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At least 433 records · Page 24Linked to original sources
PubMed1988

The relationship of embryotoxicity to disposition of 2-methoxyethanol in mice.

Paw development of CD-1 mice is uniquely sensitive to 2-methoxyethanol (ME) given by gavage (po) on gestation day (gd) 11 (copulation plug day = gd 0). The relation between induction of paw dysmorphogenesis and disposition of po ME (3.3 or 4.6 mmol/kg) in the maternal and conceptus compartments was investigated. The expression of digit malformations depends on metabolism of ME to methoxyacetic acid (MAA). ME and MAA were equipotent in causing teratogenicity. Alcohol dehydrogenase (ADH) catalyzes the initial rate-limiting oxidation that leads to embryotoxicity. The ADH inhibitor 4-methylpyrazole (0.12 or 1.2 mmol/kg) or ethanol (43.3 mmol/kg, single dose concomitant with ME or additional ethanol 5 and 10 hr later) reduced the incidence of malformations 60-100%, depending on the dosing regimen. Elimination of 14C from 1,2-14C-ME occurred predominantly via urine where 80% of a teratogenic dose was excreted and 6% appeared in CO2. Oxidation of ME to MAA was nearly complete after 1 hr when approximately 90% of 14C in maternal plasma and conceptus coeluted with authentic 14C-MAA upon HPLC. 14C-MAA levels in embryos were 1.2 X those in plasma 1 and 6 hr after dosing, although by 6 hr concentrations had declined to approximately 50% of 1-hr values. Concomitant ethanol did not affect 14C kinetics as measured in maternal blood after oral 14C-ME, but retarded ME conversion to MAA by about 2 hr. Furthermore, embryo 14C-MAA levels then reached only 50% of the peak in embryos from dams dosed with ME alone, an effect that coincided with less 14C incorporation into macromolecules synthesized by the embryo within 6 hr. These data imply that the attenuation of digit malformations by concomitant ethanol may be explained by changes in MAA disposition. However, delayed ethanol (5 and 10 hr after 3.3 mmol ME/kg) reduced teratogenicity by 25%, although MAA was present in the embryo up to 5 hr. Dams given 14C-MAA by iv injection had higher 14C blood levels than after MAA po but their offspring had fewer digit malformations. Peak and steady-state plasma levels of MAA as well as embryo concentrations of the chemical do not appear to determine the embryotoxic outcome whereas further metabolism of MAA does.

Abnormalities, Drug-Induced↗
PubMed1985

Dynamics of the control of body pattern in the development of Xenopus laevis. I. Timing and pattern in the development of dorsoanterior and posterior blastomere pairs, isolated at the 4-cell stage.

Xenopus embryos have been selected in which the second cleavage is occurring in a frontal plane, i.e. one tending to lie at right angles to the prospective plane of bilateral symmetry for the body pattern. Some of these have been used to deduce a map of the disposition of materials for the normal mesodermal pattern (the normal 'fate map') by injecting blastomeres to found fluorescently marked clones from 4- to 32-cell stages. Other such 4-cell embryos have been separated into two isolates across this second cleavage; in fate-map terms, prospective dorsoanterior and posterior isolates. These have been allowed to develop to control axial larval stages, with examination of the time schedule of their gastrulation movements in relation to cofertilized whole controls. The patterns of mesoderm produced have been examined and interpreted in the light of quantitative knowledge about the normal pattern, and our current understanding of the map. A meaningful fate map exists for the egg material even at this early, essentially acellular stage, and it differs appreciably from what might have been expected in view of that traditionally shown for early gastrula stages. The patterns developed in the isolates show that at least in many eggs, widespread information that positively specifies material as to its body position is available from at most 1 h after the events that give rise to bilateral symmetry upon fertilization. This information usually leads to a mosaic development of the appropriate mesodermal part-pattern in dorsoanterior isolates, and frequently allows development that approximates to this in the reciprocal posterior part. Regulation, i.e. the replacement of removed information to specify a development more complete than the normal contribution in isolates, is not observed. The results suggest a revision of former claims for regulative ability in at least this amphibian embryo. They also imply that systems for ascribing position value (positional information) to early embryonic tissue can be diverse in dynamics, even among embryos whose body plans are obviously homologous as are those of vertebrates.

Animals↗
PubMed1992

Biosecurity and minimal disease herds.

