阿托伐他汀钙致肝功能异常

患者,男,55岁,因"突发胸痛2h"于2010-06-20急诊入院。既往有高血压病、高血脂、高尿酸血症及糖尿病病史,无药物过敏史。体检:T36.5℃,P82次/min,R20次/min,BP 120/90mmHg。生化示:果糖胺2.44mmol·L^-1,血清总胆红素19.4μmol·L^-1,间接胆红素14.10μmol·L^-1,乳酸脱氢酶494U·L^-1,肌红蛋白91μg·L^-1,尿酸614μmol·L^-1,葡萄糖8.54mmol·L,甘油三酯2.32mmol·L^-1,ALT35U·L^-1,AST 23U·L^-1。初步诊断为心肌梗死。予肝素钠注射液5 mg+0.9%氯化钠注射液5ml q1h iv抗凝、阿     

摩罗丹致药物性肝损伤1例

患者,女,60岁,因慢性萎缩性胃炎予摩罗丹(16丸,po,tid)、奥美拉唑(20 mg,po,bid)等药物治疗后出现乏力、纳差、厌油腻、皮肤巩膜黄染、尿黄等症状,肝功能指标显著升高,丙氨酸氨基转移酶(ALT)1 483 U·L^-1,天冬氨酸氨基转移酶(AST)1 066 U·L^-1,碱性磷酸酶(AKP)351 U·L-1,γ-谷氨酰转肽酶(γ-GT)246 U·L^-1,总胆红素(TBil)28.4μmol·L^-1,直接胆红素(DBil)24.9μmol·L^-1。患者用药前肝功能正常,既往有摩罗丹导致肝功能损伤的病史,根据药物性肝损伤的Roussel Uclaf因果关系评估法,得分9分,考虑“极可能”是摩罗丹导致的药物性肝损伤,予停用摩罗丹并给予保肝治疗,肝功能恢复正常,随访半年,肝功能指标未见异常。     

注射用紫杉醇(白蛋白结合型)致下肢膝盖酸胀1例

<正>1病例资料患者,男,67岁,身高160 cm,体质量54 kg,体表面积1.55 m²。2021年2月19日,患者因肺恶性肿瘤、非角化型鳞状细胞癌,COVID-19核酸检测阴性入住六安市中医院肿瘤科。生化检查示：总胆红素9.34μmol·L^-1、直接胆红素2.71μmol·L^-1、间接胆红素6.63μmol·L^-1、白蛋白66.66 g·L^-1,电解质均在正常范围内。血常规：白细胞5.99×10⁹·L^-1、中性粒细胞绝对值3.66×10⁹·L^-1、红细胞3.64×10⁹·L^-1、血小板257.00×10⁹·L^-1、血红蛋白117.00 g·L^-1。肿瘤指标示：癌胚抗原8.76 ng·mL^-1、糖类抗原125 276.50 U·mL^-1...     

注射用丁二磺酸腺苷蛋氨酸致外周静脉炎2例

例1,女,29岁,因"孕33周,血糖偏高"入院。体检:患者一般情况可,T 36.8℃,P 80次/min,R 20次/min,BP110/80mmHg,患者否认食物、药物过敏史。入院检查全天监测血糖:6.2-11.2～10.2-12.0 mmol·L^-1,肝功能检查示提示:ALT 350 U·L^-1,AST 257 U·L^-1,ALP 351 U·L^-1,GGT 34 U·L^-1,总胆汁酸15μmol·L^-1,总胆红素15.1μmol·L^-1,直接胆红素8.2μmol·L^-1,LDH 371 U·L^-1。入院诊断:G2P1,孕33+1周,妊娠期糖尿病,妊娠期肝损。入院后保肝治疗,给予注射用丁二磺酸腺苷蛋氨酸[思美泰,意大利Hopspira S.P.A Via Pontina Km 52 04010 Campoverde（Aprilia）LT,批号:07G048E02]1.0 g,按说明书要求,先与原包装所附溶剂混合溶解后,加入到0.9%氯化钠注射液500ml（40滴/min）ivd。患者于静滴后约10 min左右出现注射部位沿静脉走向刺痛,查体发现沿注射部位左手及前臂红色条索状静脉改变,长约15cm,触之稍硬,有压痛,疑为丁二磺酸腺苷蛋氨酸引起的静脉炎。遂停药,患者注射肢体经热敷处理后逐渐好转。后改用多烯磷脂酰胆碱胶囊（易善复）保肝利胆治疗。例2,女,30岁,因"孕34+3周,孕期皮肤瘙痒,NST无反应1 d"入院。体检:T 37℃,P 80次/min,R 20次/min,BP120/60 mmHg。妇产专科检查:宫高33cm,腹围99 cm,估计胎儿体重3 000 g,胎位:头,胎心次数:145次/min。否认食     

