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Changing the tune : conceptualising the effects of the global financial crisis on stakeholder perceptions of corporate valueMyers, Jonathan January 2019 (has links)
Could shareholder primacy, with its assumed short-termist practices, have had its day when it comes to managerial activity centered on creating corporate value? Many business and opinion leaders appear to take this position, not least Jack Welch who famously declared 'shareholder primacy is the dumbest idea in the world!' Indeed, in a post-Crash economy has a wider stakeholder focus with a longer-term outlook superseded any business notions of shareholder primacy and wealth maximization? This research examines these possibilities through a consideration of the narrative companies produce, such as annual reports. From this corpus material, an assessment is made of whether UK managers' perceptions about corporate value generation changed over the period covering the worldwide financial crisis, with respect to their relative favouring of shareholders and stakeholders. The corpus of narrative material used is visualized as a conceptual space in which a conversation reflecting perceptual bias to the generation of corporate value occurs. To explore such corpuses, in order to compare narratives at points either side of the 2008 Crash, a new methodology was devised called narrative staining. Hence, a detection and visual mapping over the period was made possible of managers' changing perceptions concerning primacy (shareholder or stakeholder orientation) with its mediation by termism (a short or long-term bias). Termism is also originally conceived as part of a larger temporal category, which includes a sense of urgency to act (urgent versus non-urgent) that is similarly examined. The investigation reveals that over time perceptual change about value creation happened, though in unanticipated ways. Companies pre-Crash were often short-term stakeholder oriented then moved post-Crash to a long-term shareholder orientation. A focus for this study was the corporate domain, consisting of a selection of FT250 companies. However, managerial perceptions about corporate value creation are influenced not simply by the conversation of the corporate domain but rather by a multi-actor conversation taking place throughout the business environment. To comprehend this effect, the research mines further corpuses that comprise the UK's regulatory domain (hard and soft law), the press (Financial Times and other newspapers), and relevant peripheral stakeholder organizations (including the Confederation of British Industry, the Institute of Directors, and the Trades Union Congress). These organizations demonstrated more complex, unforeseen, perceptual effects as the financial crisis proceeded with many aligning according to their political or business agenda, which also impacted any sense of urgency to act they had. There appears to be no previous attempt at an extensive and multivariate analysis of this nature. And the findings challenge prevalent characterizations of shareholder and stakeholder behaviour. Moreover, the research shows that utilizing a wide set of stakeholder corpuses acts a viable proxy for broader financial perspectives amongst UK organizations. The technique of narrative staining therefore provides insights, hitherto inaccessible, for assessing and consolidating large-scale perceptual bias regarding value creation across the economy. The technique also has significant potential for other applications.
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ATP induced intracellular calcium response and purinergic signalling in cultured suburothelial myofibroblasts of the human bladderCheng, Sheng 11 June 2012 (has links) (PDF)
Suburothelial myofibroblasts (sMF) are located underneath the urothelium in close proximity to afferent nerves and show spontaneous calcium activity in vivo and in vitro. They express purinergic receptors and calcium transients can be evoked by ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10-16 to 10-4 mol/l) induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3) were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18% ± 1.65 (mean ± SEM) of the sMF (N=48 experiments). ATP significantly increased calcium activity even at 10-16 mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1μM; A-317491, 1μM), and were mimicked by the P2X1, P2X3 selective agonist α,β-methylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca2+ response in cultured sMF at very low concentrations, most likely involving ionotropic P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions.
