Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs

The aim of this review was to scrutinize the current literature available on teratogenic safety of third-generation antiepileptic drugs (TGAEDs) considering their clinical implications and to highlight for further research need in the interest of the diseased population in general and women with epilepsy in particular. For evaluation of the teratogenic potential of TGAEDs, this review summarized the existing information on controlled clinical trials conducted by the pharmaceutical companies, case reports, scholarly articles (prospective and retrospective studies), and experimental tests carried out so far. Firstly, clinical reports have reviewed on each drug followed by non-clinical studies reported hitherto. The Pub-Med and Google search engine was used to explore the relevant articles with pertinent keywords like pregnancy, epilepsy, seizures, women with epilepsy, antiepileptic or anticonvulsant drugs, first-second/new and third/ newest generation antiepileptic drugs, teratogenicity, teratological potential, birth defects, congenital anomalies, epilepsy and pregnancy registries, malformation surveillance program. The search was also carried out by the individual name of 20 third-generation AEDs. This review declared that although much research has been carried out on clinical and non-clinical implications for the assessment of the teratogenic potential of FGAEDs and SGAEDs, reports on the teratogenic safety of TGAEDs are still limited. It is concluded that there is an urgent need to exaggerate a large number of clinical intervention trials/reports and experimental studies to draw a definite conclusion for the teratogenic safety of TGAEDs. This is a pioneer attempt by our laboratory to review the teratogenic potential of third-generation antiepileptic drugs.     

酒精对小鼠神经母细胞发育的影响

目的探讨酒精对胚胎神经母细胞发育的影响及其与畸形发生之间的联系。方法从12d龄、体节数34～36的小鼠胚胎分离中脑神经母细胞接种培养板，给予不同剂量的酒精于体外连续培养5d后，检测酒精对细胞增殖和分化的影响，及其线粒体膜电位的变化和细胞凋亡情况。结果酒精对中脑神经母细胞增殖和分化均有抑制作用，其分化抑制剂量(ID50)和增殖抑制剂量(IP50)分别为210．29mM和336．55mM，分化比增殖更敏感。随酒精染毒剂量的增加，细胞线粒体膜电位呈下降趋势，凋亡和坏死细胞数量逐渐增加，存在剂量-反应关系。结论酒精可能通过抑制发育期神经母细胞的增殖和分化以及诱导细胞过度凋亡和死亡而导致中枢神经系统畸形的发生。     

黄芪复方营养液对大鼠致畸作用研究

对黄芪复方营养液进行了大鼠传统致畸试验。以亚慢性毒性试验得出的最大无作用剂量为高剂量，设５０ｇ／ｋｇ、１５ｇ／ｋｇ、１．５ｇ／ｋｇ体重３个剂量组。浓缩鱼肝油为阳性对照物，蒸馏水为阴性对照组。结果表明，该营养液对孕鼠无母体毒性、无胚胎毒性和致畸作用。     

Protection from Phenytoin-Induced Congenital Malformations by Coadministration of the Antiepileptic Drug Stiripentol in a Mouse Model

Summary: To test the hypothesis that the cytochrome P-450-inhibiting antiepileptic drug (AED) Stiripentol (STP) can reduce the incidence of phenytoin (PHT) induced congenital malformations, we chronically administered the AEDs to three inbred mouse strains. The frequency of congenital defects in PHT-treated animals was dosage dependent, ranging from 7 to 55%. When STP was coadministered orally with PHT, there was a significant reduction in fetal defects in SWV and C57BL/6J mouse strains. A replication of the experiment was conducted with addition of a seventh group of mice that received the high dosage of PHT together with STP. In the replicate, all three strains demonstrated a significant reduction in fetal defects in fetuses exposed to PHT (60 mg/kg) and STP (200 mg/kg) as compared with PHT (60 mg/kg) monotherapy. These results strongly suggest that oxidative metabolites activated by cytochrome P-450 are the primary teratogenic molecules involved in PHT-induced teratogenesis and that clinical management of pregnant epileptic patients may be improved through heightened awareness of these drug interactions.     

脱氧雪腐镰刀菌烯醇毒性作用研究进展

为了给真菌毒素的深入研究提供理论基础,现对国内外有关脱氧雪腐镰刀菌烯醇的毒性研究进行文献综述,重点概述近年来脱氧雪腐镰刀菌烯醇在细胞毒性、致畸、致突变和致癌方面的最新研究进展,并指出下一步的研究应侧重于脱氧雪腐镰刀菌烯醇的毒性机制、与人类疾病的关系以及多种真菌毒素的协同作用等几个方面。     

Breast cancer and pregnancy: current concepts in diagnosis and treatment

The treatment of breast cancer diagnosed during pregnancy presents a challenging situation for the patient, family, and caregivers. Case series have demonstrated the efficacy and safety of using anthracycline-based chemotherapy during the second and third trimesters. Additionally, patients should be seen, evaluated, and treated in a multidisciplinary setting with facilitated communication among the medical oncologist, surgical oncologist, obstetrician, radiation oncologist, pathologist, and radiologist. This review details the available data regarding the diagnosis and management of the pregnant breast cancer patient.