title: In the human urothelium and suburothelium, intradetrusor botulinum neurotoxin type A does not induce apoptosis: preliminary results.
abstract: BACKGROUND
  Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.
  
  
  OBJECTIVE
  To investigate BoNTA-induced apoptosis in patients with refractory neurogenic OAB.
  
  
  METHODS
  Twelve refractory OAB patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) and seven controls were included prospectively.
  
  
  METHODS
  The number of apoptotic cells before and 4 wk after first intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining.
  
  
  CONCLUSIONS
  Comparison of TUNEL-positive cells (yes vs no) in the bladder urothelium and suburothelium revealed no significant differences in OAB patients before (4 of 12, 33%) versus after (3 of 12, 25%) BoNTA treatment (p=0.99). In addition, no significant differences (p=0.99) were found in OAB patients versus controls. Because our findings are based on first intradetrusor BoNTA injections only, it is unclear whether the results could be extrapolated to repeat injections.
  
  
  CONCLUSIONS
  In contrast to preliminary animal experiments, first intradetrusor BoNTA injections for treating refractory neurogenic OAB--a highly effective treatment--did not induce apoptosis in the bladder urothelium and suburothelium.
authors.affiliation: Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and University College London Institute of Neurology, Queen Square, London, UK. tkessler@gmx.ch
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kessler
authors.forename: Shahid
authors.initials: S
authors.lastname: Khan
authors.forename: Jalesh N
authors.initials: JN
authors.lastname: Panicker
authors.forename: Sohier
authors.initials: S
authors.lastname: Elneil
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Fowler
authors.forename: Alexander
authors.initials: A
authors.lastname: Roosen
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000008:administration & dosage*; D011446:Prospective Studies; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000473:pathology*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000473:pathology*; D019459:Urothelium
chemical_list: D009498:Neurotoxins; D019274:Botulinum Toxins, Type A