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Utilisation d'une hiérarchie de compétences pour l'optimisation de sélection de tâches en crowdsourcing / Using hierarchical skills for optimized task selection in crowdsourcingMavridis, Panagiotis 17 November 2017 (has links)
Des nombreuses applications participatives, commerciales et académiques se appuient sur des volontaires ("la foule") pour acquérir, désambiguiser et nettoyer des données. Ces applications participatives sont largement connues sous le nom de plates-formes de crowdsourcing où des amateurs peuvent participer à de véritables projets scientifiques ou commerciaux. Ainsi, des demandeurs sous-traitent des tâches en les proposant sur des plates-formes telles que Amazon MTurk ou Crowdflower. Puis, des participants en ligne sélectionnent et exécutent ces tâches, appelés microtasks, acceptant un micropaiement en retour. Ces plates-formes sont confrontées à des défis tels qu'assurer la qualité des réponses acquises, aider les participants à trouver des tâches pertinentes et intéressantes, tirer parti des compétences expertes parmi la foule, respecter les délais des tâches et promouvoir les participants qui accomplissent le plus de tâches. Cependant, la plupart des plates-formes ne modélisent pas explicitement les compétences des participants, ou se basent simplement sur une description en terme de mots-clés. Dans ce travail, nous proposons de formaliser les compétences des participants au moyen d'une structure hiérarchique, une taxonomie, qui permet naturellement de raisonner sur les compétences (détecter des compétences équivalentes, substituer des participants, ...). Nous montrons comment optimiser la sélection de tâches au moyen de cette taxonomie. Par de nombreuses expériences synthétiques et réelles, nous montrons qu'il existe une amélioration significative de la qualité lorsque l'on considère une structure hiérarchique de compétences au lieu de mots-clés purs. Dans une seconde partie, nous étudions le problème du choix des tâches par les participants. En effet, choisir parmi une interminable liste de tâches possibles peut s'avérer difficile et prend beaucoup de temps, et s’avère avoir une incidence sur la qualité des réponses. Nous proposons une méthode de réduction du nombre de propositions. L'état de l'art n'utilise ni une taxonomie ni des méthodes de classement. Nous proposons un nouveau modèle de classement qui tient compte de la diversité des compétences du participant et l'urgence de la tâche. À notre connaissance, nous sommes les premiers à combiner les échéances des tâches en une métrique d'urgence avec la proposition de tâches pour le crowdsourcing. Des expériences synthétiques et réelles montre que nous pouvons respecter les délais, obtenir des réponses de haute qualité, garder l'intérêt des participants tout en leur donnant un choix de tâches ciblé. / A large number of commercial and academic participative applications rely on a crowd to acquire, disambiguate and clean data. These participative applications are widely known as crowdsourcing platforms where amateur enthusiasts are involved in real scientific or commercial projects. Requesters are outsourcing tasks by posting them on online commercial crowdsourcing platforms such as Amazon MTurk or Crowdflower. There, online participants select and perform these tasks, called microtasks, accepting a micropayment in return. These platforms face challenges such as reassuring the quality of the acquired answers, assisting participants to find relevant and interesting tasks, leveraging expert skills among the crowd, meeting tasks' deadlines and satisfying participants that will happily perform more tasks. However, related work mainly focuses on modeling skills as keywords to improve quality, in this work we formalize skills with the use a hierarchical structure, a taxonomy, that can inherently provide with a natural way to substitute tasks with similar skills. It also takes advantage of the whole crowd workforce. With extensive synthetic and real datasets, we show that there is a significant improvement in quality when someone considers a hierarchical structure of skills instead of pure keywords. On the other hand, we extend our work to study the impact of a participant’s choice given a list of tasks. While our previous solution focused on improving an overall one-to-one matching for tasks and participants we examine how participants can choose from a ranked list of tasks. Selecting from an enormous list of tasks can be challenging and time consuming and has been proved to affect the quality of answers to crowdsourcing platforms. Existing related work concerning crowdsourcing does not use either a taxonomy or ranking methods, that exist in other similar domains, to assist participants. We propose a new model that takes advantage of the diversity of the parcipant's skills and proposes him a smart list of tasks, taking into account their deadlines as well. To the best of our knowledge, we are the first to combine the deadlines of tasks into an urgency metric with the task proposition for knowledge-intensive crowdsourcing. Our extensive synthetic and real experimentation show that we can meet deadlines, get high quality answers, keep the interest of participants while giving them a choice of well selected tasks.
