Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.     

Response of amoeboid microglia/brain macrophages in fetal rat brain exposed to a teratogen

This study examined the time course response of amoeboid microglia/brain macrophages in the rat fetus induced by a single intraperitoneal injection of cyclophosphamide, a teratogen, into the mother rat at 13 days of gestation. Compared to the normal fetal brain, a marked increase in amoeboid microglia was observed in the telencephalon and diencephalon of experimental fetuses, especially in those killed at embryonic day 15. Conglomerations of microglia occurred in the dorsal and superior neuroepithelium of diencephalon, basal telencephalon, cortical neuroepithelium, and hippocampal formation as identified with OX-42, OX-18, and ED-1 by immunohistochemistry. Rhodamine isothiocynate (RhIc) as a tracer was injected via the tail vein into the pregnant rat to assess the phagocytic capability of these cells. Following the tracer injection, none of microglial cells in normal fetal brain was detectable. RhIc, however, was readily taken up by amoeboid microglia in fetal brain with injury insult. Double labeling has shown that the RhIc-labeled cells were immunoreactive with ED-1, OX-42, OX-18, and OX-6, confirming their microglial nature. Microglial proliferation was assessed by immunohistochemistry using bromodeoxyuridine, which showed a marked increase in mitotic activity. Confocal microscopic analysis revealed that a varying number of microglia coexpressed iNOS, macrophage colony-stimulating factor (M-CSF), and ICAM-1. RT-PCR analysis showed increased expression of M-CSF mRNA. Furthermore, colony-stimulating factor-1 receptor mRNA was localized in microglia by in situ hybridization. The present results suggest that NO along with M-CSF and ICAM-1 is involved in microglial proliferation in prenatal brain injury.     

敌枯双对大鼠致畸阈剂量及最大无作用剂量的研究

将60只孕鼠随机地分成A、B、C及D组,前3组于孕笫7～13d分别口服1.0、0.1及0.05mg/kg敌枯双,而D组以0.5％羧甲基纤维素钠对照。每组留3只孕鼠自然分娩,其余者于孕20d处死,检查。发现A及B组畸胎率均非常显著地高于对照组(P<0.005),亦显著高于C组(P<0.025),其子代Fb体重在2.5～3月龄间显著低于F_d(P<0.05)。提出其阈剂量及最大无作用剂量分别为0.1mg/kg及0.05mg/kg。     

二硫化碳对大鼠F_2代后遗影响的研究

本文报道大鼠妊娠7～14d以Cs_2染毒对F_2代的后遗影响。结果表明,CS_2对F_2代生长发育指标及F_1代脏器系数无明显影响,但对胎鼠有致畸作用,并可延续到第二代,以骨骼畸形为主,主要为胸骨缺失,其次为枕骨骨化延缓、肋骨延长和囱门增大等,且发生率几乎同胎鼠的F_1代。由此认为CS_2对后代的影响,主要是对F_2代的致畸作用较明显。     

Work in pregnancy

Pregnant women in the western world are increasing their part in paid employment. This can be added to their work in the home which, with their leisure and athletic activities, might add up to a considerable load; the possible effects this exertion could have on the woman and her unborn child has been realized only in the last twenty years and many attempts have been made to quantify it. The patterns of work in the home, in employment, and at sporting activity are assessed. There are two distinct areas of possible influence on the fetus: the work with its physical effort might affect respiratory and metabolic acid-base balance and specific teratogens related to activity at work may be encountered and act at nodal points during fetal growth at specific times, causing congenital abnormalities of organs. Potential hazards under chemical, physical, and biological headings are considered, while both the psychological and physical effect of energy expenditure are discussed. Possible measures of outcome are assessed and three recently published studies from the U.S. and U.K. are examined to show the difficulties of making valid measurements about the effect of work on the pregnancy, as well as that of pregnancy on the work. It is probable that ordinary work done by a fit young woman has no serious effect on herself or a healthy fetus. Research will continue, for it may be that with an impaired afferent nutrition and oxygen supply to the fetus, certain specific increases in degrees of work could have an exaggerated effect. © 1993 Wiley-Liss, Inc.     

DTPA和喹胺酸对小鼠的致畸作用

DTPA-CaNa₃ (促排灵-235)、DTPA-ZnNa₃(新促排灵)和喹胺酸为放射性核素内污染的促排药物。三药对小鼠致畸作用试验中观察到,DTPA-ZnNa₃在人常用剂量100倍和200倍(人常用剂量以1 g/50kg计算)时耒生现对胎鼠的影响,而DTpA-CaNa₃、喹胺酸在20倍剂量时对胎鼠已见一些影响,引起活胎率下降、胚胎吸收数增加。所以核素中毒后进行促排治疗时对怀孕妇女应慎用DTPA-CaNa₃和喹胺酸,以采用低毒*每DTPA-ZnNa₃治疗较为安全稳妥。     

古尼拟青霉对小白鼠的致畸试验

为确定古尼拟青霉有无胚胎毒和致畸作用,于母鼠妊娠的第6～14天每天灌胃给予0.6,2.0,6.0g/kg 古尼拟青霉。母鼠体重增长和胚胎外形、内脏及骨髓异常与阴性对照组(给予自来水)无明显差异。提示上述剂量范围内古尼拟青霉没有胚胎毒和致畸作用。给予五氯酚钠的阳性对照组则出现明显的胚胎毒和致畸作用。     

Children of Epileptic and Psychotic Mothers*

Abstract A comparison study of maternal characteristics in a sample of mentally retarded children and in paired non-retarded children from epileptic and psychotic mothers matched. for sex, age and living area was done. Thirty-two children of epileptic mothers and 42 children of psychotic mothers were classified into three and two groups according to the presence of mental retardation, respectively. The frequency of maternal epileptic seizure during pregnancy was significantly higher in the mentally retarded offspring group than in the other two groups. Almost all seizures of the mothers of children with mental retardation were taken for a type of generalized motor seizures. Generalized motor seizures during pregnancy and maternal lower mental condition would be a risk factor of mental retardation in the offspring. An impressive difference between the groups of offsprings of psychotic mothers was observed during the offspring's infancy. About 71 per cent in the group of children with mental retardation was brought up by their mostly psychotic mothers during infancy. Many of the children without mental retardation were raised in foster home care. These facts would imply that some behaviour in the children with mental retardation could be related to postnatal environmental abnormal factors.     

Risk minimization practices for pregnancy prevention: understanding risk, selecting tools

According to the March of Dimes, approximately 4% (1/28) of babies are born in the US each year with a birth defect. For the majority of birth defects the etiology is unknown, although chemicals, including drug exposures, probably account for less than 1% of all birth defects. The identification of potential human teratogenicity during drug development is important because drug-induced adverse fetal effects are potentially preventable with the application of risk assessment strategies and risk minimization tools and programs to minimize risk of pregnancy exposure while preserving access to drug benefits; risk assessment and risk minimization together comprise risk management. It is important that risk minimization programs intended to limit fetal exposure use a consistent approach and are tailored to the product-specific risk concerns in order to optimize the benefit-risk balance for a particular drug. This paper highlights general considerations in developing specific risk minimization programs to prevent fetal drug exposure including the relative advantages and disadvantages of each strategy.     

Methaquaiona a Or. Jekyll and Mr. Hyde

Cocaine is widely recognized as one of the most frequently used illicit drugs in use today. This review examines animal and clinical data concerning in utero cocaine exposure and its effect on the development of the fetus and newborn infant.