Abdullah Nor Linda, Gunasekaran Renuka, Mohd-Zin Siti Waheeda, Lim Bee-Hui, Maniam Pramila, Mohd-Salleh Anis Shuhada, Thong Meow-Keong, Chik Zamri, Nordin Noreena, Omar Zaliha, Engkasan Julia Patrick, Ganesan Dharmendra, Aiezzah Zakaria Nurul, Ahmad-Annuar Azlina, Abdul-Aziz Noraishah Mydin
Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia.
BMC Res Notes. 2018 Jul 16;11(1):475. doi: 10.1186/s13104-018-3593-1.
The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation.
Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P < 0.0001), in all litters. The TELSE tablet-treated females subsequently given folic acid did not result in pregnancies despite there being evidence of possible resorption. Furthermore, after multiple rounds of mating which did not yield viable pregnancies, eventually, 2 embryos with exencephaly were harvested in a litter of 6 at 0.05% w/v pure trimethoprim once. The use of trimethoprim, a folic acid antagonist, peri-conceptionally increased the risk of exencephaly in the mouse.
马来亚大学神经管缺陷研究小组对一种名为TELSE的片剂进行分析，该片剂可能导致在马来亚大学医学中心出生的一名婴儿患有中枢神经系统畸形。在这项动物实验研究中，我们调查了TELSE的成分及其成分暴露导致原发性神经胚形成失败的情况。
对TELSE片剂进行液相色谱串联质谱分析，证实其活性成分是甲氧苄啶。用TELSE片剂处理的雌性小鼠所产的所有窝中，都有大量无脑儿胚胎（n = 8，36.4%，*P < 0.0001）。用TELSE片剂处理的雌性小鼠随后给予叶酸，但尽管有可能发生吸收的迹象，仍未怀孕。此外，经过多轮交配均未产生 viable 妊娠后，最终在一窝6只小鼠中，有2只无脑儿胚胎在一次给予0.05% w/v纯甲氧苄啶后被收获。在受孕期间使用叶酸拮抗剂甲氧苄啶会增加小鼠患无脑儿的风险。
