bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of alcohol effects on the brain during gestation and lactation
Authors: Borges Salvador , Lewis Paul D. 
Published: June 2005

AbstractPregnant Wistar rats were maintained on a diet of food pellets and a 10% (v/v) solution of ethanol in water during pregnancy and up to 21 days postpartum. Control groups were given food pellets and water ad libitum. The consumption of food and liquid was monitored throughout this period, so that daily food‐ and ethanol‐derived caloric intake, daily liquid intake, and dose of alcohol ingested could be determined. The body weights and whole brain weights of ethanol‐exposed offspring did not differ significantly from controls at any time from birth up to 21 days postpartum. However, cerebellar weights were significantly reduced in 21‐day‐old ethanol‐exposed offspring. Areal analysis of the cerebellar vermis showed a 9% reduction in 21‐day‐old ethanol‐exposed offspring compared with controls. Although there were no differences in total vermal area between control and treated rats at 12 days, ethanol‐exposed offspring had a significantly more extensive external granular layer. In midgestation, pregnant females registered peak alcohol levels of 118 mg/100 ml blood 1 hr prior to the end of the dark cycle, while during lactation peak levels of 135 mg/100 ml blood were obtained. Neonate alcohol levels peaked slightly later and reached much lower values (44 mg/100 ml blood) during the lactation period. Ingested alcohol intake and blood alcohol levels fall within the range associated in man with the fetal alcohol syndrome, and it is suggested that the experimental regime described is a useful method for invest gating the effects of alcohol on the developing nervous system.
Malformations in infants of diabetic mothers
Authors: Mills James L. 
Published: June 2005

AbstractMaternal insulin‐dependent diabetes has long been associated with congenital malformations. As other causes of mortality and morbidity have been eliminated or reduced, malformations have become increasingly prominent. Although there is not universal agreement, the great majority of investigators find a two‐ to threefold increase in malformations in infants of insulin‐dependent diabetic mothers. This increase is not seen in infants of gestational diabetics. It probably is not present in women whose diabetes can be controlled by diet or oral hypoglycemic agents. The risk does not appear to be primarily genetic since diabetic fathers do not have an increased number of malformed offspring. Most studies show a generalized increase in malformations involving multiple organ systems. Multiple malformations seem to be more common in diabetic than non‐diabetic infants. Caudal regression has the strongest association with diabetes, occurring roughly 200 times more frequently in infants of diabetic mothers than in other infants. The teratogenic mechanism in diabetes is not known. Hyperglycemia may be important but human studies focusing on the period of organogenesis are lacking. Hypoglycemia has also been suggested based mainly on animal experiments. Insulin appears unlikely. Numerous other factors including vascular disease, hypoxia, ketone and amino acid abnormalities, glycosylation of proteins, or hormone imbalances could be teratogenic. None has been studied in sufficient detail to make a judgment. A large‐scale prospective study is required to determine early fetal loss rates, correlate metabolic status during organogenesis with outcome, and assess the effect of diabetic control on malformation rates.
Neonatal deaths and pulmonary dysplasia due to D‐penicillamine in the rat
Authors: Kilburn Kaye H. , Hess Rex A. 
Published: June 2005

AbstractD‐penicillamine, added to a low copper diet fed through pregnancy or given by gavage to pregnant rats which were on a copper‐deficient or a normal diet produced fetal resorptions and malformations. Doses of 300 to 400 mg per day for 6 days (days 9–14 of gestation) with a diet normal for copper prevented maternal weight gain and at 350 or 400 mg/day caused fetal death on day 16 or 17. Forty percent of offspring had tracheobronchomegaly and 42% had cystic lungs. Associated abnormalities included pleural hemorrhages, dilated esophagi, and unaerated lungs. The lungs had large, poorly formed, thick‐walled acini without partitioning and a thick rim of connective tissue around vessels and bronchi. At the higher doses, all members of one of 12 litters had angulation of the spine and half the members of another litter had cleft palates. A postulated mechanism for these alterations in pulmonary connective tissue productive of malformations which model human tracheobronchomegaly and cystic lungs, is interference with lysyl oxidase, a copper‐requiring enzyme, which cross‐links elastin.
The effects of chlorpromazine and phenobarbital on cerebellar Purkinje cells
Authors: Hannah R. S. , Roth S. H. , Spira A. W. 
Published: June 2005

