Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long‐term monitoring of its intake by chiral LC–MS/MS analysis of cocaine‐positive hair samples

Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R‐/S‐phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine‐positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine‐positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography–tandem mass spectrometry (LC–MS/MS). For distinction of levamisole/dexamisole chiral LC–MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut‐off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT‐adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non‐racemic PTHIT. Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.     

左旋咪唑对MANA诱发大鼠食管癌前病变及免疫功能影响

目的本文旨在探讨左旋咪唑预防食管癌的作用及与免疫的关系。方法Ｗｉｓｔａｒ大鼠９０只，随机分为三组，分别给左旋咪唑、太洛龙（阳性对照）、生理盐水（阴性对照），用甲基戊基亚硝胺ＭＡＮＡ诱发食管癌前病变，经１０５天实验后，检测食管癌前病变发生率，并测定免疫器官指数，外周血Ｔ淋巴细胞和自然杀伤细胞（ＮＫ细胞）。结果显示左旋咪唑降低食管癌前病变发生率的作用和太洛龙（Ｔｉｌ）相似，并使外周血Ｔ淋巴细胞和ＮＫ细胞明显增加。Ｔｉｌ组ＮＫ细胞无增加。结论左旋咪唑和太洛龙具有相似地预防亚硝胺诱发食管癌作用，并与增强机体免疫功能相关。     

Side effects to levamisole given to neoplastic patients as adjuvant to surgery: A new case of agranulocytosis

Side-effects to levamisole given as adjuvant to surgery in a consecutive series of 203 neoplastic patients are reported: Thirty-four patients (16.7%) suffered gastric adverse reactions; 8 (3.9%) allergic; 6 (2.9%) intestinal; 6 (2.9% neurologic; 4 (1.9%) severe hyperthermia (more than 40.5°C); 3 (1.4%) flu-like illness; 1 (0.4%) leucopenia; and 1 (0.4%) agranulocytosis. Withdrawal rate was 5.4% or 11 patients. Side effects appeared sex-related (39.0% in females, 17.7% in males; with seven female dropouts out of 11), unrelated to other eventual adjuvant treatments, and reappearing at a new challenge with levamisole. The opportunity of very close control of patients taking levamisole for at least the first months is discussed.     

左旋咪唑通过促进抗原呈递细胞MHC-Ⅱ表达而加重实验性自身免疫性脑脊髓炎

目的：探讨左旋咪唑加重大鼠实验性自身免疫性脑脊髓炎（EAE）是否通过上调抗原呈递细胞（APC）主要组织相容性复合体Ⅱ类抗原（MHC-Ⅱ）表达而实现的。方法：SD大鼠28只随机分为完全弗氏佐剂（CFA）组（n=8）,EAE组（n=10）,左旋咪唑组（n=10）。用豚鼠脊髓匀浆和CFA的混匀乳剂免疫SD大鼠制作EAE模型。在造模前3d至造模后7d腹腔注射左旋咪唑10mg·kg-1（左旋咪唑组）。分析各组行为学变化及神经组织病理学改变,用流式细胞术检测脾脏APC表面分子MHC-Ⅱ的表达。结果：左旋咪唑加速了大鼠EAE的病程,加重了神经缺损症状与中枢神经病理学损害;左旋咪唑上调了脾脏APC表面分子MHC-Ⅱ的表达,且与EAE神经缺损症状程度呈正相关。结论：左旋咪唑上调了APC表面分子MHC-Ⅱ的表达可能为左旋咪唑促发EAE的作用机制。     

The influence of nonspecific immunotherapy on the course of Murine Melanoma

BCG, Corynebacterium parvum, vitamin A, and levamisole were continuously administered to C57 BL/6 mice bearing B16 melanoma prior to, with, and following tumor implantation as well as before and coincident with surgical excision of the implanted tumor. Only the group given levamisole prophylactically for 8 weeks before tumor inplantation showed a significant difference from control mice but a tenfold increase in dosage in this drug did not exert a comparable effect.     

北京市四所幼儿园儿童蛲虫感染调查及驱虫情况报告

本文用透明胶纸法对北京四所幼儿园儿童全托266人和日托268人调查了蛲虫感染率,结果分别为44.74％、27.98％,两者有显著差异。阳性者用丙硫咪唑或左旋咪唑驱虫,以丙硫咪唑200mg一次顿服组阴转率92％,值得推广。     

免疫药物对豚鼠T细胞α醋酸荼脂酶的影响

本文报导免疫增强剂和免疫抑制剂对豚鼠T细胞α醋酸(艹佘)脂酶(ANAE)的影响。分离豚鼠外周血中淋巴细胞,与一定浓度免疫药物在28℃共温30分钟,涂片,ANAE染色,镜检。结果表明,免疫增强剂左咪唑、丹参、首乌均不能明显增加豚鼠T细胞ANAE百分率;但免疫抑制剂氢化考的松、金银花、细辛则能明显降低豚鼠T细胞ANAE百分率。对产生比结果的原因作了探讨。     

宝塔糖中盐酸左旋米唑的离子对萃取分光光度测定法

盐酸左旋米唑糖锭剂(宝塔糖)中的左旋米唑与溴甲酚绿形成离子对,用氯仿萃取后在420nm 处测定,回收率为100.2%,变异系数为0.26%。该法操作简便,分析速度快,灵敏度高。     

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200,000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties and aspects of therapeutic efficacy and adverse events in clinical human use is then discussed. The emphasis is on praziquantel, oxamniquine and artemisinin derivatives (against schistosomes) and albendazole, mebendazole, levamisole, pyrantel pamoate and other compounds (against intestinal nematodes). The experience gained with combination chemotherapy in schistosomiasis and STH is briefly discussed. Finally, current research needs and the critical importance for development of novel anthelmintic drugs, so that chemotherapy can continue to serve as the backbone of integrated and sustainable control of schistosomiasis and STH, is highlighted.