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Le renouvellement de l'office du juge administratif français / The revitalization of powers and duties of the french administrative judgeLeclerc, Caroline 05 December 2012 (has links)
L’étude de l’évolution des méthodes du juge administratif français doit être rattachée aux nouvelles priorités choisies par lui dans l’exercice de sa fonction. « Dire le droit et trancher les litiges » reste bien la principale mission du juge administratif. Certaines des composantes de son office ont néanmoins pris une importance renouvelée dans le cadre d’une politique de renforcement de sa légitimité. La juridiction administrative tient en effet de plus en plus compte de la personne du justiciable et a placé le renouveau de son office sous le signe de la protection des droits fondamentaux, terrain d’élection du dialogue des juges. Ces tendances fortes ont motivé et alimenté une profonde rénovation de ses techniques et méthodes de jugement. Le juge administratif français est aujourd’hui pleinement adapté au temps de l’action administrative et à ses enjeux. Qu’il s’agisse des opérations de contrôle de légalité ou de leur issue, l’efficacité de ses interventions est manifeste. En pleine possession de ses pouvoirs, le juge administratif français apporte une réponse adéquate à la demande de justice contemporaine et a une nouvelle fois relevé le défi du renouvellement. / The study of the evolution of the methods used by the French administrative judge is necessarily connected to the new priorities that were chosen regarding the carrying out of his functions. « Pass judgment and resolve disputes » remains the foremost mission of the administrative judge. Some of the aspects of his powers and duties have nevertheless grown in importance as part of a policy of strengthening his legitimacy.. Indeed , administrative courts increasingly take into account the persons subject to trial and they have focused the revitalization of the jurisdiction on the protection of fundamental rights, a favoured field for the dialogue of judges. Those strong orientations led to a deep reform of their techniques and methods of judgment. The French administrative judge is now fully in accordance with the requirements of administrative actions and the issues at stake. Whether it concerns reviews of legality or their outcome, those interventions are obviously efficient. Thanks to the powers he now detains, the French administrative judge brings an adequate response to the needs of modern justice and has once again taken up the tough challenge of self-reforming his functions.
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ATP induced intracellular calcium response and purinergic signalling in cultured suburothelial myofibroblasts of the human bladder: ATP induced intracellular calcium response and purinergic signalling in cultured suburothelial myofibroblasts of thehuman bladderCheng, Sheng 22 May 2012 (has links)
Suburothelial myofibroblasts (sMF) are located underneath the urothelium in close proximity to afferent nerves and show spontaneous calcium activity in vivo and in vitro. They express purinergic receptors and calcium transients can be evoked by ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10-16 to 10-4 mol/l) induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3) were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18% ± 1.65 (mean ± SEM) of the sMF (N=48 experiments). ATP significantly increased calcium activity even at 10-16 mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1μM; A-317491, 1μM), and were mimicked by the P2X1, P2X3 selective agonist α,β-methylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca2+ response in cultured sMF at very low concentrations, most likely involving ionotropic P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions.:1. Introduction............................................................................ 1
1.1. Anatomy and histology of the human urinary bladder..................... 1
1.1.1. Anatomy of the human urinary bladder..................................... 1
1.1.2. Structure of the human urinary bladder wall............................... 2
1.2. Normal bladder function and bladder dysfunction.......................... 3
1.2.1 Normal bladder function......................................................... 3
1.2.2 Sensory aspect.................................................................... 4