The minimal disease concept is a way of raising pigs so that some specific diseases are absent. Many bacteria and viruses can be transferred by pigs, air, or mechanical contact. To avoid contamination, the herd location should take into consideration disease transmission possibilities. Herd health status and source herd health status should be continuously monitored. To maintain herd health status, specific rules need to be followed for herd construction and establishment, compound perimeter, people movement, down time, animal transportation, feed use and delivery, vehicle movement, material, dead animal disposition, and rodent control. All new incoming animals should go through quarantine, and in some herds, safer methods such as AI, embryo transfer, MEW, or hysterectomy and fostering need to be used.

Animal Feed↗
PubMed1998

Disposition of the novel anti-schizophrenic drug [14C]olanzapine in male Fischer 344 and female CD rats following single oral dose administration.

These studies comprehensively evaluate the distribution of [14C]olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)-1,5)benzodiazepin e, CAS 132539-06-1, LY170053) a novel anti-schizophrenic compound, following single oral dose administration in male Fischer 344 rats, and pregnant and non-pregnant lactating female CD rats. The disposition of radiocarbon was determined and tissue pharmacokinetics evaluated in male Fischer 344 rats following a single oral 8 mg/kg dose at 2, 6, 24, 48, 72, and 96 h postdose using quantitative whole-body autoradiographic (QWBA) techniques in conjunction with image analysis. This study demonstrated that [14C]olanzapine and/or metabolites were rapidly absorbed and widely distributed with a tmax of 2 h postdose in most tissues. Persistent but declining concentrations of radiocarbon were detected in feces, kidney, liver, and Harderian, preputial, and thyroid glands at 96 h postdose. Placental transfer of [14C]olanzapine was evaluated at 0.5, 1, 3, 6, and 24 h postdose on gestation day 12, the mid-point of organogenesis, by tissue dissection and liquid scintillation spectroscopy (LSC) and on gestation day 18, a time which enabled visualization of fetal tissues by whole-body autoradiography (WBA). The placental transfer studies indicated that all tissues analyzed had a tmax of 1 or 3 h postdose with maternal liver consistently containing high concentrations of radiocarbon. Embryos contained measurable concentrations of radiocarbon throughout the time course of these studies confirming that [14C]olanzapine and/or its metabolites crossed the placenta. Additionally, the disposition of [14C]olanzapine in milk and plasma of lactating female CD rats confirmed pup exposure through milk ingestion.

Animals↗
PubMed1997

Mathematical analysis for teratogenic sensitivity.

A mathematical structure is described for determining teratogenic sensitivity or susceptibility from analysis of malformation incidence, dose-response, and pharmacokinetic data obtained during pregnancy as a result of exposure to a teratogenic agent. From the dosage or exposure of laboratory animals, embryonic and maternal concentrations of the xenobiotic are calculated using a physiologically based pharmacokinetic (PBPK) model. Malformations observed in the progeny are linked to the PBPK-derived target tissue concentrations with a model for the sensitivity calculated as a function of the embryonic age. The PBPK model for internal disposition of chemicals during pregnancy was developed previously. This report focuses on the development of the mathematical relations for the sensitivity of the embryo and effect functions on different organs. The concentrations of a xenobiotic calculated for the site of action or target tissue(s) in the embryo are weighted using both a nonlinear dose-response curve and a sensitivity distribution function that depends on the age or stage of development of the embryo. This weighted "exposure" of the target tissue is regressed with the number of observed malformations to quantify the parameters of the model. This approach lends itself to integration of diverse sources of experimental data, with hydroxyurea data taken from several sources in the literature as an example. This sensitivity function obtained from laboratory animal data serves as a vehicle for prediction and extrapolation to human pregnancy for the teratogenic potential of a substance.

Abnormalities, Drug-Induced↗
PubMed2006

The rise and demise of a collection of human fetuses at Mount Holyoke College.

When I found myself at the center of a controversy over the disposition of an old collection of human fetal specimens at Mount Holyoke College, I was motivated to explore the historical transformation that turned embryo collecting for research and pedagogical purposes from a noble to a disparaged practice, and dead fetuses from prized anatomical specimens to ugly, anomalous entities. Using Linda Layne's analysis of the literal and symbolic erasure of dead fetuses from American cultural discourse, this article examines the shifting circumstances that once encouraged the collection of fetal specimens but that now mandate their disappearance. Using Mount Holyoke as a case study, it describes the scientific logic and specific social exchange networks that led to the acquisition of hundreds of fetal specimens in the first half of the 20th century. It also examines the factors--including changes in biology education, concerns about handling hazardous fixatives, and especially the prominence of beautified and lifelike fetal images consistent with the so-called "culture of life"--that prompt the dissolution and demise of human embryo and fetal collections.

