The Norwegian experience with nationwide implementation of fetal RHD genotyping and targeted routine antenatal anti-D prophylaxis.

OBJECTIVES: To reduce the risk of RhD alloimmunization during the last trimester of pregnancy, a targeted routine antenatal anti-D prophylaxis (RAADP) programme was implemented in Norway in 2016. Here, we present and discuss our experience with the nationwide implementation of the programme, and report sample uptake and preliminary data of de novo anti-D in pregnancy. BACKGROUND: The targeted RAADP was advised by the academic community and evaluated by the health authorities. A National Working Group has conducted the implementation in the transfusion services and contributed to organise the administration of the antenatal anti-D prophylaxis. Fetal RhD type is determined by non-invasive prenatal testing at gestational week 24, and anti-D prophylaxis is administrated at gestational week 28 only to women with RhD positive fetuses. METHODS: We describe the implementation process of targeted RAADP in Norway. The sample uptake is calculated by comparing the number of fetal RHD screens with the expected number of samples. RESULTS: The sample uptake shows regional variations: 88%-100% after 3 years. Promising decrease in de novo anti-D detected during pregnancy is observed. CONCLUSIONS: Nationwide targeted RAADP is implemented and included in the Norwegian maternity care programme. Compliance to sample uptake should further improve in some regions. A remaining issue to fulfil is the documentation of the accuracy of the fetal RHD-typing at all sites. Post-natal prophylaxis will then be guided by the fetal RHD result. Dedicated registries will ensure data to evaluate the expected reduction in pregnancy-related RhD immunisations, which is the final success criterion of the programme.

Disintegration of microtubules in Arabidopsis thaliana and bladder cancer cells by isothiocyanates.

Isothiocyanates (ITCs) from biodegradation of glucosinolates comprise a group of electrophiles associated with growth-inhibitory effects in plant- and mammalian cells. The underlying modes of action of this feature are not fully understood. Clarifying this has involved mammalian cancer cells due to ITCs' chemopreventive potential. The binding of ITCs to tubulins has been reported as a mechanism by which ITCs induce cell cycle arrest and apoptosis. In the present study we demonstrate that ITCs disrupt microtubules in Arabidopsis thaliana contributing to the observed inhibited growth phenotype. We also confirmed this in rat bladder cancer cells (AY-27) suggesting that cells from plant and animals share mechanisms by which ITCs affect growth. Exposure of A. thaliana to vapor-phase of allyl ITC (AITC) inhibited growth and induced a concurrent bleaching of leaves in a dose-dependent manner. Transcriptional analysis was used to show an upregulation of heat shock-genes upon AITC-treatment. Transgenic A. thaliana expressing GFP-marked α-tubulin was employed to show a time- and dose-dependent disintegration of microtubules by AITC. Treatment of AY-27 with ITCs resulted in a time- and dose-dependent decrease of cell proliferation and G2/M-arrest. AY-27 transiently transfected to express GFP-tagged α-tubulin were treated with ITCs resulting in a loss of microtubular filaments and the subsequent formation of apoptotic bodies. In conclusion, our data demonstrate an ITC-induced mechanism leading to growth inhibition in A. thaliana and rat bladder cancer cells, and expose clues to the mechanisms underlying the physiological role of glucosinolates in vivo.