AbstractThe morphological effects of two chemically different neuroactive drugs (chlorpromazine and phenobarbital) on developing Purkinje cells in the rat cerebellum were examined to determine the presence of cytological alterations. Therapeutic dosages of both durgs were chronically administered to separate groups of maternal rats beginning on day 18 postcoitus. Entire litters were sacrificed on postnatal days 13, 15, 18, and 21. Light microscopic quantitation of Purkinje cells demonstrated a statistically significant reduction in total numbers below control levels at all ages examined for both drugs. Pyknotic Purkinje cells, which appeared more numerous in the drug tested groups, had a paucity of synaptic contacts on both the soma and dendritic branches. Both drugs tested produced similar results within the parameters examined. These alterations have been discussed in relation to possible mechanisms and sites of action.
Birth weight and birth defects in relation to maternal spermicide use
Authors: Polednak Anthony P. , Janerich Dwight T. , Glebatis Donna M. 
Published: June 2005

AbstractThe possible effects of maternal spermicide use on birth characteristics of offspring were examined in two studies. First, birth weight of offspring was examined in a cohort study of 302 women who reported using spermicides and 716 women who used no contraceptive methods in the year prior to pregnancy resulting in a 1974 live birth (without a malformation) in Upstate New York. There was no evidence that spermicide use prior to the last menstrual period (LMP) had an effect on mean birth weight or on the proportion of lower weights. Mean birth weight of female births was significantly lower in post‐LMP spermicide users than in pre‐LMP‐only spermicide users and no‐contraceptive users. In multiple linear regression analyses of birth weight among births to spermicide users, including maternal smoking during pregnancy and other variables, time of discontinuation of spermicide use was an important predictor of female (but not male) birth weight. In the second (case‐control) study of 715 Upstate New York births with selected birth defects and 715 control births (matched on maternal age and race), no significantly increased relative risks were associated with maternal spermicide use prior to LMP or after LMP. Based on small numbers, relative risks for post‐LMP spermicide use were greater than 1.00 for hypospadias (8/2 or 4.00, not significant) and for limb reduction defects (6/3 or 2.00, not significant).
X‐ray induced dysplasia in the developing telencephalic choroid plexus of mice exposed in utero
Authors: Heinzmann Ulrich 
Published: June 2005

AbstractPregnant NMRI‐mice were X‐irradiated with single doses of 0.95 Gy (100 R) and 1.9 Gy (200 R) on day of gestation (dg) 12. For sampling, anesthetized animals were perfused with buffered glutaraldehyde solution or fixed by immersion in Karnovsky solution. LM, SEM, and TEM studies were carried out on brains prenatally and up to the age of 20 months to follow the radiation effects on the developing lateral choroid plexus. Radiation‐induced changes were found using all three methods and at all stages studied. The normally sickle‐shaped and stretched choroid plexus is shortened and irregular, and the dome‐shaped plexus cells are flattened. Their superficial fine structures, i.e., the microvilli and cilia, are altered. Three stages of severity can be distinguished and the internal hydromicro‐cephalus increases from stage I to III. Intercellular spaces of the treated plexus epithelium are often dilated, but the tight junctions at the ventricular surface seem to be intact. The interstitium shows large dilations in comparison with the controls. Thus, gross changes and alterations in the fine structure can be induced in the choroid plexus by doses of 0.95 Gy and 1.9 Gy, which persist throughout postnatal life.
Teratogenicity of chlorambucil in rat embryos in vitro
Authors: Mirkes Philip E. , Greenaway Jean C. 
Published: June 2005

AbstractChlorambucil, a bifunctional alkylating agent and antitumor drug, is a potent teratogen in rodents and possibly teratogenic in humans. Unlike cyclophosphamide, a related bifunctional alkylating agent, chlorambucil is a direct‐acting cytotoxic agent. However, several studies indicate that the cytotoxic potential of chlorambucil is enhanced by metabolism of the parent compound. Using day‐10 rat embryos cultured in vitro, we have demonstrated that chlorambucil is a direct acting teratogen but that its teratogenicity can be enhanced by the addition of rat liver S‐9 preparations to culture medium containing the durg. Our data also suggest that this enhancement is not related to cytochrome P‐450 monooxygenases. This conclusion is based upon three lines of evidence. First, enhancement occurs under culture conditions which lack cofactors necessary for cytochrome P‐450 monooxygenases. Second, metyrapone, a known inhibitor of cytochrome P‐450, did not abolish the enhancement. Third, induction of cytochrome P‐450 by two specific inducers of monoxygenase activity had no effect on the observed enhancement. We postulate that the observed enhancement of chlorambucil teratogenicity is related to the β‐oxidation of the butyric acid side chain of chlorambucil generating the more cytotoxic (teratogenic) metabolite, phenylacetic acid mustard. Finally, our data indicate that the teratogenic effects elicited by chlorambucil are indistinguishable from those elicited by cyclophosphamide.
Induction of prenatal toxicity in the rat by diethylstilbestrol, zeranol, 3,4,3′,4′,‐tetrachlorobiphenyl, cadmium, and lead
Authors: Wardell R. E. , Seegmiller R. E. , Bradshaw W. S. 
Published: June 2005

