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      Novel Applications of OnabotulinumtoxinA in Lower Urinary Tract Dysfunction

      review-article
      , *
      Toxins
      MDPI
      botulinum toxin, clinical trial, human, urodynamics

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          Abstract

          OnabotulinumtoxinA (BoNT-A) was first used to treat neurogenic lower urinary tract dysfunction (LUTD) 30 years ago. Recently, application of BoNT-A in LUTD have become more common since the approval of intravesical BoNT-A injection for patients with both overactive bladders (OAB) and neurogenic detrusor overactivity (NDO) by regulatory agencies in many countries. Although unlicensed, BoNT-A has been recommended to treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS) under different guidelines. BoNT-A delivery with liposome-encapsulation and gelation hydrogel intravesical instillation provided a potentially less invasive and more convenient form of application for patients with OAB or IC/BPS. BoNT-A injections into the urethral sphincter for spinal cord injury patients with detrusor-sphincter dyssynergia have been used for a long time. New evidence revealed that it could also be applied to patients with non-neurogenic dysfunctional voiding. Previous studies and meta-analyses suggest that BoNT-A injections for patients with benign prostate hyperplasia do not have a better therapeutic effect than placebo. However, new randomized and placebo-controlled trials revealed intraprostatic BoNT-A injection is superior to placebo in specific patients. A recent trial also showed intraprostatic BoNT-A injection could significantly reduce pain in patients with chronic prostatitis. Both careful selection of patients and prudent use of urodynamic evaluation results to confirm diagnoses are essential for successful outcomes of BoNT-A treatment for LUTD.

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          Most cited references56

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          Update on AUA guideline on the management of benign prostatic hyperplasia.

          To revise the 2003 version of the American Urological Association's (AUA) Guideline on the management of benign prostatic hyperplasia (BPH). From MEDLINE® searches of English language publications (January 1999 through February 2008) using relevant MeSH terms, articles concerning the management of the index patient, a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms (LUTS) were identified. Qualitative analysis of the evidence was performed. Selected studies were stratified by design, comparator, follow-up interval, and intensity of intervention, and meta-analyses (quantitative synthesis) of outcomes of randomized controlled trials were planned. Guideline statements were drafted by an appointed expert Panel based on the evidence. The studies varied as to patient selection; randomization; blinding mechanism; run-in periods; patient demographics, comorbidities, prostate characteristics and symptoms; drug doses; other intervention characteristics; comparators; rigor and intervals of follow-up; trial duration and timing; suspected lack of applicability to current US practice; and techniques of outcomes measurement. These variations affected the quality of the evidence reviewed making formal meta-analysis impractical or futile. Instead, the Panel and extractors reviewed the data in a systematic fashion and without statistical rigor. Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases. Guideline statements concerning pharmacotherapies, watchful waiting, surgical options and minimally invasive procedures were either updated or newly drafted, peer reviewed and approved by AUA Board of Directors. New pharmacotherapies and technologies have emerged which have impacted treatment algorithms. The management of LUTS/BPH continues to evolve. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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            Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.

            The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome based upon data received since the publication of original guideline in 2011.
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              SV2 is the protein receptor for botulinum neurotoxin A.

              How the widely used botulinum neurotoxin A (BoNT/A) recognizes and enters neurons is poorly understood. We found that BoNT/A enters neurons by binding to the synaptic vesicle protein SV2 (isoforms A, B, and C). Fragments of SV2 that harbor the toxin interaction domain inhibited BoNT/A from binding to neurons. BoNT/A binding to SV2A and SV2B knockout hippocampal neurons was abolished and was restored by expressing SV2A, SV2B, or SV2C. Reduction of SV2 expression in PC12 and Neuro-2a cells also inhibited entry of BoNT/A, which could be restored by expressing SV2 isoforms. Finally, mice that lacked an SV2 isoform (SV2B) displayed reduced sensitivity to BoNT/A. Thus, SV2 acts as the protein receptor for BoNT/A.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                26 June 2018
                July 2018
                : 10
                : 7
                : 260
                Affiliations
                Department of Urology, Buddhist Tzu Chi General Hospital, and Tzu Chi University, Hualien 970, Taiwan; alur1984@ 123456hotmail.com
                Author notes
                [* ]Correspondence: hck@ 123456tzuchi.com.tw ; Tel./Fax: +886-3865-1825 (ext. 2113)
                Article
                toxins-10-00260
                10.3390/toxins10070260
                6071213
                29949878
                c4fa5dce-b267-427c-89cb-f930fc178903
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 April 2018
                : 22 June 2018
                Categories
                Review

                Molecular medicine
                botulinum toxin,clinical trial,human,urodynamics
                Molecular medicine
                botulinum toxin, clinical trial, human, urodynamics

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