Potential of various drugs to inhibit nucleoside uptake in rat syncytiotrophoblast cell line, TR-TBT 18d-1

The placenta requires nucleosides as nutrients for fetal growth, so it is important to examine potential interactions between placental transports of nucleosides and drugs to ensure the safety of pharmacotherapy during pregnancy. The purposes of this study are to clarify the uptake mechanisms of nucleosides from the maternal side of the syncytiotrophoblast and to investigate the inhibitory effect of various drugs on nucleoside uptake, using the rat syncytiotrophoblast cell line TR-TBT 18d-1, which shows syncytial-like morphology and functional expression of several transporters. Initial uptake of [(3)H]uridine or [(3)H]adenosine from the apical side of TR-TBT 18d-1 was markedly reduced by an excess of the respective unlabelled compound, and was slightly reduced by replacement of Na(+) with N-methyl-d-glucamine, indicating that both uptakes were Na(+)-independent. [(3)H]Uridine and [(3)H]adenosine uptakes in the absence of Na(+) were significantly and concentration-dependently inhibited by both 0.1 microM and 100 microM nitrobenzylthioinosine, suggesting the involvement of equilibrative nucleoside transporters (ENTs, SLC29). Kinetic analysis of adenosine uptake yielded a K(m) value of approximately 17 microM. These results are consistent with the reported uptake characteristics of uridine and adenosine by ENT1 and ENT2. The uptakes were significantly reduced by high concentrations of several nucleoside drugs, including cytarabine, vidarabine, zidovudine, mizoribine, caffeine and amitriptyline, but the effects were small within the therapeutic concentration ranges. In summary, our results suggest that ENTs are involved in apical uptake of uridine and adenosine in the syncytiotrophoblast. However, therapeutic concentrations of the drugs tested in this study might have little influence on maternal-to-fetal nucleoside transfer.     

Antenatal administration of granulocyte-macrophage colony-stimulating factor increases fetal lung maturation and endothelial nitric oxide synthase expression in the fetal rat lung

Objective

To study subsequent pregnancy outcome in women with severe, very early onset preeclampsia (onset before 24 weeks’ gestation) and to analyze cardiovascular risk profiles of these women and their partners.

Study design

Twenty women with preeclampsia with an onset before 24 weeks’ gestation, admitted between 1 January 1993 and 31 December 2002 at a tertiary university referral center, were enrolled in the study. Data on subsequent pregnancies were obtained from medical records. Their cardiovascular risk profiles and those of their partners (n = 15) were compared with those of 20 control women after uncomplicated pregnancies only, matched for age and parity, and those of their partners (n = 13). Body weight, height, waist and hip circumference, blood pressure and intima media thickness (IMT) of the common carotid artery were measured. Fasted blood samples were drawn for detection of metabolic cardiovascular risk factors.

Results

Of the 20 case women 17 women had 24 subsequent pregnancies, of which 12 (50%) were complicated by preeclampsia. Severe preeclampsia developed in five (21%) pregnancies. No perinatal deaths occurred. Case women had significantly more often chronic hypertension as compared to controls (55% vs. 10%, P = 0.002). IMT of the common carotid artery was increased in a subset of case women using antihypertensive medication (P = 0.03). Case women showed increased microalbuminuria (P < 0.05). No differences were found in cardiovascular risk profiles between partners of cases and controls.

Conclusions

Women with severe, very early onset preeclampsia have an increased risk of preeclampsia in future pregnancies, yet neonatal outcome is, in general, favourable. Regarding cardiovascular health, women after severe, very early onset preeclampsia exhibit more risk factors compared to controls whereas men who fathered these pregnancies do not.     

Effect of antioxidant lycopene on human osteoblasts

Clinical Oral Investigations - The aim of this in vitro study is to evaluate the effect of antioxidant lycopene on human osteoblasts. The human osteoblast cell line (CRL-11372) was obtained from...