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Can J Urol ; 24(4): 8922-8931, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28832313


INTRODUCTION: This study aims at analyzing the impact of reaching current markers of proficiency on intra and postoperative clinical outcomes of laser vaporization with 180W GreenLight XPS in the treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: A retrospective analysis was conducted on a prospectively collected database of 328 consecutive patients who underwent photoselective vaporization of the prostate (PVP) using Greenlight XPS performed by a single experienced laser surgeon. A logarithmic model was used to evaluate the case number to attain benchmark criteria for durable treatment. We compared clinical outcomes before and after current markers of proficiency, defined as either an energy density of 4kJ/cm³ or a 6 month prostate-specific antigen (PSA) drop of = 50%, were attained. RESULTS: Energy delivered per prostate volume increased significantly with experience. The published benchmark values of 4kJ/cm³ and 6 month PSA drop of 50% were attained after 190 and 155 cases, respectively. There were no significant differences between groups in intraoperative complications or postoperative functional outcomes. However, the number of Clavien-Dindo category I adverse events significantly decreased with experience. Sub-analysis evaluating prostate volumes ≤ 80 cm³ and > 80 cm³ demonstrated comparable clinical outcomes before and after technical proficiency. CONCLUSION: In our experience, the case volume required to achieve consistent reference values related to durable clinical outcomes and surgical proficiency was > 150 cases. However, desirable clinical outcomes were attained before reaching current markers of proficiency, regardless of preoperative prostate size. This suggests that current thresholds of technical proficiency may not be a good predictor of satisfying clinical outcomes.

Competência Clínica , Terapia a Laser , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , Humanos , Complicações Intraoperatórias/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/normas , Estudos Retrospectivos , Resultado do Tratamento
Proc Natl Acad Sci U S A ; 109(17): E1028-37, 2012 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-22493236


G protein-coupled receptors (GPCRs) have been shown to activate the mitogen-activated protein kinases, ERK1/2, through both G protein-dependent and -independent mechanisms. Here, we describe a G protein-independent mechanism that unravels an unanticipated role for ß-arrestins. Stimulation of the V2 vasopressin receptor (V2R) in cultured cells or in vivo in rat kidney medullar collecting ducts led to the activation of ERK1/2 through the metalloproteinase-mediated shedding of a factor activating the insulin-like growth factor receptor (IGFR). This process was found to be both Src- and ß-arrestin-dependent. Whereas Src was found to act upstream of the metalloproteinase activation and be required for the release of the IGFR-activating factor, ß-arrestins were found to act downstream of the IGFR transactivation. Unexpectedly, the engagement of ß-arrestins by the IGFR but not by the V2R was needed to promote the vasopressin-stimulated ERK1/2 activation, indicating that a pool of ß-arrestins distinct from those ß-arrestins recruited to the V2R acts downstream of the receptor tyrosine kinase to activate ERK1/2. Such a dual site of action for ß-arrestins helps explain the pleiotropic actions of this scaffolding protein. Given the role that V2R-stimulated ERK1/2 plays in kidney cell proliferation, this transactivation mechanism may have important implications for renal pathophysiology. Still, the role of ß-arrestins downstream of a transactivation event is not limited to the V2R, because we observed a similar involvement for an unrelated GPCR (the platelet-activating factor receptor), indicating that it may be a general mechanism shared among GPCRs.

Arrestinas/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores de Somatomedina/metabolismo , Receptores de Vasopressinas/metabolismo , Ativação Transcricional , Animais , Células Cultivadas , Ativação Enzimática , Medula Renal/citologia , Medula Renal/metabolismo , Ratos , Receptores de Somatomedina/genética , beta-Arrestinas
Biophys J ; 99(12): 4037-46, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21156147


Bioluminescence resonance energy transfer (BRET) is increasingly being used to monitor protein-protein interactions and cellular events in cells. However, the ability to monitor multiple events simultaneously is limited by the spectral properties of the existing BRET partners. Taking advantage of newly developed Renilla luciferases and blue-shifted fluorescent proteins (FPs), we explored the possibility of creating novel BRET configurations using a single luciferase substrate and distinct FPs. Three new (to our knowledge) BRET assays leading to distinct color bioluminescence emission were generated and validated. The spectral properties of two of the FPs used (enhanced blue (EB) FP2 and mAmetrine) and the selection of appropriate detection filters permitted the concomitant detection of two independent BRET signals, without cross-interference, in the same cells after addition of a unique substrate for Renilla luciferase-II, coelentrazine-400a. Using individual BRET-based biosensors to monitor the interaction between G-protein-coupled receptors and G-protein subunits or activation of different G-proteins along with the production of a second messenger, we established the proof of principle that two new BRET configurations can be multiplexed to simultaneously monitor two dependent or independent cellular events. The development of this new multiplexed BRET configuration opens the way for concomitant monitoring of various independent biological processes in living cells.

Transferência Ressonante de Energia de Fluorescência/métodos , Proteínas Luminescentes/metabolismo , Cor , AMP Cíclico/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Receptores Acoplados a Proteínas-G/metabolismo