Enantioselective renal excretion of albendazole metabolites in patients with neurocysticercosis

The present study investigates the urinary excretion of the enantiomers of (+)- and (-)-albendazole sulfoxide (ASOX) and albendazole sulfone (ASON) in 12 patients with neurocysticercosis treated with albendazole for 8 days (7.5 mg/kg/12 h). Serial blood samples (0-12 h) and urine (three periods of 8 h) were collected after administration of the last dose of albendazole. Plasma and urine (+)-ASOX, (-)-ASOX, and ASON metabolites were determined by HPLC using a chiral phase column (Chiralpak AD) with fluorescence detection. The pharmacokinetic parameters (P < 0.05) for (+)-ASOX, (-)-ASOX, and ASON metabolites are reported as means (95% CI); amount excreted (Ae) = 3.19 (1.53-4.85) vs. 0.72 (0.41-1.04) vs. 0.08 (0.03-0.13) mg; plasma concentration-time area under the curve, AUC(0-24) = 3.56 (0.93-6.18) vs. 0.60 (0.12-1.08) vs. 0.38 (0.20-0.55) microg x h/ml, and renal clearance Cl(R) = 1.20 (0.66-1.73) vs. 2.72 (0.39-5.05) vs. 0.25 (0.13-0.37) l/h. Sulfone formation capacity, expressed as the Ae ratio ASON/ASOX + ASON, was 2.21 (1.43-2.99). These data point to enantioselectivity in the renal excretion of ASOX as a complementary mechanism to the metabolism responsible for the plasma accumulation of (+)-ASOX. The results also suggest that the metabolite ASON is partially eliminated as a reaction product of the subsequent metabolism.     

Enterobius vermicularis egg positive rate in a primary school in Chungchongnam-do (province) in Korea

The egg positive rate of Enterobius vermicularis was investigated among students of a primary school and a kindergarten located in the rural area of Tangjin-gun, Chungchongnam-do in December, 1998. Of the 189 examinees, 28 (14.8%) were found to be infected with E. vermicularis by the adhesive cellotape anal swab method. The infection rates ranged from 4.2% to 26.1% among school children, and the highest rate was observed in children attending kindergarten. Three months after treatment with albendazole, four (14.3%) out of 28 infected children still remained infected with E. vermicularis. Through this survey, we were able to determine that E. vermicularis infection is still prevalent among children in rural areas of Korea.     

Direct separation of albendazole sulfoxide enantiomers by liquid chromatography on a chiral column deriving from (S)-N-(3,5-dinitrobenzoyl) tyrosine: application to enantiomeric assays on plasma samples

The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)-N-(3,5-dinitrobenzoyl)tyrosine-O-(2-propen-1-yl) methyl ester on a gamma-mercaptopropyl-silanized silica gel. A comparison with the resolution achieved on commercially available Pirkle-type CSPs obtained from N-(3,5-dinitrobenzoyl) derivatives of (R)-phenyglycine or (S)-phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane-dioxane-ethanol ternary mixture affords an almost baseline resolution (Rs = 1.25); however, in this case, albendazole sulfone (SO2ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane-ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane-ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO2ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.     

阿苯哒唑对蚯蚓的生态毒理效应

采用人工污染土壤法测定了不同浓度阿苯哒唑对蚯蚓生长、生存、繁殖以及超氧化物歧化酶（SOD）、谷胱甘肽-硫转移酶（GST-S）、乙酰胆碱酯酶（AchE）活性的影响.结果表明:低浓度阿苯哒唑（5 mg·kg^-1）对蚯蚓的繁殖有显著的抑制作用（P<0.05）;当阿苯哒唑含量达到7 mg·kg^-1时,将明显影响蚯蚓的生长和生存（P<0.05）;当其含量达到10 mg·kg^-1时,蚯蚓的死亡率为53%.阿苯哒唑浓度与蚯蚓的生长、繁殖间存在明显的剂-效关系.阿苯哒唑染毒21 d后,对蚯蚓SOD、GST-S的活性有明显影响,药物浓度与效应间没有明显的剂-效关系,对AchE活性没有表现出明显的影响.阿苯哒唑对土壤动物显示毒性作用,具有潜在的生态风险.     

