Showing papers by "Diederick E. Grobbee published in 1992"
Journal Article•
TL;DR: From results, it is suggested that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.
Abstract: Use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations. Spina bifida aperta has been linked specifically to valproic acid (VPA) (estimated risk, 1 to 2%). The actual risk, the exclusive association of VPA with spina bifida and not anencephaly, and the precise causative relation remain matters of discussion. A prospective cohort study of pregnant women with epilepsy receiving AEDs and referred for prenatal diagnosis before week 22 of gestation was conducted, with follow-up to 3 months after birth. Pregnancies (291 singleton and 6 twin) in 261 women were evaluated. The prevalence of anomalies after exposure to any AED was 6.9%. For fetuses exposed to VPA, the prevalence was 9.4%, including six cases of spina bifida, two of which were in monozygotic twins (giving a prevalence rate of 6.3%, or 5.4%, if twins counted as one). Spina bifida was associated with a significantly higher average daily dose of VPA as compared with pregnancies with normal outcome (1.640 +/- 136 mg/d vs 941 +/- 48 mg/d, p = 0.0001). No relation was observed between the occurrence of spina bifida and type of maternal seizure or epilepsy, family history of epilepsy or neural-tube defects, or medical history. From these results we suggest that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.
246 citations
TL;DR: The enzyme involved in the vitamin K-dependent carboxylation reaction is called y-glutamylcarboxylase and it is located at the luminal side of the endoplasmic reticulum along the route taken by secretory proteins on their way to the outercellular environment, where all Gla-containing proteins are calcium binding ones.
Abstract: Vitamin K functions as a cofactor in the posttranslational conversion of protein-bound glutamate residues into y-carboxyglutamate (Gla). As illustrated in FIGURE 1, the vitamin K-dependent step is a carboxylation reaction, in which the removal of the y-hydrogen precedes the addition of the CO?. The oxidation of vitamin K hydroquinone into vitamin K epoxide provides the energy required for the reaction. In this paper we will only briefly summarize the present knowledge on this subject. For more detailed information we refer to some reviews that have been published recently.'-' The enzyme involved in the vitamin K-dependent carboxylation reaction is called y-glutamylcarboxylase and it is located at the luminal side of the endoplasmic reticulum along the route taken by secretory proteins on their way to the outercellular environment. Hence Gla-residues are exclusively found in secretory proteins but only in a small fraction thereof. To be recognized by the y-glutamylcarboxylase, the nascent polypeptide chain contains an 18 amino acid residue long recognition signal (the pro-sequence) generally located in the leader sequence, directly preceding the N-terminal residue of the mature p r ~ t e i n . ~ ~ The only known function of Gla-residues in proteins is the binding of calcium. Hence all Gla-containing proteins are calcium binding ones.' In solution the binding of Ca+ to the Gla-residue of a protein frequently leads to a conformational change required for its biological activity,* whereas the presence of Gla-residues also gives proteins a high affinity for insoluble barium and calcium salts.9 In all cases in which their function is known, the Gla-residues are essential for the biological activity of the Gla-containing proteins.
22 citations