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Biomedical subjects

J G Wilson

Publications and source records attributed to J G Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1977

Non-confirmation of thalidomide induced teratogenesis in rats and mice.

It has been reported that thalidomide, dissolved in a 1:3 mixture of Tween 20 and physiological saline and administered intraperitoneally to pregnant mice and rats induces a variety of malformations, including limb deformaties, characteristic of the primate syndrome. The studies reported herein attempted to confirm these findings without success although the rodent strains used were not the same. A low level of non-specific malformations was observed in the fetuses of both species at dose levels reported to cause a 47 percent and 92 percent rate of malformation in mice and rats respectively. One possible source of difference was Tween 20 which was toxic to the point of lethality in these studies at dose levels reported to be non-toxic in the earlier studies.

Abnormalities, Drug-Induced↗
PubMed1977

Teratogenic effects of environmental chemicals.

Despite the widespread distribution of a great many chemical substances in the environment, very few have been implicated in human teratogenicity, and most of these are drugs used at relatively high biological effect levels. Although several other types of environmental chemicals such as pesticides, solvents, and metals can be shown under laboratory conditions to have some teratogenic potential, there is little evidence that these, at present ambient concentrations and conditions of exposure, represent significant hazards to human intrauterine development. An exception to the latter generalization is methylmercury which, because of peculiarities in distribution, can reach high concentration in the human diet.

Animals↗
PubMed1977

The effects of thalidomide and two analogues on the regenerating forelimb of the newt.

Oral administration (3 mg/day) of thalidomide during the dedifferentiation and early limb-bud stages of newt forelimb regeneration produced a variety of specific limb deformities. Proximal and preaxial skeletal elements were the most severely malformed, e.g. preaxial hemimelia, severe proximal deformities, and preaxial polydactyly. Likewise, oral, daily doses (3 mg) of the teratogenic analogue, EM12, on days 7 and 8 following bilateral amputation caused the same incidence and type of forelimb abnormalities as did thalidomide. Conversely, the non-teratogenic analogue, EM87, when orally administered (3 mg/day) on days 7 and 8 post-amputation resulted in a low rate of limb deformities, similar in type to those seen in control regenerates. The type of limb deformities observed in the regenerating newt forelimb following thalidomide treatment nearly mimic those seen in the human and monkey syndromes. Therefore, the newt represents a possible model for investigating some of the problems associated with thalidomide teratogenesis.

Amputation, Surgical↗
PubMed1976

Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the ""litter effect''.

Rats were mated for two or 15 hours and variability of day-12-embryos in weight, protein content, and [3H]thymidine incorporation was compared in the long mating period (LMP) and short mating period (SMP) groups by a 2-level nested analysis of variance. Variability in day-20 fetal weight was similarly compared. In both groups day-12 embryonic weight was relatively more variable than day-20 fetal weight, and variability was less in SMP than LMP animals for each comparison made, although statistical significance was attained only for thymidine incorporation. ""Litter effects'' were noted but not of the magnitude reported by other investigators. It was concluded that inappropriate statistical methods have encouraged the belief that among-litter variability usually exceeds within-litter fetal weight variability. The teratological implications of reduced development variability and the ""litter effect'' are discussed.

Abnormalities, Drug-Induced↗
PubMed1975

Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.

Hydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. According, in rats 137 mg/kg/day ip on days 9-12 resulted in a drug half-life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23-32 resulted in drug half-life in maternal plasma estimated to be 120 min and in embryos 265 min, after the last injection. Using as a baseline of biological effects the minimal concentration known to inhibit DNA synthesis in rat embryos and cancer cells, namely 10(-4) M, it was calculated that the rat embryos in the present study were exposed to this level or more for approximately 12 h whereas the monkey embryos were exposed for approximately 100 h. Although the teratogenic effects were not identical in the two species, these data are interpreted to mean that rat embryos are teratogenically much more sensitive to hydroxyurea than monkey embryos. These observations have important implications in the selection of appropriate species for tests to estimate human teratogenic risks. The rat, which is currently the most widely used animal for such tests, displays sizeable differences from rhesue monkeys, which is one of the animals thought to be most like man in teratogenic susceptibility.

Amniotic Fluid↗
PubMed1975

Inhibition of ATP synthesis associated with 6-aminonicotinamide (6-AN) teratogenesis in rat embryos.

Pregnant rats were injected ip with 6 mg/kg 6-aminonicotinamide (6-AN) at day 12 of gestation. Embryos removed between 1 and 48 h later had reduced adenosine triphosphate (ATP) concentrations, of about 50% of control values. All fetuses examined near term were malformed. Nicotinamide (NAM, 100 mg/kg) given ip 1 h after 6-AN afforded protection: malformations occurred in only 15% of the survivors; and there was minimal ATP reduction, 15% below control values. NAM given 2 and 4 h after 6-AN produced intermediate ATP concentrations and malformation frequencies. Thus, there was a relation between the embryotoxic and ATP-depressant actions of 6-AN in day 12 rat embryos.

6-Aminonicotinamide↗
PubMed1975

Reproduction and teratogenesis: current methods and suggested improvements.

The risks to human reproduction, particularly in regard to possible induction of birth defects, from present levels of environmental chemicals are thought to be low but in need of closer scrutiny than is now the case. Methods currently used to estimate the hazards to reproduction of new chemicals and drugs are reviewed and some shortcomings and potential sources of error are noted. Specific suggestions are made for improving existing methodology. In addition to the widely used treatment span encompassing all or most of the period of organogenesis, it is proposed that some exposure periods of shorter duration be added to avert possibly adaptative changes in maternal homeostatic systems. Greater diversity of test animals, beyond the rodent-rabbit species largely used today, is urged with the objective of better matching metabolic pathways in a test animal to those of man. The demonstration of an embryotoxicity effect-level must be regarded as essential in all tests, and once found this level should be used as the basis of extrapolating downward to find an acceptable tolerance level of dosage. More attention should be focused on postnatal functional evaluation after prenatal and perinatal exposure of test animals to environmental chemicals, especially those that might interfere with the maturation of the central nervous system, endocrine glands, and immunological mechanisms. The use of nonhuman primates should be reserved for the testing of drugs essential for use during human pregnancy or early pregnancy, because of the scarcity of such animals and the high costs of doing meaningful tests with them.

Animals↗