辛伐他丁致横纹肌溶解综合征1例

[病例]患者,女,73岁。10 d前出现全身酸痛,4 d前不慎跌倒致左下肢疼痛明显,活动受限,于2011-04-09来我院门诊。急诊生化:白蛋白26.5g·L^-1,血糖10.36 mmol·L^-1,肌酸激酶（CK）15 786.0 U·L^-1,a淀粉酶362.1 U·L^-1,肌酸激酶同工酶（CK-MB）469.8 U·L^-1,乳酸脱氢酶（LDH）1 880.0 U·L^-1,肌酐（Cr）668.0μmol·L^-1,尿素氮（BUN）68.84 mmol·L^-1,谷丙转氨酶（ALT）919.0 U·     

猪苓多糖联合硼替佐米促进多发性骨髓瘤U266细胞的凋亡和自噬

目的研究猪苓多糖(PPS)联合硼替佐米(BTZ)对人多发性骨髓瘤U266细胞的影响。方法 (1)PPS 12.5～400μmol·L^-1或BTZ 10～80 nmo·L^-1处理U266细胞48 h,PPS 50μmol·L^-1+BTZ 10～80 nmol·L^-1处理U266细胞48 h,CCK-8法检测细胞存活率。PPS 12.5～50μmo·L^-1+BTZ 10～80 nmol·L^-1处理U266细胞48 h,Calcusyn软件分析计算联合用药指数(CI),并确定联合用药的浓度。(2) U266细胞分为细胞对照组、PPS 20μmol·L^-1组、BTZ 25 nmol·L^-1组和PPS 20μmol·L^-1+BTZ 25 nmol·L^-1组,孵育48 h。流式细胞术检测细胞凋亡率,Western印迹法检测细胞Bax、Bcl-2、活化胱天蛋白酶3、胱天蛋白酶3、自噬...     

1例使用吉非替尼致肝损伤的病例分析

1例68岁左肺恶性肿瘤男性患者盲试吉非替尼片(250 mg,po,qd)29 d后,天门冬氨酸氨基转移酶310 U·L^-1,丙氨酸氨基转移酶493 U·L^-1,碱性磷酸酶100 U·L^-1,总胆红素18μmol·L^-1,谷氨酰转肽酶60 U·L^-1,国际标准化比值1.81,多项肝功能指标异常,符合中度肝损伤的临床表现。医生采纳临床药师的建议对患者进行护肝治疗后,患者肝功能指标好转。临床药师全面动态评估患者的状况,对患者肝损伤与吉非替尼进行关联性分析评价,判断患者肝损伤很可能由吉非替尼引起。临床药师针对1例盲试靶向药患者的用药开展了分析,对后续治疗方案提出建议,对盲试药物作了讨论,为临床安全合理用药提供参考,具有重要借鉴意义。     

胃癌化疗致慢性肝炎急性发作死亡1例

1病例介绍患者56岁,因胃癌术后4月,乏力尿黄20d入院。患者4个月前因胃部不适经胃镜检查诊断为“胃癌”,并予根除性远端胃切除术,并行ECF方案化疗加放疗治疗,20余天前行第四次化疗。化疗后患者出现乏力尿黄,门诊以“胃癌”,“药物性肝炎”“慢性乙型病毒性肝炎”收入院。有乙肝史,但一直未处理及检查。无输血史。入院时查体:慢性病容,皮肤巩膜黄染,心律齐,肝肋下未触及。辅助检查;谷草转氨酶240U/L,谷丙转氨酶280U/L,总胆红素88~mol.L-1,直接胆红素53.2μmol.L-1,间接胆红素34.8μmol.L-1,白蛋白31.3G/L。血常规:WBCl.4X10E9/L,血小…     

伊布替尼联合BH3拟似物ABT737协同抗肿瘤作用及机制

目的 研究伊布替尼联合BH3拟似物ABT737的协同抗实体肿瘤作用及机制。方法 以2种类型实体肿瘤细胞,人非小细胞肺癌细胞株A549、H1299和人脑胶质瘤细胞U251、U87为对象,采用SRB法检测不同浓度伊布替尼(20,15,10,7.5,5μmol·L^-1)和BH3拟似物ABT737(20,15,10,7.5,5μmol·L^-1)单独或共同作用24 h后的细胞增殖情况,计算细胞存活率和合用指数;采用克隆形成试验检验10μmol·L^-1伊布替尼与10μmol·L^-1 ABT737联合作用120 h后的细胞克隆形成情况;成球试验检测两药联合作用7 d对细胞成球能力的影响;采用PI染色结合流式细胞术检测10μmol·L^-1伊布替尼与10μmol·L^-1 ABT737联用对U87和U251细胞凋亡的影响;RT-PCR检测两药联合作用24 h后对U87和U251细胞中干细胞标记物Sox2、Nanog和Oct4 mRNA水平影响;Western blotting...     

丁二磺酸腺苷蛋氨酸致静脉炎1例

病例：患者,女,30岁。因＂皮肤、巩膜黄染4天＂入院治疗,否认既往食物、药物过敏史。肝功示总胆红素226.65μmol·L^-1,直接胆红素156.84μmol·L^-1,间接胆红素69.81μmol·L^-1,谷丙转氨酶301 IU·L^-1,谷草转氨酶258 IU·L^-1,碱性磷酸酶223 IU·L^-1;肝炎系列、自身免疫抗体阴性,排除病毒性肝病、自身免疫性肝病,诊断为药物性肝病。     

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.     

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.     

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.