1.2.3 Overactivity or hypersensitivity of bladder.................................. 5
1.3 The role of functional cell types and interaction in urinary bladder... 6
1.3.1 The role of urothelium.......................................................... 7 1.3.2Theroleofsuburotheliamyofibroblast...................................... 7 1.3.3Theroleofdetrusorsmoothmusclecells.................................. 9
1.3.4 Possible interactions in urinary bladder cell types........................ 10
1.4 ATP function and Purinergic signalling in bladder........................... 11
1.5 Spontaneous activity of bladder................................................... 13
2. Objective.................................................................................. 15
3. Material and methods............................................................... 16
3.1. Ethics Statement........................................................................ 16
3.2. Cell preparation.......................................................................... 16
3.3. Solutions and chemicals............................................................. 19
3.4. Intracellular calcium measurements............................................. 20
2.4.1. Preparing cells for Calcium Imaging.......................................... 20
2.4.2. Preparing workspace of calcium imaging................................... 20
2.4.3. Calcium imaging recording...................................................... 22
3.5 Data analysis with automated Fluorescence analysis..................... 22
3.6 Confocal Immunofluorescence.................................................... 25
3.7 Statistics................................................................................. 26
4. Results.................................................................................. 27
4.1 Spontaneous calcium activity of sMF........................................... 27
4.2 ATP effects on calcium response in sMF...................................... 27
4.3 Analysis of purinergic receptors involved.................................... 30
3.3.1 Agonist stimulation.............................................................. 30
3.3.2 Signal inhibition by specific antagonists................................... 31
4.4 Confocal immunofluorescence of purinergic receptors.................. 32
5. Discussion............................................................................. 34
5.1 Myofibroblast identification....................................................... 34
5.2 Spontaneous activity in the bladder............................................ 36
5.3 ATP modulated calcium activity in sMF....................................... 37
5.4 purinergic signalling in sMF........................................................ 39
6. Summary................................................................................ 42
7. References.............................................................................. 45 Declaration............................................................................. 50 Acknowledgements................................................................. 51
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Análise da expressão das metaloproteinases e seus inibidores teciduais no músculo detrusor de pacientes com obstrução infravesical por hiperplasia prostática benigna / Expression of metalloproteinases and their tissue inhibitors in the detrusor muscle of patients with bladder outlet obstruction due to benign prostatic hyperplasiaFerreira, Yuri Afonso 03 October 2014 (has links)
Introdução: A obstrução infravesical (OIV) de longo prazo secundária a hiperplasia prostática benigna (HPB) pode causar alterações funcionais e morfológicas na bexiga. Um dos principais eventos consiste no aumento da deposição de colágeno e perda de complacência vesical, levando a alteração de armazenamento e esvaziamento urinário. O aumento da deposição de colágeno na matriz extracelular (MEC) da musculatura detrusora é a principal razão para a diminuição da complacência vesical. Na bexiga, assim como em outros órgãos, este fenômeno depende da atividade equilibrada de enzimas proteolíticas, incluindo as metaloproteinases (MMP) e os seus inibidores endógenos (inibidores teciduais de metaloproteinases-TIMPs). Como estes fenômenos são desconhecidos na bexiga obstruída, o objetivo deste estudo foi avaliar a expressão gênica de colágeno, MMPs e seus inibidores na bexiga de pacientes com obstrução