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      Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity

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          To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features.

          Materials and Methods:

          The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining.


          Significant increased SPK1 urothelial immunoreactivity was shown in patients compared to control group (p=0.03). By contrast, SPK1 immunoreactivity in patients was significantly decreased in the sub-urothelium, muscles and nerves, p=0.02; 0.01 and 0.003, respectively. Patients with neurogenic detrusor overactivity (NDO) had higher SPK1 urothelium expression than those without any DO (p=0.04).


          SPK1 is expressed in the human bladder wall, specifically the urothelium, in bladder specimens from patients with NDO. The role of SPK1 in the pathophysiology of NDO needs further elucidation.

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          Most cited references 24

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          Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies.

          This is the first report of the International Continence Society (ICS) on the development of comprehensive guidelines for Good Urodynamic Practice for the measurement, quality control, and documentation of urodynamic investigations in both clinical and research environments. This report focuses on the most common urodynamics examinations; uroflowmetry, pressure recording during filling cystometry, and combined pressure-flow studies. The basic aspects of good urodynamic practice are discussed and a strategy for urodynamic measurement, equipment set-up and configuration, signal testing, plausibility controls, pattern recognition, and artifact correction are proposed. The problems of data analysis are mentioned only when they are relevant in the judgment of data quality. In general, recommendations are made for one specific technique. This does not imply that this technique is the only one possible. Rather, it means that this technique is well-established, and gives good results when used with the suggested standards of good urodynamic practice. Copyright 2002 Wiley-Liss, Inc.
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            Urinary bladder contraction and relaxation: physiology and pathophysiology.

            The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.
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              Urothelial signaling.

              The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

                Author and article information

                Int Braz J Urol
                Int Braz J Urol
                International Brazilian Journal of Urology : official journal of the Brazilian Society of Urology
                Sociedade Brasileira de Urologia
                Nov-Dec 2015
                Nov-Dec 2015
                : 41
                : 6
                : 1141-1147
                [1 ]Département d'Urologie, CHU Rangueil, Toulouse, France
                [2 ]Department of Uro-Neurology, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom
                [3 ]Laboratoire d'Anatomo-pathologie, CHU Rangueil, Toulouse, France
                [4 ]INSERM I2MC UMR1048, CHU Rangueil, Toulouse, France 1 Département d'Urologie, CHU Rangueil, Toulouse, France
                Author notes
                Correspondence address: Quentin Ballouhey, MD, Département d'Urologie, CHU Rangueil, TSA 50032, 31059, Toulouse, France, Fax: +5 61 323-230, E-mail: q.ballouhey@

                CONFLICT OF INTEREST

                None declared.


                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Figures: 3, Tables: 2, Equations: 0, References: 21, Pages: 7
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