6 062例次他克莫司全血浓度监测结果分析

目的通过监测器官移植患者他克莫司全血浓度,观察他克莫司在三联免疫抑制用药方案中的理想治疗范围,为临床合理应用该药提供参考。方法用ELISA法测定他克莫司全血浓度,对640例患者共6 062例次监测结果进行比较分析。结果他克莫司全血浓度随移植后时间延长而逐渐下降。移植后1个月内、第2～3个月、第4～6个月和＞6个月时,用ELISA法监测他克莫司全血谷浓度的治疗范围应分别为8～15,6～12,5～10和3～8 μg•L 1,较为适宜。结论常规监测他克莫司全血浓度,参考推荐治疗范围调整给药方案,可获得满意的免疫抑制治疗效果。     

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。     

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。     

初步探讨他克莫司（FK506）对肝移植受者的治疗窗浓度及其与年龄、性别的关系

目的:探讨适合我国肝移植受者他克莫司理想治疗窗浓度范围及其与年龄、性别的关系.方法:应用微粒子酶免分析法测定75例不同年龄、性别肝移植受者口服他克莫司后12h的血药谷浓度,并观察排斥反应的发生及药物不良反应.结果:他克莫司的血药浓度,术后第1个月为11.3～15.5 ngmL-1,第2、3个月为7.8～10.7 ngmL-1,3个月后为5.3～7.8 ngmL-1,比较不同时期全血他克莫司的谷浓度,均有显著差异(P<0.01).术后发生排斥反应64例次,不良反应73例次.结论:建议他克莫司治疗窗浓度范围改为:术后第1个月为10～15 ngmL-1,第2,3个月为7.0～11 ngmL-1,3月后为5.0～8.0 ngmL-1维持;此浓度范围既能达到满意的免疫抑制效果,又能减少他克莫司的不良反应,并观察到其浓度与年龄、性别有一定的相关性.     

肝移植受者他克莫司治疗窗浓度的初步确定

目的寻求适合国人肝移植受者他克莫司理想治疗窗浓度范围.方法应用微粒子酶免分析法测定69例肝移植患者口服他克莫司后12 h的血药谷浓度,并观察排斥反应的发生及药物的不良反应.结果他克莫司的血药浓度,术后第1个月为(13.1±2.0)μg*L-1,第2,3个月为(9.2±1.7)μg*L-1,3个月后为(6.3±1.2)μg*L-1,比较各时期全血他克莫司谷浓度,差异均有极显著性(P＜0.01).术后发生排斥反应64例次,不良反应73例次.结论他克莫司治疗窗浓度范围术后第1个月为10～15 μg*L-1,第2、3个月为7.0～11 μg*L-1,3个月后为5.0～8.0 μg*L-1维持,此浓度范围既能达到满意的免疫抑制效果,又能减少他克莫司的不良反应.     

肾移植患者全血他克莫司浓度监测结果分析

目的：探讨肾移植患者全血他克莫司浓度的治疗窗及对血常规和肝肾功能的影响。方法：MEIA法监测全血他克莫司谷浓度。对近4年来390例次肾移植患者全血他克莫司浓度，及他克莫司对血常规和肝肾功能的影响进行分析。结果：390例次全血他克莫司浓度中377例次（80．8％）在3～15μg·L^-1的范围内。移植后6个月内，全血他克莫司浓度差异较大。随着移植时间延长，全血他克莫司浓度逐步降低。在治疗剂量内，他克莫司对肾移植受者的血常规和肝肾功能无明显影响。结论：全血他克莫司谷浓度的治疗窗：术后1～3月为5～15·L^-1，第4～6月为5～10·L^-1，〉6个月为3～10·L^-1。他克莫司对肾移植受者的血常规和肝肾功能无明显影响。     

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。     

ELISA法监测肾移植患者FK506切换组血药浓度

目的　通过监测肾移植后FK5 0 6切换组患者全血谷浓度 ,观察并建立切换组患者治疗窗 ,为临床提供参考。方法　用ELISA法测定FK5 0 6全血谷浓度 ,对 4 5例患者的 4 11例次监测结果进行分析。结果　FK5 0 6全血谷浓度平均值随切换时间于移植后时间延长而逐渐下降。切换于肾移植后 1个月内、第 2～ 3个月、第 4～ 6个月和 >6个月时 ,用ELISA法监测FK5 0 6全血谷浓度的合理治疗窗范围应分别为 :8～ 14ng/ml,7～12ng/ml,6～ 10ng/ml和 4～ 8ng/ml。结论　常规监测FK5 0 6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。     

酶联免疫法与微粒子酶免疫法检测全血他克莫司浓度的比较

目的 :比较微粒子酶免疫法 (MEIA)和酶联免疫法 (ELISA)检测全血他克莫司浓度的特点 ,总结其在临床他克莫司全血浓度检测中的应用。方法 :分别以MEIA和ELISA平行测定高、中、低标准浓度的他克莫司血样 ,比较两种方法的准确度、精密度、相关性及各自特点。以他克莫司谷浓度测定结果结合器官移植受者的临床情况 ,比较MEIA法和ELISA法在心脏、肝脏、小肠和肾脏移植患者全血他克莫司谷浓度治疗窗的范围。结果 :MEIA和ELISA方法学的回收率分别为 (96 .4±1 .4) %和 (1 0 4.7± 1 .8) %,RSD分别为 (7.7± 2 .0 ) %和 (8.2± 1 .7) %,r =0 .96。与MEIA法相比 ,ELISA法灵敏度更高、测试成本更低 ,但分析速度较慢。MEIA和ELISA可采用相同的谷浓度治疗窗范围。结论 :两种方法均准确可靠 ,适用于临床他克莫司的治疗药物监测。     

微粒子酶免疫法监测肝移植术后他克莫司血药浓度

目的:为了避免他克莫司的不良反应,对使用他克莫司的肝移植患者实施治疗药物监测。方法:用微粒子酶免疫法测定全血他克莫司谷浓度,并对他克莫司谷浓度的监测结果进行回顾性分析。结果:当肝移植患者被给予他克莫司、泼尼松和硫唑嘌呤时,他克莫司谷浓度与剂量之间存在正相相关。为了得到理想的效果和最小的毒性,他克莫司的全血药物浓度在肝移植后的90d内应维持在10～20μg·L~(-1),90d后在5～15μg·L~(-1)。结论:对于肝移植患者,他克莫司的全血药物浓度监测是很必要的,而且对于减少毒性和排斥反应的危险性是很有帮助的。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.