infravesical. Material e Métodos: Foi realizada uma análise prospectiva e controlada de 43 pacientes com OIV devido a HPB, que foram submetidos à ressecção transuretral da próstata (RTUP) entre 2011 e 2012. Como grupo controle foram selecionados espécimes de músculo detrusor de 10 pacientes que foram submetidos a prostatectomia radical retropúbica devido adenocarcinoma de próstata. Todos estes pacientes tinham idade menor que 60 anos, tamanho de próstata menor que 30 gramas ao ultra-som e escore internacional de sintomas prostáticos (IPSS) menor que 7. Todos os pacientes foram submetidos a estudo urodinâmico pré e pós operatório (após 6 meses). A biópsia de fragmento de músculo da bexiga foi realizada ao final da RTUP e colocada em solução estabilizadora de RNA para quantificação da expressão de colágenos I e III, metaloproteinases de matriz 1, 2 e 9, e inibidores de MMPs (TIMP1, TIMP2 e RECK) na bexiga de pacientes com HPB. Os genes descritos foram avaliados através da técnica de reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR). Resultados: Todos os pacientes com HPB tinham confirmado OIV, através da análise do estudo urodinâmico (média de pressão detrusora no fluxo máximo de 78,5 cmH2O e fluxo urinário máximo de 7,7 ml / s). O gene MMP1 mostrou-se superexpresso em pacientes com HPB (mediana = 1,87). MMP9, TIMP1 e RECK estavam subexpressos na maioria dos casos, enquanto TIMP2, colágeno I e III foram superexpressos (1,5, 4,4 e 1,9 vezes, respectivamente). No que diz respeito às características clínicas e urodinâmicas encontramos que MMP2 foi mais expresso entre pacientes com um baixo IPSS global (0,005) e sem urgência (p=0,035). Colágeno III foi mais expresso em pacientes com contrações vesicais não inibidas (p = 0,049). Os outros genes não mostraram nenhuma correlação estatística com quaisquer características clínicas ou urodinâmicas. Após 6 meses de RTU, pacientes que possuíam expressão aumentada de duas ou mais MMPs, apresentaram resolução da CNI em 66,6% dos casos, contra 14,0% quando apenas uma ou nenhuma MMP estava aumentada (p=0,038) Conclusões: Encontramos um perfil de superexpressão de MMP1, TIMP2, colágenos I e III, e expressão baixa de MMP9, TIMP1 e RECK nos pacientes com OIV. Considerando o escore de sintomas prostáticos e a urgência miccional, encontramos curiosamente uma maior expressão de MMP2 em pacientes menos sintomáticos e sem urgência miccional. Encontramos uma associação entre a maior expressão de colágeno III com HD. A expressão aumentada de duas ou mais MMPs está relacionada à maiores taxas de resolução das CNIs. / Introduction: Long-term Bladder outlet obstruction (BOO) secondary to Benign prostatic Hyperplasia (BPH) can cause functional and morphological abnormalities in the bladder, such as increased collagen deposition and loss of compliance, leading to urinary storage and voiding symptoms. A decrease in bladder compliance is known to be correlated with deterioration of renal function. Increased deposition of collagen in the extracellular matrix (ECM) is the primary reason for a decreased compliance. In the bladder, as in other organs, this phenomenon is dependent on the balanced activity of proteolytic enzymes, including matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The imbalance between MMPs and TIMPs is a key regulator in ECM turnover. Since these mechanisms are unknown in the obstructed bladder, the objective of this study was to evaluate gene expression of collagen, MMPs and their inhibitors in patients with bladder outlet obstruction due to BPH. Material and Methods: We performed a prospective and controlled analysis of 43 patients with BOO due to BPH who underwent transurethral resection of the prostate (TURP) from 2011 to 2012. The control group was comprised of 10 bladder specimens from patients with < 60 years who underwent radical prostatectomy with an International Prostatic Symptom Score (IPSS) < 8 and prostate volume < 30 grams. All patients underwent urodynamic analysis pre and post operatively after 6 months. A biopsy of the bladder muscle was performed at the end of TURP for analysis of collagen, metalloproteinases and TIMPs gene expressions. For this purpose we used the quantitative real time polymerase chain reaction method (qRT-PCR). Results: All patients with BPH had confirmed BOO confirmed through urodynamic analysis (mean detrusor pressure at maximun flow 78.5 cmH2O and mean maximun flow 7.7 ml/s). MMP1 gene showed an important an overexpression in patients