Cutaneous Gnathostomiasis with Recurrent Migratory Nodule and Persistent Eosinophilia: a Case Report from China

The present study reports a human case of cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia in China. A 52-year-old woman from Henan Province, central China, presented with recurrent migratory reddish swelling and subcutaneous nodule in the left upper arm and on the back for 3 months. Blood examination showed eosinophila (21.2%), and anti-sparganum antibodies were positive. Skin biopsy of the lesion and histopathological examinations revealed dermal infiltrates of eosinophils but did not show any parasites. Thus, the patient was first diagnosed as sparganosis; however, new migratory swellings occurred after treatment with praziquantel for 3 days. On further inquiring, she recalled having eaten undercooked eels and specific antibodies to the larvae of Gnathostoma spinigerum were detected. The patient was definitely diagnosed as cutaneous gnathostomiasis caused by Gnathostoma sp. and treated with albendazole (1,000 mg/day) for 15 days, and the subsequent papule and blister developed after the treatment. After 1 month, laboratory findings indicated a reduced eosinophil count (3.3%). At her final follow-up 18 months later, the patient had no further symptoms and anti-Gnathostoma antibodies became negative. Conclusively, the present study is the first report on a human case of cutaneous gnathostomiasis in Henan Province, China, based on the past history (eating undercooked eels), clinical manifestations (migratory subcutaneous nodule and persistent eosinophilia), and a serological finding (positive for specific anti-Gnathostoma antibodies).     

Two imported cases of cutaneous larva migrans

Cutaneous larva migrans (CLM) is a rare serpiginous cutaneous eruption caused by accidental penetration and migration in the skin with infective larvae of nematode that normally do not have the human as their host. Although CLM has a worldwide distribution, the infection is most frequent in warmer climates. More recently, they have been increasingly imported from the tropics or subtropics by travelers. We experienced two patients who had pruritic serpiginous linear eruption in their skin for a few weeks after traveling to the endemic areas (Brazil and Thailand, respectively). After the treatment with albendazole, the skin lesions resolved with post-inflammatory hyperpigmentation. We report herein two cases of cutaneous larva migrans successfully treated with albendazole.     

Three clinical cases of cutaneous larva migrans

Three cases of cutaneous larva migrans (CLM) were diagnosed in a returnee from a trip to Thailand and in 2 domestic farmers during July and September, 2003. The linear and serpiginous skin lesions on the lower extremities were presented in all 3 cases. Routine laboratory findings were normal. In the imported case, a 650 x 30 micrometer sized filariform nematode larva, presumably a species of hookworm, was detected in the lesion. All cases were treated with 400 mg albendazole once daily for 3-5 days, and their skin lesions gradually improved. In the present study, a causative agent of CLM was isolated for the first time in the Republic of Korea. Moreover, we speculate that CLM is prevalent in farmers who are in frequent contact with soil in the Republic of Korea.     

捻转血矛线虫丙硫咪唑耐药相关lncRNA的转录组学测序与分析

分析捻转血矛线虫敏感株和耐药株中长链非编码RNA (Long non-coding RNA,lncRNA)的表达谱,探讨lncRNA与捻转血矛线虫丙硫咪唑耐药机制的关联性,为捻转血矛线虫耐药机理提供依据。文中对捻转血矛线虫敏感株和耐药株进行cDNA测序文库构建,使用Illumina HiSeq 4000平台进行双端测序,筛选出差异的lncRNA,基于顺式调控(cis)和反式调控(trans)对差异显著的lncRNA进行靶基因预测,并对靶基因进行过Gene Ontology (GO)功能注释和KEGG Pathway富集分析,利用FPKM法估计lncRNA和mRNA的表达水平。结果表明,敏感株和耐药株候选lncRNA分别为6 377和6 356个,两个文库中筛选出168个差异显著的lncRNA,其中在敏感株中表达上调有92个,表达下调76个。筛选得到的差异显著lncRNA候选靶基因416个,这些基因共注释到641条GO terms和92条信号通路;其中富集到耐药性相关的通路有药物代谢-其他酶、药物代谢-细胞色素P450、细胞色素P450对异生素的代谢等。综上表明,部分lncRNA介导的靶基因与捻转血矛线虫丙硫咪唑耐药性相关,lncRNA在捻转血矛线虫耐药性中具有潜在的重要的调节作用。探究了对于敏感虫株和耐药虫株中lncRNA的表达谱,发现了敏感虫株和耐药虫株中差异表达的lncRNA,有助于找出捻转血矛线虫如何抵抗丙硫咪唑的发生机制,为探讨捻转血矛线虫丙硫咪唑耐药机制提供科学的依据。     

Effect of myrrh and thyme on Trichinella spiralis enteral and parenteral phases with inducible nitric oxide expression in mice

Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis.