运用ELISA法监测器官移植患者FK 506血药浓度

目的通过监测器官移植术后服用FK506患者全血谷浓度,观察并建立治疗组患者治疗窗,为临床提供参考。方法用ELISA法测定FK506全血谷浓度,对9例患者的48例次监测结果进行分析。结果用ELISA法监测FK506全血谷浓度的治疗窗范围为,术后1个月内10～15ng·mL^-1,第二～三个月8～12ng·mL^-1,4～6个月6～10ng·mL^-1,大于6个月3～7ng·mL^-1。结论常规监测FK506全血谷浓度,按推荐治疗窗调整给药方案,可获得满意的免疫抑制治疗效果。     

肾移植术后不同时期环孢素A的血浓范围

目的:确定长期存活的肾移植术后患者环孢素 A(CsA)的治疗窗.方法:将已存活4a以上的39例肾移植患者763个血浓谷值按术后时间分为7组,按肝肾功能指标分为3组进行比较分析.结果:肾移植患者的全血CsA谷值(多克隆)维持浓度随着术后时间的延长而降低,肾移植患者各个时期CsA较适宜的治疗窗为:450～600ng/ml(0～6mo),400～550 ng/ml(6～12mo),350～500 ng/ml(1～3a),300～450ng/ml(3～5a),250～40Ong/ml(5～7a).结论:肾移植患者的全血CsA谷值维持浓度随术后时间延长而降低.     

影响肾移植术后环孢素谷浓度相关因素的研究

目的　 通过肾移植术后环孢霉素A(CsA)全血谷浓度的分析 ,提出肾移植术后CsA较理想的浓度和几个因素对浓度的影响。 方法 　利用荧光偏振免疫 (FPIA)法测定CsA谷浓度。按术后时间、临床表现、性别、用药方案进行比较。 结果 　理想治疗浓度范围 :术后 1月为 344～ 6 71ng/ml,2～ 3月为 311～ 5 83ng/ml,4～ 6月为378～ 5 16ng/ml,7～ 12月为 2 0 4～ 4 6 4ng/ml,13～ 2 4月为 15 3～ 30 8ng/ml,大于 2 4月为 10 3～ 2 0 2ng/ml,男女分组CsA浓度无显著差异 ,两种用药方案 1年内CsA浓度有显著差异。 结论 　不同时间段平均CsA浓度会有所不同 ,肾移植术后CsA浓度在性别上无差异 ,两种用药方案CsA浓度 1年内有显著差异 ,1年后无显著差异     

肾移植后FK506的监测状况

目的:研究动态监测免疫抑制剂FK506的临床意义。方法:使用ELISA法进行全血浓度测定,监测42例使用FK506的患者在肾移植后第3天、第1周、第2周、第1个月～第4个月及第6个月的血药浓度。结果:服用FK506后测得第3天平均血药浓度为(15.3±2.2)ng/mL,第1周(16.4±2.8)ng/mL,第2周(16.1±2.5)ng/mL,第1个月(16.8±2.3)ng/mL,第2个月(11.3±1.7)ng/mL,第3个月(10.8±1.4)ng/mL,第4个月(6.8±0.9)ng/mL,第6个月(6.1±0.7)ng/mL。2例发生急性排斥反应的血药浓度明显低于正常平均浓度,3例发生肾中毒患者的血药浓度明显高于正常平均浓度,及时调整用药剂量,情况有所好转。结论:由于FK506个体差异大,治疗窗窄,极易造成急性排斥反应或肾中毒,因此,对于临床医生来说,要密切监测FK506的全血浓度,以便能够及时调整用药剂量,充分发挥免疫抑制作用,最大限度地减低毒副作用,取得肾移植的理想治疗效果,延长移植物的存活率。     

