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S Pennington

Publications and source records attributed to S Pennington.

11 recordsLinked to original sources
PubMed1992

Effect of cocaine, ethanol or nicotine on ornithine decarboxylase activity in early chick embryo brain.

Fetal drug exposure causes multiple deficits in the developing child. For both humans and animal models, the single most common drug-related problem is fetal growth suppression. This defect is associated with significant perinatal morbidity and mortality and may also be related to significant behavioral problems appearing later in life. Studies focussed on the molecular mechanism of fetal drug effects in placental models are complicated by multiple interactions of the drug with mother, placenta and fetus. Using early (76-168 h) chick embryos as a non-placental model, and three common drugs of abuse (nicotine, ethanol and cocaine) it was found that each drug suppressed the peak in fetal brain ornithine decarboxylase (ODC) activity that normally occurs at 120 h of development. For each drug, the decrease in ODC activity at 120 h was followed by a small but significant increase in ODC. Thus, although the drug-treated embryos were smaller in size, they appeared to be undergoing compensatory growth and, in fact, became equal in weight to the vehicle-treated animals, if allowed to hatch.

Animals↗
PubMed1988

Ethanol-induced growth inhibition: the role of cyclic AMP-dependent protein kinase.

Growth retardation is the single most common deficit observed in infants exposed to ethanol in utero, and the molecular mechanisms responsible for this growth inhibition are a focus of ongoing research. Several lines of research have suggested that ethanol-induced changes in the adenylate cyclase-protein kinase cascade may be involved in this process. Using an embryonic chick model, it was demonstrated that ethanol exposure during early development caused increases in cellular prostaglandin E2 and cyclic AMP levels that were inversely correlated with brain weight. Paradoxically, basal adenylate cyclase and protein kinase catalytic activities, assayed in vitro, were not altered by ethanol dosing. Ethanol exposure did suppress the responsiveness of brain adenylate cyclase to exogenous PGE2. Furthermore, ethanol treatment significantly lowered the brain cytoplasmic levels of cyclic AMP binding protein.

Animals↗
PubMed1988

Ethanol-induced growth inhibition in embryonic chick brain is associated with changes in cytoplasmic cyclic AMP-dependent protein kinase regulatory subunit.

Several lines of research have suggested that ethanol-induced changes in the adenylate cyclase/protein kinase cascade may contribute to the growth retardation observed in infants exposed to ethanol in utero. Based on studies with an embryonic chick model, the data presented here suggest that chronic ethanol treatment significantly lowered the binding of cyclic AMP by protein kinase regulatory subunit (RII) and reduced the level of phosphorylation of RII by the endogenous cytoplasmic protein kinase catalytic subunit. Furthermore, ethanol treatment altered the phosphorylation of at least one other brain cytosolic protein (molecular weight = 62-65 kD).

Animals↗
PubMed1987

Brain growth during ethanol-induced hypoplasia.

The inhibition of fetal brain growth resulting from in utero ethanol exposure may impair central nervous system (CNS) development and thereby result in mental retardation. Studies of ethanol-induced brain hypoplasia using chick embryos have shown that the early development of the chick is significantly growth inhibited by a single dose of ethanol (1.0 g/kg) given at the start of incubation (day 0). However, this level of ethanol exposure has been reported to have no effect on chick weight measured at hatching, suggesting that the weights of ethanol-treated chicks were regained during their development. The present experiments were undertaken to determine the biochemical changes associated with the varying growth rates believed to occur in the alcohol-treated embryos. The results indicated that between days 5 and 8 of development, the rates of DNA and protein synthesis (measured as radioactive thymidine and leucine incorporation, respectively) were inhibited by ethanol. The growth inhibition was highly correlated with blood alcohol content and there were associated increases in brain prostaglandin E (PGE) levels relative to vehicle-treated embryos. Further, there was a significant, inverse correlation between brain cyclic AMP content and individual brain weight. By day 10, the ethanol-treated embryos remained smaller than controls but their rates of DNA and protein synthesis were comparable to those of control animals. The normal rates of synthesis observed on day 10 appeared to correlate with clearance of the ethanol dose and with restoration of normal brain levels of PGE relative to 10-day vehicle-dosed embryos.

Animals↗
PubMedDate not supplied

Prostaglandin synthesis inhibitors block alcohol-induced fetal hypoplasia.

Alcohol-induced growth retardation is a fetal effect consistently associated with maternal ethanol consumption. In humans, those infants whose mothers consume even a limited amount of ethanol during pregnancy have a significant incidence of growth inhibition. The molecular mechanism responsible for this growth deficiency is unknown, and prevention depends on maternal abstinence during pregnancy. The data reported here suggest that ethanol-mediated increases in tissue prostaglandin (PG) E levels (PGE1 plus PGE2) are correlated with the growth retardation. Further, simultaneous administration of PG synthesis inhibitors with the alcohol blocks the rise in tissue PG levels and protects against the alcohol-induced hypoplasia.

Animals↗