AbstractA teratological study was conducted in pregnant Sprague–Dawley rats dosed orally with diethylstilbestrol (DES), zeranol (ZN), 3,3′,4,4′‐tetrachlorobiphenyl (4CB), cadmium, or lead on days 6–18 of gestation. Fetuses were examined on day 19 for growth retardation, resorption, gross malformations, and organ‐level anomalies. Synthesis of protein, DNA, and proteoglycan in fetal limb cartilage was also studied by measuring the incorporation of labeled precursors in vitro. DES, ZN, and 4CB produced a dose‐dependent increase in embryolethality. Treatment with DES caused an increase in cryptorchidism and edema, and reduced average fetal weight. Zeranol also decreased fetal weight, but was not teratogenic nor did it alter rates of synthesis of macromolecules in cartilage. 4CB caused severe intestinal lesions that were associated with accumulation of blood in the digestive tract and amniotic fluid. 4CB also decreased overall fetal size and total and ossified tibia lengths. Cadmium produced no malformations although incorporation of [3H]amino acids by limb cartilage was slightly increased. Lead was not teratogenic.
Ethanol teratogenicity in mice: A light microscopic study
Authors: Bannigan John , Burke Paul 
Published: June 2005

AbstractThe objective of this study was to see what, if any, cellular changes occurred in the mouse embryo following a single injection of ethanol, a known teratogen in humans and animals, on day 9 of gestation. No changes were seen until 6 hours after injection, when many degenerating cells and necrotic fragments were seen in the neuroepithelium of the neural groove and of the neural tube. In addition, large clear vacuoles were seen in the cytoplasm of many cells and the pseudopodia at the luminal side of the neural groove appeared swollen. The cytoplasm of the latter also contained vacuoles. When tritiated thymidine was injected 5 hours after ethanol and 1 hour before sacrifice, many degenerating cells were labelled. In addition, many cells with labelled nuclei had abnormal vacuoles in the cytoplasm. Hence, it is likely that the toxicity of ethanol is exerted primarily on some component of the cytoplasm and not on DNA synthesis. Twelve hours after ethanol, the cytoplasmic vacuoles and swollen pseudopodia had disappeared, but dying cells were still evident. By 24 hours, the necrotic debris had been completely phagocytosed by healthy neuroepithelial cells. By 50 hours, the neuroepithelium had been cleared of cell debris, although many ethanol‐treated embryos had open defects of the cranial neural tube. Treatment of pregnant mice with single doses of acetaldehyde, also an established teratogen in animals, did not produce any cellular changes. However, a single dose of acetaldehyde is rapidly metabolized by the mother, and would not be comparable to the small but continuous blood levels that a dose of ethanol would produce. Hence, we could not conclude with certainty that the cytotoxic effects of ethanol were exerted directly.
Blood flow during pregnancy in the rat: II. Dynamics of and litter variability in uterine flow
Authors: Buelke‐Sam J. , Holson J. F. , Nelson C. J. 
Published: June 2005