with BPH (median = 1.87). A similar phenomenon occurred in a lesser extent to MMP2, to which 13 of 23 subjects had under-expression (mean = 1.2). MMP9, TIMP1 and RECK were under-expressed in the majority of cases, while TIMP2, colagen I and III were over-expressed (1.5, 4.4 and 1.9x respectively) (figure). With regard to clinical and urodynamic characteristics we found that MMP2 was more over-expressed among patients with a low global IPSS (0.005) and without urgency (p=0.035). Colagen III was more over-expressed in patients with non-inhibited bladder contractions (p=0.049), RECK was more over-expressed in patients with a decreased complacence (p=0.049). The other genes showed no statistical correlation with any clinical or urodynamic characteristics. After 6 months of TURP, patients with non-inhibited bladder contractions showed resolution in 66.6% of cases, when had increased expression of two or more (> 02) MMPs in patients compared with 14.0% when only 01 MMP was increased (p = 0.038) Conclusions: BOO is related with an over-expression of MMP1, TIMP2, colagens I and III, and with an under-expression of MMP9, TIMP1 and RECK. Detrusor overactivity is related with higher collagen III expression, this fact may be due to a lower MMP1 expression. A lower global IPSS and no urgency were related to a higher expression of MMP2, sugesting that this gene may be inhibiting collagen deposition in the bladder. The increased expression of two or more MMPs isrelated to greater rates of resolution of non-inhibited bladder contractions
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Análise da expressão das metaloproteinases e seus inibidores teciduais no músculo detrusor de pacientes com obstrução infravesical por hiperplasia prostática benigna / Expression of metalloproteinases and their tissue inhibitors in the detrusor muscle of patients with bladder outlet obstruction due to benign prostatic hyperplasiaYuri Afonso Ferreira 03 October 2014 (has links)
Introdução: A obstrução infravesical (OIV) de longo prazo secundária a hiperplasia prostática benigna (HPB) pode causar alterações funcionais e morfológicas na bexiga. Um dos principais eventos consiste no aumento da deposição de colágeno e perda de complacência vesical, levando a alteração de armazenamento e esvaziamento urinário. O aumento da deposição de colágeno na matriz extracelular (MEC) da musculatura detrusora é a principal razão para a diminuição da complacência vesical. Na bexiga, assim como em outros órgãos, este fenômeno depende da atividade equilibrada de enzimas proteolíticas, incluindo as metaloproteinases (MMP) e os seus inibidores endógenos (inibidores teciduais de metaloproteinases-TIMPs). Como estes fenômenos são desconhecidos na bexiga obstruída, o objetivo deste estudo foi avaliar a expressão gênica de colágeno, MMPs e seus inibidores na bexiga de pacientes com obstrução infravesical. Material e Métodos: Foi realizada uma análise prospectiva e controlada de 43 pacientes com OIV devido a HPB, que foram submetidos à ressecção transuretral da próstata (RTUP) entre 2011 e 2012. Como grupo controle foram selecionados espécimes de músculo detrusor de 10 pacientes que foram submetidos a prostatectomia radical retropúbica devido adenocarcinoma de próstata. Todos estes pacientes tinham idade menor que 60 anos, tamanho de próstata menor que 30 gramas ao ultra-som e escore internacional de sintomas prostáticos (IPSS) menor que 7. Todos os pacientes foram submetidos a estudo urodinâmico pré e pós operatório (após 6 meses). A biópsia de fragmento de músculo da bexiga foi realizada ao final da RTUP e colocada em solução estabilizadora de RNA para quantificação da expressão de colágenos I e III, metaloproteinases de matriz 1, 2 e 9, e inibidores de MMPs (TIMP1, TIMP2 e RECK) na bexiga de pacientes com HPB. Os genes descritos foram avaliados através da técnica de reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR). Resultados: Todos os pacientes com HPB tinham confirmado OIV, através da análise do estudo urodinâmico (média de pressão detrusora no fluxo máximo de 78,5 cmH2O e fluxo urinário máximo de 7,7 ml / s). O gene MMP1 mostrou-se superexpresso em pacientes com HPB (mediana = 1,87). MMP9, TIMP1 e RECK estavam subexpressos na maioria dos casos, enquanto TIMP2, colágeno I e III foram superexpressos (1,5, 4,4 e 1,9 vezes, respectivamente). No que diz respeito às características clínicas e urodinâmicas encontramos que MMP2 foi mais expresso entre pacientes com