1例长期服用华法林患者围手术期的抗凝策略

目的：探索长期接受抗凝治疗患者围手术期的抗凝治疗策略,体现临床药师参与药物治疗的作用。方法：回顾临床药师参与1例长期接受华法林抗凝治疗患者围手术期抗凝方案,结合相关的文献资料,从药物的选择、使用时机、剂量、疗程等方面进行分析。结果：临床药师结合药动学知识,制定抗凝方案,最大程度上降低了患者出血和栓塞的风险。结论：围手术期应该至少提前5d停用华法林,并监测国际标准化比值（INR）;术后无继续出血可在12h内开始使用低分子肝素,同时服用华法林,并监测INR,待达标后停用低分子肝素。如果患者要连续进行多次手术,则在整个手术期间建议使用低分子肝素进行抗凝。     

桥接抗凝在心房颤动患者PCI围手术期的应用及对靶血管重建、预后的影响

目的:探究桥接抗凝在心房颤动患者PCI围手术期的应用效果及对靶血管重建、预后的影响.方法:回顾性分析某院97例需要接受冠状动脉介入手术(PCI)且术前长期服用华法林的心房颤动患者为研究对象,其中49例术前停用华法林并采用低分子肝素桥接抗凝治疗为桥接组,48例围手术期维持使用华法林抗凝治疗为非桥接组,比较两组围手术期出血...     

长期服用华法林患者围手术期抗凝治疗分析及药学监护

目的 探讨临床药师在长期服用华法林抗凝患者围手术期的药学服务内容和作用。方法 通过对长期服用华法林抗凝患者围手术期出血风险及栓塞风险评估,临床药师帮助临床医师制定规范、合理的个体化抗凝方案,并提出围手术期抗凝治疗的监护重点。结果 通过合理、有效的围手术期抗凝治疗,可在不增加栓塞风险的基础上避免围手术期不良出血事件;同时还可通过药物合理选用及剂量调控,积极有效的规避抗凝药物相关的不良反应。结论 在长期服用华法林抗凝患者的围手术期治疗中,临床药师应根据患者栓塞及手术风险,从术前评估、是否给予桥接治疗、术后抗凝、抗凝药物选择及剂量等方面,为患者提供个体化的抗凝治疗方面。     

持续华法林治疗对起搏器植入术后囊袋血肿的影响

目的观察围术期继续应用华法林对起搏器囊袋血肿发生率的影响。方法180例服用华法林的患者接受永久起搏器植入,按照随机表随机分成继续华法林组和肝素桥接组,各90例。继续华法林组患者给予围术期内监测凝血酶原国际化比值,并维持华法林治疗（华法林剂量3．0—6．0mg）;肝素桥接组患者围术期内采用低分子肝素桥接[1mg／（kg·12h）],观察住院期间2周内囊袋的血肿发生率。结果继续华法林组囊袋血肿发生率为6．7％（6／90）,肝素桥接组为17．8％（16／90）,2组比较差异有统计学意义（P=0．023）。Logistic回归分析显示低分子肝素为发生囊袋血肿的独立危险因素（RR=2．665,95％CI=1．073—8．156,P=0．023）。结论与肝素桥接法比较,围术期继续服用华法林不明显增加起搏器囊袋血肿发生率。     

1例左心耳封堵联合射频消融抗栓治疗病例分析及文献复习

通过1例行左心耳封堵联合射频消融术患者的围术期及术后抗栓治疗方案调整情况,结合最新国际相关临床使用指南和治疗进展,总结、分析左心耳封堵联合射频消融术的围术期及术后抗栓治疗的选择。左心耳封堵联合射频消融手术适合高危房颤患者,既可以改善房颤症状,又能减少卒中和出血风险。使用新型口服抗凝药的患者术前一般需停药24 h以上,术中使用肝素,术后6 h以上即可恢复抗凝。使用华法林患者术前一般需停药3d以上,低分子肝素进行桥接。手术后抗凝6周可进行超声评估,内皮化完全后停止抗凝,之后使用双抗6个月,阿司匹林终身服用。患者在使用抗凝、双抗期间,如果出现出血事件,根据临床实际情况停用抗栓药物。医生和药师需权衡患者病情及出血风险决定术后的抗血小板治疗方案。     

