Nanomolar Levels Of Pahs In Extracts From Urban Air Induce Mapk Signaling In Hepg2 Cells.

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that occur naturally in complex mixtures. Many of the adverse health effects of PAHs including cancer are linked to the activation of intracellular stress response signaling. This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2 cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and c-Jun. ATF2 was also identified as a sensitive stress responsive protein with activation observed at extract concentrations equivalent to 0.1 nM BP. We show that exposure to low levels of environmental PAH mixtures more strongly activates these signaling pathways compared to BP alone suggesting effects due to interactions. Taken together, this is the first study showing the involvement of MEK4/JNK/AP-1 pathway in regulating the intracellular stress response after exposure to nanomolar levels of PAHs in environmental mixtures.

Paired Evaluation Of Calvarial Reconstruction With Prototyped Titanium Implants With And Without Ceramic Coating.

To investigate the osseointegration properties of prototyped implants with tridimensionally interconnected pores made of the Ti6Al4V alloy and the influence of a thin calcium phosphate coating. Bilateral critical size calvarial defects were created in thirty Wistar rats and filled with coated and uncoated implants in a randomized fashion. The animals were kept for 15, 45 and 90 days. Implant mechanical integration was evaluated with a push-out test. Bone-implant interface was analyzed using scanning electron microscopy. The maximum force to produce initial displacement of the implants increased during the study period, reaching values around 100N for both types of implants. Intimate contact between bone and implant was present, with progressive bone growth into the pores. No significant differences were seen between coated and uncoated implants. Adequate osseointegration can be achieved in calvarial reconstructions using prototyped Ti6Al4V Implants with the described characteristics of surface and porosity.