Liposome-Mediated Cellular Delivery of Active gp91phox

International audienceBACKGROUND: Gp91(phox) is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY: Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. CONCLUSIONS: Using this system, we over-express truncated forms of the gp91(phox) protein under soluble form in the presence of detergents or lipids resulting in active proteins with a "native-like" conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67(phox), p47(phox), p40(phox) and Rac) and arachidonic acid. We also produce proteoliposomes containing gp91(phox) protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91(phox) proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91(phox) protein

Place de la néphrectomie partielle assistée par robot : revue de la littérature à l’heure d’une demande de nomenclature spécifique

International audienceRobot-assisted surgery is practiced more and more frequently in urology. Besides its place in prostatectomy for cancer, it also concerns partial nephrectomy (NP), in the treatment of renal tumors. The objective of this review is to compare the robot-assisted approach with laparoscopic or open approaches in partial nephrectomy in terms of functional or oncological outcomes and per- and postoperative complications.MATERIAL AND METHODS:A systematic review of the literature published from 2009 was carried out on PubMed. Clinical studies or meta-analyzes comparing robot-assisted surgery versus laparoscopic or open surgery in the NP domain were used.RESULTS:The clinical data presented in this review of the literature are based mainly on meta-analyzes of comparative studies. Patients operated with robotic assistance (NPAR) had significantly fewer postoperative complications than patients operated by open (RR 0.61; P=0.0002) or laparoscopic surgery (RR 0.84; P=0.007). Positive margins, at equivalent pathological stages, are comparable to the open and appear to be lower than the laparoscopic surgery (RR 0.53; P<0.001). After NP, the change in postoperative glomerular filtration rate (GFR) appears to be identical between the 3 pathways. Hot ischemia time is significantly shorter for NPAR compared to NPL. Finally, the estimated blood loss and length of stay are less severe in patients operated by NPAR compared to those operated by open surgery.CONCLUSION:Robot-assisted surgery offers the same oncological results (in the short and medium term) and appears to improve functional outcomes and morbidity. However, these findings need to be carefully analyzed, due to the low level of evidence from the studies presented and included in the meta-analyzes, and the lack of randomized clinical studies

[Postoperative C-reactive protein is a reliable marker to detect complications after radical cystectomy]

International audiencePURPOSE: Postoperative serum C-reactive protein (CRP) can be measured after major abdominal surgery to predict of complications at postoperative day (POD) 4. However, in urology, no studies have been conduced to analyze the role of CRP after radical cystectomy. The present study aims to analyze the relationship between a high postoperative level of CRP and the presence of complications after radical cystectomy for cancer. MATERIALS AND METHODS: This multicenter retrospective study included 313 patients treated with radical cystectomy for cancer between January 2013 and July 2016. Among the patients, 57.5% of patients received urinary diversion using a Bricker ileal conduit, 30.5% an orthotropic ileal neobladder, and 11.5% had an ureterocutaneostomy. RESULTS: Three hundred and thirteen patients were included (mean age 68.1\textpm9.2 years). Among the patients, 26.5% had grade>=2 complications, according to the Clavien-Dindo classification. In multivariate analysis, only CRP level at POD 4 predicted the risk of a complication (P\textless0.001). CRP\textgreater150mg/L at POD 4 was strongly associated with a risk of a postoperative complication after a cystectomy (OR=81.42, 95% CI [25.6-258.3], P\textless0.001). CRP assessed on POD4 was reliable at ruling out the existence of an infectious complications with a negative predictive value of 0.94. The main limitation of our study was it observational design. CONCLUSIONS: CRP at POD4 with a threshold of 150mg/L would reliably predict the risk of postoperative complications after cystectomy. Monitoring postoperative CRP could help adapt rehabilitation protocols after radical cystectomy and also the early management of complications