Biological Specimen Banks↗
PubMed1966

Death in embryonic systems.

The principal conclusion to be drawn from the foregoing discussion is that the death of cells and the destruction of tissues, organs, and organ systems are programmed as normal morphogenetic events in the development of multicellular organisms. Death in embryonic systems may thus be explored within the same conceptual framework as growth and differentiation. The present exploration has revealed that death during embryogenesis serves utilitarian goals in some instances, at least, that its occurrence is subject to control by factors of the immediate cellular and humoral environment, and that aberrations in its normal pattern of expression provide the mechanism for realization of many mutant phenotypes. Hopefully, it has also pointed toward the appropriate formulation of some of the problems that confront us in understanding the control of death at the level of genetic transcription, the biochemical events which determine and accompany its occurrence, and the pathways of disposition and the developmental significance of disassembled cellular building blocks.

Animals↗
PubMed1986

Disposition of homocysteine and S-3-deazaadenosylhomocysteine in cells exposed to 3-deazaadenosine.

The nucleoside analogue, 3-deazaadenosine (c3-Ado), serves both as a substrate and as an inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, and the ability of this compound to induce accumulation of intracellular AdoHcy and S-3-deazaadenosylhomocysteine (c3-AdoHcy) in various cells and species has been widely documented. We here report on the effect of c3-Ado on the disposition of homocysteine (Hcy) and c3-AdoHcy in isolated rat hepatocytes and in non-transformed (Cl 8) and malignant (Cl 16) C3H/10T1/2 mouse embryo fibroblasts in culture. Both the liver cells and fibroblasts release large amounts of Hcy into the extracellular medium, whereas small amounts are retained within the cells. c3-Ado (100-300 microM) nearly completely inhibits cellular Hcy egress. Intracellular Hcy in liver cells exposed to c3-Ado is in fact increased in proportion to intracellular buildup of AdoHcy, whereas c3-Ado nearly deprives the malignant Cl 16 cells of intracellular Hcy and decreases it markedly in Cl 8 cells. Adenosine exerts a similar effect as c3-Ado on Hcy and AdoHcy in liver cells, but concentrations in the mM range are required, and the effect subsides within hours. In liver cells, c3-Ado(300 microm) induces a higher level of c3-AdoHcy than of AdoHcy. In the malignant (Cl 16) fibroblasts, c3-AdoHcy content approaches the amount of AdoHcy whereas, in the non-transformed (Cl 8) fibroblasts, relatively small amounts of c3-AdoHcy are formed. Notably, c3-AdoHcy is released from all cell types in proportion to the intracellular amount, suggesting that c3-AdoHcy is efficiently handled by the mechanism responsible for the cellular egress of nucleosidylhomocysteine. The possible role of Hcy and c3-AdoHcy in the mechanism of action of c3-Ado is discussed.

Adenosine↗
PubMed1984

[Ultrastructure of the mitotic apparatus of metaphase cells in a pig embryo kidney tissue culture after stopping the action of 2-mercaptoethanol].

The ultrastructure of the metaphase mitotic apparatus has been studied in the KEPV cells during 6 hours after the removal of 2-mercaptoethanol (0.001 M). Starting from the analysis of chromosome disposition, the structures of the kinetochore regions and of the mitotic spindle poles, and the degree of integrity of the mitotic spindle microtubules, six types of metaphase cells were revealed. A comparison of the results of the present paper with those of the earlier studies enabled us to present the dynamics of the metaphase mitotic apparatus reconstruction. Four basic stages are revealed in this process. At the first stage, the K-metaphase centrioles form diplosomes again, the number and extent of kinetochore microtubules increase too. At the second stage, the metaphase plate forms, but interpolar and astral microtubules are absent. At the third stage, the structure of the kinetochore regions becomes normal. Thus, the metaphase plate may have formed before the orientation of kinetochores to the poles took place. At the fourth stage, the interpolar and astral microtubules appear; the mitotic spindle reestablishes completely. It is supposed that the formation and functioning of the mitotic apparatus is not confined to the interaction of microtubules of different types.