56例患者肾移植术后他克莫司治疗窗浓度范围再探讨

目的:探讨适合中国人的肾移植术后他克莫司(FK506)治疗窗浓度范围。方法:采用微粒子酶免疫法测定56例肾移植术后患者口服FK506后12h的全血谷浓度,并观察排斥反应及肾毒性反应的发生情况。结果:肾移植术后FK506的推荐治疗窗浓度范围0mo~1mo为9~14μg/L,2mo~3mo为8~12μg/L,4mo~6mo为6~10μg/L,7mo~12mo为4~6μg/L。结论:在上述治疗窗浓度范围内,既能达到满意的免疫抑制效果,又能减少排斥反应和肾毒性反应的发生。     

微粒子酶免分析法测定他可莫司全血浓度结果分析

采用微粒子酶免分析法测定肾移植患者FK506全血谷浓度.结果发现:食物、合并用药等均是影响其全血谷浓度的重要因素;从免疫抑制效果看,术后第1个月、第2个月、第3个月和3个月以上的理想稳态血药浓度范围分别为15～18ng*ml-1、13～16ng*ml-1、12～15ng*ml-1、10～12ng*ml-1.     

肝移植受者他克莫司治疗窗浓度的初步探讨

目的探讨肝移植受者他克莫司治疗窗浓度参考范围。方法采用化学发光微粒子免疫法(CMIA)监测他克莫司全血谷浓度(C0),结合受者的临床表现及生化指标,对74例肝移植受者的305例次监测结果进行分析。结果肝移植术后前3个月他克莫司C0为(7.0±3.6)ng/ml,3个月后为(5.5±2.3)ng/ml。术后发生急性排斥反应4例次,肝、肾毒性54例次。结论建议将实验室他克莫司治疗窗范围进行调整:肝移植术后前3个月为7～15ng/ml,3个月后为5～10ng/ml,以保证免疫抑制效果,减少排斥反应和肝、肾毒性。     

微粒子酶免分析法测定他可莫司全血浓度结果分析

采用微粒子酶免分析法测定肾移植患者FK5 0 6全血谷浓度。结果发现 :食物、合并用药等均是影响其全血谷浓度的重要因素 ;从免疫抑制效果看 ,术后第 1个月、第 2个月、第 3个月和 3个月以上的理想稳态血药浓度范围分别为 15～ 18ng·ml-1、13～ 16ng·ml-1、12～ 15ng·ml-1、10～ 12ng·ml-1。     

肾移植术后患者全血西罗莫司浓度监测结果分析

目的:探讨肾移植术后患者全血西罗莫司浓度的治疗窗以及西罗莫司对血常规、肝肾功能、血脂和尿蛋白的影响。方法:采用微粒子发光免疫分析技术（MEIA）测全血西罗莫司谷浓度。对3年来294例次肾移植术后患者全血西罗莫司浓度,以及西罗莫司对血常规、肝肾功能、血脂和尿蛋白的影响进行分析。结果:294例次全血西罗莫司浓度中有206例次（70%）在3～8ng·ml^-1范围内。肾移植6个月后,全血西罗莫司浓度测定值随移植时间延长而降低。服用西罗莫司后的尿蛋白数值升高,与服用之前相比差异有统计学意义（P<0.05或0.01）。结论:全血西罗莫司谷浓度治疗窗:术后1～3个月为4～6ng·ml^-1,第4～6个月为3～6ng·ml^-1,>6个月为3～5ng·ml^-1。     

ELISA法监测肾移植患者他克莫司全血浓度448例次结果分析

为探讨肾移植后患者他克莫司的治疗窗，为临床应用提供参考依据，用ELISA法测定448例次他克莫司全血浓度。结果表明，肾移植后用三联免疫抑制给药方案时，他克莫司全血谷浓度的治疗窗范围以术后1个月内8—15μg&;#183;L^-1、第2—3个月6—12μg&;#183;L^-1、第4—6个月5-10μg&;#183;L^-1、＞6个月3—8μg&;#183;L^-1较为适宜。结论：根据监测结果调整他克莫司给药方案，可获得满意的免疫抑制治疗效果。     

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.