ISSN:0040-3709    

DOI:10.1002/tera.1420460102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThis article describes some of the contributions that in vitro methods have made to our progress, albeit slow, toward understanding mechanisms of chemical teratogenesis. Emphasis is given to the painstaking and time consuming nature of approaches required to elucidate mechanisms. The examples considered are cyclophosphamide, 2‐methoxyethanol, and retinoids. Some of the newer methods that take advantage of the recent advances in molecular biology and analytical chemistry have already been applied to studies on teratogenic mechanisms. Prospects for the 1990s are excellent and promise more rapid progress than during the past decade toward unraveling the mysteries of normal developmental biology. That knowledge in turn should be immediately applicable for investigations on developmental toxicant‐induced abnormal development. © 1992 Wiley‐Lis

ISSN:0040-3709    

DOI:10.1002/tera.1420460103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA review of current literature suggests that maternal nutritional status can be an important modulator of the developmental toxicity of a number of agents in the environment. While the provision of multivitamin/multimineral supplements during the periconceptional period is often associated with improved pregnancy outcome, it has been difficult to identify specific nutrient deficiencies as causative factors of abnormal development in humans. One explanation for this is that nutrient deficiencies can arise through a number of means in addition to a simple dietary deficit of the nutrient. The hypothesis is proposed that one mechanism contributing to the embryotoxicity of a diverse group of insults is an alteration in the metabolism of select nutrients. Evidence is presented that zinc is one nutrient whose metabolism can be markedly influenced by a variety of insults. One consequence of this alteration can be a reduction in embryonic zinc uptake, the development of embryonic zinc deficiency and abnormal development. © 1992 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420460104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractClinical teratologists will have new challenges during the 1990s as birth defects are diagnosed more frequently than in previous decades. Malformations and genetic disorders will be diagnosed in utero during all three trimesters of pregnancy. The teratologist may participate in or lead a multispecialty group to give the involved family optimal interpretation of test results, counseling, and recommendations regarding subsequent clinical management. © 1992 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420460105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420460106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe Teratogenic Agent Information Centre was set up 15 years ago in response to a growing demand from a medical profession struggling to cope with the problem of teratogenic risk. Our goal was to provide information on the real nature of the risk and to monitor all at‐risk pregnancies so as to obtain data in a field where there are still, unfortunately, many gaps in our knowledge. The results of these 15 years have been most encouraging, in that physicians have been provided with specialized information and the follow‐up of gestations had provided considerable clinical data, which has contributed to advancing our understanding in this domain. © 1992 Wiley‐Lis

ISSN:0040-3709    

DOI:10.1002/tera.1420460107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractFetal glucocorticoid exposure retards postnatal growth and evokes abnormalities of nervous system structure and function. To examine the underlying mechanisms, we administered 0.2 or 0.8 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19 and assessed brain region cell development with indices of DNA content (total cell numbers), DNA concentration (cell packing density), and protein/DNA ratio (relative cell size). Dexamethasone evoked deficits of pup body and brain region weights, but the brain regions displayed growth‐sparing associated initially with preservation of cell numbers (normal or elevated DNA content and concentration), at the expense of relative cell size (decreased protein/DNA). Subsequently, brain cell acquisition lagged behind that of controls, with deficits in DNA and elevations of protein/DNA. In midbrain + brainstem and in cerebellum, cell markers returned to normal by weaning. However, the forebrain showed persistent elevations of DNA and reduced protein/DNA, indicative of replacement of neurons with glia. Because the treatment period coincided with the timing of neuronal cell replication in the forebrain, but not in the other regions, these results suggest that the critical period for lasting deficits of dexamethasone coincides with the peak of neuronal mitosis. © 1992 Wiley‐Liss,