um baixo IPSS global (0,005) e sem urgência (p=0,035). Colágeno III foi mais expresso em pacientes com contrações vesicais não inibidas (p = 0,049). Os outros genes não mostraram nenhuma correlação estatística com quaisquer características clínicas ou urodinâmicas. Após 6 meses de RTU, pacientes que possuíam expressão aumentada de duas ou mais MMPs, apresentaram resolução da CNI em 66,6% dos casos, contra 14,0% quando apenas uma ou nenhuma MMP estava aumentada (p=0,038) Conclusões: Encontramos um perfil de superexpressão de MMP1, TIMP2, colágenos I e III, e expressão baixa de MMP9, TIMP1 e RECK nos pacientes com OIV. Considerando o escore de sintomas prostáticos e a urgência miccional, encontramos curiosamente uma maior expressão de MMP2 em pacientes menos sintomáticos e sem urgência miccional. Encontramos uma associação entre a maior expressão de colágeno III com HD. A expressão aumentada de duas ou mais MMPs está relacionada à maiores taxas de resolução das CNIs. / Introduction: Long-term Bladder outlet obstruction (BOO) secondary to Benign prostatic Hyperplasia (BPH) can cause functional and morphological abnormalities in the bladder, such as increased collagen deposition and loss of compliance, leading to urinary storage and voiding symptoms. A decrease in bladder compliance is known to be correlated with deterioration of renal function. Increased deposition of collagen in the extracellular matrix (ECM) is the primary reason for a decreased compliance. In the bladder, as in other organs, this phenomenon is dependent on the balanced activity of proteolytic enzymes, including matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The imbalance between MMPs and TIMPs is a key regulator in ECM turnover. Since these mechanisms are unknown in the obstructed bladder, the objective of this study was to evaluate gene expression of collagen, MMPs and their inhibitors in patients with bladder outlet obstruction due to BPH. Material and Methods: We performed a prospective and controlled analysis of 43 patients with BOO due to BPH who underwent transurethral resection of the prostate (TURP) from 2011 to 2012. The control group was comprised of 10 bladder specimens from patients with < 60 years who underwent radical prostatectomy with an International Prostatic Symptom Score (IPSS) < 8 and prostate volume < 30 grams. All patients underwent urodynamic analysis pre and post operatively after 6 months. A biopsy of the bladder muscle was performed at the end of TURP for analysis of collagen, metalloproteinases and TIMPs gene expressions. For this purpose we used the quantitative real time polymerase chain reaction method (qRT-PCR). Results: All patients with BPH had confirmed BOO confirmed through urodynamic analysis (mean detrusor pressure at maximun flow 78.5 cmH2O and mean maximun flow 7.7 ml/s). MMP1 gene showed an important an overexpression in patients with BPH (median = 1.87). A similar phenomenon occurred in a lesser extent to MMP2, to which 13 of 23 subjects had under-expression (mean = 1.2). MMP9, TIMP1 and RECK were under-expressed in the majority of cases, while TIMP2, colagen I and III were over-expressed (1.5, 4.4 and 1.9x respectively) (figure). With regard to clinical and urodynamic characteristics we found that MMP2 was more over-expressed among patients with a low global IPSS (0.005) and without urgency (p=0.035). Colagen III was more over-expressed in patients with non-inhibited bladder contractions (p=0.049), RECK was more over-expressed in patients with a decreased complacence (p=0.049). The other genes showed no statistical correlation with any clinical or urodynamic characteristics. After 6 months of TURP, patients with non-inhibited bladder contractions showed resolution in 66.6% of cases, when had increased expression of two or more (> 02) MMPs in patients compared with 14.0% when only 01 MMP was increased (p = 0.038) Conclusions: BOO is related with an over-expression of MMP1, TIMP2, colagens I and III, and with an under-expression of MMP9, TIMP1 and RECK. Detrusor overactivity is related with higher collagen III expression, this fact may be due to a lower MMP1 expression. A lower global IPSS and no urgency were related to a higher expression of MMP2, sugesting that this gene may be inhibiting collagen deposition in the bladder. The increased expression of two or more MMPs isrelated to greater rates of resolution of non-inhibited bladder contractions
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