Objective To assess lipid peroxidation and antioxidant function in hypertensive complications of pregnancy. Design Cross sectional study comparing pre‐eclamptic and control patients. Setting Tampere University Hospital, Finland. Subjects Twenty healthy women with normal, uncomplicated pregnancy; 23 women with severe pre‐eclampsia; 20 women with mild pre‐eclampsia; and 13 women with pregnancy‐induced hypertension. Main outcome measures Conjugated dienes; tiobarbituric acid—reactive material or malondialdehyde (MDA); fluorescent chromolipids (FCL); glutathione peroxidase (GSHPx); selenium; uric acid; and vitamin E. Results Lipid peroxidation assessed by the appearance of conjugated dienes and malondialdehyde was significantly increased in the hypertensive patients as compared with control patients. Lipid peroxidation products also showed high correlation to the level of blood pressure, but failed to show significant relation to the outcome of the fetus. The activities of erythrocyte and plasma glutathione preoxidase were increased in severe pre‐eclampsia, and high levels of plasma or platelet glutathione peroxidase were found to have some association with fetal growth retardation or asphyxia. Conclusions Our findings give support to those few studies considering lipid peroxidation as an important factor in the pathogenesis of pre‐eclampsia. The rise in antioxidants is probably of compensatory nature responding to the increased peroxide load in pre‐eclampsia and may reflect the severity of the disease.

Aims Hydroxychloroquine (HCQ) is used widely in the treatment of chronic in¯ammatory diseases such as rheumatoid arthritis. Since there is great interindividual variability in the pharmacokinetics of HCQ and chloroquine is a potent inhibitor of CYP2D6-catalysed pathways in vitro, we wished to study the interaction of HCQ with CYP2D6-mediated metabolism of other drugs in vivo. Methods Metoprolol and dextromethorphan (DM) were selected as probe drugs because they are well-studied and widely used test substrates of CYP2D6. In this randomized, double-blind crossover study, seven healthy volunteers with extensive metabolizer phenotype for CYP2D6 ingested either 400 mg hydroxychloroquine or placebo daily for 8 days after which single oral dose pharmacokinetics of metoprolol were investigated. Dextromethorphan metabolic ratio (DM-MR) was also determined at baseline and after the ingestion of HCQ or placebo. Results Concomitant administration of HCQ increased the bioavailability of metoprolol, as indicated by signi®cant increases in the area under the plasma concentration-time curve (65t4.6%) and maximal plasma concentrations (72t6.9%) of metoprolol. While the DM-MR values were not signi®cantly changed, the phenotypic classi®cation of one individual, who was heterozygous for a mutant CYP2D6 allele, was converted to a poor metabolizer by HCQ administration. Conclusions HCQ inhibits metoprolol metabolism most probably by inhibiting its biotransformation by CYP2D6. The inhibitory effect of HCQ on dextromethorphan metabolism was not apparent when DM-MR was used as an indicator, except in an individual with limited CYP2D6 capacity.

No abstract

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A‐ type of the enzyme, were administered to eight young, healthy male volunteers in a double‐blind, random‐order, placebo‐controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO‐B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose‐dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non‐ deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4‐dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4‐dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5‐hydroxyindoleacetic acid (5‐HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO‐B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose‐dependent and MAO‐A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO‐A inhibition in man. 4. Sympatho‐adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose‐dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

Seventeen pregnancies with pregnancy-induced hypertension (PIH) and 28 control pregnancies were analyzed with regard to maternal and fetal blood antioxidants and lipid peroxidation products (conjugated dienes). In PIH, maternal blood levels of conjugated dienes were higher than in normal pregnancy. Also the activities of platelet and plasma glutathione peroxidase (GSHPx) were higher in PIH. In umbilical cord blood, the appearance of conjugated dienes, the concentration of vitamin E and the activity of erythrocyte GSHPx were lower than the corresponding maternal values. There was no difference between PIH and normal pregnancy in the appearance of conjugated dienes in cord blood, but erythrocyte GSHPx and plasma vitamin A were lower in PIH. Cord blood plasma vitamin A showed a negative correlation to maternal mean arterial pressure. We suggest that lipid peroxidation is involved in the pathogenesis of maternal PIH, and it may also have effects on the vascular function and antioxidant status of the fetus.