Occurrence of NTDs was evaluated at embryonic day 11.5 and compared between wild type (WT) and PKC delta homozygous (pkc delta(-/-)) embryos. Changes in oxidative and endoplasmic reticulum (ER) stress-associated factors and stress-response c-Jun N-terminal kinases (JNKs) were assessed PD173074 using Western blot assay. Results: Compared to DM/WT, the DM/PKC delta(-/-) embryos had significantly lower NTD rate and lower levels of oxidative and ER stress factors and JNK activation. These
values were similar to those in the non-diabetic control group. Conclusion: PKC delta plays a critical role in diabetes-induced NTDs, potentially through increasing oxidative and ER stress and JNK-associated stress-response pathways.”
“An in vitro perfusion model of human
placenta was used to study the transplacental passage of iron applied in the form of the drug compound ferric carboxymaltose (FCM) which had been radio-labelled with (59)Fe. In four placental perfusion experiments, two simulated circuits for the maternal and fetal sides of the placenta were set up with two experimental phases each lasting 3 h. FCM was added click here to the maternal circuit at the beginning of each phase to a final iron concentration of 11 mM, which is at least 10 times higher than the maximal predicted level in blood after an administration of 200 mg iron as FCM. The effects of adding transferrin at a physiological concentration of 1.67 mg/ml were also tested.
The concentration profiles of 59Fe showed a 10% decrease within the first 30 min of perfusion on the maternal side. Thereafter the radioactivity levels remained unchanged. The addition of transferrin had no effect on the tissue uptake of (59)Fe-FCM. No transferred
iron radioactivity could be detected in the fetal circuit. Despite a loss of approximately 10% of the radio-labelled iron observed on the maternal side, only 0.5-2% of the radioactivity was detected in the placental tissue after perfusion.
No free iron could be detected at the end of perfusion on the maternal side using ultrafiltration or acid precipitation methods. In addition, the production of transferrin receptor remained unchanged, Flavopiridol with similar concentrations in placental tissue before and after perfusion.
No effects of FCM on placental viability were observed in terms of energy metabolism (glucose consumption and lactate production), hormone release or placental permeability (assessed by the transfer rates of creatinine and antipyrine). However, two additional observations were made: firstly, a significant reduction in the rate of cell death compared to control conditions was observed in the presence of FCM; secondly, the integrity of the fetal capillary system was improved on the fetal side of the perfusion system. It is concluded that the iron compound FCM does not cross the placenta and may increase the integrity of placental tissue (at least under in vitro conditions), but this latter observation needs further investigation.