ISSN:0040-3709    

DOI:10.1002/tera.1420460108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractMethyl isocyanate, the chemical involved in the 1984 accident at Bhopal, India, forms a labile conjugate, S‐(N‐methylcarbamoyl)GSH (SMG), by way of a reversible reaction with GSH. We studied the toxicity of SMG on mouse embryos explanted on day 8 of gestation and cultured in rat serum for 42 hr. SMG caused concentration‐dependent decreases in growth and development over the range 0.1–2 mM, without causing significant mortality. At a concentration of 2 mM, SMG completely arrested embryo development, but heartbeat was absent in only one of nine embryos at 42 hr. At a concentration of 0.25 mM, SMG reduced embryo size to 75% and protein content to 63% of the control; 18% of embryos failed to rotate. At this concentration (0.25 mM), which was selected for all other studies, spinal kinks and somite pair distortion in the region of the forelimb were evident in 38% of embryos; no other abnormalities were noted. DNA content of and thymidine incorporation by embryos and yolk sacs was reduced by SMG, although this was more pronounced in the yolk sac than in embryos. At subtoxic concentrations, the L‐cysteine precursor (−)‐2‐oxo‐4‐thiazolidine‐carboxylic acid did not, but GSH did, inhibit embryotoxicity of SMG. It is concluded that SMG exerts embryotoxic and dysmorphogenic effects and may contribute to systemic toxicity of methyl isocyanate.

ISSN:0040-3709    

DOI:10.1002/tera.1420460109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractEpidemiological studies of suspected human teratogens not infrequently lead to recurring weak or moderate associations (relative risks or odds ratios ranging from>1 to 3 for adverse effects and from 1/3 to<1 for protective effects) between specific defects and prenatal exposures. Examples of such associations include cigarette smoking and oral clefts (odds ratios between 1 and 2) and periconceptional multivitamin/folic acid supplementation and neural tube defects (odds ratios from 1/3 to 1). In this paper, we illustrate that low relative risk recurring in well‐designed studies may reflect underlying biologic mechanisms and should not be readily dismissed. Low relative risks could be the result of a combination of the following factors: 1) unmeasured confounding, 2) exposure misclassification (often related to the inability to pinpoint relevant dose and timing), 3) outcome misclassification (related to the etiologic heterogeneity of birth defects), 4) biologic interactions (related to teratogenic effects in population subgroups defined by genetic susceptibility or the presence of other exposures), and 5) differential prenatal survival (related to the combined impact of the exposure and the defect on prenatal survival). These issues can be addressed in epidemiologic studies by using biological markers of exposure and susceptibility, dysmorphologic evaluation of affected infants, subgroup analysis for etiologic heterogeneity, a search for biologic interactions, and the use of prospective cohort studies. Finally, low relative risks in the face of common exposures can reflect an important public health contribution of the exposure to the occurrence of the defect in the population. © 1992 Wiley‐Liss,

ISSN:0040-3709    

DOI:10.1002/tera.1420460110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe transverse grwoth of long bones during intrauterine development was studied in rat fetuses subjected to experimental oligohydramnios in order to determine wheter the skeletal changes, if any, in extrinsic fetal akinesia were similar to those observed in curarized rat fetuses with the fetal akinesia deformation sequence. Oligohydramnios was induced by daily extraction of amniotic fluid from day 17 of gestation until term. Experimental fetuses were compared with a sham‐operated control group. The total area and perimeter, the absolute and relative amount of periosteum and bone trabeculae, the major and minor axes, and the elongation factor were measured in histological cross sections of the femoral metaphysis and diaphysis with an IBAS 1 image analysis system. Rat fetuses in the experimental group showed multiple articular contractures, redundant skin, and lung hypoplasia, a phenotype consistent with the oligohydramnios sequence. No alterations in femoral shape and transverse growth of the metaphysis and diaphysis were noted in these fetuses. These results suggest that the main mechanical factor related to fetal bone modeling is muscular strength, while motion would be mainly involved in fetal joint development. © 1992 Wiley‐Liss,

ISSN:0040-3709    

DOI:10.1002/tera.1420460111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY