口服硫唑嘌呤片致重症肌无力患者急性胰腺炎

1例65岁男性患者因患重症肌无力口服溴吡斯的明片(30mg、3次/d)、硫唑嘌呤片(75mg、2次/d)和醋酸泼尼松片(15mg、1次/d)治疗。2个月后患者出现腹痛伴恶心、呕吐症状。实验室检查示血脂肪酶(LPS)909U/L、尿淀粉酶(AMS)3838U/L,腹部超声及影像学检查均符合胰腺炎表现。未停用上述药物,按急性胰腺炎常规方案治疗,无明显好转。发病第11天开始给予奥曲肽注射液皮下注射、注射用泮托拉唑静脉滴注、甲硝唑口服及补液、纠正水电解质紊乱等支持治疗。次日实验室检查示血LPS 3332U/L、血AMS 139U/L,考虑患者的急性胰腺炎可能与硫唑嘌呤片有关,停用该药,其他治疗未变。患者症状很快缓解,4 d后复查,血LPS 546U/L,血AMS 49U/L。     

柳氮磺胺吡啶致急性胰腺炎

28岁男性患者,因再发溃疡性结肠炎,口服柳氮磺胺吡啶1g,4次/d,1周后出现上腹部持续性绞痛,恶心、呕吐,血清淀粉酶601U/L,尿淀粉酶1703U/L,诊断为急性胰腺炎入院。立即停用柳氮磺胺吡啶,经对症保守治疗后痊愈出院。随访2年7个月未再复发。     

西格列汀致急性胰腺炎

1例58岁女性2型糖尿病患者应用盐酸二甲双胍（0．5g,2次／d口服）及胰岛素（三餐前分别皮下注射胰岛素8、8、10U,睡前皮下注射甘精胰岛素8u）治疗,因效果不佳加用西格列汀（100mg,1次／d口服）。3周后,患者出现恶心、呕吐伴腹痛。实验室检查：血清淀粉酶499U／L,尿淀粉酶933U／L。腹部超声检查示腹腔积液。诊断为急性胰腺炎。停用西格列汀、盐酸二甲双胍,继续应用胰岛素,并给予抑酸、抑酶、补液等治疗。6d后,患者病情好转,血清淀粉酶76U／L,尿淀粉酶288U／L。     

维迪西妥单抗与特瑞普利单抗联用致心肌炎

1例68岁女性浸润性尿路上皮癌患者术后接受免疫治疗(维迪西妥单抗120 mg+特瑞普利单抗240 mg静脉滴注、第1天, 14 d为1个周期)。首次用药后19 d, 患者诉腰部肌肉酸痛, 实验室检查示肌酸激酶(CK)1 079 U/L, CK-MB 33 U/L。暂停第2个周期免疫治疗, 并予泼尼松20 mg口服、1次/d。5 d后, 患者出现胸闷, 实验室检查示CK 3 366 U/L, CK-MB 91 U/L, 乳酸脱氢酶518 U/L, 肌红蛋白1 282 μg/L, 高敏肌钙蛋白T 0.068 μg/L, 氨基末端脑利钠肽前体148 ng/L。结合心脏彩色多普勒超声检查结果, 考虑为维迪西妥单抗和特瑞普利单抗联用所致心肌炎, 将泼尼松换为甲泼尼龙160 mg静脉滴注、1次/d。患者上述实验室检查指标逐渐下降, 但心电图检查示异位心律, 给予胺碘酮等治疗。甲泼尼龙静脉滴注11 d后, 改为甲泼尼龙片20 mg口服、1次/d(逐渐减量并停用)。停用激素后4 d复查, 患者实验室指标和心电图未见异常。     

硫唑嘌呤致严重胃肠道反应

1例28岁女性患者,因垂体炎所致中枢性尿崩症给予甲泼尼龙40 mg、1次/d静脉注射。2周后改为泼尼松10 mg、3次/d口服,硫唑嘌呤50 mg、2次/d口服。第4天,患者出现上腹胀、反酸、恶心。给予对症治疗,效果不佳。1周后停用泼尼松。2周后患者出现剧烈上腹痛伴呕吐。胃镜检查示慢性胃炎。遂停用硫唑嘌呤。2 d后胃肠道症状明显缓解。1周后胃肠道症状消失,但尿量逐渐增多,再次给予硫唑嘌呤50 mg口服。服药后约1 h,再次出现相同胃肠道症状,对症治疗后缓解。     

