流动相∶甲醇-水(80∶20),流速1.0mL/min,检测波长:241nm,进样量:20μL。结果依托咪酯的浓度在5～50μg/mL范围内与峰面积呈良好线性关系(r=0.9990),高、中、低3种浓度的平均回收率(n=3)为99.3%(RSD=0.11%)、98.1%(RSD=0.08%)、100.3%(RSD=0.14%)。结论该方法操作简便,结果可靠,适用于依托咪酯脂肪乳注射液的含量测定。     

HPLC梯度洗脱法测定依托咪酯乳状注射液的有关物质

目的:建立测定依托咪酯乳状注射液中的有关物质的HPLC方法。方法:色谱柱为Waters SpherisorbC₈(4.6 mm×250 mm, 10μm);流动相为磷酸二氢钾溶液-乙腈-80%-四氢呋喃,梯度洗脱;柱温为40℃;检测波长为220 nm,采用外标法与自身对照法。结果:依托咪酯与依托咪酸能较好分离,依托咪酸相邻各峰间分离度均大于1.5;依托咪酸的线性范围为10.0～100.0μg·mL^-1(r=0.999 9);平均回收率(n=9)为99.5%。结果表明,B企业产品中依托咪酸的含量相对较高,其他杂质也高于A企业产品。结论:所建方法简便快捷、专属性强、重复性好,可用于依托咪酯乳状注射液中的有关物质检查。     

舒芬太尼和布托啡诺分别复合依托咪酯用于门诊无痛胃镜的观察

目的研究舒芬太尼和布托啡诺分别复合依托咪酯应用于门诊无痛胃镜检查的临床效果和安全性。方法选择进行无痛胃镜检查的患者60例,随机分成布舒芬太尼组(S组)和托啡诺组(B组)各30例,S组:舒芬太尼0.1μg/kg,依托咪酯脂肪乳注射液0.2~0.3mg/kg,B组:布托啡诺1mg,依托咪酯脂肪乳注射液0.2~0.3mg/kg。分别记录舒芬太尼和布托啡诺的用量,依托咪酯脂肪乳注射液的追加情况以及血压、心率、血氧饱和度、术中并发症情况、苏醒时间、术后发生眩晕、恶性、呕吐的情况和留观时间。结果两组患者的血压、心率、血氧饱和度变化差异无统计意义,术中S组需追加依托咪酯的例数与B组相当(P>0.05),苏醒时间相当,但术后不良反应如眩晕、恶心、呕吐发生率B组较S组高,留观时间明显长于S组。结论舒芬太尼复合依托咪酯脂肪注射液用于无痛胃镜的安全性与布托啡诺相似,苏醒时间相当,但术后不良反应发生率少,留观时间短,更适于门诊无痛胃镜检查。     

丙泊酚注射液联合依托咪酯注射液用于老年脊柱手术患者的临床研究

目的观察丙泊酚注射液联合依托咪酯注射液用于老年脊柱手术患者的临床疗效及安全性。方法将58例脊柱手术老年患者随机分为对照组和试验组,每组29例。对照组给予4μg·kg^-1芬太尼+0.6 mg·kg^-1罗库溴铵+0.3 mg·kg^-1依托咪酯,静脉滴注,进行麻醉诱导,之后给予0.6 mg·kg^-1·h^-1依托咪酯,持续静脉泵注,进行麻醉维持;试验组给予4μg·kg^-1芬太尼+0.6 mg·kg^-1罗库溴铵+0.15 mg·kg^-1依托咪酯+1.5 mg·kg^-1丙泊酚,静脉滴注,进行麻醉诱导,之后给予0.3 mg·kg^-1·h^-1依托咪酯+3 mg·kg^-1·h^-1丙泊酚,持续静脉泵注,进行麻醉维持。比较2组患者的血流动力学和脑氧代谢指标,以及药物不良反应的发生情况。结果麻醉诱导30 min时,试验组和对照组的收缩压分别为(120.24±17.10)和(115.02±17.95)mmHg,动脉-颈内静脉血氧含量差分别为(41.20±10.53)和(49.10±10.27)mL·L^-1,脑氧摄取率分别为(24.91±5.07)%和(31.91±5.12)%,差异均有统计学意义(均P<0.05)。试验组的药物不良反应主要有恶心呕吐和肌颤,对照组的药物不良反应主要有恶心呕吐。试验组和对照组的总药物不良反应发生率分别为10.34%和6.90%,差异无统计学意义(P>0.05)。结论丙泊酚注射液联合依托咪酯注射液用于老年脊柱手术患者的临床疗效确切,其能维持血流动力学稳定,降低脑氧代谢,提高术后认知功能,且不增加药物不良反应的发生率。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.