Nutrition in the management of inborn errors of metabolism.

The determination of specific nutrients is important in the diagnosis of several inborn errors of metabolism. Phenylketonuria (PKU) is a well-known example. In this case, the nutrient, phenylalanine, is assayed to confirm a diagnosis and is routinely measured to monitor therapy, which consists of a diet low in this particular amino acid. Although many of the described inborn errors of metabolism are uncommon, or even rare, in occurrence, the laboratory plays an essential role in the diagnosis and management of these diseases.

Teratogenicity of etretinate during early pregnancy in the rat and its correlation with maternal plasma concentrations of the drug.

Sprague-Dawley female rats were treated with a single oral dose of 0 (vehicle), 10, or 25 mg/kg of etretinate (ET), an aromatic retinoid, on gestation day 6, 7, or 8. While treatment on day 8 with both dosages of ET was highly teratogenic, no evidence of embryotoxicity, considered to be treatment related, was observed when the same doses were administered on day 6 or 7. We concluded that the rat embryo is not susceptible to teratogenic effects of ET on gestation day 6 or 7 and that day 8 is the earliest susceptible period for ET teratogenesis. This may well be true of retinoids as a class since we have observed similar results for all-trans- and 13-cis-retinoic acids (unpublished findings). In another study, mated rats were treated with a single oral dose of ET on day 8. No evidence of embryotoxicity was observed at dosages of 1, 3, and 6 mg/kg; in contrast, treatment with 10, 15, or 25 mg/kg of ET resulted in an increasingly greater number of malformed fetuses and resorptions. Plasma concentrations of ET and three metabolites [acitretin (AC), 13-cis-etretinate (13-cis-ET), and 13-cis-acitretin (13-cis-AC)) were determined in mated rats given a single oral non-teratogenic (3 or 6 mg/kg) or teratogenic (10 or 25 mg/kg) dose of ET on gestation day 8. The AUC0----24hr values of ET and AC, the major metabolite and suspected proximal teratogen, were roughly proportional to the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary, fecal and urinary excretion of [3H]-prostaglandins in the rat.

The profiles of biliary, fecal and urinary excretion of tritium labeled prostaglandins (PG's) of differing biological activity were investigated in the rat. The PG's (10 micrograms/kg: 2 to 50 microCi/rat, in 1 ml polyethylene glycol-400) were administered intragastrically. Excretion data were expressed as a percentage of the total administered radioactivity. For the orally administered PG's 11R-methyl-16R-fluoro-15R-hydroxy-9-oxoprosta-ci s-5-trans-13-dienoic acid and its methyl ester, excretion was equally divided between urine and feces. The fecal and urinary profile of excretion of 3H after prostacyclin (PGI2) was similar to that following administration of 11R, 16, 16-trimethyl-15R-hydroxy-9-oxoprosta-cis-5-trans-13-dienoic acid (trimoprostil), a PG with antisecretory-antiulcer potential. However, PGI2 was very poorly absorbed from the intestine, while the absorption of trimoprostil was very efficient. Biliary excretion, with little entero-porto-hepatic biliary circulation, was the main route of elimination of trimoprostil, thereby resulting in rapid elimination of drug-related products and diminishing the potential for systemic liability in the rat.

Protective effect of ascorbic acid on hepatotoxicity caused by sodium nitrite plus aminopyrine.

The oral treatment of rats with sodium ascorbate in combination with sodium nitrite and aminopyrine prevents the rise in serum alanine aminotransferase (EC 2.6.1.2) observed when nitrite and aminopyrine are given alone. Ascorbic acid also affords protection, whereas dehydroascorbic acid exerts no protective effect.