洛美沙星静脉滴注致严重肝损害

1例44岁女性患者,因急性咽炎静脉滴注洛美沙星0.2 g加入5%葡萄糖注射液250 ml,2次/d。治疗2 d后患者出现乏力、多汗。肝功能检查:丙氨酸转氨酶(ALT)1076 U/L,天冬氨酸转氨酶(AST)653 U/L,总胆红素(TBil)43.1μmol/L,直接胆红素(DBil)32.3μmol/L。诊断:急性肝损害。立即停用洛美沙星,给予保肝药物。停药第4天患者症状好转,但出现巩膜及皮肤黄染。复查肝功能:ALT 731 U/L,AST 420 U/L,TBil 164.8μmol/L,DBil 122.9μmol/L。14 d后患者黄染消退,肝功能恢复正常。     

何首乌引起肝炎

患者女,42岁。因反复肝功能异常,伴黄疸,于2005年11月在当地住院治疗,诊断为急性肝炎,但甲、乙、丙、丁、戊型肝炎病毒学检测均阴性。经保肝治疗,1个月后好转出院。2006年4月,患者肝病复发,ALT535U/L,AST717U/L,T-Bil43.8μmol/L,D-Bil12.5μmol/L,I-Bil31.3μmol/L,再次住院治疗2个月。6月23日,ALT16U/L,AST32U/L,T-Bil12.4μmol/L,D-Bil4.1μmol/L,I-Bil8.3μmol/L,肝功能正常出院。但7月初,患者第3次出现肝功能异常,ALT87U/L,AST117U/L,胆红素正常,为明确诊断,在北京某医院就诊,复查乙肝五项及甲、丙、戊型肝炎病毒…     

氟伐他汀致肝损害

1例47岁女性患者行冠状动脉支架术后给予氟伐他汀40mg,每晚1次,并同时给予阿司匹林、氯吡格雷、美托洛尔、单硝酸异山梨酯联合治疗。2个月后患者出现乏力、消瘦、纳差、恶心,伴随皮肤黄染、尿色加深。血生化检查：ALT777U/L,AST903U/L,ALP367U/L,γ-GT678U/L,TBil158.78μmol/L,DBil123.86μmol/L,IBil34.92μmol/L,TBA139.7μmol/L。自身抗体检查：抗核抗体及抗干燥综合征A抗原抗体阳性。停用氟伐他汀,继续服用阿司匹林、氯吡格雷、美托洛尔、单硝酸异山梨酯,并给予复方甘草酸苷、还原型谷胱甘肽及熊去氧胆酸等治疗。随后患者肝功能逐渐好转,1个月后血生化检查：ALT29U/L,AST33U/L,ALP122U/L,γ-GT150U/L,TBil40.04μmol/L,DBil26.84μmol/L,IBil13.20μmol/L,TBA25μmol/L,遂出院。出院后1个月复查肝功能恢复正常。     

联苯双酯引起肝损害加重

1例30岁妊娠女性,因慢性乙型肝炎入院。经保肝药物治疗,患者肝功能好转。为进一步降低氨基转移酶水平,加用联苯双酯15mg,3次/d治疗。2周后,患者肝功能恶化。实验室检测示：ALT24.9U/L,AST328.9U/L,TBil32.0μmol/L,DBil20μmol/L。停用联苯双酯,其他保肝药物继续使用,患者肝功能恢复正常。     

索拉非尼滥用致肝损害

1例60岁男性患者肾癌术后自行口服索拉非尼0.2 g、2次/d。2个月后患者出现全身乏力伴巩膜黄染、尿黄。实验室检查：总胆红素（TBil）146μmol/L,直接胆红素（DBil）94μmol/L,丙氨酸转氨酶（ALT）959 U/L,天冬氨酸转氨酶（AST）1150 U/L,γ-L-谷氨酰转肽酶（γ-GT）507 U/L。停用索拉非尼,给予三磷酸胞苷二钠、还原型谷胱甘肽、腺苷蛋氨酸治疗。24 d后复查肝功能：TBil 19μmol/L,DBil 10μmol/L,ALT 54 U/L,AST 40 U/L,γ-GT 22 U/L。     

胃刻宁片致急性肝损伤CSCD

1例58岁男性患者因胃溃疡自行口服胃刻宁片1.24 g、3次/d,同期未合并服用其他药物。1个月后患者出现腹胀、巩膜黄染、尿液发黄和乏力等症状,实验室检查示丙氨酸转氨酶(ALT)1272 U/L,天冬氨酸转氨酶(AST)507 U/L,总胆红素(TBil)59μmol/L,直接胆红素(DBil)34μmol/L。考虑为胃刻宁片导致的急性肝损伤。停用该药,予以保肝、利胆、降酶等治疗。10 d后,患者上述症状消失,肝功能检查示ALT 163 U/L、AST 43 U/L、TBil 23μmol/L、DBil 17μmol/L;1个月后,患者肝功能检查示ALT 31 U/L、AST 24 U/L、TBil 14μmol/L、DBil 6μmol/L。考虑患者的肝损伤可能与胃刻宁片所含的白屈菜有关。     

