造血干细胞移植患者中伏立康唑与环孢素及他克莫司的相互作用

目的 通过监测造血干细胞移植患者伏立康唑和免疫抑制剂（环孢素A、他克莫司）的稳态血药谷浓度,探讨伏立康唑与环孢素及他克莫司之间的作用。方法 回顾性分析2016年6月-12月于宁波市第一医院血液科住院治疗的造血干细胞移植患者的伏立康唑、环孢素A以及他克莫司的稳态血药浓度数据。结果 伏立康唑与环孢素A合用后,环孢素A稳态谷浓度升高41.55%（P<0.05）,伏立康唑稳态谷浓度下降23.31%;伏立康唑与他克莫司合用后,他克莫司稳态谷浓度升高17.52%,伏立康唑稳态谷浓度下降29.45%（P<0.05）。结论 伏立康唑联用环孢素A或他克莫司时,建议诊疗过程严密监测免疫抑制剂及伏立康唑的血药浓度,以便及时调整治疗药物剂量,保障安全、有效、合理用药。     

伏立康唑治疗儿童侵袭性真菌感染血药浓度与疗效相关性研究

目的 探索伏立康唑治疗儿童侵袭性真菌感染的剂量、血药浓度与疗效的相关性。方法 收集2019年1月至2019年12月,使用伏立康唑治疗的68例儿童侵袭性深部真菌感染病例,采用高效液相色谱法检测伏立康唑的血药谷浓度,统计分析伏立康唑的不同剂量与血药浓度和临床疗效的相关性。结果 检测显示不同给药剂量的血药谷浓度分别为：<4.0 mg/kg（6例）,谷浓度在0.4~3.31 μg/ml (r=0.613,P=0.195);4.0~7.0 mg/kg（44例）,谷浓度在0.35~7.02 μg/ml（r=0.325,P=0.018）;>7.0 mg/kg（18例）,谷浓度在1.46~12.45 μg/ml (r=0.584,P＜0.023),3组间差异有统计学意义(F=7.270, P=0.026)。68例患儿中总体有效58例（85.3%）,无效10例（14.7%）。上述不同谷浓度的疗效分别为：<1.0 μg/ml组14例,有效10例（71.4％）,无效4例;1.0~5.5 μg/ml组48例,有效44例（91.7％）,无效4例;>5.5 μg/ml组6例,有效4例（66.7%）,无效2例。3组间差异有统计学意义（χ^２=5.360, P=0.039）。10例出现不良反应（14.7%）,主要为轻度肝功能损伤,不影响治疗,保肝治疗后可恢复。结论 研究显示伏立康唑治疗儿童侵袭性真菌感染总体安全有效,且存在明显的剂量-血药浓度与疗效的相关性。因此,进一步开展药动学与疗效相关研究,有利于实现理想的个体化治疗。     

奥曲肽与泮托拉唑单独与联合治疗非静脉曲张性上消化道出血的有效性及安全性

目的 研究奥曲肽与泮托拉唑单独与联合治疗非静脉曲张性上消化道出血的有效性及安全性。方法 选择2013年1月~2015年12月在延安大学附属医院进行诊治的非静脉曲张性上消化道出血患者162例,随机分为3组,每组54例。奥曲肽组给予奥曲肽单独治疗,泮托拉唑组给予泮托拉唑单独治疗,联合组给予奥曲肽与泮托拉唑联合治疗。比较3组的疗效、失血量、出血时间、血红蛋白水平和胃管引流液pH值。结果 联合组的有效率为94.44%,明显高于奥曲肽组的75.93%和泮托拉唑组的77.78%（P<0.05）;联合组的失血量和止血时间均明显低于奥曲肽组和泮托拉唑组（P<0.05）,治疗后3组的血红蛋白水平均明显升高（P<0.05）,且联合组明显高于奥曲肽组和泮托拉唑组（P<0.05）;治疗后3组的胃管引流液pH值均明显升高（P<0.05）,且联合组明显高于奥曲肽组和泮托拉唑组（P<0.05）。结论 奥曲肽与泮托拉唑联合治疗非静脉曲张性上消化道出血的疗效明显由于单独治疗,安全有效,值得应用推广。     

