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Richard H Finnell - One of the best experts on this subject based on the ideXlab platform.

  • biochemical and molecular teratology of Fetal Hydantoin Syndrome
    Neurologic Clinics, 1994
    Co-Authors: Bruce A Buehler, Velidi H Rao, Richard H Finnell
    Abstract:

    The question of maternal seizures as a teratogen was raised 30 years ago. Since then, a great deal of controversy has existed about the role of seizures in pregnant mothers as opposed to the direct effects of anticonvulsant medications. Animal and human research has clearly shown that anticonvulsants are teratogens and pose a risk for Fetal malformations. In the case of dilantin, it appears that Fetal susceptibility correlates with the Fetal level of the microsomal detoxifying enzyme epoxide hydrolase.

  • prenatal prediction of risk of the Fetal Hydantoin Syndrome
    Obstetrical & Gynecological Survey, 1991
    Co-Authors: Bruce A Buehler, Richard H Finnell, Duane Delimont, Michael Van Waes
    Abstract:

    Abstract The well-known teratogenicity of several anticonvulsant medications is associated with an elevated level of oxidative metabolites that are normally eliminated by the enzyme epoxide hydrolase. In this study, we attempted to determine whether infants who are at risk for congenital malformations could be identified prenatally by the measurement of epoxide hydrolase activity. Before fetuses at risk could be identified, it was necessary to measure epoxide hydrolase activity in a randomly selected sample of amniocytes from 100 pregnant women. According to a thin-layer Chromatographic ssay, the randomly selected sample population had an apparently trimodal distribution, suggestive of an enzyme regulated by a single gene with two allelic forms. Fetuses homozygous for the recessive allele would have low epoxide hydrolase activity and would therefore be at risk if exposed to anticonvulsant drugs during gestation. In a prospective study of 19 pregnancies monitored by amniocentesis, an adverse outcome was pr...

Bengt R Danielsson - One of the best experts on this subject based on the ideXlab platform.

William S Webster - One of the best experts on this subject based on the ideXlab platform.

Annacarin Skold - One of the best experts on this subject based on the ideXlab platform.

Mary Ellen Mortensen - One of the best experts on this subject based on the ideXlab platform.

  • kids are different developmental variability in toxicology
    Toxicology, 1996
    Co-Authors: Linda J Graeter, Mary Ellen Mortensen
    Abstract:

    Data on the impact of many environmental compounds to human health is often lacking, particularly when considering the risk to the unborn and developing child. The stage of development of the individual at the time of exposure to a toxicant has not always been considered. For example, a higher percentage of ingested lead is absorbed from the gastrointestinal tract of infants than adults. Renal elimination also follows a developmental pattern, being very limited during the newborn period, increasing during infancy and childhood, and declining gradually after puberty. Genetic polymorphisms in metabolic enzyme activity add another dimension of variability. Depending on the particular chemical, this may serve as a protective factor or increase susceptibility to toxic effects (e.g. epoxide hydrolase and Fetal Hydantoin Syndrome). Children also have distinctive behaviors and target organ susceptibilities that warrant special consideration. The consequences of developmental changes are well-known in medical practice, and many drug doses are modified based on age, liver, and renal function, and other factors that may influence pharmacokinetic behavior of drugs. There is a sizable body of such information available, in part, in the pediatric and clinical pharmacology and toxicology literature. The concept of the significance of developmental stage is becoming increasingly important in toxicological risk assessment as well.