Search

Background: Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss ® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss ® in ethanol (EtOH) treated osteoblasts., Methods: The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss ® were assessed., Results: The application of PRGF and Bio-Oss ® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss ® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss ® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells., Conclusions: These results indicate that the simultaneous application of PRGF and Bio-Oss ® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Excess release of reactive oxygen species (ROS) is a major cause of oxidative stress. This disturbance has been implicated as a cause of preeclampsia, a pregnancy-related disorder characterized by hypertension and proteinuria. Increased oxidative stress leads to trophoblast apoptosis/necrosis and alters the balance between pro- and anti-angiogenic factors, resulting in generalized maternal endothelial dysfunction. Trials using antioxidants have significantly failed to improve the condition of, or in any way protect, the mother from the life-threatening complications of this syndrome. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent transcription activator that regulates the expression of a multitude of genes that encode detoxification enzymes and anti-oxidative proteins. Recent discussion on evidence of a link between Nrf2 and vascular angiogenic balance has focussed on the downstream target protein, heme oxygenase-1 (HO-1). HO-1 metabolizes heme to biliverdin, iron and carbon monoxide (CO). HO-1/CO protects against hypertensive cardiovascular disease and contributes to the sustained health of the vascular system. In one animal model, sFlt-1 (soluble fms-like tyrosine kinase-1) has induced blood pressure elevation, but the induction of HO-1 attenuated the hypertensive response in the pregnant animals. The special conditions under which Nrf2 participates in the pathogenesis of preeclampsia are still unclear, as is whether Nrf2 attenuates or stimulates the processes involved in this syndrome. In this review, we summarize recent theories about how Nrf2 is involved in the pathogenesis of preeclampsia and present the reasons for considering Nrf2 as a therapeutic target for the treatment of preeclampsia., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Aims: Trophoblast fusion in the placenta is prerequisite to successful pregnancy and the pathological conditions related to it. The presence of syncytin-1, is not sufficient to explain the complete event and ADAM12 is a major co-player candidate. Via differential splicing, the ADAM12 gene produces a short and a long form, being the ADAM12-S and the ADAM12-L respectively., Methods and Results: We investigated the localisation of both variants in the human placenta using whole mount in situ hybridisation, immunohistochemistry and Northern blotting in 1st (n=8) and 3rd (n=8) trimester placentae and in the case of NB in several cell lines. In Northern blotting, 1st and 3rd trimester placentae were positive for the ADAM12-S and Bewo, 293HEK, JAR, leucocytes, macrophages, 1st and 3rd trimester placentae were positive for ADAM12-L. In whole mount in situ hybridisation, the 1st and 3rd trimester placental syncytium was positive for both variants. In immunohistochemistry, ADAM12-L localised in the cytotrophoblast of both 1st and 3rd trimester placentae, while ADAM12-S localised in the complete syncytium, often including the cytotrophoblast., Conclusion: The different localisation of ADAM12-S and ADAM12-L indicates a possible different role making ADAM12-L a candidate for the fusion event, while the syncytial localisation of the ADAM12-S makes it a candidate for cell-cell and cell-matrix interactions between the placental syncytium and the maternal interface., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Invasion of the nervous system and neuronal spread of infection are critical, but poorly understood steps in the pathogenesis of prion diseases. We have thus analyzed the internalization and signal transduction of the neurotoxic fragment of the prion protein PrP(106-126) in the rat neuroblastoma cell line B104 by fluorescence microscopy and quantification by ELISA and in primary neuronal cells from mice. Phospholipase D (PLD) is known to be an enzyme involved in the regulation of secretion, endocytosis and receptor signalling. We determined the PLD activity using a transphosphatidylation assay and could show that PLD is involved in PrP(106-126) internalization. The determination of receptor activity via quantification of ERK1/2 phosphorylation and cAMP level measurement verified the PrP(106-126)-induced signal transduction in B104 cells and primary neuronal cells. PrP(106-126)-induced a decrease in cAMP level in neuronal cells. These studies indicate the involvement of PLD in PrP(106-126)-endocytosis and mediated cellular signalling by an unidentified inhibitory G-protein-coupled receptor and may allow the development of therapeutic agents interfering with prion uptake and/or PLD function using PLD as a possible pharmaceutical target.