金刚藤胶囊及丹莪妇康煎膏致重症肝炎

1例34岁女性因慢性盆腔炎服用0.5 g金刚藤胶囊4粒,3次/d;丹莪妇康煎膏10 g,2次/d.患者既往无药物过敏史及慢性肝病史.治疗17 d后患者出现皮肤巩膜黄染、恶心、呕吐、腹胀、纳差.肝功能:ALT828 U/L,AST 768 U/L,TBil 222.1μmol/L,DBil 100.8 μmol/L,TBA 283.0 μmol/L.入院后患者黄疸持续,TBil最高达273.4μmol/L,PTA 45.6%,INR 1.63,肝穿刺病理检查提示肝小叶片状坏死,汇管区重度碎屑状坏死及桥接坏死,诊为重症药物性肝炎.停用两种药物,给予保肝和支持治疗,以及血浆置换治疗.入院12周后实验室检查示:ALT 49 U/L,AST 47 U/L,TBil 52.0μmol/L,DBil 44.3μmol/L和TBA 37.9μmol/L.出院3个月后肝功能恢复正常.     

复方雪莲胶囊致急性重症肝损害

患者男,64岁。因恶心、呕吐、尿黄、皮肤黄染5d,于2004年10月18日入我院消化科治疗。入院时患者体温38℃、畏寒。患者于5d前自觉恶心,呕吐,尿黄及皮肤黄染,2d前到我院门诊检测肝功能:ALT2571U/L,AST1984U/L;次日复查肝功能:ALT2001U/L,AST1350U/L;血常规:WBC6.0×109/L,L0.157,M0.083,N0.76。入院时初步诊断为呕吐原因待查,疑急性肝损害和胆道感染。入院后再次检测肝功能:ALT1484U/L,AST918U/L,r-GT71.9U/L,AKP141.3U/L,T-Bil276.8μmol/L,D-Bil157.2μmol/L,LDH687μmol/L,CHOL2.5mmol/L,白蛋白39.0g/L,球蛋白46g…     

氯雷他定致肝损害2例

2例女性患者(例1为67岁,例2为34岁)因皮疹分别服用氯雷他定10 mg,1次/d。于服药第67、天分别出现皮肤、巩膜黄染,并伴有尿色加深、食欲不振。实验室检查:例1总胆红素(TBil)204.3μmol/L,直接胆红素(DBil)108.24μmol/L,间接胆红素(IBil)96.06μmol/L,丙氨酸转氨酶(ALT)917 U/L,天冬氨酸转氨酶(AST)904 U/L;例2 TBil 85.3μmol/L,DBil 44.80μmol/LI,Bil 40.50μmol/L,ALT1565 U/L。均给予保肝、退黄治疗,症状逐渐好转,肝功能分别于治疗后40和14 d恢复正常。     

环丙沙星致肝细胞严重损害1例

患者,女,69岁,医生,于2000年8月14日因腹泻入院,临床诊断为急性肠炎,予静滴环丙沙星(批号:20000221)200mg.8月15日查肝功能:总胆红素(TB)31.1μmol/L,结合胆红素(DB)16.3 μmol/L,谷氨酸转氨酶(ALT)27U/L,天冬氨酸转氨酶(AST)52U/L,胆碱酯酶(CHE)5032U/L.用药3 d症状缓解后停药,因首次查肝功能部分指标偏高,8月21日复查肝功能:TB 15.4μmol/L,DB 2.9μmol/L,ALT21U/L,AST40U/L,CHE4830U/L.8月27日患者又一次腹泻,再次予以静滴环丙沙星200 mg,注射后约30min,患者自述四肢瘙痒,并沿输注静脉向心方向发红,继而出现寒战、高热、恶心、呕吐等症状,测BP100/70 mmHg、T40.3℃、HR120次/min,立即给予静注地塞米松20 mg,肌注苯海拉明20 mg,安痛定2 mL及物理降温等处理后,体温逐渐下降至正常.3 d后患者出现皮肤巩膜高度黄染,查肝功能:TB 242.7μmol/L,DB 140.2 μmol/L,ALT 36U/L,AST 65 U/L,CHE 3513U/L.临床诊断为药物性肝细胞损害,立即给予护肝治疗(复方氨基酸注射液250 mL,肌苷0.6 g,VitC 2.0 g,VitK1 30mg,iv,qd),病情逐渐好转,应患者家属要求转院治疗.     

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.

     

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.     

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.     

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.