AbstractNormal blood flow patterns were characterized in individual CD rats, nonpregnant (NP) or on day 6, 7, 8, 10, 11, 12, 13, 16, 18, or 20 of gestation using the radioactive microsphere technique. Five animals were evaluated at each stage of pregnancy. Weights and flow values were determined for several maternal organs and uterine tissue samples. Embryo/fetal (E/F) sex was determined from day 11 on by measuring the prevalence of nuclei with sex chromatin in amnion smears. There was a marked increase in absolute flow to the uterus and all uterine contents during gestation (0.28 ± 0.13 ml/min to the NP, diestrous uterus; 9.07 ± 0.97 ml/min on day 20 of pregnancy). However, relative blood flow (ml/min/g tissue) decreased by day 20 to one‐third NP values. Thus, though blood flow greatly increased, it did so at a rate lower than total tissue growth (including the uterus, placental tissues, and the E/F itself). There was a rapid redistribution of blood flow from the decidua parietalis (DEC) to the chorioallantoic placenta (CAP) on days 11–13, with nearly equal flow being delivered to the CAP and DEC of the “average” embryo on day 12 of gestation. By day 16 the DEC functionally had atrophied, and nearly 100% of the flow was delivered to the CAP. Male E/Fs tended to weigh more than female; however, these differences were statistically significant only on days 13, 18, and 20. E/F sex was not found to be strongly related to any of the variable evaluated in this study except E/F weight. Significant interlitter variability in E/F weight and blood flow consistently was observed at all gestational stages. Differences in litter size and E/F distribution within the two uterine horns did not account for the majority of this variability.
Trypan blue teratogenesis in the rat: Further observations in vitro
Authors: Gulamhusein Amir P. , Moore Weiland J. , Gupta Madhu , Beck Felix 
Published: June 2005

AbstractExplanted 9½‐ and 10½‐day rat conceptuses were cultured for 24 or 48 hours and 24 hours respectively in immediately centrifuged, heat‐inactivated rat serum to which trypan blue was added at concentration of 150 μg/ml or 300 μg/ml or 450 μg/ml. The embryos were assessed for normal growth and differentiation using the following criteria: heart beat, vitelline circulation, fusion of the allantois with the chorion, normal turning, normally closed neural tube, presence of optic vesicles, presence of forelimb buds, tail, somites, somite number, yolk sac diameter, crown‐rump length, and protein content. The results indicated that trypan blue is more teratogenic when 9½‐day conceptuses are cultured for the first 24 hours, and that its teratogenicity decreases after 10½ days. Morphological abnormalities produced included neural tube defects, turning defects, and tail defects, the tail abnormalities being manifest as fluid‐filled blebs. Ten and one‐half–day conceptuses cultured for 24 hours in treated serum produced predominantly tail defects. The conceptuses were cultured at 11 days, when the embryo lies completely within the yolk sac. Culture of such conceptuses in serum containing 450 μg/ml trypan blue produced mainly tail defects. Injection of 0.5 μl of 0.5% dye solution into the yolk sac cavity also produced tail abnormalities; sham treatment, or the injection of sterile water or a nonteratogenic dye, azo blue, did not affect embryonic development.
Craniofacial, caudal, and visceral anomalies associated with mutant sirenomelic mice
Authors: Orr Beatrice Y. , Long Sally Y. , Steffek Anthony J. 
Published: June 2005

AbstractCraniofacial anomalies were correlated with mutant murine sirenomelia. Ninety‐eight newborn sirens from heterozygous matings were examined and analyzed. In the 96 sirens that had intact craniofacial structures, micrognathia was seen in 39% of the sirens, microstomia in 34%, macroglossia in 26%, and cleft palate in 21%. Even when not cleft, the siren palates were narrower and more highly arched than those of nonsiren littermates. The frequency of abnormal craniofacial development was greater in those sirens that were more severely affected caudally. Even though some earlier studies had indicated a preponderance of males, 46 of the 95 sirens with intact pelvic viscera were females. Fifth‐three percent of the sirens were monopodal, 35% were apodal, and 11% were dipodal. A penile‐like projection on the genital tubercle occurred on 15 apodal sirens and four monopodal sirens; all but three of these sirens were males. Bladder agenesis was seen in 100% of the sirens, anal atresia in 80%, and bilateral renal agenesis in 43%. No siren was found with bilaterally normal kidneys. The srn gene responsible for sirenomelia might either directly affect the embryo at both the caudal and cranial regions or indirectly affect the embryo by producing lateral mechanical compression at both these sites. The srn gene was earlier characterized as autosomal‐recessive; our data confirm this. Sirenomelia was found in only 11% of the newborns from crosses of carrier mice in the colony. Analyses of uterine contents at days 12–14 suggest that the srn gene is fully penetrant, but often lethal, during the fetal period.
Prospective study of suspected associations between certain drugs administered during early pregnancy and congenital malformations
Authors: Michaelis J. , Michaelis H. , Glück E. , Koller S. 
Published: June 2005