伏立康唑血药浓度监测结果评析

目的 通过对不同临床专科伏立康唑进行治疗药物监测（TDM）,并比较调整剂量前后的血药谷浓度数据,阐明TDM对伏立康唑合理用药的必要性,并给出相关的临床提示。方法 本研究通过回顾性分析伏立康唑TDM的数据,对收治入院的154位患者的435例次伏立康唑血药谷浓度测定结果做一个初期评估。结果 肾移植科仅有4.3%的测定结果高于5.5 μg/ml,而有26.5%的测定结果低于1.0 μg/ml。感染科有52.3%的测定结果高于5.5 μg/ml,没有出现低于1.0 μg/ml的测定结果。结论 TDM对伏立康唑的合理用药十分必要,肾移植科患者伏立康唑TDM不在建议浓度区间的结果以低于1.0 μg/ml居多,而感染科患者则以高于5.5 μg/ml居多,临床上应予以重视。临床药师可根据TDM结果更密切地参与伏立康唑的临床用药。     

泮托拉唑与奥美拉唑治疗消化道溃疡出血的临床对照研究

目的 对比泮托拉唑与奥美拉唑治疗消化道溃疡出血的疗效。方法 选取80例消化道溃疡患者,随机分为两组,观察组静脉滴注泮托拉唑,对照组静脉滴注奥美拉唑,两组均治疗7 d。观察并记录两组患者治疗后的疗效、治疗前后胃液pH值、出血时间、住院时间及出血量和治疗期间不良反应情况,评价奥美拉唑与泮托拉唑治疗消化道溃疡出血的疗效及安全性。结果 观察组有效率92.7%,对照组有效率89.7%,两组治疗有效率无明显差异;但观察组显效率（85.4%）明显高于对照组（56.4%）,差异有统计学意义（P<0.05）。治疗前两组胃液呈酸性,pH值相比无统计学差异,治疗后两组胃液pH有所提高,观察组胃液pH值高于对照组,差异有统计学意义（P<0.05）。观察组患者住院时间、止血时间均短于对照组,差异有统计学意义（P<0.05）;出血量明显少于对照组,差异有统计学意义（P<0.05）。治疗期间,观察组患者不良反应明显少于对照组,差异有统计学意义（P<0.05）。结论 泮托拉唑与奥美拉唑均适用于消化道溃疡出血的治疗,但泮托拉唑抗酸和止血效果更好,药物安全性更高,值得临床推广使用。     

注射用泮托拉唑合理使用的影响因素分析

目的 探讨注射用泮托拉唑临床合理用药的影响因素。方法 采用简单随机抽样方法抽取蚌埠医学院第二附属医院住院患者2014年度至少使用一次注射用泮托拉唑的住院病历300例,分析其用药合理性,并对用药指征合理性的影响因素进行多因素logistic回归分析。结果 注射用泮托拉唑用药总不合理率为73.00%,logistic回归分析结果显示,合并使用皮质类固醇药物、禁食、内镜检查和用药指征不合理呈负相关,年龄段与用药指征不合理呈正相关（P<0.05）。结论 年龄段为注射用泮托拉唑用药指征合理性的独立危险因素,合并使用皮质类固醇药物、禁食和内镜检查为保护因素。     

2012-2016年西安市第一医院质子泵抑制剂的使用情况分析

目的 对2012-2016年西安市第一医院质子泵抑制剂（PPIs）的使用情况进行分析,为临床合理用药提供参考。方法 采用回顾性方法,对2012-2016年西安市第一医院PPIs的销售金额、用药频度（DDDs）、日均费用（DDC）和排序比（B/A）等进行统计分析。结果 2012-2016年,PPIs的销售金额呈逐年增长的趋势;门诊和住院患者PPIs的销售金额、DDDs整体呈增加趋势;口服PPIs的销售金额和DDDs分别占24.4%、71.3%;注射用PPIs的销售金额和DDDs占比分别为75.6%、28.7%;5年来销售金额排名前3位的是注射用泮托拉唑（40 mg）、注射用兰索拉唑和雷贝拉唑钠肠溶片;DDDs排名前3位的是兰索拉唑肠溶片、雷贝拉唑钠肠溶片和注射用泮托拉唑（40 mg）。奥美拉唑肠溶胶囊、兰索拉唑肠溶片和泮托拉唑肠溶胶囊的DDC在5年中均小于10元。注射用兰索拉唑和注射用泮托拉唑（40 mg）5年的B/A均小于1.00。消化科PPIs的用药金额始终为第1位。结论 西安市第一医院注射用泮托拉唑的用量相对较大,可能存在一定程度的过度用药和不合理用药。     