Animals↗
PubMed1984

Effects on pregnancy in mice of passive immunization against ovine LH and human chorionic gonadotrophin.

Mice given daily i.p. injections of immunoglobulins against ovine LH on Days 3-7 of pregnancy were devoid of implantation sites on Day 8 whereas mice treated with antibodies to hCG had embryos of normal number and appearance on Day 8. These antibody treatments reduced the mean +/- s.d. serum progesterone concentrations from 65.4 +/- 15.3 ng/ml (control globulins) to 8.6 +/- 4.9 ng/ml (anti-LH) and 9.2 +/- 3.1 ng/ml (anti-hCG) on Day 8 and had no differential effect on serum oestrogen levels on Day 4. However, the mice treated with anti-hCG did not litter; resorption of the embryos took place between Days 10 and 14 of pregnancy. Indirect immunofluorescence and quantitative immunoenzymic assays showed the presence of anti-ovine LH and anti-hCG reacting antigens in the mouse feto-placental unit. On Day 6, the values of reacting antigens (mean +/- s.d. absorbance units/10 micron section of embryo) were 0.050 +/- 0.002 with control globulins, 0.059 +/- 0.002 with anti-hCG-Ig and 0.196 +/- 0.018 with anti-LH-Ig; the corresponding values on Day 12 were 0.075 +/- 0.009, 0.402 +/- 0.02 and 0.416 +/- 0.015. The quantitative disposition of the reacting antigens to the two types of anti-gonadotrophins seems to bear a temporal relationship to their respective antifertility action. The pregnancy terminating action of immunoglobulins to ovine LH (Days 6, 7 & 8) and hCG (Days 8, 9 & 10) was counteracted by administration of 2 mg medroxyprogesterone acetate on Days 6, 9 and 12, indicating the importance of progesterone in the maintenance of pregnancy in the mouse.

Animals↗
PubMed1981

[Ultrastructure of the mitotic apparatus in metaphase cells exposed to 2-mercaptoethanol in embryonic swine kidney tissue culture].

The ultrastructure of the mitotic apparatus in metaphasic cells of the porcine embryo kidney culture was studied in the course of the 20 hour treatment with 2-mercaptoethanol (0.001M). In these conditions metaphasic cells were recognized according to the following signs: chromosome disposition; the degree of spindle microtubule destruction; the structure of spindle poles, and the organization of kinetochore regions. On this basis, five types of metaphasic cells have been distinguished. It is suggested that modifications of the mitotic apparatus in these metaphasic types may reflect the reorganization of all its parts (metaphasic plate, mitotic spindle, spindle poles) that occur in the process of the transformation of mitotic cells, from the normal metaphase stage to the stage of C-metaphase under the influence of 2-mercaptoethanol treatment.

Animals↗
PubMed1991

Transplacental distribution of weak acids in mice: accumulation in compartments of high pH.

The transplacental distribution of three weak acids was measured in mice on gestational day 11. The ratio of drug concentration in maternal, embryonic, and extraembryonic compartments compared to maternal plasma followed a consistent hierarchy such that amniotic fluid greater than or equal to exocoelomic fluid greater than embryo greater than embryo plasma greater than maternal skeletal muscle. This distribution pattern correlates well with pH in these compartments and suggests that pH gradients between compartments are an influential factor in determining weak acid drug disposition during pregnancy.

Acids↗
PubMed1976

[Localization and volume of the derivatives of the prechordal plate of the cephalic gut in vertebrates].

In order to determine the localization and volume of the prechordal lamina derivatives the initial stages of histogenesis of the cephalic gut epithelium lining were studied in embryos of chickens and mammals (rabbits, rats, mice) in early terms of the formation of the fore-part of their digestive tube. It has been established that the derivatives characteristics of the prechordal lamina such as the cephalic end of the chordal, larval mesodermal somites, are formed by the real enterocelic means only from the entodermal epithelium of the Seessel's pouch walls which is the most cranial end of the cephalic gut. In other parts of the dorsal wall of the pharynx, the more of the oesophagus, the prechordal lamina derivatives fail to be determined. This fact shows that the localization of the prechordal lamina coincides with the disposition of the Seessel's pouch lining, the histological nature of its material being identical to the entoderm.

Animals↗