[Nitric oxide pathway and female lower urinary tract. Physiological and pathophysiological role].

International audienceGOAL: The aim was to review the literature on nitric oxide and female lower urinary tract. MATERIAL: A literature review through the PubMed library until December, 31 2012 was carried out using the following keywords: lower urinary tract, bladder, urethra, nervous central system, innervation, female, women, nitric oxide, phosphodiesterase, bladder outlet obstruction, urinary incontinence, overactive bladder, urinary tract infection. RESULTS: Two nitric oxide synthase isoforms, the neuronal (nNOS) and the endothelial (eNOS), are constitutively expressed in the lower urinary tract. Nevertheless, nNOS is mainly expressed in the bladder neck and the urethra. In the bladder, NO modulates the afferent neurons activity. In pathological condition, inducible NOS expression induces an increase in detrusor contractility and bladder wall thickness and eNOS facilitates Escherichia coli bladder wall invasion inducing recurrent urinary tract infections. In the urethra, NO play a major role in smooth muscle cells relaxation. CONCLUSION: The NO pathway plays a major role in the female lower urinary tract physiology and physiopathology. While it acts mainly on bladder outlet, in pathological condition, it is involved in bladder dysfunction occurrence

Characterization and Validation of a Chronic Model of Cyclophosphamide-Induced Interstitial Cystitis/Bladder Pain Syndrome in Rats

Interstitial cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease characterized by visceral pain and voiding symptoms. IC/BPS is still an unsolved enigma with ineffective diagnosis criteria and treatment. A main limitation in IC/BPS understanding is the lack of appropriate preclinical model. Cyclophosphamide (CYP) is commonly used as an experimental model for IC/BPS in rodent. However, the proposed models are very aggressive, contrasting with what occurs in clinic, and often associated with severe toxicity and high mortality rate. In addition, visceral pain, the hallmark symptom of IC/BPS, has been validated in only few of them. In this study, we developed a chronic model of CYP-induced IC/BPS in female rat. In our protocol, no severe weight loss occurred and the survival rate was 100%. In accordance to human pathology, chronic CYP-injected rats developed severe painful behavior whereas only sparse inflammation was observed. Inflammatory response was characterized by bladder edema and focal urothelial damage but absence of massive infiltrate. This chronic model showed persistent symptoms indicative for a central sensitization mechanism. We further demonstrate that CYP-induced chronic visceral pain was significantly reduced by curative treatment with clinically relevant compounds (gabapentin, ibuprofen, and Ialuril ®). We therefore developed and validated a rat model of chronic cystitis that shares strong similarity with human non-ulcerative IC/BPS features without overtly affecting the animal health. This model will thus provide mechanistic insights of the disease and help to evaluate therapeutic agents for IC/BPS

Widespread Postponement of Functional Urology Cases During the COVID-19 Pandemic: Rationale, Potential Pitfalls, and Future Consequences

International audienceOwing to the recent emergence and rapid spread of SARS coronavirus 2, many national health authorities are recommending cancellation of scheduled elective surgeries and office visits [1–5]. The objectives are to increase the availability of inpatient and intensive care unit beds, to permit internal redeployment of medical staff and nurses, and to avoid overwhelming the health care systems. Another goal is to minimise exposure to COVID-19 by reducing visits to hospital by asking patients to stay at home to flatten the pandemic curve

Transcutaneous posterior tibial nerve stimulation: Ready for prime time?

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The Changing Face of Artificial Urinary Sphincter Use in France The Future is Female

International audienceAnalyzing concurrently data from the manufacturer and from a national comprehensive administrative claim database (PMSI)we found that, overall, the total number of AUS implanted (male+female) increased from 2012 to 2017 (+8.8%). This growth was driven by a strong increase in the number of female implants from 2015 to 2017 (+28.9%). Meanwhile, the number of AUS implanted in male patients remained roughly stable and the total number of anti-incontinence surgery in men (slings+AUS) decreased steadily over the period studied

Cellular Senescence in Renal and Urinary Tract Disorders

International audienceCellular senescence is a state of cell cycle arrest induced by repetitive cell mitoses or different stresses, which is implicated in various physiological or pathological processes. The beneficial or adverse effects of senescent cells depend on their transitory or persistent state. Transient senescence has major beneficial roles promoting successful post-injury repair and inhibiting malignant transformation. On the other hand, persistent accumulation of senescent cells has been associated with chronic diseases and age-related illnesses like renal/urinary tract disorders. The deleterious effects of persistent senescent cells have been related, in part, to their senescence-associated secretory phenotype (SASP) characterized by the release of a variety of factors responsible for chronic inflammation, extracellular matrix adverse remodeling, and fibrosis. Recently, an increase in senescent cell burden has been reported in renal, prostate, and bladder disorders. In this review, we will summarize the molecular mechanisms of senescence and their implication in renal and urinary tract diseases. We will also discuss the differential impacts of transient versus persistent status of cellular senescence, as well as the therapeutic potential of senescent cell targeting in these diseases

