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Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

ABSTRACT: Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, ?SMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

SUBMITTER: Traini C

PROVIDER: S-EPMC5742717 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

Traini Chiara C Fausssone-Pellegrini Maria-Simonetta MS Guasti Daniele D Del Popolo Giulio G Frizzi Jacopo J Serni Sergio S Vannucchi Maria-Giuliana MG

Journal of cellular and molecular medicine 20170807 1

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains ...[more]

PMID: 28782880

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Project description:To evaluate the effects of onabotulinumtoxinA on patient-reported outcomes including health-related quality of life (HRQOL), treatment satisfaction, and treatment goal attainment in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).In this multicenter, double-blind, randomized, placebo-controlled, phase III, 52-week study (ClinicalTrials.gov NCT00311376), patients with UI due to NDO who were not adequately managed with anticholinergic therapy were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo (0.9% saline). HRQOL measures included the Incontinence Quality of Life (I-QOL) Questionnaire total score, and the 3 domain scores (avoidance and limiting behavior, psychosocial, and social embarrassment), the modified Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ), and Patient Global Assessment. Assessments were made at baseline, posttreatment week 6 (primary time point), week 12, and at 12-week intervals.Patients (mean age of 46 years with 30.5 weekly UI episodes at baseline) were randomized to receive placebo (n = 149) or onabotulinumtoxinA (200 U [n = 135] or 300 U [n = 132]). At week 6, improvements from baseline in I-QOL Questionnaire total score were greater (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo. Responses to the OAB-PSTQ also demonstrated greater mean improvements from baseline (p < 0.001) in both onabotulinumtoxinA-treated groups vs placebo at week 6. Patients who received onabotulinumtoxinA also reported greater improvement in the Patient Global Assessment than those in the placebo group (p ? 0.001 vs placebo).Patients with UI due to NDO reported greater improvement in HRQOL and treatment satisfaction with onabotulinumtoxinA than with placebo consistently across several patient-reported outcome instruments.This study provides Class I evidence that onabotulinumtoxinA intradetrusor injections (200 or 300 U) can improve quality of life measures in patients with NDO not adequately managed with anticholinergic therapy.

Project description:Neurogenic detrusor overactivity (NDO) affects the quality of life (QoL) of millions of individuals worldwide. The purpose of this study was to assess the efficacy and safety of onabotulinumtoxinA in patients with NDO using a network meta-analytic approach, which can also quantify and compare the efficacy of onabotulinumtoxinA across different dosages.PubMed, EMBASE, and the Controlled Trials Register were searched to identify randomized controlled trials comparing onabotulinumtoxinA to a control for NDO in adult patients. The primary outcome was the mean number of urinary incontinence (UI) episodes per week. Urodynamic parameters included the maximum cystometric capacity (MCC) and the maximum detrusor pressure (MDP). The safety of onabotulinumtoxinA was determined by the incidence of various frequent adverse events (AEs). Two authors extracted data independently, and the statistical analyses were performed using RevMan 5.1.0 software.A total of 1,915 patients from six randomized controlled trials were included in this meta-analysis. The onabotulinumtoxinA-treated groups had a significantly decreased mean number of urinary incontinence episodes per week (at week 6) (onabotulinumtoxinA200U: MD: -10.72, 95% CI: -13.4 to -8.04, P<0.00001; 300 U: MD: -11.42, 95% CI: -13.91 to -8.93, P<0.00001), MDP (200 U: MD: -33.46, 95% CI: -39.74 to -27.18, P<0.00001; 300 U: MD: -31.72, 95% CI: -37.69 to -25.75, P<0.00001), and greater increased MCC (200 U: MD: 141.30, 95% CI: 121.28 to 161.32, P<0.00001; 300 U: MD: 151.39, 95% CI: 130.43 to 172.34, P<0.00001) compared to the placebo-treated groups. However, there were no significant differences between the onabotulinumtoxinA-treated groups for the number of weekly UI episodes at 6 weeks (MD: 0.08, 95% CI: -2.57 to 2.73, P = 0.95). Similarly, we also observed that there were no significant differences in MCC (MD: -9.97, 95% CI: -33.15 to 13.20, P = 0.40) and MDP (MD: -1.86, 95% CI: -8.09 to 4.37, P = 0.56). Considering the AEs, the onabotulinumtoxinA-treated groups were often associated with more complications, including urinary tract infections (UTIs) (RR: 1.47, 95% CI: 1.29 to 1.67, P<0.00001), urinary retention (RR: 5.58, 95% CI: 3.53 to 8.83, P<0.00001), hematuria (RR: 1.70, 95% CI: 1.01 to 2.85, P = 0.05), and muscle weakness (RR: 2.59, 95% CI: 1.36 to 4.91, P = 0.004).OnabotulinumtoxinA can significantly reduce the frequency of urge urinary incontinence and improve urodynamic parameters (MCC and MDP) in patients with NDO at 6 weeks after treatment. This meta-analysis indicates that onabotulinumtoxinA is effective and safe for treating patients with NDO compared to placebo. Additionally, we did not observe any statistical or clinical differences in efficacy between 300 and 200 U dosages.

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Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

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Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

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