泮托拉唑对比奥美拉唑治疗胃溃疡的Meta-分析

目的 系统评价泮托拉唑对比奥美拉唑治疗胃溃疡的疗效和安全性。方法 计算机检索PubMed、EmBase、Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文期刊全文数据库（VIP）和万方数据库,从建库至2018年7月公开发表的泮托拉唑和奥美拉唑治疗胃溃疡的随机临床对照试验（RCT）,由两位研究者独立筛选评价文献并提取资料,采用RevMan 5.3软件行系统评价。结果 共纳入15项RCTs,合计1 482例患者。Meta-分析结果显示：泮托拉唑组相对于奥美拉唑组在溃疡治愈率［RR=1.12,95% CI（1.02,1.24）,P=0.02］和幽门螺杆菌根除率［RR=1.40,95% CI（1.22,1.61）,P<0.000 01］方面的差异均有统计学意义;两组总有效率［RR=1.03,95% CI（1.00,1.07）,P=0.09］以及不良反应发生率［RR=1.34,95% CI（0.89,2.04）,P=0.16］比较无显著性差异。结论 泮托拉唑的胃溃疡治愈率和幽门螺杆菌根除率优于奥美拉唑,两者总有效率和不良反应发生率相当,安全性、耐受性均较好。     

HPLC法测定人血浆中伏立康唑及其代谢物的浓度

目的 建立一种快速、灵敏、准确、稳定的测定人血浆中伏立康唑及其代谢物浓度的方法,用于伏立康唑临床治疗药物监测。方法 采用高效液相色谱（HPLC）-紫外（UV）检测法,以罂粟碱为内标,乙腈蛋白沉淀法处理血浆样品。色谱柱为ACE5C₁₈-AR （150 mm×4.6 mm）,流动相为0.025 mol/L磷酸二氢钠（含三乙胺400 μl/L,用0.25 mol/L的氢氧化钠调至pH=7.0）-乙腈（67：33）,流速为l ml/min,柱温为40℃,检测波长为255、276 nm （双波长检测）,进样量为20 μl。结果 伏立康唑氮氧化物、伏立康唑和罂粟碱的保留时间分别为4.5、11.3、13.7 min;血浆中伏立康唑、伏立康唑氮氧化物线性范围均为0.5~20.0 μg/ml （r=0.999 5）,定量下限均为0.5 μg/ml,批内、批间RSD均<11%,定量下限、低、中、高梯度浓度提取回收率在90.3%~109.9%之间。结论 该方法操作简便,结果准确,适用于伏立康唑的临床治疗药物监测和对其主要代谢物的测定。     

利奈唑胺相关性血液毒性的危险因素分析

目的 探讨接受利奈唑胺治疗住院患者发生相关性血液毒性的危险因素。方法 采用单中心、观察性、回顾性研究。收集78例接受利奈唑胺治疗且监测血药浓度的住院患者的临床资料,多因素Logistic回归分析其相关危险因素。结果 Logistic回归分析显示利奈唑胺疗程[OR=1.296（1.094~1.53）,P=0.003],肾小球滤过率估计值<30 mL·min^-1·（1.73 m²）^-1[OR=11.582（1.870~71.729）,P=0.008]是白细胞减少症的显著危险因素;利奈唑胺首次谷浓度[OR=1.178（1.052~1.318）,P=0.005],基础血白蛋白值< 30 g·L^-1[OR=4.175（1.315~13.254）,P=0.015]是血小板减少症的显著危险因素。结论 利奈唑胺相关性白细胞减少症呈时间依赖,相关性血小板减少症呈浓度依赖,患者在治疗期间应密切监测血常规,情况许可下建议监测血药浓度,行个体化治疗。     

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.