C019 Protéine C activ ée et glucocorticoïdes sont synergiques dans le choc septique expérimental

IntroductionLa Protéine C Activée (PCa) et les glucocorticoïdes sont recommandés dans le traitement du choc septique. Le but de notre étude est de comparer dans deux modèles de choc expérimentaux les effets de la dexaméthasone (glucocorticoïde de référence chez le rat) (Dexa) et de la PCa, seuls ou en association.Matériels et MéthodesDeux modèles de choc chez le rat Wistar : LPS sédaté (10mg/kg) ou CLP chroniquement perfusé + antibiothérapie plus expansion volémique continue (10ml/kg/h) 4 heures après la chirurgie.Traitements et groupes : Sham LPS ou CLP, Dexa [(1mg/kg IV bolus (LPS) ou 2mg/kg/24h IV continue (CLP)], PCa : Xigris, 33 μg/kg/h, PCa + D exa (PCaD)Mesures : PAM, Fc, débit aortique, laser-doppler et PO2 musculaire, lactates, vasoréactivité à la noradrénaline, TNF, NOx et prélèvements tissulaires pour études des voies de signalisation (MAPk, ERK1/2, iNOS, eNOS, glucocorticoïde receptor, ..).Résultats+/- = p<0.05vs LPS/CLP ++/-- = p<0.05vs autres groupesDans le groupe LPS, le débit et la PO2 musculaire sont améliorés par PCa+Dexa. La vasoréactivité diminuée par le sepsis est améliorée par tous les traitements sans différence entre les groupes.ConclusionDans les deux modèles, la combinaison PCa+Dexa est associé à une amélioration marquée des paramètres hémodynamiques et de perfusion tissulaire, une baisse importante des lactates ainsi qu’une amélioration de la survie. L’étude des voies de signalisation à venir devrait nous permettre de mieux préciser les mécanismes en cause

A Novel Constellation Shaping Technique for Bit-Interleaved Coded Modulation

International audienceWe present a new and simple method which consists to apply constellation shaping to bit-interleaved turbo-coded modulation (BICTM) over additive white Gaussian noise channels. By assuming the example of a 3-bit/dim 16-PAM BITCM, it is shown that this technique can provide shaping gain of 0.79 dB

Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone

Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRα in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFβ1 were upregulated by ERRα in tumor cells and all of these factors also significantly and positively correlated with ERRα expression in CRPC patient specimens. Finally, high levels of ERRα in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRα regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRα is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRα may constitute a new therapeutic strategy for prostate cancer skeletal-related events

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

Harnessing on site renewable energy through pile foundations

Incorporation of heat exchangers into pile foundations is a relatively novel sustainable technology for the intermittent storage of energy in soils with a view of utilising it for space heating and cooling of buildings by means of suitable systems integrated into buildings. This innovative technology can provide not only substantial long-term cost savings in relation to conventional energy systems but also can make an important contribution to environmental protection by reducing fossil energy use and minimising the carbon footprint of built structures. This paper reports on an ongoing project on heat exchanger pile foundations taking place at Monash University. It discusses the basic concept of an energy pile and governing design parameters such as thermo-mechanical loading and soil thermal properties and presents the field test set up currently running

Harnessing on site renewable energy through pile foundations

Incorporation of heat exchangers into pile foundations is a relatively novel sustainable technology for the intermittent storage of energy in soils with a view of utilising it for space heating and cooling of buildings by means of suitable systems integrated into buildings. This innovative technology can provide not only substantial long-term cost savings in relation to conventional energy systems but also can make an important contribution to environmental protection by reducing fossil energy use and minimising the carbon footprint of built structures. This paper reports on an ongoing project on heat exchanger pile foundations taking place at Monash University. It discusses the basic concept of an energy pile and governing design parameters such as thermo-mechanical loading and soil thermal properties and presents the field test set up currently running