家蝇蛆粉的临床前致畸性研究

目的探讨家蝇蛆粉对大鼠的致畸性,以评价其安全性。方法家蝇蛆粉按比例定量添加到普通饲料原料中混匀,干燥,做成高、中、低剂量家蝇蛆粉饲料。将性成熟的98只SD大鼠按雌雄2：1的比例同笼交配。取64只孕鼠平均分为四组：家蝇蛆粉饲料低剂量组;家蝇蛆粉饲料中剂量组;家蝇蛆粉饲料高剂量组;普通饲料对照组。于受孕后称量体重增长情况。最后脱颈椎处死孕鼠,称子宫重量,并进行胎鼠检查。结果家蝇蛆粉饲料高、中、低剂量组与对照组相比,雌鼠体重增长未见显著差异,子宫重量未见显著差异,无吸收胎、早死胎、晚死胎;各组间雄性与雌性胎鼠数均未见显著差异;各组间雄性与雌性胎鼠的外观、体重、体长均未见显著差异。各组间胎鼠骨骼和胎鼠内脏均未见显著差异。结论家蝇蛆粉对SD大鼠未见致畸性。     

应用大鼠体外胚胎培养模型研究生草乌对胚胎发育的影响

目的探讨生草乌对胚胎发育的毒性作用及机制。方法应用大鼠着床后体外全胚胎培养模型,将9.5dSD大鼠胚胎与含不同浓度(终浓度分别为:0、0.63、1.25、2.5、5mg生药/mL)生草乌的大鼠即刻离心血清共培养48h,观察其对大鼠胚胎生长发育和组织器官形态分化的影响。结果随着生草乌剂量增加,胚胎生长发育和器官分化的各项指标均呈现下降趋势,有一定的剂量-效应关系。生草乌最大无作用剂量为1.25mg生药/mL,2.5mg生药/mL以上剂量可诱发卵黄囊生长和血管分化不良、生长迟缓及形态分化异常,严重者出现体节紊乱、小头、心脏发育迟滞(心小,停留在心管期)及心脏空泡等。结论较高剂量生草乌对体外培养大鼠胚胎具有一定的毒性作用,建议孕妇妊娠期间(特别是妊娠前3个月)慎用或禁用草乌。     

异麦芽酮糖醇致突变性及致畸性试验研究

目的 为确保异麦芽酮糖醇的食用安全,对其进行了致突变性和致畸性研究.方法 采用小鼠精子畸形试验、小鼠胸骨髓微核试验、Ames试验及大鼠传统致畸试验进行检测.结果 3个剂量组的微核率和精子畸形率与阴性对照组比较差异无统计学意义,各剂量组的回变菌落数均未超过溶剂对照组的2倍,未见母体毒性、胚胎毒性和致畸性.结论 在本实验条件下,异麦芽酮糖醇未见致突变性和致畸性.     

某保健酒的30天喂养及致畸作用试验研究

目的 评价某保健酒的食用安全性。方法 按照我国食品安全性毒理学评价方法，对该保健酒进行了传统致畸试验和30天喂养试验。结果 30天喂养雄性动物的血清肌酐含量与对照组差别有显著性意义，未发现其他不良作用。结论 某保健酒对大鼠的生长发育、组织病理学、血液系统、肝功能、肾功能等无明显不良影响，亦无致畸作用。     

硒对植入后大鼠胚胎致畸作用的时间－效应关系

应用体外全胚胎培养模型并结合电镜技术探讨了硒暴露不同时间对大鼠胚胎的致畸作用，染毒剂量为４．０μｇ／ｍｌ。结果显示硒对器官形成早期的胚胎具有明显的时间－效应关系。早期暴露１２ｈ，胚胎干重和视觉系统指标值明显低于对照组（Ｐ＜０．０５）．而晚期（第３６～４８ｈ）暴露１２ｈ，未见胚胎有任何发育异常．硒暴露２４ｈ和４８ｈ，对胚胎的生长发育和器官形态分化均有明显的抑制作用，５０％以上的胚胎出现多种畸形。结果还提示视觉系统是硒致畸作用的主要靶位点；体外培养胚胎对硒的敏感期在１～２４ｈ这一时段，相当于器官形成期的第９，５～１０．５ｄ。     

Middle and inner ear malformations in two siblings exposed to valproic acid during pregnancy: A case report

Valproic acid (VPA) is a known teratogenic drug. Exposure to VPA during the pregnancy can lead to a distinct facial appearance, a cluster of major and minor anomalies and developmental delay. In this case report, two siblings with fetal valproate syndrome and a mild conductive hearing loss were investigated. Radiologic evaluation showed middle and inner ear malformations in both children. Audiologic, vestibular and motor examination was performed. This is the first case report to describe middle and inner ear malformations in children exposed to VPA.     

Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice

Di(2-ethylhexyl)phthalate (DEHP) and mono(2-ethylhexyl)phthalate (MEHP) were administered PO or IP to pregnant ICR mice at varying doses on days 7, 8, and 9 of gestation. In groups given DEHP orally, resorptions and malformed fetuses increased significantly at 1,000 mg/kg. Fetal weights were also significantly suppressed. Anterior neural tube defects (anencephaly and exencephaly) were the malformations most commonly produced. No teratogenic effects were revealed by IP doses of DEHP and PO or IP doses of MEHP, although high doses were abortifacient and lethal to pregnant females. Thus DEHP is highly embryotoxic and teratogenic in mice when given PO but not IP. The difference in metabolism, disposition, or excretion by the route of administration may be responsible for the difference in DEHP teratogenicity. Although MEHP is a principal metabolite of DEHP and is several times more toxic than DEHP to adult mice, it seems that MEHP and its metabolites are not teratogenic in ICR mice.     