达比加群、华法林分别用于心房颤动患者射频消融术后疗效与安全性的比较

目的:比较达比加群、华法林用于心房颤动患者射频消融术(RFCA)后的疗效和安全性。方法:回顾性分析141例非瓣膜性心房颤动并拟行RFCA患者资料,按用药的不同分为华法林组(71例)和达比加群组(70例)。华法林组患者入院前曾服华法林者入院后需停用,改为低分子肝素钙注射液100 U/kg,皮下注射,待INR<1.5时行RFCA,术前12 h停用低分子肝素钙注射液;术中静脉注射肝素钙注射液100 U/kg;术后4~6 h口服华法林钠片4.5 mg,每日1次,同时与低分子肝素桥接重叠治疗至少3~5 d;术后每3 d监测1次国际标准化比值(INR),维持INR 2.0~3.0,至少服用华法林3个月。达比加群组患者入院后停用曾服用的抗凝药物,改为口服达比加群酯胶囊110 mg(年龄≥70岁或体质量<60 kg)或150 mg(年龄<70岁或体质量≥60 kg),每日2次;术前24 h停用达比加群酯胶囊,术中用药同华法林组;术后6 h口服达比加群酯胶囊,至少服用3个月。观察两组患者术后第1、3个月总死亡率、脑卒中(短暂性脑缺血,缺血性脑病)发生率、外周血管栓塞率及出血情况。结果:两组患者术后第1、3个月总死亡率、脑卒中发生率、外周血管栓塞率、出血发生率比较,差异均无统计学意义(P>0.05)。结论:达比加群用于非瓣膜性心房颤动患者RFCA的抗凝疗效和安全性均与华法林相当。     

长期使用华法林抗凝的非瓣膜性房颤患者围手术/操作期使用NOAC桥接的抗凝方案研究

目的:探讨使用非维生素K拮抗剂的口服抗凝药物(NOAC)代替肝素类药物在围手术/操作期患者进行桥接抗凝的可行性.方法:本研究为前瞻性观察研究,2018年8月至2021年5月入选长期使用华法林抗凝的非瓣膜性房颤患者,观察患者在围手术/操作期使用NOAC桥接抗凝后,围手术/操作期以及术后30天内栓塞事件与出血事件的发生率....     

心脏机械瓣膜置换术后行骨科手术患者围术期抗凝治疗探讨

目的 探讨心脏机械瓣膜置换术后行骨科手术患者围术期抗凝治疗的方法.方法 回顾性分析1998年10月至2014年10月首都医科大学附属北京安贞医院人工心脏机械瓣膜置换术后行骨科手术的50例患者临床资料.患者术前3d开始停用华法林,采用1 mg/kg低分子肝素替代治疗,皮下注射,1次/12 h,术前12h停用,术后24h开始恢复使用低分子肝素,术后48 h开始口服华法林,凝血酶原时间国际标准化比值大于1.5时停用低分子肝素,逐渐调整华法林至合适用量.记录患者围术期出血量、卡瓣率(超声心动复查是否有瓣膜血栓形成,瓣膜功能是否正常)和深静脉血栓发生率,比较患者手术前后血红蛋白水平.结果 50例患者术中出血量为200 ～ 550 ml,平均(320±75) ml;术后引流量为380～ 750 ml,平均(580±85)ml.术后5例患者出现出血,给予相应治疗后好转.所有患者未发现瓣膜血栓形成和下肢深静脉血栓.术前与术后第4、10天的血红蛋白比较,差异无统计学意义[(120±9)g/L比(117±11)、(118±12)g/L,均P＞0.05].结论 心脏瓣膜置换术后行骨科手术患者围术期应用低分子肝素替代华法林抗凝治疗可有效防止大量失血、卡瓣、深静脉血栓形成等严重并发症.     

长期服用华法林患者围手术期抗凝治疗与药学监护分析

目的 分析长期服用华法林患者围手术期抗凝治疗与药学监护结果,总结治疗、监护经验.方法 2012年1月~2017年2月,医院共为长期服用华法林手术患者进行围术期抗凝治疗、药学监护,所有患者都进行会诊,进行详细的风险评估,指导侨联抗凝治疗.结果 入院时~出院后首次复查INR,共开展118次INR检查,全部受控,控制水平达到预期目标.未见大出血、血管栓塞并发症,出现2例牙龈出血、皮下瘀斑,1例患者监测了APTT,共监测12次,均全部受控.术后开始联合华法林时间(15.6±3.4)d,停止抗凝时间(19.6±5.5)d.结论 加强药学监护,指导开展围术期华法林的停用、复用、抗凝治疗,是保障抗凝治疗安全性,降低大出血、血管栓塞等并发症的关键.     

华法林在低栓塞风险的心房颤动患者射频消融术后的应用

目的探讨消融治疗获得成功的持续性心房颤动患者,特别是栓塞风险低的个体,术后是否需要继续应用华法林抗凝治疗。方法入选低危栓塞风险的持续性心房颤动患者107例,射频消融术后随机分为华法林治疗组(55例)和非华法林组(52例),华法林治疗组患者术后服用华法林治疗至少3个月,抗凝治疗强度为INR2.0～3.0;非华法林组只服用阿司匹林,每日100mg。所有患者术后均进行随访,观察比较两组患者血栓栓塞和出血事件发生率的差异。结果所有患者均成功完成射频消融术,即刻成功率为100%。两组患者术中均未发生栓塞或出血事件。随访6～18个月,华法林组发生血栓栓塞事件2例(3.6%),非华法林组发生2例(3.7%),两组患者栓塞发生率无统计学差异,P>0.1。华法林组有3例(5.5%)出血事件,非华法林组无出血事件发生。结论对于射频消融取得成功的低危心房颤动患者,可以考虑不应用华法林抗凝,而只服用阿司匹林。     

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.