转乙肝抗原蛋白基因苜蓿胚胎毒性和致畸性研究

目的采用动物实验对转乙肝抗原蛋白基因苜蓿（ATHAPG）的大鼠胚胎毒性和致畸性进行研究,为探索ATHAPG对人体健康影响和制订每日允许摄入量提供依据。方法将受孕sD大鼠随机分为40、200和1000mg／kg3个剂量组及阴性对照组（蒸馏水）。每组12～14只孕鼠,于孕期7～16d每天给受试动物灌胃1次,妊娠第20天处死,检查孕鼠妊娠与胎鼠畸形情况。结果3个剂量组的孕鼠生殖能力、体熏及胎鼠体重、外观发育、骨骼和内脏畸形率与阴性对照组比较,差异均无统计学意义（P〉0．05）。结论在该试验条件下,ATHAPG在40～1000mg／kg剂量范围对大鼠无明显的母体毒性、胚胎毒性和致畸性。     

Pharmacotherapy in pregnancy and lactation

Prescribing for patients who are pregnant and breastfeeding can be a challenge for clinicians facing insufficient information regarding medication safety, overestimation of perceived risk of medication both by patients and care providers, and increasing litigation costs. This article aims to guide the clinician in choosing the safest and most effective strategy when prescribing medications to patients who are pregnant and breastfeeding.     

Valproic acid and its derivatives enhanced estrogenic activity but not androgenic activity in a structure dependent manner

Steroid hormones affect metabolic pathways and cellular functions. Valproic acid (VPA), used as antiepileptic drug, inhibits histone deacetylases and interacts with intracellular receptors. We analyzed the impact of VPA and VPA derivatives on activation of estrogen and androgen receptors (ER and AR) using reporter gene assays. VPA and its long-chain derivatives 2-(2-propynyl)-hexanoic acid [butyl-4-yn-VPA], 2-(2-propynyl)-heptanoic acid [S-pentyl-4-yn-VPA] and 2-(2-propynyl)-nonanoic acid [heptyl-4-yn-VPA] enhanced 17β-estradiol-induced ERα and ERβ activation partly synergistically with a structure–activity correlation. The extent of this effect regarding to ERα activation increased with prolongation of the aliphatic side chain. Regarding AR activation, VPA, S-pentyl-4-yn- and heptyl-4-yn-VPA slightly induced AR activity when tested alone. In combination with the AR agonist 5α-dihydrotestosterone, VPA, S-pentyl-4-yn- and heptyl-4-yn-VPA showed anti-androgenic effects without an apparent structural relation. Our results indicate that VPA and its derivatives affect estrogen signaling with a structural specificity, while the (anti-)androgenic effects of these compounds are not structurally correlated.     

二硝酰胺铵的致突变性和致畸性研究

目的 对新型含能材料二硝酰胺铵(ADN)的致突变性和致畸性进行研究,为进一步研究ADN对人体健康影响和制订职业接触限值提供依据.方法 根据《化学品毒性鉴定技术规范》,采用鼠伤寒沙门杆菌回复突变试验(Ames试验)、体内哺乳动物骨髓嗜多染红细胞微核试验、精子畸形试验和致畸试验研究ADN的致突变性和致畸性.结果 (1)ADN在8～5000 μg/皿剂量范围内未发现诱变作用;113.8mg/kg剂量染毒组与阴性对照相比,诱发小鼠的微核率明显升高,差异有统计学意义(P＜0.05);54.4～272.0 mg/kg剂量范围内小鼠精子畸形试验结果为阴性.(2)319 mg/kg剂量组活胎率低于阴性对照组,吸收胎率高于阴性对照组;319 mg/kg剂量组胎鼠胸骨1发育不全率高于阴性对照,21.3、79.7、319 mg/kg 3个剂量组胎鼠胸骨4～6发育不全率高于阴性对照组;319 mg/kg剂量组胎鼠内脏畸形率高于阴性对照组.ADN对大鼠的致畸指数为30.结论 ADN属可疑诱变剂,有致畸危害.     

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.     

Antiseizure medications use during pregnancy and congenital malformations: A retrospective study in Saudi Arabia

AimTo evaluate the incidence of congenital malformations in children exposed prenatally to antiseizure medications (ASMs), to assess other perinatal and fetal complications, and to determine the potential predictors for these complications.MethodA retrospective review of pregnancy outcomes of women with epilepsy. Patients were followed up at the King Faisal Specialist Hospital and Research Centre, Riyadh and Jeddah, Saudi Arabia, between Dec 1993 and Oct 2020.ResultsOf 162 pregnancies included, 10 (6.17%) congenital malformations were observed, 6.82% in ASM-exposed babies versus 3.33% in babies of epilepsy-untreated mothers (P = 0.69). The overall incidence of perinatal and fetal complications was 53%; most frequent were low birth weight (24%), preterm birth (19%), transfer to neonatal intensive care unit (18%) and abortion (8%). These complications were higher in the untreated group (66.67%) than in the ASM group (50%). The use of other non-antiseizure medications during pregnancy was the only factor that significantly increased the risk of complications.ConclusionPrenatal exposure to ASMs was associated with increased risk of congenital malformations. However, overall perinatal and fetal complications were higher in the untreated group than in the ASM group, which could be explained by maternal seizures. Therefore, taking ASMs to control epilepsy and prevent perinatal complications may outweigh the risks of teratogenicity.     

Genetic syndromes and prenatally detected renal anomalies

Renal anomalies are frequently detected on the routine second trimester scan offered to all pregnant women in the UK. These anomalies may be isolated but can also be associated with other congenital anomalies. Many combinations of ultrasound scan findings constitute recognised genetic entities. Knowledge of these conditions is essential for adequate management of the pregnancy and subsequent balanced parental counselling. This short review discusses the common genetic syndromes associated with the renal abnormalities identified on the antenatal ultrasound scan, and also provides an overview of renal symptoms in chromosome imbalances and after teratogenic influences.     

常青胶囊对大鼠致畸作用的影响

目的 观察常青胶囊对大鼠致畸敏感期的毒性。方法 采用灌胃给药，观察对孕鼠的体重、胎仔数、胎仔体重、活胎数、死胎数、吸收胎数以及对胎鼠骨骼发育和内脏畸形率的影响。结果 常青胶囊对大鼠胚胎毒性和致畸潜力与空白对照组比较无显著性差异。结论 常青胶囊对大鼠无致畸作用。     

混合氨基酸稀土配合物的胚胎毒性研究

在孕鼠“致畸敏感期”分别给予农药混合氨基酸稀土配合物（简称ＭＡＲ）１４２８、７１４、３５７ｍｇ／ｋｇ。１４２８ｍｍ／ｋｍ组胎鼠体重、身长、骨化程度和孕鼠体重增值显著降低，胚胎吸收和胎鼠死亡则增高。提示该剂量ＭＡＲ具有明显胚胎毒性。７１４、３５７ｍｇ／ｋｇ剂量组各项指标与对照组比较则无统计差异。