Evaluation of stereoselective anticonvulsant,teratogenic, and pharmacokinetic profile of valnoctylurea (capuride): A chiral stereoisomer of valproic acid urea derivative

Purpose: The purpose of this study was to evaluate the stereoselective anticonvulsant activity, neurotoxicity, pharmacokinetics, and teratogenic potential of two stereoisomers of valnoctylurea (VCU), a central nervous system (CNS)–active urea derivative of valnoctic acid, which is a constitutional isomer of valproic acid (VPA). Methods: VCU stereoisomers (2S,3S)‐VCU and (2R,3S)‐VCU were synthesized. Their anticonvulsant activity was determined and compared to VPA and racemic‐VCU in rats utilizing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scMet) tests. Neurotoxicity was determined in rats using the positional sense test, muscle tone test, and gait and stance test. The induction of neural tube defects (NTDs) by VCU stereoisomers was evaluated in a mouse strain highly susceptible to VPA‐induced teratogenicity. The pharmacokinetics of VCU was studied in a stereoselective manner following intraperitoneal (i.p.) administration to rats. Results: (2S,3S)‐VCU and (2R,3S)‐VCU median effective dose ED₅₀ values were 29 mg/kg [95% confidence interval (CI) = 8–60 mg/kg] and 42 mg/kg (95% CI = 36–51 mg/kg) (MES) and 22 mg/kg (95% CI = 13–51 mg/kg) and 12 mg/kg (95%CI = 7–21 mg/kg) (scMet), respectively. (2S,3S)‐VCU was more potent and had a wider safety margin (p < 0.05), defined as the protective index (PI = TD₅₀/ED₅₀), at both the MES (PI > 17) and scMet (PI > 23) tests than racemic‐VCU or (R,S)‐VCU (PI = 2.8 and 9.9, respectively). VCU stereoisomers caused NTDs at doses >4 times that of their anticonvulsant ED₅₀ values. At a dose of 112 mg/kg, (2R,3S)‐VCU was nonteratogenic and less embryotoxic than its stereoisomer (2S,3S)‐VCU. No stereoselective pharmacokinetics was observed following intraperitoneal dosing of racemic‐VCU to rats. VCU was mainly eliminated by metabolism with a half‐life of 2 h. Conclusions: VCU anticonvulsant activity and wide PI values make it a potential candidate for development as a new, potent antiepileptic drug (AED).     

PGLC对小鼠致畸实验研究

观察了乙交酯-L-丙交酯-ε-己内酯三元无规共聚物材料(PGLC)对昆明种小鼠孕期和胎鼠的影响。结果表明，PGLCA组(1000mg／kg)、B组(500mg／kg)、C组(250mg／kg)各组孕鼠和胎鼠各项指标与阴性对照组(c^-，PBS液每日0．5ml／鼠)差异无显性(P＞0．05)，与阳性对照组(c^ ，CP，14mg／kg)差异有高度显性(P＜0．01)。PGLC剂量在1000～250mg／kg范围内对小鼠生殖能力和胎鼠发育无明显影响。PGLC作为植入体内的长效药物载体无生殖毒性作用。     

Use of low-molecular-weight heparin from the first trimester of pregnancy: a retrospective study of 111 consecutive pregnancies

BACKGROUND: During the first trimester of pregnancy, unfractionated heparin is the standard anticoagulant treatment for pregnant women at high risk of thrombosis. OBJECTIVE: To observe maternal and fetal tolerance for low-molecular-weight heparin begun in the first trimester of pregnancy. METHODS: Observational study conducted from 1 January 1997 to 31 May 2001. All patients began treatment before the 15th week of pregnancy. The outcome measures were the incidence and causality of adverse events in mother and fetus. RESULTS: The study included 97 patients (and 111 pregnancies) at very high risk for thrombosis. Seven fetal losses (6.3%) were observed: three early spontaneous abortions, three late spontaneous abortions and one medically indicated abortion. Twenty-five (22.5%) bleeding events occurred during pregnancy, seven (6.3%) of which required medical intervention: five curettages for first trimester spontaneous abortions, one late abortion at 21 weeks and one placental abruption at 25 weeks. Of nine (8.1%) primary postpartum hemorrhages involving a blood loss > or = 500 mL, three involved losses of 1000 mL or more and one required embolization of the uterine arteries. Five patients had thrombocytopenia, but none was treatment-related. Local cutaneous reactions occurred in 33 (29.7%) patients. Six (5.4%) maternal thromboembolic complications occurred during pregnancy or postpartum. At birth, two children had non-chromosomal congenital malformations (pyelectasia, cleft lip and palate). No fetal or neonatal complication was attributed to the treatment. CONCLUSION: The use of low-molecular-weight heparin (LMWH) for patients requiring anticoagulant treatment from the first trimester appears safe for mother and fetus.