AbstractFrom 1964 to 1976, a cohort study was performed in West Germany to study the possible influence of various factors on pregnancy and child development. Results of the evaluation of 13,643 pregnancies are given with respect to possible teratogenetic effects of antiemetic drugs and sex hormones administered in early pregnancy. There was no evidence of an increased risk of major malformations following the intake of certain antiemetic drugs and progesterone. Also, the use of a hormonal pregnancy test was not significantly associated with an increase of major malformations.
Supradiaphragmatic accessory lobe of the liver in BB Wistar rats
Authors: Wright James R. , Sharma Hari M. , Yates Allan J. , Thompson Bruce M. , Thibert Pierre 
Published: June 2005

AbstractSupradiaphragmatic accessory livers were observed in two closely related rats in a series of 172 necropsies on BB Wistar rats. The gross and histological appearance of both accessory lobes are described. This abnormality has been reported in only one other inbred strain of rats where it also arose with a very low incidence. As in the previous report, the pattern of occurrence of these accessory lobes suggests a mode of inheritance that is either polygenic or autosomal recessive with low penetrance.
Congenital tibial aplasia with preaxial polydactyly: Soft tissue anatomy as a clue to teratogenesis
Authors: Hootnick David R. , Packard David S. , Levinsohn E. Mark 
Published: June 2005

AbstractWe performed preoperative arteriography and postamputation dissection on a human limb having complete tibial aplasia and preaxial polydactyly. The tibia was replaced by a tendinous band with an attached connective tissue mass. In the leg, the muscles were normal. Muscles usually arising from the tibia arose from the tendinous band. Intrinsic muscles of the foot were absent where skeletal elements were absent and there were supernumerary muscles where there were supernumerary skeletal elements. The tendinous insertions of the muscles that originated in the leg followed the skeletal pattern of the foot. The nerves were normally distributed with the exception that extra branches innervated the supernumerary toes. Both the anterior tibial and peroneal arteries were smaller than normal and progressively reduced in size as they coursed distally and could not be identified below the ankle. The dorsalis pedis artery was absent. The other arteries of the leg and foot were normal with the exception of extra branches supplying the supernumerary toes. The anatomy indicates that the foot is probably a double posterior duplication. Such a defect implies abnormal specification of the foot pattern due to a prespecification event. The tibial remnant with normal leg soft tissues indicates normal specification of the leg pattern and subsequent interruption of tibial morphogenesis due to a postspecification event. The presence of these different types of malformations in the same limb may seem to be contradictory. We suggest, however, that a single teratogenic event occurring at one moment in time could cause combined pre‐ and postspecification malformations. We further suggest that a diminished anterior tibial artery reduced the number of vessels available for collateral circulation and thus put the limb at risk for subsequent malformation.
Postnatal behavioral effects of ochratoxin a in offspring of treated mice
Authors: Poppe Susan M. , Stuckhardt Jeffery L. , Szczech George M. 
Published: June 2005

AbstractOchratoxin A is a toxic isocoumarin derivative produced by Aspergillus ochraceus and several Penicillium species, which are storage fungi. Many kinds of agricultural commodities can be contaminated with ochratoxin A, which has been reported in both animal and human foods. Pure crystalline ochratoxin A was dissolved in 0.1 N sodium bicarbonate solution and given intraperitoneally to pregnant ICR‐derived mice at dose levels of 1.25 and 2.25 mg/kg on gestation days 15, 16, and 17 (day 0, day of insemination). Dams were allowed to deliver, and their litters were culled to eight pups. During postnatal development, selected pups were tested for surface righting (days 3–12), swimming (even days 6–20) and pivoting (days 7, 9, and 11). Statistically significant differences for all three tests indicated that a developmental delay had occurred. Brains from the tested offspring were examined by light microscopy; no treatment or dose‐related pathoanatomic alterations were found.
Asplenia syndrome in conjoined twins: A case report
Authors: Ursell Philip C. , Wigger H. Joachim 
Published: June 2005

AbstractIncomplete fission of the primordial cell mass is generally believed to be the cause of conjoined twinning. It may also explain the tendency towards increased symmetry in these twins. We report a case of the rostral duplication type of conjoined twins with an absence of symmetry; one twin had the asplenia syndrome, whereas the other twin was normal. Local environmental factors acting upon the organ anlage may explain the asymmetric development in these conjoined twins.