Progrès dans l’étude du cancer de la prostate : la culture cellulaire en trois dimensions reproduit ex vivo les caractéristiques des tumeurs prostatiques

Malgré les progrès thérapeutiques, le cancer de la prostate (CaP) reste un enjeu de santé publique par son incidence et sa mortalité élevée. Les difficultés de la recherche sur le CaP viennent du manque de modèles précliniques in vitro et in vivo capables de reproduire ses caractéristiques. Actuellement, les cultures de lignées cellulaires de CaP in vitro en 2D sont les plus répandues, mais elles ont de nombreuses limites. Elles ne reproduisent pas la morphologie cellulaire, l’architecture tissulaire, et ne reflètent pas l’hétérogénéité tumorale entre les patients et au sein même de la tumeur. De plus, elles sont dépourvues du microenvironnement tumoral et des cellules souches cancéreuses qui sont deux acteurs incontournables du CaP. Les modèles in vivo murins du CaP ne représentent pas le spectre des altérations génétiques de la maladie et ont des difficultés à reproduire le processus métastatique. Par conséquent, la physiologie de ces modèles in vitro et in vivo est extrêmement éloignée de celle des tumeurs prostatiques des patients. Les modèles de culture cellulaire en 3D s’affranchissent de ces limites en partageant les caractéristiques des tumeurs in vivo tout en en gardant la reproductibilité expérimentale des modèles in vitro. Les modèles en 3D du CaP comprennent les sphéroïdes qui dérivent des lignées cellulaires tumorales, et les organoïdes issus des tumeurs primaires ou des métastases du CaP. Dans ces structures, la morphologie cellulaire est conservée, une matrice extracellulaire entoure les cellules et les interactions cellules-cellules et cellules-matrice sont préservées. De plus, les organoïdes conservent les altérations génétiques des tumeurs prostatiques dont ils dérivent et ils permettent l’étude des cellules souches cancéreuses au sein d’un microenvironnement. Les organoïdes ouvrent la perspective de tests thérapeutiques couvrant le large spectre des phénotypes du CaP. Les organoïdes générés à partir de biopsies de patients pourraient de plus, mener vers une médecine personnalisée.Despite new therapeutics options, Prostate Cancer (PCa) remains a public health challenge because of its high incidence and mortality. Limits in PCa research come from the lack of in vitro and in vivo models that mimic the human disease. Currently, 2D in vitro tissue culture models of PCa are widely used but they present numerous limits. They do not reproduce cellular morphology, tissue architecture, inter-patients and intratumor heterogeneity. Furthermore, they lack two key components of PCa tumors, the tumoral microenvironment and the cancer stem cells. In vivo murine models of PCa cannot be representative of all the genetic alterations known in prostate tumors and they hardly reproduce the pathophysiology of human metastatic progression. Consequently, the physiology of these in vitro and in vivo models do not well represent patients tumors. 3D cell cultures overcome many of these limits by sharing morphologic characteristics with in vivo tumors as well as reproducibility of in vitro models. 3D models of PCa include spheroids derived from tumor cell lines, and organoids, derived from patient. In 3D cell cultures, cell fitness is maintained, the physiological cells-cells and cell-matrix interactions are restored and an extracellular matrix surrounds the cells. Organoids, generated from PCa primary tumors or metastases, allow studies on cancer stem cells and their microenvironment. Moreover, organoids retain genetic integrity of PCa tumors. PCa organoid model is an innovative tool that offers great perspectives of therapeutic screening. In the future, organoids generated from patients’ biopsies may also lead to personalized medicine

Intermittent Self-catheterization in Older Adults: Predictors of Success for Technique Learning

Purpose The main goal of this retrospective study is to explore the predictors of success in learning clean intermittent self-catheterization (CISC) in patients over 65 years of age. The secondary goal is to assess whether in this population, the risk of failure to perform CISC is greater, compared with patients under 65 with similar pathologies. Methods All patients older than 65 consulting between January 2011 and January 2016 for learning CISC were included. A control population younger than 65 matching with sex, body mass index, and pathology was selected. Results One hundred sixty-nine of the 202 patients (83.7%) over 65 succeeded in learning CISC. Obesity (P<0.05), low pencil and paper test (PP test) (P<0.01) and low functional independence measure (FIM) (P<0.01) scores were risk factors of failure. No significant differences were found with sex or pathology. In multivariate analysis, low PP test perineum access (odds ratio [95% confidence interval], 2.30 [1.32–4.42]), low FIM motor (1.04 [1.01–1.08]), and FIM cognition (1.18 [1.03–1.37]) scores were independent factors of learning failure. Compared to control group, age over 65 was not predictive of failure (P=0.15). Conclusions Our study shows that success in learning CISC does not depend on age but on difficulties in mobility, access to perineum and probably cognitive disorders

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

Objectives: 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. Results: 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). Conclusions: 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