莫西沙星与阿托伐他汀钙联用相关横纹肌溶解

1例80岁男性患者,因脑梗死及高脂血症口服阿托伐他汀钙20 mg,1次/d。服药20 d后出现胸痛、胸闷、无力,实验室检查示肌酸激酶(CK)由130 U/L升至741 U/L,同时出现肾功能异常和电解质紊乱。第28天,患者因肺部感染给予莫西沙星注射液0.4 g静脉滴注,之后患者CK由741 U/L升至3565 U/L,停用阿托伐他汀钙;莫西沙星改为头孢哌酮舒巴坦钠。10 d后CK逐渐下降至54 U/L,其他血生化检查均恢复正常。     

英夫利西单抗治疗溃疡性结肠炎合并强直性脊柱炎临床分析

目的探讨英夫利西单抗治疗溃疡性结肠炎合并强直性脊柱炎的临床效果。方法对我院收治的5例溃疡性结肠炎合并强直性脊柱炎患者进行英夫利西单抗治疗,6周后观察患者临床表现,分析并总结英夫利西单抗的治疗效果。结果 2例溃疡性结肠炎合并强直性脊柱炎患者经过英夫利西单抗治疗2周后,胸部、腰背部疼痛明显缓解;6周后C反应蛋白（CRP）、红细胞沉降率（ESR）较治疗前明显降低。结论英夫利西单抗能迅速减轻溃疡性结肠炎合并强直性脊柱炎患者的临床症状与体征,对显著改善患者功能与生活质量具有重要的临床作用。     

替雷利珠单抗致肝损伤和糖尿病酮症酸中毒

1例63岁女性食管癌患者, 既往无慢性肝病和糖尿病史, 手术后接受替雷利珠单抗200 mg静脉滴注、1次/21 d单药治疗。替雷利珠单抗第4个周期治疗后39 d发现肝功能异常, 丙氨酸转氨酶494 U/L, 天冬氨酸转氨酶442 U/L, 碱性磷酸酶1 161 U/L, 总胆红素21.4 μmol/L。停用替雷利珠单抗。经肝脏病理学检查及相关实验室检查排除其他原因导致的肝损伤, 考虑其与替雷利珠单抗有关。给予甲泼尼龙(32 mg/d口服)及保肝治疗后, 患者肝功能逐渐好转。甲泼尼龙治疗2周后, 减量至16 mg/d, 减量2周后发现患者空腹血糖升高至19.4 mmol/L。甲泼尼龙减量至8 mg/d, 2 d后血糖升至33.7 mmol/L, 血乳酸3.66 mmol/L, 尿酮(++++), 诊断为糖尿病酮症酸中毒, 停用甲泼尼龙。实验室检查示空腹和餐后血胰岛素和C肽水平明显降低, 提示胰岛功能损伤, 考虑为替雷利珠单抗所致的1型糖尿病。经补充胰岛素、纠正酸中毒等治疗后患者肝功能好转。8个月后随访, 患者肝功能恢复正常, 但需长期依赖胰岛素控制血糖。     

红曲米致横纹肌溶解症2例

2例患者(例1男, 61岁;例2女, 58岁)均因血脂异常使用红曲米6 g口服、1次/d。例1有血吸虫性肝硬化、胆汁淤积性肝炎, 三酰甘油5.32 mmol/L, 口服红曲米26 d后出现四肢无力、肌酸激酶(CK)604 U/L。立即停用红曲米, 3 d后患者出现下肢肌肉酸痛, CK最高达117 748 U/L, 经地塞米松、补液水化治疗12 d后上述症状逐渐消失, CK 79 U/L。例2为急性肝炎患者, 三酰甘油2.34 mmol/L, 口服红曲米24 d后出现双下肢乏力、肌肉酸痛, CK最高达52 222 U/L。立即停用红曲米, 予甲泼尼龙、补液水化等治疗12 d后病情好转, CK 210 U/L。     

辛伐他汀致横纹肌溶解症

1例57岁男性患者因急性心肌梗死行冠状动脉支架置入术。术后给予阿司匹林100 mg,1次/d口服;氯吡格雷75 mg,1次/d口服;辛伐他汀40 mg,1次/d睡前口服。第5天患者出现右下肢酸痛。第8天肌酸激酶2085 U/L,血清肌酐187μmol/L,同时出现尿色加深,尿潜血(+)。停用辛伐他汀,继续使用阿司匹林及氯吡格雷,同时给予辅酶Q10口服。停药第2天患者右下肢酸痛症状明显缓解,肌酸激酶1337 U/L。停药第11天,其肌酸激酶降至186 U/L,血清肌酐101μmol/L,遂出院。     

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.